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100 Cases in Clinical Pharmacology Therapeutics and Prescribing 1st edition

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1.5: Case Study - Anticholinesterase

• Last updated
• Save as PDF
• Page ID 10626

• Carl Rosow, David Standaert, & Gary Strichartz
• Massachusetts Institute of Technology via MIT OpenCourseWare

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Case 1: AnticholinesteraseFebruary 3, 2005

• Cholinergic Pharmacology
• Anticholinesterase inhibitors
• Therapeutic use
• Managing toxicity

Case: Organophosphate Poisoning

A 55 yr old crop duster calls because he has lost control over his chronic twitch, and he is now beginning to have problems with blurry vision andcontrol of his bowels and bladder. He wants to go back to the airfield to finish his crop dusting, but his supervisor makes him call you first.

Synthesized from acetyl-CoA and choline by choline acetyltransferase (ChAT).

Poor absorption and low lipophilicity due to charge on quaternary ammonium.

Multiple systemic effects, esp autonomic pathways and at the neuromuscular junction (NMJ).

Acetylcholinesterase (AChE)

Clears Ach from site of action (also degraded by plasma butyrylcholinesterase)

Bound on post-synaptic membrane

Rate = 400,000 per min

Inhibition of AchE results in build up of Ach at muscarinic and nicotinic synapses!

Step 1: Binding

Step 2: Formation of covalent intermediate and release choline

Step 3: Hydrolysis of acyl-enzyme intermediate

Direct-acting agonists

Mimics acetylcholine by binding Ach receptor and activating downstream signaling

Examples: methacholine, carbachol, bethanechol, pilocarpine

Indirect agonists

Inhibits AchE from breaking down acetylcholine at synapse

- competes w/ ACh for binding to AChE (step 1)

Examples: edrophonium

- formation of carbamylated enzyme intermediate (step 2)

Examples: neostigmine, pryidostigmine

- formation of phosphorylated enzyme intermediate (step 2)

Examples: parathion, malathion are insecticides soman, sarin are nerve agents

AchE inhibitors: reversible versus irreversible

Inhibition by organophosphate: "Aging"

Pharmacokinetics of organophosphates

Parathion and malathion are biotransformed in the liver to become active (insects perform this process more efficiently)

Highly lipid soluble, widely distributed and penetrates CNS

When used as insecticides, can be dispersed as aerosols or dusts and absorbed by all possible routes: GI, skin, mucous membranes, lungs

Slow hepatic metabolism; urine excretion of hydrolysis products Lipid-soluble drug can remain in systems for weeks to months!

Effects of acute O/P overdose

DUMBBELLS: Diarrhea (Diaphoresis), Urination, Miosis, Bronchospasm (secretion) Bradycardia, Excite skeletal muscle and CNS (Emesis), Lacrimation, Lethargy, Salivate

Mode of death: respiratory failure via flaccid muscular paralysis exacerbated by bronchosecretion and bronchoconstriction

Chronic Exposure to Low Doses: blurred vision, incontinence, twitching*** neuropathy associated with axonal demyelination

Lethal Dose Remove contaminated clothing; remove from exposure site Wash skin with soap, bleach (alkaline hydrolysis) Respiratory support (O2, ventilatory assistance, treat Sz)

Atropine – anti-muscarinic agent

• reverses dangerous parasympathetic effects (respiratory)

• 0.5-2 mg IV q15min until respiratory secretions dry (days!)

Pralidoxime (2-PAM) - specific for organophosphate poisoning

Therapeutic use of AchE inhibitors​​​​​​​

Myasthenia gravis (edrophonium, pyridostigmine, neostigmine)

Alzheimer's Disease (tacrine and donepezil)

Reversal of neuromuscular blockers (neostigmine, physostigmine)

Glaucoma (physostigmine, echothiophate)

Summary of Key Points ​​​​​​​

Reversible versus irreversible inhibition of AchE causes build up of Ach at synapse

Toxicity associated with AchE inhibitors (patient case!) include global nicotinic, muscarinic, & CNS effects ( DUMBBELLS )

Treatment for Exposure to Irreversible Inhibitors Atropine – counteract ACh agonism 2-Pralidoxime – prevent aging

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Appendix C:  Answers to Case Study Questions

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Disclaimer: These citations have been automatically generated based on the information we have and it may not be 100% accurate. Please consult the latest official manual style if you have any questions regarding the format accuracy.

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Chapter 6 case study, chapter 7 case study.

• CHAPTER 8 CASE STUDY
• CHAPTER 9 CASE STUDY
• CHAPTER 10 CASE STUDY
• CHAPTER 11 CASE STUDY
• CHAPTER 12 CASE STUDY
• CHAPTER 13 CASE STUDY
• CHAPTER 14 CASE STUDY
• CHAPTER 15 CASE STUDY
• CHAPTER 16 CASE STUDY
• CHAPTER 17 CASE STUDY
• CHAPTER 21 CASE STUDY
• CHAPTER 22 CASE STUDY
• CHAPTER 23 CASE STUDY
• CHAPTER 24 CASE STUDY
• CHAPTER 25 CASE STUDY
• CHAPTER 26 CASE STUDY
• CHAPTER 27 CASE STUDY
• CHAPTER 29 CASE STUDY
• CHAPTER 30 CASE STUDY
• CHAPTER 31 CASE STUDY
• CHAPTER 32 CASE STUDY
• CHAPTER 33 CASE STUDY
• CHAPTER 34 CASE STUDY
• CHAPTER 35 CASE STUDY
• CHAPTER 36 CASE STUDY
• CHAPTER 37 CASE STUDY
• CHAPTER 38 CASE STUDY
• Full Chapter
• Supplementary Content

Sedative-Hypnotic Drugs

What is the most likely reason for R.S.’s poor performance in the morning rehabilitation sessions?

The sedative-hypnotic (flurazepam) appeared to be producing a hangover-like effect, which limited the patient’s cognitive skills during the early daily activities. Flurazepam is a benzodiazepine drug with a half-life of 2.3 hours and a duration of action of 7 to 8 hours. This drug, however, is metabolized in the liver to active metabolites with half-lives ranging from 30 to 200 hours. It seems likely that R.S. was continuing to experience sedative effects from these active metabolites well into the next morning.

What would be the likely solution?

The therapists can deal with this problem initially by reserving the early morning session for stretching and ROM activities and then gradually moving into upper-body strengthening. Activities that require more patient learning and comprehension can be done later in the morning or in the afternoon. The hangover-like problem should also be brought to the attention of the physician. In this case, the physician switched the hypnotic drug to zolpidem (Ambien), 10 mg administered at bedtime. Zolpidem has a half-life of 2.5 hours and a duration of action of 6 to 8 hours, so R.S. should still get the benefit of a full night’s sleep. Because zolpidem is not metabolized to active metabolites, it is unlikely that it will continue to exert sedative-hypnotic effects into the next morning. Zolpidem also affects neuronal GABA receptors differently than benzodiazepines such as flurazepam. This difference might reduce the risk of problems, such as rebound insomnia, when it is time to discontinue the drug.

Antidepressant Drugs

How can the therapist reduce the risk of orthostatic hypotension during rehabilitation sessions?

To reduce orthostatic hypotension, the therapist decided to place the patient on the tilt table for the first day after imipramine was started and to monitor blood pressure regularly. The therapist had the patient perform weight shifting and upper-extremity facilitation activities while he was on the tilt table. The patient tolerated this well, so the therapist had him resume ambulation activities using the parallel bars on the following day. With the patient standing inside the bars, the therapist carefully watched for any subjective signs of dizziness or syncope in the patient (i.e., facial pallor, inability to follow instructions). Standing bouts were also limited in duration. By the third day, ambulation training continued with the patient outside the parallel bars, but the therapist made a point of having the patient’s wheelchair close at hand in case the patient began to appear faint. These precautions of careful observation and short, controlled bouts of ambulation were continued throughout the remainder of the patient’s hospital stay, and the therapist observed no incident of orthostatic hypotension during physical therapy.

Will clinicians notice an immediate improvement in J.G.’s mood after starting this?

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Clinical Pharmacology: Current Topics and Case Studies

• © 2016
• Latest edition
• Markus Müller 0

Universitätsklinik für Klinische, Medizinische Universität Wien, Wien, Austria

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Updated and revised 2nd edition

Summarizes the latest topics, tools and clinical trials in clinical pharmacology

Added value for employees in drug research and development

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Table of contents (23 chapters)

Front matter, introduction, the discipline of clinical pharmacology.

Markus Müller

Current Issues in Drug Development

Current issues in drug regulation.

• Christa Wirthumer-Hoche, Brigitte Bloechl-Daum

Current Topics in Drug Reimbursement

• Anna Bucsics, Robert Sauermann, Valerie Nell-Duxneuner

Clinical Trials

Ethics in clinical research.

• Ernst Singer, Christiane Druml

Good Clinical Practice (GCP) and Scientific Misconduct

• Brigitte Bloechl-Daum

Phase I Studies and First-In-Human Trials

• Ulla Derhaschnig, Bernd Jilma

Clinical Trials: Interventional Studies

• Michael Wolzt, Stefan Aschauer

Observational Studies

• Harald Herkner, Christoph Male

Tools in Clinical Pharmacology

Tools in clinical pharmacology: imaging techniques.

• Martin Bauer, Oliver Langer

Pharmacokinetics II: 14C-Labelled Microdosing in Assessing Drug Pharmacokinetics at Phase 0

• Graham Lappin

Current Concepts of Pharmacogenetics, Pharmacogenomics, and the “Druggable” Genome

• Wolfgang M. Schmidt, Robert M. Mader

Pharmacokinetics I: PK-PD Approach, the Case of Antibiotic Drug Development

• Sherwin K. B. Sy, Hartmut Derendorf

Epidemiology and Biostatistics

• Gerhard Garhöfer, Leopold Schmetterer

Placebo Effects and Placebo Control in Clinical Trials

• Johannes Pleiner-Duxneuner

Topics in Clinical Pharmacology

• drug development
• clinical trial
• gene therapy
• pharmacodynamics
• drug research
• pharmacotherapy

About this book

“The aim is to describe the role of the discipline of clinical pharmacology in drug discovery. … The intended audience is faculty, researchers, and advanced students from academia and the pharmaceutical industry who are learning about or involved in the process of drug discovery. … This book provides a multitude of very useful insights about the successes and failures in drug development for scientists who are, or will be, involved in the process of drug discovery.” (Thomas L. Pazdernik, Doody's Book Reviews, May, 2016)

Editors and Affiliations

About the editor, bibliographic information.

Book Title : Clinical Pharmacology: Current Topics and Case Studies

Editors : Markus Müller

DOI : https://doi.org/10.1007/978-3-319-27347-1

Publisher : Springer Cham

eBook Packages : Biomedical and Life Sciences , Biomedical and Life Sciences (R0)

Copyright Information : Springer International Publishing Switzerland 2016

Hardcover ISBN : 978-3-319-27345-7 Published: 25 March 2016

Softcover ISBN : 978-3-319-80118-6 Published: 25 April 2018

eBook ISBN : 978-3-319-27347-1 Published: 15 March 2016

Edition Number : 2

Number of Pages : VI, 405

Number of Illustrations : 14 b/w illustrations, 16 illustrations in colour

Topics : Pharmacology/Toxicology , Pharmacy , Pharmacotherapy

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Our Pharmacy Blog

Mastering pharmacy case studies.

Introduction

If you are training to become a pharmacist, you will have had experience with pharmacy case studies. But why are pharmacy case studies so important?

As a qualifying pharmacist, case studies bring together the threads of study over the past four years. This includes your study of subjects such as:

• Pharmacology
• Pharmaceutical chemistry
• Pharmaceutics
• Clinical pharmacy practice

In practice, pharmacists are expected to draw on this knowledge and clinically apply it where necessary. These subjects feed into one another where knowledge of one subject became necessary to advance in a second subject and so forth. University staff overseeing the course structure put that structure together with these factors in mind. Pharmacy case studies are an important component, often toward the end of your pharmacy degree, that aim to establish the most relevant details that play a role in the career of a qualified pharmacist.

Case studies give pharmacy students an opportunity to test their understanding of a specialist topic. This may be anything from the formulation and dosing of medicines; to a drug’s mechanism of action, drug interactions, and clinical appropriateness for a medicine in a given scenario for a patient with specific factors to keep in mind. Evidently, this takes practice. There are many possible case study scenarios to consider. It can be difficult to always get things right.

Case studies are, then, a special kind of barometer through which we measure the professional competency of pharmacy students .

That is why pharmacy case studies are popular in degree programs – forcing students to think critically about a given topic – whether it be blood diagnostics, epidemiology, treatment options, or drug monitoring – tying together their past year’s study and how to apply this knowledge to (potentially) real-life situations.

Below, we’ve put together an introductory case study to provide you with a clear example of what kinds of questions can be asked and how best you should approach each question. With enough practice, clinical case studies become that much easier. And with time, students learn to enjoy case studies – as they are often your first direct experience of learning real and relevant facts that have an impact on your long-term professional career.

Pharmacy Case Study – Osteoporosis

A 49-year old woman with osteoporosis has been taking Fosamax for 6-months. She visits her GP complaining of acid reflux and pain radiating down her esophagus.

• What is the active ingredient of Fosamax?
• What is the mechanism of action of this medicine?
• Suggest a reason why this patient is taking Fosamax.
• How should the GP respond to the patient’s symptoms?
• What foods and/or medicines should the patient avoid?

Explanation

The questions ask more about the medicine – how it works, what it’s indicated for, how the GP should respond to patient symptoms and what interactions, from both food and drug sources, the prescriber and pharmacist must consider.

A – The active ingredient of Fosamax is alendronate; a bisphosphonate drug.

B – Alendronate works by inhibiting osteoclast-mediated bone resorption (the process whereby bone is broken down and minerals are released into the blood).

C – As a 49-year old woman, the patient is likely post-menopausal. Bisphosphonates are routinely prescribed to prevent osteoporosis in these patients.

D – The patient may be improperly administering the medicine. Patients who do not follow the correct protocol of administering bisphosphonates are likely to experience specific symptoms, particularly relating to the esophagus and GI tract. Patients should be counseled to take the medicine in the morning on an empty stomach, whilst remaining upright, and taken with a full glass of water. This eases the bisphosphonate through the digestive tract without irritating the esophageal wall. Patients should avoid taking and food or medicines, both before and for at least 30-minutes after taking the bisphosphonate.

E – Two groups of medicines should be avoided. First, NSAIDs should be avoided; as they increase the risk of gastrointestinal side effects. Second, patients should avoid foods or supplements that contain multivalent ions such as magnesium, aluminum, or calcium. This category includes dairy products and antacids. As we learned above, bisphosphonates should be avoided with these medicines/foods for at least 30-minutes after the bisphosphonate has been taken (on an empty stomach).

Practice More Pharmacy Case Studies

The more pharmacy case studies you practice , the better prepared you are for the needs and demands that present during the licensing end of your pharmacy program. Pharmacy case studies help guide students through the must-know clinical facts about drugs and medicines; both theoretical and practical knowledge.

Clinical case studies are one of the ways in which students make the transition between an experienced, knowledgeable student and a clinical professional whose expertise can be trusted in the real world. Case studies bring pharmacy students to the next level. The more practice you put in, the better results you can expect as you progress through the licensing stage of your nascent career. That, in the end, is what matters.

That’s about it for our discussion of case studies! Check back to our pharmacy blog soon for more exclusive content to help you master the science of drugs and medicines and build your long-term career.

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Top 125 Drug Card Case Quiz

• Katzung Pharmacology Cases
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Author(s): Jill M. Kolesar, PharmD, MS, BCPS, FCCP; Lee C. Vermeulen, BSPharm, MS, FCCP, FFIP

• 001 Case 001-Surgical Care
• 002 Case 002-Hypertension Case # 1
• 003 Case 003-Hypertension Case # 2
• 004 Case 004-Hypertension Case # 3
• 005 Case 005-Hypertension Case # 4
• 006 Case 006-Hypertension Case # 5
• 007 Case 007-Dyslipidemia Case # 1
• 008 Case 008-Dyslipidemia Case # 2
• 009 Case 009-Stable Ischemic Heart Disease
• 010 Case 010-Acute Coronary Syndromes
• 011 Case 011-Cardiovascular Respiratory Decompensation
• 012 Case 012-Chronic Heart Failure Case # 1
• 013 Case 013-Chronic Heart Failure Case # 2
• 014 Case 014-Venous Thromboembolism-Pulmonary Embolism Case # 1
• 015 Case 015-Venous Thromboembolism-Pulmonary Embolism Case # 2
• 016 Case 016-Stroke
• 017 Case 017-Arrhythmias
• 018 Case 018-Cardiac Arrest, Resuscitation
• 019 Case 019-Acne and Pediatric Dermatology Disorders
• 020 Case 020-Psoriasis
• 021 Case 021-Atopic Dermatitis
• 022 Case 022-Miscellaneous Dermatology
• 023 Case 023-Peptic Ulcer Disease, GERD Case # 1
• 024 Case 024-Peptic Ulcer Disease, GERD Case # 2
• 025 Case 025-Irritable Bowel Syndrome
• 026 Case 026-Diarrhea
• 027 Case 027-Constipation
• 028 Case 028-Crohn Disease
• 029 Case 029-Anemia
• 030 Case 030-CNS Infections
• 031 Case 031-Lower Respiratory Tract Infection
• 032 Case 032-Upper Respiratory Tract Infection
• 033 Case 033-Skin and Soft-Tissue Infections; Fungal (Multiple Patient Case)
• 034 Case 034-Infective Endocarditis
• 035 Case 035-Gastrointestinal Infections
• 036 Case 036-Intra-Abdominal Infections
• 037 Case 037-Urinary Tract Infection
• 038 Case 038-Skin and Soft Tissue Infection (Bacterial), Bone and Joint Infections
• 039 Case 039-Miscellaneous Bacterial Infections
• 040 Case 040-Sexually Transmitted Infections
• 041 Case 041-Sepsis and Septic Shock
• 042 Case 042-Fungal Infections Case # 1
• 043 Case 043-Fungal Infections Case # 2
• 044 Case 044-Viral Infections
• 045 Case 045-Parasitic Infections
• 046 Case 046-Infectious Endocarditis
• 047 Case 047-Viral Hepatitis, Hepatitis Vaccination
• 048 Case 048-Influenza and Influenza Vaccination (Multiple Patient Case)
• 049 Case 049-Foot and Nail Fungal Infection
• 050 Case 050-Vaccines Case # 1
• 051 Case 051-Vaccines Case # 2
• 052 Case 052-Travel Health (Multiple Patient Case)
• 053 Case 053-Human Immunodeficiency Virus Infection
• 054 Case 054-Systemic Lupus Erythematosus
• 055 Case 055-Solid Organ Transplantation
• 056 Case 056-Erectile Dysfunction
• 057 Case 057-Benign Prostatic Hyperplasia
• 058 Case 058-Attention Deficit Hyperactivity Disorder
• 059 Case 059-Substance Use Disorders (Opioids)
• 060 Case 060-Substance-Related Disorders (Alcohol, Nicotine)
• 061 Case 061-Schizophrenia
• 062 Case 062-Depression Case # 1
• 063 Case 063-Depression Case # 2
• 064 Case 064-Panic Disorder
• 065 Case 065-Bipolar Disorder
• 066 Case 066-Anxiety Disorders Case # 1
• 067 Case 067-Anxiety Disorders Case # 2
• 068 Case 068-Sleep-Wake Disorders
• 069 Case 069-Diabetes Mellitus (Type 2) Case # 1
• 070 Case 070-Diabetes Mellitus (Type 2) Case # 2
• 071 Case 071-Diabetes Mellitus (Type 2) Case # 3
• 072 Case 072-Thyroid Disorders
• 073 Case 073-Obesity
• 074 Case 074-Migraine Headache
• 075 Case 075-Critical Care Pain, Agitation, Delirium
• 076 Case 076-Alzheimer Disease
• 077 Case 077-Multiple Sclerosis
• 078 Case 078-Epilepsy Case # 1
• 079 Case 079-Epilepsy Case # 2
• 080 Case 080-Parkinson Disease
• 081 Case 081-Pain Management Case # 1
• 082 Case 082-Pain Management Case # 2
• 083 Case 083-Pain Management Case # 3
• 084 Case 084-Brain Cancer
• 085 Case 085-Breast Cancer
• 086 Case 086-Lung Cancer
• 087 Case 087-Colorectal Cancer
• 088 Case 088-Prostate Cancer
• 089 Case 089-Hodgkin Lymphoma
• 090 Case 090-Lymphoma
• 091 Case 091-Acute Myeloid Leukemia
• 092 Case 092-Chronic Lymphocytic Leukemia
• 093 Case 093-Multiple Myeloma
• 094 Case 094-Myelodysplastic Syndrome
• 095 Case 095-Renal Cell Cancer
• 096 Case 096-Melanoma
• 097 Case 097-Ovarian Cancer
• 098 Case 098-Chemotherapy-Induced Emesis
• 099 Case 099-Cancer Pain
• 100 Case 100-Stem Cell Transplant
• 101 Case 101-Idiopathic Thrombocytopenic Purpura, Thrombotic Thrombocytopenic Purpura
• 102 Case 102-Glaucoma
• 103 Case 103-Bacterial Conjunctivitis
• 104 Case 104-Allergic Conjunctivitis
• 105 Case 105-Asthma Case # 1
• 106 Case 106-Asthma Case # 2
• 107 Case 107-Allergic Rhinitis Case # 1
• 108 Case 108-Allergic Rhinitis Case # 2
• 109 Case 109-Chronic Obstructive Pulmonary Disease
• 110 Case 110-Osteoarthritis
• 111 Case 111-Rheumatoid Arthritis
• 112 Case 112-Osteoporosis
• 113 Case 113-Gout
• 114 Case 114-Urinary Disorders – Male
• 115 Case 115-Urinary Disorders – Female
• 116 Case 116-Menopause Care
• 117 Case 117-Menstruation-Related Disorders
• 118 Case 118-Contraception
• 119 Case 119-Obstetric Care
• 120 Case 120-Family Medicine Case # 1 (Multiple Patient Case)
• 121 Case 121-Family Medicine Case # 2 (Multiple Patient Case)
• 122 Case 122-Family Medicine Case # 3 (Multiple Patient Case)
• 123 Case 123-Family Medicine Case # 4 (Multiple Patient Case)
• 124 Case 124-Family Medicine Case # 5 (Multiple Patient Case)
• 125 Case 125-Family Medicine Case # 6 (Multiple Patient Case)