Anticholinesterase effects on ganglia, circulation and skeletal muscle
THE CONTEXT
Anticholinesterases prolong acetylcholine action, but their effects differ by site and dose because muscarinic, ganglionic and neuromuscular responses interact.
Ganglia
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Local acetylcholine hydrolysis is less important in ganglia; inactivation occurs partly through diffusion and hydrolysis in plasma.
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Anticholinesterases stimulate ganglia primarily through ganglionic muscarinic receptors.
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High doses cause persistent depolarization of ganglionic nicotinic receptors, leading to transmission blockade.
Cardiovascular effects
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Muscarinic action produces bradycardia and hypotension, with the fall in blood pressure mainly attributable to bradycardia.
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Ganglionic stimulation tends to increase heart rate and blood pressure.
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Medullary stimulation followed by depression, and ganglionic blockade at high doses, further complicate the response.
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Overall cardiovascular effects depend on the agent and dose and are often unpredictable. Moderate doses of many anticholinesterases commonly produce bradycardia with a small rise in blood pressure.
Skeletal muscle effects
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Acetylcholine released by a single nerve impulse persists, rebinds the same receptor, diffuses to neighbouring receptors and causes retrograde activation of prejunctional fibres.
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The resulting repetitive firing produces twitching and fasciculations.
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Contractile force increases in partially curarized and myasthenic muscles, while twitching is not prominent in these muscles.