Pharm7 Cholinergics

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prototype indirect-acting cholnesterase inhibitor

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Neostigmine

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Muscarinic cholinomimetic which is resistant to ChE with poor lipid solubility

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Bethanechol

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Muscarinic cholinomimetic with good lipid solubility used as an insecticide which causes mood elevation

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Pilocarpine

also not hydrolyzed by ChE

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Cycloplegia

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Paralysis of accommodation

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Side effects of ChE inhibitors

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Diarrhea
Urination
Miosis
Bradycardia
Bronchoconstriction
Excitement (SkM/CNS)
Lacrimation
Salivation
Sweating

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alcohol used for testing of Myasthenia Gravis + Results

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Endrophonim

if MG, will improve symptoms
if Choline Crisis, will make worse

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Muscarinic activation of DAG pathway results in

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Secretion

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Muscarinic activation of the IP3 pathway results in

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Smooth muscle activation

M3 most responsible

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What is the mechanism of Nicotinic stimulation

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Acts @ Na/K channel causing depolarization and AP

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Parasympathetic effect on blood vessels?

Cholinomimetic effect on blood vessels?

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PS does not effect the uninnervated muscarinic receptors, therefore causes bradycardia

Cholinomimetics cause vasodilation and reflex tacchycardia

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Sweating is a _____ response, therefore caused by cholinomimetics and not their PS stimulation

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sympathetic

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Nicotinic (varencycline) response in:
1 BV
2 Gut
3 SkM

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1 vasodilation
2 motility and secretion
3 fasiculations and spasm --> paralysis

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Successful at producing paralysis

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Succinylcholine

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Used to reduce nicotine cravings

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Varencycline

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responsible for mushroom poisoning symtoms of NVD

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Muscarine

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Serious effects of Amanita Phalloides mushroom

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Hepatic and renal necrosis

caused by Amanitin/Phalloidin, RNA polymerase inhibitors

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Nicotinic Toxicity effects

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Fasculations and paralysis
Convulsions and depression

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Prototype carbamic acid ester (ChEi)

duration?

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Neostigmine

2-8 hours

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Prototypic Organophosphate (ChEi)

duration?

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Parathion, insecticide

irreversible, days to weeks

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Mechanism of ChEis

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binding to ChEi acidic portion prevents hydrolysis of endogenous ACh

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Difference in site of action between direct and indirect Cholinomimetics?

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Indirects (ChEis) do not act at uninnervated sites, therefore do not cause vasodilation and reflex tachycardia

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Treatment for Myasthenia Gravis

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Neostigmine

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ChEi used in Alzheimers

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Rivastigmine

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Organophosphate used as a scabicide

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Malathion

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Organophosphate used as anti-helminthic

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Metrifonate

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ChEi used for rapid reversal of MG and MG testing

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Endrophonium

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Antidote for organophosphate toxicity?

no effect on?

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Atropine

nicotinic signs

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Antidote for Organophosphate toxicity if acute?

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Pralidoxime

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Toxcity of Indirects?

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DUMBBELSS

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Why are Malathion/Dichlorvos safe in humans?

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metabolized to inactive state by humans, not insects

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-thions are lipid soluble, readily entering the ___/____

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skin/lungs

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#1 cause of death in ChEis (organophosphates/carbamates)

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Respiratory Failure

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used in bladder and bowel atony

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Bethanechol

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used in Sjogren's Syndrome

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Pilocarpine (increases salivation)

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Reversal of severe Atropine poisoning

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Physostigmine

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Organophosphate which is a terrorist threat

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Sarin

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Indirect Cholinomimetics used in Alzheimers (3)

side fx?

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Rivastigmine
Galantamine
Donepezil

N/V

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Which is more toxic, parathion or malathion

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Parathion

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Pilocarpine's effect on SmM is mainly through which receptor

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M3

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Indirect with poor lipid solubility (poor CNS effects)

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Neostigmine

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Indirect with good lipid solubility and significant CNS effects

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Physostigmine

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Primary secondary messenger used in the contraction of ciliary muscles in accommodation

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IP3

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Glaucoma, Pupillary contraction, relief of intraocular pressure

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Carbachol

direct Ch agonist

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Potent stimulator of sweat, tears, saliva

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PILOcarpine

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Challenge test for diagnosis of Asthma

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Methacholine

stimulates muscarinic receptors when inhaled

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Reversal of postoperative neuromuscular junction blockade (no CNS effects)

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NEOstigmine

NEO-effects on CNS

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long acting treatment of MG

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Pyridostigmine

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Atropine overdose

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Physostigmine

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Watch for exacerbation of __(3) with cholinomimetic agents

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COPD
Asthma
Peptic Ulcers

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used for postoperative and neurogenic ileus and urinary retention

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bethanechol

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only direct acting agent that is very lipid soluble and used in glaucoma

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Pilocarpine

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This agent used to treat dry mouth in Sjogrens syndrome

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cevimeline

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indirect acting ACh agonist, alcohol, short DOA and used in dx of MG

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Endrophonium

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Carbamate with intermediate action, used for +A1170 postoperative and neurogenic ileus and urinary retention

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neostigmine

NeO CNS effects

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Tx of atropine OD and glaucoma (bc lipid sol). enters CNS rapidly and has a stimulant effect which may lead to convusiols

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physostigmine

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tx of MG

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Pyridostigmine

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antiglaucoma organophosphate

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echothiophate

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assoc with an increased incidence of cataracts in patients treated for glaucoma

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long acting ChI inhibitors

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Scabicide organophosphate

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malathion

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antihelminth ChIi

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Metrifonate

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organophosphate tox

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DUMBBELSS
diarrhea
urination
miosis
bronchoconstriction
bradycardia
excitation
lacrimation
salivation
sweating

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The most frequent cause of acute deaths in ChI toxicity

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Resp failure

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the most toxic organophosphate

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parathion

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tx of organophosphate OD

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atropine

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acute organophos OD tx

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Pralidoxime