Pharmacology of Cholinergic Agents
44 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which compound is a non-selective muscarinic and nicotinic agonist with high hydrolysis by cholinesterase?

  • Bethanechol
  • Muscarine
  • Carbachol (correct)
  • Methacholine

Which of the following agents is known to have muscarinic activity but no nicotinic activity?

  • Arecoline
  • Oxotremorine
  • Nicotine
  • Cevimeline (correct)

What is the common characteristic of compounds like Bethanechol and Muscarine?

  • Low muscarinic activity
  • Resistant to cholinesterase
  • High nicotinic activity
  • No nicotinic activity (correct)

Identify the agent with the highest muscarinic activity and moderate nicotinic activity.

<p>Acetylcholine (B)</p> Signup and view all the answers

Which of these compounds has a unique property of being a selective muscarinic agonist that is hydrolyzed less effectively by cholinesterase than Methacholine?

<p>Pilocarpine (C)</p> Signup and view all the answers

What is the primary therapeutic use of neostigmine in the context of muscle disorders?

<p>Reversal of non-depolarizing neuromuscular blocking drugs (D)</p> Signup and view all the answers

Which of the following distinguishes pyridostigmine from neostigmine?

<p>Pyridostigmine is better absorbed and has a longer duration of action (D)</p> Signup and view all the answers

What is the mechanism of action of reversible long anticholinesterases like donepezil?

<p>Inhibition of acetylcholinesterase, leading to increased acetylcholine levels (A)</p> Signup and view all the answers

Which of the following is NOT a characteristic of physostigmine?

<p>Has longer duration of action than neostigmine (C)</p> Signup and view all the answers

What role do carbamyl groups play in the action of intermediate acting anticholinesterases?

<p>They replace acetyl groups in binding to the enzyme (B)</p> Signup and view all the answers

Which of the following accurately describes the natural substrate of plasma cholinesterase?

<p>Fatty acyl esters (A), Aromatic esters (D)</p> Signup and view all the answers

What is the primary location of acetylcholinesterase within the body?

<p>Cholinergic nerve terminals (C)</p> Signup and view all the answers

What differentiates short-acting anticholinesterases from others?

<p>They only bind to the anionic site of the enzyme. (C)</p> Signup and view all the answers

What clinical condition is most commonly treated using cholinesterase inhibitors?

<p>Myasthenia gravis (C)</p> Signup and view all the answers

Which of the following is NOT classified as a short-acting anticholinesterase?

<p>Neostigmine (A), Butyrylcholine (B), Physostigmine (D)</p> Signup and view all the answers

What is the effect of anticholinesterase inhibitors on acetylcholine levels in the body?

<p>They increase the levels and duration of action of ACh. (A)</p> Signup and view all the answers

Which compound is primarily used as an antidote in anticholinergic poisoning?

<p>Physostigmine (C)</p> Signup and view all the answers

Which active site of the cholinesterase enzyme binds the acetyl group during hydrolysis?

<p>Esteric site (A)</p> Signup and view all the answers

What is the primary mechanism through which Pralidoxime (2-PAM) reactivates the phosphorylated enzyme?

<p>It releases the phosphate group from the esteric site. (C)</p> Signup and view all the answers

What limitation affects the efficacy of Pralidoxime in treating organophosphate poisoning?

<p>Ageing of the enzyme renders it no longer susceptible to reactivation. (C)</p> Signup and view all the answers

Which statement about Pralidoxime is true regarding its impact on the nervous system?

<p>It does not affect the central actions of organophosphate poisoning. (D)</p> Signup and view all the answers

In conjunction with Pralidoxime, which drug is commonly used to relieve neuromuscular weakness caused by organophosphate poisoning?

<p>Atropine (B)</p> Signup and view all the answers

Why is Pralidoxime not approved for the treatment of carbamate poisoning?

<p>It is ineffective against the mechanisms of carbamate action. (C)</p> Signup and view all the answers

What is a significant contraindication for muscarinic agonists?

<p>Asthma (B)</p> Signup and view all the answers

Which muscarinic antagonist primarily reduces gastric acid secretion?

<p>Pirenzepine (C)</p> Signup and view all the answers

What effect do muscarinic antagonists have on the heart?

<p>Increase heart rate (C)</p> Signup and view all the answers

Which of the following is a central nervous system effect of atropine?

<p>Hyperactivity and hyperthermia from sweating loss (D)</p> Signup and view all the answers

Which muscarinic antagonist is specifically used for motion sickness?

<p>Hyoscine (B)</p> Signup and view all the answers

What is the primary clinical use of Tiotropium?

<p>Asthma and COPD (D)</p> Signup and view all the answers

Which of the following effects is NOT produced by muscarinic antagonists?

<p>Bronchoconstriction (C)</p> Signup and view all the answers

What is the mechanism of action for muscarinic antagonists?

<p>Blockade of cholinergic receptors (A)</p> Signup and view all the answers

Which medication is associated with the treatment of excessive salivation?

<p>Glycopyrrolate (A)</p> Signup and view all the answers

Which of the following agents is a selective M3 antagonist?

<p>Darifenacin (B)</p> Signup and view all the answers

What adverse effect is most commonly associated with overdose of muscarinic antagonists?

<p>Dry mouth and skin (A)</p> Signup and view all the answers

Which muscarinic antagonist is primarily used in the management of organophosphate poisoning?

<p>Atropine (B)</p> Signup and view all the answers

Which of the following substances is a toxic alkaloid found in mushrooms?

<p>Muscarine (B)</p> Signup and view all the answers

What is the primary mechanism by which irreversible anticholinesterases exert their action?

<p>They phosphorylate the esteric site of the enzyme. (A)</p> Signup and view all the answers

Which of the following statements about the aging process of organophosphate-inhibited cholinesterases is true?

<p>Aging decreases the potential for reactivation of the inhibited enzyme. (B)</p> Signup and view all the answers

Which compound is classified as a pseudo-irreversible anticholinesterase and is used in treating glaucoma?

<p>Ecothiophate (D)</p> Signup and view all the answers

What is the core reason for the toxicity of Dyflos?

<p>It has a highly toxic nature with prolonged action. (D)</p> Signup and view all the answers

Under what condition can organophosphate poisoning become particularly dangerous?

<p>When aging of the phosphorylated enzyme starts to occur. (B)</p> Signup and view all the answers

Which of the following statements correctly describes the action of irreversible anticholinesterases?

<p>They irreversibly inhibit acetylcholinesterase by binding to the esteric site. (C)</p> Signup and view all the answers

What type of compounds are primarily used in pesticides and biowarfare, related to irreversible anticholinesterases?

<p>Organophosphates (B)</p> Signup and view all the answers

What is the elimination half-life of the compounds discussed in relation to anticholinesterases?

<p>70 hours (B)</p> Signup and view all the answers

Flashcards

Muscarinic Agonists

Drugs that mimic the effects of the parasympathetic nervous system. They activate muscarinic receptors, which are found in various organs like the heart, lungs, and digestive system.

Methacholine

A type of drug that stimulates muscarinic receptors. It is commonly used to diagnose and treat asthma by constricting the airways.

Bethanechol

A drug that selectively activates muscarinic receptors, found in the heart and digestive system. It's useful in treating urinary retention and gastrointestinal disorders.

Nicotine

A drug that stimulates both nicotinic and muscarinic receptors. It has a wide range of effects, including increased heart rate, blood pressure, and alertness.

Signup and view all the flashcards

Pilocarpine

A drug that activates muscarinic receptors and is used in treating dry mouth and other conditions caused by reduced saliva production.

Signup and view all the flashcards

Plasma Cholinesterase

A type of cholinesterase primarily found in the plasma, liver, skin, brain, and digestive system. Its natural substrates include fatty acyl esters and aromatic esters.

Signup and view all the flashcards

Acetylcholinesterase

An enzyme that plays a crucial role in breaking down acetylcholine, a neurotransmitter responsible for signaling between nerve cells.

Signup and view all the flashcards

Anionic Site

A site on the cholinesterase enzyme that binds to the positively charged quaternary amine group of acetylcholine.

Signup and view all the flashcards

Esteric Site

The site on the cholinesterase enzyme that binds to the acetyl group (ester) of acetylcholine. This is where the hydrolysis of acetylcholine occurs, breaking it down into acetic acid and choline.

Signup and view all the flashcards

Cholinesterase Inhibitors

Drugs that inhibit the activity of cholinesterases, preventing the breakdown of acetylcholine and other related compounds. This leads to increased levels and duration of action of acetylcholine in the central and peripheral nervous systems.

Signup and view all the flashcards

Edrophonium

A short-acting cholinesterase inhibitor that binds only to the anionic site of the enzyme.

Signup and view all the flashcards

Treating Neurodegenerative Diseases

The use of cholinesterase inhibitors in treating Alzheimer's disease and Parkinson's disease. It aims to improve cognitive function and motor control.

Signup and view all the flashcards

Reversal of Neuromuscular Blockade

The use of cholinesterase inhibitors to reverse the effects of non-depolarizing neuromuscular blocking drugs used in surgery.

Signup and view all the flashcards

Intermediate-Acting Anticholinesterase

A type of cholinesterase inhibitor that has a shorter duration of action than long-acting inhibitors, lasting for only minutes. Examples include neostigmine, pyridostigmine, and physostigmine.

Signup and view all the flashcards

Neostigmine

A drug used to diagnose and treat myasthenia gravis. It is also used to reverse the effects of non-depolarizing muscle relaxants.

Signup and view all the flashcards

Pyridostigmine

A drug used to treat myasthenia gravis. This drug is better absorbed and has a longer duration of action than neostigmine.

Signup and view all the flashcards

Physostigmine

A drug used to reverse the effects of atropine poisoning. It is also used as eye drops to treat glaucoma.

Signup and view all the flashcards

Reversible Long-Acting Anticholinesterase

A type of cholinesterase inhibitor that has a longer duration of action than intermediate-acting inhibitors, lasting for hours. Examples include donepezil, rivastigmine, and galantamine.

Signup and view all the flashcards

DUMBBELSS

A group of side effects seen with muscarinic agonists. Stands for Diarrhea, Urination, Miosis (constriction of the pupil), Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, Salivation.

Signup and view all the flashcards

Xerostomia

A condition commonly treated with muscarinic agonists due to insufficient saliva production.

Signup and view all the flashcards

Sjögren’s syndrome

A condition affecting the exocrine glands, often causing dry eyes and mouth, treated with muscarinic agonists.

Signup and view all the flashcards

Cevimeline

A muscarinic agonist used to treat xerostomia and Sjögren’s syndrome.

Signup and view all the flashcards

Hyoscine (Scopolamine)

A muscarinic antagonist used to treat motion sickness.

Signup and view all the flashcards

Atropine

A widely used muscarinic antagonist with a variety of applications including treatments for bradycardia and organophosphate poisoning.

Signup and view all the flashcards

Oxybutynin

A muscarinic antagonist used to treat overactive bladder.

Signup and view all the flashcards

Tolterodine

A muscarinic antagonist used to treat overactive bladder and bladder spasms.

Signup and view all the flashcards

Mydriasis

A primary side effect of muscarinic antagonists, characterized by dilated pupils.

Signup and view all the flashcards

Tachycardia

A primary side effect of muscarinic antagonists, characterized by a rapid heart rate.

Signup and view all the flashcards

Decreased Salivation

A primary side effect of muscarinic antagonists, characterized by a reduction in saliva production.

Signup and view all the flashcards

Urinary Retention

A primary side effect of muscarinic antagonists, characterized by difficulty urinating.

Signup and view all the flashcards

Atropine Toxicity

A serious condition resulting from atropine overdose, characterized by high body temperature, confusion, and delirium.

Signup and view all the flashcards

Elimination half life

The time it takes for the concentration of a drug in the body to reduce by half.

Signup and view all the flashcards

Anticholinesterases

A group of drugs that inhibit the enzyme cholinesterase, leading to an accumulation of acetylcholine in the synapse.

Signup and view all the flashcards

Irreversible Anticholinesterases

A type of anticholinesterase that permanently binds to cholinesterase, leading to irreversible inhibition.

Signup and view all the flashcards

Pseudo irreversible Anticholinesterases

A type of anticholinesterase that binds to cholinesterase but can be reversed over time.

Signup and view all the flashcards

Cholinesterase Reactivation

The process of restoring the activity of cholinesterase after it has been inhibited by organophosphates.

Signup and view all the flashcards

Ageing

A chemical change that occurs in the phosphorylated enzyme, making it more stable and difficult to reactivate.

Signup and view all the flashcards

Pentavalent Phosphorous Group

A compound that binds to the esteric site of cholinesterase, preventing it from breaking down acetylcholine.

Signup and view all the flashcards

Organophosphate Compounds

A group of organic compounds that inhibit cholinesterase and are commonly used in pesticides and biological warfare.

Signup and view all the flashcards

Pralidoxime (2-PAM)

A drug that reactivates cholinesterase by attaching to the enzyme's anionic site and removing the phosphate group from the esteric site. It's used to treat organophosphate poisoning by restoring the enzyme's function.

Signup and view all the flashcards

Pralidoxime and Aging

A limitation of pralidoxime is that it's ineffective against aged organophosphates, which have permanently bound to the enzyme. This means it is only beneficial when given early in the poisoning process.

Signup and view all the flashcards

Pralidoxime's Brain Barrier

Pralidoxime does not cross the blood-brain barrier effectively, meaning it mainly acts at the neuromuscular junction and has limited ability to reverse central nervous system effects of organophosphates.

Signup and view all the flashcards

Pralidoxime for Anticholinesterase Toxicity

Pralidoxime is used to reverse the effects of some anticholinesterase drugs like neostigmine and pyridostigmine, often used in the treatment of conditions like myasthenia gravis.

Signup and view all the flashcards

Pralidoxime and Atropine: A Team Effort

Pralidoxime is one part of the treatment for organophosphate poisoning, primarily addressing neuromuscular weakness by reversing the cholinesterase inhibition at skeletal muscles. Atropine, acting on the muscarinic receptors, is used to counteract the parasympathetic effects.

Signup and view all the flashcards

Study Notes

Cholinergic Pharmacology

  • Cholinergic pharmacology studies agents that act on the cholinergic system.
  • The cholinergic system is composed of nerve cells that use acetylcholine as a neurotransmitter for action potentials.
  • Acetylcholine is the neurotransmitter released during nerve impulse propagation

Cholinergic Nerve Anatomy

  • A cholinergic nerve has a presynaptic neuron and a postsynaptic neuron separated by a synaptic cleft.
  • Vesicles containing acetylcholine (ACh) are present in the presynaptic neuron.
  • Acetylcholinesterase (AChE) is located in the synaptic cleft.

Anabolism of Acetylcholine

  • Biosynthesis: Acetylcholine (ACh) is synthesized within cholinergic neurons by transferring an acetyl group from acetyl CoA to choline.The enzyme choline-acetyltransferase (ChAT) catalyzes this reaction.
  • Uptake into storage vesicles: Synaptic vesicles, primarily located at nerve endings, store the synthesized neuronal acetylcholine (ACh). Vesicular ACh transporter (VACHT) transports ACh into these vesicles.
  • Release: Calcium influx is essential for acetylcholine (ACh) release from synaptic vesicles.
  • Neurotransmission: After release, ACh diffuses across the synaptic cleft and binds to postsynaptic receptors, triggering a physiological response

Catabolism of Acetylcholine

  • Degradation (Hydrolysis): Acetylcholinesterase (AChE) in the synaptic cleft breaks down ACh into choline and acetate.
  • Recycling: Choline transporter (ChT) returns choline to the presynaptic neuron to synthesize new ACh. Acetate is also recycled for further ACh synthesis.

Agents Affecting ACh

  • Biosynthesis inhibition: a-ketoacids and naphthoquinones directly inhibit the enzyme choline acetyltransferase (ChAT), thus interfering with ACh synthesis.
  • Vesicle uptake blockage: Vesamicol blocks the specific ACh transporter (VACHT), preventing ACh from entering synaptic vesicles. This compound is poisonous.
  • Release inhibition: Botulinum toxin inhibits ACh release from presynaptic nerve terminals.
  • Release increase: Latrotoxin (from black widow spider) causes an explosive release of ACh.
  • Neurotransmission blockade: Atropine blocks postsynaptic muscarinic ACh receptors, preventing ACh's action. a-Bungarotoxin irreversibly binds to postsynaptic nicotinic ACh receptors. D-tubocurarine blocks nicotinic ACh receptors

Cholinergic Receptors

  • Nicotinic ACh receptors (nAChRs): These receptors are located at the preganglionic, ganglion, and postganglionic regions. Excess activation can result in desensitization. They are ionotropic receptors.
  • Muscarinic ACh receptors (mAChRs): Primarily postganglionic and not prone to desensitization after excess activation. They are metabotropic. There are five subtypes

Effects of Cholinergic Transmission

  • Muscarinic agonists/antagonists
  • Ganglion-stimulating/blocking agents
  • Neuromuscular-blocking agents
  • Anticholinesterases

Structure Activity Relationship (SAR) of Muscarinic Agonists

  • Key features for activity include a quaternary ammonium group (reducing CNS penetration), an ester group (susceptible to cholinesterase hydrolysis), and a choline structure (affinity for both mAChRs and nAChRs).

Muscarinic Agonists

  • Substances that mimic the effects of ACh on muscarinic receptors.
  • Types: quaternary ammonium and tertiary ammonium.
  • Examples: Acetylcholine, Carbachol, Methacholine, Bethanechol, Pilocarpine, Cevimeline, Oxotremorine, Arecoline, Muscarine

Muscarinic Agonists Effects

  • Organs/Systems: Smooth muscles (bronchi, GI tract, bladder), eye (pupil, ciliary muscles), glands (salivary, lacrimal, sweat), blood vessels, heart (SA and AV nodes).

Muscarinic Antagonists

  • Substances that block the effects of ACh on muscarinic receptors.
  • Types: tertiary and quaternary ammonium salts
  • Examples: Atropine, Hyoscine, Dicycloverine, Propantheline, Tolterodine, Darifenacin, Ipratropium, Glycopyrrolate

Muscarinic Antagonists Effects

  • Effects on smooth muscles, glands, eye, and heart are opposite to those of muscarinic agonists.

Ganglion Agonists

  • These agents stimulate both sympathetic and parasympathetic ganglia.
  • Examples: Nicotine, Varenicline, Lobeline, Epibatidine

Ganglion Blockers

  • These agents inhibit transmission between preganglionic and postganglionic neurons in autonomic ganglia.
  • Examples: Tetraethyl ammonium, Hexamethonium, Trimetaphan, Mecamylamine, D-tubocurarine, Pentamine

Neuromuscular Blockers

  • Agents that block neuromuscular transmission (cholinergic).
  • Types: non-depolarizing, depolarizing
  • Non-depolarizing: Act postsynaptically, block nAChRs or Na+ channels.
  • Examples: Mivacurium, Atracurium, Vecuronium, Pipecuronium

Depolarizing Blockers

  • Agents that induce persistent depolarization of the motor endplate.
  • Example: Suxamethonium, Decamethonium.
  • More rapidly in onset compared to non-depolarizing.

Cholinesterases

  • Enzymes in the neuromuscular junction that break down acetylcholine (ACh) and other cholinergic compounds. Two main types: AChE, BuChE

Anticholinesterases

  • Compounds that inhibit the cholinesterase enzyme.
  • Most commonly used in diseases like Alzheimer's or Parkinson's.
  • Two types: Reversible and Irreversible

Cholinesterase Reactivation

  • Pralidoxime (2-PAM) reactivates phosphorylated cholinesterase.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

Cholinergic Pharmacology PDF

Description

Explore the key concepts surrounding non-selective muscarinic and nicotinic agonists, including the characteristics and applications of various compounds. This quiz covers their mechanisms of action, therapeutic uses, and differences among agents like neostigmine and pyridostigmine. Test your knowledge on the pharmacological aspects of cholinergic agents.

More Like This

Use Quizgecko on...
Browser
Open
Browser
Browser