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Monoamine Oxidase Inhibitors

Chemistry

Hydrazine derivative –Phenelzine/Isocarboxazid

Non-hydrazine derivatives –rest all

Tranylcypromine also has amphetamine like activity

Pharmacokinetics

Monoamine oxidase is present in many areas of the body, in vast numbers in gut wall, when given orally extensive blocking of enzymes in gut wall takes place. Other routes of administration are also tried e.g. Selegiline is prepared as transdermal patch as well as sublingual preparation. These drugs undergo metabolism via different pathways e.g. hydroxylation, acetylation, N and D methylation.

Mechanism of action

MAO exists in two isoforms:

  1. A –present in noradrenergic, dopaminergic neurons mainly responsible for degradation of norepinephrine, epinephrine, serotonin, dopamine and tryptamine. This enzyme is mainly found in gut, liver, placenta and brain.
  2. B –mainly responsible for degradation of monoamines. Mainly present in serotonergic, histaminergic neurons, responsible for degradation of phenyl ethyl amine, tyrramine, benzylamine, dopamine, tryptamine.

This enzyme is present mainly in brain, in platelets and in liver.

These drugs also cause CNS stimulation, responsible for adverse effects, like agitation, insomnia, irritability, etc.

Adverse effects
  1. Orthostatic hypotension –seen because MAO inhibitors change amines in food or other into octopamine, replacing norepinephrine acting as false neurotransmitter, leading to decreased levels of released norepinephrine.
  2. Weight gain
  3. Sedation
  4. Also amphetamine like effects –CNS stimulation, insomnia, irritability
  5. Cause diminished sexual functions, like other antidepressants when discontinued abruptly
  6. Discontinuation syndrome
  7. Excitement, confusion, delirium
Drug interactions
  1. Cheese reaction

Food –containing tyramine or other amines when given in large quantity to patient on MAO inhibitors, normally tyramine is taken from food and metabolized by MAO in gut, so less reaches circulation. If MAO is blocked, amines are not metabolized and pass from gut to circulation, to sympathetic nerve endings. Acting indirectly, displace norepinephrine from nerve endings, leading to episodes of malignant hypertension, which may lead to stroke, cerebral hemorrhage, MI.

Foods like cheese, sugar products, beer, and dried sausages are avoided.

  1. Same is true for sympathomimetic drugs which increase sympathetic activity, leading to hypertension.

At times patient is ignorant of taking drugs like over the counter medications have pseudoephedrine. This has some effects.

  1. Selective serotonin reuptake inhibitors may lead to serotonin syndrome.
Over dosage

Also have over dosage. Patient shows:

  1. Signs of CNS excitement
  2. CVS hyper excitability

Treated conservatively by gastric lavage, vitals, airway, etc.

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