K2iv: MoA, AE of TCAs, SSRIs & MAOIs

  • Amine hypothesis = basis of AntiD’s
  • Brain amines (5HT, NA) are NT3 which function in mood regulation
    • ↓amine activity = D symptoms
    • ↑amine activity = mood elevation

5 MAJOR groups of AntiD’s to ↑amine activity

  • TCAs
  • SSRI
  • SNRI
  • MAOI
  • Others

Example

TCAs

Amitriptyline

SSRIs

Fluoxetine

MAOIs

Phenelzine

MoA

TCAs

Competitively block neuronal uptake (uptake 1) of NA & 5HT

↑[NTs] at synapse

SSRIs

Selectively inhibit 5HT reuptake

MAOIs

MAO = enzyme of nerves, gut, liver which deaminates & inactivates any excess NA, dopamine, 5HT

MAO binds reversibly/irreversibly to inactivate this enzyme

∴↑[NTs]

2 types:

  1. Older = inhibits MAO A+B, irreversible
  2. Newer = inhibit MAO A, reversible

A/E

TCAs

Also blocks muscarinic, histaminergic, α-adrenoreceptors

CNS – sedation, seizures

Antichols – dry mouth, constipation, urinary retention, blurry vision

CVS – postural hypotension

SSRIs

Less sedation/antichol/cardiotoxic

But must NOT be started until 2/52 after stopping MAOIs

Headache, sweating, anxiety

GI – N&V, diarrhoea

Sexual dysfunction, Weakness, Fatigue

SEROTONIN SYNDROME – admin of multiple serotonergic drugs → fatal

  • SSRI + MAOI
  • SSRI + pethidine
Libby Zion Law

MAOIs

MAOIs somprimise metabolisms of exogenous amines

 TYRAMINE (cheese, wine) → causes excess catecholamine release

Severe hypertension

Headache

↑HR

Arrhythmias

Drug Interactions

TCAs

↑sensitivity to catechols

Predispose to arrhythmias with sympathomimetics

Enhance CNS depressant effects (i.e. EtOH)

Drugs which inhibit CYP450 = ↓TCA metabolism = ↑[TCA] plasma

SSRIs

Inhibits CYP450

∴↑plasma [  ] of TCAs, neuroleptics, anti-arrhythmics & β-blockers

MAOIs

Linezolid → also a MAOI

Indirect sympathomimetics (cough medicines, ephedrine, pethidine)

Must stop MAO 2/52 before starting new antidepressant Rx