Cholinoceptor-Activating Drugs Quiz

Study Notes

Cholinoceptor-Activating & Cholinesterase-Inhibiting Drugs

Cholinomimetics either directly act on acetylcholine receptors or indirectly inhibit cholinesterase.
There are two types of acetylcholine receptors: muscarinic and nicotinic.
Muscarinic receptors are G protein-coupled receptors (GPCRs).
Nicotinic receptors are located on a channel protein that is selective for sodium and potassium.
Neostigmine is a prototypic carbamate, whereas parathion, an important insecticide, is a prototypic organophosphate.
Organophosphates are clinically important due to accidental exposure.
Edrophonium has a very short duration of action.
Carbamates are released by cholinesterase in 2-8 hours, while organophosphates form a stable complex and release the phosphoric acid residue over days to weeks.
Inhibiting cholinesterase increases acetylcholine concentration, half-life, and actions in synapses, leading to both muscarinic and nicotinic effects.
Carbamates are used for therapeutics, particularly for myasthenia treatment (an autoimmune disorder).
Rivastigmine, a carbamate, is used for Alzheimer's disease.
Some carbamates and organophosphates are used as pesticides.
Symptoms of organophosphate poisoning include: diarrhea, urination, miosis, bronchoconstriction, bradycardia, excitation, lacrimation, salivation, and sweating (DUMBBELSS).
Bethanechol and neostigmine have significantly different effects on vascular endothelium.
Parathion is highly lipid-soluble; Duration: days to weeks.
Parathion is highly dangerous; causes all parasympathetic effects plus muscle paralysis and coma.

Direct-Acting Cholinergic Drugs

These are choline esters and alkaloids.
Some drugs are used for specialized applications (e.g., neonicotinoids).
Muscarinic agonists mimic parasympathetic nerve stimulation, affecting additional functions.
There are five subgroups of muscarinic receptors.

Indirect-Acting Cholinergic Drugs

These include organophosphates (very long-acting) and carbamates (intermediate to long-acting).

Clinical Uses

Direct-acting nicotinic agonists are used in medicine to assist smoking cessation (varenicline) and to produce skeletal muscle paralysis (succinylcholine).
Indirect-acting agents are used when increased nicotinic activation is needed at the neuromuscular junction (see discussion of myasthenia gravis).
Nicotine and related neonicotinoids are used as insecticides despite reported toxic effects on bee colonies.

Toxicity

Toxic effects of muscarinic agonists include: CNS stimulation, miosis, spasm of accommodation, bronchoconstriction, excessive gastrointestinal and genitourinary smooth muscle activity, increased secretory activity, and vasodilation.
Toxic effects of nicotinic agonists include: ganglionic stimulation and block and neuromuscular end-plate depolarization leading to fasciculations and then paralysis.

Effects of cholinoceptor-activating and cholinesterase-inhibiting drugs on major organ systems.

CNS: complex stimulatory effects. Nicotine: in small doses elevation of mood, alerting, addiction (nicotine-naïve individuals often suffer nausea and vomiting on initial exposure); large doses: seizures.
Eye: Sphincter muscle of iris: contraction (miosis). Ciliary muscle: contraction (accommodation for near vision), cyclospasm.
Heart: Sinoatrial node: Decrease in rate (negative chronotropy). Atria: Decrease in contractile force (negative inotropy), decrease in refractory period. Atrioventricular node: Decrease in conduction velocity (negative dromotropy), increase in refractory period. Ventricles: Small decrease in contractile force.
Blood vessels: Dilation via release of EDRF from endothelium.
Bronchi: Contraction (bronchoconstriction).
Gastrointestinal tract: Increase in smooth muscle contraction, increased peristalsis. Motility: Increase in motility. Sphincters: Decrease in tone, relaxation (Exception: gastroesophageal sphincter contracts).
Urinary bladder: Detrusor: Increase in contraction. Trigone and sphincter: Relaxation; voiding.
Skeletal muscle: Activation of neuromuscular end plates, contraction.
Glands (exocrine): Increased secretion (thermoregulatory sweating, lacrimation, salivation, bronchial secretion, gastrointestinal glands).

Description

Test your knowledge on cholinomimetics and cholinesterase inhibitors, including drug mechanisms and receptor types. Dive into the specifics of drugs like neostigmine, edrophonium, and parathion, along with their clinical relevance. This quiz will challenge your understanding of acetylcholine's role in the body.