A.26 Flashcards
Tricyclic, tetracyclic and unicyclic antidepressants. MAO-inhibitors
Clomipramine,
Amitriptyline,
Moclobemide
MAO
-MAO-A breaks down: Dopamine, Serotonin, Norepinephrine
-MAO-B breaks down: Dopamine
Clomipramine, Amitryptiline
MOA: Tricyclic ADs (TCAs) inhibit the NE and 5HT reuptake transporters (NET & SERT),
antagonizes: M-AChR, α1, H1, 5HT2;
Effect: elevate mood, improved mental alertness, increase physical activity;
IND: 2nd choice of drug for major depression, phobia/manic anxiety, neuropathic pain, migraine, enuresis;
SEs: -anti-M- delirium, dry mouth, blurred vision, urinary retention, constipation.
-anti-α1- dizziness, hypotension, reflex tachycardia.
-anti-H1- sedation, dizziness, confusion, weight gain.
-anti-5HT2- weight gain, sexual dysfunction.
TCAs are cardiotoxic (arrhythmias, QT↑);
ROA: p.o;
Extra: good BAp.o, lipophilic (can cross BBB), hepatic metabolism by CYP2C19;
T1/2: 8-36h;
Intoxication antidote: NaHCO3;
Contra-IND: can’t take it with serotonergic agents (serotonin syndrome)
Moclobemide
MOA: selective and reversible MAO-A inhibitor;
Effect: Increased NE→ hypertensive crisis (symptoms: ↑BP, arrhythmias, hyperthermia, excitation);
IND: depressed patients who do not respond to the classic treatment of reuptake inhibitors (TCAs/SSRIs); SEs: (!less severe SEs than irreversible MAO-A inhibitors!) “cheese effect”, orthostatic hypotension, insomnia, sexual dysfunction, seizures;
Extra: antidepressant effect achieved after 2-4 weeks; ROA: p.o; T1/2: long
MAO-A
found in GI and neurons, has affinity to NA, 5HT and tyramine
MAO-B
found in glial cells and platelets, has affinity to DA
“Cheese effect”: MAO inactivates tyramine (naturally occuring monoamine found in aged cheese and wine). Tyramine acts as a cathecolamine releasing agent→ if MAO is inhibited more tyramine will result in the release of large amounts of cathecolamines→ HTN crisis, tachycardia, arrhythmias and possibly stroke.
