Фенфлурамин: Құрамы, жанама әсерлері мен қауіптері

Medication used to treat seizures
Side effects of fenfluramine in people treated for seizures include decreased appetite, somnolence, sedation, lethargy, diarrhea, constipation, abnormal echocardiogram, fatigue, malaise, asthenia, ataxia, balance disorder, gait disturbance, increased blood pressure, drooling, excessive salivation, fever, upper respiratory tract infection, vomiting, appetite loss, weight loss, falls, and status epilepticus. Fenfluramine was developed in the early 1960s and was first introduced for medical use as an appetite suppressant in France in 1963 followed by approval in the United States in 1973.

Fenfluramine is indicated for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome in people age two and older. It has been suggested that some of these effects may be mediated by serotonergic neurotoxicity/depletion of serotonin with chronic administration and/or activation of serotonin 5 HT2A receptors.

The distinctive valvular abnormality seen with fenfluramine is a thickening of the leaflet and chordae tendineae. One mechanism used to explain this phenomenon involves heart valve serotonin receptors, which are thought to help regulate growth. Since fenfluramine and its active metabolite norfenfluramine stimulate serotonin receptors, this may have led to the valvular abnormalities found in patients using fenfluramine. In particular norfenfluramine is a potent inhibitor of the re uptake of 5 HT into nerve terminals. Fenfluramine and its active metabolite norfenfluramine affect the 5 HT2B receptors, which are plentiful in human cardiac valves. The suggested mechanism by which fenfluramine causes damage is through over or inappropriate stimulation of these receptors leading to inappropriate valve cell division. Supporting this idea is the fact that this valve abnormality has also occurred in patients using other drugs that act on 5 HT2B receptors. According to a study of 5,743 former users conducted by a plaintiff's expert cardiologist, damage to the heart valve continued long after stopping the medication. Of the users tested, 20% of women, and 12% of men were affected. For all ex users, there was a 7 fold increase of chances of needing surgery for faulty heart valves caused by the drug.

The elimination half life of fenfluramine has been reported as ranging from 13 to 30 hours. The mean elimination half lives of its enantiomers have been found to be 19 hours for dexfenfluramine and 25 hours for levfenfluramine. and continued findings of pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from other markets around the world. It was banned in India in 1998. Fenfluramine was an appetite suppressant which was used to treat obesity. It was used both on its own and, in combination with phentermine, as part of the anti obesity medication Fen Phen. The effectiveness of fenfluramine for the treatment of seizures associated with Dravet syndrome was demonstrated in two clinical studies in 202 subjects between ages two and eighteen. The FDA granted approval of Fintepla to Zogenix, Inc. Fenfluramine was approved for medical use in the European Union in December 2020.

Unlike various other amphetamine derivatives, fenfluramine is reported to be dysphoric, "unpleasantly lethargic", and non addictive at therapeutic doses. However, it has been reported to be used recreationally at high doses ranging between 80 and 400 mg, which have been described as producing euphoria, amphetamine like effects, sedation, and hallucinogenic effects, along with anxiety, nausea, diarrhea, and sometimes panic attacks, as well as depressive symptoms once the drug had worn off. At very high doses (e. g., 240 mg, or between 200 and 600 mg), fenfluramine induces a psychedelic state resembling that produced by lysergic acid diethylamide (LSD). Indirect (via induction of serotonin release) and/or direct activation of the 5 HT2A receptor would be expected to be responsible for the psychedelic effects of the drug at sufficient doses.