Parasympathomimetic Case Studies

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Carbachol = cholinomimetic drug that binds and activates the acetylcholine receptor. It is a cholinergic agonist used for treating glaucoma or during ophthalmic surgery.
Choline carbamate
Positively charged quaternary ammonium compound
Not well absorbed in GIT tract and does not cross the BBB
Not easily metabolised by cholinesterase
2-5 min onset of action
Duration of action 4-8 hours (topical), 24 hours for intraocular administration
Parasympathomimetic that sitmulates both muscarinic and nicotinic receptors

Methacholine = Synthetic choline ester, acts as a non-selective muscarinic receptor agonist in the parasympathetic nervous system. Used to diagnose bronchial hyperreactivity (asthma and chronic pulmonary obstructive disease).
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Interferes with the breakdown of ACh – stimulates nicotinic and muscarinic receptors. Unlike physostigmine, neostigmine has a quatermary nitrogen, thus is more polar and does not enter the CNS. Effect on skeletal muscle is greater than physostigmine. Moderate duration of action, like 2-4 hours. Binds to the anionic and esteric site of AChE. Drug blocks active site of AChE so it can’t break down the ACh before they reach the postsynaptic membrane receptors. Used to improve muscle tone in people with myasthenia gravis and in anaethesia to reverse effects of nnon-depolarising muscle relaxants.
Edrophonium readily reversible AChE inhibitor. Prevents breakdown of ACh by competitively inhibiting ACHe mainly at the neurmuscular
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Edrophonium reduces the muscle weakness prolonging ACh presence in synaptic cleft.
Myasthenia gravis – the antibodies attack/block/destroy the nicotinic acetylcholine receptors so edrophonium reduces muscle weakness.
In cholinergic crisis (person has too much stimulation) edrophonium makes muscle weakness worse by inducing a depolarising block.
LEMS – neuron is unable to release enough ACh for normal muscle function due to autoantibodies P/Q type calcium channel necessary for acetylcholine release so there is insufficient calcium ion influx thus reduced ACh release. Thus not much increase in muscle strength after edrophonium injection, if any.

Malathion = organophosphate parasympathomimetic – irreversible binding to cholinesterase. Used as an insecticide of low human toxicity.

Malaoxon - a phosphorothioate – breakdown product of malathion and is much more toxic. Ester.
Atropine
Tropane alkaloid extracted from deadly nightshade (atropa bellabonna) etc. Secondary metabolite of these plants. Drug – wide variety of

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