Toxicity Interactions, drug

TABLE 78-3. Selective Toxicities and Drug Interactions Associated with Antimicrobials6 12,17 18... 

The approach to antifungal therapy in patients with endemic fungal infections is determined by the severity of clinical presentation, the patient s underlying immunosuppression, and potential toxicities and drug interactions associated with antifungal treatment. 

About a week later, the patient was admitted to the hospital with acute onset of confusion and possible seizurelike activity. His wife states that he is compliant with medications and even felt well after initiation of antibiotics. Possible ciprofloxacin-induced acute CNS toxicity or drug interaction was suspected, and all his medications were discontinued. Which of the following is the possible explanation for the patient s acute onset of CNS toxicity ... 

This may be the result of systemic toxicity, hypersensitivity, drug interactions and agent-specific effects. Serious toxicity is almost always the result of overdosage or inadvertent intravascular injection. The maximum recommended doses are shown in Table 5.2. 

Neither selegiline nor rasagiline should be taken by patients receiving meperidine. They should be used with care in patients receiving tricyclic antidepressants or serotonin reuptake inhibitors because of the theoretical risk of acute toxic interactions of the serotonin syndrome type (see Chapter 16), but this is rarely encountered in practice. The adverse effects of levodopa may be increased by these drugs. 

The drawback of combination therapy is, of course, the potential for increased toxicity and drug interactions when several DMARDs are used simulta-... 

Vermes A, Guchelaar HJ, Dankert J. Flucytosine a review of its pharmacology, clinical indications, pharmacokinetics, toxicity, and drug interactions. J Antimi-crob Chemother. 2000 46 171-179. 

Although the CYP enzymes are the most abundant in the liver, they are also present in other tissues including the skin, kidney, intestine, lung, placenta, and nasal mucosa. Because CYP exists as multiple isozymes with different substrate specificities, the presence or absence of a particular CYP isozyme may contribute to tissue-specific toxicities. Many drugs and other foreign compounds are known to induce one or more of the CYP isozymes, resulting in an increase, decrease, or an alteration in the metabolic pathway of chemicals metabolized by the CYP isozymes involved. Specific examples of these types of interactions are given later in this section. 

Mitigation strategies developed for other peroxisome proliferators such as the fibric acid drugs should be investigated for their applicability to DEHP. Consideration should be given to the fact that other peroxisome proliferators, such as trichloroethylene, might be commonly found at the same NPL sites and toxic interactions could occur. 

Concomitant administration of paracetamol with other hepatotoxic drugs or drugs acting on liver microsomal enzymes enhances paracetamol toxicity. Other drugs that interact with paracetamol are metoclopramide, probenecid, and cholestyramine.81... 

As noted, a toxicant or drug receptor may be defined loosely as a macromolecule with which a drug (or toxicant) interacts with high affinity to produce its character-... 

The object of this chapter is to provide the foundation necessary for understanding the interactions of small molecules (ligands, be they toxicants or drugs) with receptors, and also the fundamentals of the techniques commonly employed for such analysis. It should be noted that the same theory is also useful for understanding the interaction of two large molecules, and the application of similar theory to such problems has increased as the importance of macromolecular interactions has been realized in recent years. 

Kudo K, Imamura T, Jitsufuchi N, Zhang XX, Tokunaga H, Nagata T. Death attributed to the toxic interaction of triazolam, amitriptyline and other psychotropic drugs. Forensic Sci Int 1997 86(1-2) 35 11. 

The rate of myopathy with a statin alone in the general population is 0.1-0.5% and 0.2-2.5% with combination therapy. Rhabdomyolysis is very rare at 0.02-0.04%. However, the latter carries a significant morbidity and mortality. In a review of Food and Drug Administration (FDA) reports published in 2002, there were 38 deaths in 631 patients (6.3%) [31]. Pravastatin and fluvastatin have been less frequently implicated in fatal cases of rhabdomyolysis [31]. It is postulated that the more hepatoselective hydrophilic statins, such as pravastatin, are less likely to penetrate muscle cells than are lipophilic statins, and therefore represent a lower risk for myopathy, particularly in the event of an interacting drug increasing their blood levels to within the toxic range [26, 32]. 

Verapamil Carbamazepine Phenytoin High risk of carbamazepine toxicity interaction with phenytoin inconsistent Inhibition of metabolism of the object drugs... 

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