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:
- Older = inhibits MAO A+B, irreversible
- 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
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