Serotonin antagonists toxicity

Short-term toxicities of adjuvant chemotherapy are generally well tolerated, especially with the availability of serotonin-antagonist and substance P/neurokinin 1-antagonist antiemetics and colony-stimulating factors. 

After overdosage with ergotamine and similar agents, vasospasm is severe and prolonged (see Toxicity, below). This vasospasm is not easily reversed by antagonists, serotonin antagonists, or combinations of both. 

SAFETY PROFILE Poison by intraperitoneal route. A serotonin antagonist that causes psychotropic effects in humans. Experimental reproductive effects. When heated to decomposition it emits very toxic fumes of HCl and NOx. 

Sumatriptan is a 5HT (serotonin) agonist indicated in the treatment of migraine. Sumatriptan causes vasoconstriction and must therefore be used with caution in patients with coronary heart disease, such as angina. Concurrent administration of the agonist, sumatriptan and antagonists, such as fluoxetine, which is a selective serotonin re-uptake inhibitor, leads to increased CNS toxicity. 

The TCA drugs have lost their place as first-line therapy for depression because of their bothersome side effects (Table 33.2) at therapeutic doses and lethal effects in toxic doses. In addition to their presynaptic effects on the neuronal uptake of norepinephrine and serotonin, they block several postsynaptic receptors. They are potent cholinergic muscarinic receptor antagonists, resulting in symptoms such as dry mouth, constipation, tachycardia, blurred vision and urinary retention. Blockade of histamine receptors (Hi) often results in sedation and weight gain. Antagonism of aj-adrenoceptors in the vasculature can cause orthostatic hypotension. 

Nefazodone. Nefazodone is an antidepressant that inhibits neuronal uptake of serotonin and norepinephrine, Nefazodone is a 5-HT2 antagonist that is rapidly absorbed and has low bioavailabiiity (20%) because it undergoes first-pass metabolism. In March of 2004, the U.S. FDA issued a Pubhc Health Advisory that called attention to reports of both suicidal ideation and suicide attempts in children taking antidepressant drugs such as nefazodone for the treatment of major depressive disorder (MDD), Because of several cases of fiver toxicity, nefazodone (Serzone) was taken off the market in lune of 2004. An HPLC method with electrochemical detection has been published for the analysis of nefazodone. ... 

PCP has widely varied actions including CNS stimulation, depression, and hallucinogenic properties. Pharmacologically, it is known to block reuptake of serotonin, dopamine, and norepinephrine, but neurotransmitter antagonists do not effectively block its effects. In low doses, PCP causes sedation, ataxia, nystagmus, slurred speech, and paresthesias. At higher doses, users experience an increase in heart rate, blood pressure, temperature, diaphoresis, and muscle rigidity. At acutely toxic doses, coma and seizures may occur." ... 

Studies in experimental animals with toxic or ischemic liver failure demonstrate that antagonists of certain serotonin receptor subtypes and administration of the glutamate (NMDA) receptor antagonist memantime improve neurological function and/or prevent brain edema in these animals (Vogels et al., 1997). 

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