Fluoxetine Pharmacology: SSRI Drug Class, Effects & Uses

PM 719 Pharmacology II Seven Things Document **Fluoxetine** \(1) Drug Class and Stem: Selective Serotonin Reuptake Inhibitor (SSRI) Stems "ine" or "pram" Examples: citalopram, fluoxetine, paroxetine, sertraline etc. Fluoxetine was the first SSRI introduced in 1988 and became one of the world'...

PM 719 Pharmacology II Seven Things Document **Fluoxetine** \(1) Drug Class and Stem: Selective Serotonin Reuptake Inhibitor (SSRI) Stems "ine" or "pram" Examples: citalopram, fluoxetine, paroxetine, sertraline etc. Fluoxetine was the first SSRI introduced in 1988 and became one of the world's largest selling drug. \(2) Primary Clinical Use: To treat clinical depression and anxiety disorders, and many other CNS \(3) Site of Action and Receptor(s): Fluoxetine binds to and inhibits the serotonin transporter (SERT) which raises the levels of serotonin (5HT). One hypothesis about the cause of clinical depression is that the CNS has lowered levels of serotonin. \(4) Mechanism of Action: Raise serotonin levels in the CNS through inhibition of the serotonin reuptake pump which moves the neurotransmitter from the synapse back into the neuron that released it. \(5) Physiological Effects: SSRIs have a very broad range of clinical uses. Fluoxetine has a wide safety range which makes it relatively safe. Its wide range of allowed plasma levels (Cp) makes overdose difficult to impossible. \(6) Major ADRs: Fluoxetine unlike the others in the class is biotransformed into norfluoxetine which has a half-life three times longer which can result in accumulation. This drug must be stopped for weeks before any other class of drug which raises serotonin levels which could lead to the fatal condition called Serotonin Syndrome. Fluoxetine and the SSRIs increase serotonin levels in the CNS and to some extent in the peripheral nervous system (PNS) also. Increased serotonin levels in the PNS can account for the GI symptoms of nausea, GI upset and diarrhea. Increased serotonin in the spinal cord may account for loss of libido, lack of interest in sex. Most SSRIs are FDA Pregnancy category C. Fluoxetine is a potent inhibitor of CYP2D6. Addition of another drug that requires Simultaneous use of fluoxetine and a Monoamine Oxidase Inhibitor (MAO) which also raises serotonin levels can lead to an often-fatal Serotonin Syndrome. \(7) Modes of Administration: Long half-life of 48-72 hours makes once a day PO dosing possible.