indication

For the management of exogenous obesity as a short-term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction.

pharmacology

Used to treat obesity, Fenfluramine decreases caloric intake by increasing serotonin levels in the brain's synapses. Fenfluramine acts as a serotonin reuptake inhibitor. It also causes release of serotonin from the synaptosomes. This in turn increases serotonin transmission in the feeding centre of the brain which suppresses appetite.

mechanism of action

Fenfluramine binds to the serotonin reuptake pump. This causes inhbition of serotonin uptake and release of serotonin. The increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding behavior located in the hypothalamus. This suppresses the appetite for carbohydrates.

toxicity

Agitation and drowsiness, confusion, flushing, tremor (or shivering), fever, sweating, abdominal pain, hyperventilation, and dilated non-reactive pupils seem frequent in fenfluramine overdosage. Reflexes may be either exaggerated or depressed and some patients may have rotary nystagmus. Tachycardia may be present, but blood pressure may be normal or only slightly elevated. Convulsions, coma, and ventricular extrasystoles, culminating in ventricular fibrillation, and cardiac arrest, may occur at higher dosages. Less than 5 mg/kg are toxic to humans. Five-ten mg/kg may produce coma and convulsions. Reported single overdoses have ranged from 300 to 2000 mg; the lowest reported fatal dose was a few hundred mg in a small child, and the highest reported nonfatal dose was 1800 mg in an adult. Most deaths were apparently due to respiratory failure and cardiac arrest. Toxic effects will appear within 30 to 60 minutes and may progress rapidly to potentially fatal complications in 90 to 240 minutes. Symptoms may persist for extended periods depending upon the dose ingested.

biotransformation

Hepatic.

absorption

Fenfluramine is well-absorbed from the gastrointestinal tract, and a maximal anorectic effect is generally seen after 2 to 4 hours.

half life

20 hours

drug interactions

Acetophenazine: Decreased anorexic effect, may increase psychotic symptoms

Chlorpromazine: Decreased anorexic effect, may increase psychotic symptoms

Ethopropazine: Decreased anorexic effect, may increase psychotic symptoms

Fluoxetine: Risk of serotoninergic syndrome

Fluphenazine: Decreased anorexic effect, may increase psychotic symptoms

Fluvoxamine: Risk of serotoninergic syndrome

Guanethidine: Fenfluramine may decrease the effect of guanethidine.

Insulin Aspart: Fenfluramine increases the effect of insulin

Insulin Detemir: Fenfluramine increases the effect of insulin

Insulin Glulisine: Fenfluramine increases the effect of insulin

Isocarboxazid: Possible hypertensive crisis

Mesoridazine: Decreased anorexic effect, may increase psychotic symptoms

Methdilazine: Decreased anorexic effect, may increase psychotic symptoms

Methotrimeprazine: Decreased anorexic effect, may increase psychotic symptoms

Paroxetine: Risk of serotoninergic syndrome

Perphenazine: Decreased anorexic effect, may increase psychotic symptoms

Phenelzine: Possible hypertensive crisis

Prochlorperazine: Decreased anorexic effect, may increase psychotic symptoms.

Promazine: Decreased anorexic effect, may increase psychotic symptoms

Promethazine: Decreased anorexic effect, may increase psychotic symptoms.

Propericiazine: Decreased anorexic effect, may increase psychotic symptoms.

Propiomazine: Decreased anorexic effect, may increase psychotic symptoms

Rasagiline: Possible hypertensive crisis

Thiethylperazine: Decreased anorexic effect, may increase psychotic symptoms

Thioridazine: Decreased anorexic effect, may increase psychotic symptoms

Tranylcypromine: Possible hypertensive crisis

Trifluoperazine: Decreased anorexic effect, may increase psychotic symptoms

Triflupromazine: Decreased anorexic effect, may increase psychotic symptoms

Trimeprazine: Decreased anorexic effect, may increase psychotic symptoms

Venlafaxine: Risk of serotoninergic syndrome