Cholinergic

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Questions and Answers

What is a primary therapeutic use of atropine in a pre-operative setting?

Inducing muscle spasms

Increasing salivary secretion

Reducing salivary secretion (correct)

Causing urinary retention

Which of the following conditions is NOT a contraindication for the use of antimuscarinic drugs?

Myasthenia gravis

Glaucoma

Myocardial ischemia

Constipation (correct)

What mechanism do antimuscarinic drugs primarily utilize to achieve their effects?

Occupying muscarinic receptors (correct)

Inhibition of serotonin

Enhancing acetylcholine action

Inhibition of dopamine

Which of the following drugs is primarily used as an antidote for muscarinic agonist poisoning?

Atropine Signup and view all the answers

Which of the following is a characteristic adverse effect of antimuscarinic drugs?

Dry mouth Signup and view all the answers

What is the primary clinical use of Pilocarpine?

Inducing saliva secretion Signup and view all the answers

Which of the following statements is true regarding indirect-acting cholinergic agonists?

They increase the concentration of acetylcholine in the synapse. Signup and view all the answers

What is the antidote for sarin poisoning?

Atropine Signup and view all the answers

Which of the following is a reversible anticholinesterase?

Neostigmine Signup and view all the answers

What condition is NOT treated by indirect-acting cholinergic agonists?

Hypertension Signup and view all the answers

What function do organophosphates primarily serve?

Insecticides Signup and view all the answers

What adverse effect can occur from direct cholinergic agonists?

Blurred vision Signup and view all the answers

What is the primary cause of muscle weakness in myasthenia gravis?

Autoantibodies blocking NM receptors Signup and view all the answers

Which drug is considered first-line treatment for Alzheimer’s disease?

Rivastigmine Signup and view all the answers

Which of the following is not a clinical use of cholinergic antagonists?

Promotion of pupil constriction Signup and view all the answers

Which statement correctly describes the effect of cholinesterase inhibitors in myasthenia gravis?

They increase levels of ACh by inhibiting its breakdown. Signup and view all the answers

Which of the following is NOT classified as a cholinergic antagonist?

Rivastigmine Signup and view all the answers

What neurological change is primarily observed in Alzheimer’s disease?

Deficiency in ACh due to cholinergic neuron degeneration Signup and view all the answers

In the context of cholinergic antagonists, which drug is used as a neuromuscular blocker?

Succinylcholine Signup and view all the answers

Which symptoms are associated with increased activity of the cholinergic system?

Increased muscle tone and salivation Signup and view all the answers

Which of the following is classified as an antimuscarinic drug?

Scopolamine Signup and view all the answers

What is the primary neurotransmitter used in cholinergic pathways?

Acetylcholine Signup and view all the answers

What triggers the release of acetylcholine (ACh) into the synaptic cleft?

Action potential-induced calcium influx Signup and view all the answers

Which enzyme is responsible for the breakdown of acetylcholine in the synaptic cleft?

Acetylcholinesterase Signup and view all the answers

Where is acetylcholine synthesized in cholinergic neurons?

Presynaptic terminal from choline and acetyl-CoA Signup and view all the answers

Which drug inhibits the uptake of choline into the cholinergic neuron?

Hemicholinium Signup and view all the answers

Which pathway does not utilize acetylcholine as a neurotransmitter?

Sympathetic postganglionic nerve terminals exclusively Signup and view all the answers

What happens to choline after the breakdown of acetylcholine?

It is reused via the presynaptic terminal Signup and view all the answers

What is the primary action of acetylcholinesterase (AChE) inhibitors?

Decrease the degradation of acetylcholine Signup and view all the answers

Which of the following describes the release mechanism of acetylcholine?

Exocytosis triggered by calcium influx Signup and view all the answers

Which type of receptor is associated with ligand-gated ion channels?

Nicotinic receptors Signup and view all the answers

What type of drug is Methacholine classified as?

Direct acting cholinergic agonist Signup and view all the answers

What role does choline acetyltransferase (ChAT) play in cholinergic neurotransmission?

It synthesizes acetylcholine from choline and acetyl-CoA Signup and view all the answers

Which of the following statements about the reuptake of acetylcholine is correct?

There is no direct reuptake; it is metabolized instead. Signup and view all the answers

Which of the following cholinergic agonists is completely selective for muscarinic receptors?

Bethanechol Signup and view all the answers

Which cholinergic pathway is primarily involved in the sympathetic nervous system?

Sympathetic postganglionic terminals supplying sweat glands Signup and view all the answers

What is the primary role of Vesamicol in the cholinergic system?

Block choline uptake Signup and view all the answers

Which type of receptor is NOT classified under Muscarinic receptors?

Nm Signup and view all the answers

What type of drug is Atropine considered?

Antimuscarinic agent Signup and view all the answers

Which cholinergic antagonist is considered a neuromuscular blocker?

Succinylcholine Signup and view all the answers

Which muscarinic receptor subtype primarily affects cardiac muscle?

M2 Signup and view all the answers

Study Notes

Cholinergic Pharmacology

Lecture Objectives:
- Understanding the synthesis, storage, release, and metabolism of catecholamines.
- Identifying physiological effects mediated by adrenergic receptors (alpha and beta).
- Examining the mechanisms of action of adrenergic agonists and antagonists.
- Exploring therapeutic uses and side effects of drugs modulating adrenergic neurotransmission.

Overview of Cholinergic Pharmacology

Cholinergic Pathways:
- Neuro-muscular Junction (NMJ): All autonomic ganglia, parasympathetic postganglionic nerve terminals, sympathetic postganglionic nerve terminals supplying sweat glands.
- Central Nervous System (CNS): Non-neuronal cholinergic system.
Neurotransmitter: Acetylcholine (ACh).

Neurotransmitter: Acetylcholine (ACh)

Synthesis: Synthesized from choline and acetyl-CoA by choline acetyltransferase (ChAT).
Storage: Stored in synaptic vesicles in cholinergic neurons.
Release: Released into the synaptic cleft via exocytosis when an action potential reaches the nerve terminal. Action potential causes depolarization of the nerve terminal, calcium influx, and vesicle fusion with cell membranes, releasing acetylcholine into the synaptic cleft. Acetylcholine then binds to muscarinic or nicotinic receptors.
Reuptake: No direct reuptake of ACh; instead, it is broken down into choline and acetate. Choline is taken up by the presynaptic terminal for reuse.
Metabolism: Broken down by acetylcholinesterase (AChE) into choline and acetate in the synaptic cleft.

Cholinergic Receptors

Types of Receptors:
- Muscarinic Receptors (M1-M5): Member of G-protein-coupled receptors.
- Nicotinic Receptors (Nn and Nm): Member of ligand-gated ion channels.
Locations:
- Muscarinic Receptors: Pre/postganglionic parasympathetic effectors (M1-in CNS and autonomic ganglia; M2-in cardiac muscle; M3-in smooth muscle and glands; M4 and M5-in CNS).
- Nicotinic Receptors: Autonomic ganglia (Nn) and neuromuscular junction (NMJ) (Nm).

Drugs that affect ACh synthesis and metabolism

Storage: Vesamicol is a reversible blocker of the intracellular transporter responsible for ensuring acetylcholine storage into vesicles.
Uptake: Hemicholinium blocks the uptake of choline into the nerve ending.
Release: Botulinus toxin (Botox) prevents acetylcholine release by inhibiting the exocytosis of presynaptic vesicles.
Metabolism: Acetylcholinesterase (AChE) inhibitors like neostigmine prevent acetylcholine degradation.

Direct Cholinergic Agonists

Muscarinic Receptor Agonists:
- Acetylcholine (not clinically used due to rapid breakdown)
- Methacholine: 3X more resistant to hydrolysis by AChE compared with acetylcholine, selective to cardiovascular muscarinic cholinergic receptor (M2). Uses: diagnosis of asthma.
- Bethanechol: completely selective for muscarinic cholinergic receptors and resists AChE. Uses to promote GI and urinary tract motility, particularly postoperatively or postpartum, or urinary retention.
- Pilocarpine: most clinically used alkaloid; used to treat glaucoma by relieving fluid (intraocular) pressure and to treat dryness of the mouth secondary to reduced salivary secretion.

Adverse effects of direct cholinergic agonists

Nausea
Miosis
Diaphoresis
Diarrhea
Urinary urgency

Indirect-acting cholinergic agonists

They inhibit acetylcholinesterase, preventing the breakdown of ACh, increasing ACh concentration in the synaptic cleft.
Also called anticholinesterases, acetylcholinesterase inhibitors.
Reversible: Neostigmine (myasthenia gravis, post-operative urinary retention), Rivastigmine (Alzheimer's disease), Physostigmine (reverse anticholinergic drug toxicity/antidote)
Irreversible: Organophosphates (Sarin, Malathion).

Indirect-acting cholinergic agonists: Uses

Increasing muscular strength in patients with myasthenia gravis.
Treating glaucoma.
Treating Alzheimer's disease.
Treating dementia.
Reversing poisoning from anticholinergic drugs.

Indirect-acting cholinergic agonists: Symptoms of Sarin poisoning

Muscarinic: Runny nose, tearing, abdominal pain, vomiting, defecation, urination, and pupil constriction.
Neuromuscular: Twitching, convulsions, bronchoconstriction, and suffocation.
Other: Salivation, lacrimation, urination, defecation, gastrointestinal distress, and emesis.

Myasthenia Gravis

Autoantibodies generated against NM receptors, blocking the ability of ACh to activate the receptors.
Cholinesterase inhibitors help improve symptoms by increasing ACh levels in the neuromuscular junction, increasing muscle tone.

Alzheimer's Disease

An incurable dementia illness characterized by chronic, progressive neurodegeneration.
Onset usually between ages 45 and 65.
Degeneration of cholinergic neurons and deficiency in ACh is one theory.
Current therapies aim to improve cholinergic transmission within the CNS.

Cholinergic Antagonists (Parasympatholytics)

Antimuscarinic drugs:
- Atropine: inhibits ACh, occupying mainly muscarinic receptors. Used for preoperative medication, to dilate pupils for eye exams, antispasmodic treatment of peptic ulcers, and to treat bradycardia.
- Ipratropium bromide: anticholinergic bronchodilator used for asthma and COPD.
- Scopolamine: available orally/topically; used for motion sickness.
Ganglionic blockers: Hexamethonium inhibits nicotinic receptors at autonomic ganglia, preventing nerve signal transmission. Affects sympathetic (decreases heart rate, lowers blood pressure, vasodilation) and parasympathetic (reduces GI motility, secretions).
Neuromuscular blockers (NMB):
- Competitive blockers (Nondepolarizing): D-tubocurarine (Curare), Atracurium
- Depolarizing: Succinylcholine (SCh): used in rapid endotracheal intubation; a quaternary ammonium compound that mimics acetylcholine, causing persistent depolarization leading to flaccid paralysis.

Anticholinergic Uses

Glaucoma.
Asthma.
Irritable bowel.
Urinary urgency.
Poisoning/overdose of cholinesterase inhibitors.
Muscle spasms

Other Anticholinergic Drugs

Botulinum Toxin (Botox): Inhibits acetylcholine release from presynaptic nerve terminals, causing flaccid paralysis. Used for treating muscle spasms, chronic migraines, and cosmetic treatment for facial lines.

Adverse Effects of Cholinergic Antagonists

Dry mouth
Constipation
Flushing
Dry skin (decreased sweating)
Mydriasis
Blurred vision
Palpitations
Tachycardia
Urinary Retention

Contraindications of Cholinergic Antagonists

Glaucoma
Myasthenia gravis
Myocardial ischemia

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