Ach Blockers

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Questions and Answers

What is the primary effect of atropine on the eye?

Reduction of eye pressure

Mydriasis (correct)

Pupil constriction

Increased tear production

Which receptor does atropine target to induce bronchodilation?

Nicotinic

M3 (correct)

In which situation is atropine likely to cause tachycardia?

When used for patients with bradycardia

All doses are equally effective

Low doses occurring naturally

Moderate to high doses (correct)

What is a possible side effect of using scopolamine patches?

Dry mouth Signup and view all the answers

Atropine's action in the gastrointestinal system primarily causes:

Relaxation of smooth muscles Signup and view all the answers

When used in the respiratory system, what effect does atropine have?

Reduced secretions Signup and view all the answers

What effect does atropine have on the genitourinary tract?

Relaxation of bladder walls Signup and view all the answers

What is one of the primary limitations of using antimuscarinics in Parkinson's disease?

Limited therapeutic benefits Signup and view all the answers

Which muscarinic receptor subtype is primarily associated with the myocardium?

M2 Signup and view all the answers

Atropine is characterized as which type of drug in the context of muscarinic receptors?

Non-selective muscarinic antagonist Signup and view all the answers

What is a common effect of antimuscarinics at low doses in the CNS?

Sedation Signup and view all the answers

Which antimuscarinic drug is typically used via a transdermal patch?

Scopolamine Signup and view all the answers

Which of the following statements about competitive antagonists is true?

Their blockade can be surmounted by higher concentrations of acetylcholine. Signup and view all the answers

What effect do synthetic antimuscarinics have compared to traditional antimuscarinics?

Higher selectivity for specific muscarinic receptor subtypes. Signup and view all the answers

Which antimuscarinic drug is known for its use in reducing bronchial secretions?

Ipratropium Signup and view all the answers

What determines the distribution of antimuscarinic drugs in the body?

Presence of a quaternary amine group. Signup and view all the answers

What condition does atropine specifically treat by inhibiting excess acetylcholine activity?

Bradycardia Signup and view all the answers

What is the primary method to reverse an atropine overdose?

Increase Ach levels through inhibition of Acetylcholinesterase Signup and view all the answers

Which of the following is a clinical application of atropine related to the eyes?

Causing mydriasis Signup and view all the answers

What source is primarily responsible for the muscarine that causes rapid onset mushroom poisoning?

Amanita muscaria Signup and view all the answers

In the context of antimuscarinic therapy, what does an excess of acetylcholine lead to?

Paralysis Signup and view all the answers

Which side effect is associated with atropine usage due to its anticholinergic properties?

Tachycardia Signup and view all the answers

What is the mechanism of action of atropine on acetylcholine receptors?

It competes with acetylcholine for binding to muscarinic receptors Signup and view all the answers

What is a common use of scopolamine in relation to acetylcholine?

To mitigate nausea and vomiting Signup and view all the answers

What substance found in certain mushrooms can cause liver failure?

Alpha-amanitin Signup and view all the answers

Which type of mushroom is specifically associated with producing rapid toxic reactions?

Amanita muscaria Signup and view all the answers

What is the primary treatment for severe poisoning caused by cholinesterase inhibitors?

Atropine Signup and view all the answers

What are the common symptoms associated with muscarine toxicity?

Diarrhea, sweating, and pupil constriction Signup and view all the answers

Which mushroom is known as a 'Death Cap'?

Amanita virosa Signup and view all the answers

What is one of the main components of cholinesterase inhibitors found in nerve agents?

Sarin Signup and view all the answers

What is the effect of alpha-amanitin on liver hepatocytes?

Inhibits RNA polymerase function Signup and view all the answers

Which edible mushroom is commonly used in various cuisines and has gained widespread popularity?

Pleurotus ostreatus Signup and view all the answers

Which type of drug is classified as a nondepolarizing neuromuscular blocker?

Tubocurarine Signup and view all the answers

What is a significant issue with ganglion blocking drugs?

They block neurotransmission at both sympathetic and parasympathetic ganglia. Signup and view all the answers

What distinguishes succinylcholine from nondepolarizing neuromuscular blocking drugs?

It depolarizes the motor end plate initially before causing paralysis. Signup and view all the answers

Hexamethonium, once used as an antihypertensive, primarily acts on which type of receptor?

Nicotinic receptors Signup and view all the answers

Which of the following is NOT a method of action for ganglion blocking drugs?

Blocking adrenergic receptor activity Signup and view all the answers

Which group of cholinoceptor blockers does mecamilamine belong to?

Ganglion-blocking drugs Signup and view all the answers

Which of the following statements about ganglion-blocking drugs is true?

They can cause complete loss of sympathetic outflow without selectivity. Signup and view all the answers

The term 'mad as a hatter' is often associated with which of the following conditions?

Mercury poisoning impact on the central nervous system Signup and view all the answers

What is the primary action of atropine in treating nerve gas exposure?

Competes with excess Ach for binding to muscarinic receptors Signup and view all the answers

Which of the following symptoms is NOT associated with cholinergic crisis as described by Foroutan?

Hypertension Signup and view all the answers

Which chemical agent is classified as a blistering agent developed during WWI?

Mustard gas Signup and view all the answers

What was the main focus of Dr. S.A. Foroutan's publications between 1996 and 1999?

Experiences in treating nerve gas exposure Signup and view all the answers

Which of the following treatments is specifically used to counteract seizures in nerve gas exposure?

Diazepam Signup and view all the answers

What synergistic effect do atropine and 2PAM have in treating nerve gas exposure?

One blocks receptor sites while the other reactivates enzyme activity Signup and view all the answers

What significant recommendation did Foroutan make for recovered troops?

2-3 weeks rest before returning to the field Signup and view all the answers

What major event did Iraq perform between 1984 and 1987 regarding nerve gas?

Used Sarin nerve gas in warfare Signup and view all the answers

Study Notes

Pharmacology I, Chapter 8: Ach Blockers (Cholinolytics)

Case Study 1: A 63-year-old patient with urinary symptoms, on thiazide diuretic and ACE inhibitor for hypertension, developed benign prostatic hypertrophy (BHP) requiring prostatectomy. Now experiencing urinary frequency and urgency. What is the diagnosis and treatment?
Case Study 2 (Urge Incontinence): Urge incontinence may follow prostate removal, potentially leaving the bladder detrusor muscle unstable. Symptoms typically resolve with time, though a patient may use tolterodine or oxybutynin once daily. Slight muscarinic antagonists reduce detrusor smooth muscle spasms.

Cholinolytics

Cholinergic antagonists, cholinergic blockers, anticholinergic drugs, and acetylcholine blockers are synonymous with cholinolytics.

Classification of Cholinolytics

Group I (Antimuscarinics): This group blocks parasympathetic autonomic discharge. This is an important group.
Group II (Ganglionic Blockers): Has limited clinical use.
Group III (Neuromuscular Blockers): Further discussed later in the course.

Receptor Organization

Sympathetic Pathway: CNS → Ach → NE → Adrenergic Receptors (alpha 1, alpha 2, beta 1, beta 2)
Parasympathetic Pathway: CNS → Ach → Ach → Muscarinic Receptors
Somatic Pathway: CNS → Ach → Nicotinic Receptors → Skeletal Muscle

Nicotinic and Muscarinic Blockers

Nicotinic Blockers: Ganglion blockers (Group II), neuromuscular blockers (Group III).
Muscarinic Blockers: Group I drugs.

Muscarinic Receptor Subtypes

M1: CNS, sympathetic postganglionic cell bodies
M2: Myocardium, smooth muscle
M3: Effector cell membranes (glands and smooth muscle)

Antimuscarinic Drugs

Atropine (Atropa belladonna)
Scopolamine
Propantheline (Pro-Banthine)
Glycopyrrolate (Robinul)
Tolterodine (Detrol)
Dicyclomine (Bentyl)
Ipratropium (Atrovent)

Atropine Structure

Atropine has a complex structure containing tropic acid and a base. The structure can vary slightly based on the specific molecule.

Antimuscarinic Mechanisms

Competitive Antagonists: Block Ach receptors; increasing Ach levels overcomes blockade. More effective blocking drug agonists than endogenous agonists (Ach)
Non-selective: Atropine is non-selective for the muscarinic receptor subtypes (M1, M2, M3), though certain synthetic types are more selective.

Antimuscarinic Distribution

Quaternary amine group prevents drug entry to lipid membranes (BBB). Used for antisecretory/antispastic activity in GI and bronchi; limited CNS effects.
Tertiary amine readily crosses BBB and all tissues; high lipid solubility. Atropine is an example.

Antimuscarinic Effects

CNS: Sedative at low doses, excitation, agitation, hallucinations, and coma at higher doses.
Eye: Blocks Ach activation of pupillary constrictor muscles; causes mydriasis (pupil dilation). Renaissance eye drops used to cause dilation.
Cardiac: Blocks vagus nerve slowing of SA node; causes tachycardia.

Antimuscarinics and Specific Applications

Respiratory: Ipratropium (analog to atropine) used in inhalant asthma to cause bronchodilation
Cardiovascular: Blocks reflex vagal discharge in MI with atropine-like drugs
Gastrointestinal: Lomotil (atropine + diphenoxylate) for traveler's diarrhea to keep opioid dose lower.
Urinary: Oxybutynin to reduce involuntary voiding

Atropine

Plant Source: Belladonna (deadly nightshade), jimsonweed, and other plants.
Action: Blocks Ach receptors. Effects include cardiac slowing, dry mouth, sweat inhibition, pupil dilation, blurred vision, and coma in high doses.
Overdose Treatment: Increase Ach at the receptor using anticholinesterase drugs which degrade Ach.

Clinical Uses of Atropine

Heart: Treat excess vagus nerve stimulation causing bradycardia.
Eye: Cause pupil dilation for retina examination
GI: Used in irritable colon to block Ach-induced motility increases.
Motion Sickness: Scopolamine patches to reduce nausea and vomiting.
Anticholinesterase Poisons: Overcomes wild mushroom, insecticides, and warfare agent inhibition.

Antimuscarinic Therapy Mechanisms

Mechanism of Action: Agents inhibit AchE, which increases Ach levels, and excess Ach causes paralysis. Drugs block nicotinic and muscarinic receptors to block excess Ach.
Treatment: Atropine (1-2 mg IV every 5-15 minutes until effect appears) to treat nerve gas and poisoning. Higher doses to support for a month, if necessary.

Mushroom Poisoning

Rapid onset poisoning: Amanita muscaria contain muscarine (acetylcholine agonist). Treatment: atropine.
Delayed onset poisoning: Other Amanita species and similar fungi possess amatoxins which cause liver failure; require liver transplant.

Food Examples

Edible Mushrooms: Shiitake, oyster mushrooms.
Mold-containing Cheese: Stilton or blue cheese.

Poisonous Mushrooms (Rapid Onset)

Amanita muscaria: Causes hallucinations, diarrhea, sweating, and pupil constriction (miosis).

Poisonous Mushrooms (Slow Onset)

Amanita virosa (Death Cap): Causes slow toxic reactions; contains alpha-amanitin, which binds to RNA polymerase in hepatocytes and shuts down protein synthesis. Characterized by liver failure and requires a liver transplant.

Poisoning with Cholinesterase Inhibitors

Exposure to insecticides, wild mushrooms, and nerve gas causes excess Ach buildup due to cholinesterase (AchE) disruption. Treatment: antimuscarinics such as atropine. High doses.

Nerve Agents (ACE Inhibitors)

Examples: Sarin, tabun.
Mechanism: Potent AchE inhibitors, causing excess Ach and paralysis.

Antidotes for Nerve Agents

Atropine injection: Blocks excess Ach actions on nicotinic and muscarinic receptors.

AchE inhibitor Nerve agents

Newmark, J. The Birth of Nerve Agent Warfare lessons from Syed Abbas Foroutan, Neurology 62:1590-1596(2004).
Foroutan, S.A. the world's first physician to report on the treatment of Sarin nerve gas.

Nerve Gas (Iraq -Iran war):

Sarin Nerve Gases: Used in the Iran-Iraq war.
Casualties: 450,000
Dr. Foroutan: Sent by Iran to establish field hospitals and treat wounded combatants.
Papers Published: 11 papers in the Farsi Kowsar Medical Journal addressing their experiences and treatment protocols.
Mustard Gas Exposure: Some patients also exposed to WWI mustard gas. Description of disfiguration and how these patients were treated

Treatment

Atropine: To counteract excess Ach at muscarinic receptors. US, NATO, and Iran each carry 2mg auto injectors.
2PAM: (2-pralidoxime): Reactivates AchE, restoring its catalytic activity. US and NATO carry 600mg auto injectors.
Diazepam: Used to counteract seizures. All forces, including US, NATO, and Iran carry 10mg auto injectors.

Foroutan's Recommendations

Rest Period: Allowed recovered troops post treatment.
Dosage Adjustments: Adjust the atropine dose based on pulse rate (60-70 bpm is the target range when increasing/decreasing the dose). High doses required if symptoms severe.
Mask Fitting: Higher casualties from the Pasdaran due to inadequate mask fitting and beards impeding proper mask seal.
Large-scale Tragedies: The scale of attacks necessitated triage. Estimates ranged up to 2000 casualties within a 5-hour period.

Tolterodine (Detrol)

Mechanism: Potent muscarinic antagonist, shows selectivity for the bladder.
Indication: Overactive bladder.

Antimuscarinics (General Notes)

Specificity: Non-specific, inducing unwanted effects on various organs.
Overdose Symptoms: Dry as a bone, red as a beet, mad as a hatter. Symptoms include dry mouth, mydriasis, and tachycardia.

ADRs (Adverse Drug Reactions) and Toxicity

CNS Toxicity: Sedation, amnesia, delirium, hallucinations. Convulsions might occur. Treatment: supportive care.
Cutaneous Effects: Vasodilation; atropine flush; diagnostic symptom in overdose cases.

Ganglion Blockers,

Mechanism: Block the action of Ach on nicotinic receptors in autonomic ganglia.
Limited Clinical Use: Seldom used due to non-selectivity. Block all sympathetic outflow.

Examples of Ganglion Blockers

Hexamethonium: First antihypertensive, no longer used.
Mecamylamine:
Trimethaphan: Short-acting, IV administration.

Cholinergic Poisoning

Cause: Excess Ach or other agonist activity. Can be from AchE inhibitors (insecticides and nerve gasses), or mushroom poisoning.
Treatment: Cholinesterase regenerators (e.g., pralidoxime) and antimuscarinics (e.g., atropine).

AchE Regenerator Drugs

Pralidoxime (2-PAM): Hydrolyzes the phosphorylated AchE-organophosphate complex, regenerating AchE. Does not cross BBB; does not reverse CNS actions from organophosphates.

Muscarinic Agonists (Summary)

Causes: Constriction of smooth muscles in gut, bladder; pupil constriction. Decreased heart rate and force; increased glandular secretions; vasodilation via nitric oxide; etc.

Muscarinic Antagonists (Summary)

Causes: Reduced secretions (dry mouth), tachycardia; pupil dilation; relaxation of smooth muscles; CNS excitation; anti-emetic actions.

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