Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated several factors that might be related to the occurrence of toxic effects during the performance of a urinary test with caffeine (300 mg p.o.), in 120 healthy volunteers. A total of 218 toxic effects were self-reported by eighty-two (68%) subjects. Females and nonsmokers were at the highest risk (chi-square test, P = 0.01). Furthermore, two nonsmoking females experienced a symptomatology with delirium, restlessness, muscle tremor, vomiting and wakefulness. Among females and nonsmokers, those subjects who experienced toxic effects had lower caffeine N3-demethylation index (CYP1A2 activity) compared with unaffected females (1.87 +/- 0.51 vs 1.47 +/- 0.27, P < 0.0005) and nonsmokers (1.69 +/- 0.23 vs 1.49 +/- 0.31, P < 0.02). Caffeine N1- and N7-demethylations indices were also lower among females (P < 0.0005) and nonsmokers (P < 0.02) who reported toxic symptoms. We conclude that CYP1A2 activity, gender and smoking are variables to be considered as influencing the toxicity of caffeine.
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PMID:CYP1A2 activity, gender and smoking, as variables influencing the toxicity of caffeine. 879 28

An adverse event is described which appeared when the macrolide antibiotic erythromycin was added to a regimen of risperidone 0.5 mg bid and clomipramine 50 mg tid in a 15-year-old male being treated for Tourette's, obsessive-compulsive, and attention-deficit hyperactivity disorders. An acute onset of behavioral symptoms, including agitation, labile mood, incessant talking, and argumentativeness, began within 24 h of starting the erythromycin and persisted for 9 days after its discontinuation. It was followed by a return to stable functioning on the prior risperidone-clomipramine regimen. Erythromycin, risperidone, and clomipramine are all metabolized by the hepatic cytochrome P450 system. It is postulated that the addition of erythromycin, a known inhibitor of CYP3A and CYP1A2, resulted in alterations in the metabolism of clomipramine and risperidone. Clomipramine metabolism is dependent upon the isoenzymes CYP2D6 and CYP1A2, and risperidone is a substrate for CYP2D6. Erythromycin would inhibit demethylation of clomipramine at the 1A2 isoenzyme and lead to a dual interaction between risperidone and clomipramine at the CYP2D6 isoenzyme. The subsequent increases in plasma levels of clomipramine, risperidone, their metabolites, or a combination of these agents could explain the adverse effects noted in this patient. In the absence of risperidone, clomipramine could have been metabolically cleared by CYP2D6. In the absence of clomipramine, risperidone clearance would not be affected by erythromycin. So the proposed mechanism requires an interaction involving all three agents: erythromycin, clomipramine, and risperidone. Alterations in plasma protein binding may also have played a role, because all three agents are extensively protein bound. Caution is urged when prescribing erythromycin with psychotropic drugs that are highly protein bound and/or are metabolized by the same P450 isoenzymes.
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PMID:Erythromycin interaction with risperidone or clomipramine in an adolescent. 923 5