- Block both SERT (sertraline) and NET (noradrenaline) re-uptake transporters on pre-synaptic membranes
- Increased levels of 5-HT, noradrenaline and dopamine within neuronal synapses
Serotonin and Noradrenaline Reuptake Inhibitors
Serotonin and Noradrenaline Reuptake Inhibitors
- SNRIs are second-generation anti-depressants
- Examples include:
- Duloxetine
- Venlafaxine
- In addition, duloxetine is the first-line drug in painful diabetic neuropathy
Absorption
- Duloxetine is enteric coated to prevent degradation by stomach acid
- Oral bioavailability 50%
- Venlafaxine oral bioavailability 92%
Distribution
- Duloxetine
- >90% plasma protein bound to albumin and a1-acid glycoprotein
- Volume of distribution of 1640L
Metabolism
- Duloxetine undergoes hepatic metabolism via CYP1A2 and CYP2D6 to inactive metabolites
- Venlafaxine undergoes hepatic metabolism via CYP2D6 to the active metabolite desmethylvenlafaxine, which retains 100% activity
Excretion
- Duloxetine
- Single-dose elimination half-life is 10-12hrs
- 70% excreted in urine as inactive metabolites
- 20% excreted in faeces
- <1% excreted unchanged
- Venlafaxine
- Predominantly renally excreted
- Has a short elimination half-life, meaning even single missed doses can trigger withdrawal
Cardiovascular
- Dose-dependent hypertension
Neurological
- Drowsiness, headache, agitation
- Risk of serotonin syndrome
Gastrointestinal
- Nausea
- Vomiting
- Diarrhoea
- Venlafaxine can cause hepatic injury, believed to be related to CYP2D6 polymorphisms