This panel provides drug-protein interaction and their ADRs along with references
| Interacting Drugs |
Toxicity |
Mechanism |
Reference |
|---|
| Acetaminophen | Hepatotoxicity | Particularly at high doses@ cytochrome P-450 enzymes--especially CYP1A2@ CYP2E1@ and isoforms of CYP3A--convert APAP to a reactive quinone form@ N-acetyl-p-benzoquinone imine (NAPQI)@that covalently binds to cellular macromolecules and also causes production of reactive oxygen species@ and leads to acetaminophen-induced hepatotoxicity. [ ADR Type 1 ] | Toxicology Protecting liver from painkiller's lethal dose
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| Acetylsalicylic acid | Increases Anticoagulant Effects | Methyl salicylate is systemically absorbed through the skin in measurable amounts@ and may increase warfarin action by affecting vitamin K metabolism or by displacing warfarin from protein-binding sites@ which increases anticoagulant effects [ ADR Type 4 ] | Potentiation of warfarin anticoagulation associated with topical methyl salicylate
|
| Clonidine | Decreasing Clozapine Plasma Level | Concomitant administration of drugs known to induce cytochrome P450 enzymes(CYP1A2@CYP2D6) may decrease the plasma levels of clozapine Phenytoin@ nicotine@ carbamazepine@ and rifampin may decrease FazaClo (clozapine@ USP) plasma levels resulting in a decrease in effectiveness of a previously effective FazaClo (clozapine@ USP) dose [ ADR Type 4 ] | Drug interactions with selective serotonin reuptake inhibitors, especially with other psychotropics
|
| Dihydralazine | Hepatotoxicity | The reactive metabolites produced are very short-lived and bind directly to the enzymes which generated them.A neoantigen is thus formed which triggers an immune response@characterized by the presence of autoantibodies in the patient#s serum.The autoantibodies are directed against the cytochrome P450 which generated the metabolite(s). [ ADR Type 2 ] | Immunotoxicology of the liver: adverse reactions to drugs
|
| Nicotine | Tardive Dyskinesia | A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene is associated with tardive dyskinesia in schizophrenia. [ ADR Type 3 ] | A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia
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| Sulfasalazine | Leucopenia | In patients with Crohn#s disease receiving azathioprine or 6-mercaptopurine@ coadministration of mesalamine@ sulphasalazine@ and possibly balsalazide results in an increase in whole blood 6-thioguanine nucleotide concentrations and a high frequency of leucopenia [ ADR Type 4 ] | Lowry PW, Franklin CL, Weaver AL, Szumlanski CL, Mays DC, Loftus EV, Tremaine WJ, Lipsky JJ, Weinshilboum RM, Sandborn WJ Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide
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| Tacrine | Hepatotoxicity | CBT will not be clinically useful in determining the subset of patients most susceptible to tacrine hepatotoxicity However@ the correlation between CBT results and tacrine blood levels is the first evidence supporting a critical role for CYP1A2 activity in the disposition of the drug in vivo [ ADR Type 2 ] | The caffeine breath test does not identify patients susceptible to tacrine hepatotoxicity
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| Valproic Acid | Clinical Failure | Sodium valproate was found to elevate clozapine plasma level while lowering norclozapine/clozapine ratio by inhibition of Cytochrome P450 1A2 activity@ which leads to enhancement of clozapine clearance and sometimes clinical failure [ ADR Type 4 ] | A case of pharmacokinetic interference in comedication of clozapine and valproic acid
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