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Pharm2 Lect 5

Pharm2 AChEsterase Inhibitors

QuestionAnswer
Reversible AChE Inhibitors 1.Physostigmine. 2.Neostigmine. 3.Edrophonium. 4.Edrophonium + Atropine. 5.Pyridostigmine. 6.Ambenonium. 7.Donepezil. 8.Tacrine. 9.Rviastigmine. 10.Galatamine.
Reversible AChE Inhibitors: Physostigmine 1.Mech of action: ALL cholinergic synapses, slows AChE so ACh remains longer, Dec IOP. 2.Boiav: Lipid soluble/crosses BBB. 3.used to treat miotic glaucoma & reverses antimuscarini effects. 4.Adverse effects: Asystole, seizures, Resp problems.
Reversible AChE Inhibitors: Neostigmine 1.Mech of action: Mainly Nm receptors in NMJ than ANS ganglia, Inc muscle strength (if too long: muscle weakness b/c no repolariz). 2.Bioav: Quaternary ammonia compound. 3.Used to treat post-op urinary retention & abdominal distention, Myasthenia gravis
Reversible AChE Inhibitors: Edrophonium 1.Mech of action: reversible AChE inhibitor at NMJ (Inc muscle strengthh). 2.Bioav: Short (less potent than neostigmine). 3.Used to asses adequacy of neo/pyridostigmine, differentiate b/w Myasth Gravis or cholinergic crisis
How is Edrophonium used to asses Neostigmine dosage in Myasthenia Gravis patients? Pt is weak, give Edrophonium: 1.If Inc or no change in Weakness: neostig dose is too HIGH. 2.If Dec in Weakness, neostig dose is too LOW
Reversible AChE Inhibitors: Pyridostigmine 1.Mech of action: reversible AChE inhibitor at NMJ, direct action of Nm receptors (Inc muscle strength). 2.Quaternary ammonia compound. 3.Myasthenia gravis.
Difference in treatment time using Neostigmine, Edrophonium, & Pyridostigmine 1.Neo: lasts 2-4hrs. 2.Edroph: lasts 3-4min (IV only). 3.Pyrido: lasts 3-6hrs (XR lasts 12 hrs). **short half-life decreases side effects.
Reversible AChE Inhibitors: Ambenonium Mechanism of action: Reversible AChE inhibitor.
Reversible AChE Inhibitors: Donepezil 1.Mech of action: reversible AChE inhibitor slows AChE activity. 2.Bioav: Works in CNS. 3.Used to treat Alzheimer's Disease
Reversible AChE Inhibitors: Tacrine 1.Mech of action: reversible AChE inhibitor slows AChE activity. 2.Bioav: Works in CNS. 3.Used to treat Alzheimer's Disease
Reversible AChE Inhibitors: Rivastigmine 1.Mech of action: reversible AChE inhibitor slows AChE activity. 2.Bioav: Works in CNS. 3.Used to treat Alzheimer's Disease
Reversible AChE Inhibitors: Galantamine 1.Mech of action: reversible AChE inhibitor slows AChE activity. 2.Bioav: Works in CNS. 3.Used to treat Alzheimer's Disease
What is the ultimate effect of all reversible AChE inhibitors? Prolonged ACh activity. **the Inhibitors take several hours for AChE to hydrolyze
Which reversible AChE inhibitor will have Inc CNS side effects? Physostigmine, b/c it is lipid soluble and can cross the BBB.
2 reversible AChE inhibitors that have a direct action on Nm receptors 1.Neostigmine. 2.Pyridostigmine. **Both used to treat MG. **NOT lipid soluble
2 drugs used to treat Post-op abdominal distention & urinary retention? 1.M3 Agonist: Bethanechol. 2.Reversible AChE Inhibitor: Neostigmine
Why are reversible AChE inhibitors better at treating MG than M3 agonist? B/c AChE inhibitors allow for that NMJ contraction ONLY when the brain wants it to happen instead of a generalize NMJ contraction thoughout the body
Would you use Edrophonium for chronic muscle weakness (ex: MG)? NO, it is IV only and only lasts 3-4mins
Why does too much neostigmine cause muscle weakness? Depolarization blockade: constant depolarization from ACh activation prevents repolarization which affects ion balances.
Irreversible AChE Inhibitors 1.Echothiophate. 2.Diisoprophyl fluorophosphates (DFP). 3.Tetraethyl pyrophosphate (TEPP). 4.Parathion. 5.Malathion. 6.Sarin. 7.Soman. 8.Tabun. **6-8 nerve gas, 3-5 insecticides
Adverse Effects of Irreversible AChE inhibitors 1.Lens Opacities (Echothiophate only). 2.Chronic Neurotoxicity. 3.Cholinergic overstimulation. 4.Cholinergic crisis.
Irreversible AChE Inhibitors: Echothiophate 1.Mech of action: Contracts ciliary m, Inc aq humour outflow, Dec IOP. 2.Bioav: (+) charged, not volatile (preferred over DFP). 3.Used to treat Mitotic glaucoma (LAST RESORT).
Irreversible AChE Inhibitors: Diisoprophyl fluorophosphates (DFP) 1.Mech of action: Contracts ciliary m, Inc aq humour outflow, Dec IOP. 2.Bioav: Highly lipid soluble, volatile. 3.Used to treat Mitotic glaucoma (LAST RESORT).
Irreversible AChE Inhibitors: Tetraethyl pyrophosphate (TEPP) Irreversible AChE inhibitor that is well absorbed in gut, skin, & conjunctiva. Dangerous to humans. **Organophosphate insecticide
Irreversible AChE Inhibitors: Parathion Not used clinically, accidental poisoning. well absorbed in gut, skin, & conjuctiva. **Organophosphate insecticide
Irreversible AChE Inhibitors: Malathion 1.Mech of action: detoxed by plasma carboxylesterases. 2.Bioav: well absorbed in gut, skin, & conjuctiva. 3.Used to treat Head lice.
Irreversible AChE Inhibitors: Sarin, Soman, & Tabun Lethal nerve gas AChE irreversible inhibitors
Mechanism behind all Irreversible AChE inhibitors? Irreversibly phosphorylate AChE. **EX: P-O bond formed by sarin can't be hydrolyzed.
Rank toxicities of Malathion, Parathion, & Sarin Sarin >>>>> Parathion > Malathion.
Differentiate b/w Neostigmine, Physostigmine, & Organophosphates 1.Neo: reversible, does NOT cross BBB. 2.Physo: reversible, DOES cross BBB. 3.Organophosphate: IRreversible, DOES cross BBB.
Symptoms of Cholinergic Overstimulation/Crisis 1.Miosis. 2.Spasm of accomodation. 3.Inc Salivation. 4.Inc Sweating. 5.Bronchoconstriction. 6.Vomiting (GI stim). 7.Diarrhea (GI stim). 8.Bradycardia. 9.Hypotension. 10.Urinary urgency.
Pralidoxime (2-PAM) 1.Mech of action: AChE reactivator. 2.Bioav: NMJ & ANS ganglia effector site. 3.Used to treat cholinergic crisis from organophosphate poisoning.
Will 2-PAM prevent cholinergic chrisis from neostigmine overdose? NO!! it only works on organophosphates by breaking the P=O bond. (Sarin, Soman, Tabun). **there is a C=O bond with neostigmine.
Created by: WeeG
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