Selective serotonin reuptake interactions

The answer is d. (Kai ung, p 505.) Fluoxetine is a highly selective serotonin re uptake inhibitor (55RI) acting on the 5-1 IT transporter. It forms an active metabolite that is effective for several days. Selective serotonin reuptake inhibitors are inhibitors of cytochrome P450 isoenzymes, which is the basis of potential drug-drug interactions... 

Naranjo, C.A., Sproule, B.A. and Knoke, D.M. (1999) Metabolic interactions of central nervous system medications and selective serotonin reuptake inhibitors. International Clinical Psychopharmacology, 14 (Suppl. 2), S35-S47. 

Psychiatric medicines exert multiple effects for two principal reasons. First, they usually interact with more than one receptor type. There are two ways to look at this. You will often hear a medication with multiple receptor interactions called a dirty drug. This is because the more receptor interactions it has, the more effects, and hence side effects, it produces. As a result, great effort has been made to develop newer medications with fewer receptor interactions and, thus, fewer side effects. This effort has been quite successful with antidepressants, as we have moved from the effective but side effect-laden tricyclic antidepressants to newer antidepressants such as selective serotonin reuptake inhibitors. 

Ramamoorthy S, Leibach FH, Mahesh VB, Ganapathy V (1993) Partial purification and characterization of the human placental serotonin transporter. Placenta 14 449-461 Rasmussen BB, Brosen K (2000) Is therapeutic drug monitoring a case for optimizing clinical outcome and avoiding interactions of the selective serotonin reuptake inhibitors Ther DrugMonit 22 143-154... 

Structure is also essential in complex biological molecules. A lot of medicines used for psychiatric illnesses such as depression rely on their ability to interact with certain proteins in the brain. For instance, a class of antidepressants—medications that alleviate the symptoms of depression—act on proteins involved with the collection (reuptake) of the chemical serotonin, and they are known as selective serotonin reuptake inhibitors (SSRIs). This class of antidepressants includes Prozac and Zoloft. Earlier medications were also effective and are still sometimes used though they produce a number of side effects, such as dietary problems. Although an SSRI can also generate potentially dangerous side effects, psychiatrists tend to observe these effects less often. (Brain chemistry is the subject of chapter 3.)... 

Wetzel H, Anghelescu 1, Szegedi A, et al Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors differential effects of fluvoxamine and paroxetine in a prospective study. J Clin Psy-chopharmacol 18 2-9, 1998... 

Harvey AT, Preskorn SH. Cytochrome P450 enzymes interpretation of their interactions with selective serotonin reuptake inhibitors (Part II). J Clin Psychopharmacol 1996 16 345-355. 

The similar pharmacological profile of selective serotonin reuptake inhibitors and St. John s wort would suggest the potential of a pharmacodynamic interaction due to an additive effect. A case of concurrent use of sertraline and St. John s wort, resulting in mania, was reported for a patient with a history of depression who was prescribed sertraline and who also took St. John s wort against medical advice (58). A similar potentiation of serotonergic effect was reported by Gordon (49). 

A growing number of drugs are used that affect the many neurotransmitters in the brain benzodiazepines and others act on GABAergic transmission antidepressants, such as monoamine oxidase inhibitors and tricyclic antidepressants, are thought to increase the concentration of transmitter amines in the brain and so elevate mood—these will also act at peripheral nerve terminals, so interactions with them are a combination of peripheral and central actions. Levodopa (L-dopa) increases central as well as peripheral dopamine, and the newer class of psychoactive drugs, the selective serotonin reuptake inhibitors (SSRIs) of which the ubiquitous fluoxetine (Prozac) is best known, act in a similar way on serotonergic pathways. 

Rasagiline Inhibits MAO-B selectively, higher doses also inhibit MAO-A Increases dopamine stores in neurons may have neuroprotective effects Parkinson s disease adjunctive to levodopa smooths levodopa response Oral Toxicity interactions may cause serotonin syndrome with meperidine, and theoretically also with selective serotonin reuptake inhibitors, tricyclic antidepressants... 

Monoamine oxidase inhibitors (eg, tranylcypromine, phenelzine) are older antidepressants that are occasionally used for resistant depression. They can cause severe hypertensive reactions when interacting foods or drugs are taken (see Chapters 9 and 30), and they can interact with the selective serotonin reuptake inhibitors (SSRIs). 

A dangerous pharmacodynamic interaction may occur when fluoxetine or one of the newer selective serotonin reuptake inhibitors is used in the presence of a monoamine oxidase inhibitor. 

Newer antidepressants (eg, fluoxetine, paroxetine, citalopram, venlafaxine) are mostly selective serotonin reuptake inhibitors and are generally safer than the tricyclic antidepressants and monoamine oxidase inhibitors, although they can can cause seizures. Bupropion (not an SSRI) has caused seizures even in therapeutic doses. Some antidepressants have been associated with QT prolongation and torsade de pointes arrhythmia. The SSRIs may interact with each other or especially with monoamine oxidase inhibitors to cause the serotonin syndrome, characterized by agitation, muscle hyperactivity, and hyperthermia. 

Lane RM. Pharmacokinetic drug-interaction potential of selective serotonin reuptake inhibitors. Int Clin Psychopharmacol 1996 11 31-61. 

Mitchell PB. Drug interactions of clinical significance with selective serotonin reuptake inhibitors. Drug Saf 1997 17 390 106. 

Sproule BA, Naranjo CA, Bremner KE, et al. Selective serotonin reuptake inhibitors and CNS drug interactions-a critical review of the evidence. Clin Pharmacokinet 1997 33 454-471. 

Baker GB, Fang J, Sinha S, et al. Metabolic drug interactions with selective serotonin reuptake inhibitor (SSRI) antidepressants. Neurosci Biobehav Rev 1998 22 325-333. 

Hemeryck A, Belpaire FM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions an update. Curr Drug Metab 2002 3 13-37. 

Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, interact with drugs including clarithromycin, warfarin, phenelzine, benzotropine, chlorpromazine, diazepam, and cyproheptadine. Cigarette smokers metabolize SSRIs faster. 

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