Slowly replace some norepinephrine at the synapse

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Unformatted text preview: first increases – then decreases norepi False Transmitter Hypothesis MAO Inhibitors prevent breakdown of all these compounds MAO Inhibitors cause excess tyrosine byproducts peripherally because gut and liver enzymes Are also inhibited Tyrosine and its byproducts Look enough like transmitter That they slowly replace some Norepinephrine at the synapse Early extra NE stimulates synapse… Followed by decreased activity As percentage of partial agonist increases However: Sudden food intake Displaces NE from vessicles Resulting in stimulation not inhibition “Lesser” transmitter Decreases effectiveness TYROSINE TYROSINE Autonomic modifiers Autonomic • Monoamine Oxidase Inhibitors - Pargyline Hydrochloride – Mechanism of action - confusing • in CNS, increases norepinephrine (good antidepressant) – Because the MAO can’t break it down (expected) • in SNS, MAO inhibitors first increase norepi – Because the MAO is not breaking it down as much (expected) • then decrease norepi (making it an effective antihypertensive) – Excess of tyrosine (no GI breakdown) replaces some of the NE as tranmitter and it is less effective at stimulating the receptor (false transmitter) – This effect does not occur in CNS because of BB Barrier Autonomic modifiers Autonomic • Monoamine Oxidase Inhibitors - Pargyline Hydrochloride – Mechanism of action - confusing • in CNS, increases norepinephrine • in SNS, first increases then decreases norepi – Side or toxic effects • Acute: – CNS stimulation - hallucination, agitation, convulsions – hypo or hypertension • Chronic: – CNS stimulation - tremors, insomnia, nightmares, mood elevation – rarely confusion & hallucinations – Inhibition of sympathetic nervous system » G.I. - nausea, constipation (common, but cause unknown) » postural hypotension » decreased sexual function » hypertensive crisis may occur (see contraindications) – Contraindications: Foods, Drugs, Renal Failure & Accumulation Non-Autonomic Inhibitors Smooth Muscle Non-Autonomic • Direct Peripheral Vasodilators - hydralazine, minoxidil, pinacidil – Mechanism of action - relaxes smooth muscle of vessels – Side or toxic effects • Na++ fluid retention in some individuals – used with a diuretic • reflex tachycardia due to decreased B.P. – given with beta blockers • some CNS & G.I. effects - mechanism? – Very Common – headache – nausea, loss of appetite – dizziness, sweating +++Do not get...
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This document was uploaded on 02/07/2014.

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