O'Donnell's Drug Injury

James J. O’Donnell III, M.S., Ph.D., is a chemist and research pharmacologist. He is an Associate Professor at Rosalind Franklin University of Medicine and Science, where he teaches at the Chicago Medical School and the College of Pharmacy. He is the pharmacology coordinator at the Chicago Medical School, and in the College of Pharmacy he was the founding course director of the core pharmacology courses as well as a forensic toxicology and pharmacology elective. He has also given guest lectures at Rush University on pharmacokinetics and other pharmacology topics. He served as an NIH T32 Training Grant Postdoctoral Fellow in Respiratory Biology at the University of Chicago. He has also held a postdoctoral appointment at the Indiana University School of Medicine at South Bend. His research has primarily focused on inflammatory diseases and pharmacokinetics. He has conducted organometallic chemistry research at University of Wisconsin-Madison and at Northwestern University in Evanston, IL. He currently serves as President of the American Society for Pharmacology and Experimental Therapeutics – Great Lakes Chapter (ASPET-GLC) and is a member of the American College of Clinical Pharmacology (AACP) and the American Academy of Clinical Toxicology (AACT). He is a Co-Editor of O’Donnell’s Drug Injury, Fourth Edition, and the Chief Editor of Drug Discovery and Development, Third Edition. He consults in drug injury, analytical toxicology, and other related matters. Dr. O’Donnell received a Bachelor of Science Degree in Electrical Engineering and Computer Science from the Massachusetts Institute of Technology (MIT), a Master of Science Degree in Chemistry from the University of Wisconsin-Madison, and a Doctor of Philosophy in Pharmacology from Rush University in Chicago, IL.James T. O’Donnell, Pharm.D., M.S., FCP, ABCP, FACN, is a pharmacologist, pharmacist, and nutritionist in Barrington Hills, Illinois. He is an Associate Professor of Pharmacology at Rush University Medical Center in Chicago, IL where he served as the Course Director of the Medical Pharmacology course. He also held faculty appointments at the University of Illinois Colleges of Medicine and Pharmacy. Dr. O’Donnell is a Diplomate of the American Board of Clinical Pharmacology, a Fellow of the American College of Clinical Pharmacology, a Fellow of the American College of Nutrition, Founding Editor-in-Chief of the Journal of Pharmacy Practice, and Editor of Drug Injury: Liability, Analysis, and Prevention, First Edition, Second Edition, Third Edition; Co-Editor of O’Donnell’s Drug Injury, Fourth Edition, a Co-Editor of Pharmacy Law: Litigating Pharmaceutical Cases, and Co-Editor of Drug Discovery and Development, Second and Third Editions. He consults and testifies in matters involving pharmaceuticals, medication errors, nutritionals, dietary supplements, alcohol and recreational drug toxicity, and drug injuries throughout the United States, for defense and plaintiffs’ counsel. Dr. O’Donnell received a Bachelor of Science in Pharmacy from the University of Illinois, a Doctor of Pharmacy from the University of Michigan, and a Master of Science in Clinical Nutrition from Rush University.Gourang Patel, Pharm.D., M.Sc., BCPS, BCCCP, FCCP, FCCM, is the Director of Clinical Pharmacy Services at the University of Chicago Medicine – Chicago, IL. Dr. Patel earned a Bachelor of Chemistry from Truman State University, Doctorate in Pharmacy from the St. Louis College of Pharmacy, and his Masters in Clinical Research from the Rush Graduate College. He also reviews medical malpractice cases for both Defense and Plaintiff sides in the areas of pharmacology, toxicology, and pharmacy practices. Dr. Patel is dual board certified in Pharmacotherapy (BCPS) and Critical Care (BCCCP) and is a Fellow within the American College of Clinical Pharmacy (FCCP) and within the Society of Critical Care Medicine (FCCM).Jennifer Splawski, Pharm.D., M.S., BCPS, is currently a Director of Clinical Value at BluesightTM, A Medication Intelligence Company, where she leads clients in creating successful controlled substance diversion programs incorporating artificial intelligence-based software. Her experience includes clinical pharmacy practice specializing in emergency medicine, operational leadership, and implementing technology within the healthcare space. She also consults and testifies on legal matters for both Defense and Plaintiff cases related to medication errors and clinical pharmacology/toxicology throughout the United States. Dr. Splawski earned a Bachelor of Science in Psychology and Doctor of Pharmacy degree from the University of Illinois at Chicago, and a Master of Science degree in Pharmacy focusing in Clinical Toxicology and a Forensic Toxicology Certificate from the University of Florida. She served a postgraduate Pharmacy Residency at the University of California in San Francisco and is a Board-Certified Clinical Pharmacy Specialist (BCPS).

• PART I: THE PHARMACEUTICAL PROCESSChapters 1 – 9Chapter 1: FDA and Drug Approval ProcessMegan Walter and Lindsay E. Wagner 1.1 Introduction1.2 The New Drug Development ProcessA. Discovery and Preclinical ResearchB. Clinical ResearchC. Investigational New Drug ApplicationD. Phases of Clinical StudiesE. Expanded Access ProgramsF. Right to Try1.3 New Drug and Therapeutic Biologic Application ProcessA. New Drug Applications and Biologic License ApplicationsB. Fundamentals of NDA and BLA SubmissionsC. NDA Classifications1.4 FDA ReviewA. Expedited Development and Review Programs1. Accelerated Approval2. Priority Review3. Fast Track4. Breakthrough TherapyB. Labeling Review1. Physician Labeling Rule (PLR)2. Pregnancy and Lactation Labeling Rule (PLLR)3. Additional FDA-Approved Patient LabelingC. Risk Evaluation and Mitigation StrategiesD. Advisory Committee Meetings1.5 The Generic Drug Approval ProcessA. Abbreviated New Drug ApplicationsB. ANDA ApprovalC. Generic Drug User Fee Amendments1.6 Biosimilar Pathway1.7 Over-the-Counter Drug Products1.8 Postmarketing SurveillanceA. Adverse Event ReportingB. FDA Adverse Event Reporting SystemC. Post Marketing Requirements and CommitmentsD. Sentinel NetworkE. Drug Safety Oversight Board1.9 Applicable Statutes and Implementing RegulationsA. Food and Drug Acts – 1906B. Food, Drug and Cosmetic Act – 1938C. Durham-Humphrey Amendment – 1951D. Kefauver-Harris Amendment – 1962E. Orphan Drug Act – 1983F. Drug Price and Competition and Patent Term Restoration Act – 19841. Revision of New Drug Application Regulations - 19852. Revision of Investigational New Drug Application Regulations - 19873. Treatment Use of Investigational New Drugs - 1987G. Prescription Drug User Fee Act (PDUFA) – 1992H. FDA Modernization Act (FDAMA) – 1997I. FDA Amendments Act (FDAAA) – 2007J. Food and Drug Administration Safety and Innovation Act (FDASIA) – 2012K. The Drug Quality and Security Act (DQSA) – 2013L. 21st Century Cures Act – 2016M. Food and Drug Administration Reauthorization Act (FDARA) – 2017N. Coronavirus Aid, Relief, and Economic Security Act (CARES Act) – 20201.10 Conclusion1.11 Glossary of TermsReferencesChapter 2: The Front Lines of Clinical Research: The Industry and Ethical ConsiderationsJonathan C. Young2.1 Introduction2.2 Clinical Trial Service ProvidersA. Food and Drug AdministrationB. Clinical Trial SponsorC. Contract Research OrganizationsD. Study Monitors2.3 Clinical Trial SiteA. Site Management OrganizationsB. Institutional Review Boards2.4 The Evolution of Ethical Principles in Clinical ResearchA. Respect for PersonsB. BeneficenceC. JusticeD. How the Investigator Applies Ethical Principles2.5 Regulations Governing Institutional Review BoardsA. What Institutional Review Board Members Should Know about Clinical ResearchB. What Institutional Review Board Members Should Know about Their Responsibilities2.6 What the Site Should Know about Institutional Review BoardsA. What Research Requires Institutional Review Board Approval and OversightB. Requirements of an Investigator for Institutional Review Board Research Approval2.7 Risks-vs.-Benefits Analysis: The Human AdvocateA. Identifying and Assessing the RisksB. Minimal Risk vs. Greater-than-Minimal RiskC. Vulnerable Populations and Minimal RiskD. Determining Whether Risks Are MinimizedE. Assessing Anticipated BenefitsF. Determining Whether Risks Are ReasonableG. Continuing Review and Monitoring of Data2.8 Informed Consent: Not Just a DocumentA. Elements of an Informed ConsentB. Additional Required Elements2.9 Research Participants2.10 Industry Trade Organizations and Support Services2.11 Summary: Ethical Dilemmas in Clinical ResearchReferencesChapter 3: Search and Analysis of the Food and Drug Administration’s FDA Adverse Event Reporting System (FAERS)Paul N. Danese3.1 Introduction3.2 BackgroundA. Small Clinical Trial PopulationsB. Narrow Patient DemographicsC. Restricted Co-Administration of Medications3.3 History of the FDA’s Drug Safety Surveillance Systems3.4 Submission of Adverse Event Reports to the FDAA. Mandatory ReportsB. Voluntary Reports3.5 Adverse Drug Reaction Information Captured by FAERS3.6 Searching FAERS Data to Identify Possible Safety ProblemsA. Statistical Methods to Identify Drug Safety SignalsB. Dechallenge and Rechallenge Data and CausalityC. Identifying Drug-Drug InteractionsD. Timelines and Deadlines of Adverse Event Reporting3.7 The Food and Drug Administration’s Use of FAERS in Regulatory DecisionsA. Boxed WarningsB. Other Changes to a Medication’s Prescribing InformationC. Determinations that No Action is needed and Continuing Investigations3.8 Limitations of FAERSA. Lack of Demonstration of Causality for Individual ReportsB. Extensive Under-reportingC. Reporting BiasesD. Lack of Comparator Populations (Lack of a Denominator)3.9 Search and Retrieval of Adverse Event Reports from the FDA’s FAERSA. Raw Data FilesB. FDA Public DashboardC. FOIA RequestsD. Commercial Vendors3.10 Other FDA Adverse Event Reporting SystemsA. VAERSB. MAUDEC. Sentinel Initiative3.11 Summary and ConclusionsReferencesChapter 4: The Safety of Medicines: PharmacoVigilance, PharmacoSurveillance, PharmacoEmpowerment?David Healy4.1 RxISK.org4.2 Antidepressants: Data Based or Evidence Based?4.3 Access to Adverse Event Data4.4 RCTs and Adverse Events // Ghost Writers4.5 RCTs & Primary Endpoints4.6 Post 1962: Confounding & Causality4.7 Pharmacovigilance4.8 RxISK.org and Pharmacovigilance 1.04.9 Pharmacosurveillance4.10 TaperMD and Pharmacovigilance 2.04.11 Summary and ConclusionsReferencesChapter 5: Important Code of Federal Regulations Applicable to Drug Product Liability SuitsS. Albert EdwardsChapter 6: The Regulation of Drug Product Information to ConsumersFrank J. Ascione6.1 The Historical Development of Food and Drug Administration (FDA)’s Regulatory RoleA. Early phase (prior to 1906): No significant government interventionB. Early Regulatory Phase (1906-1938): Minimal Government ControlC. 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 Consumers6.3 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 AdvertisingA. Advantages and Disadvantages of DTCA6.4 Summary and ConclusionsReferencesChapter 7: The Role of Investigative Journalism in Improving Drug SafetyMartha Rosenberg7.1 Introduction7.2 Direct-To-Consumer Advertising Increased with CovidA. Unbranded DTC AdvertisingB. Industry Funded Disease Awareness GroupsC. Encouraging Victim Politics7.3 The Opioid EpidemicA. Growing an Untapped MarketB. Aggressive Opioid MarketingC. Fostering Opioid AddictionD. Pill Mills and Addiction MedicineE. Opioid Lawsuits SurfaceF. Lack of Opioid Efficacy and Serious Side EffectsG. Paying for the Opioid Epidemic7.4 Effective Hepatitis C Drugs DebutA. Lawmakers Investigate Hep C PricesB. Aggressive Hep C MarketingC. Screening as a Hep C Sales ToolD. Hepatitis C Safety Signals Emerge7.5 Asthma Drug Safety SignalsA. Xolair Leaves a Trail of QuestionsB. More Improper Xolair MarketingC. Safety Signals Surface with Xolair and a Lawsuit is Dismissed7.6 Long-Acting Beta AgonistsA. Glaxosmithkline Settlement included a Laba7.7 Safety Questions About Leukotriene Receptor AntagonistsA. Parents Report LTRA Side EffectsB. LTRA Safety Signals Emerged EarlyC. Patients and Parents Fight BackD. Black Box Added to Singulair7.8 Baldness Treatments Become Popular and ControversialA. Finasteride Side Effects Create ConcernB. Medical Literature Confirms Finasteride Side EffectsC. FDA Adds Warnings to FinasterideD. Finasteride User Speaks OutE. No Satisfying End for Finasteride Users7.9 Biologic DrugsA. Tumor Necrosis Factor (Tnf) BlockersB. Tnf Blocker Risks7.10 Other Popular Medications Come Under New ScrutinyA. N-Nitrosodimethylamine (NDMA) Found in Medicines1. Zantac Taken Off Shelves2. NDMA Also Found in Metformin7.11 Popular Stimulant Drugs Reveal RisksA. Risks Seen with ModafinilB. Fetal Risks Seen with Modafinil and ArmodafinilC. European Union Sues Provigil Makers7.12 Fetal Risk Seen with NSAIDs7.13 Bisphosphonates Continue to Present Risks7.14 SSRI Antidepressants Linked to New RisksA. SSRI Bone ThinningB. SSRI Addictive Potential7.15 Belviq, A Diet Drug Withdrawn from Market7.16 Sleeping Pills Given Boxed WarningsA. Public Figures on Sleeping Pills Make the NewsB. Other Sleeping Pill Risks7.17 Risks Associated with Fluoroquinolone AntibioticsA. Fluoroquinolones Warnings ContinueB. Hormone Therapy Still Linked to RisksC. Beware of Testosterone MarketingD. New PPI QuestionsReferencesChapter 8: Evaluation of Causation in Drug Injury CasesDonald H. Marks and James T. O'Donnell8.1 What is Causation?8.2 Importance of Establishing Causation8.3 Definitions8.4 Degree of Adverse Effects Relate to Intervention8.5 Methodology to Investigate Causation8.6 Structured Algorithms for Determination of CausationA. Hill Criteria—Expanded Discussion1. Strength of Association2. Consistency of Results3. Specificity4. Temporal Relationship5. Dose Response6. Biological Plausibility7. Biological Coherence8. Experimentation9. Analogy8.7 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 PrinciplesA. Case Report: Acyclovir Overdose – Pharmacist Recommended OverdoseB. Case Report: Challenging Cause of Death in a Malpractice MatterC. Case Report: Determination of the Effects of Morphine in a Will ContestD. Case Report: Proof of Drug-Induced Mental Changes in Complainant in Sexual Abuse Case8.12 Summary and ConclusionsReferencesChapter 9: General Principles of PharmacologyJames J. O'Donnell III, James T. O'Donnell, and Vanessa Juettner9.1 Introduction9.2 Basic PrinciplesA. AbsorptionB. Lipid DiffusionC. Determinants of Absorption1. Lipid/aqueous partition coefficient and pH2. Bioavailability3. First pass effect9.3 Routes of Administration9.4 Extravascular AdministrationA. Oral AdministrationB. Rectal AdministrationC. Other Routes of Administration9.5 Intravascular Administration9.6 DistributionA. DiffusionB. Volume of DistributionC. Binding to Plasma Proteins and Cellular ConstituentsD. Re-DistributionE. Blood-Brain Barrier (BBB)F. Placental BarrierG. Therapeutic RangeH. Bioequivalence vs. Bioinequivalence10.7 Drug Metabolism (Biotransformation)A. Phase I Reactions1. The families of human P450s2. Induction of P450 enzymes3. P450 InhibitionB. Phase II Reactions1. Metabolism of drugs to toxic products9.8 Factors Affecting Drug MetabolismA. DiseaseB. AgeC. GenderD. Genetic Factors9.9 Drug ExcretionA. Urinary Excretion1. Glomerular filtration2. Tubular secretion (active secretion)3. Tubular reabsorption4. Effects of pH on urinary excretion of ionizable drugs9.10 PharmacokineticsA. IntroductionB. Therapeutic Window and Therapeutic IndexC. Blood Levels for Narrow Therapeutic Index (NDI) DrugsD. Kinetic ModelingE. Drug Absorption and Elimination1. Absorption rate2. Elimination rate3. Clearance (CL)4. Area Under the Curve (AUC)5. Elimination (k)6. Elimination half-life7. Steady stateF. Dosing1. Loading dose2. Maintenance doses (MD)3. Example—dosage adjustment in renal impairmentG. Therapeutic Drug Monitoring (TDM)H. Pharmacokinetics Summary9.11 Drug Receptor and PharmacodynamicsA. Agonists and AntagonistsB. Drug-Receptor Interactions9.12 Dose ResponsesA. PotencyB. Agonism and Antagonism1. Partial agonists9.13 Competitive Antagonism9.14 Non-Competitive Antagonism9.15 Summary and ConclusionsPART II: HIGH-RISK DRUG THERAPIES RESULTING IN INJURY AND LITIGATIONChapters 10 - 25Chapter 10: Adverse Drug ReactionsJames T. O'Donnell and James J. O'Donnell III 10.1 Adverse Drug Reactions: How Large is the Problem? What Drugs are Involved? What are the Injuries?A. Historical PerspectiveB. Incidence of Adverse Drug ReactionsC. Food and Drug Administration Reporting RequirementsD. The “Seven Deadly Sins”: Why Doctors Fail to Report Adverse Drug ReactionsE. Attitudes Toward Adverse Drug ReactionsF. Investigator Fraud10.2 Classification of Adverse Drug ReactionsA. Categories of Adverse Drug Reactions1. Type A reactions: Augmentation of the Pharmacological Response2. Type B reactions: Bizarre (idiosyncratic)10.3 Types of Drug Allergy and HypersensitivityA. The Nature of Drug AllergyB. Dangerous Drug-Allergy ReactionsC. Drug Sensitivities Mimic Allergy SymptomsD. Definitions of Allergic/Hypersensitivity ReactionsE. Idiosyncratic ReactionsF. IntoleranceG. ToxicityH. Hypersensitivity VasculitisI. Predominantly Organ-Specific ReactionsJ. UrticariaK. Fixed Drug EruptionsL. Photosensitivity ReactionsM. Generalized Exfoliative DermatitisN. ThrombocytopeniaO. Hemolytic AnemiaP. AgranulocytosisQ. Treatment: Withdrawal of the Suspected DrugR. Symptomatic TreatmentS. Prevention of Allergic Drug ReactionsT. PseudoallergyU. AngioedemaV. Hypersensitivity Reactions10.4 Risk Factors, Drugs and PatientsA. Hypersensitivity Risk FactorsB. Identification of a Drug AllergyC. Allergy to AntibioticsD. Case Report: Cross-Allergenicity10.5 Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal NecrolysisA. Fixed Drug EruptionsB. Erythema Multiforme-Like EruptionsCase Report: Lamictal Induced Stevens Johnson SyndromeC. FluoroquinolonesE. NSAIDs Cross Reactivity Case ReportF. Radiographic Contrast MediaG. Local AnestheticsH. Anticonvulsants (AED)10.6 Summary and ConclusionsReferencesChapter 11: Drug-Induced FallsJames T. O'Donnell and James J. O'Donnell III11.1 Introduction11.2 The Definition of Fall11.3 Epidemiology11.4 Causes and Risk FactorsA. Physiological Risk Factors for Falls in the ElderlyB. Psychological Risk FactorsC. Medical Conditions11.5 Medication-related Falls11.6 Types of Medications that Increase the Risk of FallA. Centrally Active MedicationsB. BenzodiazepinesC. AntipsychoticsD. Antihypertensives1. Orthostatic Hypertension and Risk of FallE. Opioids11.7 Marijuana11.8 Alcohol11.9 Hip Fractures11.10 Polypharmacy11.11 Fall Risk Assessment11.12 Types of Assessments11.13 Strategies for Fall Prevention in Institutionalized SettingsA. ScreeningB. Addressing Risk Factors1. Monitoring Patients2. Environmental Interventions3. Educational Programs4. Reducing Fall InjuryC. Discharge PlanningD. Disseminating Evidence: Awareness and Intervention Work!11.14 Summary and ConclusionsReferencesChapter 12: Drug-Induced Movement DisordersJadwiga Najib and Meagan Bailey12.1 Introduction12.2 Presentation12.3 Agents Associated with Drug-Induced Movement Disorders12.4 Risk Factors12.5 Sequelae of Drug-Induced Movement Disorders12.6 Theories of Causation12.7 Drug-Induced Movement Disorders in Children and Adolescents12.8 Drug-Induced Movement Disorders in the Elderly12.9 Acute/Intermediate Drug-Induced Movement DisordersA. Dystonia1. Presentation2. Implicated agents3. Risks4. ManagementB. AtaxiaC. BruxismD. Neuroleptic Malignant SyndromeE. Serotonin Syndrome12.10 Chronic Drug-Induced Movement DisordersA. Akathisia1. Presentation2. Case study: Trazodone-induced akathisia3. Implicated agents4. Other drugs5. Risks6. ManagementB. Parkinsonism1. Presentation2. Case Study: Neuroleptic-Induced Parkinsonism3. Implicated agents4. Other drugs5. Risks6. ManagementC. Myoclonus, Tremor, Tics, Asterixis12.11 Persistent/Tardive Drug-Induced Movement DisordersA. Tardive Dyskinesia1. Presentation2. Case Study: Neuroleptic induced oral buccal dyskinesia and akathisia3. Implicated agents4. Case Study: Metoclopramide induced oral buccal lingual dyskinesia5. Risks6. ManagementB. Tardive AkathisiaC. Tardive Dystonia1. Case Report: Neuroleptic induced cervical dystoniaD. Other Tardive Variants12.12 Drugs Used for Movement Disorders12.13 Monitoring12.14 Clinical and Legal Issues in Psychiatry12.15 Summary and ConclusionsReferencesChapter 13 Acute Adverse Drug Events in Critical Care, Emergency Department and Intensive Care UnitsGourang P. Patel13.1 BackgroundA. EpidemiologyB. Environment13.2 High-Risk Medication-Related EventsA. Hypersensitivity ReactionsB. Cardiovascular Reactions1. Blood pressure (BP)2. Heart rate (HR)3. ArrhythmiasC. Nephrotoxicity1. Aminoglycosides 2. Amphotericin B3. Intravenous contrastD. Hypoglycemic EventsE. Infusion-Related Reactions1. Extravasations2. Propofol-related infusion syndrome (PRIS)3. Intravenous N-acetylcysteine (NAC)F. Reversal Agents1. Protamine2. Vitamin K3. Naloxone4. Flumazenil13.3 Summary and ConclusionsReferencesChapter 14: Nephrotoxic DrugsJason M. Kidd, Domenic A. Sica, and Todd W. B. Gehr 14.1 Introduction14.2 Framework of the problem14.3 Basis for the kidney being susceptible to damage14.4 Patient groups most susceptible to nephrotoxicity14.5 Demographics of chronic kidney disease14.6 Methods to assess renal function and/or damage14.7 Level of renal function at which drug accumulation occurs14.8 Nephrotoxic drugsA. What constitutes prompt clinical action in the face of nephrotoxicity?14.9 Nephrotoxicity scenariosA. Lithium toxicityB. Gentamicin toxicityC. Dialysis-related issuesD. Drug Clearance in Relationship to Renal Failure1. Case 12. Case 2E. Angioedema with an ACE inhibitorF. Fatal hyperkalemia with medicationsG. Statin therapy and the development of myopathyH. Nephrotoxicity related to checkpoint inhibitor use14.10 Summary and ConclusionsReferencesChapter 15: Drug-Induced Liver DiseaseJames T. O’Donnell, James J. O’Donnell III, Donald H. Marks, and Paul Danese15.1 Introduction: The Problem of Drug-Induced Liver Disease15.2 History of Adverse Drug Reactions15.3 Overview of DILD, Epidemiology Risk Factors, Histopathology, and DiagnosesA. Epidemiology of Drug HepatotoxicityB. Risk FactorsC. HistopathologyD. Diagnosis15.4 Hepatic Drug Metabolism15.5 FDA and DILD15.6 Types of Liver InjuryA. HepatitisB. Massive Hepatic Necrosis (Fulminant Hepatitis)C. Drug-induced Vanishing Bile Duct Syndrome15.7 Specific DILD Product Areas and Case DiscussionsA. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Use and HepatoxicityB. Isoniazid-Induced HepatotoxicityC. Acetaminophen1. Acetaminophen Toxicity Assessment Nomograms2. FDA Report - Acetaminophen Induced Liver DiseaseD. Macrolide HepatotoxicityE. Methotrexate (MTX) HepatotoxicityF. Estrogens and Oral Contraceptive SteroidsG. StatinsH. TiclopidineI. ACE Inhibitors and AT II Receptor AntagonistsJ. FluoroquinolonesK. TerbinafineL. KetoconazoleM. Selective Serotonin Reuptake Inhibitors – Serzone Liver ToxicityN. Herbal and Other Dietary Supplements and Hepatotoxicity15.8 Summary and ConclusionsReferencesChapter 16: Antineoplastic Therapy Kathryn Schultz and Eris Tollkuci16.1 Background16.2 Chemotherapy - Antimetabolites16.3 Chemotherapy - Antimicrotubules16.4 Chemotherapy - Alkylators16.5 Chemotherapy - Topoisomerase I Inhibitors16.6 Chemotherapy - Topoisomerase II Inhibitors16.7 Chemotherapy - Antitumor Antibiotics16.8 Chemotherapy - Miscellaneous16.9 Targeted TherapyA. Infusion-related reactions (IRRs)B. Immunotherapy (Immune Checkpoint Inhibitors)1. Infusion-related reactions2. Immune-Related Adverse Events (irAEs)16.10 Tumor Lysis Syndrome16.11 Hepatotoxicity16.12 Summary and ConclusionsReferencesChapter 17: Dangers of OpioidsJennifer Splawski, James T. O’Donnell, and James J. O’Donnell III.17.1 IntroductionA. DefinitionsB. History17.2 Pharmacology of OpioidsA. EffectsB. Opioid Neural Receptors1. Central Nervous System (CNS) Receptors2. Peripheral Nervous System (PNS) ReceptorsC. Routes of Administration1. Oral2. Intramuscular3. Subcutaneous4. Intravenous5. Transdermal6. Sublingual and Buccal7. NeuraxialD. MetabolismE. Excretion17.3 Toxicity of OpioidsA. Respiratory DepressionB. Symptoms of Overdose17.4 Epidemiology of Opioid AbuseA. Opioid Abuse in Adolescents and Young AdultsB. Opioids in Pregnancy17.5 Contributions to the Opioid EpidemicA. Opiates Handed Out Like Candy to ‘Doped-up’ VeteransB. United States Reaches $22 Million Settlement Agreement with CVS For Unlawful Distribution of Controlled SubstancesC. Former Walmart Pharmacists Say Company Ignored Red Flags as Opioid Sales BoomedD. Federal Judge Approves Landmark $8.3 Billion Purdue Pharma Opioid Settlement17.6 Combatting the Opioid EpidemicA. Prescription Monitoring Programs (PDMP)B. Naloxone DispensingC. Medication for Opioid Use Disorder (MOUD)1. BuprenorphineA. PharmacokineticsB. Adverse EffectsC. Place in therapy1. MethadoneA. PharmacokineticsB. Equianalgesic DosingC. Drug InteractionsD. Cardiovascular EffectsE. Consequences of Ignorance of Proper Dosing of MethadoneF. Methadone Legal Case Examples Involving Patient DemiseG. Applying Lessons Learned and Action for Institutional Committees17.7 Case Reports: Opioid Toxicity Causing Respiratory Arrest, Brain Damage, and DeathA. Case Report: Respiratory Arrest and Brain Damage Following Morphine OverdoseB. Case Report: Fentanyl Epidural Respiratory ArrestC. Case Report: Fentanyl (Duragesic®) Death in Discharged PatientD. Case Report: High Dose Fentanyl Patch Prescribed in Opiate-Naïve Patient—DeathE. Case Report: Heroin and Other OpioidsF. Case Report: Hydromorphone (Dilaudid®) Respiratory Arrest17.8 Investigation and Prosecution of Pain Clinics by the Department of Justice (DOJ)17.9 Summary and ConclusionsReferencesChapter 18: Adverse Effects of Diabetic Drugs: Focus on HypoglycemiaGourang P. Patel and James T. O’Donnell 18.1 Diabetes Demographics and Epidemiology18.2 Insulin18.3 Insulin Preparations18.4 Clinical Use of InsulinA. Dosing18.5 Hypoglycemia (Low Blood Sugar)A. Etiologies of hypoglycemiaB. Insulin-induced hypoglycemiaC. Deaths by Hypoglycemia18.6 Pathophysiology and Clinical Symptoms of Hypoglycemia18.7 Incidence18.8 Pathophysiology and Biochemistry of Hypoglycemia18.9 Adverse Reactions Involving HypoglycemiaA. Insulin damages baby’s brain; pharmacist error suggested18.10 End Product Testing Recommended18.11 Insulin Murders18.12 Hypoglycemia from the Sulfonylurea Derivatives18.13 Adverse Effects of the Sulfonylureas18.14 Drug Interactions with Sulfonylureas18.15 The Gliptin Class New drugs for Diabetes Treatment Type 2 Diabetes18.16 ThiazolidinedionesA. Hepatic FailureB. Bladder Cancer18.18 Summary and ConclusionsReferencesChapter 19: Parenteral Nutrition-Related Errors and ComplicationsErica M. Fernandez19.1 Introduction19.2. Basic principles of PN19.3 PN Provision CategoriesA. PrescribingB. Transcribing and VerificationC. CompoundingD. Administration19.4. Monitoring and ComplicationsA. Glycemic ControlB. Refeeding SyndromeC. Hepatobiliary ComplicationsD. Complications involving micronutrients19.5 PN Component Shortages and Adverse Events19.6 Summary and ConclusionReferencesChapter 20: Antidepressants: Clinical Use and Litigation Henry Cohen and Michael Liu20.1 Major Depressive Disorders20.2 Antidepressant Pharmacology20.3 Antidepressant OverdoseA. Trazodone and Permanent Neurologic Sequelae20.4 Antidepressants and the Patient with Suicidal IdeationA. Prozac and Suicidal Ideation1. Woulfe v. Eli Lilly & Co.2. Espinoza v. Eli Lilly & Co.3. Cassidy v. Eli Lilly & CoB. Paxil and Suicidal Ideation1. Dolin v. GlaxoSmithKlineC. Antidepressant and Increased Suicidality in Pediatrics1. Schilf v. Eli Lilly & Co.20.5 Broken Heart Syndrome: Tako Tsubo Cardiomyopathy Associated with Use of Antidepressants20.6 The Adverse Effects of Antidepressants and the Duty to WarnA. Docken v. Ciba-GeigyB. Stebbins v. Concord Wrigley Drugs, Inc. et al.C. Morgan et al. v. Wal-Mart Stores, Inc.D. Kampmann v. MasonE. Cottam v. CVS20.7 Antidepressants and AlcoholA. Kirk v. Michael Reese HospitalB. Hand v. Krakowski20.8 Selective Serotonin Reuptake Inhibitors and the Serotonin Syndrome20.9 Hepatic Cytochrome P450 Drug Interactions and Cyclic Antidepressants20.10 Antidepressants and Herbal Agents Drug Interactions20.11 Serzone and Liver Disease20.12 High Blood Pressure Associated with Venlafaxine Use20.13 SSRI use and Birth Defects20.14 Bupropion XL and Seizures20.15 The Pharmacist’s Role20.16 The Omnibus Budget Reconciliation Act20.17 How Safe is it to Buy Prescription Medications Over the Internet?20.18 In a Perfect World20.19 Summary and ConclusionsReferencesChapter 21: Contrast Media Neurotoxicity Following MyelographyStephanie E. Tedford and James T. O’Donnell21.1 Introduction21.2 Case ReportsA. Case I Intrathecal IopamidolB. Case II Intrathecal Iothalamate21.3 DiscussionA. Mechanisms for cerebral (neurotoxic) injuryB. Contrast-induced neurological and cognitive deficitsC. Contrast-induced visual and auditory impairment: Further evidence for cerebral insult to cortical brain structures21.4 Summary and ConclusionsReferencesChapter 22: Fetal Drug ExposureDamani Parran, James T. O’Donnell, and James J. O’Donnell III 22.1 Introduction22.2 Critical Periods of Human Development and Susceptibility22.3 Special Considerations of Drug Exposure during Pregnancy22.4 Historical Human Developmental ToxicantsA. ThalidomideB. EthanolC. DiethylstilbestrolD. RetinoidsE. Cocaine22.5 Developmental Toxicity of Prescription DrugsA. Valproic AcidB. PhenytoinC. WarfarinD. Benzodiazepines22.6 Additional Prenatal Environmental InfluencesA. MalnutritionB. PovertyC. Emotional StateD. Mother’s AgeE. Infections and Diseases22.7 FDA Pregnancy Categories for Prescription Drug Labeling; Final Rule22.8 Analyses of Litigated Cases Alleging Fetal Drug InjuryA. Effects of Methadone and Smoking on the FetusB. Effects of Lisinopril on Fetus – Defense of Causation22.9 Summary and ConclusionsReferencesChapter 23: Geriatric Medication Misadventures Rodney G. Richmond and James C. Norris23.1 IntroductionA. Outpatient Medication UseB. Hospital Medication UseC. Long-Term Care Medication Use23.2 Altered Clinical Response to DrugsA. PharmacokineticsB. Pharmacodynamics23.3 Preventable Drug-Related ProblemsA. PolypharmacyB. Transitions of CareC. Inadequate MonitoringD. Potentially Inappropriate Medication Use23.4 Legal Cases Application23.5 Summary and ConclusionsReferencesChapter 24: Medication ErrorsJames T. O’Donnell and James J. O’Donnell III24.1 History and Overview24.2 Medication Errors in Epidemic Proportions24.3 Types of Medication ErrorsA. Enhancing Healthcare Team OutcomesB. Improving Reporting of Medication Errors24.4 Medication Use Process24.5 System Errors24.6 Which Drugs are Most Often Involved in Medication Errors?24.7 Prevalence of Medication Errors24.8 Vaccine Errors24.9 How has Modern Research Improved Therapeutics and Reduced Drug-Related Morbidity? Pharmacogenomics24.10 Systems for Medical Error PreventionA. Electronic Prescribing (E-prescribing)B. When Electronic Prescribing is UnavailableC. Effective Drug Monitoring SystemsD. The Importance of Continuing EducationE. Reporting All Adverse Drug Events24.11 Summary and ConclusionsReferencesChapter 25: Anticoagulants: Therapeutics, Risks, and ToxicitiesJames T. O’Donnell, James J. O’Donnell III, and Stephanie E. Tedford25.1 Introduction25.2 Summary of Anticoagulant TherapyA. DefinitionB. Use1. Treatment of coronary heart disease2. Warfarin and dabigatran3. Treatment of thrombogenesis25.3 Limitations of Current TherapyA. HeparinB. Low Molecular Weight Heparin (LMWH)C. Heparin-Induced Thrombocytopenia (HIT)1. Pathogenesis of the autoimmune response2. Pathogenesis of the prothrombotic state3. Clinical presentation of HIT4. Diagnosisa. Dismissing HITb. Diagnosing HIT2. Two Approaches: class and titer5. Treatment of HITa. Fondaparinuxb. Re-exposure to heparin6. Conclusion HIT and HITTD. Warfarin25.4 Monitoring Warfarin Oral Anticoagulation25.5 Alternatives to Warfarin - DOACsA. Pradaxa (Dabigatran) vs. WarfarinB. Direct Oral Anticoagulation (DOAC) TherapiesC. DOAC reversal agentsD. Antiplatelet Therapy25.6 Summary and ConclusionsReferencesPart III: PHARMACISTS, PHARMACY, AND PHARMACY PRACTICEChapters 26 - 33Chapter 26: Pharmacy Practice, Managed Care, And Manufacturers F. Randy Vogenberg and Rita Marcoux 26.1 Introduction to Pharmacy and the Related Managed Health Care Environment26.2 Pharmacists as Health Care Professionals: Training, Support Staff, and Life-long LearningA. Registration, Certifications, Credentialing, Colleges Of Pharmacy, And Accreditation Matters For Pharmacy Professional Staff26.3 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 matters26.4 Issues for Pharmacy Practice, Insurance, and Managed Care In the Near FutureA. The landscape of Practice Sites and Changing Business of Health Landscape26.5 Current and Near Future Issues for PharmacistsA. Landscape of Pharmacy Practice, The Changing Professional Marketplace26.6 Pharmaceutical Manufacturer Through Wholesaler and Distribution Supply Chain26.7 Manufacturers: Traditional and Innovative SegmentsA. Non-Biologic MedicationsB. Research­Intensive, Biologics, Gene, and Generic Segments1. Biologic Medications26.8 Pharmaceutical Manufacturer CustomersA. Organization and OperationsB. Other Targeted Customer and Class of Trade SegmentsC. Contracting and Change in the Pharmaceutical Industry26.9 Health Care Industry Changes in the Near Future26.10 Summary and ConclusionsReferencesChapter 27: The Pharmacist’s Utilization of the National Patient Safety Goals to Contribute to Safe and Effective Medication UseJennifer Splawski and Heather Minger27.1 IntroductionA. Overview of ‘The Goals’27.2 Goal 3 and the Pharmacist's RoleA. NPSG.03.05.01 relating to Anticoagulation1. Introduction2. Warfarin Overview3. Patient monitoring4. Patient Education5. Direct Oral Anticoagulant6. Anticoagulation Reversal Overview7. Anticoagulation Reversal Programs8. Patient EducationB. NPSG.03.06.01 relating to Reconciling Medication Information1. Introduction2. The Process of Medication Reconciliation3. Improved Accuracy4. Decreased Mortality5. Allergy Identification6. Discharge Medication Reconciliation7. Utilization of the Pharmacist Extenders in Medication Reconciliation27.3 Summary and ConclusionsReferencesChapter 28: Pharmacist Malpractice and LiabilityJames T. O’Donnell and James J. O’Donnell III28.1 Introduction28.2 The Science of Risk Management28.3 Claims StudiesThe Pharmacists Mutual Claims StudyCNA Claims Study (CNA/HPSO)A. CNA Database and MethodologyB. Most Common Categories of ErrorsC. Claim Analysis by Insurance Source & Licensure Type: Pharmacists v. TechniciansD. Factors Affecting Wrong Drug Dispensing ErrorsE. Drugs Involved in ClaimsF. Most Common Error: Wrong DrugG. Wrong Drug StrengthH. Wrong DirectionsI. Wrong Route of AdministrationJ. Lack of Drug ReviewK. Counseling: A Powerful Weapon Against LiabilityL. Non-Bodily InjuryM. Miscellaneous ErrorsN. Wrong DirectionsO. Lack of Drug ReviewP. Avoiding Errors and Malpractice28.4 Specific Pharmacist Malpractice Case Reports / TopicsA. Duty to Warn?B. Wrong DrugC. Quotas and Metrics: Contributing to the Problem?D. Controlled Substances Violations by PharmacistsE. Methotrexate (MTX) errors28.5 Pharmacists Need to do the Right Thing28.6 Steps Toward a Better Outcome28.7 Summary and ConclusionsReferencesChapter 29: Regulation of Pharmacy PracticeNed Milenkovich29.1 Introduction29.2 Licensure of Professional ActivitiesA. Boards of Pharmacy – A Closer LookB. National Association of Boards of Pharmacy29.3 Practice StandardsA. Legally Circumscribing Pharmacy Practice29.4 Licensure Process to Practice PharmacyA. LicensingB. Licensing of Pharmacists29.5 The Different Types of Pharmacy LicensesA. Disciplinary ActionsB. Causes of Disciplinary ActionC. Practice Focus on LicensureD. Ongoing Professional EducationE. Support Personnel29.6 Federal Drug LawsA. Obra ‘90B. MedicareC. Medicare Part DD. MedicaidE. Prescription Drug CoverageF. Fraud, Waste and AbuseG. 340b DrugsH. Pharmacy CompoundingI. FDA RemsJ. DEA29.7 Pharmacy Practice: Putting it TogetherA. Pharmacy Practice: An Ongoing ProgressionB. Collaborative Practice AgreementsC. Drug Utilization Review (DUR)D. Other Mandates Impacting Pharmacy Practice Quality Assurance RegulationsE. Health Insurance Portability and Accountability Act Of 1996, As AmendedChapter 30: Emergency Department PharmacistVictor Cohen, Samantha P. Jellinek-Cohen, and Megan Musselman 30.1 Introduction30.2 Epidemiology of Drug Injury and Contributing Risk FactorsA. Contributing Risk Factors30.3. Etiology and Sources of Drug Injury in the ED30.4 Clinical Pharmacy in the ED: A Historical Perspective30.5 The ED Pharmacist Plays a Dual Role at Maimonides Medical Center30.6 The ED Pharmacist: A Sub-specialist in Emergency MedicineA. Training and EducationB. Certification30.7 The ED Pharmacist as a Generalist30.8 The ED Pharmacist Ensuring Optimal Continuum of CareA. The ED and Infectious DiseasesB. The ED Pharmacist and the Ambulatory Care InterphaseC. The ED Pharmacist and Transitions of Care (TOC)1. Medication admission notes in the EDD. The ED Pharmacist as a Clinical Toxicology ConsultantE. The ED Pharmacist and the Cardiology InterfaceF. The ED Pharmacist and Neurological EmergenciesG. The ED Pharmacist and Pulmonary EmergenciesH. The ED Pharmacist and Public Health Services in the ED30.9 Building Layers of Defense Against Drug InjuryA. Detecting and Preventing Drug Injury in the EDB. The ED Pharmacist and Community Surveillance for Adverse Drug Reactions30.10 Pharmacy Practice in the ED: Pharmacotherapy Specialty30.11 Summary and ConclusionsReferencesChapter 31: Pharmacy Case Law Review Roger N. Morris and William J. Stilling31.1 Administrative LawA. Due Process–Pharmacist Licensure1. 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 AntitrustA. State Regulatory Boards Immunity1. North Carolina Bd. of Dental Examiners. v. Federal Trade Commission, 135 S. Ct. 1101 (Feb. 25, 2015)31.3 Civil ProcedureA. Spoliation of evidence–Pharmacy’s Duty to Maintain Evidence of Misfill1. Burton v. Walgreen Co., 2015 WL 4228854 (D. Nev. July 10, 2015)31.4 Conscientious ObjectionA. Emergency Contraception1. Stormans, Inc. v. Wiesman, 794 F.3d 1064 (9th Cir. 2015)31.5 Controlled SubstancesA. Duty to Verify DEA Registration1. 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. Constitutionality1. McFadden v. United States, 135 S. Ct. 2298 (June 18, 2015)31.6 CriminalA. Violations of Pharmacy Law Applied to Non-pharmacists1. 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 Records1. Lundy v. State, 26 N.E.3d 656 (Ind. Ct. App. Feb. 20, 2015)C. Second Degree Murder1. U.S. v. Barry J. Cadden, et al., 2014 WL 7151586 (D. Mass. Dec. 16, 2014)31.7 DefamationA. Physician against Pharmacist1. LeFrock v. Walgreen Co., 77 F. Supp.3d 1199 (M.D. Fla. Jan. 16, 2015)B. Duty to Fill1. Kadambi v. Express Scripts, 2015 WL 475373 (N.D. Ind. February 5, 2015)31.8 EmploymentA. Discrimination (Pregnancy)1. Torres-Skair v. Medco Health Solutions, Inc., 595 F.App’x 847 (11th Cir. Dec., 4, 2014)B. Employment at Will1. Hoven v. Walgreen Co., 751 F.3d 778 (6th Cir. June 2, 2014)C. Americans with Disability Act1. Stevens v. Rite Aid Corp., et al., 6:13-cv-00783 (N.D.N.Y., September 23, 2015)D. Overtime Class Action1. Baugh v. CVS Health, et al., 2:15-cv-00014 (E.D. Penn., July 27, 2015)E. Medical Marijuana1. Coats v. Dish Network, 350 P. 3d, 849 (Colo. June 15, 2015)31.9 Fraud and AbuseF. False Claims1. United States v. Express Scripts, Inc., 602 F. App’x 880 (3rd. Cir. Feb. 20, 2015)G. False Claims–Generic Substitutions1. 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 Statute1. 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 Fraud1. City of Chicago v. Purdue Pharma L.P., 2015 WL 2208423 (N.D. Ill. May 8, 2015)31.10 NegligenceA. Duty to Provide Medication1. 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 Dispense1. Oleckna v. Daytona Disc. Pharmacy, 162 So. 3d 178 (Fla. Dist. Ct. App. 2015)31.11 PrivacyC. Patient Privacy–Vicarious Liability1. 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 Messages1. Thompson v. CVS Pharmacy, Inc., 6:204-cv-02081 (M.D. Fla. Dec. 19, 2014)E. Robocalls1. Kolinek v. Walgreen Co., 2014 WL 3056813, (N.D. Ill. July 7, 2014)31.12 Product liabilityA. Learned Intermediary Doctrine1. 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 ComplianceWillis C. Triplett 32.1 Introduction32.2 Compounding Trends and Driving Forces32.3 Optimizing the Regulatory Balance Between “Manufacturing” versus “Compounding”32.4 Investigations, Indictments, Convictions, and Acquittals after the Fungal Meningitis Outbreak32.5 Memorandum of Understanding (MOU)32.6 U SP, NABP, and the State Pharmacy Regulatory Authorities32.7 Physician and Medical Office Compounding32.8 Compounding “Center of Excellence” (“COE”) and the Quality Assurance Paradigm Shift32.9 Conclusions and Forecasts Regarding Patient Injury from Healthcare Compounding32.10 Recommended ReadingsCHAPTER 33: Compounding Pharmacy Fraud and Unethical PracticesJames T. O'Donnell33.1 Introduction33.2 Criminal Prosecutions of Pharmacy Compounders33.3 Over-Prescribing and Over-Charging of Compounded DrugsA. Department of Justice News ReleasesB. News Reports in Newspapers33.4 Not Yet Criminal? Insurance Companies Fighting BackA. No-Fault Pain Compounded and Topical Pain ProductB. Report Challenging the Pricing and Efficacy of a Compounded Pain Cream PrescriptionC. Ingredients and Costs of Pain Cream33.5 General Discussion – Compounded Pain Topical CreamsA. Evidence of Efficacy?B. Expensive Ingredients33.6 Ingredients Review of Efficacy and Mechanism of ActionA. DiclofenacB. Menthol (Methyl Salicylate)C. Lidocaine1. Lidocaine Topical ToxicityD. AmitriptylineE. CyclobenzaprineF. Dimethylsulfoxide (DMSO)33.7 Global Opinions for the Prescription CPTM formula 8-NC Claim Challenge33.8 Discussion and Further Bases of Opinions33.9 Overbilling of Topical Diclofenac Gels, Lidocaine Creams and Ointments and PatchesA. Diclofenac 3” (Solaraze)B. Lidocaine Topical Commercial Products33.10 Recommendations33.11 Summary and ConclusionsReferencesPart IV: FORENSIC AND TOXICOLOGY ISSUESChapters 34 – 42Chapter 34: AlcoholJames T. O’Donnell and James J. O’Donnell III34.1 Introduction34.2Alcohol Injury Epidemiology34.3 Alcohol Intoxication Effects in Litigation34.4 Differences between Civil litigation involving alcohol from Criminal/DUI34.5 Settings for Alcohol Related Civil LitigationA. Employment34.6 Police ActivitiesA. Police PursuitB. Excessive Police ForceC. Alcohol Effects on Aggression and Judgment34.7 Motor Vehicle CollisionsA. Vehicle/VehicleB. Motorcycle CasesC. BoatingD. Vehicle/ Pedestrian34.8 Alcohol and FallsA. Stairs - no alcohol test - fall down bar stairsB. Stairs - Residential Stairs Fall -Adjustment of Calculated BAC due to Morbid ObesityC. Tripped on Threshold – Sued Condominium Association34.9 Dram Shop (Bar Liability for Serving Intoxicated Persons)34.10 Biomarkers for AlcoholA. Family LawB. False Positive Alcohol Biomarkers in Diabetes34.11 Miscellaneous Topics ReportsA. Retrograde Extrapolation (See also legal cases Floyd and Cuellar earlier in this chapter.B. Appellate Court reverses Trial Court Barring of BAC34.13 Summary and ConclusionsReferencesChapter 35: CocaineJames C. Norris and Rodney G. Richmond35.1 Historical Background35.2 Medical Usages of Cocaine35.3 Illegal Usage of Cocaine35.4 Routes of Administration35.5 Effects of Cocaine35.6 Psychotic Disorders Induced by Cocaine35.7 Addiction35.8 Cognitive Deficits35.9 Prenatal Cocaine Exposure (PCE)35.10 Violence35.11 Tolerance35.12 Withdrawal or Abstinence Effects35.13 Mechanisms of Action35.14 Metabolism35.15 Blood Levels35.16 Urine Levels35.17 Impairment35.18 Associated Deaths with Cocaine Usage35.19 Summary and ConclusionsReferencesChapter 36: Marijuana: Pharmacology, Toxicology and Forensic IssuesStephanie E. Tedford, James T. O’Donnell, and James J. O’Donnell III 36.1 Introduction36.2 Federal Law vs. State LawA. Harrison Narcotics Tax ActB. Comprehensive Drug Abuse Control and Prevention ActC. Marijuana Drug Laws at the State LevelD. LegalizationE. DecriminalizationF. Marijuana Policy Project36.3 Controlled Prescription and Distribution of Medical MarijuanaA. Medical Conditions Approved for Treatment with Medical MarijuanaB. Marijuana and EpilepsyC. Marijuana and Endometriosis36.4 Pharmacological Properties of MarijuanaA. Active Compounds and Overview of PharmacologyB. Variability in Marijuana Regulation and Content UniformityC. Routes of AdministrationD. Pharmacokinetics – Time Course of THC and MetabolitesE. PharmacodynamicsF. Vaping vs. Traditional Smoking of CannabinoidsG. Traditional Smoking vs. Ingestion of CannabinoidsH. Pharmacokinetics Applications: Timing of the Peak Euphoric EffectI. Bioavailability1. 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 SafetyA. Serious Adverse EffectsB. Risk of Psychosis1. Drug-induced Psychosis: Potential Mechanisms2. Vaping and Associated Risk for PsychosisC. Pulmonary FunctionD. Risk of AddictionE. Effect on Brain DevelopmentF. Long Term Behavioral EffectsG. Age of Onset of Use36.6 Impact of LegalizationA. Hospital ResourcesB. Driving Under the Influence of DrugsC. Relationship of Marijuana Use and Co-Use with other Substances36.7 Analysis and Testing for Marijuana Use36.8 Scientific Data Relating to THCA. Blood THC vs. Brain THC: Any Relationships?B. Relationships Between Percent Plant-THC and Plasma-THCC. Is There a Relationship Between Percent THC in the Smoked Cigarette and Plasma THC?D. Relation Between Degree of “High” and Plasma THCE. Occasional Marijuana Users vs. Practiced UsersF. 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 DataI. Hospital and Provider Considerations36.9 Forensic Case Reports36.10 Summary and ConclusionsReferencesChapter 37: Drug Evaluation and Classification Program: An Evidence-Based Analysis Fran M. Gengo and Anna G. Mattle37.1 Introduction37.2 The 12 Steps of DRE Examinations37.3 Scientific Evaluation of DRE ExaminationsA. Step 2: Interview of Arresting OfficerB. Step 3: Preliminary Examination and Initial Pulse MeasurementC. Step 4: Eye ExaminationD. Step 5: Divided Attention TestsE. Step 6: Second Pulse Reading, Body Temperature, and Blood Pressure MeasurementF. Step 7: Eye Examination of Pupil Size in Various Lighting ConditionsG. Step 8: Assessment of Muscle ToneH. Step 11: DRE Officer Opinion StatementI. Step 12: Toxicology Sample37.4 Literature Evaluations And Critiques Of Dre37.5 Cannabis37.6 Statistical Validity and Overall Strength of DRE Studies37.7 DRE Support LiteratureA. Bigelow et al. 1985 StudyB. Heishman et al. 1996 and 1998 StudiesC. Smith et al. 2002 StudyD. Shinar and Schechtman 2005 StudyE. Specific Identification of Drug Class by DRE Officers in Validation Studies37.9 Summary37.10 Summary and ConclusionsReferencesChapter 38: Involuntary IntoxicationJames T. O’Donnell, James J. O’Donnell III, and William Vaughn38.1 Introduction38.2 Legal Defense Considerations for a Violent Crime38.3 Confirming That Drugs are Involved in a Violent Crime38.4 Beyond Pharmacology: The Multifactorial Role of Drugs in Aggression and Violence38.5 Association of Drugs with Aggression and Violence38.6 Mechanisms of Drug-Induced Violence38.7 Intoxication of Victim Defense38.8 Summary and ConclusionsReferencesChapter 39: Drug-Induced Aggression and ViolencePeter D. Anderson39.1 Classification of Aggression39.2 Causes of Aggression and ViolenceA. Neurobiology of AggressionB. Medical and Psychiatric Causes of Aggression39.3 The Role of Drugs as a Cause of ViolenceA. IntroductionB. Problems with the LiteratureC. Specific Drugs or Drug Classes that cause aggression1. Ethanol2. Lysergic Acid Diethylamide3. Phencyclidine and Ketamine4. Anabolic Steroids5. Insulin6. Psychostimulants7. Benzodiazepines8. Selective Serotonin Reuptake Inhibitors9. Varenicline10. Environmental Chemicals39.4 The Drug-Induced Insanity Defense39.5 Summary and ConclusionsReferencesChapter 40: Forensic Drug Testing James J. O’Donnell III and James T. O’Donnell40.1 Introduction40.2 Non-Regulated Drug Testing40.3 Regulated Drug Testing40.4 Voluntary Programs40.5 Establishment of a Workplace ProgramA. Written PolicyB. Employee Assistance ProgramsC. Employee Awareness TrainingD. Supervisor TrainingE. Drug Testing40.6 The Drug-Testing ProcessA. Specimen CollectionB. AccessioningC. Drugs to Be TestedD. Screening TestsE. Confirmation TestsF. Reporting and Storage of SamplesG. Prevention Against and Detection of Drug Test Cheating40.7 Additional Program AspectsA. The Medical Review Officer (MRO)B. Public Interest Exclusions (PIE)C. Blind Performance TestingD. Alcohol Testing40.8 Special Drug-Testing IssuesA. Type of Matrix1. Hair Testing2. Saliva Testing3. Sweat Testing4. Blood5. UrineB. Alternate Sources of Drug ExposureC. Amphetamine Testing IssuesD. Medical Use of Drugs40.9 Legal Aspects of Workplace Drug-TestingA. Constitutional IssuesB. State and Federal Mandates40.10 Discovery: The “Litigation Package”40.11 Case Reports40.12 Summary and ConclusionsReferencesChapter 41: Postmortem Redistribution and Interpretation of Drug Levels Gourang P. Patel 41.1 Abstract41.2 Introduction41.3 Review of a Case File41.4 Postmortem ConsiderationsA. Physiologic Changes in the Body After DeathB. Drug Characteristics41.5 Analysis of Drug Level Information41.6 Summary and ConclusionsReferences Chapter 42: Addiction as MitigationBarry D. Hargan and James T. O’Donnell42.1 Introduction42.2 Clinical Variables Which Contribute to the Onset of AddictionA. Genetic PredispositionB. Learned BehaviorC. Psychopathological Exposure42.3 Substance/Medication-Induced Mental DisorderA. Executive Summary of OpinionB. Neurotoxicity Mechanisms of Alcohol and Anabolic Steroids in the Developing BrainC. Anabolic Steroid Effects on Brain Structure and FunctionD. Translational Impact – what does this mean to a teenager abusing large amounts of alcohol and steroids?E. Clinical and Practical Applications of the Basic NeuroscienceF. Behavioral Abnormalities Associated with Anabolic Steroid UseG. Defendant’s Alcohol and Anabolic Steroid Use1. AlcoholH. Expert Opinions Regarding Substance-Induced Brain Damage Affecting Behavior42.4 The Simplified Version of Neurobiology and the Addicted Brain42.5 Cocaine42.6 Expert Testimony Concerning Addictive DisordersA. Role of the Addictions ExpertB. Some Testimony Experiences and the Limits of OpinionsC. Preparation42.7 Additional Considerations Concerning Addiction MitigationA. Neuropsychological Evaluation42.8 Summary and ConclusionsReferences