Pharmacology Of Sertraline

Indication	For the management of major depressive disorder, posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder with or without agoraphobia, premenstrual dysphoric disorder, social phobia, premature ejaculation, and vascular headaches.
Pharmacodynamics	Sertraline, an antidepressant drug similar to citalopram, fluoxetine, and paroxetine, is of the selective serotonin reuptake inhibitor (SSRI) type. Sertraline has one active metabolite and, like the other SSRIs, have less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because it does not have clinically important anticholinergic, antihistamine, or adrenergic blocking activity.
Mechanism of action	The exact mechanism of action sertraline is not fully known, but the drug appears to selectively inhibit the reuptake of serotonin at the presynaptic membrane. This results in an increased synaptic concentration of serotonin in the CNS, which leads to numerous functional changes associated with enhanced serotonergic neurotransmission. It is suggested that these modifications are responsible for the antidepressant action observed during long term administration of antidepressants. It has also been hypothesized that obsessive-compulsive disorder is caused by the dysregulation of serotonin, as it is treated by sertraline, and the drug corrects this imbalance.
Absorption	The effects of food on the bioavailability of the sertraline tablet and oral concentrate were studied in subjects administered a single dose with and without food. For the tablet, AUC was slightly increased when drug was administered with food but the Cmax was 25% greater, while the time to reach peak plasma concentration (Tmax) decreased from 8 hours post-dosing to 5.5 hours. For the oral concentrate, Tmax was slightly prolonged from 5.9 hours to 7.0 hours with food.
Volume of distribution	Not Available
Protein binding	98% bound to serum proteins, principally to albumin and α1-acid glycoprotein
Metabolism	Extensively metabolized in the liver. Sertraline metabolism involves N-demethylation, N-hydroxylation, oxidative deamination, and glucuronidation of sertraline carbamic acid. Sertraline undergoes N-demethylation primarily catalyzed by cytochrome P450 (CYP) 2B6, with CYP2C19, CYP3A4 and CYP2D6 contributing to a lesser extent. Deamination occurs via CYP3A4 and CYP2C19. In vitro studies have shown that monoamine oxidase A and B may also catalyze sertraline deamination. Sertraline N-carbamoyl glucuronidation has also been observed in human liver microsomes.
Route of elimination	Sertraline is extensively metabolized and excretion of unchanged drug in urine is a minor route of elimination.
Half life	The elimination half-life of sertraline is approximately 25-26 hours. The elimination half-life of desmethylsertraline is approximately 62-104 hours.
Clearance	Not Available
Toxicity	Symptoms of toxicity include alopecia, decreased libido, diarrhea, ejaculation disorder, fatigue, insomnia, somnolence and serotonin syndrome. The most frequently observed side effects include: GI effects such as nausea, diarrhea or loose stools, dyspepsia, and dry mouth; nervous system effects such as somnolence, dizziness, insomnia, and tremor; sexual dysfunction in males (principally ejaculatory delay); and sweating.