Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of many neuroleptics cosegregates catalyzed by the polymorphic cytochrome P450 CYP2D6. The population can be phenotyped into extensive metabolizers (EM) and poor metabolizers (PM) with respect to this enzyme's activity. PM are likely to achieve higher than average concentrations of neuroleptic drugs in plasma, with an increased risk of extrapyramidal side effects, possibly including tardive dyskinesia. Sixteen white schizophrenic patients who had developed tardive dyskinesia during long-term neuroleptic treatment were phenotyped with debrisoquine and genotyped by CYP2D6-specific DNA amplification and EcoRI restriction fragment length polymorphism analysis. Only 1 (6%) of the 16 patients had a PM genotype, 8 (50%) were homozygous, and 7 (44%) were heterozygous EM. None had a CYP2D6 genotype indicative of ultrarapid debrisoquine hydroxylation capacity. The patients were also phenotyped with mephenytoin, a probe drug for another polymorphic cytochrome P450, CYP2C19. One patient was a PM of S-mephenytoin, which corresponds to the frequency found in healthy white volunteers. In conclusion, there was no overrepresentation of PM of debrisoquine or of S-mephenytoin among the 16 patients with neuroleptic-induced tardive dyskinesia. However, the PM of debrisoquine had the highest score on the Simpson-Angus Rating Scale and the second highest on the Abnormal Involuntary Movement Scale, despite a very low neuroleptic dose. Also, the debrisoquine MR correlated significantly with the SARS score (rs = 0.685, p < 0.05, N = 10), indicating a relationship between the degree of impaired CYP2D5 activity and the severity of extrapyramidal side effects during neuroleptic treatment.
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PMID:Polymorphic drug metabolism in schizophrenic patients with tardive dyskinesia. 763 99

Lopinavir-ritonavir combination is being used for the treatment of SARS-CoV-2 infection. A low dose of ritonavir is added to other protease inhibitors to take advantage of potent inhibition of cytochrome (CYP) P450 3A4, thereby significantly increasing the plasma concentration of coadministered lopinavir. Ritonavir also inhibits CYP2D6 and induces CYP2B6, CYP2C19, CYP2C9, and CYP1A2. This potent, time-dependent interference of major hepatic drug-metabolizing enzymes by ritonavir leads to several clinically important drug-drug interactions. A number of patients presenting with acute coronary syndrome and acute heart failure may have SARS-CoV-2 infection simultaneously. Lopinavir-ritonavir is added to their prescription of multiple cardiac medications leading to potential drug-drug interactions. Many cardiology, pulmonology, and intensivist physicians have never been exposed to clinical scenarios requiring co-prescription of cardiac and antiviral therapies. Therefore, it is essential to enumerate these drug-drug interactions, to avoid any serious drug toxicity, to consider alternate and safer drugs, and to ensure better patient care.
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PMID:Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications. 3291 56