O'Donnell's Drug Injury
portes grátis
O'Donnell's Drug Injury
Patel, Gourang; Splawski, Jennifer; O'Donnell III, James J.; O'Donnell, James T.
Taylor & Francis Ltd
07/2025
856
Dura
Inglês
9781041015451
Pré-lançamento - envio 15 a 20 dias após a sua edição
Descrição não disponível.
PART I: THE PHARMACEUTICAL PROCESS
Chapters 1 - 9
Chapter 1: FDA and Drug Approval Process
Megan Walter, Pharm.D. and CDR Lindsay Wagner, Pharm.D., BCPS
1.1 Introduction
1.2 The New Drug Development Process
A. Discovery and Preclinical Research
B. Clinical Research
C. Investigational New Drug Application
D. Phases of Clinical Studies
E. Expanded Access Programs
F. Right to Try
1.3 New Drug and Therapeutic Biologic Application Process
A. New Drug Applications and Biologic License Applications
B. Fundamentals of NDA and BLA Submissions
C. NDA Classifications
1.4 FDA Review
A. Expedited Development and Review Programs
1. Accelerated Approval
2. Priority Review
3. Fast Track
4. Breakthrough Therapy
B. Labeling Review
1. Physician Labeling Rule (PLR)
2. Pregnancy and Lactation Labeling Rule (PLLR)
3. Additional FDA-Approved Patient Labeling
C. Risk Evaluation and Mitigation Strategies
D. Advisory Committee Meetings
1.5 The Generic Drug Approval Process
A. Abbreviated New Drug Applications
B. ANDA Approval
C. Generic Drug User Fee Amendments
1.6 Biosimilar Pathway
1.7 Over-the-Counter Drug Products
1.8 Postmarketing Surveillance
A. Adverse Event Reporting
B. FDA Adverse Event Reporting System
C. Post Marketing Requirements and Commitments
D. Sentinel Network
E. Drug Safety Oversight Board
1.9 Applicable Statutes and Implementing Regulations
A. Food and Drug Acts - 1906
B. Food, Drug and Cosmetic Act - 1938
C. Durham-Humphrey Amendment - 1951
D. Kefauver-Harris Amendment - 1962
E. Orphan Drug Act - 1983
F. Drug Price and Competition and Patent Term Restoration Act - 1984
1. Revision of New Drug Application Regulations - 1985
2. Revision of Investigational New Drug Application Regulations - 1987
3. Treatment Use of Investigational New Drugs - 1987
G. Prescription Drug User Fee Act (PDUFA) - 1992
H. FDA Modernization Act (FDAMA) - 1997
I. FDA Amendments Act (FDAAA) - 2007
J. Food and Drug Administration Safety and Innovation Act (FDASIA) - 2012
K. The Drug Quality and Security Act (DQSA) - 2013
L. 21st Century Cures Act - 2016
M. Food and Drug Administration Reauthorization Act (FDARA) - 2017
N. Coronavirus Aid, Relief, and Economic Security Act (CARES Act) - 2020
1.10 Conclusion
1.11 Glossary of Terms
References
Chapter 2: The Front Lines of Clinical Research: The Industry and Ethical Considerations
Jonathan Young, Ph.D.
2.1 Introduction
2.2 Clinical Trial Service Providers
A. Food and Drug Administration
B. Clinical Trial Sponsor
C. Contract Research Organizations
D. Study Monitors
2.3 Clinical Trial Site
A. Site Management Organizations
B. Institutional Review Boards
2.4 The Evolution of Ethical Principles in Clinical Research
A. Respect for Persons
B. Beneficence
C. Justice
D. How the Investigator Applies Ethical Principles
2.5 Regulations Governing Institutional Review Boards
A. What Institutional Review Board Members Should Know about Clinical Research
B. What Institutional Review Board Members Should Know about Their Responsibilities
2.6 What the Site Should Know about Institutional Review Boards
A. What Research Requires Institutional Review Board Approval and Oversight
B. Requirements of an Investigator for Institutional Review Board Research Approval
2.7 Risks-vs.-Benefits Analysis: The Human Advocate
A. Identifying and Assessing the Risks
B. Minimal Risk vs. Greater-than-Minimal Risk
C. Vulnerable Populations and Minimal Risk
D. Determining Whether Risks Are Minimized
E. Assessing Anticipated Benefits
F. Determining Whether Risks Are Reasonable
G. Continuing Review and Monitoring of Data
2.8 Informed Consent: Not Just a Document
A. Elements of an Informed Consent
B. Additional Required Elements
2.9 Research Participants
2.10 Industry Trade Organizations and Support Services
2.11 Summary: Ethical Dilemmas in Clinical Research
References
Chapter 3: Search and Analysis of the Food and Drug Administration's FDA Adverse Event Reporting System (FAERS)
Paul N. Danese, Ph.D.
3.1 Introduction
3.2 Background
A. Small Clinical Trial Populations
B. Narrow Patient Demographics
C. Restricted Co-Administration of Medications
3.3 History of the FDA's Drug Safety Surveillance Systems
3.4 Submission of Adverse Event Reports to the FDA
A. Mandatory Reports
B. Voluntary Reports
3.5 Adverse Drug Reaction Information Captured by FAERS
3.6 Searching FAERS Data to Identify Possible Safety Problems
A. Statistical Methods to Identify Drug Safety Signals
B. Dechallenge and Rechallenge Data and Causality
C. Identifying Drug-Drug Interactions
D. Timelines and Deadlines of Adverse Event Reporting
3.7 The Food and Drug Administration's Use of FAERS in Regulatory Decisions
A. Boxed Warnings
B. Other Changes to a Medication's Prescribing Information
C. Determinations that No Action is needed and Continuing Investigations
3.8 Limitations of FAERS
A. Lack of Demonstration of Causality for Individual Reports
B. Extensive Under-reporting
C. Reporting Biases
D. Lack of Comparator Populations (Lack of a Denominator)
3.9 Search and Retrieval of Adverse Event Reports from the FDA's FAERS
A. Raw Data Files
B. FDA Public Dashboard
C. FOIA Requests
D. Commercial Vendors
3.10 Other FDA Adverse Event Reporting Systems
A. VAERS
B. MAUDE
C. Sentinel Initiative
3.11 Summary and Conclusions
References
Chapter 4: The Safety of Medicines: PharmacoVigilance, PharmacoSurveillance, PharmacoEmpowerment?
David Healy, M.D.
4.1 RxISK.org
4.2 Antidepressants: Data Based or Evidence Based?
4.3 Access to Adverse Event Data
4.4 RCTs and Adverse Events // Ghost Writers
4.5 RCTs & Primary Endpoints
4.6 Post 1962: Confounding & Causality
4.7 Pharmacovigilance
4.8 RxISK.org and Pharmacovigilance 1.0
4.9 Pharmacosurveillance
4.10 TaperMD and Pharmacovigilance 2.0
4.11 Summary and Conclusions
References
Chapter 5: Important Code of Federal Regulations Applicable to Drug Product Liability Suits
S. Albert Edwards, Pharm.D., RAC, FRAPS
Chapter 6: The Regulation of Drug Product Information to Consumers
Frank J. Ascione, Pharm.D., MPH, PhD
6.1 The Historical Development of Food and Drug Administration (FDA)'s Regulatory Role
A. Early phase (prior to 1906): No significant government intervention
B. Early Regulatory Phase (1906-1938): Minimal Government Control
C. Greater Government Control (1938-1961)
D. Debating Increased Consumer Access to Drug Product Information (1962-1983)
E. Expanding Information Available to Consumers (1983-present)
6.2 Current State of Prescription Drug Product-Related Information Provided to Consumers
6.3 Evolution of Drug Advertising to US Consumers (DTCA)
A. Emergence of DTCA (1981-1982)
B. Voluntary Moratorium Period of DTCA (1983-1985)
C. Establishment of DTCA Regulations (1985-1999)
6.4 Current State of Direct-to-Consumer Advertising
A. Advantages and Disadvantages of DTCA
6.4 Summary and Conclusions
References
Chapter 7: The Role of Investigative Journalism in Improving Drug Safety
Martha Rosenberg
7.1 Introduction
7.2 Direct-To-Consumer Advertising Increased with Covid
A. Unbranded DTC Advertising
B. Industry Funded Disease Awareness Groups
C. Encouraging Victim Politics
7.3 The Opioid Epidemic
A. Growing an Untapped Market
B. Aggressive Opioid Marketing
C. Fostering Opioid Addiction
D. Pill Mills and Addiction Medicine
E. Opioid Lawsuits Surface
F. Lack of Opioid Efficacy and Serious Side Effects
G. Paying for the Opioid Epidemic
7.4 Effective Hepatitis C Drugs Debut
A. Lawmakers Investigate Hep C Prices
B. Aggressive Hep C Marketing
C. Screening as a Hep C Sales Tool
D. Hepatitis C Safety Signals Emerge
7.5 Asthma Drug Safety Signals
A. Xolair Leaves a Trail of Questions
B. More Improper Xolair Marketing
C. Safety Signals Surface with Xolair and a Lawsuit is Dismissed
7.6 Long-Acting Beta Agonists
A. Glaxosmithkline Settlement included a Laba
7.7 Safety Questions About Leukotriene Receptor Antagonists
A. Parents Report LTRA Side Effects
B. LTRA Safety Signals Emerged Early
C. Patients and Parents Fight Back
D. Black Box Added to Singulair
7.8 Baldness Treatments Become Popular and Controversial
A. Finasteride Side Effects Create Concern
B. Medical Literature Confirms Finasteride Side Effects
C. FDA Adds Warnings to Finasteride
D. Finasteride User Speaks Out
E. No Satisfying End for Finasteride Users
7.9 Biologic Drugs
A. Tumor Necrosis Factor (Tnf) Blockers
B. Tnf Blocker Risks
7.10 Other Popular Medications Come Under New Scrutiny
A. N-Nitrosodimethylamine (NDMA
) Found in Medicines
1. Zantac Taken Off Shelves
2. NDMA Also Found in Metformin
7.11 Popular Stimulant Drugs Reveal Risks
A. Risks Seen with Modafinil
B. Fetal Risks Seen with Modafinil and Armodafinil
C. European Union Sues Provigil Makers
7.12 Fetal Risk Seen with NSAIDs
7.13 Bisphosphonates Continue to Present Risks
7.14 SSRI Antidepressants Linked to New Risks
A. SSRI Bone Thinning
B. SSRI Addictive Potential
7.15 Belviq, A Diet Drug Withdrawn from Market
7.16 Sleeping Pills Given Boxed Warnings
A. Public Figures on Sleeping Pills Make the News
B. Other Sleeping Pill Risks
7.17 Risks Associated with Fluoroquinolone Antibiotics
A. Fluoroquinolones Warnings Continue
B. Hormone Therapy Still Linked to Risks
C. Beware of Testosterone Marketing
D. New PPI Questions
References
Chapter 8: Evaluation of Causation in Drug Injury Cases
Donald H. Marks, M.D., Ph.D. and James T. O'Donnell, Pharm.D., M.S., FCP
8.1 What is Causation?
8.2 Importance of Establishing Causation
8.3 Definitions
8.4 Degree of Adverse Effects Relate to Intervention
8.5 Methodology to Investigate Causation
8.6 Structured Algorithms for Determination of Causation
A. Hill Criteria-Expanded Discussion
1. Strength of Association
2. Consistency of Results
3. Specificity
4. Temporal Relationship
5. Dose Response
6. Biological Plausibility
7. Biological Coherence
8. Experimentation
9. Analogy
8.7 Comments on the Individual Riddell Criteria for Causation,
8.8 Daubert and the Evolution of Causation,
8.9 Does Causation Need to be Established Before a Warning is Given?
8.10 What are the Qualifications needed to Give Expert Causation Opinions?
8.11 Case Reports Demonstrating Applications of Causation Principles
A. Case Report: Acyclovir Overdose - Pharmacist Recommended Overdose
B. Case Report: Challenging Cause of Death in a Malpractice Matter
C. Case Report: Determination of the Effects of Morphine in a Will Contest
D. Case Report: Proof of Drug-Induced Mental Changes in Complainant in Sexual Abuse Case
8.12 Summary and Conclusions
References
Chapter 9: General Principles of Pharmacology
James J. O'Donnell III, M.S., Ph.D., James T. O'Donnell, Pharm.D., M.S., FCP, and Vanessa Juettner, Ph.D.
9.1 Introduction
9.2 Basic Principles
A. Absorption
B. Lipid Diffusion
C. Determinants of Absorption
1. Lipid/aqueous partition coefficient and pH
2. Bioavailability
3. First pass effect
9.3 Routes of Administration
9.4 Extravascular Administration
A. Oral Administration
B. Rectal Administration
C. Other Routes of Administration
9.5 Intravascular Administration
9.6 Distribution
A. Diffusion
B. Volume of Distribution
C. Binding to Plasma Proteins and Cellular Constituents
D. Re-Distribution
E. Blood-Brain Barrier (BBB)
F. Placental Barrier
G. Therapeutic Range
H. Bioequivalence vs. Bioinequivalence
10.7 Drug Metabolism (Biotransformation)
A. Phase I Reactions
1. The families of human P450s
2. Induction of P450 enzymes
3. P450 Inhibition
B. Phase II Reactions
1. Metabolism of drugs to toxic products
9.8 Factors Affecting Drug Metabolism
A. Disease
B. Age
C. Gender
D. Genetic Factors
9.9 Drug Excretion
A. Urinary Excretion
1. Glomerular filtration
2. Tubular secretion (active secretion)
3. Tubular reabsorption
4. Effects of pH on urinary excretion of ionizable drugs
9.10 Pharmacokinetics
A. Introduction
B. Therapeutic Window and Therapeutic Index
C. Blood Levels for Narrow Therapeutic Index (NDI) Drugs
D. Kinetic Modeling
E. Drug Absorption and Elimination
1. Absorption rate
2. Elimination rate
3. Clearance (CL)
4. Area Under the Curve (AUC)
5. Elimination (k)
6. Elimination half-life
7. Steady state
F. Dosing
1. Loading dose
2. Maintenance doses (MD)
3. Example-dosage adjustment in renal impairment
G. Therapeutic Drug Monitoring (TDM)
H. Pharmacokinetics Summary
9.11 Drug Receptor and Pharmacodynamics
A. Agonists and Antagonists
B. Drug-Receptor Interactions
9.12 Dose Responses
A. Potency
B. Agonism and Antagonism
1. Partial agonists
9.13 Competitive Antagonism
9.14 Non-Competitive Antagonism
9.15 Summary and Conclusions
PART II: HIGH RISK DRUG THERAPIES RESULTING IN INJURY AND LITIGATION
Chapters 10 - 25
Chapter 10: Adverse Drug Reactions: Allergic Focus
James T. O'Donnell Pharm.D., M.S., FCP and James J. O'Donnell III, M.S., Ph.D.
10.1 Adverse Drug Reactions: How Large is the Problem? What Drugs are Involved? What are the Injuries?
A. Historical Perspective
B. Incidence of Adverse Drug Reactions
C. Food and Drug Administration Reporting Requirements
D. The "Seven Deadly Sins": Why Doctors Fail to Report Adverse Drug Reactions
E. Attitudes Toward Adverse Drug Reactions
F. Investigator Fraud
10.2 Classification of Adverse Drug Reactions
A. Categories of Adverse Drug Reactions
1. Type A reactions: Augmentation of the Pharmacological Response
2. Type B reactions: Bizarre (idiosyncratic)
10.3 Types of Drug Allergy and Hypersensitivity
A. The Nature of Drug Allergy
B. Dangerous Drug-Allergy Reactions
C. Drug Sensitivities Mimic Allergy Symptoms
D. Definitions of Allergic/Hypersensitivity Reactions
E. Idiosyncratic Reactions
F. Intolerance
G. Toxicity
H. Hypersensitivity Vasculitis
I. Predominantly Organ-Specific Reactions
J. Urticaria
K. Fixed Drug Eruptions
L. Photosensitivity Reactions
M. Generalized Exfoliative Dermatitis
N. Thrombocytopenia
O. Hemolytic Anemia
P. Agranulocytosis
Q. Treatment: Withdrawal of the Suspected Drug
R. Symptomatic Treatment
S. Prevention of Allergic Drug Reactions
T. Pseudoallergy
U. Angioedema
V. Hypersensitivity Reactions
10.4 Risk Factors, Drugs and Patients
A. Hypersensitivity Risk Factors
B. Identification of a Drug Allergy
C. Allergy to Antibiotics
D. Case Report: Cross-Allergenicity
10.5 Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
A. Fixed Drug Eruptions
B. Erythema Multiforme-Like Eruptions
Case Report: Lamictal Induced Stevens Johnson Syndrome
C. Fluoroquinolones
E. NSAIDs Cross Reactivity Case Report
F. Radiographic Contrast Media
G. Local Anesthetics
H. Anticonvulsants (AED)
10.6 Summary and Conclusions
References
Chapter 11: Drug Induced Falls
James T. O'Donnell Pharm.D., M.S., FCP and James J. O'Donnell III, M.S., Ph.D.
11.1 Introduction
11.2 The Definition of Fall
11.3 Epidemiology
11.4 Causes and Risk Factors
A. Physiological Risk Factors for Falls in the Elderly
B. Psychological Risk Factors
C. Medical Conditions
11.5 Medication-related Falls
11.6 Types of Medications that Increase the Risk of Fall
A. Centrally Active Medications
B. Benzodiazepines
C. Antipsychotics
D. Antihypertensives
1. Orthostatic Hypertension and Risk of Fall
E. Opioids
11.7 Marijuana
11.8 Alcohol
11.9 Hip Fractures
11.10 Polypharmacy
11.11 Fall Risk Assessment
11.12 Types of Assessments
11.13 Strategies for Fall Prevention in Institutionalized Settings
A. Screening
B. Addressing Risk Factors
1. Monitoring Patients
2. Environmental Interventions
3. Educational Programs
4. Reducing Fall Injury
C. Discharge Planning
D. Disseminating Evidence: Awareness and Intervention Work!
11.14 Summary and Conclusions
References
Chapter 12: Drug Induced Movement Disorders
Jadwiga Najib, B.S. Pharm.D., BCPS, and Meagan Bailey, M.D.
12.1 Introduction
12.2 Presentation
12.3 Agents Associated with Drug-Induced Movement Disorders
12.4 Risk Factors
12.5 Sequelae of Drug-Induced Movement Disorders
12.6 Theories of Causation
12.7 Drug-Induced Movement Disorders in Children and Adolescents
12.8 Drug-Induced Movement Disorders in the Elderly
12.9 Acute/Intermediate Drug-Induced Movement Disorders
A. Dystonia
1. Presentation
2. Implicated agents
3. Risks
4. Management
B. Ataxia
C. Bruxism
D. Neuroleptic Malignant Syndrome
E. Serotonin Syndrome
12.10 Chronic Drug-Induced Movement Disorders
A. Akathisia
1. Presentation
2. Case study: Trazodone-induced akathisia
3. Implicated agents
4. Other drugs
5. Risks
6. Management
B. Parkinsonism
1. Presentation
2. Case Study: Neuroleptic-Induced Parkinsonism
3. Implicated agents
4. Other drugs
5. Risks
6. Management
C. Myoclonus, Tremor, Tics, Asterixis
12.11 Persistent/Tardive Drug-Induced Movement Disorders
A. Tardive Dyskinesia
1. Presentation
2. Case Study: Neuroleptic induced oral buccal dyskinesia and akathisia
3. Implicated agents
4. Case Study: Metoclopramide induced oral buccal lingual dyskinesia
5. Risks
6. Management
B. Tardive Akathisia
C. Tardive Dystonia
1. Case Report: Neuroleptic induced cervical dystonia
D. Other Tardive Variants
12.12 Drugs Used for Movement Disorders
12.13 Monitoring
12.14 Clinical and Legal Issues in Psychiatry
12.15 Summary and Conclusions
References
Chapter 13: Acute Adverse Drug Events in Critical Care Emergency Department and Intensive Care Units
Gourang P. Patel, Pharm.D., M.Sc., BCPS, BCCCP, FCCM
13.1 Background
A. Epidemiology
B. Environment
13.2 High-Risk Medication-Related Events
A. Hypersensitivity Reactions
B. Cardiovascular Reactions
1. Blood pressure (BP)
2. Heart rate (HR)
3. Arrhythmias
C. Nephrotoxicity
1. Aminoglycosides
2. Amphotericin B
3. Intravenous contrast
D. Hypoglycemic Events
E. Infusion-Related Reactions
1. Extravasations
2. Propofol-related infusion syndrome (PRIS)
3. Intravenous N-acetylcysteine (NAC)
F. Reversal Agents
1. Protamine
2. Vitamin K
3. Naloxone
4. Flumazenil
13.3 Summary and Conclusions
References
Chapter 14: Nephrotoxic Drugs
Jason M. Kidd MD, Domenic A. Sica, M.D. and Todd W. B. Gehr, M.D.
14.1 Introduction
14.2 Framework of the problem
14.3 Basis for the kidney being susceptible to damage
14.4 Patient groups most susceptible to nephrotoxicity
14.5 Demographics of chronic kidney disease
14.6 Methods to assess renal function and/or damage
14.7 Level of renal function at which drug accumulation occurs
14.8 Nephrotoxic drugs
A. What constitutes prompt clinical action in the face of nephrotoxicity?
14.9 Nephrotoxicity scenarios
A. Lithium toxicity
B. Gentamicin toxicity
C. Dialysis-related issues
D. Drug Clearance in Relationship to Renal Failure
1. Case 1
2. Case 2
E. Angioedema with an ACE inhibitor
F. Fatal hyperkalemia with medications
G. Statin therapy and the development of myopathy
H. Nephrotoxicity related to checkpoint inhibitor use
14.10 Summary and Conclusions
References
Chapter 15: Drug Induced Liver Disease
James T. O'Donnell, Pharm.D., M.S., FCP, James J. O'Donnell III, M.S., Ph.D., Donald H. Marks, M.D., Ph.D., Paul Danese, Ph.D.
15.1 Introduction: The Problem of Drug-Induced Liver Disease
15.2 History of Adverse Drug Reactions
15.3 Overview of DILD, Epidemiology Risk Factors, Histopathology, and Diagnoses
A. Epidemiology of Drug Hepatotoxicity
B. Risk Factors
C. Histopathology
D. Diagnosis
15.4 Hepatic Drug Metabolism
15.5 FDA and DILD
15.6 Types of Liver Injury
A. Hepatitis
B. Massive Hepatic Necrosis (Fulminant Hepatitis)
C. Drug-induced Vanishing Bile Duct Syndrome
15.7 Specific DILD Product Areas and Case Discussions
A. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Use and Hepatoxicity
B. Isoniazid-Induced Hepatotoxicity
C. Acetaminophen
1. Acetaminophen Toxicity Assessment Nomograms
2. FDA Report - Acetaminophen Induced Liver Disease
D. Macrolide Hepatotoxicity
E. Methotrexate (MTX) Hepatotoxicity
F. Estrogens and Oral Contraceptive Steroids
G. Statins
H. Ticlopidine
I. ACE Inhibitors and AT II Receptor Antagonists
J. Fluoroquinolones
K. Terbinafine
L. Ketoconazole
M. Selective Serotonin Reuptake Inhibitors - Serzone Liver Toxicity
N. Herbal and Other Dietary Supplements and Hepatotoxicity
15.8 Summary and Conclusions
References
Chapter 16: Antineoplastic Therapy
Kathryn Schultz, Pharm.D. and Eris Tollkuci, Pharm.D.
16.1 Background
16.2 Chemotherapy - Antimetabolites
16.3 Chemotherapy - Antimicrotubules
16.4 Chemotherapy - Alkylators
16.5 Chemotherapy - Topoisomerase I Inhibitors
16.6 Chemotherapy - Topoisomerase II Inhibitors
16.7 Chemotherapy - Antitumor Antibiotics
16.8 Chemotherapy - Miscellaneous
16.9 Targeted Therapy
A. Infusion-related reactions (IRRs)
B. Immunotherapy (Immune Checkpoint Inhibitors)
1. Infusion-related reactions
2. Immune-Related Adverse Events (irAEs)
16.10 Tumor Lysis Syndrome
16.11 Hepatotoxicity
16.12 Summary and Conclusions
References
Chapter 17: Dangers of Opioids
Jennifer Splawski, M.S., Pharm.D., BCPS, James T. O'Donnell, M.S., Pharm.D., James J. O'Donnell III, M.S., Ph.D.
17.1 Introduction
A. Definitions
B. History
17.2 Pharmacology of Opioids
A. Effects
B. Opioid Neural Receptors
1. Central Nervous System (CNS) Receptors
2. Peripheral Nervous System (PNS) Receptors
C. Routes of Administration
1. Oral
2. Intramuscular
3. Subcutaneous
4. Intravenous
5. Transdermal
6. Sublingual and Buccal
7. Neuraxial
D. Metabolism
E. Excretion
17.3 Toxicity of Opioids
A. Respiratory Depression
B. Symptoms of Overdose
17.4 Epidemiology of Opioid Abuse
A. Opioid Abuse in Adolescents and Young Adults
B. Opioids in Pregnancy
17.5 Contributions to the Opioid Epidemic
A. Opiates Handed Out Like Candy to 'Doped-up' Veterans
B. United States Reaches $22 Million Settlement Agreement with CVS For Unlawful Distribution of Controlled Substances
C. Former Walmart Pharmacists Say Company Ignored Red Flags as Opioid Sales Boomed
D. Federal Judge Approves Landmark $8.3 Billion Purdue Pharma Opioid Settlement
17.6 Combatting the Opioid Epidemic
A. Prescription Monitoring Programs (PDMP)
B. Naloxone Dispensing
C. Medication for Opioid Use Disorder (MOUD)
1. Buprenorphine
A. Pharmacokinetics
B. Adverse Effects
C. Place in therapy
1. Methadone
A. Pharmacokinetics
B. Equianalgesic Dosing
C. Drug Interactions
D. Cardiovascular Effects
E. Consequences of Ignorance of Proper Dosing of Methadone
F. Methadone Legal Case Examples Involving Patient Demise
G. Applying Lessons Learned and Action for Institutional Committees
17.7 Case Reports: Opioid Toxicity Causing Respiratory Arrest, Brain Damage, and Death
A. Case Report: Respiratory Arrest and Brain Damage Following Morphine Overdose
B. Case Report: Fentanyl Epidural Respiratory Arrest
C. Case Report: Fentanyl (Duragesic (R)) Death in Discharged Patient
D. Case Report: High Dose Fentanyl Patch Prescribed in Opiate-Naive Patient-Death
E. Case Report: Heroin and Other Opioids
F. Case Report: Hydromorphone (Dilaudid (R)) Respiratory Arrest
17.8 Investigation and Prosecution of Pain Clinics by the Department of Justice (DOJ)
17.9 Summary and Conclusions
References
Chapter 18: Adverse Effects of Diabetic Drugs: Focus on Hypoglycemia
Gourang P. Patel, BS Chem, PharmD, MSc, BCPS and James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN
18.1 Diabetes Demographics and Epidemiology
18.2 Insulin
18.3 Insulin Preparations
18.4 Clinical Use of Insulin
A. Dosing
18.5 Hypoglycemia (Low Blood Sugar)
A. Etiologies of hypoglycemia
B. Insulin-induced hypoglycemia
C. Deaths by Hypoglycemia
18.6 Pathophysiology and Clinical Symptoms of Hypoglycemia
18.7 Incidence
18.8 Pathophysiology and Biochemistry of Hypoglycemia
18.9 Adverse Reactions Involving Hypoglycemia
A. Insulin damages baby's brain; pharmacist error suggested
18.10 End Product Testing Recommended
18.11 Insulin Murders
18.12 Hypoglycemia from the Sulfonylurea Derivatives
18.13 Adverse Effects of the Sulfonylureas
18.14 Drug Interactions with Sulfonylureas
18.15 The Gliptin Class New drugs for Diabetes Treatment Type 2 Diabetes
18.16 Thiazolidinediones
A. Hepatic Failure
B. Bladder Cancer
18.18 Summary and Conclusions
References
Chapter 19: Parenteral Nutrition Related Errors and Complications
Erica M. Fernandez, Pharm.D., BCCCP, BCPS
19.1 Introduction
19.2. Basic principles of PN
19.3 PN Provision Categories
A. Prescribing
B. Transcribing and Verification
C. Compounding
D. Administration
19.4. Monitoring and Complications
A. Glycemic Control
B. Refeeding Syndrome
C. Hepatobiliary Complications
D. Complications involving micronutrients
19.5 PN Component Shortages and Adverse Events
19.6 Summary and Conclusion
References
Chapter 20: Antidepressants: Clinical Use and Litigation
Henry Cohen, Pharm.D., M.Sc., FCCM, BCPP, BCGP and Michael Liu, Pharm.D., MBA, BCCCP, BCNSP, BCPS
20.1 Major Depressive Disorders
20.2 Antidepressant Pharmacology
20.3 Antidepressant Overdose
A. Trazodone and Permanent Neurologic Sequelae
20.4 Antidepressants and the Patient with Suicidal Ideation
A. Prozac and Suicidal Ideation
1. Woulfe v. Eli Lilly & Co.
2. Espinoza v. Eli Lilly & Co.
3. Cassidy v. Eli Lilly & Co
B. Paxil and Suicidal Ideation
1. Dolin v. GlaxoSmithKline
C. Antidepressant and Increased Suicidality in Pediatrics
1. Schilf v. Eli Lilly & Co.
20.5 Broken Heart Syndrome: Tako Tsubo Cardiomyopathy Associated with Use of Antidepressants
20.6 The Adverse Effects of Antidepressants and the Duty to Warn
A. Docken v. Ciba-Geigy
B. Stebbins v. Concord Wrigley Drugs, Inc. et al.
C. Morgan et al. v. Wal-Mart Stores, Inc.
D. Kampmann v. Mason
E. Cottam v. CVS
20.7 Antidepressants and Alcohol
A. Kirk v. Michael Reese Hospital
B. Hand v. Krakowski
20.8 Selective Serotonin Reuptake Inhibitors and the Serotonin Syndrome
20.9 Hepatic Cytochrome P450 Drug Interactions and Cyclic Antidepressants
20.10 Antidepressants and Herbal Agents Drug Interactions
20.11 Serzone and Liver Disease
20.12 High Blood Pressure Associated with Venlafaxine Use
20.13 SSRI use and Birth Defects
20.14 Bupropion XL and Seizures
20.15 The Pharmacist's Role
20.16 The Omnibus Budget Reconciliation Act
20.17 How Safe is it to Buy Prescription Medications Over the Internet?
20.18 In a Perfect World
20.19 Summary and Conclusions
References
Chapter 21: Contrast Media Neurotoxicity Following Myelography
Stephanie E. Tedford, Ph.D., and James T. O'Donnell, Pharm.D., M.S., FCP
21.1 Introduction
21.2 Case Reports
A. Case I Intrathecal Iopamidol
B. Case II Intrathecal Iothalamate
21.3 Discussion
A. Mechanisms for cerebral (neurotoxic) injury
B. Contrast-induced neurological and cognitive deficits
C. Contrast-induced visual and auditory impairment: Further evidence for cerebral insult to cortical brain structures
21.4 Summary and Conclusions
References
Chapter 22: Fetal Drug Exposure
Damani Parran, Ph.D., MBA, DABT, James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D.
22.1 Introduction
22.2 Critical Periods of Human Development and Susceptibility
22.3 Special Considerations of Drug Exposure during Pregnancy
22.4 Historical Human Developmental Toxicants
A. Thalidomide
B. Ethanol
C. Diethylstilbestrol
D. Retinoids
E. Cocaine
22.5 Developmental Toxicity of Prescription Drugs
A. Valproic Acid
B. Phenytoin
C. Warfarin
D. Benzodiazepines
22.6 Additional Prenatal Environmental Influences
A. Malnutrition
B. Poverty
C. Emotional State
D. Mother's Age
E. Infections and Diseases
22.7 FDA Pregnancy Categories for Prescription Drug Labeling; Final Rule
22.8 Analyses of Litigated Cases Alleging Fetal Drug Injury
A. Effects of Methadone and Smoking on the Fetus
B. Effects of Lisinopril on Fetus - Defense of Causation
22.9 Summary and Conclusions
References
Chapter 23: Geriatric Medication Misadventures
Rodney G. Richmond, M.S., Pharm.D., BCGP, FASCP and James C. Norris, Ph.D., DABT, ERT
23.1 Introduction
A. Outpatient Medication Use
B. Hospital Medication Use
C. Long-Term Care Medication Use
23.2 Altered Clinical Response to Drugs
A. Pharmacokinetics
B. Pharmacodynamics
23.3 Preventable Drug-Related Problems
A. Polypharmacy
B. Transitions of Care
C. Inadequate Monitoring
D. Potentially Inappropriate Medication Use
23.4 Legal Cases Application
23.5 Summary and Conclusions
References
Chapter 24: Medication Errors
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, R.Ph. and James J. O'Donnell III, M.S., Ph.D.
24.1 History and Overview
24.2 Medication Errors in Epidemic Proportions
24.3 Types of Medication Errors
A. Enhancing Healthcare Team Outcomes
B. Improving Reporting of Medication Errors
24.4 Medication Use Process
24.5 System Errors
24.6 Which Drugs are Most Often Involved in Medication Errors?
24.7 Prevalence of Medication Errors
24.8 Vaccine Errors
24.9 How has Modern Research Improved Therapeutics and Reduced Drug-Related Morbidity? Pharmacogenomics
24.10 Systems for Medical Error Prevention
A. Electronic Prescribing (E-prescribing)
B. When Electronic Prescribing is Unavailable
C. Effective Drug Monitoring Systems
D. The Importance of Continuing Education
E. Reporting All Adverse Drug Events
24.11 Summary and Conclusions
References
Chapter 25: Anticoagulants: Therapeutics, Risks, And Toxicities
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D., Stephanie E. Tedford, Ph.D.
25.1 Introduction
25.2 Summary of Anticoagulant Therapy
A. Definition
B. Use
1. Treatment of coronary heart disease
2. Warfarin and dabigatran
3. Treatment of thrombogenesis
25.3 Limitations of Current Therapy
A. Heparin
B. Low Molecular Weight Heparin (LMWH)
C. Heparin-Induced Thrombocytopenia (HIT)
1. Pathogenesis of the autoimmune response
2. Pathogenesis of the prothrombotic state
3. Clinical presentation of HIT
4. Diagnosis
a. Dismissing HIT
b. Diagnosing HIT
2. Two Approaches: class and titer
5. Treatment of HIT
a. Fondaparinux
b. Re-exposure to heparin
6. Conclusion HIT and HITT
D. Warfarin
25.4 Monitoring Warfarin Oral Anticoagulation
25.5 Alternatives to Warfarin - DOACs
A. Pradaxa (Dabigatran) vs. Warfarin
B. Direct Oral Anticoagulation (DOAC) Therapies
C. DOAC reversal agents
D. Antiplatelet Therapy
25.6 Summary and Conclusions
References
Part III: PHARMACISTS, PHARMACY AND PHARMACY PRACTICE
Chapters 26 - 33
Chapter 26: Pharmacy Practice, Managed Care, And Manufacturers
F. Randy Vogenberg R.Ph., Ph.D. and Rita Marcoux R.Ph., MBA
26.1 Introduction to Pharmacy and the Related Managed Health Care Environment
26.2 Pharmacists as Health Care Professionals: Training, Support Staff, and Life-long Learning
A. Registration, Certifications, Credentialing, Colleges Of Pharmacy, And Accreditation Matters For Pharmacy Professional Staff
26.3 Practice Sites: Inpatient, Ambulatory/Community, Specialty, Long Term Care, and Other (compounding, nuclear)
A. Practice settings, Practice site Certification, Pharmacist practice versus the Business of pharmacy, Credentialing, and Accreditation matters
26.4 Issues for Pharmacy Practice, Insurance, and Managed Care In the Near Future
A. The landscape of Practice Sites and Changing Business of Health Landscape
26.5 Current and Near Future Issues for Pharmacists
A. Landscape of Pharmacy Practice, The Changing Professional Marketplace
26.6 Pharmaceutical Manufacturer Through Wholesaler and Distribution Supply Chain
26.7 Manufacturers: Traditional and Innovative Segments
A. Non-Biologic Medications
B. Research-Intensive, Biologics, Gene, and Generic Segments
1. Biologic Medications
26.8 Pharmaceutical Manufacturer Customers
A. Organization and Operations
B. Other Targeted Customer and Class of Trade Segments
C. Contracting and Change in the Pharmaceutical Industry
26.9 Health Care Industry Changes in the Near Future
26.10 Summary and Conclusions
References
Chapter 27: The Pharmacist's Utilization of the National Patient Safety Goals to Contribute to Safe and Effective Medication Use
Jennifer Splawski, Pharm.D., MS, BCPS and Heather Minger, Pharm.D., BCPS
27.1 Introduction
A. Overview of 'The Goals'
27.2 Goal 3 and the Pharmacist's Role
A. NPSG.03.05.01 relating to Anticoagulation
1. Introduction
2. Warfarin Overview
3. Patient monitoring
4. Patient Education
5. Direct Oral Anticoagulant
6. Anticoagulation Reversal Overview
7. Anticoagulation Reversal Programs
8. Patient Education
B. NPSG.03.06.01 relating to Reconciling Medication Information
1. Introduction
2. The Process of Medication Reconciliation
3. Improved Accuracy
4. Decreased Mortality
5. Allergy Identification
6. Discharge Medication Reconciliation
7. Utilization of the Pharmacist Extenders in Medication Reconciliation
27.3 Summary and Conclusions
References
Chapter 28: Pharmacist Malpractice and Liability
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN and James J. O'Donnell III, M.S., Ph.D.
28.1 Introduction
28.2 The Science of Risk Management
28.3 Claims Studies
The Pharmacists Mutual Claims Study
CNA Claims Study (CNA/HPSO)
A. CNA Database and Methodology
B. Most Common Categories of Errors
C. Claim Analysis by Insurance Source & Licensure Type: Pharmacists v. Technicians
D. Factors Affecting Wrong Drug Dispensing Errors
E. Drugs Involved in Claims
F. Most Common Error: Wrong Drug
G. Wrong Drug Strength
H. Wrong Directions
I. Wrong Route of Administration
J. Lack of Drug Review
K. Counseling: A Powerful Weapon Against Liability
L. Non-Bodily Injury
M. Miscellaneous Errors
N. Wrong Directions
O. Lack of Drug Review
P. Avoiding Errors and Malpractice
28.4 Specific Pharmacist Malpractice Case Reports / Topics
A. Duty to Warn?
B. Wrong Drug
C. Quotas and Metrics: Contributing to the Problem?
D. Controlled Substances Violations by Pharmacists
E. Methotrexate (MTX) errors
28.5 Pharmacists Need to do the Right Thing
28.6 Steps Toward a Better Outcome
28.7 Summary and Conclusions
References
Chapter 29: Regulation of Pharmacy Practice
Ned Milenkovich, Pharm.D., J.D.
29.1 Introduction
29.2 Licensure of Professional Activities
A. Boards of Pharmacy - A Closer Look
B. National Association of Boards of Pharmacy
29.3 Practice Standards
A. Legally Circumscribing Pharmacy Practice
29.4 Licensure Process to Practice Pharmacy
A. Licensing
B. Licensing of Pharmacists
29.5 The Different Types of Pharmacy Licenses
A. Disciplinary Actions
B. Causes of Disciplinary Action
C. Practice Focus on Licensure
D. Ongoing Professional Education
E. Support Personnel
29.6 Federal Drug Laws
A. Obra '90
B. Medicare
C. Medicare Part D
D. Medicaid
E. Prescription Drug Coverage
F. Fraud, Waste and Abuse
G. 340b Drugs
H. Pharmacy Compounding
I. FDA Rems
J. DEA
29.7 Pharmacy Practice: Putting it Together
A. Pharmacy Practice: An Ongoing Progression
B. Collaborative Practice Agreements
C. Drug Utilization Review (DUR)
D. Other Mandates Impacting Pharmacy Practice Quality Assurance Regulations
E. Health Insurance Portability and Accountability Act Of 1996, As Amended
Chapter 30: Emergency Department Pharmacist
Victor Cohen, B.S., Pharm.D., BCPS, CGP, Samantha P. Jellinek-Cohen, Pharm.D., BCPS, CGP, Megan Musselman Pharm.D., M.S., BCPS, BCCP
30.1 Introduction
30.2 Epidemiology of Drug Injury and Contributing Risk Factors
A. Contributing Risk Factors
30.3. Etiology and Sources of Drug Injury in the ED
30.4 Clinical Pharmacy in the ED: A Historical Perspective
30.5 The ED Pharmacist Plays a Dual Role at Maimonides Medical Center
30.6 The ED Pharmacist: A Sub-specialist in Emergency Medicine
A. Training and Education
B. Certification
30.7 The ED Pharmacist as a Generalist
30.8 The ED Pharmacist Ensuring Optimal Continuum of Care
A. The ED and Infectious Diseases
B. The ED Pharmacist and the Ambulatory Care Interphase
C. The ED Pharmacist and Transitions of Care (TOC)
1. Medication admission notes in the ED
D. The ED Pharmacist as a Clinical Toxicology Consultant
E. The ED Pharmacist and the Cardiology Interface
F. The ED Pharmacist and Neurological Emergencies
G. The ED Pharmacist and Pulmonary Emergencies
H. The ED Pharmacist and Public Health Services in the ED
30.9 Building Layers of Defense Against Drug Injury
A. Detecting and Preventing Drug Injury in the ED
B. The ED Pharmacist and Community Surveillance for Adverse Drug Reactions
30.10 Pharmacy Practice in the ED: Pharmacotherapy Specialty
30.11 Summary and Conclusions
References
Chapter 31: Pharmacy Case Law Review
Roger N. Morris, R.Ph., J.D., and William J. Stilling, R.Ph., M.S., J.D.
31.1 Administrative Law
A. Due Process-Pharmacist Licensure
1. Berjikian, et al. v. Franchise Tax Board et al., No. CV 13-06301 DDP, 2015 WL 1185472 (C.D. Cal. March 12, 2015)
31.2 Antitrust
A. State Regulatory Boards Immunity
1. North Carolina Bd. of Dental Examiners. v. Federal Trade Commission, 135 S. Ct. 1101 (Feb. 25, 2015)
31.3 Civil Procedure
A. Spoliation of evidence-Pharmacy's Duty to Maintain Evidence of Misfill
1. Burton v. Walgreen Co., 2015 WL 4228854 (D. Nev. July 10, 2015)
31.4 Conscientious Objection
A. Emergency Contraception
1. Stormans, Inc. v. Wiesman, 794 F.3d 1064 (9th Cir. 2015)
31.5 Controlled Substances
A. Duty to Verify DEA Registration
1. Farmacia, Yani, 80 Fed. Reg. 29,053 (May 20, 2015)
2. JM Pharmacy Group Inc., d/b/a/ Farmacia Nueva and Best Pharma Corp., 80 Fed. Reg. 28,667 (May 19, 2015)
B. Constitutionality
1. McFadden v. United States, 135 S. Ct. 2298 (June 18, 2015)
31.6 Criminal
A. Violations of Pharmacy Law Applied to Non-pharmacists
1. Moore v. State of Florida, NO. 1D14-3527, 2015 WL 4464689 (Fla. Dist. Ct. App. July 21, 2015), reh'g denied (Sept. 1, 2015)
B. PMP Records
1. Lundy v. State, 26 N.E.3d 656 (Ind. Ct. App. Feb. 20, 2015)
C. Second Degree Murder
1. U.S. v. Barry J. Cadden, et al., 2014 WL 7151586 (D. Mass. Dec. 16, 2014)
31.7 Defamation
A. Physician against Pharmacist
1. LeFrock v. Walgreen Co., 77 F. Supp.3d 1199 (M.D. Fla. Jan. 16, 2015)
B. Duty to Fill
1. Kadambi v. Express Scripts, 2015 WL 475373 (N.D. Ind. February 5, 2015)
31.8 Employment
A. Discrimination (Pregnancy)
1. Torres-Skair v. Medco Health Solutions, Inc., 595 F.App'x 847 (11th Cir. Dec., 4, 2014)
B. Employment at Will
1. Hoven v. Walgreen Co., 751 F.3d 778 (6th Cir. June 2, 2014)
C. Americans with Disability Act
1. Stevens v. Rite Aid Corp., et al., 6:13-cv-00783 (N.D.N.Y., September 23, 2015)
D. Overtime Class Action
1. Baugh v. CVS Health, et al., 2:15-cv-00014 (E.D. Penn., July 27, 2015)
E. Medical Marijuana
1. Coats v. Dish Network, 350 P. 3d, 849 (Colo. June 15, 2015)
31.9 Fraud and Abuse
F. False Claims
1. United States v. Express Scripts, Inc., 602 F. App'x 880 (3rd. Cir. Feb. 20, 2015)
G. False Claims-Generic Substitutions
1. Doe v. Houchens Indus., Inc., No. 1:13-CV-00196-RLY, 2015 WL 133706 (S.D. Ind. Jan. 9, 2015)
H. False Claims & Anti-Kickback Statute
1. U.S. ex rel. Kester v. Novartis Pharm. Corp., No. 11 CIV. 8196 CM, 2015WL 1650767 (S.D.N.Y. Apr. 10, 2015)
I. Consumer Fraud
1. City of Chicago v. Purdue Pharma L.P., 2015 WL 2208423 (N.D. Ill. May 8, 2015)
31.10 Negligence
A. Duty to Provide Medication
1. Davies v. Virginia CVS Pharmacy, LLC, et al., 7:14-CV-00175, 2014 WL 6460787 (W.D. Va. Nov. 17, 2014)
B. Duty Not to Dispense
1. Oleckna v. Daytona Disc. Pharmacy, 162 So. 3d 178 (Fla. Dist. Ct. App. 2015)
31.11 Privacy
C. Patient Privacy-Vicarious Liability
1. Walgreen Co. v. Hinchy, 25 N.E.3d 748 (Ind. Ct. App. Jn. 15, 2015) reh'g of, 21 N.E.3d 99 (Ind. Ct. App. Nov. 14, 2014)
D. Text Messages
1. Thompson v. CVS Pharmacy, Inc., 6:204-cv-02081 (M.D. Fla. Dec. 19, 2014)
E. Robocalls
1. Kolinek v. Walgreen Co., 2014 WL 3056813, (N.D. Ill. July 7, 2014)
31.12 Product liability
A. Learned Intermediary Doctrine
1. Watts v. Medicis Pharm. Corp., 342 P.3d 847 (Ct. App. 2015), review granted in part (Sept. 22, 2015)
B. Product Liability (applicability to pharmacists)
1. Randol Mill Pharmacy v. Miller, 465 S.W.3d 612 (Tex. 2015), reh'g denied (Sept. 11, 2015)
Chapter 32: Pharmacy Compounding - Patient Injury and Regulatory Compliance
Willis C. Triplett, Pharm.D.
32.1 Introduction
32.2 Compounding Trends and Driving Forces
32.3 Optimizing the Regulatory Balance Between "Manufacturing" versus "Compounding"
32.4 Investigations, Indictments, Convictions, and Acquittals after the Fungal Meningitis Outbreak
32.5 Memorandum of Understanding (MOU)
32.6 U SP, NABP, and the State Pharmacy Regulatory Authorities
32.7 Physician and Medical Office Compounding
32.8 Compounding "Center of Excellence" ("COE") and the Quality Assurance Paradigm Shift
32.9 Conclusions and Forecasts Regarding Patient Injury from Healthcare Compounding
32.10 Recommended Readings
CHAPTER 33: Compounding Pharmacy Fraud and Unethical Practices
James T. O'Donnell, Pharm.D., M.S., FCP
33.1 Introduction
33.2 Criminal Prosecutions of Pharmacy Compounders
33.3 Over-Prescribing and Over-Charging of Compounded Drugs
A. Department of Justice News Releases
B. News Reports in Newspapers
33.4 Not Yet Criminal? Insurance Companies Fighting Back
A. No-Fault Pain Compounded and Topical Pain Product
B. Report Challenging the Pricing and Efficacy of a Compounded Pain Cream Prescription
C. Ingredients and Costs of Pain Cream
33.5 General Discussion - Compounded Pain Topical Creams
A. Evidence of Efficacy?
B. Expensive Ingredients
33.6 Ingredients Review of Efficacy and Mechanism of Action
A. Diclofenac
B. Menthol (Methyl Salicylate)
C. Lidocaine
1. Lidocaine Topical Toxicity
D. Amitriptyline
E. Cyclobenzaprine
F. Dimethylsulfoxide (DMSO)
33.7 Global Opinions for the Prescription CPTM formula 8-NC Claim Challenge
33.8 Discussion and Further Bases of Opinions
33.9 Overbilling of Topical Diclofenac Gels, Lidocaine Creams and Ointments and Patches
A. Diclofenac 3" (Solaraze)
B. Lidocaine Topical Commercial Products
33.10 Recommendations
33.11 Summary and Conclusions
References
Part IV: FORENSIC AND TOXICOLOGY ISSUES
Chapters 34 - 42
Chapter 34: Alcohol
James T. O'Donnell, Pharm.D., M.S.. FCP and James J. O'Donnell III, M.S., Ph.D.
34.1 Introduction
34.2Alcohol Injury Epidemiology
34.3 Alcohol Intoxication Effects in Litigation
34.4 Differences between Civil litigation involving alcohol from Criminal/DUI
34.5 Settings for Alcohol Related Civil Litigation
A. Employment
34.6 Police Activities
A. Police Pursuit
B. Excessive Police Force
C. Alcohol Effects on Aggression and Judgment
34.7 Motor Vehicle Collisions
A. Vehicle/Vehicle
B. Motorcycle Cases
C. Boating
D. Vehicle/ Pedestrian
34.8 Alcohol and Falls
A. Stairs - no alcohol test - fall down bar stairs
B. Stairs - Residential Stairs Fall -Adjustment of Calculated BAC due to Morbid Obesity
C. Tripped on Threshold - Sued Condominium Association
34.9 Dram Shop (Bar Liability for Serving Intoxicated Persons)
34.10 Biomarkers for Alcohol
A. Family Law
B. False Positive Alcohol Biomarkers in Diabetes
34.11 Miscellaneous Topics Reports
A. Retrograde Extrapolation (See also legal cases Floyd and Cuellar earlier in this chapter.
B. Appellate Court reverses Trial Court Barring of BAC
34.13 Summary and Conclusions
References
Chapter 35: Cocaine
James C Norris, Ph.D., D.A.B.T and Rodney G Richmond, R.Ph., MS, CGP, FASCP, FACFE
35.1 Historical Background
35.2 Medical Usages of Cocaine
35.3 Illegal Usage of Cocaine
35.4 Routes of Administration
35.5 Effects of Cocaine
35.6 Psychotic Disorders Induced by Cocaine
35.7 Addiction
35.8 Cognitive Deficits
35.9 Prenatal Cocaine Exposure (PCE)
35.10 Violence
35.11 Tolerance
35.12 Withdrawal or Abstinence Effects
35.13 Mechanisms of Action
35.14 Metabolism
35.15 Blood Levels
35.16 Urine Levels
35.17 Impairment
35.18 Associated Deaths with Cocaine Usage
35.19 Summary and Conclusions
References
Chapter 36: Marijuana: Pharmacology, Toxicology and Forensic Issues
Stephanie E. Tedford, Ph.D., James T. O'Donnell PharmD, MS, FCP, and James J. O'Donnell III MS, Ph.D.
36.1 Introduction
36.2 Federal Law vs. State Law
A. Harrison Narcotics Tax Act
B. Comprehensive Drug Abuse Control and Prevention Act
C. Marijuana Drug Laws at the State Level
D. Legalization
E. Decriminalization
F. Marijuana Policy Project
36.3 Controlled Prescription and Distribution of Medical Marijuana
A. Medical Conditions Approved for Treatment with Medical Marijuana
B. Marijuana and Epilepsy
C. Marijuana and Endometriosis
36.4 Pharmacological Properties of Marijuana
A. Active Compounds and Overview of Pharmacology
B. Variability in Marijuana Regulation and Content Uniformity
C. Routes of Administration
D. Pharmacokinetics - Time Course of THC and Metabolites
E. Pharmacodynamics
F. Vaping vs. Traditional Smoking of Cannabinoids
G. Traditional Smoking vs. Ingestion of Cannabinoids
H. Pharmacokinetics Applications: Timing of the Peak Euphoric Effect
I. Bioavailability
1. Is There a Good Model for Marijuana Ingestion?
2. Overall Advantages of the Oromucosal Route?
3. Can the Effects After Ingestion of Marijuana be Made More Objective?
36.5 Marijuana Safety
A. Serious Adverse Effects
B. Risk of Psychosis
1. Drug-induced Psychosis: Potential Mechanisms
2. Vaping and Associated Risk for Psychosis
C. Pulmonary Function
D. Risk of Addiction
E. Effect on Brain Development
F. Long Term Behavioral Effects
G. Age of Onset of Use
36.6 Impact of Legalization
A. Hospital Resources
B. Driving Under the Influence of Drugs
C. Relationship of Marijuana Use and Co-Use with other Substances
36.7 Analysis and Testing for Marijuana Use
36.8 Scientific Data Relating to THC
A. Blood THC vs. Brain THC: Any Relationships?
B. Relationships Between Percent Plant-THC and Plasma-THC
C. Is There a Relationship Between Percent THC in the Smoked Cigarette and Plasma THC?
D. Relation Between Degree of "High" and Plasma THC
E. Occasional Marijuana Users vs. Practiced Users
F. Is THC the Only Psychoactive Cannabinoid?
G. Urine Testing for Cannabinoids: Clinical or Evidentiary Value?
H. Impairment and Marijuana: Laboratory and On-Road Driving Performance Data
I. Hospital and Provider Considerations
36.9 Forensic Case Reports
36.10 Summary and Conclusions
References
Chapter 37: Drug Evaluation and Classification Program: An Evidence-Based Analysis
Fran M. Gengo Pharm.D., FCP and Anna Mattle, Pharm.D., M.S.
37.1 Introduction
37.2 The 12 Steps of DRE Examinations
37.3 Scientific Evaluation of DRE Examinations
A. Step 2: Interview of Arresting Officer
B. Step 3: Preliminary Examination and Initial Pulse Measurement
C. Step 4: Eye Examination
D. Step 5: Divided Attention Tests
E. Step 6: Second Pulse Reading, Body Temperature, and Blood Pressure Measurement
F. Step 7: Eye Examination of Pupil Size in Various Lighting Conditions
G. Step 8: Assessment of Muscle Tone
H. Step 11: DRE Officer Opinion Statement
I. Step 12: Toxicology Sample
37.4 Literature Evaluations And Critiques Of Dre
37.5 Cannabis
37.6 Statistical Validity and Overall Strength of DRE Studies
37.7 DRE Support Literature
A. Bigelow et al. 1985 Study
B. Heishman et al. 1996 and 1998 Studies
C. Smith et al. 2002 Study
D. Shinar and Schechtman 2005 Study
E. Specific Identification of Drug Class by DRE Officers in Validation Studies
37.9 Summary
37.10 Summary and Conclusions
References
Chapter 38: Involuntary Intoxication
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D., William Vaughn, J.D.
38.1 Introduction
38.2 Legal Defense Considerations for a Violent Crime
38.3 Confirming That Drugs are Involved in a Violent Crime
38.4 Beyond Pharmacology: The Multifactorial Role of Drugs in Aggression and Violence
38.5 Association of Drugs with Aggression and Violence
38.6 Mechanisms of Drug-Induced Violence
38.7 Intoxication of Victim Defense
38.8 Summary and Conclusions
References
Chapter 39: Drug-Induced Aggression and Violence
Peter D. Anderson, Pharm.D., BCPP
39.1 Classification of Aggression
39.2 Causes of Aggression and Violence
A. Neurobiology of Aggression
B. Medical and Psychiatric Causes of Aggression
39.3 The Role of Drugs as a Cause of Violence
A. Introduction
B. Problems with the Literature
C. Specific Drugs or Drug Classes that cause aggression
1. Ethanol
2. Lysergic Acid Diethylamide
3. Phencyclidine and Ketamine
4. Anabolic Steroids
5. Insulin
6. Psychostimulants
7. Benzodiazepines
8. Selective Serotonin Reuptake Inhibitors
9. Varenicline
10. Environmental Chemicals
39.4 The Drug-Induced Insanity Defense
39.5 Summary and Conclusions
References
Chapter 40: Forensic Drug Testing Chapter
James J. O'Donnell III, M.S., Ph.D, and James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN
40.1 Introduction
40.2 Non-Regulated Drug Testing
40.3 Regulated Drug Testing
40.4 Voluntary Programs
40.5 Establishment of a Workplace Program
A. Written Policy
B. Employee Assistance Programs
C. Employee Awareness Training
D. Supervisor Training
E. Drug Testing
40.6 The Drug-Testing Process
A. Specimen Collection
B. Accessioning
C. Drugs to Be Tested
D. Screening Tests
E. Confirmation Tests
F. Reporting and Storage of Samples
G. Prevention Against and Detection of Drug Test Cheating
40.7 Additional Program Aspects
A. The Medical Review Officer (MRO)
B. Public Interest Exclusions (PIE)
C. Blind Performance Testing
D. Alcohol Testing
40.8 Special Drug-Testing Issues
A. Type of Matrix
1. Hair Testing
2. Saliva Testing
3. Sweat Testing
4. Blood
5. Urine
B. Alternate Sources of Drug Exposure
C. Amphetamine Testing Issues
D. Medical Use of Drugs
40.9 Legal Aspects of Workplace Drug-Testing
A. Constitutional Issues
B. State and Federal Mandates
40.10 Discovery: The "Litigation Package"
40.11 Case Reports
40.12 Summary and Conclusions
References
Chapter 41: Postmortem Redistribution and Interpretation of Drug Levels
Gourang P. Patel Pharm.D., M.Sc., BCPS, BCCCP, FCCM
41.1 Abstract
41.2 Introduction
41.3 Review of a Case File
41.4 Postmortem Considerations
A. Physiologic Changes in the Body After Death
B. Drug Characteristics
41.5 Analysis of Drug Level Information
41.6 Summary and Conclusions
References
Chapter 42: Addiction as Mitigation
Barry D. Hargan, M.S., MHA and James T. O'Donnell, Pharm.D., M.S., FCP
42.1 Introduction
42.2 Clinical Variables Which Contribute to the Onset of Addiction
A. Genetic Predisposition
B. Learned Behavior
C. Psychopathological Exposure
42.3 Substance/Medication-Induced Mental Disorder
A. Executive Summary of Opinion
B. Neurotoxicity Mechanisms of Alcohol and Anabolic Steroids in the Developing Brain
C. Anabolic Steroid Effects on Brain Structure and Function
D. Translational Impact - what does this mean to a teenager abusing large amounts of alcohol and steroids?
E. Clinical and Practical Applications of the Basic Neuroscience
F. Behavioral Abnormalities Associated with Anabolic Steroid Use
G. Defendant's Alcohol and Anabolic Steroid Use
1. Alcohol
H. Expert Opinions Regarding Substance-Induced Brain Damage Affecting Behavior
42.4 The Simplified Version of Neurobiology and the Addicted Brain
42.5 Cocaine
42.6 Expert Testimony Concerning Addictive Disorders
A. Role of the Addictions Expert
B. Some Testimony Experiences and the Limits of Opinions
C. Preparation
42.7 Additional Considerations Concerning Addiction Mitigation
A. Neuropsychological Evaluation
42.8 Summary and Conclusions
References
Chapters 1 - 9
Chapter 1: FDA and Drug Approval Process
Megan Walter, Pharm.D. and CDR Lindsay Wagner, Pharm.D., BCPS
1.1 Introduction
1.2 The New Drug Development Process
A. Discovery and Preclinical Research
B. Clinical Research
C. Investigational New Drug Application
D. Phases of Clinical Studies
E. Expanded Access Programs
F. Right to Try
1.3 New Drug and Therapeutic Biologic Application Process
A. New Drug Applications and Biologic License Applications
B. Fundamentals of NDA and BLA Submissions
C. NDA Classifications
1.4 FDA Review
A. Expedited Development and Review Programs
1. Accelerated Approval
2. Priority Review
3. Fast Track
4. Breakthrough Therapy
B. Labeling Review
1. Physician Labeling Rule (PLR)
2. Pregnancy and Lactation Labeling Rule (PLLR)
3. Additional FDA-Approved Patient Labeling
C. Risk Evaluation and Mitigation Strategies
D. Advisory Committee Meetings
1.5 The Generic Drug Approval Process
A. Abbreviated New Drug Applications
B. ANDA Approval
C. Generic Drug User Fee Amendments
1.6 Biosimilar Pathway
1.7 Over-the-Counter Drug Products
1.8 Postmarketing Surveillance
A. Adverse Event Reporting
B. FDA Adverse Event Reporting System
C. Post Marketing Requirements and Commitments
D. Sentinel Network
E. Drug Safety Oversight Board
1.9 Applicable Statutes and Implementing Regulations
A. Food and Drug Acts - 1906
B. Food, Drug and Cosmetic Act - 1938
C. Durham-Humphrey Amendment - 1951
D. Kefauver-Harris Amendment - 1962
E. Orphan Drug Act - 1983
F. Drug Price and Competition and Patent Term Restoration Act - 1984
1. Revision of New Drug Application Regulations - 1985
2. Revision of Investigational New Drug Application Regulations - 1987
3. Treatment Use of Investigational New Drugs - 1987
G. Prescription Drug User Fee Act (PDUFA) - 1992
H. FDA Modernization Act (FDAMA) - 1997
I. FDA Amendments Act (FDAAA) - 2007
J. Food and Drug Administration Safety and Innovation Act (FDASIA) - 2012
K. The Drug Quality and Security Act (DQSA) - 2013
L. 21st Century Cures Act - 2016
M. Food and Drug Administration Reauthorization Act (FDARA) - 2017
N. Coronavirus Aid, Relief, and Economic Security Act (CARES Act) - 2020
1.10 Conclusion
1.11 Glossary of Terms
References
Chapter 2: The Front Lines of Clinical Research: The Industry and Ethical Considerations
Jonathan Young, Ph.D.
2.1 Introduction
2.2 Clinical Trial Service Providers
A. Food and Drug Administration
B. Clinical Trial Sponsor
C. Contract Research Organizations
D. Study Monitors
2.3 Clinical Trial Site
A. Site Management Organizations
B. Institutional Review Boards
2.4 The Evolution of Ethical Principles in Clinical Research
A. Respect for Persons
B. Beneficence
C. Justice
D. How the Investigator Applies Ethical Principles
2.5 Regulations Governing Institutional Review Boards
A. What Institutional Review Board Members Should Know about Clinical Research
B. What Institutional Review Board Members Should Know about Their Responsibilities
2.6 What the Site Should Know about Institutional Review Boards
A. What Research Requires Institutional Review Board Approval and Oversight
B. Requirements of an Investigator for Institutional Review Board Research Approval
2.7 Risks-vs.-Benefits Analysis: The Human Advocate
A. Identifying and Assessing the Risks
B. Minimal Risk vs. Greater-than-Minimal Risk
C. Vulnerable Populations and Minimal Risk
D. Determining Whether Risks Are Minimized
E. Assessing Anticipated Benefits
F. Determining Whether Risks Are Reasonable
G. Continuing Review and Monitoring of Data
2.8 Informed Consent: Not Just a Document
A. Elements of an Informed Consent
B. Additional Required Elements
2.9 Research Participants
2.10 Industry Trade Organizations and Support Services
2.11 Summary: Ethical Dilemmas in Clinical Research
References
Chapter 3: Search and Analysis of the Food and Drug Administration's FDA Adverse Event Reporting System (FAERS)
Paul N. Danese, Ph.D.
3.1 Introduction
3.2 Background
A. Small Clinical Trial Populations
B. Narrow Patient Demographics
C. Restricted Co-Administration of Medications
3.3 History of the FDA's Drug Safety Surveillance Systems
3.4 Submission of Adverse Event Reports to the FDA
A. Mandatory Reports
B. Voluntary Reports
3.5 Adverse Drug Reaction Information Captured by FAERS
3.6 Searching FAERS Data to Identify Possible Safety Problems
A. Statistical Methods to Identify Drug Safety Signals
B. Dechallenge and Rechallenge Data and Causality
C. Identifying Drug-Drug Interactions
D. Timelines and Deadlines of Adverse Event Reporting
3.7 The Food and Drug Administration's Use of FAERS in Regulatory Decisions
A. Boxed Warnings
B. Other Changes to a Medication's Prescribing Information
C. Determinations that No Action is needed and Continuing Investigations
3.8 Limitations of FAERS
A. Lack of Demonstration of Causality for Individual Reports
B. Extensive Under-reporting
C. Reporting Biases
D. Lack of Comparator Populations (Lack of a Denominator)
3.9 Search and Retrieval of Adverse Event Reports from the FDA's FAERS
A. Raw Data Files
B. FDA Public Dashboard
C. FOIA Requests
D. Commercial Vendors
3.10 Other FDA Adverse Event Reporting Systems
A. VAERS
B. MAUDE
C. Sentinel Initiative
3.11 Summary and Conclusions
References
Chapter 4: The Safety of Medicines: PharmacoVigilance, PharmacoSurveillance, PharmacoEmpowerment?
David Healy, M.D.
4.1 RxISK.org
4.2 Antidepressants: Data Based or Evidence Based?
4.3 Access to Adverse Event Data
4.4 RCTs and Adverse Events // Ghost Writers
4.5 RCTs & Primary Endpoints
4.6 Post 1962: Confounding & Causality
4.7 Pharmacovigilance
4.8 RxISK.org and Pharmacovigilance 1.0
4.9 Pharmacosurveillance
4.10 TaperMD and Pharmacovigilance 2.0
4.11 Summary and Conclusions
References
Chapter 5: Important Code of Federal Regulations Applicable to Drug Product Liability Suits
S. Albert Edwards, Pharm.D., RAC, FRAPS
Chapter 6: The Regulation of Drug Product Information to Consumers
Frank J. Ascione, Pharm.D., MPH, PhD
6.1 The Historical Development of Food and Drug Administration (FDA)'s Regulatory Role
A. Early phase (prior to 1906): No significant government intervention
B. Early Regulatory Phase (1906-1938): Minimal Government Control
C. Greater Government Control (1938-1961)
D. Debating Increased Consumer Access to Drug Product Information (1962-1983)
E. Expanding Information Available to Consumers (1983-present)
6.2 Current State of Prescription Drug Product-Related Information Provided to Consumers
6.3 Evolution of Drug Advertising to US Consumers (DTCA)
A. Emergence of DTCA (1981-1982)
B. Voluntary Moratorium Period of DTCA (1983-1985)
C. Establishment of DTCA Regulations (1985-1999)
6.4 Current State of Direct-to-Consumer Advertising
A. Advantages and Disadvantages of DTCA
6.4 Summary and Conclusions
References
Chapter 7: The Role of Investigative Journalism in Improving Drug Safety
Martha Rosenberg
7.1 Introduction
7.2 Direct-To-Consumer Advertising Increased with Covid
A. Unbranded DTC Advertising
B. Industry Funded Disease Awareness Groups
C. Encouraging Victim Politics
7.3 The Opioid Epidemic
A. Growing an Untapped Market
B. Aggressive Opioid Marketing
C. Fostering Opioid Addiction
D. Pill Mills and Addiction Medicine
E. Opioid Lawsuits Surface
F. Lack of Opioid Efficacy and Serious Side Effects
G. Paying for the Opioid Epidemic
7.4 Effective Hepatitis C Drugs Debut
A. Lawmakers Investigate Hep C Prices
B. Aggressive Hep C Marketing
C. Screening as a Hep C Sales Tool
D. Hepatitis C Safety Signals Emerge
7.5 Asthma Drug Safety Signals
A. Xolair Leaves a Trail of Questions
B. More Improper Xolair Marketing
C. Safety Signals Surface with Xolair and a Lawsuit is Dismissed
7.6 Long-Acting Beta Agonists
A. Glaxosmithkline Settlement included a Laba
7.7 Safety Questions About Leukotriene Receptor Antagonists
A. Parents Report LTRA Side Effects
B. LTRA Safety Signals Emerged Early
C. Patients and Parents Fight Back
D. Black Box Added to Singulair
7.8 Baldness Treatments Become Popular and Controversial
A. Finasteride Side Effects Create Concern
B. Medical Literature Confirms Finasteride Side Effects
C. FDA Adds Warnings to Finasteride
D. Finasteride User Speaks Out
E. No Satisfying End for Finasteride Users
7.9 Biologic Drugs
A. Tumor Necrosis Factor (Tnf) Blockers
B. Tnf Blocker Risks
7.10 Other Popular Medications Come Under New Scrutiny
A. N-Nitrosodimethylamine (NDMA
) Found in Medicines
1. Zantac Taken Off Shelves
2. NDMA Also Found in Metformin
7.11 Popular Stimulant Drugs Reveal Risks
A. Risks Seen with Modafinil
B. Fetal Risks Seen with Modafinil and Armodafinil
C. European Union Sues Provigil Makers
7.12 Fetal Risk Seen with NSAIDs
7.13 Bisphosphonates Continue to Present Risks
7.14 SSRI Antidepressants Linked to New Risks
A. SSRI Bone Thinning
B. SSRI Addictive Potential
7.15 Belviq, A Diet Drug Withdrawn from Market
7.16 Sleeping Pills Given Boxed Warnings
A. Public Figures on Sleeping Pills Make the News
B. Other Sleeping Pill Risks
7.17 Risks Associated with Fluoroquinolone Antibiotics
A. Fluoroquinolones Warnings Continue
B. Hormone Therapy Still Linked to Risks
C. Beware of Testosterone Marketing
D. New PPI Questions
References
Chapter 8: Evaluation of Causation in Drug Injury Cases
Donald H. Marks, M.D., Ph.D. and James T. O'Donnell, Pharm.D., M.S., FCP
8.1 What is Causation?
8.2 Importance of Establishing Causation
8.3 Definitions
8.4 Degree of Adverse Effects Relate to Intervention
8.5 Methodology to Investigate Causation
8.6 Structured Algorithms for Determination of Causation
A. Hill Criteria-Expanded Discussion
1. Strength of Association
2. Consistency of Results
3. Specificity
4. Temporal Relationship
5. Dose Response
6. Biological Plausibility
7. Biological Coherence
8. Experimentation
9. Analogy
8.7 Comments on the Individual Riddell Criteria for Causation,
8.8 Daubert and the Evolution of Causation,
8.9 Does Causation Need to be Established Before a Warning is Given?
8.10 What are the Qualifications needed to Give Expert Causation Opinions?
8.11 Case Reports Demonstrating Applications of Causation Principles
A. Case Report: Acyclovir Overdose - Pharmacist Recommended Overdose
B. Case Report: Challenging Cause of Death in a Malpractice Matter
C. Case Report: Determination of the Effects of Morphine in a Will Contest
D. Case Report: Proof of Drug-Induced Mental Changes in Complainant in Sexual Abuse Case
8.12 Summary and Conclusions
References
Chapter 9: General Principles of Pharmacology
James J. O'Donnell III, M.S., Ph.D., James T. O'Donnell, Pharm.D., M.S., FCP, and Vanessa Juettner, Ph.D.
9.1 Introduction
9.2 Basic Principles
A. Absorption
B. Lipid Diffusion
C. Determinants of Absorption
1. Lipid/aqueous partition coefficient and pH
2. Bioavailability
3. First pass effect
9.3 Routes of Administration
9.4 Extravascular Administration
A. Oral Administration
B. Rectal Administration
C. Other Routes of Administration
9.5 Intravascular Administration
9.6 Distribution
A. Diffusion
B. Volume of Distribution
C. Binding to Plasma Proteins and Cellular Constituents
D. Re-Distribution
E. Blood-Brain Barrier (BBB)
F. Placental Barrier
G. Therapeutic Range
H. Bioequivalence vs. Bioinequivalence
10.7 Drug Metabolism (Biotransformation)
A. Phase I Reactions
1. The families of human P450s
2. Induction of P450 enzymes
3. P450 Inhibition
B. Phase II Reactions
1. Metabolism of drugs to toxic products
9.8 Factors Affecting Drug Metabolism
A. Disease
B. Age
C. Gender
D. Genetic Factors
9.9 Drug Excretion
A. Urinary Excretion
1. Glomerular filtration
2. Tubular secretion (active secretion)
3. Tubular reabsorption
4. Effects of pH on urinary excretion of ionizable drugs
9.10 Pharmacokinetics
A. Introduction
B. Therapeutic Window and Therapeutic Index
C. Blood Levels for Narrow Therapeutic Index (NDI) Drugs
D. Kinetic Modeling
E. Drug Absorption and Elimination
1. Absorption rate
2. Elimination rate
3. Clearance (CL)
4. Area Under the Curve (AUC)
5. Elimination (k)
6. Elimination half-life
7. Steady state
F. Dosing
1. Loading dose
2. Maintenance doses (MD)
3. Example-dosage adjustment in renal impairment
G. Therapeutic Drug Monitoring (TDM)
H. Pharmacokinetics Summary
9.11 Drug Receptor and Pharmacodynamics
A. Agonists and Antagonists
B. Drug-Receptor Interactions
9.12 Dose Responses
A. Potency
B. Agonism and Antagonism
1. Partial agonists
9.13 Competitive Antagonism
9.14 Non-Competitive Antagonism
9.15 Summary and Conclusions
PART II: HIGH RISK DRUG THERAPIES RESULTING IN INJURY AND LITIGATION
Chapters 10 - 25
Chapter 10: Adverse Drug Reactions: Allergic Focus
James T. O'Donnell Pharm.D., M.S., FCP and James J. O'Donnell III, M.S., Ph.D.
10.1 Adverse Drug Reactions: How Large is the Problem? What Drugs are Involved? What are the Injuries?
A. Historical Perspective
B. Incidence of Adverse Drug Reactions
C. Food and Drug Administration Reporting Requirements
D. The "Seven Deadly Sins": Why Doctors Fail to Report Adverse Drug Reactions
E. Attitudes Toward Adverse Drug Reactions
F. Investigator Fraud
10.2 Classification of Adverse Drug Reactions
A. Categories of Adverse Drug Reactions
1. Type A reactions: Augmentation of the Pharmacological Response
2. Type B reactions: Bizarre (idiosyncratic)
10.3 Types of Drug Allergy and Hypersensitivity
A. The Nature of Drug Allergy
B. Dangerous Drug-Allergy Reactions
C. Drug Sensitivities Mimic Allergy Symptoms
D. Definitions of Allergic/Hypersensitivity Reactions
E. Idiosyncratic Reactions
F. Intolerance
G. Toxicity
H. Hypersensitivity Vasculitis
I. Predominantly Organ-Specific Reactions
J. Urticaria
K. Fixed Drug Eruptions
L. Photosensitivity Reactions
M. Generalized Exfoliative Dermatitis
N. Thrombocytopenia
O. Hemolytic Anemia
P. Agranulocytosis
Q. Treatment: Withdrawal of the Suspected Drug
R. Symptomatic Treatment
S. Prevention of Allergic Drug Reactions
T. Pseudoallergy
U. Angioedema
V. Hypersensitivity Reactions
10.4 Risk Factors, Drugs and Patients
A. Hypersensitivity Risk Factors
B. Identification of a Drug Allergy
C. Allergy to Antibiotics
D. Case Report: Cross-Allergenicity
10.5 Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
A. Fixed Drug Eruptions
B. Erythema Multiforme-Like Eruptions
Case Report: Lamictal Induced Stevens Johnson Syndrome
C. Fluoroquinolones
E. NSAIDs Cross Reactivity Case Report
F. Radiographic Contrast Media
G. Local Anesthetics
H. Anticonvulsants (AED)
10.6 Summary and Conclusions
References
Chapter 11: Drug Induced Falls
James T. O'Donnell Pharm.D., M.S., FCP and James J. O'Donnell III, M.S., Ph.D.
11.1 Introduction
11.2 The Definition of Fall
11.3 Epidemiology
11.4 Causes and Risk Factors
A. Physiological Risk Factors for Falls in the Elderly
B. Psychological Risk Factors
C. Medical Conditions
11.5 Medication-related Falls
11.6 Types of Medications that Increase the Risk of Fall
A. Centrally Active Medications
B. Benzodiazepines
C. Antipsychotics
D. Antihypertensives
1. Orthostatic Hypertension and Risk of Fall
E. Opioids
11.7 Marijuana
11.8 Alcohol
11.9 Hip Fractures
11.10 Polypharmacy
11.11 Fall Risk Assessment
11.12 Types of Assessments
11.13 Strategies for Fall Prevention in Institutionalized Settings
A. Screening
B. Addressing Risk Factors
1. Monitoring Patients
2. Environmental Interventions
3. Educational Programs
4. Reducing Fall Injury
C. Discharge Planning
D. Disseminating Evidence: Awareness and Intervention Work!
11.14 Summary and Conclusions
References
Chapter 12: Drug Induced Movement Disorders
Jadwiga Najib, B.S. Pharm.D., BCPS, and Meagan Bailey, M.D.
12.1 Introduction
12.2 Presentation
12.3 Agents Associated with Drug-Induced Movement Disorders
12.4 Risk Factors
12.5 Sequelae of Drug-Induced Movement Disorders
12.6 Theories of Causation
12.7 Drug-Induced Movement Disorders in Children and Adolescents
12.8 Drug-Induced Movement Disorders in the Elderly
12.9 Acute/Intermediate Drug-Induced Movement Disorders
A. Dystonia
1. Presentation
2. Implicated agents
3. Risks
4. Management
B. Ataxia
C. Bruxism
D. Neuroleptic Malignant Syndrome
E. Serotonin Syndrome
12.10 Chronic Drug-Induced Movement Disorders
A. Akathisia
1. Presentation
2. Case study: Trazodone-induced akathisia
3. Implicated agents
4. Other drugs
5. Risks
6. Management
B. Parkinsonism
1. Presentation
2. Case Study: Neuroleptic-Induced Parkinsonism
3. Implicated agents
4. Other drugs
5. Risks
6. Management
C. Myoclonus, Tremor, Tics, Asterixis
12.11 Persistent/Tardive Drug-Induced Movement Disorders
A. Tardive Dyskinesia
1. Presentation
2. Case Study: Neuroleptic induced oral buccal dyskinesia and akathisia
3. Implicated agents
4. Case Study: Metoclopramide induced oral buccal lingual dyskinesia
5. Risks
6. Management
B. Tardive Akathisia
C. Tardive Dystonia
1. Case Report: Neuroleptic induced cervical dystonia
D. Other Tardive Variants
12.12 Drugs Used for Movement Disorders
12.13 Monitoring
12.14 Clinical and Legal Issues in Psychiatry
12.15 Summary and Conclusions
References
Chapter 13: Acute Adverse Drug Events in Critical Care Emergency Department and Intensive Care Units
Gourang P. Patel, Pharm.D., M.Sc., BCPS, BCCCP, FCCM
13.1 Background
A. Epidemiology
B. Environment
13.2 High-Risk Medication-Related Events
A. Hypersensitivity Reactions
B. Cardiovascular Reactions
1. Blood pressure (BP)
2. Heart rate (HR)
3. Arrhythmias
C. Nephrotoxicity
1. Aminoglycosides
2. Amphotericin B
3. Intravenous contrast
D. Hypoglycemic Events
E. Infusion-Related Reactions
1. Extravasations
2. Propofol-related infusion syndrome (PRIS)
3. Intravenous N-acetylcysteine (NAC)
F. Reversal Agents
1. Protamine
2. Vitamin K
3. Naloxone
4. Flumazenil
13.3 Summary and Conclusions
References
Chapter 14: Nephrotoxic Drugs
Jason M. Kidd MD, Domenic A. Sica, M.D. and Todd W. B. Gehr, M.D.
14.1 Introduction
14.2 Framework of the problem
14.3 Basis for the kidney being susceptible to damage
14.4 Patient groups most susceptible to nephrotoxicity
14.5 Demographics of chronic kidney disease
14.6 Methods to assess renal function and/or damage
14.7 Level of renal function at which drug accumulation occurs
14.8 Nephrotoxic drugs
A. What constitutes prompt clinical action in the face of nephrotoxicity?
14.9 Nephrotoxicity scenarios
A. Lithium toxicity
B. Gentamicin toxicity
C. Dialysis-related issues
D. Drug Clearance in Relationship to Renal Failure
1. Case 1
2. Case 2
E. Angioedema with an ACE inhibitor
F. Fatal hyperkalemia with medications
G. Statin therapy and the development of myopathy
H. Nephrotoxicity related to checkpoint inhibitor use
14.10 Summary and Conclusions
References
Chapter 15: Drug Induced Liver Disease
James T. O'Donnell, Pharm.D., M.S., FCP, James J. O'Donnell III, M.S., Ph.D., Donald H. Marks, M.D., Ph.D., Paul Danese, Ph.D.
15.1 Introduction: The Problem of Drug-Induced Liver Disease
15.2 History of Adverse Drug Reactions
15.3 Overview of DILD, Epidemiology Risk Factors, Histopathology, and Diagnoses
A. Epidemiology of Drug Hepatotoxicity
B. Risk Factors
C. Histopathology
D. Diagnosis
15.4 Hepatic Drug Metabolism
15.5 FDA and DILD
15.6 Types of Liver Injury
A. Hepatitis
B. Massive Hepatic Necrosis (Fulminant Hepatitis)
C. Drug-induced Vanishing Bile Duct Syndrome
15.7 Specific DILD Product Areas and Case Discussions
A. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Use and Hepatoxicity
B. Isoniazid-Induced Hepatotoxicity
C. Acetaminophen
1. Acetaminophen Toxicity Assessment Nomograms
2. FDA Report - Acetaminophen Induced Liver Disease
D. Macrolide Hepatotoxicity
E. Methotrexate (MTX) Hepatotoxicity
F. Estrogens and Oral Contraceptive Steroids
G. Statins
H. Ticlopidine
I. ACE Inhibitors and AT II Receptor Antagonists
J. Fluoroquinolones
K. Terbinafine
L. Ketoconazole
M. Selective Serotonin Reuptake Inhibitors - Serzone Liver Toxicity
N. Herbal and Other Dietary Supplements and Hepatotoxicity
15.8 Summary and Conclusions
References
Chapter 16: Antineoplastic Therapy
Kathryn Schultz, Pharm.D. and Eris Tollkuci, Pharm.D.
16.1 Background
16.2 Chemotherapy - Antimetabolites
16.3 Chemotherapy - Antimicrotubules
16.4 Chemotherapy - Alkylators
16.5 Chemotherapy - Topoisomerase I Inhibitors
16.6 Chemotherapy - Topoisomerase II Inhibitors
16.7 Chemotherapy - Antitumor Antibiotics
16.8 Chemotherapy - Miscellaneous
16.9 Targeted Therapy
A. Infusion-related reactions (IRRs)
B. Immunotherapy (Immune Checkpoint Inhibitors)
1. Infusion-related reactions
2. Immune-Related Adverse Events (irAEs)
16.10 Tumor Lysis Syndrome
16.11 Hepatotoxicity
16.12 Summary and Conclusions
References
Chapter 17: Dangers of Opioids
Jennifer Splawski, M.S., Pharm.D., BCPS, James T. O'Donnell, M.S., Pharm.D., James J. O'Donnell III, M.S., Ph.D.
17.1 Introduction
A. Definitions
B. History
17.2 Pharmacology of Opioids
A. Effects
B. Opioid Neural Receptors
1. Central Nervous System (CNS) Receptors
2. Peripheral Nervous System (PNS) Receptors
C. Routes of Administration
1. Oral
2. Intramuscular
3. Subcutaneous
4. Intravenous
5. Transdermal
6. Sublingual and Buccal
7. Neuraxial
D. Metabolism
E. Excretion
17.3 Toxicity of Opioids
A. Respiratory Depression
B. Symptoms of Overdose
17.4 Epidemiology of Opioid Abuse
A. Opioid Abuse in Adolescents and Young Adults
B. Opioids in Pregnancy
17.5 Contributions to the Opioid Epidemic
A. Opiates Handed Out Like Candy to 'Doped-up' Veterans
B. United States Reaches $22 Million Settlement Agreement with CVS For Unlawful Distribution of Controlled Substances
C. Former Walmart Pharmacists Say Company Ignored Red Flags as Opioid Sales Boomed
D. Federal Judge Approves Landmark $8.3 Billion Purdue Pharma Opioid Settlement
17.6 Combatting the Opioid Epidemic
A. Prescription Monitoring Programs (PDMP)
B. Naloxone Dispensing
C. Medication for Opioid Use Disorder (MOUD)
1. Buprenorphine
A. Pharmacokinetics
B. Adverse Effects
C. Place in therapy
1. Methadone
A. Pharmacokinetics
B. Equianalgesic Dosing
C. Drug Interactions
D. Cardiovascular Effects
E. Consequences of Ignorance of Proper Dosing of Methadone
F. Methadone Legal Case Examples Involving Patient Demise
G. Applying Lessons Learned and Action for Institutional Committees
17.7 Case Reports: Opioid Toxicity Causing Respiratory Arrest, Brain Damage, and Death
A. Case Report: Respiratory Arrest and Brain Damage Following Morphine Overdose
B. Case Report: Fentanyl Epidural Respiratory Arrest
C. Case Report: Fentanyl (Duragesic (R)) Death in Discharged Patient
D. Case Report: High Dose Fentanyl Patch Prescribed in Opiate-Naive Patient-Death
E. Case Report: Heroin and Other Opioids
F. Case Report: Hydromorphone (Dilaudid (R)) Respiratory Arrest
17.8 Investigation and Prosecution of Pain Clinics by the Department of Justice (DOJ)
17.9 Summary and Conclusions
References
Chapter 18: Adverse Effects of Diabetic Drugs: Focus on Hypoglycemia
Gourang P. Patel, BS Chem, PharmD, MSc, BCPS and James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN
18.1 Diabetes Demographics and Epidemiology
18.2 Insulin
18.3 Insulin Preparations
18.4 Clinical Use of Insulin
A. Dosing
18.5 Hypoglycemia (Low Blood Sugar)
A. Etiologies of hypoglycemia
B. Insulin-induced hypoglycemia
C. Deaths by Hypoglycemia
18.6 Pathophysiology and Clinical Symptoms of Hypoglycemia
18.7 Incidence
18.8 Pathophysiology and Biochemistry of Hypoglycemia
18.9 Adverse Reactions Involving Hypoglycemia
A. Insulin damages baby's brain; pharmacist error suggested
18.10 End Product Testing Recommended
18.11 Insulin Murders
18.12 Hypoglycemia from the Sulfonylurea Derivatives
18.13 Adverse Effects of the Sulfonylureas
18.14 Drug Interactions with Sulfonylureas
18.15 The Gliptin Class New drugs for Diabetes Treatment Type 2 Diabetes
18.16 Thiazolidinediones
A. Hepatic Failure
B. Bladder Cancer
18.18 Summary and Conclusions
References
Chapter 19: Parenteral Nutrition Related Errors and Complications
Erica M. Fernandez, Pharm.D., BCCCP, BCPS
19.1 Introduction
19.2. Basic principles of PN
19.3 PN Provision Categories
A. Prescribing
B. Transcribing and Verification
C. Compounding
D. Administration
19.4. Monitoring and Complications
A. Glycemic Control
B. Refeeding Syndrome
C. Hepatobiliary Complications
D. Complications involving micronutrients
19.5 PN Component Shortages and Adverse Events
19.6 Summary and Conclusion
References
Chapter 20: Antidepressants: Clinical Use and Litigation
Henry Cohen, Pharm.D., M.Sc., FCCM, BCPP, BCGP and Michael Liu, Pharm.D., MBA, BCCCP, BCNSP, BCPS
20.1 Major Depressive Disorders
20.2 Antidepressant Pharmacology
20.3 Antidepressant Overdose
A. Trazodone and Permanent Neurologic Sequelae
20.4 Antidepressants and the Patient with Suicidal Ideation
A. Prozac and Suicidal Ideation
1. Woulfe v. Eli Lilly & Co.
2. Espinoza v. Eli Lilly & Co.
3. Cassidy v. Eli Lilly & Co
B. Paxil and Suicidal Ideation
1. Dolin v. GlaxoSmithKline
C. Antidepressant and Increased Suicidality in Pediatrics
1. Schilf v. Eli Lilly & Co.
20.5 Broken Heart Syndrome: Tako Tsubo Cardiomyopathy Associated with Use of Antidepressants
20.6 The Adverse Effects of Antidepressants and the Duty to Warn
A. Docken v. Ciba-Geigy
B. Stebbins v. Concord Wrigley Drugs, Inc. et al.
C. Morgan et al. v. Wal-Mart Stores, Inc.
D. Kampmann v. Mason
E. Cottam v. CVS
20.7 Antidepressants and Alcohol
A. Kirk v. Michael Reese Hospital
B. Hand v. Krakowski
20.8 Selective Serotonin Reuptake Inhibitors and the Serotonin Syndrome
20.9 Hepatic Cytochrome P450 Drug Interactions and Cyclic Antidepressants
20.10 Antidepressants and Herbal Agents Drug Interactions
20.11 Serzone and Liver Disease
20.12 High Blood Pressure Associated with Venlafaxine Use
20.13 SSRI use and Birth Defects
20.14 Bupropion XL and Seizures
20.15 The Pharmacist's Role
20.16 The Omnibus Budget Reconciliation Act
20.17 How Safe is it to Buy Prescription Medications Over the Internet?
20.18 In a Perfect World
20.19 Summary and Conclusions
References
Chapter 21: Contrast Media Neurotoxicity Following Myelography
Stephanie E. Tedford, Ph.D., and James T. O'Donnell, Pharm.D., M.S., FCP
21.1 Introduction
21.2 Case Reports
A. Case I Intrathecal Iopamidol
B. Case II Intrathecal Iothalamate
21.3 Discussion
A. Mechanisms for cerebral (neurotoxic) injury
B. Contrast-induced neurological and cognitive deficits
C. Contrast-induced visual and auditory impairment: Further evidence for cerebral insult to cortical brain structures
21.4 Summary and Conclusions
References
Chapter 22: Fetal Drug Exposure
Damani Parran, Ph.D., MBA, DABT, James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D.
22.1 Introduction
22.2 Critical Periods of Human Development and Susceptibility
22.3 Special Considerations of Drug Exposure during Pregnancy
22.4 Historical Human Developmental Toxicants
A. Thalidomide
B. Ethanol
C. Diethylstilbestrol
D. Retinoids
E. Cocaine
22.5 Developmental Toxicity of Prescription Drugs
A. Valproic Acid
B. Phenytoin
C. Warfarin
D. Benzodiazepines
22.6 Additional Prenatal Environmental Influences
A. Malnutrition
B. Poverty
C. Emotional State
D. Mother's Age
E. Infections and Diseases
22.7 FDA Pregnancy Categories for Prescription Drug Labeling; Final Rule
22.8 Analyses of Litigated Cases Alleging Fetal Drug Injury
A. Effects of Methadone and Smoking on the Fetus
B. Effects of Lisinopril on Fetus - Defense of Causation
22.9 Summary and Conclusions
References
Chapter 23: Geriatric Medication Misadventures
Rodney G. Richmond, M.S., Pharm.D., BCGP, FASCP and James C. Norris, Ph.D., DABT, ERT
23.1 Introduction
A. Outpatient Medication Use
B. Hospital Medication Use
C. Long-Term Care Medication Use
23.2 Altered Clinical Response to Drugs
A. Pharmacokinetics
B. Pharmacodynamics
23.3 Preventable Drug-Related Problems
A. Polypharmacy
B. Transitions of Care
C. Inadequate Monitoring
D. Potentially Inappropriate Medication Use
23.4 Legal Cases Application
23.5 Summary and Conclusions
References
Chapter 24: Medication Errors
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, R.Ph. and James J. O'Donnell III, M.S., Ph.D.
24.1 History and Overview
24.2 Medication Errors in Epidemic Proportions
24.3 Types of Medication Errors
A. Enhancing Healthcare Team Outcomes
B. Improving Reporting of Medication Errors
24.4 Medication Use Process
24.5 System Errors
24.6 Which Drugs are Most Often Involved in Medication Errors?
24.7 Prevalence of Medication Errors
24.8 Vaccine Errors
24.9 How has Modern Research Improved Therapeutics and Reduced Drug-Related Morbidity? Pharmacogenomics
24.10 Systems for Medical Error Prevention
A. Electronic Prescribing (E-prescribing)
B. When Electronic Prescribing is Unavailable
C. Effective Drug Monitoring Systems
D. The Importance of Continuing Education
E. Reporting All Adverse Drug Events
24.11 Summary and Conclusions
References
Chapter 25: Anticoagulants: Therapeutics, Risks, And Toxicities
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D., Stephanie E. Tedford, Ph.D.
25.1 Introduction
25.2 Summary of Anticoagulant Therapy
A. Definition
B. Use
1. Treatment of coronary heart disease
2. Warfarin and dabigatran
3. Treatment of thrombogenesis
25.3 Limitations of Current Therapy
A. Heparin
B. Low Molecular Weight Heparin (LMWH)
C. Heparin-Induced Thrombocytopenia (HIT)
1. Pathogenesis of the autoimmune response
2. Pathogenesis of the prothrombotic state
3. Clinical presentation of HIT
4. Diagnosis
a. Dismissing HIT
b. Diagnosing HIT
2. Two Approaches: class and titer
5. Treatment of HIT
a. Fondaparinux
b. Re-exposure to heparin
6. Conclusion HIT and HITT
D. Warfarin
25.4 Monitoring Warfarin Oral Anticoagulation
25.5 Alternatives to Warfarin - DOACs
A. Pradaxa (Dabigatran) vs. Warfarin
B. Direct Oral Anticoagulation (DOAC) Therapies
C. DOAC reversal agents
D. Antiplatelet Therapy
25.6 Summary and Conclusions
References
Part III: PHARMACISTS, PHARMACY AND PHARMACY PRACTICE
Chapters 26 - 33
Chapter 26: Pharmacy Practice, Managed Care, And Manufacturers
F. Randy Vogenberg R.Ph., Ph.D. and Rita Marcoux R.Ph., MBA
26.1 Introduction to Pharmacy and the Related Managed Health Care Environment
26.2 Pharmacists as Health Care Professionals: Training, Support Staff, and Life-long Learning
A. Registration, Certifications, Credentialing, Colleges Of Pharmacy, And Accreditation Matters For Pharmacy Professional Staff
26.3 Practice Sites: Inpatient, Ambulatory/Community, Specialty, Long Term Care, and Other (compounding, nuclear)
A. Practice settings, Practice site Certification, Pharmacist practice versus the Business of pharmacy, Credentialing, and Accreditation matters
26.4 Issues for Pharmacy Practice, Insurance, and Managed Care In the Near Future
A. The landscape of Practice Sites and Changing Business of Health Landscape
26.5 Current and Near Future Issues for Pharmacists
A. Landscape of Pharmacy Practice, The Changing Professional Marketplace
26.6 Pharmaceutical Manufacturer Through Wholesaler and Distribution Supply Chain
26.7 Manufacturers: Traditional and Innovative Segments
A. Non-Biologic Medications
B. Research-Intensive, Biologics, Gene, and Generic Segments
1. Biologic Medications
26.8 Pharmaceutical Manufacturer Customers
A. Organization and Operations
B. Other Targeted Customer and Class of Trade Segments
C. Contracting and Change in the Pharmaceutical Industry
26.9 Health Care Industry Changes in the Near Future
26.10 Summary and Conclusions
References
Chapter 27: The Pharmacist's Utilization of the National Patient Safety Goals to Contribute to Safe and Effective Medication Use
Jennifer Splawski, Pharm.D., MS, BCPS and Heather Minger, Pharm.D., BCPS
27.1 Introduction
A. Overview of 'The Goals'
27.2 Goal 3 and the Pharmacist's Role
A. NPSG.03.05.01 relating to Anticoagulation
1. Introduction
2. Warfarin Overview
3. Patient monitoring
4. Patient Education
5. Direct Oral Anticoagulant
6. Anticoagulation Reversal Overview
7. Anticoagulation Reversal Programs
8. Patient Education
B. NPSG.03.06.01 relating to Reconciling Medication Information
1. Introduction
2. The Process of Medication Reconciliation
3. Improved Accuracy
4. Decreased Mortality
5. Allergy Identification
6. Discharge Medication Reconciliation
7. Utilization of the Pharmacist Extenders in Medication Reconciliation
27.3 Summary and Conclusions
References
Chapter 28: Pharmacist Malpractice and Liability
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN and James J. O'Donnell III, M.S., Ph.D.
28.1 Introduction
28.2 The Science of Risk Management
28.3 Claims Studies
The Pharmacists Mutual Claims Study
CNA Claims Study (CNA/HPSO)
A. CNA Database and Methodology
B. Most Common Categories of Errors
C. Claim Analysis by Insurance Source & Licensure Type: Pharmacists v. Technicians
D. Factors Affecting Wrong Drug Dispensing Errors
E. Drugs Involved in Claims
F. Most Common Error: Wrong Drug
G. Wrong Drug Strength
H. Wrong Directions
I. Wrong Route of Administration
J. Lack of Drug Review
K. Counseling: A Powerful Weapon Against Liability
L. Non-Bodily Injury
M. Miscellaneous Errors
N. Wrong Directions
O. Lack of Drug Review
P. Avoiding Errors and Malpractice
28.4 Specific Pharmacist Malpractice Case Reports / Topics
A. Duty to Warn?
B. Wrong Drug
C. Quotas and Metrics: Contributing to the Problem?
D. Controlled Substances Violations by Pharmacists
E. Methotrexate (MTX) errors
28.5 Pharmacists Need to do the Right Thing
28.6 Steps Toward a Better Outcome
28.7 Summary and Conclusions
References
Chapter 29: Regulation of Pharmacy Practice
Ned Milenkovich, Pharm.D., J.D.
29.1 Introduction
29.2 Licensure of Professional Activities
A. Boards of Pharmacy - A Closer Look
B. National Association of Boards of Pharmacy
29.3 Practice Standards
A. Legally Circumscribing Pharmacy Practice
29.4 Licensure Process to Practice Pharmacy
A. Licensing
B. Licensing of Pharmacists
29.5 The Different Types of Pharmacy Licenses
A. Disciplinary Actions
B. Causes of Disciplinary Action
C. Practice Focus on Licensure
D. Ongoing Professional Education
E. Support Personnel
29.6 Federal Drug Laws
A. Obra '90
B. Medicare
C. Medicare Part D
D. Medicaid
E. Prescription Drug Coverage
F. Fraud, Waste and Abuse
G. 340b Drugs
H. Pharmacy Compounding
I. FDA Rems
J. DEA
29.7 Pharmacy Practice: Putting it Together
A. Pharmacy Practice: An Ongoing Progression
B. Collaborative Practice Agreements
C. Drug Utilization Review (DUR)
D. Other Mandates Impacting Pharmacy Practice Quality Assurance Regulations
E. Health Insurance Portability and Accountability Act Of 1996, As Amended
Chapter 30: Emergency Department Pharmacist
Victor Cohen, B.S., Pharm.D., BCPS, CGP, Samantha P. Jellinek-Cohen, Pharm.D., BCPS, CGP, Megan Musselman Pharm.D., M.S., BCPS, BCCP
30.1 Introduction
30.2 Epidemiology of Drug Injury and Contributing Risk Factors
A. Contributing Risk Factors
30.3. Etiology and Sources of Drug Injury in the ED
30.4 Clinical Pharmacy in the ED: A Historical Perspective
30.5 The ED Pharmacist Plays a Dual Role at Maimonides Medical Center
30.6 The ED Pharmacist: A Sub-specialist in Emergency Medicine
A. Training and Education
B. Certification
30.7 The ED Pharmacist as a Generalist
30.8 The ED Pharmacist Ensuring Optimal Continuum of Care
A. The ED and Infectious Diseases
B. The ED Pharmacist and the Ambulatory Care Interphase
C. The ED Pharmacist and Transitions of Care (TOC)
1. Medication admission notes in the ED
D. The ED Pharmacist as a Clinical Toxicology Consultant
E. The ED Pharmacist and the Cardiology Interface
F. The ED Pharmacist and Neurological Emergencies
G. The ED Pharmacist and Pulmonary Emergencies
H. The ED Pharmacist and Public Health Services in the ED
30.9 Building Layers of Defense Against Drug Injury
A. Detecting and Preventing Drug Injury in the ED
B. The ED Pharmacist and Community Surveillance for Adverse Drug Reactions
30.10 Pharmacy Practice in the ED: Pharmacotherapy Specialty
30.11 Summary and Conclusions
References
Chapter 31: Pharmacy Case Law Review
Roger N. Morris, R.Ph., J.D., and William J. Stilling, R.Ph., M.S., J.D.
31.1 Administrative Law
A. Due Process-Pharmacist Licensure
1. Berjikian, et al. v. Franchise Tax Board et al., No. CV 13-06301 DDP, 2015 WL 1185472 (C.D. Cal. March 12, 2015)
31.2 Antitrust
A. State Regulatory Boards Immunity
1. North Carolina Bd. of Dental Examiners. v. Federal Trade Commission, 135 S. Ct. 1101 (Feb. 25, 2015)
31.3 Civil Procedure
A. Spoliation of evidence-Pharmacy's Duty to Maintain Evidence of Misfill
1. Burton v. Walgreen Co., 2015 WL 4228854 (D. Nev. July 10, 2015)
31.4 Conscientious Objection
A. Emergency Contraception
1. Stormans, Inc. v. Wiesman, 794 F.3d 1064 (9th Cir. 2015)
31.5 Controlled Substances
A. Duty to Verify DEA Registration
1. Farmacia, Yani, 80 Fed. Reg. 29,053 (May 20, 2015)
2. JM Pharmacy Group Inc., d/b/a/ Farmacia Nueva and Best Pharma Corp., 80 Fed. Reg. 28,667 (May 19, 2015)
B. Constitutionality
1. McFadden v. United States, 135 S. Ct. 2298 (June 18, 2015)
31.6 Criminal
A. Violations of Pharmacy Law Applied to Non-pharmacists
1. Moore v. State of Florida, NO. 1D14-3527, 2015 WL 4464689 (Fla. Dist. Ct. App. July 21, 2015), reh'g denied (Sept. 1, 2015)
B. PMP Records
1. Lundy v. State, 26 N.E.3d 656 (Ind. Ct. App. Feb. 20, 2015)
C. Second Degree Murder
1. U.S. v. Barry J. Cadden, et al., 2014 WL 7151586 (D. Mass. Dec. 16, 2014)
31.7 Defamation
A. Physician against Pharmacist
1. LeFrock v. Walgreen Co., 77 F. Supp.3d 1199 (M.D. Fla. Jan. 16, 2015)
B. Duty to Fill
1. Kadambi v. Express Scripts, 2015 WL 475373 (N.D. Ind. February 5, 2015)
31.8 Employment
A. Discrimination (Pregnancy)
1. Torres-Skair v. Medco Health Solutions, Inc., 595 F.App'x 847 (11th Cir. Dec., 4, 2014)
B. Employment at Will
1. Hoven v. Walgreen Co., 751 F.3d 778 (6th Cir. June 2, 2014)
C. Americans with Disability Act
1. Stevens v. Rite Aid Corp., et al., 6:13-cv-00783 (N.D.N.Y., September 23, 2015)
D. Overtime Class Action
1. Baugh v. CVS Health, et al., 2:15-cv-00014 (E.D. Penn., July 27, 2015)
E. Medical Marijuana
1. Coats v. Dish Network, 350 P. 3d, 849 (Colo. June 15, 2015)
31.9 Fraud and Abuse
F. False Claims
1. United States v. Express Scripts, Inc., 602 F. App'x 880 (3rd. Cir. Feb. 20, 2015)
G. False Claims-Generic Substitutions
1. Doe v. Houchens Indus., Inc., No. 1:13-CV-00196-RLY, 2015 WL 133706 (S.D. Ind. Jan. 9, 2015)
H. False Claims & Anti-Kickback Statute
1. U.S. ex rel. Kester v. Novartis Pharm. Corp., No. 11 CIV. 8196 CM, 2015WL 1650767 (S.D.N.Y. Apr. 10, 2015)
I. Consumer Fraud
1. City of Chicago v. Purdue Pharma L.P., 2015 WL 2208423 (N.D. Ill. May 8, 2015)
31.10 Negligence
A. Duty to Provide Medication
1. Davies v. Virginia CVS Pharmacy, LLC, et al., 7:14-CV-00175, 2014 WL 6460787 (W.D. Va. Nov. 17, 2014)
B. Duty Not to Dispense
1. Oleckna v. Daytona Disc. Pharmacy, 162 So. 3d 178 (Fla. Dist. Ct. App. 2015)
31.11 Privacy
C. Patient Privacy-Vicarious Liability
1. Walgreen Co. v. Hinchy, 25 N.E.3d 748 (Ind. Ct. App. Jn. 15, 2015) reh'g of, 21 N.E.3d 99 (Ind. Ct. App. Nov. 14, 2014)
D. Text Messages
1. Thompson v. CVS Pharmacy, Inc., 6:204-cv-02081 (M.D. Fla. Dec. 19, 2014)
E. Robocalls
1. Kolinek v. Walgreen Co., 2014 WL 3056813, (N.D. Ill. July 7, 2014)
31.12 Product liability
A. Learned Intermediary Doctrine
1. Watts v. Medicis Pharm. Corp., 342 P.3d 847 (Ct. App. 2015), review granted in part (Sept. 22, 2015)
B. Product Liability (applicability to pharmacists)
1. Randol Mill Pharmacy v. Miller, 465 S.W.3d 612 (Tex. 2015), reh'g denied (Sept. 11, 2015)
Chapter 32: Pharmacy Compounding - Patient Injury and Regulatory Compliance
Willis C. Triplett, Pharm.D.
32.1 Introduction
32.2 Compounding Trends and Driving Forces
32.3 Optimizing the Regulatory Balance Between "Manufacturing" versus "Compounding"
32.4 Investigations, Indictments, Convictions, and Acquittals after the Fungal Meningitis Outbreak
32.5 Memorandum of Understanding (MOU)
32.6 U SP, NABP, and the State Pharmacy Regulatory Authorities
32.7 Physician and Medical Office Compounding
32.8 Compounding "Center of Excellence" ("COE") and the Quality Assurance Paradigm Shift
32.9 Conclusions and Forecasts Regarding Patient Injury from Healthcare Compounding
32.10 Recommended Readings
CHAPTER 33: Compounding Pharmacy Fraud and Unethical Practices
James T. O'Donnell, Pharm.D., M.S., FCP
33.1 Introduction
33.2 Criminal Prosecutions of Pharmacy Compounders
33.3 Over-Prescribing and Over-Charging of Compounded Drugs
A. Department of Justice News Releases
B. News Reports in Newspapers
33.4 Not Yet Criminal? Insurance Companies Fighting Back
A. No-Fault Pain Compounded and Topical Pain Product
B. Report Challenging the Pricing and Efficacy of a Compounded Pain Cream Prescription
C. Ingredients and Costs of Pain Cream
33.5 General Discussion - Compounded Pain Topical Creams
A. Evidence of Efficacy?
B. Expensive Ingredients
33.6 Ingredients Review of Efficacy and Mechanism of Action
A. Diclofenac
B. Menthol (Methyl Salicylate)
C. Lidocaine
1. Lidocaine Topical Toxicity
D. Amitriptyline
E. Cyclobenzaprine
F. Dimethylsulfoxide (DMSO)
33.7 Global Opinions for the Prescription CPTM formula 8-NC Claim Challenge
33.8 Discussion and Further Bases of Opinions
33.9 Overbilling of Topical Diclofenac Gels, Lidocaine Creams and Ointments and Patches
A. Diclofenac 3" (Solaraze)
B. Lidocaine Topical Commercial Products
33.10 Recommendations
33.11 Summary and Conclusions
References
Part IV: FORENSIC AND TOXICOLOGY ISSUES
Chapters 34 - 42
Chapter 34: Alcohol
James T. O'Donnell, Pharm.D., M.S.. FCP and James J. O'Donnell III, M.S., Ph.D.
34.1 Introduction
34.2Alcohol Injury Epidemiology
34.3 Alcohol Intoxication Effects in Litigation
34.4 Differences between Civil litigation involving alcohol from Criminal/DUI
34.5 Settings for Alcohol Related Civil Litigation
A. Employment
34.6 Police Activities
A. Police Pursuit
B. Excessive Police Force
C. Alcohol Effects on Aggression and Judgment
34.7 Motor Vehicle Collisions
A. Vehicle/Vehicle
B. Motorcycle Cases
C. Boating
D. Vehicle/ Pedestrian
34.8 Alcohol and Falls
A. Stairs - no alcohol test - fall down bar stairs
B. Stairs - Residential Stairs Fall -Adjustment of Calculated BAC due to Morbid Obesity
C. Tripped on Threshold - Sued Condominium Association
34.9 Dram Shop (Bar Liability for Serving Intoxicated Persons)
34.10 Biomarkers for Alcohol
A. Family Law
B. False Positive Alcohol Biomarkers in Diabetes
34.11 Miscellaneous Topics Reports
A. Retrograde Extrapolation (See also legal cases Floyd and Cuellar earlier in this chapter.
B. Appellate Court reverses Trial Court Barring of BAC
34.13 Summary and Conclusions
References
Chapter 35: Cocaine
James C Norris, Ph.D., D.A.B.T and Rodney G Richmond, R.Ph., MS, CGP, FASCP, FACFE
35.1 Historical Background
35.2 Medical Usages of Cocaine
35.3 Illegal Usage of Cocaine
35.4 Routes of Administration
35.5 Effects of Cocaine
35.6 Psychotic Disorders Induced by Cocaine
35.7 Addiction
35.8 Cognitive Deficits
35.9 Prenatal Cocaine Exposure (PCE)
35.10 Violence
35.11 Tolerance
35.12 Withdrawal or Abstinence Effects
35.13 Mechanisms of Action
35.14 Metabolism
35.15 Blood Levels
35.16 Urine Levels
35.17 Impairment
35.18 Associated Deaths with Cocaine Usage
35.19 Summary and Conclusions
References
Chapter 36: Marijuana: Pharmacology, Toxicology and Forensic Issues
Stephanie E. Tedford, Ph.D., James T. O'Donnell PharmD, MS, FCP, and James J. O'Donnell III MS, Ph.D.
36.1 Introduction
36.2 Federal Law vs. State Law
A. Harrison Narcotics Tax Act
B. Comprehensive Drug Abuse Control and Prevention Act
C. Marijuana Drug Laws at the State Level
D. Legalization
E. Decriminalization
F. Marijuana Policy Project
36.3 Controlled Prescription and Distribution of Medical Marijuana
A. Medical Conditions Approved for Treatment with Medical Marijuana
B. Marijuana and Epilepsy
C. Marijuana and Endometriosis
36.4 Pharmacological Properties of Marijuana
A. Active Compounds and Overview of Pharmacology
B. Variability in Marijuana Regulation and Content Uniformity
C. Routes of Administration
D. Pharmacokinetics - Time Course of THC and Metabolites
E. Pharmacodynamics
F. Vaping vs. Traditional Smoking of Cannabinoids
G. Traditional Smoking vs. Ingestion of Cannabinoids
H. Pharmacokinetics Applications: Timing of the Peak Euphoric Effect
I. Bioavailability
1. Is There a Good Model for Marijuana Ingestion?
2. Overall Advantages of the Oromucosal Route?
3. Can the Effects After Ingestion of Marijuana be Made More Objective?
36.5 Marijuana Safety
A. Serious Adverse Effects
B. Risk of Psychosis
1. Drug-induced Psychosis: Potential Mechanisms
2. Vaping and Associated Risk for Psychosis
C. Pulmonary Function
D. Risk of Addiction
E. Effect on Brain Development
F. Long Term Behavioral Effects
G. Age of Onset of Use
36.6 Impact of Legalization
A. Hospital Resources
B. Driving Under the Influence of Drugs
C. Relationship of Marijuana Use and Co-Use with other Substances
36.7 Analysis and Testing for Marijuana Use
36.8 Scientific Data Relating to THC
A. Blood THC vs. Brain THC: Any Relationships?
B. Relationships Between Percent Plant-THC and Plasma-THC
C. Is There a Relationship Between Percent THC in the Smoked Cigarette and Plasma THC?
D. Relation Between Degree of "High" and Plasma THC
E. Occasional Marijuana Users vs. Practiced Users
F. Is THC the Only Psychoactive Cannabinoid?
G. Urine Testing for Cannabinoids: Clinical or Evidentiary Value?
H. Impairment and Marijuana: Laboratory and On-Road Driving Performance Data
I. Hospital and Provider Considerations
36.9 Forensic Case Reports
36.10 Summary and Conclusions
References
Chapter 37: Drug Evaluation and Classification Program: An Evidence-Based Analysis
Fran M. Gengo Pharm.D., FCP and Anna Mattle, Pharm.D., M.S.
37.1 Introduction
37.2 The 12 Steps of DRE Examinations
37.3 Scientific Evaluation of DRE Examinations
A. Step 2: Interview of Arresting Officer
B. Step 3: Preliminary Examination and Initial Pulse Measurement
C. Step 4: Eye Examination
D. Step 5: Divided Attention Tests
E. Step 6: Second Pulse Reading, Body Temperature, and Blood Pressure Measurement
F. Step 7: Eye Examination of Pupil Size in Various Lighting Conditions
G. Step 8: Assessment of Muscle Tone
H. Step 11: DRE Officer Opinion Statement
I. Step 12: Toxicology Sample
37.4 Literature Evaluations And Critiques Of Dre
37.5 Cannabis
37.6 Statistical Validity and Overall Strength of DRE Studies
37.7 DRE Support Literature
A. Bigelow et al. 1985 Study
B. Heishman et al. 1996 and 1998 Studies
C. Smith et al. 2002 Study
D. Shinar and Schechtman 2005 Study
E. Specific Identification of Drug Class by DRE Officers in Validation Studies
37.9 Summary
37.10 Summary and Conclusions
References
Chapter 38: Involuntary Intoxication
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D., William Vaughn, J.D.
38.1 Introduction
38.2 Legal Defense Considerations for a Violent Crime
38.3 Confirming That Drugs are Involved in a Violent Crime
38.4 Beyond Pharmacology: The Multifactorial Role of Drugs in Aggression and Violence
38.5 Association of Drugs with Aggression and Violence
38.6 Mechanisms of Drug-Induced Violence
38.7 Intoxication of Victim Defense
38.8 Summary and Conclusions
References
Chapter 39: Drug-Induced Aggression and Violence
Peter D. Anderson, Pharm.D., BCPP
39.1 Classification of Aggression
39.2 Causes of Aggression and Violence
A. Neurobiology of Aggression
B. Medical and Psychiatric Causes of Aggression
39.3 The Role of Drugs as a Cause of Violence
A. Introduction
B. Problems with the Literature
C. Specific Drugs or Drug Classes that cause aggression
1. Ethanol
2. Lysergic Acid Diethylamide
3. Phencyclidine and Ketamine
4. Anabolic Steroids
5. Insulin
6. Psychostimulants
7. Benzodiazepines
8. Selective Serotonin Reuptake Inhibitors
9. Varenicline
10. Environmental Chemicals
39.4 The Drug-Induced Insanity Defense
39.5 Summary and Conclusions
References
Chapter 40: Forensic Drug Testing Chapter
James J. O'Donnell III, M.S., Ph.D, and James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN
40.1 Introduction
40.2 Non-Regulated Drug Testing
40.3 Regulated Drug Testing
40.4 Voluntary Programs
40.5 Establishment of a Workplace Program
A. Written Policy
B. Employee Assistance Programs
C. Employee Awareness Training
D. Supervisor Training
E. Drug Testing
40.6 The Drug-Testing Process
A. Specimen Collection
B. Accessioning
C. Drugs to Be Tested
D. Screening Tests
E. Confirmation Tests
F. Reporting and Storage of Samples
G. Prevention Against and Detection of Drug Test Cheating
40.7 Additional Program Aspects
A. The Medical Review Officer (MRO)
B. Public Interest Exclusions (PIE)
C. Blind Performance Testing
D. Alcohol Testing
40.8 Special Drug-Testing Issues
A. Type of Matrix
1. Hair Testing
2. Saliva Testing
3. Sweat Testing
4. Blood
5. Urine
B. Alternate Sources of Drug Exposure
C. Amphetamine Testing Issues
D. Medical Use of Drugs
40.9 Legal Aspects of Workplace Drug-Testing
A. Constitutional Issues
B. State and Federal Mandates
40.10 Discovery: The "Litigation Package"
40.11 Case Reports
40.12 Summary and Conclusions
References
Chapter 41: Postmortem Redistribution and Interpretation of Drug Levels
Gourang P. Patel Pharm.D., M.Sc., BCPS, BCCCP, FCCM
41.1 Abstract
41.2 Introduction
41.3 Review of a Case File
41.4 Postmortem Considerations
A. Physiologic Changes in the Body After Death
B. Drug Characteristics
41.5 Analysis of Drug Level Information
41.6 Summary and Conclusions
References
Chapter 42: Addiction as Mitigation
Barry D. Hargan, M.S., MHA and James T. O'Donnell, Pharm.D., M.S., FCP
42.1 Introduction
42.2 Clinical Variables Which Contribute to the Onset of Addiction
A. Genetic Predisposition
B. Learned Behavior
C. Psychopathological Exposure
42.3 Substance/Medication-Induced Mental Disorder
A. Executive Summary of Opinion
B. Neurotoxicity Mechanisms of Alcohol and Anabolic Steroids in the Developing Brain
C. Anabolic Steroid Effects on Brain Structure and Function
D. Translational Impact - what does this mean to a teenager abusing large amounts of alcohol and steroids?
E. Clinical and Practical Applications of the Basic Neuroscience
F. Behavioral Abnormalities Associated with Anabolic Steroid Use
G. Defendant's Alcohol and Anabolic Steroid Use
1. Alcohol
H. Expert Opinions Regarding Substance-Induced Brain Damage Affecting Behavior
42.4 The Simplified Version of Neurobiology and the Addicted Brain
42.5 Cocaine
42.6 Expert Testimony Concerning Addictive Disorders
A. Role of the Addictions Expert
B. Some Testimony Experiences and the Limits of Opinions
C. Preparation
42.7 Additional Considerations Concerning Addiction Mitigation
A. Neuropsychological Evaluation
42.8 Summary and Conclusions
References
Este título pertence ao(s) assunto(s) indicados(s). Para ver outros títulos clique no assunto desejado.
Adverse event processing system;Clinical trials;FDA and drug approval process;Couterfeit drugs;Pharmacokinetics and pharmacodynamics;Principles of pharmacology
PART I: THE PHARMACEUTICAL PROCESS
Chapters 1 - 9
Chapter 1: FDA and Drug Approval Process
Megan Walter, Pharm.D. and CDR Lindsay Wagner, Pharm.D., BCPS
1.1 Introduction
1.2 The New Drug Development Process
A. Discovery and Preclinical Research
B. Clinical Research
C. Investigational New Drug Application
D. Phases of Clinical Studies
E. Expanded Access Programs
F. Right to Try
1.3 New Drug and Therapeutic Biologic Application Process
A. New Drug Applications and Biologic License Applications
B. Fundamentals of NDA and BLA Submissions
C. NDA Classifications
1.4 FDA Review
A. Expedited Development and Review Programs
1. Accelerated Approval
2. Priority Review
3. Fast Track
4. Breakthrough Therapy
B. Labeling Review
1. Physician Labeling Rule (PLR)
2. Pregnancy and Lactation Labeling Rule (PLLR)
3. Additional FDA-Approved Patient Labeling
C. Risk Evaluation and Mitigation Strategies
D. Advisory Committee Meetings
1.5 The Generic Drug Approval Process
A. Abbreviated New Drug Applications
B. ANDA Approval
C. Generic Drug User Fee Amendments
1.6 Biosimilar Pathway
1.7 Over-the-Counter Drug Products
1.8 Postmarketing Surveillance
A. Adverse Event Reporting
B. FDA Adverse Event Reporting System
C. Post Marketing Requirements and Commitments
D. Sentinel Network
E. Drug Safety Oversight Board
1.9 Applicable Statutes and Implementing Regulations
A. Food and Drug Acts - 1906
B. Food, Drug and Cosmetic Act - 1938
C. Durham-Humphrey Amendment - 1951
D. Kefauver-Harris Amendment - 1962
E. Orphan Drug Act - 1983
F. Drug Price and Competition and Patent Term Restoration Act - 1984
1. Revision of New Drug Application Regulations - 1985
2. Revision of Investigational New Drug Application Regulations - 1987
3. Treatment Use of Investigational New Drugs - 1987
G. Prescription Drug User Fee Act (PDUFA) - 1992
H. FDA Modernization Act (FDAMA) - 1997
I. FDA Amendments Act (FDAAA) - 2007
J. Food and Drug Administration Safety and Innovation Act (FDASIA) - 2012
K. The Drug Quality and Security Act (DQSA) - 2013
L. 21st Century Cures Act - 2016
M. Food and Drug Administration Reauthorization Act (FDARA) - 2017
N. Coronavirus Aid, Relief, and Economic Security Act (CARES Act) - 2020
1.10 Conclusion
1.11 Glossary of Terms
References
Chapter 2: The Front Lines of Clinical Research: The Industry and Ethical Considerations
Jonathan Young, Ph.D.
2.1 Introduction
2.2 Clinical Trial Service Providers
A. Food and Drug Administration
B. Clinical Trial Sponsor
C. Contract Research Organizations
D. Study Monitors
2.3 Clinical Trial Site
A. Site Management Organizations
B. Institutional Review Boards
2.4 The Evolution of Ethical Principles in Clinical Research
A. Respect for Persons
B. Beneficence
C. Justice
D. How the Investigator Applies Ethical Principles
2.5 Regulations Governing Institutional Review Boards
A. What Institutional Review Board Members Should Know about Clinical Research
B. What Institutional Review Board Members Should Know about Their Responsibilities
2.6 What the Site Should Know about Institutional Review Boards
A. What Research Requires Institutional Review Board Approval and Oversight
B. Requirements of an Investigator for Institutional Review Board Research Approval
2.7 Risks-vs.-Benefits Analysis: The Human Advocate
A. Identifying and Assessing the Risks
B. Minimal Risk vs. Greater-than-Minimal Risk
C. Vulnerable Populations and Minimal Risk
D. Determining Whether Risks Are Minimized
E. Assessing Anticipated Benefits
F. Determining Whether Risks Are Reasonable
G. Continuing Review and Monitoring of Data
2.8 Informed Consent: Not Just a Document
A. Elements of an Informed Consent
B. Additional Required Elements
2.9 Research Participants
2.10 Industry Trade Organizations and Support Services
2.11 Summary: Ethical Dilemmas in Clinical Research
References
Chapter 3: Search and Analysis of the Food and Drug Administration's FDA Adverse Event Reporting System (FAERS)
Paul N. Danese, Ph.D.
3.1 Introduction
3.2 Background
A. Small Clinical Trial Populations
B. Narrow Patient Demographics
C. Restricted Co-Administration of Medications
3.3 History of the FDA's Drug Safety Surveillance Systems
3.4 Submission of Adverse Event Reports to the FDA
A. Mandatory Reports
B. Voluntary Reports
3.5 Adverse Drug Reaction Information Captured by FAERS
3.6 Searching FAERS Data to Identify Possible Safety Problems
A. Statistical Methods to Identify Drug Safety Signals
B. Dechallenge and Rechallenge Data and Causality
C. Identifying Drug-Drug Interactions
D. Timelines and Deadlines of Adverse Event Reporting
3.7 The Food and Drug Administration's Use of FAERS in Regulatory Decisions
A. Boxed Warnings
B. Other Changes to a Medication's Prescribing Information
C. Determinations that No Action is needed and Continuing Investigations
3.8 Limitations of FAERS
A. Lack of Demonstration of Causality for Individual Reports
B. Extensive Under-reporting
C. Reporting Biases
D. Lack of Comparator Populations (Lack of a Denominator)
3.9 Search and Retrieval of Adverse Event Reports from the FDA's FAERS
A. Raw Data Files
B. FDA Public Dashboard
C. FOIA Requests
D. Commercial Vendors
3.10 Other FDA Adverse Event Reporting Systems
A. VAERS
B. MAUDE
C. Sentinel Initiative
3.11 Summary and Conclusions
References
Chapter 4: The Safety of Medicines: PharmacoVigilance, PharmacoSurveillance, PharmacoEmpowerment?
David Healy, M.D.
4.1 RxISK.org
4.2 Antidepressants: Data Based or Evidence Based?
4.3 Access to Adverse Event Data
4.4 RCTs and Adverse Events // Ghost Writers
4.5 RCTs & Primary Endpoints
4.6 Post 1962: Confounding & Causality
4.7 Pharmacovigilance
4.8 RxISK.org and Pharmacovigilance 1.0
4.9 Pharmacosurveillance
4.10 TaperMD and Pharmacovigilance 2.0
4.11 Summary and Conclusions
References
Chapter 5: Important Code of Federal Regulations Applicable to Drug Product Liability Suits
S. Albert Edwards, Pharm.D., RAC, FRAPS
Chapter 6: The Regulation of Drug Product Information to Consumers
Frank J. Ascione, Pharm.D., MPH, PhD
6.1 The Historical Development of Food and Drug Administration (FDA)'s Regulatory Role
A. Early phase (prior to 1906): No significant government intervention
B. Early Regulatory Phase (1906-1938): Minimal Government Control
C. Greater Government Control (1938-1961)
D. Debating Increased Consumer Access to Drug Product Information (1962-1983)
E. Expanding Information Available to Consumers (1983-present)
6.2 Current State of Prescription Drug Product-Related Information Provided to Consumers
6.3 Evolution of Drug Advertising to US Consumers (DTCA)
A. Emergence of DTCA (1981-1982)
B. Voluntary Moratorium Period of DTCA (1983-1985)
C. Establishment of DTCA Regulations (1985-1999)
6.4 Current State of Direct-to-Consumer Advertising
A. Advantages and Disadvantages of DTCA
6.4 Summary and Conclusions
References
Chapter 7: The Role of Investigative Journalism in Improving Drug Safety
Martha Rosenberg
7.1 Introduction
7.2 Direct-To-Consumer Advertising Increased with Covid
A. Unbranded DTC Advertising
B. Industry Funded Disease Awareness Groups
C. Encouraging Victim Politics
7.3 The Opioid Epidemic
A. Growing an Untapped Market
B. Aggressive Opioid Marketing
C. Fostering Opioid Addiction
D. Pill Mills and Addiction Medicine
E. Opioid Lawsuits Surface
F. Lack of Opioid Efficacy and Serious Side Effects
G. Paying for the Opioid Epidemic
7.4 Effective Hepatitis C Drugs Debut
A. Lawmakers Investigate Hep C Prices
B. Aggressive Hep C Marketing
C. Screening as a Hep C Sales Tool
D. Hepatitis C Safety Signals Emerge
7.5 Asthma Drug Safety Signals
A. Xolair Leaves a Trail of Questions
B. More Improper Xolair Marketing
C. Safety Signals Surface with Xolair and a Lawsuit is Dismissed
7.6 Long-Acting Beta Agonists
A. Glaxosmithkline Settlement included a Laba
7.7 Safety Questions About Leukotriene Receptor Antagonists
A. Parents Report LTRA Side Effects
B. LTRA Safety Signals Emerged Early
C. Patients and Parents Fight Back
D. Black Box Added to Singulair
7.8 Baldness Treatments Become Popular and Controversial
A. Finasteride Side Effects Create Concern
B. Medical Literature Confirms Finasteride Side Effects
C. FDA Adds Warnings to Finasteride
D. Finasteride User Speaks Out
E. No Satisfying End for Finasteride Users
7.9 Biologic Drugs
A. Tumor Necrosis Factor (Tnf) Blockers
B. Tnf Blocker Risks
7.10 Other Popular Medications Come Under New Scrutiny
A. N-Nitrosodimethylamine (NDMA
) Found in Medicines
1. Zantac Taken Off Shelves
2. NDMA Also Found in Metformin
7.11 Popular Stimulant Drugs Reveal Risks
A. Risks Seen with Modafinil
B. Fetal Risks Seen with Modafinil and Armodafinil
C. European Union Sues Provigil Makers
7.12 Fetal Risk Seen with NSAIDs
7.13 Bisphosphonates Continue to Present Risks
7.14 SSRI Antidepressants Linked to New Risks
A. SSRI Bone Thinning
B. SSRI Addictive Potential
7.15 Belviq, A Diet Drug Withdrawn from Market
7.16 Sleeping Pills Given Boxed Warnings
A. Public Figures on Sleeping Pills Make the News
B. Other Sleeping Pill Risks
7.17 Risks Associated with Fluoroquinolone Antibiotics
A. Fluoroquinolones Warnings Continue
B. Hormone Therapy Still Linked to Risks
C. Beware of Testosterone Marketing
D. New PPI Questions
References
Chapter 8: Evaluation of Causation in Drug Injury Cases
Donald H. Marks, M.D., Ph.D. and James T. O'Donnell, Pharm.D., M.S., FCP
8.1 What is Causation?
8.2 Importance of Establishing Causation
8.3 Definitions
8.4 Degree of Adverse Effects Relate to Intervention
8.5 Methodology to Investigate Causation
8.6 Structured Algorithms for Determination of Causation
A. Hill Criteria-Expanded Discussion
1. Strength of Association
2. Consistency of Results
3. Specificity
4. Temporal Relationship
5. Dose Response
6. Biological Plausibility
7. Biological Coherence
8. Experimentation
9. Analogy
8.7 Comments on the Individual Riddell Criteria for Causation,
8.8 Daubert and the Evolution of Causation,
8.9 Does Causation Need to be Established Before a Warning is Given?
8.10 What are the Qualifications needed to Give Expert Causation Opinions?
8.11 Case Reports Demonstrating Applications of Causation Principles
A. Case Report: Acyclovir Overdose - Pharmacist Recommended Overdose
B. Case Report: Challenging Cause of Death in a Malpractice Matter
C. Case Report: Determination of the Effects of Morphine in a Will Contest
D. Case Report: Proof of Drug-Induced Mental Changes in Complainant in Sexual Abuse Case
8.12 Summary and Conclusions
References
Chapter 9: General Principles of Pharmacology
James J. O'Donnell III, M.S., Ph.D., James T. O'Donnell, Pharm.D., M.S., FCP, and Vanessa Juettner, Ph.D.
9.1 Introduction
9.2 Basic Principles
A. Absorption
B. Lipid Diffusion
C. Determinants of Absorption
1. Lipid/aqueous partition coefficient and pH
2. Bioavailability
3. First pass effect
9.3 Routes of Administration
9.4 Extravascular Administration
A. Oral Administration
B. Rectal Administration
C. Other Routes of Administration
9.5 Intravascular Administration
9.6 Distribution
A. Diffusion
B. Volume of Distribution
C. Binding to Plasma Proteins and Cellular Constituents
D. Re-Distribution
E. Blood-Brain Barrier (BBB)
F. Placental Barrier
G. Therapeutic Range
H. Bioequivalence vs. Bioinequivalence
10.7 Drug Metabolism (Biotransformation)
A. Phase I Reactions
1. The families of human P450s
2. Induction of P450 enzymes
3. P450 Inhibition
B. Phase II Reactions
1. Metabolism of drugs to toxic products
9.8 Factors Affecting Drug Metabolism
A. Disease
B. Age
C. Gender
D. Genetic Factors
9.9 Drug Excretion
A. Urinary Excretion
1. Glomerular filtration
2. Tubular secretion (active secretion)
3. Tubular reabsorption
4. Effects of pH on urinary excretion of ionizable drugs
9.10 Pharmacokinetics
A. Introduction
B. Therapeutic Window and Therapeutic Index
C. Blood Levels for Narrow Therapeutic Index (NDI) Drugs
D. Kinetic Modeling
E. Drug Absorption and Elimination
1. Absorption rate
2. Elimination rate
3. Clearance (CL)
4. Area Under the Curve (AUC)
5. Elimination (k)
6. Elimination half-life
7. Steady state
F. Dosing
1. Loading dose
2. Maintenance doses (MD)
3. Example-dosage adjustment in renal impairment
G. Therapeutic Drug Monitoring (TDM)
H. Pharmacokinetics Summary
9.11 Drug Receptor and Pharmacodynamics
A. Agonists and Antagonists
B. Drug-Receptor Interactions
9.12 Dose Responses
A. Potency
B. Agonism and Antagonism
1. Partial agonists
9.13 Competitive Antagonism
9.14 Non-Competitive Antagonism
9.15 Summary and Conclusions
PART II: HIGH RISK DRUG THERAPIES RESULTING IN INJURY AND LITIGATION
Chapters 10 - 25
Chapter 10: Adverse Drug Reactions: Allergic Focus
James T. O'Donnell Pharm.D., M.S., FCP and James J. O'Donnell III, M.S., Ph.D.
10.1 Adverse Drug Reactions: How Large is the Problem? What Drugs are Involved? What are the Injuries?
A. Historical Perspective
B. Incidence of Adverse Drug Reactions
C. Food and Drug Administration Reporting Requirements
D. The "Seven Deadly Sins": Why Doctors Fail to Report Adverse Drug Reactions
E. Attitudes Toward Adverse Drug Reactions
F. Investigator Fraud
10.2 Classification of Adverse Drug Reactions
A. Categories of Adverse Drug Reactions
1. Type A reactions: Augmentation of the Pharmacological Response
2. Type B reactions: Bizarre (idiosyncratic)
10.3 Types of Drug Allergy and Hypersensitivity
A. The Nature of Drug Allergy
B. Dangerous Drug-Allergy Reactions
C. Drug Sensitivities Mimic Allergy Symptoms
D. Definitions of Allergic/Hypersensitivity Reactions
E. Idiosyncratic Reactions
F. Intolerance
G. Toxicity
H. Hypersensitivity Vasculitis
I. Predominantly Organ-Specific Reactions
J. Urticaria
K. Fixed Drug Eruptions
L. Photosensitivity Reactions
M. Generalized Exfoliative Dermatitis
N. Thrombocytopenia
O. Hemolytic Anemia
P. Agranulocytosis
Q. Treatment: Withdrawal of the Suspected Drug
R. Symptomatic Treatment
S. Prevention of Allergic Drug Reactions
T. Pseudoallergy
U. Angioedema
V. Hypersensitivity Reactions
10.4 Risk Factors, Drugs and Patients
A. Hypersensitivity Risk Factors
B. Identification of a Drug Allergy
C. Allergy to Antibiotics
D. Case Report: Cross-Allergenicity
10.5 Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
A. Fixed Drug Eruptions
B. Erythema Multiforme-Like Eruptions
Case Report: Lamictal Induced Stevens Johnson Syndrome
C. Fluoroquinolones
E. NSAIDs Cross Reactivity Case Report
F. Radiographic Contrast Media
G. Local Anesthetics
H. Anticonvulsants (AED)
10.6 Summary and Conclusions
References
Chapter 11: Drug Induced Falls
James T. O'Donnell Pharm.D., M.S., FCP and James J. O'Donnell III, M.S., Ph.D.
11.1 Introduction
11.2 The Definition of Fall
11.3 Epidemiology
11.4 Causes and Risk Factors
A. Physiological Risk Factors for Falls in the Elderly
B. Psychological Risk Factors
C. Medical Conditions
11.5 Medication-related Falls
11.6 Types of Medications that Increase the Risk of Fall
A. Centrally Active Medications
B. Benzodiazepines
C. Antipsychotics
D. Antihypertensives
1. Orthostatic Hypertension and Risk of Fall
E. Opioids
11.7 Marijuana
11.8 Alcohol
11.9 Hip Fractures
11.10 Polypharmacy
11.11 Fall Risk Assessment
11.12 Types of Assessments
11.13 Strategies for Fall Prevention in Institutionalized Settings
A. Screening
B. Addressing Risk Factors
1. Monitoring Patients
2. Environmental Interventions
3. Educational Programs
4. Reducing Fall Injury
C. Discharge Planning
D. Disseminating Evidence: Awareness and Intervention Work!
11.14 Summary and Conclusions
References
Chapter 12: Drug Induced Movement Disorders
Jadwiga Najib, B.S. Pharm.D., BCPS, and Meagan Bailey, M.D.
12.1 Introduction
12.2 Presentation
12.3 Agents Associated with Drug-Induced Movement Disorders
12.4 Risk Factors
12.5 Sequelae of Drug-Induced Movement Disorders
12.6 Theories of Causation
12.7 Drug-Induced Movement Disorders in Children and Adolescents
12.8 Drug-Induced Movement Disorders in the Elderly
12.9 Acute/Intermediate Drug-Induced Movement Disorders
A. Dystonia
1. Presentation
2. Implicated agents
3. Risks
4. Management
B. Ataxia
C. Bruxism
D. Neuroleptic Malignant Syndrome
E. Serotonin Syndrome
12.10 Chronic Drug-Induced Movement Disorders
A. Akathisia
1. Presentation
2. Case study: Trazodone-induced akathisia
3. Implicated agents
4. Other drugs
5. Risks
6. Management
B. Parkinsonism
1. Presentation
2. Case Study: Neuroleptic-Induced Parkinsonism
3. Implicated agents
4. Other drugs
5. Risks
6. Management
C. Myoclonus, Tremor, Tics, Asterixis
12.11 Persistent/Tardive Drug-Induced Movement Disorders
A. Tardive Dyskinesia
1. Presentation
2. Case Study: Neuroleptic induced oral buccal dyskinesia and akathisia
3. Implicated agents
4. Case Study: Metoclopramide induced oral buccal lingual dyskinesia
5. Risks
6. Management
B. Tardive Akathisia
C. Tardive Dystonia
1. Case Report: Neuroleptic induced cervical dystonia
D. Other Tardive Variants
12.12 Drugs Used for Movement Disorders
12.13 Monitoring
12.14 Clinical and Legal Issues in Psychiatry
12.15 Summary and Conclusions
References
Chapter 13: Acute Adverse Drug Events in Critical Care Emergency Department and Intensive Care Units
Gourang P. Patel, Pharm.D., M.Sc., BCPS, BCCCP, FCCM
13.1 Background
A. Epidemiology
B. Environment
13.2 High-Risk Medication-Related Events
A. Hypersensitivity Reactions
B. Cardiovascular Reactions
1. Blood pressure (BP)
2. Heart rate (HR)
3. Arrhythmias
C. Nephrotoxicity
1. Aminoglycosides
2. Amphotericin B
3. Intravenous contrast
D. Hypoglycemic Events
E. Infusion-Related Reactions
1. Extravasations
2. Propofol-related infusion syndrome (PRIS)
3. Intravenous N-acetylcysteine (NAC)
F. Reversal Agents
1. Protamine
2. Vitamin K
3. Naloxone
4. Flumazenil
13.3 Summary and Conclusions
References
Chapter 14: Nephrotoxic Drugs
Jason M. Kidd MD, Domenic A. Sica, M.D. and Todd W. B. Gehr, M.D.
14.1 Introduction
14.2 Framework of the problem
14.3 Basis for the kidney being susceptible to damage
14.4 Patient groups most susceptible to nephrotoxicity
14.5 Demographics of chronic kidney disease
14.6 Methods to assess renal function and/or damage
14.7 Level of renal function at which drug accumulation occurs
14.8 Nephrotoxic drugs
A. What constitutes prompt clinical action in the face of nephrotoxicity?
14.9 Nephrotoxicity scenarios
A. Lithium toxicity
B. Gentamicin toxicity
C. Dialysis-related issues
D. Drug Clearance in Relationship to Renal Failure
1. Case 1
2. Case 2
E. Angioedema with an ACE inhibitor
F. Fatal hyperkalemia with medications
G. Statin therapy and the development of myopathy
H. Nephrotoxicity related to checkpoint inhibitor use
14.10 Summary and Conclusions
References
Chapter 15: Drug Induced Liver Disease
James T. O'Donnell, Pharm.D., M.S., FCP, James J. O'Donnell III, M.S., Ph.D., Donald H. Marks, M.D., Ph.D., Paul Danese, Ph.D.
15.1 Introduction: The Problem of Drug-Induced Liver Disease
15.2 History of Adverse Drug Reactions
15.3 Overview of DILD, Epidemiology Risk Factors, Histopathology, and Diagnoses
A. Epidemiology of Drug Hepatotoxicity
B. Risk Factors
C. Histopathology
D. Diagnosis
15.4 Hepatic Drug Metabolism
15.5 FDA and DILD
15.6 Types of Liver Injury
A. Hepatitis
B. Massive Hepatic Necrosis (Fulminant Hepatitis)
C. Drug-induced Vanishing Bile Duct Syndrome
15.7 Specific DILD Product Areas and Case Discussions
A. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Use and Hepatoxicity
B. Isoniazid-Induced Hepatotoxicity
C. Acetaminophen
1. Acetaminophen Toxicity Assessment Nomograms
2. FDA Report - Acetaminophen Induced Liver Disease
D. Macrolide Hepatotoxicity
E. Methotrexate (MTX) Hepatotoxicity
F. Estrogens and Oral Contraceptive Steroids
G. Statins
H. Ticlopidine
I. ACE Inhibitors and AT II Receptor Antagonists
J. Fluoroquinolones
K. Terbinafine
L. Ketoconazole
M. Selective Serotonin Reuptake Inhibitors - Serzone Liver Toxicity
N. Herbal and Other Dietary Supplements and Hepatotoxicity
15.8 Summary and Conclusions
References
Chapter 16: Antineoplastic Therapy
Kathryn Schultz, Pharm.D. and Eris Tollkuci, Pharm.D.
16.1 Background
16.2 Chemotherapy - Antimetabolites
16.3 Chemotherapy - Antimicrotubules
16.4 Chemotherapy - Alkylators
16.5 Chemotherapy - Topoisomerase I Inhibitors
16.6 Chemotherapy - Topoisomerase II Inhibitors
16.7 Chemotherapy - Antitumor Antibiotics
16.8 Chemotherapy - Miscellaneous
16.9 Targeted Therapy
A. Infusion-related reactions (IRRs)
B. Immunotherapy (Immune Checkpoint Inhibitors)
1. Infusion-related reactions
2. Immune-Related Adverse Events (irAEs)
16.10 Tumor Lysis Syndrome
16.11 Hepatotoxicity
16.12 Summary and Conclusions
References
Chapter 17: Dangers of Opioids
Jennifer Splawski, M.S., Pharm.D., BCPS, James T. O'Donnell, M.S., Pharm.D., James J. O'Donnell III, M.S., Ph.D.
17.1 Introduction
A. Definitions
B. History
17.2 Pharmacology of Opioids
A. Effects
B. Opioid Neural Receptors
1. Central Nervous System (CNS) Receptors
2. Peripheral Nervous System (PNS) Receptors
C. Routes of Administration
1. Oral
2. Intramuscular
3. Subcutaneous
4. Intravenous
5. Transdermal
6. Sublingual and Buccal
7. Neuraxial
D. Metabolism
E. Excretion
17.3 Toxicity of Opioids
A. Respiratory Depression
B. Symptoms of Overdose
17.4 Epidemiology of Opioid Abuse
A. Opioid Abuse in Adolescents and Young Adults
B. Opioids in Pregnancy
17.5 Contributions to the Opioid Epidemic
A. Opiates Handed Out Like Candy to 'Doped-up' Veterans
B. United States Reaches $22 Million Settlement Agreement with CVS For Unlawful Distribution of Controlled Substances
C. Former Walmart Pharmacists Say Company Ignored Red Flags as Opioid Sales Boomed
D. Federal Judge Approves Landmark $8.3 Billion Purdue Pharma Opioid Settlement
17.6 Combatting the Opioid Epidemic
A. Prescription Monitoring Programs (PDMP)
B. Naloxone Dispensing
C. Medication for Opioid Use Disorder (MOUD)
1. Buprenorphine
A. Pharmacokinetics
B. Adverse Effects
C. Place in therapy
1. Methadone
A. Pharmacokinetics
B. Equianalgesic Dosing
C. Drug Interactions
D. Cardiovascular Effects
E. Consequences of Ignorance of Proper Dosing of Methadone
F. Methadone Legal Case Examples Involving Patient Demise
G. Applying Lessons Learned and Action for Institutional Committees
17.7 Case Reports: Opioid Toxicity Causing Respiratory Arrest, Brain Damage, and Death
A. Case Report: Respiratory Arrest and Brain Damage Following Morphine Overdose
B. Case Report: Fentanyl Epidural Respiratory Arrest
C. Case Report: Fentanyl (Duragesic (R)) Death in Discharged Patient
D. Case Report: High Dose Fentanyl Patch Prescribed in Opiate-Naive Patient-Death
E. Case Report: Heroin and Other Opioids
F. Case Report: Hydromorphone (Dilaudid (R)) Respiratory Arrest
17.8 Investigation and Prosecution of Pain Clinics by the Department of Justice (DOJ)
17.9 Summary and Conclusions
References
Chapter 18: Adverse Effects of Diabetic Drugs: Focus on Hypoglycemia
Gourang P. Patel, BS Chem, PharmD, MSc, BCPS and James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN
18.1 Diabetes Demographics and Epidemiology
18.2 Insulin
18.3 Insulin Preparations
18.4 Clinical Use of Insulin
A. Dosing
18.5 Hypoglycemia (Low Blood Sugar)
A. Etiologies of hypoglycemia
B. Insulin-induced hypoglycemia
C. Deaths by Hypoglycemia
18.6 Pathophysiology and Clinical Symptoms of Hypoglycemia
18.7 Incidence
18.8 Pathophysiology and Biochemistry of Hypoglycemia
18.9 Adverse Reactions Involving Hypoglycemia
A. Insulin damages baby's brain; pharmacist error suggested
18.10 End Product Testing Recommended
18.11 Insulin Murders
18.12 Hypoglycemia from the Sulfonylurea Derivatives
18.13 Adverse Effects of the Sulfonylureas
18.14 Drug Interactions with Sulfonylureas
18.15 The Gliptin Class New drugs for Diabetes Treatment Type 2 Diabetes
18.16 Thiazolidinediones
A. Hepatic Failure
B. Bladder Cancer
18.18 Summary and Conclusions
References
Chapter 19: Parenteral Nutrition Related Errors and Complications
Erica M. Fernandez, Pharm.D., BCCCP, BCPS
19.1 Introduction
19.2. Basic principles of PN
19.3 PN Provision Categories
A. Prescribing
B. Transcribing and Verification
C. Compounding
D. Administration
19.4. Monitoring and Complications
A. Glycemic Control
B. Refeeding Syndrome
C. Hepatobiliary Complications
D. Complications involving micronutrients
19.5 PN Component Shortages and Adverse Events
19.6 Summary and Conclusion
References
Chapter 20: Antidepressants: Clinical Use and Litigation
Henry Cohen, Pharm.D., M.Sc., FCCM, BCPP, BCGP and Michael Liu, Pharm.D., MBA, BCCCP, BCNSP, BCPS
20.1 Major Depressive Disorders
20.2 Antidepressant Pharmacology
20.3 Antidepressant Overdose
A. Trazodone and Permanent Neurologic Sequelae
20.4 Antidepressants and the Patient with Suicidal Ideation
A. Prozac and Suicidal Ideation
1. Woulfe v. Eli Lilly & Co.
2. Espinoza v. Eli Lilly & Co.
3. Cassidy v. Eli Lilly & Co
B. Paxil and Suicidal Ideation
1. Dolin v. GlaxoSmithKline
C. Antidepressant and Increased Suicidality in Pediatrics
1. Schilf v. Eli Lilly & Co.
20.5 Broken Heart Syndrome: Tako Tsubo Cardiomyopathy Associated with Use of Antidepressants
20.6 The Adverse Effects of Antidepressants and the Duty to Warn
A. Docken v. Ciba-Geigy
B. Stebbins v. Concord Wrigley Drugs, Inc. et al.
C. Morgan et al. v. Wal-Mart Stores, Inc.
D. Kampmann v. Mason
E. Cottam v. CVS
20.7 Antidepressants and Alcohol
A. Kirk v. Michael Reese Hospital
B. Hand v. Krakowski
20.8 Selective Serotonin Reuptake Inhibitors and the Serotonin Syndrome
20.9 Hepatic Cytochrome P450 Drug Interactions and Cyclic Antidepressants
20.10 Antidepressants and Herbal Agents Drug Interactions
20.11 Serzone and Liver Disease
20.12 High Blood Pressure Associated with Venlafaxine Use
20.13 SSRI use and Birth Defects
20.14 Bupropion XL and Seizures
20.15 The Pharmacist's Role
20.16 The Omnibus Budget Reconciliation Act
20.17 How Safe is it to Buy Prescription Medications Over the Internet?
20.18 In a Perfect World
20.19 Summary and Conclusions
References
Chapter 21: Contrast Media Neurotoxicity Following Myelography
Stephanie E. Tedford, Ph.D., and James T. O'Donnell, Pharm.D., M.S., FCP
21.1 Introduction
21.2 Case Reports
A. Case I Intrathecal Iopamidol
B. Case II Intrathecal Iothalamate
21.3 Discussion
A. Mechanisms for cerebral (neurotoxic) injury
B. Contrast-induced neurological and cognitive deficits
C. Contrast-induced visual and auditory impairment: Further evidence for cerebral insult to cortical brain structures
21.4 Summary and Conclusions
References
Chapter 22: Fetal Drug Exposure
Damani Parran, Ph.D., MBA, DABT, James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D.
22.1 Introduction
22.2 Critical Periods of Human Development and Susceptibility
22.3 Special Considerations of Drug Exposure during Pregnancy
22.4 Historical Human Developmental Toxicants
A. Thalidomide
B. Ethanol
C. Diethylstilbestrol
D. Retinoids
E. Cocaine
22.5 Developmental Toxicity of Prescription Drugs
A. Valproic Acid
B. Phenytoin
C. Warfarin
D. Benzodiazepines
22.6 Additional Prenatal Environmental Influences
A. Malnutrition
B. Poverty
C. Emotional State
D. Mother's Age
E. Infections and Diseases
22.7 FDA Pregnancy Categories for Prescription Drug Labeling; Final Rule
22.8 Analyses of Litigated Cases Alleging Fetal Drug Injury
A. Effects of Methadone and Smoking on the Fetus
B. Effects of Lisinopril on Fetus - Defense of Causation
22.9 Summary and Conclusions
References
Chapter 23: Geriatric Medication Misadventures
Rodney G. Richmond, M.S., Pharm.D., BCGP, FASCP and James C. Norris, Ph.D., DABT, ERT
23.1 Introduction
A. Outpatient Medication Use
B. Hospital Medication Use
C. Long-Term Care Medication Use
23.2 Altered Clinical Response to Drugs
A. Pharmacokinetics
B. Pharmacodynamics
23.3 Preventable Drug-Related Problems
A. Polypharmacy
B. Transitions of Care
C. Inadequate Monitoring
D. Potentially Inappropriate Medication Use
23.4 Legal Cases Application
23.5 Summary and Conclusions
References
Chapter 24: Medication Errors
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, R.Ph. and James J. O'Donnell III, M.S., Ph.D.
24.1 History and Overview
24.2 Medication Errors in Epidemic Proportions
24.3 Types of Medication Errors
A. Enhancing Healthcare Team Outcomes
B. Improving Reporting of Medication Errors
24.4 Medication Use Process
24.5 System Errors
24.6 Which Drugs are Most Often Involved in Medication Errors?
24.7 Prevalence of Medication Errors
24.8 Vaccine Errors
24.9 How has Modern Research Improved Therapeutics and Reduced Drug-Related Morbidity? Pharmacogenomics
24.10 Systems for Medical Error Prevention
A. Electronic Prescribing (E-prescribing)
B. When Electronic Prescribing is Unavailable
C. Effective Drug Monitoring Systems
D. The Importance of Continuing Education
E. Reporting All Adverse Drug Events
24.11 Summary and Conclusions
References
Chapter 25: Anticoagulants: Therapeutics, Risks, And Toxicities
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D., Stephanie E. Tedford, Ph.D.
25.1 Introduction
25.2 Summary of Anticoagulant Therapy
A. Definition
B. Use
1. Treatment of coronary heart disease
2. Warfarin and dabigatran
3. Treatment of thrombogenesis
25.3 Limitations of Current Therapy
A. Heparin
B. Low Molecular Weight Heparin (LMWH)
C. Heparin-Induced Thrombocytopenia (HIT)
1. Pathogenesis of the autoimmune response
2. Pathogenesis of the prothrombotic state
3. Clinical presentation of HIT
4. Diagnosis
a. Dismissing HIT
b. Diagnosing HIT
2. Two Approaches: class and titer
5. Treatment of HIT
a. Fondaparinux
b. Re-exposure to heparin
6. Conclusion HIT and HITT
D. Warfarin
25.4 Monitoring Warfarin Oral Anticoagulation
25.5 Alternatives to Warfarin - DOACs
A. Pradaxa (Dabigatran) vs. Warfarin
B. Direct Oral Anticoagulation (DOAC) Therapies
C. DOAC reversal agents
D. Antiplatelet Therapy
25.6 Summary and Conclusions
References
Part III: PHARMACISTS, PHARMACY AND PHARMACY PRACTICE
Chapters 26 - 33
Chapter 26: Pharmacy Practice, Managed Care, And Manufacturers
F. Randy Vogenberg R.Ph., Ph.D. and Rita Marcoux R.Ph., MBA
26.1 Introduction to Pharmacy and the Related Managed Health Care Environment
26.2 Pharmacists as Health Care Professionals: Training, Support Staff, and Life-long Learning
A. Registration, Certifications, Credentialing, Colleges Of Pharmacy, And Accreditation Matters For Pharmacy Professional Staff
26.3 Practice Sites: Inpatient, Ambulatory/Community, Specialty, Long Term Care, and Other (compounding, nuclear)
A. Practice settings, Practice site Certification, Pharmacist practice versus the Business of pharmacy, Credentialing, and Accreditation matters
26.4 Issues for Pharmacy Practice, Insurance, and Managed Care In the Near Future
A. The landscape of Practice Sites and Changing Business of Health Landscape
26.5 Current and Near Future Issues for Pharmacists
A. Landscape of Pharmacy Practice, The Changing Professional Marketplace
26.6 Pharmaceutical Manufacturer Through Wholesaler and Distribution Supply Chain
26.7 Manufacturers: Traditional and Innovative Segments
A. Non-Biologic Medications
B. Research-Intensive, Biologics, Gene, and Generic Segments
1. Biologic Medications
26.8 Pharmaceutical Manufacturer Customers
A. Organization and Operations
B. Other Targeted Customer and Class of Trade Segments
C. Contracting and Change in the Pharmaceutical Industry
26.9 Health Care Industry Changes in the Near Future
26.10 Summary and Conclusions
References
Chapter 27: The Pharmacist's Utilization of the National Patient Safety Goals to Contribute to Safe and Effective Medication Use
Jennifer Splawski, Pharm.D., MS, BCPS and Heather Minger, Pharm.D., BCPS
27.1 Introduction
A. Overview of 'The Goals'
27.2 Goal 3 and the Pharmacist's Role
A. NPSG.03.05.01 relating to Anticoagulation
1. Introduction
2. Warfarin Overview
3. Patient monitoring
4. Patient Education
5. Direct Oral Anticoagulant
6. Anticoagulation Reversal Overview
7. Anticoagulation Reversal Programs
8. Patient Education
B. NPSG.03.06.01 relating to Reconciling Medication Information
1. Introduction
2. The Process of Medication Reconciliation
3. Improved Accuracy
4. Decreased Mortality
5. Allergy Identification
6. Discharge Medication Reconciliation
7. Utilization of the Pharmacist Extenders in Medication Reconciliation
27.3 Summary and Conclusions
References
Chapter 28: Pharmacist Malpractice and Liability
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN and James J. O'Donnell III, M.S., Ph.D.
28.1 Introduction
28.2 The Science of Risk Management
28.3 Claims Studies
The Pharmacists Mutual Claims Study
CNA Claims Study (CNA/HPSO)
A. CNA Database and Methodology
B. Most Common Categories of Errors
C. Claim Analysis by Insurance Source & Licensure Type: Pharmacists v. Technicians
D. Factors Affecting Wrong Drug Dispensing Errors
E. Drugs Involved in Claims
F. Most Common Error: Wrong Drug
G. Wrong Drug Strength
H. Wrong Directions
I. Wrong Route of Administration
J. Lack of Drug Review
K. Counseling: A Powerful Weapon Against Liability
L. Non-Bodily Injury
M. Miscellaneous Errors
N. Wrong Directions
O. Lack of Drug Review
P. Avoiding Errors and Malpractice
28.4 Specific Pharmacist Malpractice Case Reports / Topics
A. Duty to Warn?
B. Wrong Drug
C. Quotas and Metrics: Contributing to the Problem?
D. Controlled Substances Violations by Pharmacists
E. Methotrexate (MTX) errors
28.5 Pharmacists Need to do the Right Thing
28.6 Steps Toward a Better Outcome
28.7 Summary and Conclusions
References
Chapter 29: Regulation of Pharmacy Practice
Ned Milenkovich, Pharm.D., J.D.
29.1 Introduction
29.2 Licensure of Professional Activities
A. Boards of Pharmacy - A Closer Look
B. National Association of Boards of Pharmacy
29.3 Practice Standards
A. Legally Circumscribing Pharmacy Practice
29.4 Licensure Process to Practice Pharmacy
A. Licensing
B. Licensing of Pharmacists
29.5 The Different Types of Pharmacy Licenses
A. Disciplinary Actions
B. Causes of Disciplinary Action
C. Practice Focus on Licensure
D. Ongoing Professional Education
E. Support Personnel
29.6 Federal Drug Laws
A. Obra '90
B. Medicare
C. Medicare Part D
D. Medicaid
E. Prescription Drug Coverage
F. Fraud, Waste and Abuse
G. 340b Drugs
H. Pharmacy Compounding
I. FDA Rems
J. DEA
29.7 Pharmacy Practice: Putting it Together
A. Pharmacy Practice: An Ongoing Progression
B. Collaborative Practice Agreements
C. Drug Utilization Review (DUR)
D. Other Mandates Impacting Pharmacy Practice Quality Assurance Regulations
E. Health Insurance Portability and Accountability Act Of 1996, As Amended
Chapter 30: Emergency Department Pharmacist
Victor Cohen, B.S., Pharm.D., BCPS, CGP, Samantha P. Jellinek-Cohen, Pharm.D., BCPS, CGP, Megan Musselman Pharm.D., M.S., BCPS, BCCP
30.1 Introduction
30.2 Epidemiology of Drug Injury and Contributing Risk Factors
A. Contributing Risk Factors
30.3. Etiology and Sources of Drug Injury in the ED
30.4 Clinical Pharmacy in the ED: A Historical Perspective
30.5 The ED Pharmacist Plays a Dual Role at Maimonides Medical Center
30.6 The ED Pharmacist: A Sub-specialist in Emergency Medicine
A. Training and Education
B. Certification
30.7 The ED Pharmacist as a Generalist
30.8 The ED Pharmacist Ensuring Optimal Continuum of Care
A. The ED and Infectious Diseases
B. The ED Pharmacist and the Ambulatory Care Interphase
C. The ED Pharmacist and Transitions of Care (TOC)
1. Medication admission notes in the ED
D. The ED Pharmacist as a Clinical Toxicology Consultant
E. The ED Pharmacist and the Cardiology Interface
F. The ED Pharmacist and Neurological Emergencies
G. The ED Pharmacist and Pulmonary Emergencies
H. The ED Pharmacist and Public Health Services in the ED
30.9 Building Layers of Defense Against Drug Injury
A. Detecting and Preventing Drug Injury in the ED
B. The ED Pharmacist and Community Surveillance for Adverse Drug Reactions
30.10 Pharmacy Practice in the ED: Pharmacotherapy Specialty
30.11 Summary and Conclusions
References
Chapter 31: Pharmacy Case Law Review
Roger N. Morris, R.Ph., J.D., and William J. Stilling, R.Ph., M.S., J.D.
31.1 Administrative Law
A. Due Process-Pharmacist Licensure
1. Berjikian, et al. v. Franchise Tax Board et al., No. CV 13-06301 DDP, 2015 WL 1185472 (C.D. Cal. March 12, 2015)
31.2 Antitrust
A. State Regulatory Boards Immunity
1. North Carolina Bd. of Dental Examiners. v. Federal Trade Commission, 135 S. Ct. 1101 (Feb. 25, 2015)
31.3 Civil Procedure
A. Spoliation of evidence-Pharmacy's Duty to Maintain Evidence of Misfill
1. Burton v. Walgreen Co., 2015 WL 4228854 (D. Nev. July 10, 2015)
31.4 Conscientious Objection
A. Emergency Contraception
1. Stormans, Inc. v. Wiesman, 794 F.3d 1064 (9th Cir. 2015)
31.5 Controlled Substances
A. Duty to Verify DEA Registration
1. Farmacia, Yani, 80 Fed. Reg. 29,053 (May 20, 2015)
2. JM Pharmacy Group Inc., d/b/a/ Farmacia Nueva and Best Pharma Corp., 80 Fed. Reg. 28,667 (May 19, 2015)
B. Constitutionality
1. McFadden v. United States, 135 S. Ct. 2298 (June 18, 2015)
31.6 Criminal
A. Violations of Pharmacy Law Applied to Non-pharmacists
1. Moore v. State of Florida, NO. 1D14-3527, 2015 WL 4464689 (Fla. Dist. Ct. App. July 21, 2015), reh'g denied (Sept. 1, 2015)
B. PMP Records
1. Lundy v. State, 26 N.E.3d 656 (Ind. Ct. App. Feb. 20, 2015)
C. Second Degree Murder
1. U.S. v. Barry J. Cadden, et al., 2014 WL 7151586 (D. Mass. Dec. 16, 2014)
31.7 Defamation
A. Physician against Pharmacist
1. LeFrock v. Walgreen Co., 77 F. Supp.3d 1199 (M.D. Fla. Jan. 16, 2015)
B. Duty to Fill
1. Kadambi v. Express Scripts, 2015 WL 475373 (N.D. Ind. February 5, 2015)
31.8 Employment
A. Discrimination (Pregnancy)
1. Torres-Skair v. Medco Health Solutions, Inc., 595 F.App'x 847 (11th Cir. Dec., 4, 2014)
B. Employment at Will
1. Hoven v. Walgreen Co., 751 F.3d 778 (6th Cir. June 2, 2014)
C. Americans with Disability Act
1. Stevens v. Rite Aid Corp., et al., 6:13-cv-00783 (N.D.N.Y., September 23, 2015)
D. Overtime Class Action
1. Baugh v. CVS Health, et al., 2:15-cv-00014 (E.D. Penn., July 27, 2015)
E. Medical Marijuana
1. Coats v. Dish Network, 350 P. 3d, 849 (Colo. June 15, 2015)
31.9 Fraud and Abuse
F. False Claims
1. United States v. Express Scripts, Inc., 602 F. App'x 880 (3rd. Cir. Feb. 20, 2015)
G. False Claims-Generic Substitutions
1. Doe v. Houchens Indus., Inc., No. 1:13-CV-00196-RLY, 2015 WL 133706 (S.D. Ind. Jan. 9, 2015)
H. False Claims & Anti-Kickback Statute
1. U.S. ex rel. Kester v. Novartis Pharm. Corp., No. 11 CIV. 8196 CM, 2015WL 1650767 (S.D.N.Y. Apr. 10, 2015)
I. Consumer Fraud
1. City of Chicago v. Purdue Pharma L.P., 2015 WL 2208423 (N.D. Ill. May 8, 2015)
31.10 Negligence
A. Duty to Provide Medication
1. Davies v. Virginia CVS Pharmacy, LLC, et al., 7:14-CV-00175, 2014 WL 6460787 (W.D. Va. Nov. 17, 2014)
B. Duty Not to Dispense
1. Oleckna v. Daytona Disc. Pharmacy, 162 So. 3d 178 (Fla. Dist. Ct. App. 2015)
31.11 Privacy
C. Patient Privacy-Vicarious Liability
1. Walgreen Co. v. Hinchy, 25 N.E.3d 748 (Ind. Ct. App. Jn. 15, 2015) reh'g of, 21 N.E.3d 99 (Ind. Ct. App. Nov. 14, 2014)
D. Text Messages
1. Thompson v. CVS Pharmacy, Inc., 6:204-cv-02081 (M.D. Fla. Dec. 19, 2014)
E. Robocalls
1. Kolinek v. Walgreen Co., 2014 WL 3056813, (N.D. Ill. July 7, 2014)
31.12 Product liability
A. Learned Intermediary Doctrine
1. Watts v. Medicis Pharm. Corp., 342 P.3d 847 (Ct. App. 2015), review granted in part (Sept. 22, 2015)
B. Product Liability (applicability to pharmacists)
1. Randol Mill Pharmacy v. Miller, 465 S.W.3d 612 (Tex. 2015), reh'g denied (Sept. 11, 2015)
Chapter 32: Pharmacy Compounding - Patient Injury and Regulatory Compliance
Willis C. Triplett, Pharm.D.
32.1 Introduction
32.2 Compounding Trends and Driving Forces
32.3 Optimizing the Regulatory Balance Between "Manufacturing" versus "Compounding"
32.4 Investigations, Indictments, Convictions, and Acquittals after the Fungal Meningitis Outbreak
32.5 Memorandum of Understanding (MOU)
32.6 U SP, NABP, and the State Pharmacy Regulatory Authorities
32.7 Physician and Medical Office Compounding
32.8 Compounding "Center of Excellence" ("COE") and the Quality Assurance Paradigm Shift
32.9 Conclusions and Forecasts Regarding Patient Injury from Healthcare Compounding
32.10 Recommended Readings
CHAPTER 33: Compounding Pharmacy Fraud and Unethical Practices
James T. O'Donnell, Pharm.D., M.S., FCP
33.1 Introduction
33.2 Criminal Prosecutions of Pharmacy Compounders
33.3 Over-Prescribing and Over-Charging of Compounded Drugs
A. Department of Justice News Releases
B. News Reports in Newspapers
33.4 Not Yet Criminal? Insurance Companies Fighting Back
A. No-Fault Pain Compounded and Topical Pain Product
B. Report Challenging the Pricing and Efficacy of a Compounded Pain Cream Prescription
C. Ingredients and Costs of Pain Cream
33.5 General Discussion - Compounded Pain Topical Creams
A. Evidence of Efficacy?
B. Expensive Ingredients
33.6 Ingredients Review of Efficacy and Mechanism of Action
A. Diclofenac
B. Menthol (Methyl Salicylate)
C. Lidocaine
1. Lidocaine Topical Toxicity
D. Amitriptyline
E. Cyclobenzaprine
F. Dimethylsulfoxide (DMSO)
33.7 Global Opinions for the Prescription CPTM formula 8-NC Claim Challenge
33.8 Discussion and Further Bases of Opinions
33.9 Overbilling of Topical Diclofenac Gels, Lidocaine Creams and Ointments and Patches
A. Diclofenac 3" (Solaraze)
B. Lidocaine Topical Commercial Products
33.10 Recommendations
33.11 Summary and Conclusions
References
Part IV: FORENSIC AND TOXICOLOGY ISSUES
Chapters 34 - 42
Chapter 34: Alcohol
James T. O'Donnell, Pharm.D., M.S.. FCP and James J. O'Donnell III, M.S., Ph.D.
34.1 Introduction
34.2Alcohol Injury Epidemiology
34.3 Alcohol Intoxication Effects in Litigation
34.4 Differences between Civil litigation involving alcohol from Criminal/DUI
34.5 Settings for Alcohol Related Civil Litigation
A. Employment
34.6 Police Activities
A. Police Pursuit
B. Excessive Police Force
C. Alcohol Effects on Aggression and Judgment
34.7 Motor Vehicle Collisions
A. Vehicle/Vehicle
B. Motorcycle Cases
C. Boating
D. Vehicle/ Pedestrian
34.8 Alcohol and Falls
A. Stairs - no alcohol test - fall down bar stairs
B. Stairs - Residential Stairs Fall -Adjustment of Calculated BAC due to Morbid Obesity
C. Tripped on Threshold - Sued Condominium Association
34.9 Dram Shop (Bar Liability for Serving Intoxicated Persons)
34.10 Biomarkers for Alcohol
A. Family Law
B. False Positive Alcohol Biomarkers in Diabetes
34.11 Miscellaneous Topics Reports
A. Retrograde Extrapolation (See also legal cases Floyd and Cuellar earlier in this chapter.
B. Appellate Court reverses Trial Court Barring of BAC
34.13 Summary and Conclusions
References
Chapter 35: Cocaine
James C Norris, Ph.D., D.A.B.T and Rodney G Richmond, R.Ph., MS, CGP, FASCP, FACFE
35.1 Historical Background
35.2 Medical Usages of Cocaine
35.3 Illegal Usage of Cocaine
35.4 Routes of Administration
35.5 Effects of Cocaine
35.6 Psychotic Disorders Induced by Cocaine
35.7 Addiction
35.8 Cognitive Deficits
35.9 Prenatal Cocaine Exposure (PCE)
35.10 Violence
35.11 Tolerance
35.12 Withdrawal or Abstinence Effects
35.13 Mechanisms of Action
35.14 Metabolism
35.15 Blood Levels
35.16 Urine Levels
35.17 Impairment
35.18 Associated Deaths with Cocaine Usage
35.19 Summary and Conclusions
References
Chapter 36: Marijuana: Pharmacology, Toxicology and Forensic Issues
Stephanie E. Tedford, Ph.D., James T. O'Donnell PharmD, MS, FCP, and James J. O'Donnell III MS, Ph.D.
36.1 Introduction
36.2 Federal Law vs. State Law
A. Harrison Narcotics Tax Act
B. Comprehensive Drug Abuse Control and Prevention Act
C. Marijuana Drug Laws at the State Level
D. Legalization
E. Decriminalization
F. Marijuana Policy Project
36.3 Controlled Prescription and Distribution of Medical Marijuana
A. Medical Conditions Approved for Treatment with Medical Marijuana
B. Marijuana and Epilepsy
C. Marijuana and Endometriosis
36.4 Pharmacological Properties of Marijuana
A. Active Compounds and Overview of Pharmacology
B. Variability in Marijuana Regulation and Content Uniformity
C. Routes of Administration
D. Pharmacokinetics - Time Course of THC and Metabolites
E. Pharmacodynamics
F. Vaping vs. Traditional Smoking of Cannabinoids
G. Traditional Smoking vs. Ingestion of Cannabinoids
H. Pharmacokinetics Applications: Timing of the Peak Euphoric Effect
I. Bioavailability
1. Is There a Good Model for Marijuana Ingestion?
2. Overall Advantages of the Oromucosal Route?
3. Can the Effects After Ingestion of Marijuana be Made More Objective?
36.5 Marijuana Safety
A. Serious Adverse Effects
B. Risk of Psychosis
1. Drug-induced Psychosis: Potential Mechanisms
2. Vaping and Associated Risk for Psychosis
C. Pulmonary Function
D. Risk of Addiction
E. Effect on Brain Development
F. Long Term Behavioral Effects
G. Age of Onset of Use
36.6 Impact of Legalization
A. Hospital Resources
B. Driving Under the Influence of Drugs
C. Relationship of Marijuana Use and Co-Use with other Substances
36.7 Analysis and Testing for Marijuana Use
36.8 Scientific Data Relating to THC
A. Blood THC vs. Brain THC: Any Relationships?
B. Relationships Between Percent Plant-THC and Plasma-THC
C. Is There a Relationship Between Percent THC in the Smoked Cigarette and Plasma THC?
D. Relation Between Degree of "High" and Plasma THC
E. Occasional Marijuana Users vs. Practiced Users
F. Is THC the Only Psychoactive Cannabinoid?
G. Urine Testing for Cannabinoids: Clinical or Evidentiary Value?
H. Impairment and Marijuana: Laboratory and On-Road Driving Performance Data
I. Hospital and Provider Considerations
36.9 Forensic Case Reports
36.10 Summary and Conclusions
References
Chapter 37: Drug Evaluation and Classification Program: An Evidence-Based Analysis
Fran M. Gengo Pharm.D., FCP and Anna Mattle, Pharm.D., M.S.
37.1 Introduction
37.2 The 12 Steps of DRE Examinations
37.3 Scientific Evaluation of DRE Examinations
A. Step 2: Interview of Arresting Officer
B. Step 3: Preliminary Examination and Initial Pulse Measurement
C. Step 4: Eye Examination
D. Step 5: Divided Attention Tests
E. Step 6: Second Pulse Reading, Body Temperature, and Blood Pressure Measurement
F. Step 7: Eye Examination of Pupil Size in Various Lighting Conditions
G. Step 8: Assessment of Muscle Tone
H. Step 11: DRE Officer Opinion Statement
I. Step 12: Toxicology Sample
37.4 Literature Evaluations And Critiques Of Dre
37.5 Cannabis
37.6 Statistical Validity and Overall Strength of DRE Studies
37.7 DRE Support Literature
A. Bigelow et al. 1985 Study
B. Heishman et al. 1996 and 1998 Studies
C. Smith et al. 2002 Study
D. Shinar and Schechtman 2005 Study
E. Specific Identification of Drug Class by DRE Officers in Validation Studies
37.9 Summary
37.10 Summary and Conclusions
References
Chapter 38: Involuntary Intoxication
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D., William Vaughn, J.D.
38.1 Introduction
38.2 Legal Defense Considerations for a Violent Crime
38.3 Confirming That Drugs are Involved in a Violent Crime
38.4 Beyond Pharmacology: The Multifactorial Role of Drugs in Aggression and Violence
38.5 Association of Drugs with Aggression and Violence
38.6 Mechanisms of Drug-Induced Violence
38.7 Intoxication of Victim Defense
38.8 Summary and Conclusions
References
Chapter 39: Drug-Induced Aggression and Violence
Peter D. Anderson, Pharm.D., BCPP
39.1 Classification of Aggression
39.2 Causes of Aggression and Violence
A. Neurobiology of Aggression
B. Medical and Psychiatric Causes of Aggression
39.3 The Role of Drugs as a Cause of Violence
A. Introduction
B. Problems with the Literature
C. Specific Drugs or Drug Classes that cause aggression
1. Ethanol
2. Lysergic Acid Diethylamide
3. Phencyclidine and Ketamine
4. Anabolic Steroids
5. Insulin
6. Psychostimulants
7. Benzodiazepines
8. Selective Serotonin Reuptake Inhibitors
9. Varenicline
10. Environmental Chemicals
39.4 The Drug-Induced Insanity Defense
39.5 Summary and Conclusions
References
Chapter 40: Forensic Drug Testing Chapter
James J. O'Donnell III, M.S., Ph.D, and James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN
40.1 Introduction
40.2 Non-Regulated Drug Testing
40.3 Regulated Drug Testing
40.4 Voluntary Programs
40.5 Establishment of a Workplace Program
A. Written Policy
B. Employee Assistance Programs
C. Employee Awareness Training
D. Supervisor Training
E. Drug Testing
40.6 The Drug-Testing Process
A. Specimen Collection
B. Accessioning
C. Drugs to Be Tested
D. Screening Tests
E. Confirmation Tests
F. Reporting and Storage of Samples
G. Prevention Against and Detection of Drug Test Cheating
40.7 Additional Program Aspects
A. The Medical Review Officer (MRO)
B. Public Interest Exclusions (PIE)
C. Blind Performance Testing
D. Alcohol Testing
40.8 Special Drug-Testing Issues
A. Type of Matrix
1. Hair Testing
2. Saliva Testing
3. Sweat Testing
4. Blood
5. Urine
B. Alternate Sources of Drug Exposure
C. Amphetamine Testing Issues
D. Medical Use of Drugs
40.9 Legal Aspects of Workplace Drug-Testing
A. Constitutional Issues
B. State and Federal Mandates
40.10 Discovery: The "Litigation Package"
40.11 Case Reports
40.12 Summary and Conclusions
References
Chapter 41: Postmortem Redistribution and Interpretation of Drug Levels
Gourang P. Patel Pharm.D., M.Sc., BCPS, BCCCP, FCCM
41.1 Abstract
41.2 Introduction
41.3 Review of a Case File
41.4 Postmortem Considerations
A. Physiologic Changes in the Body After Death
B. Drug Characteristics
41.5 Analysis of Drug Level Information
41.6 Summary and Conclusions
References
Chapter 42: Addiction as Mitigation
Barry D. Hargan, M.S., MHA and James T. O'Donnell, Pharm.D., M.S., FCP
42.1 Introduction
42.2 Clinical Variables Which Contribute to the Onset of Addiction
A. Genetic Predisposition
B. Learned Behavior
C. Psychopathological Exposure
42.3 Substance/Medication-Induced Mental Disorder
A. Executive Summary of Opinion
B. Neurotoxicity Mechanisms of Alcohol and Anabolic Steroids in the Developing Brain
C. Anabolic Steroid Effects on Brain Structure and Function
D. Translational Impact - what does this mean to a teenager abusing large amounts of alcohol and steroids?
E. Clinical and Practical Applications of the Basic Neuroscience
F. Behavioral Abnormalities Associated with Anabolic Steroid Use
G. Defendant's Alcohol and Anabolic Steroid Use
1. Alcohol
H. Expert Opinions Regarding Substance-Induced Brain Damage Affecting Behavior
42.4 The Simplified Version of Neurobiology and the Addicted Brain
42.5 Cocaine
42.6 Expert Testimony Concerning Addictive Disorders
A. Role of the Addictions Expert
B. Some Testimony Experiences and the Limits of Opinions
C. Preparation
42.7 Additional Considerations Concerning Addiction Mitigation
A. Neuropsychological Evaluation
42.8 Summary and Conclusions
References
Chapters 1 - 9
Chapter 1: FDA and Drug Approval Process
Megan Walter, Pharm.D. and CDR Lindsay Wagner, Pharm.D., BCPS
1.1 Introduction
1.2 The New Drug Development Process
A. Discovery and Preclinical Research
B. Clinical Research
C. Investigational New Drug Application
D. Phases of Clinical Studies
E. Expanded Access Programs
F. Right to Try
1.3 New Drug and Therapeutic Biologic Application Process
A. New Drug Applications and Biologic License Applications
B. Fundamentals of NDA and BLA Submissions
C. NDA Classifications
1.4 FDA Review
A. Expedited Development and Review Programs
1. Accelerated Approval
2. Priority Review
3. Fast Track
4. Breakthrough Therapy
B. Labeling Review
1. Physician Labeling Rule (PLR)
2. Pregnancy and Lactation Labeling Rule (PLLR)
3. Additional FDA-Approved Patient Labeling
C. Risk Evaluation and Mitigation Strategies
D. Advisory Committee Meetings
1.5 The Generic Drug Approval Process
A. Abbreviated New Drug Applications
B. ANDA Approval
C. Generic Drug User Fee Amendments
1.6 Biosimilar Pathway
1.7 Over-the-Counter Drug Products
1.8 Postmarketing Surveillance
A. Adverse Event Reporting
B. FDA Adverse Event Reporting System
C. Post Marketing Requirements and Commitments
D. Sentinel Network
E. Drug Safety Oversight Board
1.9 Applicable Statutes and Implementing Regulations
A. Food and Drug Acts - 1906
B. Food, Drug and Cosmetic Act - 1938
C. Durham-Humphrey Amendment - 1951
D. Kefauver-Harris Amendment - 1962
E. Orphan Drug Act - 1983
F. Drug Price and Competition and Patent Term Restoration Act - 1984
1. Revision of New Drug Application Regulations - 1985
2. Revision of Investigational New Drug Application Regulations - 1987
3. Treatment Use of Investigational New Drugs - 1987
G. Prescription Drug User Fee Act (PDUFA) - 1992
H. FDA Modernization Act (FDAMA) - 1997
I. FDA Amendments Act (FDAAA) - 2007
J. Food and Drug Administration Safety and Innovation Act (FDASIA) - 2012
K. The Drug Quality and Security Act (DQSA) - 2013
L. 21st Century Cures Act - 2016
M. Food and Drug Administration Reauthorization Act (FDARA) - 2017
N. Coronavirus Aid, Relief, and Economic Security Act (CARES Act) - 2020
1.10 Conclusion
1.11 Glossary of Terms
References
Chapter 2: The Front Lines of Clinical Research: The Industry and Ethical Considerations
Jonathan Young, Ph.D.
2.1 Introduction
2.2 Clinical Trial Service Providers
A. Food and Drug Administration
B. Clinical Trial Sponsor
C. Contract Research Organizations
D. Study Monitors
2.3 Clinical Trial Site
A. Site Management Organizations
B. Institutional Review Boards
2.4 The Evolution of Ethical Principles in Clinical Research
A. Respect for Persons
B. Beneficence
C. Justice
D. How the Investigator Applies Ethical Principles
2.5 Regulations Governing Institutional Review Boards
A. What Institutional Review Board Members Should Know about Clinical Research
B. What Institutional Review Board Members Should Know about Their Responsibilities
2.6 What the Site Should Know about Institutional Review Boards
A. What Research Requires Institutional Review Board Approval and Oversight
B. Requirements of an Investigator for Institutional Review Board Research Approval
2.7 Risks-vs.-Benefits Analysis: The Human Advocate
A. Identifying and Assessing the Risks
B. Minimal Risk vs. Greater-than-Minimal Risk
C. Vulnerable Populations and Minimal Risk
D. Determining Whether Risks Are Minimized
E. Assessing Anticipated Benefits
F. Determining Whether Risks Are Reasonable
G. Continuing Review and Monitoring of Data
2.8 Informed Consent: Not Just a Document
A. Elements of an Informed Consent
B. Additional Required Elements
2.9 Research Participants
2.10 Industry Trade Organizations and Support Services
2.11 Summary: Ethical Dilemmas in Clinical Research
References
Chapter 3: Search and Analysis of the Food and Drug Administration's FDA Adverse Event Reporting System (FAERS)
Paul N. Danese, Ph.D.
3.1 Introduction
3.2 Background
A. Small Clinical Trial Populations
B. Narrow Patient Demographics
C. Restricted Co-Administration of Medications
3.3 History of the FDA's Drug Safety Surveillance Systems
3.4 Submission of Adverse Event Reports to the FDA
A. Mandatory Reports
B. Voluntary Reports
3.5 Adverse Drug Reaction Information Captured by FAERS
3.6 Searching FAERS Data to Identify Possible Safety Problems
A. Statistical Methods to Identify Drug Safety Signals
B. Dechallenge and Rechallenge Data and Causality
C. Identifying Drug-Drug Interactions
D. Timelines and Deadlines of Adverse Event Reporting
3.7 The Food and Drug Administration's Use of FAERS in Regulatory Decisions
A. Boxed Warnings
B. Other Changes to a Medication's Prescribing Information
C. Determinations that No Action is needed and Continuing Investigations
3.8 Limitations of FAERS
A. Lack of Demonstration of Causality for Individual Reports
B. Extensive Under-reporting
C. Reporting Biases
D. Lack of Comparator Populations (Lack of a Denominator)
3.9 Search and Retrieval of Adverse Event Reports from the FDA's FAERS
A. Raw Data Files
B. FDA Public Dashboard
C. FOIA Requests
D. Commercial Vendors
3.10 Other FDA Adverse Event Reporting Systems
A. VAERS
B. MAUDE
C. Sentinel Initiative
3.11 Summary and Conclusions
References
Chapter 4: The Safety of Medicines: PharmacoVigilance, PharmacoSurveillance, PharmacoEmpowerment?
David Healy, M.D.
4.1 RxISK.org
4.2 Antidepressants: Data Based or Evidence Based?
4.3 Access to Adverse Event Data
4.4 RCTs and Adverse Events // Ghost Writers
4.5 RCTs & Primary Endpoints
4.6 Post 1962: Confounding & Causality
4.7 Pharmacovigilance
4.8 RxISK.org and Pharmacovigilance 1.0
4.9 Pharmacosurveillance
4.10 TaperMD and Pharmacovigilance 2.0
4.11 Summary and Conclusions
References
Chapter 5: Important Code of Federal Regulations Applicable to Drug Product Liability Suits
S. Albert Edwards, Pharm.D., RAC, FRAPS
Chapter 6: The Regulation of Drug Product Information to Consumers
Frank J. Ascione, Pharm.D., MPH, PhD
6.1 The Historical Development of Food and Drug Administration (FDA)'s Regulatory Role
A. Early phase (prior to 1906): No significant government intervention
B. Early Regulatory Phase (1906-1938): Minimal Government Control
C. Greater Government Control (1938-1961)
D. Debating Increased Consumer Access to Drug Product Information (1962-1983)
E. Expanding Information Available to Consumers (1983-present)
6.2 Current State of Prescription Drug Product-Related Information Provided to Consumers
6.3 Evolution of Drug Advertising to US Consumers (DTCA)
A. Emergence of DTCA (1981-1982)
B. Voluntary Moratorium Period of DTCA (1983-1985)
C. Establishment of DTCA Regulations (1985-1999)
6.4 Current State of Direct-to-Consumer Advertising
A. Advantages and Disadvantages of DTCA
6.4 Summary and Conclusions
References
Chapter 7: The Role of Investigative Journalism in Improving Drug Safety
Martha Rosenberg
7.1 Introduction
7.2 Direct-To-Consumer Advertising Increased with Covid
A. Unbranded DTC Advertising
B. Industry Funded Disease Awareness Groups
C. Encouraging Victim Politics
7.3 The Opioid Epidemic
A. Growing an Untapped Market
B. Aggressive Opioid Marketing
C. Fostering Opioid Addiction
D. Pill Mills and Addiction Medicine
E. Opioid Lawsuits Surface
F. Lack of Opioid Efficacy and Serious Side Effects
G. Paying for the Opioid Epidemic
7.4 Effective Hepatitis C Drugs Debut
A. Lawmakers Investigate Hep C Prices
B. Aggressive Hep C Marketing
C. Screening as a Hep C Sales Tool
D. Hepatitis C Safety Signals Emerge
7.5 Asthma Drug Safety Signals
A. Xolair Leaves a Trail of Questions
B. More Improper Xolair Marketing
C. Safety Signals Surface with Xolair and a Lawsuit is Dismissed
7.6 Long-Acting Beta Agonists
A. Glaxosmithkline Settlement included a Laba
7.7 Safety Questions About Leukotriene Receptor Antagonists
A. Parents Report LTRA Side Effects
B. LTRA Safety Signals Emerged Early
C. Patients and Parents Fight Back
D. Black Box Added to Singulair
7.8 Baldness Treatments Become Popular and Controversial
A. Finasteride Side Effects Create Concern
B. Medical Literature Confirms Finasteride Side Effects
C. FDA Adds Warnings to Finasteride
D. Finasteride User Speaks Out
E. No Satisfying End for Finasteride Users
7.9 Biologic Drugs
A. Tumor Necrosis Factor (Tnf) Blockers
B. Tnf Blocker Risks
7.10 Other Popular Medications Come Under New Scrutiny
A. N-Nitrosodimethylamine (NDMA
) Found in Medicines
1. Zantac Taken Off Shelves
2. NDMA Also Found in Metformin
7.11 Popular Stimulant Drugs Reveal Risks
A. Risks Seen with Modafinil
B. Fetal Risks Seen with Modafinil and Armodafinil
C. European Union Sues Provigil Makers
7.12 Fetal Risk Seen with NSAIDs
7.13 Bisphosphonates Continue to Present Risks
7.14 SSRI Antidepressants Linked to New Risks
A. SSRI Bone Thinning
B. SSRI Addictive Potential
7.15 Belviq, A Diet Drug Withdrawn from Market
7.16 Sleeping Pills Given Boxed Warnings
A. Public Figures on Sleeping Pills Make the News
B. Other Sleeping Pill Risks
7.17 Risks Associated with Fluoroquinolone Antibiotics
A. Fluoroquinolones Warnings Continue
B. Hormone Therapy Still Linked to Risks
C. Beware of Testosterone Marketing
D. New PPI Questions
References
Chapter 8: Evaluation of Causation in Drug Injury Cases
Donald H. Marks, M.D., Ph.D. and James T. O'Donnell, Pharm.D., M.S., FCP
8.1 What is Causation?
8.2 Importance of Establishing Causation
8.3 Definitions
8.4 Degree of Adverse Effects Relate to Intervention
8.5 Methodology to Investigate Causation
8.6 Structured Algorithms for Determination of Causation
A. Hill Criteria-Expanded Discussion
1. Strength of Association
2. Consistency of Results
3. Specificity
4. Temporal Relationship
5. Dose Response
6. Biological Plausibility
7. Biological Coherence
8. Experimentation
9. Analogy
8.7 Comments on the Individual Riddell Criteria for Causation,
8.8 Daubert and the Evolution of Causation,
8.9 Does Causation Need to be Established Before a Warning is Given?
8.10 What are the Qualifications needed to Give Expert Causation Opinions?
8.11 Case Reports Demonstrating Applications of Causation Principles
A. Case Report: Acyclovir Overdose - Pharmacist Recommended Overdose
B. Case Report: Challenging Cause of Death in a Malpractice Matter
C. Case Report: Determination of the Effects of Morphine in a Will Contest
D. Case Report: Proof of Drug-Induced Mental Changes in Complainant in Sexual Abuse Case
8.12 Summary and Conclusions
References
Chapter 9: General Principles of Pharmacology
James J. O'Donnell III, M.S., Ph.D., James T. O'Donnell, Pharm.D., M.S., FCP, and Vanessa Juettner, Ph.D.
9.1 Introduction
9.2 Basic Principles
A. Absorption
B. Lipid Diffusion
C. Determinants of Absorption
1. Lipid/aqueous partition coefficient and pH
2. Bioavailability
3. First pass effect
9.3 Routes of Administration
9.4 Extravascular Administration
A. Oral Administration
B. Rectal Administration
C. Other Routes of Administration
9.5 Intravascular Administration
9.6 Distribution
A. Diffusion
B. Volume of Distribution
C. Binding to Plasma Proteins and Cellular Constituents
D. Re-Distribution
E. Blood-Brain Barrier (BBB)
F. Placental Barrier
G. Therapeutic Range
H. Bioequivalence vs. Bioinequivalence
10.7 Drug Metabolism (Biotransformation)
A. Phase I Reactions
1. The families of human P450s
2. Induction of P450 enzymes
3. P450 Inhibition
B. Phase II Reactions
1. Metabolism of drugs to toxic products
9.8 Factors Affecting Drug Metabolism
A. Disease
B. Age
C. Gender
D. Genetic Factors
9.9 Drug Excretion
A. Urinary Excretion
1. Glomerular filtration
2. Tubular secretion (active secretion)
3. Tubular reabsorption
4. Effects of pH on urinary excretion of ionizable drugs
9.10 Pharmacokinetics
A. Introduction
B. Therapeutic Window and Therapeutic Index
C. Blood Levels for Narrow Therapeutic Index (NDI) Drugs
D. Kinetic Modeling
E. Drug Absorption and Elimination
1. Absorption rate
2. Elimination rate
3. Clearance (CL)
4. Area Under the Curve (AUC)
5. Elimination (k)
6. Elimination half-life
7. Steady state
F. Dosing
1. Loading dose
2. Maintenance doses (MD)
3. Example-dosage adjustment in renal impairment
G. Therapeutic Drug Monitoring (TDM)
H. Pharmacokinetics Summary
9.11 Drug Receptor and Pharmacodynamics
A. Agonists and Antagonists
B. Drug-Receptor Interactions
9.12 Dose Responses
A. Potency
B. Agonism and Antagonism
1. Partial agonists
9.13 Competitive Antagonism
9.14 Non-Competitive Antagonism
9.15 Summary and Conclusions
PART II: HIGH RISK DRUG THERAPIES RESULTING IN INJURY AND LITIGATION
Chapters 10 - 25
Chapter 10: Adverse Drug Reactions: Allergic Focus
James T. O'Donnell Pharm.D., M.S., FCP and James J. O'Donnell III, M.S., Ph.D.
10.1 Adverse Drug Reactions: How Large is the Problem? What Drugs are Involved? What are the Injuries?
A. Historical Perspective
B. Incidence of Adverse Drug Reactions
C. Food and Drug Administration Reporting Requirements
D. The "Seven Deadly Sins": Why Doctors Fail to Report Adverse Drug Reactions
E. Attitudes Toward Adverse Drug Reactions
F. Investigator Fraud
10.2 Classification of Adverse Drug Reactions
A. Categories of Adverse Drug Reactions
1. Type A reactions: Augmentation of the Pharmacological Response
2. Type B reactions: Bizarre (idiosyncratic)
10.3 Types of Drug Allergy and Hypersensitivity
A. The Nature of Drug Allergy
B. Dangerous Drug-Allergy Reactions
C. Drug Sensitivities Mimic Allergy Symptoms
D. Definitions of Allergic/Hypersensitivity Reactions
E. Idiosyncratic Reactions
F. Intolerance
G. Toxicity
H. Hypersensitivity Vasculitis
I. Predominantly Organ-Specific Reactions
J. Urticaria
K. Fixed Drug Eruptions
L. Photosensitivity Reactions
M. Generalized Exfoliative Dermatitis
N. Thrombocytopenia
O. Hemolytic Anemia
P. Agranulocytosis
Q. Treatment: Withdrawal of the Suspected Drug
R. Symptomatic Treatment
S. Prevention of Allergic Drug Reactions
T. Pseudoallergy
U. Angioedema
V. Hypersensitivity Reactions
10.4 Risk Factors, Drugs and Patients
A. Hypersensitivity Risk Factors
B. Identification of a Drug Allergy
C. Allergy to Antibiotics
D. Case Report: Cross-Allergenicity
10.5 Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
A. Fixed Drug Eruptions
B. Erythema Multiforme-Like Eruptions
Case Report: Lamictal Induced Stevens Johnson Syndrome
C. Fluoroquinolones
E. NSAIDs Cross Reactivity Case Report
F. Radiographic Contrast Media
G. Local Anesthetics
H. Anticonvulsants (AED)
10.6 Summary and Conclusions
References
Chapter 11: Drug Induced Falls
James T. O'Donnell Pharm.D., M.S., FCP and James J. O'Donnell III, M.S., Ph.D.
11.1 Introduction
11.2 The Definition of Fall
11.3 Epidemiology
11.4 Causes and Risk Factors
A. Physiological Risk Factors for Falls in the Elderly
B. Psychological Risk Factors
C. Medical Conditions
11.5 Medication-related Falls
11.6 Types of Medications that Increase the Risk of Fall
A. Centrally Active Medications
B. Benzodiazepines
C. Antipsychotics
D. Antihypertensives
1. Orthostatic Hypertension and Risk of Fall
E. Opioids
11.7 Marijuana
11.8 Alcohol
11.9 Hip Fractures
11.10 Polypharmacy
11.11 Fall Risk Assessment
11.12 Types of Assessments
11.13 Strategies for Fall Prevention in Institutionalized Settings
A. Screening
B. Addressing Risk Factors
1. Monitoring Patients
2. Environmental Interventions
3. Educational Programs
4. Reducing Fall Injury
C. Discharge Planning
D. Disseminating Evidence: Awareness and Intervention Work!
11.14 Summary and Conclusions
References
Chapter 12: Drug Induced Movement Disorders
Jadwiga Najib, B.S. Pharm.D., BCPS, and Meagan Bailey, M.D.
12.1 Introduction
12.2 Presentation
12.3 Agents Associated with Drug-Induced Movement Disorders
12.4 Risk Factors
12.5 Sequelae of Drug-Induced Movement Disorders
12.6 Theories of Causation
12.7 Drug-Induced Movement Disorders in Children and Adolescents
12.8 Drug-Induced Movement Disorders in the Elderly
12.9 Acute/Intermediate Drug-Induced Movement Disorders
A. Dystonia
1. Presentation
2. Implicated agents
3. Risks
4. Management
B. Ataxia
C. Bruxism
D. Neuroleptic Malignant Syndrome
E. Serotonin Syndrome
12.10 Chronic Drug-Induced Movement Disorders
A. Akathisia
1. Presentation
2. Case study: Trazodone-induced akathisia
3. Implicated agents
4. Other drugs
5. Risks
6. Management
B. Parkinsonism
1. Presentation
2. Case Study: Neuroleptic-Induced Parkinsonism
3. Implicated agents
4. Other drugs
5. Risks
6. Management
C. Myoclonus, Tremor, Tics, Asterixis
12.11 Persistent/Tardive Drug-Induced Movement Disorders
A. Tardive Dyskinesia
1. Presentation
2. Case Study: Neuroleptic induced oral buccal dyskinesia and akathisia
3. Implicated agents
4. Case Study: Metoclopramide induced oral buccal lingual dyskinesia
5. Risks
6. Management
B. Tardive Akathisia
C. Tardive Dystonia
1. Case Report: Neuroleptic induced cervical dystonia
D. Other Tardive Variants
12.12 Drugs Used for Movement Disorders
12.13 Monitoring
12.14 Clinical and Legal Issues in Psychiatry
12.15 Summary and Conclusions
References
Chapter 13: Acute Adverse Drug Events in Critical Care Emergency Department and Intensive Care Units
Gourang P. Patel, Pharm.D., M.Sc., BCPS, BCCCP, FCCM
13.1 Background
A. Epidemiology
B. Environment
13.2 High-Risk Medication-Related Events
A. Hypersensitivity Reactions
B. Cardiovascular Reactions
1. Blood pressure (BP)
2. Heart rate (HR)
3. Arrhythmias
C. Nephrotoxicity
1. Aminoglycosides
2. Amphotericin B
3. Intravenous contrast
D. Hypoglycemic Events
E. Infusion-Related Reactions
1. Extravasations
2. Propofol-related infusion syndrome (PRIS)
3. Intravenous N-acetylcysteine (NAC)
F. Reversal Agents
1. Protamine
2. Vitamin K
3. Naloxone
4. Flumazenil
13.3 Summary and Conclusions
References
Chapter 14: Nephrotoxic Drugs
Jason M. Kidd MD, Domenic A. Sica, M.D. and Todd W. B. Gehr, M.D.
14.1 Introduction
14.2 Framework of the problem
14.3 Basis for the kidney being susceptible to damage
14.4 Patient groups most susceptible to nephrotoxicity
14.5 Demographics of chronic kidney disease
14.6 Methods to assess renal function and/or damage
14.7 Level of renal function at which drug accumulation occurs
14.8 Nephrotoxic drugs
A. What constitutes prompt clinical action in the face of nephrotoxicity?
14.9 Nephrotoxicity scenarios
A. Lithium toxicity
B. Gentamicin toxicity
C. Dialysis-related issues
D. Drug Clearance in Relationship to Renal Failure
1. Case 1
2. Case 2
E. Angioedema with an ACE inhibitor
F. Fatal hyperkalemia with medications
G. Statin therapy and the development of myopathy
H. Nephrotoxicity related to checkpoint inhibitor use
14.10 Summary and Conclusions
References
Chapter 15: Drug Induced Liver Disease
James T. O'Donnell, Pharm.D., M.S., FCP, James J. O'Donnell III, M.S., Ph.D., Donald H. Marks, M.D., Ph.D., Paul Danese, Ph.D.
15.1 Introduction: The Problem of Drug-Induced Liver Disease
15.2 History of Adverse Drug Reactions
15.3 Overview of DILD, Epidemiology Risk Factors, Histopathology, and Diagnoses
A. Epidemiology of Drug Hepatotoxicity
B. Risk Factors
C. Histopathology
D. Diagnosis
15.4 Hepatic Drug Metabolism
15.5 FDA and DILD
15.6 Types of Liver Injury
A. Hepatitis
B. Massive Hepatic Necrosis (Fulminant Hepatitis)
C. Drug-induced Vanishing Bile Duct Syndrome
15.7 Specific DILD Product Areas and Case Discussions
A. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Use and Hepatoxicity
B. Isoniazid-Induced Hepatotoxicity
C. Acetaminophen
1. Acetaminophen Toxicity Assessment Nomograms
2. FDA Report - Acetaminophen Induced Liver Disease
D. Macrolide Hepatotoxicity
E. Methotrexate (MTX) Hepatotoxicity
F. Estrogens and Oral Contraceptive Steroids
G. Statins
H. Ticlopidine
I. ACE Inhibitors and AT II Receptor Antagonists
J. Fluoroquinolones
K. Terbinafine
L. Ketoconazole
M. Selective Serotonin Reuptake Inhibitors - Serzone Liver Toxicity
N. Herbal and Other Dietary Supplements and Hepatotoxicity
15.8 Summary and Conclusions
References
Chapter 16: Antineoplastic Therapy
Kathryn Schultz, Pharm.D. and Eris Tollkuci, Pharm.D.
16.1 Background
16.2 Chemotherapy - Antimetabolites
16.3 Chemotherapy - Antimicrotubules
16.4 Chemotherapy - Alkylators
16.5 Chemotherapy - Topoisomerase I Inhibitors
16.6 Chemotherapy - Topoisomerase II Inhibitors
16.7 Chemotherapy - Antitumor Antibiotics
16.8 Chemotherapy - Miscellaneous
16.9 Targeted Therapy
A. Infusion-related reactions (IRRs)
B. Immunotherapy (Immune Checkpoint Inhibitors)
1. Infusion-related reactions
2. Immune-Related Adverse Events (irAEs)
16.10 Tumor Lysis Syndrome
16.11 Hepatotoxicity
16.12 Summary and Conclusions
References
Chapter 17: Dangers of Opioids
Jennifer Splawski, M.S., Pharm.D., BCPS, James T. O'Donnell, M.S., Pharm.D., James J. O'Donnell III, M.S., Ph.D.
17.1 Introduction
A. Definitions
B. History
17.2 Pharmacology of Opioids
A. Effects
B. Opioid Neural Receptors
1. Central Nervous System (CNS) Receptors
2. Peripheral Nervous System (PNS) Receptors
C. Routes of Administration
1. Oral
2. Intramuscular
3. Subcutaneous
4. Intravenous
5. Transdermal
6. Sublingual and Buccal
7. Neuraxial
D. Metabolism
E. Excretion
17.3 Toxicity of Opioids
A. Respiratory Depression
B. Symptoms of Overdose
17.4 Epidemiology of Opioid Abuse
A. Opioid Abuse in Adolescents and Young Adults
B. Opioids in Pregnancy
17.5 Contributions to the Opioid Epidemic
A. Opiates Handed Out Like Candy to 'Doped-up' Veterans
B. United States Reaches $22 Million Settlement Agreement with CVS For Unlawful Distribution of Controlled Substances
C. Former Walmart Pharmacists Say Company Ignored Red Flags as Opioid Sales Boomed
D. Federal Judge Approves Landmark $8.3 Billion Purdue Pharma Opioid Settlement
17.6 Combatting the Opioid Epidemic
A. Prescription Monitoring Programs (PDMP)
B. Naloxone Dispensing
C. Medication for Opioid Use Disorder (MOUD)
1. Buprenorphine
A. Pharmacokinetics
B. Adverse Effects
C. Place in therapy
1. Methadone
A. Pharmacokinetics
B. Equianalgesic Dosing
C. Drug Interactions
D. Cardiovascular Effects
E. Consequences of Ignorance of Proper Dosing of Methadone
F. Methadone Legal Case Examples Involving Patient Demise
G. Applying Lessons Learned and Action for Institutional Committees
17.7 Case Reports: Opioid Toxicity Causing Respiratory Arrest, Brain Damage, and Death
A. Case Report: Respiratory Arrest and Brain Damage Following Morphine Overdose
B. Case Report: Fentanyl Epidural Respiratory Arrest
C. Case Report: Fentanyl (Duragesic (R)) Death in Discharged Patient
D. Case Report: High Dose Fentanyl Patch Prescribed in Opiate-Naive Patient-Death
E. Case Report: Heroin and Other Opioids
F. Case Report: Hydromorphone (Dilaudid (R)) Respiratory Arrest
17.8 Investigation and Prosecution of Pain Clinics by the Department of Justice (DOJ)
17.9 Summary and Conclusions
References
Chapter 18: Adverse Effects of Diabetic Drugs: Focus on Hypoglycemia
Gourang P. Patel, BS Chem, PharmD, MSc, BCPS and James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN
18.1 Diabetes Demographics and Epidemiology
18.2 Insulin
18.3 Insulin Preparations
18.4 Clinical Use of Insulin
A. Dosing
18.5 Hypoglycemia (Low Blood Sugar)
A. Etiologies of hypoglycemia
B. Insulin-induced hypoglycemia
C. Deaths by Hypoglycemia
18.6 Pathophysiology and Clinical Symptoms of Hypoglycemia
18.7 Incidence
18.8 Pathophysiology and Biochemistry of Hypoglycemia
18.9 Adverse Reactions Involving Hypoglycemia
A. Insulin damages baby's brain; pharmacist error suggested
18.10 End Product Testing Recommended
18.11 Insulin Murders
18.12 Hypoglycemia from the Sulfonylurea Derivatives
18.13 Adverse Effects of the Sulfonylureas
18.14 Drug Interactions with Sulfonylureas
18.15 The Gliptin Class New drugs for Diabetes Treatment Type 2 Diabetes
18.16 Thiazolidinediones
A. Hepatic Failure
B. Bladder Cancer
18.18 Summary and Conclusions
References
Chapter 19: Parenteral Nutrition Related Errors and Complications
Erica M. Fernandez, Pharm.D., BCCCP, BCPS
19.1 Introduction
19.2. Basic principles of PN
19.3 PN Provision Categories
A. Prescribing
B. Transcribing and Verification
C. Compounding
D. Administration
19.4. Monitoring and Complications
A. Glycemic Control
B. Refeeding Syndrome
C. Hepatobiliary Complications
D. Complications involving micronutrients
19.5 PN Component Shortages and Adverse Events
19.6 Summary and Conclusion
References
Chapter 20: Antidepressants: Clinical Use and Litigation
Henry Cohen, Pharm.D., M.Sc., FCCM, BCPP, BCGP and Michael Liu, Pharm.D., MBA, BCCCP, BCNSP, BCPS
20.1 Major Depressive Disorders
20.2 Antidepressant Pharmacology
20.3 Antidepressant Overdose
A. Trazodone and Permanent Neurologic Sequelae
20.4 Antidepressants and the Patient with Suicidal Ideation
A. Prozac and Suicidal Ideation
1. Woulfe v. Eli Lilly & Co.
2. Espinoza v. Eli Lilly & Co.
3. Cassidy v. Eli Lilly & Co
B. Paxil and Suicidal Ideation
1. Dolin v. GlaxoSmithKline
C. Antidepressant and Increased Suicidality in Pediatrics
1. Schilf v. Eli Lilly & Co.
20.5 Broken Heart Syndrome: Tako Tsubo Cardiomyopathy Associated with Use of Antidepressants
20.6 The Adverse Effects of Antidepressants and the Duty to Warn
A. Docken v. Ciba-Geigy
B. Stebbins v. Concord Wrigley Drugs, Inc. et al.
C. Morgan et al. v. Wal-Mart Stores, Inc.
D. Kampmann v. Mason
E. Cottam v. CVS
20.7 Antidepressants and Alcohol
A. Kirk v. Michael Reese Hospital
B. Hand v. Krakowski
20.8 Selective Serotonin Reuptake Inhibitors and the Serotonin Syndrome
20.9 Hepatic Cytochrome P450 Drug Interactions and Cyclic Antidepressants
20.10 Antidepressants and Herbal Agents Drug Interactions
20.11 Serzone and Liver Disease
20.12 High Blood Pressure Associated with Venlafaxine Use
20.13 SSRI use and Birth Defects
20.14 Bupropion XL and Seizures
20.15 The Pharmacist's Role
20.16 The Omnibus Budget Reconciliation Act
20.17 How Safe is it to Buy Prescription Medications Over the Internet?
20.18 In a Perfect World
20.19 Summary and Conclusions
References
Chapter 21: Contrast Media Neurotoxicity Following Myelography
Stephanie E. Tedford, Ph.D., and James T. O'Donnell, Pharm.D., M.S., FCP
21.1 Introduction
21.2 Case Reports
A. Case I Intrathecal Iopamidol
B. Case II Intrathecal Iothalamate
21.3 Discussion
A. Mechanisms for cerebral (neurotoxic) injury
B. Contrast-induced neurological and cognitive deficits
C. Contrast-induced visual and auditory impairment: Further evidence for cerebral insult to cortical brain structures
21.4 Summary and Conclusions
References
Chapter 22: Fetal Drug Exposure
Damani Parran, Ph.D., MBA, DABT, James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D.
22.1 Introduction
22.2 Critical Periods of Human Development and Susceptibility
22.3 Special Considerations of Drug Exposure during Pregnancy
22.4 Historical Human Developmental Toxicants
A. Thalidomide
B. Ethanol
C. Diethylstilbestrol
D. Retinoids
E. Cocaine
22.5 Developmental Toxicity of Prescription Drugs
A. Valproic Acid
B. Phenytoin
C. Warfarin
D. Benzodiazepines
22.6 Additional Prenatal Environmental Influences
A. Malnutrition
B. Poverty
C. Emotional State
D. Mother's Age
E. Infections and Diseases
22.7 FDA Pregnancy Categories for Prescription Drug Labeling; Final Rule
22.8 Analyses of Litigated Cases Alleging Fetal Drug Injury
A. Effects of Methadone and Smoking on the Fetus
B. Effects of Lisinopril on Fetus - Defense of Causation
22.9 Summary and Conclusions
References
Chapter 23: Geriatric Medication Misadventures
Rodney G. Richmond, M.S., Pharm.D., BCGP, FASCP and James C. Norris, Ph.D., DABT, ERT
23.1 Introduction
A. Outpatient Medication Use
B. Hospital Medication Use
C. Long-Term Care Medication Use
23.2 Altered Clinical Response to Drugs
A. Pharmacokinetics
B. Pharmacodynamics
23.3 Preventable Drug-Related Problems
A. Polypharmacy
B. Transitions of Care
C. Inadequate Monitoring
D. Potentially Inappropriate Medication Use
23.4 Legal Cases Application
23.5 Summary and Conclusions
References
Chapter 24: Medication Errors
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, R.Ph. and James J. O'Donnell III, M.S., Ph.D.
24.1 History and Overview
24.2 Medication Errors in Epidemic Proportions
24.3 Types of Medication Errors
A. Enhancing Healthcare Team Outcomes
B. Improving Reporting of Medication Errors
24.4 Medication Use Process
24.5 System Errors
24.6 Which Drugs are Most Often Involved in Medication Errors?
24.7 Prevalence of Medication Errors
24.8 Vaccine Errors
24.9 How has Modern Research Improved Therapeutics and Reduced Drug-Related Morbidity? Pharmacogenomics
24.10 Systems for Medical Error Prevention
A. Electronic Prescribing (E-prescribing)
B. When Electronic Prescribing is Unavailable
C. Effective Drug Monitoring Systems
D. The Importance of Continuing Education
E. Reporting All Adverse Drug Events
24.11 Summary and Conclusions
References
Chapter 25: Anticoagulants: Therapeutics, Risks, And Toxicities
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D., Stephanie E. Tedford, Ph.D.
25.1 Introduction
25.2 Summary of Anticoagulant Therapy
A. Definition
B. Use
1. Treatment of coronary heart disease
2. Warfarin and dabigatran
3. Treatment of thrombogenesis
25.3 Limitations of Current Therapy
A. Heparin
B. Low Molecular Weight Heparin (LMWH)
C. Heparin-Induced Thrombocytopenia (HIT)
1. Pathogenesis of the autoimmune response
2. Pathogenesis of the prothrombotic state
3. Clinical presentation of HIT
4. Diagnosis
a. Dismissing HIT
b. Diagnosing HIT
2. Two Approaches: class and titer
5. Treatment of HIT
a. Fondaparinux
b. Re-exposure to heparin
6. Conclusion HIT and HITT
D. Warfarin
25.4 Monitoring Warfarin Oral Anticoagulation
25.5 Alternatives to Warfarin - DOACs
A. Pradaxa (Dabigatran) vs. Warfarin
B. Direct Oral Anticoagulation (DOAC) Therapies
C. DOAC reversal agents
D. Antiplatelet Therapy
25.6 Summary and Conclusions
References
Part III: PHARMACISTS, PHARMACY AND PHARMACY PRACTICE
Chapters 26 - 33
Chapter 26: Pharmacy Practice, Managed Care, And Manufacturers
F. Randy Vogenberg R.Ph., Ph.D. and Rita Marcoux R.Ph., MBA
26.1 Introduction to Pharmacy and the Related Managed Health Care Environment
26.2 Pharmacists as Health Care Professionals: Training, Support Staff, and Life-long Learning
A. Registration, Certifications, Credentialing, Colleges Of Pharmacy, And Accreditation Matters For Pharmacy Professional Staff
26.3 Practice Sites: Inpatient, Ambulatory/Community, Specialty, Long Term Care, and Other (compounding, nuclear)
A. Practice settings, Practice site Certification, Pharmacist practice versus the Business of pharmacy, Credentialing, and Accreditation matters
26.4 Issues for Pharmacy Practice, Insurance, and Managed Care In the Near Future
A. The landscape of Practice Sites and Changing Business of Health Landscape
26.5 Current and Near Future Issues for Pharmacists
A. Landscape of Pharmacy Practice, The Changing Professional Marketplace
26.6 Pharmaceutical Manufacturer Through Wholesaler and Distribution Supply Chain
26.7 Manufacturers: Traditional and Innovative Segments
A. Non-Biologic Medications
B. Research-Intensive, Biologics, Gene, and Generic Segments
1. Biologic Medications
26.8 Pharmaceutical Manufacturer Customers
A. Organization and Operations
B. Other Targeted Customer and Class of Trade Segments
C. Contracting and Change in the Pharmaceutical Industry
26.9 Health Care Industry Changes in the Near Future
26.10 Summary and Conclusions
References
Chapter 27: The Pharmacist's Utilization of the National Patient Safety Goals to Contribute to Safe and Effective Medication Use
Jennifer Splawski, Pharm.D., MS, BCPS and Heather Minger, Pharm.D., BCPS
27.1 Introduction
A. Overview of 'The Goals'
27.2 Goal 3 and the Pharmacist's Role
A. NPSG.03.05.01 relating to Anticoagulation
1. Introduction
2. Warfarin Overview
3. Patient monitoring
4. Patient Education
5. Direct Oral Anticoagulant
6. Anticoagulation Reversal Overview
7. Anticoagulation Reversal Programs
8. Patient Education
B. NPSG.03.06.01 relating to Reconciling Medication Information
1. Introduction
2. The Process of Medication Reconciliation
3. Improved Accuracy
4. Decreased Mortality
5. Allergy Identification
6. Discharge Medication Reconciliation
7. Utilization of the Pharmacist Extenders in Medication Reconciliation
27.3 Summary and Conclusions
References
Chapter 28: Pharmacist Malpractice and Liability
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN and James J. O'Donnell III, M.S., Ph.D.
28.1 Introduction
28.2 The Science of Risk Management
28.3 Claims Studies
The Pharmacists Mutual Claims Study
CNA Claims Study (CNA/HPSO)
A. CNA Database and Methodology
B. Most Common Categories of Errors
C. Claim Analysis by Insurance Source & Licensure Type: Pharmacists v. Technicians
D. Factors Affecting Wrong Drug Dispensing Errors
E. Drugs Involved in Claims
F. Most Common Error: Wrong Drug
G. Wrong Drug Strength
H. Wrong Directions
I. Wrong Route of Administration
J. Lack of Drug Review
K. Counseling: A Powerful Weapon Against Liability
L. Non-Bodily Injury
M. Miscellaneous Errors
N. Wrong Directions
O. Lack of Drug Review
P. Avoiding Errors and Malpractice
28.4 Specific Pharmacist Malpractice Case Reports / Topics
A. Duty to Warn?
B. Wrong Drug
C. Quotas and Metrics: Contributing to the Problem?
D. Controlled Substances Violations by Pharmacists
E. Methotrexate (MTX) errors
28.5 Pharmacists Need to do the Right Thing
28.6 Steps Toward a Better Outcome
28.7 Summary and Conclusions
References
Chapter 29: Regulation of Pharmacy Practice
Ned Milenkovich, Pharm.D., J.D.
29.1 Introduction
29.2 Licensure of Professional Activities
A. Boards of Pharmacy - A Closer Look
B. National Association of Boards of Pharmacy
29.3 Practice Standards
A. Legally Circumscribing Pharmacy Practice
29.4 Licensure Process to Practice Pharmacy
A. Licensing
B. Licensing of Pharmacists
29.5 The Different Types of Pharmacy Licenses
A. Disciplinary Actions
B. Causes of Disciplinary Action
C. Practice Focus on Licensure
D. Ongoing Professional Education
E. Support Personnel
29.6 Federal Drug Laws
A. Obra '90
B. Medicare
C. Medicare Part D
D. Medicaid
E. Prescription Drug Coverage
F. Fraud, Waste and Abuse
G. 340b Drugs
H. Pharmacy Compounding
I. FDA Rems
J. DEA
29.7 Pharmacy Practice: Putting it Together
A. Pharmacy Practice: An Ongoing Progression
B. Collaborative Practice Agreements
C. Drug Utilization Review (DUR)
D. Other Mandates Impacting Pharmacy Practice Quality Assurance Regulations
E. Health Insurance Portability and Accountability Act Of 1996, As Amended
Chapter 30: Emergency Department Pharmacist
Victor Cohen, B.S., Pharm.D., BCPS, CGP, Samantha P. Jellinek-Cohen, Pharm.D., BCPS, CGP, Megan Musselman Pharm.D., M.S., BCPS, BCCP
30.1 Introduction
30.2 Epidemiology of Drug Injury and Contributing Risk Factors
A. Contributing Risk Factors
30.3. Etiology and Sources of Drug Injury in the ED
30.4 Clinical Pharmacy in the ED: A Historical Perspective
30.5 The ED Pharmacist Plays a Dual Role at Maimonides Medical Center
30.6 The ED Pharmacist: A Sub-specialist in Emergency Medicine
A. Training and Education
B. Certification
30.7 The ED Pharmacist as a Generalist
30.8 The ED Pharmacist Ensuring Optimal Continuum of Care
A. The ED and Infectious Diseases
B. The ED Pharmacist and the Ambulatory Care Interphase
C. The ED Pharmacist and Transitions of Care (TOC)
1. Medication admission notes in the ED
D. The ED Pharmacist as a Clinical Toxicology Consultant
E. The ED Pharmacist and the Cardiology Interface
F. The ED Pharmacist and Neurological Emergencies
G. The ED Pharmacist and Pulmonary Emergencies
H. The ED Pharmacist and Public Health Services in the ED
30.9 Building Layers of Defense Against Drug Injury
A. Detecting and Preventing Drug Injury in the ED
B. The ED Pharmacist and Community Surveillance for Adverse Drug Reactions
30.10 Pharmacy Practice in the ED: Pharmacotherapy Specialty
30.11 Summary and Conclusions
References
Chapter 31: Pharmacy Case Law Review
Roger N. Morris, R.Ph., J.D., and William J. Stilling, R.Ph., M.S., J.D.
31.1 Administrative Law
A. Due Process-Pharmacist Licensure
1. Berjikian, et al. v. Franchise Tax Board et al., No. CV 13-06301 DDP, 2015 WL 1185472 (C.D. Cal. March 12, 2015)
31.2 Antitrust
A. State Regulatory Boards Immunity
1. North Carolina Bd. of Dental Examiners. v. Federal Trade Commission, 135 S. Ct. 1101 (Feb. 25, 2015)
31.3 Civil Procedure
A. Spoliation of evidence-Pharmacy's Duty to Maintain Evidence of Misfill
1. Burton v. Walgreen Co., 2015 WL 4228854 (D. Nev. July 10, 2015)
31.4 Conscientious Objection
A. Emergency Contraception
1. Stormans, Inc. v. Wiesman, 794 F.3d 1064 (9th Cir. 2015)
31.5 Controlled Substances
A. Duty to Verify DEA Registration
1. Farmacia, Yani, 80 Fed. Reg. 29,053 (May 20, 2015)
2. JM Pharmacy Group Inc., d/b/a/ Farmacia Nueva and Best Pharma Corp., 80 Fed. Reg. 28,667 (May 19, 2015)
B. Constitutionality
1. McFadden v. United States, 135 S. Ct. 2298 (June 18, 2015)
31.6 Criminal
A. Violations of Pharmacy Law Applied to Non-pharmacists
1. Moore v. State of Florida, NO. 1D14-3527, 2015 WL 4464689 (Fla. Dist. Ct. App. July 21, 2015), reh'g denied (Sept. 1, 2015)
B. PMP Records
1. Lundy v. State, 26 N.E.3d 656 (Ind. Ct. App. Feb. 20, 2015)
C. Second Degree Murder
1. U.S. v. Barry J. Cadden, et al., 2014 WL 7151586 (D. Mass. Dec. 16, 2014)
31.7 Defamation
A. Physician against Pharmacist
1. LeFrock v. Walgreen Co., 77 F. Supp.3d 1199 (M.D. Fla. Jan. 16, 2015)
B. Duty to Fill
1. Kadambi v. Express Scripts, 2015 WL 475373 (N.D. Ind. February 5, 2015)
31.8 Employment
A. Discrimination (Pregnancy)
1. Torres-Skair v. Medco Health Solutions, Inc., 595 F.App'x 847 (11th Cir. Dec., 4, 2014)
B. Employment at Will
1. Hoven v. Walgreen Co., 751 F.3d 778 (6th Cir. June 2, 2014)
C. Americans with Disability Act
1. Stevens v. Rite Aid Corp., et al., 6:13-cv-00783 (N.D.N.Y., September 23, 2015)
D. Overtime Class Action
1. Baugh v. CVS Health, et al., 2:15-cv-00014 (E.D. Penn., July 27, 2015)
E. Medical Marijuana
1. Coats v. Dish Network, 350 P. 3d, 849 (Colo. June 15, 2015)
31.9 Fraud and Abuse
F. False Claims
1. United States v. Express Scripts, Inc., 602 F. App'x 880 (3rd. Cir. Feb. 20, 2015)
G. False Claims-Generic Substitutions
1. Doe v. Houchens Indus., Inc., No. 1:13-CV-00196-RLY, 2015 WL 133706 (S.D. Ind. Jan. 9, 2015)
H. False Claims & Anti-Kickback Statute
1. U.S. ex rel. Kester v. Novartis Pharm. Corp., No. 11 CIV. 8196 CM, 2015WL 1650767 (S.D.N.Y. Apr. 10, 2015)
I. Consumer Fraud
1. City of Chicago v. Purdue Pharma L.P., 2015 WL 2208423 (N.D. Ill. May 8, 2015)
31.10 Negligence
A. Duty to Provide Medication
1. Davies v. Virginia CVS Pharmacy, LLC, et al., 7:14-CV-00175, 2014 WL 6460787 (W.D. Va. Nov. 17, 2014)
B. Duty Not to Dispense
1. Oleckna v. Daytona Disc. Pharmacy, 162 So. 3d 178 (Fla. Dist. Ct. App. 2015)
31.11 Privacy
C. Patient Privacy-Vicarious Liability
1. Walgreen Co. v. Hinchy, 25 N.E.3d 748 (Ind. Ct. App. Jn. 15, 2015) reh'g of, 21 N.E.3d 99 (Ind. Ct. App. Nov. 14, 2014)
D. Text Messages
1. Thompson v. CVS Pharmacy, Inc., 6:204-cv-02081 (M.D. Fla. Dec. 19, 2014)
E. Robocalls
1. Kolinek v. Walgreen Co., 2014 WL 3056813, (N.D. Ill. July 7, 2014)
31.12 Product liability
A. Learned Intermediary Doctrine
1. Watts v. Medicis Pharm. Corp., 342 P.3d 847 (Ct. App. 2015), review granted in part (Sept. 22, 2015)
B. Product Liability (applicability to pharmacists)
1. Randol Mill Pharmacy v. Miller, 465 S.W.3d 612 (Tex. 2015), reh'g denied (Sept. 11, 2015)
Chapter 32: Pharmacy Compounding - Patient Injury and Regulatory Compliance
Willis C. Triplett, Pharm.D.
32.1 Introduction
32.2 Compounding Trends and Driving Forces
32.3 Optimizing the Regulatory Balance Between "Manufacturing" versus "Compounding"
32.4 Investigations, Indictments, Convictions, and Acquittals after the Fungal Meningitis Outbreak
32.5 Memorandum of Understanding (MOU)
32.6 U SP, NABP, and the State Pharmacy Regulatory Authorities
32.7 Physician and Medical Office Compounding
32.8 Compounding "Center of Excellence" ("COE") and the Quality Assurance Paradigm Shift
32.9 Conclusions and Forecasts Regarding Patient Injury from Healthcare Compounding
32.10 Recommended Readings
CHAPTER 33: Compounding Pharmacy Fraud and Unethical Practices
James T. O'Donnell, Pharm.D., M.S., FCP
33.1 Introduction
33.2 Criminal Prosecutions of Pharmacy Compounders
33.3 Over-Prescribing and Over-Charging of Compounded Drugs
A. Department of Justice News Releases
B. News Reports in Newspapers
33.4 Not Yet Criminal? Insurance Companies Fighting Back
A. No-Fault Pain Compounded and Topical Pain Product
B. Report Challenging the Pricing and Efficacy of a Compounded Pain Cream Prescription
C. Ingredients and Costs of Pain Cream
33.5 General Discussion - Compounded Pain Topical Creams
A. Evidence of Efficacy?
B. Expensive Ingredients
33.6 Ingredients Review of Efficacy and Mechanism of Action
A. Diclofenac
B. Menthol (Methyl Salicylate)
C. Lidocaine
1. Lidocaine Topical Toxicity
D. Amitriptyline
E. Cyclobenzaprine
F. Dimethylsulfoxide (DMSO)
33.7 Global Opinions for the Prescription CPTM formula 8-NC Claim Challenge
33.8 Discussion and Further Bases of Opinions
33.9 Overbilling of Topical Diclofenac Gels, Lidocaine Creams and Ointments and Patches
A. Diclofenac 3" (Solaraze)
B. Lidocaine Topical Commercial Products
33.10 Recommendations
33.11 Summary and Conclusions
References
Part IV: FORENSIC AND TOXICOLOGY ISSUES
Chapters 34 - 42
Chapter 34: Alcohol
James T. O'Donnell, Pharm.D., M.S.. FCP and James J. O'Donnell III, M.S., Ph.D.
34.1 Introduction
34.2Alcohol Injury Epidemiology
34.3 Alcohol Intoxication Effects in Litigation
34.4 Differences between Civil litigation involving alcohol from Criminal/DUI
34.5 Settings for Alcohol Related Civil Litigation
A. Employment
34.6 Police Activities
A. Police Pursuit
B. Excessive Police Force
C. Alcohol Effects on Aggression and Judgment
34.7 Motor Vehicle Collisions
A. Vehicle/Vehicle
B. Motorcycle Cases
C. Boating
D. Vehicle/ Pedestrian
34.8 Alcohol and Falls
A. Stairs - no alcohol test - fall down bar stairs
B. Stairs - Residential Stairs Fall -Adjustment of Calculated BAC due to Morbid Obesity
C. Tripped on Threshold - Sued Condominium Association
34.9 Dram Shop (Bar Liability for Serving Intoxicated Persons)
34.10 Biomarkers for Alcohol
A. Family Law
B. False Positive Alcohol Biomarkers in Diabetes
34.11 Miscellaneous Topics Reports
A. Retrograde Extrapolation (See also legal cases Floyd and Cuellar earlier in this chapter.
B. Appellate Court reverses Trial Court Barring of BAC
34.13 Summary and Conclusions
References
Chapter 35: Cocaine
James C Norris, Ph.D., D.A.B.T and Rodney G Richmond, R.Ph., MS, CGP, FASCP, FACFE
35.1 Historical Background
35.2 Medical Usages of Cocaine
35.3 Illegal Usage of Cocaine
35.4 Routes of Administration
35.5 Effects of Cocaine
35.6 Psychotic Disorders Induced by Cocaine
35.7 Addiction
35.8 Cognitive Deficits
35.9 Prenatal Cocaine Exposure (PCE)
35.10 Violence
35.11 Tolerance
35.12 Withdrawal or Abstinence Effects
35.13 Mechanisms of Action
35.14 Metabolism
35.15 Blood Levels
35.16 Urine Levels
35.17 Impairment
35.18 Associated Deaths with Cocaine Usage
35.19 Summary and Conclusions
References
Chapter 36: Marijuana: Pharmacology, Toxicology and Forensic Issues
Stephanie E. Tedford, Ph.D., James T. O'Donnell PharmD, MS, FCP, and James J. O'Donnell III MS, Ph.D.
36.1 Introduction
36.2 Federal Law vs. State Law
A. Harrison Narcotics Tax Act
B. Comprehensive Drug Abuse Control and Prevention Act
C. Marijuana Drug Laws at the State Level
D. Legalization
E. Decriminalization
F. Marijuana Policy Project
36.3 Controlled Prescription and Distribution of Medical Marijuana
A. Medical Conditions Approved for Treatment with Medical Marijuana
B. Marijuana and Epilepsy
C. Marijuana and Endometriosis
36.4 Pharmacological Properties of Marijuana
A. Active Compounds and Overview of Pharmacology
B. Variability in Marijuana Regulation and Content Uniformity
C. Routes of Administration
D. Pharmacokinetics - Time Course of THC and Metabolites
E. Pharmacodynamics
F. Vaping vs. Traditional Smoking of Cannabinoids
G. Traditional Smoking vs. Ingestion of Cannabinoids
H. Pharmacokinetics Applications: Timing of the Peak Euphoric Effect
I. Bioavailability
1. Is There a Good Model for Marijuana Ingestion?
2. Overall Advantages of the Oromucosal Route?
3. Can the Effects After Ingestion of Marijuana be Made More Objective?
36.5 Marijuana Safety
A. Serious Adverse Effects
B. Risk of Psychosis
1. Drug-induced Psychosis: Potential Mechanisms
2. Vaping and Associated Risk for Psychosis
C. Pulmonary Function
D. Risk of Addiction
E. Effect on Brain Development
F. Long Term Behavioral Effects
G. Age of Onset of Use
36.6 Impact of Legalization
A. Hospital Resources
B. Driving Under the Influence of Drugs
C. Relationship of Marijuana Use and Co-Use with other Substances
36.7 Analysis and Testing for Marijuana Use
36.8 Scientific Data Relating to THC
A. Blood THC vs. Brain THC: Any Relationships?
B. Relationships Between Percent Plant-THC and Plasma-THC
C. Is There a Relationship Between Percent THC in the Smoked Cigarette and Plasma THC?
D. Relation Between Degree of "High" and Plasma THC
E. Occasional Marijuana Users vs. Practiced Users
F. Is THC the Only Psychoactive Cannabinoid?
G. Urine Testing for Cannabinoids: Clinical or Evidentiary Value?
H. Impairment and Marijuana: Laboratory and On-Road Driving Performance Data
I. Hospital and Provider Considerations
36.9 Forensic Case Reports
36.10 Summary and Conclusions
References
Chapter 37: Drug Evaluation and Classification Program: An Evidence-Based Analysis
Fran M. Gengo Pharm.D., FCP and Anna Mattle, Pharm.D., M.S.
37.1 Introduction
37.2 The 12 Steps of DRE Examinations
37.3 Scientific Evaluation of DRE Examinations
A. Step 2: Interview of Arresting Officer
B. Step 3: Preliminary Examination and Initial Pulse Measurement
C. Step 4: Eye Examination
D. Step 5: Divided Attention Tests
E. Step 6: Second Pulse Reading, Body Temperature, and Blood Pressure Measurement
F. Step 7: Eye Examination of Pupil Size in Various Lighting Conditions
G. Step 8: Assessment of Muscle Tone
H. Step 11: DRE Officer Opinion Statement
I. Step 12: Toxicology Sample
37.4 Literature Evaluations And Critiques Of Dre
37.5 Cannabis
37.6 Statistical Validity and Overall Strength of DRE Studies
37.7 DRE Support Literature
A. Bigelow et al. 1985 Study
B. Heishman et al. 1996 and 1998 Studies
C. Smith et al. 2002 Study
D. Shinar and Schechtman 2005 Study
E. Specific Identification of Drug Class by DRE Officers in Validation Studies
37.9 Summary
37.10 Summary and Conclusions
References
Chapter 38: Involuntary Intoxication
James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN, James J. O'Donnell III, M.S., Ph.D., William Vaughn, J.D.
38.1 Introduction
38.2 Legal Defense Considerations for a Violent Crime
38.3 Confirming That Drugs are Involved in a Violent Crime
38.4 Beyond Pharmacology: The Multifactorial Role of Drugs in Aggression and Violence
38.5 Association of Drugs with Aggression and Violence
38.6 Mechanisms of Drug-Induced Violence
38.7 Intoxication of Victim Defense
38.8 Summary and Conclusions
References
Chapter 39: Drug-Induced Aggression and Violence
Peter D. Anderson, Pharm.D., BCPP
39.1 Classification of Aggression
39.2 Causes of Aggression and Violence
A. Neurobiology of Aggression
B. Medical and Psychiatric Causes of Aggression
39.3 The Role of Drugs as a Cause of Violence
A. Introduction
B. Problems with the Literature
C. Specific Drugs or Drug Classes that cause aggression
1. Ethanol
2. Lysergic Acid Diethylamide
3. Phencyclidine and Ketamine
4. Anabolic Steroids
5. Insulin
6. Psychostimulants
7. Benzodiazepines
8. Selective Serotonin Reuptake Inhibitors
9. Varenicline
10. Environmental Chemicals
39.4 The Drug-Induced Insanity Defense
39.5 Summary and Conclusions
References
Chapter 40: Forensic Drug Testing Chapter
James J. O'Donnell III, M.S., Ph.D, and James T. O'Donnell, Pharm.D., M.S., FCP, ABCP, FACN
40.1 Introduction
40.2 Non-Regulated Drug Testing
40.3 Regulated Drug Testing
40.4 Voluntary Programs
40.5 Establishment of a Workplace Program
A. Written Policy
B. Employee Assistance Programs
C. Employee Awareness Training
D. Supervisor Training
E. Drug Testing
40.6 The Drug-Testing Process
A. Specimen Collection
B. Accessioning
C. Drugs to Be Tested
D. Screening Tests
E. Confirmation Tests
F. Reporting and Storage of Samples
G. Prevention Against and Detection of Drug Test Cheating
40.7 Additional Program Aspects
A. The Medical Review Officer (MRO)
B. Public Interest Exclusions (PIE)
C. Blind Performance Testing
D. Alcohol Testing
40.8 Special Drug-Testing Issues
A. Type of Matrix
1. Hair Testing
2. Saliva Testing
3. Sweat Testing
4. Blood
5. Urine
B. Alternate Sources of Drug Exposure
C. Amphetamine Testing Issues
D. Medical Use of Drugs
40.9 Legal Aspects of Workplace Drug-Testing
A. Constitutional Issues
B. State and Federal Mandates
40.10 Discovery: The "Litigation Package"
40.11 Case Reports
40.12 Summary and Conclusions
References
Chapter 41: Postmortem Redistribution and Interpretation of Drug Levels
Gourang P. Patel Pharm.D., M.Sc., BCPS, BCCCP, FCCM
41.1 Abstract
41.2 Introduction
41.3 Review of a Case File
41.4 Postmortem Considerations
A. Physiologic Changes in the Body After Death
B. Drug Characteristics
41.5 Analysis of Drug Level Information
41.6 Summary and Conclusions
References
Chapter 42: Addiction as Mitigation
Barry D. Hargan, M.S., MHA and James T. O'Donnell, Pharm.D., M.S., FCP
42.1 Introduction
42.2 Clinical Variables Which Contribute to the Onset of Addiction
A. Genetic Predisposition
B. Learned Behavior
C. Psychopathological Exposure
42.3 Substance/Medication-Induced Mental Disorder
A. Executive Summary of Opinion
B. Neurotoxicity Mechanisms of Alcohol and Anabolic Steroids in the Developing Brain
C. Anabolic Steroid Effects on Brain Structure and Function
D. Translational Impact - what does this mean to a teenager abusing large amounts of alcohol and steroids?
E. Clinical and Practical Applications of the Basic Neuroscience
F. Behavioral Abnormalities Associated with Anabolic Steroid Use
G. Defendant's Alcohol and Anabolic Steroid Use
1. Alcohol
H. Expert Opinions Regarding Substance-Induced Brain Damage Affecting Behavior
42.4 The Simplified Version of Neurobiology and the Addicted Brain
42.5 Cocaine
42.6 Expert Testimony Concerning Addictive Disorders
A. Role of the Addictions Expert
B. Some Testimony Experiences and the Limits of Opinions
C. Preparation
42.7 Additional Considerations Concerning Addiction Mitigation
A. Neuropsychological Evaluation
42.8 Summary and Conclusions
References
Este título pertence ao(s) assunto(s) indicados(s). Para ver outros títulos clique no assunto desejado.
