Pharmacology of Cholinergic Agonists

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Questions and Answers

Which muscarinic receptor type is primarily involved in inhibitory actions in the heart?

Nicotinic

M2 (correct)

What is the main effect of M3 receptor activation in the gastrointestinal tract?

Inhibition of motility

Increase in motility (correct)

Relaxation of sphincters

Decrease in secretion

Which of the following antagonists targets M1 receptors?

Atropine (correct)

Glycopyrrolate (correct)

Dopamine

Nicotine

What secondary messenger is produced by M3 receptor activation in vascular smooth muscle?

IP3 Signup and view all the answers

In the urinary tract, what effect do M3 receptors have on the bladder wall?

Contraction Signup and view all the answers

Which receptor type is primarily involved in excitatory functions in the CNS?

M1 Signup and view all the answers

What is the effect of M3 receptor activation in the eye?

Contraction of the ciliary muscle Signup and view all the answers

Which of these functions is NOT related to M3 receptor activation?

Increase in heart rate Signup and view all the answers

What is myasthenia gravis primarily characterized by?

Autoimmune disease affecting skeletal muscle Signup and view all the answers

Which of the following is NOT a treatment option for myasthenia gravis?

Physical therapy Signup and view all the answers

What may result from an excess intravenous injection of edrophonium?

Cholinergic crisis Signup and view all the answers

Which drug is described as a synthetic, quaternary amine used in myasthenia gravis treatment?

Neostigmine Signup and view all the answers

Which of the following adverse effects is associated with physostigmine?

Bradycardia Signup and view all the answers

What is the effect of binding two acetylcholine molecules to its receptor?

Conformational change allowing sodium ions entry Signup and view all the answers

Which of the following is a reversible anticholinesterase?

Physostigmine Signup and view all the answers

What is the duration of action of pyridostigmine?

3 to 6 hours Signup and view all the answers

What is a characteristic of organophosphate compounds?

They bind covalently to AChE Signup and view all the answers

What is the main action of acetylcholine on the cardiovascular system?

Negative chronotropic effect Signup and view all the answers

Which drug can penetrate the blood-brain barrier?

Physostigmine Signup and view all the answers

Carbachol has which of the following properties?

Non-selective and acts on both nicotinic and muscarinic receptors Signup and view all the answers

What occurs in the absence of administered cholinergic agents regarding vascular receptors?

They have no known function Signup and view all the answers

Which of the following statements about acetylcholine is true?

It is non-selective and rapidly inactivated by cholinesterase Signup and view all the answers

Which of the following is NOT an effect of acetylcholine on the eye?

Contraction of radial muscles Signup and view all the answers

What is the key mechanism by which acetylcholine causes vasodilation?

Activation of M3 receptors leading to nitric oxide release Signup and view all the answers

What is the primary therapeutic use of carbachol?

As a miotic agent for glaucoma treatment Signup and view all the answers

What distinguishes bethanechol from acetylcholine regarding its metabolism?

It is an ester of carbamic acid and poorly hydrolyzed Signup and view all the answers

Which of the following is a common adverse effect of bethanechol?

Abdominal pain and diarrhea Signup and view all the answers

What is the effect of pilocarpine on the eye?

Causes miosis and ciliary muscle contraction Signup and view all the answers

Which condition is bethanechol primarily used to treat?

Atonic bladder Signup and view all the answers

What type of action does carbachol exhibit in the nervous system?

Non-selective with long duration of action Signup and view all the answers

Which statement about pilocarpine is correct?

Has strong muscarinic activity and penetrates the CNS Signup and view all the answers

How does carbachol affect intraocular pressure?

Reduces the pressure through drainage stimulation Signup and view all the answers

What effect do cholinomimetics have on closed angle glaucoma?

They open the ocular angle. Signup and view all the answers

Which condition is Cevimeline primarily used to treat?

Xerostomia Signup and view all the answers

What side effect is associated with direct acting parasympathomimetics?

Miosis Signup and view all the answers

Which of the following is classified as a reversible indirect-acting cholinergic agonist?

Neostigmine Signup and view all the answers

What is a primary action of indirect acting cholinergic agonists?

Inhibition of acetylcholinesterase Signup and view all the answers

What is the duration of action for Edrophonium as an AChE inhibitor?

10-20 minutes Signup and view all the answers

Which of the following side effects is NOT commonly associated with direct-acting parasympathomimetics?

Dry mouth Signup and view all the answers

What type of agent are organophosphates considered in relation to cholinergic activity?

Irreversible anticholinesterases Signup and view all the answers

What are the origins of the sympathetic and parasympathetic nervous systems?

Thoraco-lumbar and Cranio-sacral segments Signup and view all the answers

Which enzyme is responsible for the synthesis of acetylcholine in cholinergic neurons?

Choline acetyltransferase Signup and view all the answers

Which receptors primarily bind to acetylcholine in the central and peripheral nervous systems?

Muscarinic receptors Signup and view all the answers

What is the mechanism of action for the termination of acetylcholine's function?

Hydrolysis by acetylcholinesterase Signup and view all the answers

Which parasympathetic pre-ganglionic fiber characteristic distinguishes it from sympathetic fibers?

Long length Signup and view all the answers

Which of the following subclasses of muscarinic receptors is present in the CNS?

M4 and M5 Signup and view all the answers

What role does acetyl coenzyme A play in acetylcholine synthesis?

It acts as an acetyl donor. Signup and view all the answers

Which statement correctly differentiates between the lengths of post-ganglionic fibers in the sympathetic and parasympathetic systems?

Sympathetic fibers are long and parasympathetic fibers are short. Signup and view all the answers

Study Notes

Cholinergic Agonists Overview

The lecture covers pharmacology of drugs acting on the autonomic nervous system and autacoids.
It includes topics on pharmacological actions, side effects, drug interactions, and uses.
The lecture notes cover data from basic sciences to address therapeutic issues.
Learning objectives include selecting appropriate pharmacotherapeutic approaches based on etiology, pathophysiology, laboratory diagnosis, and clinical features.
Recognizing pharmacological properties of diverse drugs is also a learning objective.

Parasympathetic vs. Sympathetic

Sympathetic: Originates in thoraco-lumbar segments, has short preganglionic fibers and long postganglionic fibers.
Parasympathetic: Originates in cranio-sacral segments, has long preganglionic fibers and short postganglionic fibers.

Cholinergic Neurotransmission

Acetylcholine (ACh) synthesis occurs in cholinergic nerve terminals.
Acetylcholine is formed via acetylation of choline by choline acetyltransferase (ChAT).
Acetyl Coenzyme A (acetyl donor) and choline are required; choline is provided from high-affinity uptake after ACh hydrolysis and phospholipid hydrolysis within the neuron.
ACh is transported to vesicles and released by exocytosis to bind to muscarinic or nicotinic receptors.
Acetylcholinesterase (AChE) terminates ACh action by hydrolyzing it into acetic acid and choline. More than 50% of choline is recycled for ACh synthesis.

Cholinergic Receptors

Muscarinic receptors: G protein-coupled (metabotropic) receptors.
- Bind to acetylcholine and muscarine, with weaker affinity to nicotine.
- Five subtypes (M1, M2, M3, M4, and M5).
- M1, M2 and M3 are found peripherally and centrally and M4, M5 present only centrally.
Receptor activation leads to different intracellular responses.
- M1: IP3, DAG pathway.
- M2: cAMP pathway (inhibition).
- M3: IP3, DAG pathway.
Nicotinic receptors: Ligand-gated ion channels (ionotropic receptors).
- Bind to acetylcholine and nicotine.
- Show weak affinity to muscarine.
- Binding of two acetylcholine molecules causes a conformational change allowing sodium ions entry.

Cholinergic Actions and Receptors

Heart: M2 receptors result in negative inotropic and chronotropic effects.
Vascular smooth muscle: M3 receptors activate nitric oxide production causing vasodilation.
GIT: M1 and M3 receptors regulate secretion and motility
Urinary Tract: M3 receptors contract sphincter and bladder wall.
Eye: M3 receptors cause miosis (pupil constriction) and accommodate near vision.
Bronchi: M3 receptors cause constriction.

Direct Acting Parasympathomimetics

Acetylcholine (ACh): Quaternary ammonium, cannot penetrate membranes, and inactivated by cholinesterase, has both muscarinic and nicotinic activities, of no therapeutic significance.
2-Carbachol: Muscarinic and nicotinic activity, mimics ACh effects on CVS, GIT, and eye (miosis), a poor substrate for acetylcholinesterase. Also, used to treat glaucoma by decreasing intraocular pressure. Has less adverse effects ophthalmologically.
3-Bethanechol: Structurally related to ACh, not hydrolyzed by acetylcholinesterase, has strong muscarinic activity, primarily acting on the GIT and bladder, is used for atonic bladder, neurogenic atony, and megacolon. Adverse effects include sweating, salivation, flushing, hypotension, abdominal pain, and diarrhea.
4-Pilocarpine: Tertiary amine, stable to acetylcholinesterase, less potent than acetylcholine, enters the CNS at therapeutic doses, shows muscarinic activity, used in glaucoma treatment, and causes miosis, and increased secretions of sweat, tears, and saliva. Adverse effects include CNS side effects and sweating/salivation.
5-Cevimeline: Selective M3 agonist, used to treat xerostomia and Sjogren's syndrome, has fewer adverse effects than pilocarpine.

Indirect Acting Parasympathomimetics: Anticholinesterases

1-Edrophonium: Prototype short-acting acetylcholinesterase (AChE) inhibitor, used for diagnosing myasthenia gravis, with a short duration of action (10-20 minutes).
2-Physostigmine: Naturally occurring tertiary amine, intermediate-acting AChE inhibitor stimulating M and N receptors and able to cross the BBB.
3-Neostigmine: Synthetic quaternary amine, intermediate-acting AChE inhibitor with more skeletal muscle effects compared to physostigmine, not crossing the BBB, used in myasthenia gravis treatment and antidote for competitive neuro-muscular blocking agents like tubocurarine.
4-Pyridostigmine: Similar to Neostigmine but has a longer duration of action (3-6 hours).
5-Organophosphates: Covalently bind to AChE, extremely stable and require enzyme synthesis to recover, toxic insecticides (e.g., parathion, malathion) and nerve agents (e.g., sarin), treated with pralidoxime.

Additional Information

Myasthenia Gravis: An autoimmune disease impacting the skeletal muscle, characterized by antibody binding to nicotinic receptors in the neuromuscular junction (NMJ), leading to muscle weakness, involving eye, face and limb muscles. Treated with immunosuppressant drugs, neostigmine (a cholinesterase inhibitor that inhibits the breakdown of acetylcholine, thus increasing its action), or surgical removal of the thymus gland.
Cholinergic Crisis: Excess cholinergic stimulation producing adverse symptoms such as diarrhea, urination, miosis, and bradycardia.

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Description

This quiz provides an overview of cholinergic agonists, covering pharmacological actions, uses, and side effects. It distinguishes between parasympathetic and sympathetic nervous system functions and explores cholinergic neurotransmission. Test your knowledge on the autonomic nervous system and its pharmacotherapy.