By H. Jick (auth.), E. Grundmann (eds.)
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Extra resources for Drug-Induced Pathology
For example, organic acids such as penicillin and salicylic acid are transported from the cerebrospinal fluid (CSF) to plasma by an energy-requiring pump localized in the choroid plexuses. Probenecid competes for the carrier mechanism and its administration can markedly prolong the. elimination of these drugs from the CSF. g. meningitis, resulting in substantial penetration into the central nervous system (CNS) of drugs that would not normally have access to it. g. enhanced penetration of an antibiotic into a septic focus, but CNS toxicity can also result.
1974). Although the precise nature of the toxic metabolite is still unknown, it is considered to be a precursor of the cysteine and mercapturic acid conjugates which are found in urine after therapeutic and toxic doses (Davis et al. 1976). Following therapeutic doses the drug is predominantly converted to paracetamol glucuronide and paracetamol sulphate (Perucca and Richens 1979), only 20% of the metabolites recovered in urine being accounted for by cysteine and mercapturic acid conjugates (Davis et al.
A similar mechanism is also likely to mediate the increased sensitivity to nitrazepam in old age (Castleden et a1. 1977). c) Pathological Factors Adverse drug reactions most frequently arise when the pharmacological action is potentiated by the effects of concurring disease. A typical example of this phenomenon is provided by the enhancement of digitalis toxicity (cardiac dysrhythmias in particular) in the presence of potassium depletion. This is easy to overlook because relatively large decreases in intracellular potassium can occur in spite of nonnokalemia.
Drug-Induced Pathology by H. Jick (auth.), E. Grundmann (eds.)