25 - Pharmacology of the Neuromuscular Junction: Lecture Notes Review

Flashcards covering key concepts, drugs, and mechanisms related to the pharmacology of the neuromuscular junction, based on Dr. Kevin Whitehead's lecture notes.

Neuromuscular Junction (NMJ)

The synapse between a motor neuron and a muscle fiber.

Acetylcholine (ACh)

A neurotransmitter involved in synaptic transmission at the NMJ.

Nicotinic Acetylcholine Receptor (nAChR)

A type of receptor found at the muscle endplate that binds to ACh, functioning as an ionotropic or ligand-gated ion channel.

Ionotropic Receptor

A type of receptor that is also an ion channel, opening directly upon ligand binding.

Choline Acetyltransferase (CAT)

An enzyme responsible for the synthesis of acetylcholine from Acetyl CoA and Choline.

Acetylcholinesterase (AChE)

An enzyme that breaks down acetylcholine in the synaptic cleft into Choline and Acetate.

Vesamicol

A drug that blocks the carrier transport of ACh into vesicles in the presynaptic terminal.

Hemicholinium

A drug that blocks the choline transporter, preventing choline uptake for ACh synthesis.

Exocytosis

The process by which neurotransmitter-containing vesicles fuse with the presynaptic membrane to release their contents into the synaptic cleft.

Botulinum Toxin

A presynaptic toxin produced by Clostridium botulinum that blocks the exocytosis of acetylcholine, leading to muscle paralysis.

Clostridium botulinum

The anaerobic bacterium that produces botulinum toxin.

BOTOX

A commercial preparation of botulinum toxin used for local injection to relax muscles, e.g., for wrinkle reduction.

4-aminopyridine (4-AP)

A pharmacological treatment for botulinum poisoning that acts as a blocker of voltage-gated K+ channels, leading to increased ACh release.

Antitoxin

An immunological treatment for botulinum poisoning that involves antibodies against the toxin to prevent its entry into the nerve terminal.

Neuromuscular Blockers

Drugs that act at the nicotinic AChR at the postsynaptic membrane to prevent muscle contraction, often used as an adjunct to general anaesthesia.

Non-depolarising Blockers

A category of neuromuscular blockers that act as competitive antagonists at nAChRs.

Depolarising Blockers

A category of neuromuscular blockers that act as agonists at nAChRs, causing initial depolarization followed by paralysis.

Curare (D-tubocurarine)

An original non-depolarising neuromuscular blocker, derived from a blow-dart poison, acting as a competitive antagonist at nAChRs.

Competitive Antagonists

Drugs that bind to the same receptor site as the natural ligand (ACh) but do not activate it, thereby blocking its action.

Suxamethonium

A depolarising neuromuscular blocker (composed of two ACh molecules linked) that acts as an agonist at nAChRs, causing initial fasciculations followed by prolonged depolarization and paralysis (Phase 1 block).

Fasciculations

Uncoordinated, fine muscle contractions caused by the initial action of depolarising blockers like suxamethonium.

Phase 1 Block

The initial paralysis caused by depolarising blockers due to prolonged depolarization and inactivation of voltage-gated Na+ channels.

Plasma Cholinesterase

An enzyme in the plasma that breaks down suxamethonium, contributing to its rapid action and recovery.

Phase 2 Block

A prolonged paralysis that can occur with suxamethonium, sometimes due to inactivation of nAChRs.

Cholinesterase Inhibitors

Drugs that interact with AChE (and plasma cholinesterase) to prevent the breakdown of ACh, thereby enhancing synaptic function.

Edrophonium

A short-acting cholinesterase inhibitor that interacts ionically with AChE, used diagnostically for Myasthenia Gravis.

Neostigmine

A medium-acting cholinesterase inhibitor that forms covalent bonds with AChE.

Organophosphates

Irreversible cholinesterase inhibitors, often found in chemical weapons and pesticides.

Pralidoxime

A drug used to reactivate AChE after organophosphate poisoning, most effective when given early.

Myasthenia Gravis

An autoimmune disease characterized by muscle weakness due to antibodies attacking and reducing the number of nicotinic AChRs at the NMJ.

Pyridostigmine

A cholinesterase inhibitor with better oral absorption and longer duration of action than neostigmine, used for Myasthenia Gravis.