Duloxetine

Class SSRI/SNRI
Chemistry
Phenoxyphenylpropylamine
Routes of administration

Oral only

Absorption
Acid-labile; degraded by stomach acid (thus, requires enteric-coated tablets). Bioavailability is 50%
Solubility
pKa 9.34; very poor water solubility
Distribution
VOD=25L/kg; 90% protein bound
Metabolism
Hepatic metabolism into numerous metabolites, mainly by oxidation in the naphthyl ring followed by further oxidation, methylation and conjugation
Elimination
Elimination of inactive metabolites is mainly renal
Time course of action
Half life is about 12 hours
Target receptor

Serotonin reuptake transport protein (SCL6A4, or SERT), as well as noradrenaline reuptake transporter (NET).

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). Additionally, duloxetine can sometimes have anticholinergic side effects, such as xerostomia and urinary retention

Literature reference

Knadler et al (2011)

CICM details of understanding Not specifically listed in the CICM syllabus
Mentioned around Deranged Physiology
Related SAQs