Pharmacology of Cholinergic Transmission

Comprehensive practice flashcards based on lecture notes for cholinergic transmission, covering neurotransmitter synthesis, receptor types, and major pharmacological agonists and antagonists.

Cholinergic transmission

Neurohumoral transmission at a synapse or neuroeffector junction in which acetylcholine acts as a humoral agent for the transmission of action potential across the junction.

Choline acetyl transferase (CAT)

The enzyme synthesized in the perikaryon and transported to the axon terminal that catalyzes the final step in the synthesis of acetylcholine: the acetylation of choline with acetyl coenzyme A.

Hemicholinium

A substance that inhibits the transport of choline from extracellular fluid to the cytoplasm.

Vesamicol

A drug that blocks the carrier-mediated transport used to package acetylcholine into synaptic vesicles at high concentrations.

Exocytosis

The process by which acetylcholine is released, triggered by $Ca^{2+}$ mediation; at the neuromuscular junction, one presynaptic nerve impulse releases $100-500$ vesicles.

Acetylcholine esterase (AChE)

Specific enzyme bound to the basement membrane between pre- and post-synaptic membranes that rapidly inactivates acetylcholine by hydrolysis into acetic acid and choline.

True Cholinesterase (Acetylcholinesterase)

A type of cholinesterase found at all cholinergic sites, RBCs, and gray matter; it hydrolyzes acetylcholine very fast and is more sensitive to Physostigmine.

Pseudo-cholinesterase (Butyrylcholinesterase)

A type of cholinesterase found in plasma, liver, intestine, and white matter; it is more sensitive to organophosphates and hydrolyzes ingested esters.

Parasympathomimetics (Cholinomimetics)

Drugs that facilitate or mimic some or all of the actions of the parasympathetic nervous system, classified as direct acting (agonists) or indirect acting (anticholinesterases).

Bethanechol (Urecholine)

A direct-acting muscarinic agonist indicated for urinary retention after surgery or postpartum.

Succinylcholine

The only depolarizing muscle relaxant currently in use; it causes overstimulation resulting in depolarizing blockade and is used for muscle relaxation/paralysis during intubation.

Edrophonium (Tensilon)

A reversible indirect-acting cholinergic agonist used in the diagnosis of Myasthenia Gravis.

Donepezil (Aricept)

A reversible Indirect Acting Cholinergic Agonist used to increase cerebral concentrations of acetylcholine in patients with Alzheimer's disease.

Echothiophate (Phospholine)

An irreversible indirect-acting cholinergic agonist that permanently inactivates acetylcholinesterase, used to treat Glaucoma.

SLUDWARMF

A mnemonic for the toxic effects of cholinergic agonists: Sweating, Lacrimation, Urination, Diarrhea, Wheezing, Accommodation, Rhinorrhea, Miosis, and Fasciculations.

Parasympatholytics (Anticholinergics)

Drugs that reduce or inhibit the actions of the parasympathetic nervous system by blocking muscarinic or nicotinic receptors.

Atropine

A competitive tertiary amine belladonna alkaloid that blocks muscarinic receptors both centrally and peripherally, lasting about $4$ hours (except topically in the eye).

Mydriasis

The dilation of the pupil, often resulting from muscarinic receptor blockade in the eye by drugs like atropine.

Cycloplegia

The inability to focus for near vision due to paralysis of the ciliary muscle.

Xerostomia

Dryness of the mouth produced by atropine through the blockade of muscarinic receptors in the salivary glands.

Scopolamine

A tertiary amine plant alkaloid more effective than atropine on the CNS; it is one of the most effective anti-motion sickness drugs available.

Ipratropium and Tiotropium

Quaternary derivatives of atropine delivered via inhalation for the treatment of bronchospasm associated with COPD; they do not enter the systemic circulation or CNS.

Tropicamide

An ophthalmic solution used for mydriasis and cycloplegia that has a duration of action of approximately $6$ hours.

Neuromuscular-blocking agents

Drugs that block cholinergic transmission between motor nerve endings and nicotinic receptors on skeletal muscle, primarily used as muscle relaxant adjuvants in anesthesia.

Nondepolarizing (competitive) blockers

Drugs like tubocurarine, cisatracurium, and rocuronium that compete with ACh at nicotinic receptors without stimulating them, preventing muscle contraction.

Depolarizing Phase I

The initial stage of succinylcholine action where the membrane depolarizes, resulting in transient fasciculations followed by flaccid paralysis.

Depolarizing Phase II

The stage where the muscle membrane repolarizes but the receptor is desensitized to the effect of acetylcholine, leading to a resistance to depolarization.

Malignant hyperthermia

A potentially fatal adverse effect induced by succinylcholine in susceptible patients, characterized by a rapid rise in body temperature.