Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a new, potentially fatal disorder that is infrequently reported. The apparent rareness may be because of a lack of recognition of the syndrome or its predisposing factors. Fluoxetine (Prozac, Dista Products Co, Division of Eli Lilly Co, Indianapolis, IN), sertraline (Zoloft, Roerig Division, Pfizer Inc, New York, NY), and paroxetine (Paxil, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) belong to a new class of antidepressant medication: the serotonin reuptake-inhibitors (SRIs). The relative safety profile of the SRIs has led to their widespread use. However, a syndrome of excessive serotonergic activity, the "serotonin syndrome" (SS), has recently been recognized. It is characterized by changes in mental status, hypertension, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. A high index of suspicion is required to make the diagnosis in these acutely ill patients. The most common agents implicated in SS are the monoamine oxidase inhibitors in combination with L-tryptophan or fluoxetine. A case of a patient with significant peripheral vascular disease who developed SS while taking paroxetine and an over-the-counter cold medicine is reported. There have been no prior reports of this interaction. Discontinuation of the offending agents, sedation, and supportive care are the mainstays of treatment. The interactions of serotonin with platelets and vascular endothelium are also discussed.
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PMID:The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease. 766 67

Paroxetine, also known by the trade names Aropax, Paxil, Pexeva, Seroxat, Sereupin and Brisdelle, was first marketed in the U.S. in 1992. Effective for major depression and various anxiety disorders, it quickly gained a sizable share of the antidepressant prescription market. By the late 1990s, paroxetine frequently was being associated with serious drug interactions and medication side effects. Most significantly, in a major Canadian epidemiological study examining the relationship between antidepressants and diseases, paroxetine was associated with a 620 percent increase in the rate of breast cancer in women who had taken it over a four-year period. Though re-analyses of this investigation discounted the magnitude of these findings, other studies have associated paroxetine with numerous side effects and adverse events not reported in clinical trials. Among these are effects on male fertility, birth defects, gestational hypertension, prolonged QT interval in infants, hyperprolactinemia, cognitive impairment in the elderly, autism, sexual side effects, weight gain, and suicidality, aggression, and akathisia in children and adolescents. Paroxetine has the highest inhibitory constant for the P450 2D6 isoenzyme of all antidepressants (Ki = 0.065-4.65 micromoles). This high affinity explains its high inhibitory interaction profile with substrates for 2D6. Paroxetine's potent 2D6 inhibition also implies that significant inhibition of the metabolism of 2D6 carcinogen substrates occurs which implies an increased probability of oncogenesis. Through 2D6 inhibition, tamoxifen metabolism is inhibited, which has been found to increase the risk of dying from breast cancer over a five-year period in women on both medications. Paroxetine also is a potent inhibitor of 3A4 with multiple 3A4 substrate interactions. Paroxetine has the highest known affinity for the serotonin transporter (0.13 nanomoles) of any currently used antidepressant. These characteristics and their potential negative consequences along with other adverse effects are considered and weighed against paroxetine's efficacious antidepressant and anxiolytic effects.
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PMID:Paroxetine-The Antidepressant from Hell? Probably Not, But Caution Required. 2773 76