Selective serotonin reuptake activation effects

MDMA overdose as well as the concomitant consumption of selective serotonin reuptake inhibitors (SSRI) with other dmgs that exert serotoninergic effects (such as inhibitors of monoamine oxidase) can rapidly lead to the serotonin syndrome. Its symptoms, which are reversible upon cessation, of the drug include confusion, muscle rigidity in the lower limbs, and hyperthermia suggesting an acute reaction to serotonin overflow in the CNS. Blocking the function of SERT outside the brain causes side effects (e.g., nausea), which may be due to elevated 5HT however , impairment of transporter function is not equivalent to direct activation of 5HT recqrtors in causing adverse effects such as fibrosis and pulmonary hypertension. 

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... 

Venlafaxine extended release, duloxetine, paroxetine, and escitalopram are FDA approved for treatment of GAD. Sertraline is also effective. Acute response and remission rates are approximately 65% and 30%, respectively. Imipramine may be used when patients fail to respond to selective serotonin reuptake inhibitors (SSRIs). In one trial, diazepam, trazodone, and imipramine had greater anxiolytic activity than placebo. 

Many psychoactive drugs act to alter neurotransmitter functions either through effects on their synthesis, metabolism or reuptake or by directly affecting the receptors for naturally occurring compounds. For example, drugs such as prozac increase serotoniner-gic activity by selective serotonin reuptake inhibition (SSRI). 

Figure 5. The effect of the selective serotonin reuptake inhibitor, escitalopram, on firing activity of norepinephrine neurons. Norepinephrine neurons exhibit tonic-phasic firing activity of 1.5-3.0 Hz, with small (2-3/min) number of short burst ( ). Escitalopram inhibits the firing activity of norepinephrine...

Kobayashi K, Yamamoto T, Chiba K, et al. The effects of selective serotonin reuptake inhibitors and their metabolites on S-mephenytoin 4 -hydroxylase activity in human liver-microsomes. Br J Cbn Pharmacol 1995 40 481 -85. 

St. John s wort also exhibits anti-inflammatory and antibacterial activity. Reports of antiviral activity arc unsubstantiated. The main adverse effect with St. John s wort is severe phototoxicity. A sunbum-like condition may occur at normal dosages. St. John s wort. should never be taken with MAOIs because of the risk of potentiation of the effects. Selective serotonin reuptake inhibitors (SSRIs) likewise should not be taken with St. John s wort because of the ri.sk of serotonergic syndrome. 

When they occur, depressive symptoms should be treated actively using a combination of cognitive-behavioral therapy and an antidepressant drug. Of the available antidepressants, selective serotonin reuptake inhibitors (SSRIs) have the most favourable combination of efficacy and side-effect profile for the elderly, regardless of the presence of medical co-morbidities. Although the dual agent venlafaxine has been proposed as an alternative agent for older patients who are either non-responders or partial responders to SSRIs, the frail elderly may be particularly vulnerable to its side effects (Hayes 2004). 

Some selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, fluvoxamine, and paroxetine, are potent inhibitors of CYP2D6 activity. Therefore, multiple dosing causes autoinhibition of CYP2D6 and conversion from extensive to slow metabolizer phenotype and from ultrafast to extensive metabolism [16,17]. In the case of fluvoxamine, diflerences in areas under the curve (AUCs) were described after single doses [18,19], whereas multiple doses result in similar AUCs in PMs and EMs, indicating a strong inhibitory effect on CYP2D6 in EMs [20]. 

A mechanism for altering synaptic availability of 5-HT is inhibition of presynaptic reaccumulation of neuronally released 5-HT. Selective serotonin reuptake inhibitors (SSRIs e.g., fluoxetine [PROZAC]) potentiate and prolong the action of 5-HT released by neuronal activity. Effects of 5-HT-active drugs, like the SSRIs, in anxiety and depressive disorders strongly suggest an effect of 5-HT in the neurochemical mediation of these disorders. SSRIs are the most widely used treatment for endogenous depression (see Chapter 17). 

When compared with the selective serotonin reuptake inhibitors (SSRIs), mirtazapine may show an earlier onset of action (although data are currently not well established). Mirtazapine has also been found to be efficacious in the treatment of elderly patients with depression. Mirtazapine has been shown to be effective in the treatment of panic disorder, social phobia, and post-traumatic stress disorder. In one study, mirtazapine combined with citalopram in obsessive-compulsive patients induced an earlier response when compared with citalopram plus placebo. It was suggested that antagonism of presynaptic a2-adrenergic receptors does not enhance serotonin neurotransmission directly, but rather disinhibits the norepinephrine activation of serotonergic neurons and thereby increases serotonergic neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. 

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