Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Sep 2010
The specialty of medical toxicology: beyond poisonous arrows and activated charcoal.
Medical toxicology is a subspecialty focusing on the diagnosis, management and prevention of poisoning effects due to medications, occupational and environmental toxins and xenobiotics, radiological and biological agents. This subspecialty provides an array of opportunities for physicians to care for patients in different settings: medication overdoses, substance abuse management, adverse drug events, exposures to industrial chemical products, and envenomations. Many medical toxicologists work in the pharmaceutical industry and in many government agencies such as as the Centers for Disease Control and Prevention (CDC), the Environmental Protection Agency (EPA), the US Food and Drug Administration (FDA), and the Department of Homeland Security.
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Levamisole has increasingly been discovered in street cocaine as an adulterant. Recent reports have linked levamisole in street cocaine to agranulocytosis in cocaine users. It is well known that agranulocytosis is associated with therapeutic use of levamisole, and this may have led to the withdrawal of the drug from the US market. ⋯ This may be supported by the recent report of metabolism of levamisole to aminorex in racehorses. Aminorex and related compounds, specifically 4-methylaminorex, or "ice," have high abuse potential because of their amphetamine-like pharmacological activity. This metabolism has not been reported in humans, and therefore the intended role of levamisole in street cocaine remains an enigma.
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Clin. Pharmacol. Ther. · Aug 2010
Randomized Controlled TrialBiological and hemodynamic effects of low doses of fludrocortisone and hydrocortisone, alone or in combination, in healthy volunteers with hypoaldosteronism.
Low doses of hydrocortisone (HC) and fludrocortisone (FC) administered together improve the prognosis after septic shock; however, there continues to be disagreement about the utility of FC for this indication. The biological and hemodynamic effects of HC (50 mg intravenously) and FC (50 microg orally) were assessed in 12 healthy male volunteers with saline-induced hypoaldosteronism in a placebo-controlled, randomized, double-blind, crossover study performed according to a 2 x 2 factorial design. HC and FC significantly decreased urinary sodium and potassium levels (from -58% at 4 h to -28% at 10 h and from -35% at 8 h to -24% at 12 h, respectively) with additive effects. ⋯ At doses used in septic shock, HC induced greater mineralocorticoid effect than FC did. HC also induced transient systemic hemodynamic effects, whereas FC did not. New studies are required to better define the optimal dose of FC in septic shock.