| Class | SSRI/SNRI |
|---|---|
| Chemistry |
Too chemically diverse to group
|
| Routes of administration |
Oral only |
| Absorption |
They vary: eg. venlafaxine is well absorbed but duloxetine is acid-labile and degraded by stomach acid (thus, requires enteric-coated tablets).
|
| Solubility |
pKa ~10, highly lipophilic
|
| Distribution |
Again tyhey differ: venlafaxine has minimal interest in binding to protein and has a VOD of ~ 6-7L/kg; whereas others (eg. duloxetine) are highly protein-bound and have VODs in the 20-25L/kg range
|
| Metabolism |
Extensive hepatic metabolism to mostly inactive metabolites
|
| Elimination |
Elimination is mostly hepatic and of its metabolites is mainly renal.
|
| Time course of action |
For some (eg venlafaxine) half-life is about 4 hours, which called for an extended release formulation; whereas for others (eg. duloxetine) the half life is about 12 hours. These get longer in overdose, as gut motility becomes affected.
|
| Target receptor |
Serotonin reuptake transport protein (SCL6A4, or SERT), as well as noradrenaline reuptake transporter (NET). Of its two enantiomers, (−) enantiomer inhibits noradrenaline and serotonin presynaptic reuptake, while the (+) enantiomer primarily inhibits serotonin reuptake |
| Mechanism of action |
By inhibiting the reuptake of serotonin and noradrenaline from the synaptic cleft, SSRI/SNRI drugs increase monoamine neurotransmission, which is thought to be involved in mood regulation. |
| Clinical effects |
Agitation, diarrhoea, loss or gain of weight, vertigo; risk of serotonin syndrome with overdose (i.e. similar side effect profile to SSRIs) |
| Literature reference |
Holliday (1995) |
| CICM details of understanding | Level 3 |
| Mentioned around Deranged Physiology | |
| Related SAQs |