Page 566 - Basic _ Clinical Pharmacology ( PDFDrive )

552 SECTION V Drugs That Act in the Central Nervous System

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C ASE STUD Y ANSWER

The patient has previously responded to fluoxetine, so this As a potent inhibitor of the serotonin transporter, fluox-
drug is an obvious choice. However, she is taking other drugs etine is associated with a number of pharmacodynamic
and fluoxetine, the prototype SSRI, has a number of pharma- interactions involving serotonergic neurotransmission. The
cokinetic and pharmacodynamic interactions. Fluoxetine is a combination of tramadol with fluoxetine has occasionally
CYP450 2D6 inhibitor and thus can inhibit the metabolism been associated with a serotonin syndrome, characterized
of 2D6 substrates such as propranolol and other β block- by diaphoreses, autonomic instability, myoclonus, seizures,
ers; tricyclic antidepressants; tramadol; opioids such as and coma. The combination of fluoxetine with an MAOI
methadone, codeine, and oxycodone; antipsychotics such as is contraindicated because of the risk of a fatal serotonin
haloperidol and thioridazine; and many other drugs. This syndrome. In addition, meperidine is specifically contrain-
inhibition of metabolism can result in significantly higher dicated in combination with an MAOI. An interaction with
plasma levels of the concurrent drug, and this may lead to hydrochlorothiazide is not likely.
an increase in adverse reactions associated with that drug.