Cholingergics, Anticholingergics and Ganglionic Drugs
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- What receptors are at the end organs?
- Muscarinic ... so no stimulation there by nicotine
- What are muscarinic receptor subtypes?
- M1, M2, M3
- M1 receptor expressed where?
-
CNS, secretory glands in GI
for example: pirenzepine - M2 expression
- myocardium i.e. AF-DX 116
- M3 expression
- everywhere else i.e. tiotropium
- cholinergic agonists?
- bethanecol, muscarine, pilocarpine, methacholine etc
- Bethanecol does what?
- Chol. agonist... trt urinary retention, abd. distension, gastric atony
- Muscarine?
- from Amanita muscarina mushrooms
- Pilocarpine?
- natural cholinergic agonist... topical miotic, glaucoma to decrease pressure
- ACh action on arterioles?
- acts on M3 receptors on vessels, to increase Calcium, activating NO, generating cGMP causing muscle relaxation and reduction in peripheral resistance.
- Mushroom poisoning: inocybe species
- high concentration, fast onset (salivation, lacrimation, headache, nausea, hypotension, shock)... trt with atropine
- Mushroom poisoning: Amanita muscaria
- low conc., fast onset... sx inocybe plus CNS ataxia , mania, hallucinations etc
- Mushroom poisoning: Amanita phalloides
- slow onset.. liver and renal damage, grave prognosis... only supportive trt
- Some Anti-cholinergics Teritary amines
- ipratropium, tiotropium (asthma propylaxis), Tiotropium is M1, M3 selective*** , glycopyrrolate (pre-anesthetic)
- Some signs of atropine toxicity
-
Hot (no sweating), dry, red (peripheral vasodilation), blind (can't focus due to cycloplegia), Mad (stimulations)
trt with: AChE-I (increase local ACh) - Pirenzepine
-
M1 selective antagonist, used in peptic ulcer pts
pire= burning??? - Scopolamine
- sedation drug and antimotion drug
- Nicotine actions?
-
In ganglia, both SNS and PANS activated... at high doses may close a blockade there.
Sensory stim: respir stim., nausea, vomiting, ADH secretion, depression of knee jerk.
Nm receptors on muscle < little activity - What's the oxidation product of nicotine
- cotinine, negligible activity
- therapies for nicotine dependance
- nicotine replacement therapy by patches//// buproprion, an antidepressant that increases dopamine./// varenicline: nicotine receptor partial agonist at alpha 4 beta 2 form.
- non-depolarizing ganglionic blockers
-
hexamethonium, trimethaphan: competitive blockade of nicotinic receptors at ganglion.
Mecamylamine: enters CNS and blocks central nicotine action. ...
No longer used clinically - problems with non-depolarizing ganglionic blockers
- orthostatic hypotension, tachycardia, urinary hesitancy, constipation, cycloplegia, impotence!!!