Sarala, 28 years old lady was suffering from depression. The physician prescribed
tablet fluoxetine 20mg/day for her. Answer the following:
What is the mechanism of action of fluoxetine.
What is the advantage of this drug compared to tricyclic antidepressants.
What can happen if this patient is administered pethidine concurrently (2+2+2)
Q26 marksEssays
Answer
Mechanism of action of fluoxetine
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI)
It selectively inhibits presynaptic reuptake of serotonin (5-HT) at the serotonin transporter, increasing synaptic serotonin availability
Chronic use leads to downregulation of postsynaptic 5-HT receptors, correlating with the delayed onset of antidepressant effect (2–4 weeks)
Advantage compared to tricyclic antidepressants
Much safer cardiotoxicity profile — safer in overdose (TCAs can cause fatal arrhythmias in overdose)
Fewer anticholinergic side effects (no significant dry mouth, blurred vision, constipation, urinary retention)
Fewer sedative/antihistaminic effects and no significant orthostatic hypotension
Better tolerability leads to improved patient compliance
Concurrent administration with pethidine
Pethidine has serotonergic activity (weak serotonin reuptake inhibition), and combining it with an SSRI like fluoxetine can precipitate serotonin syndrome — a potentially life-threatening condition characterized by hyperthermia, autonomic instability, altered mental status, and neuromuscular abnormalities (rigidity, myoclonus, hyperreflexia)
This combination should be avoided; an alternative analgesic should be used
