Drug Interaction - Enzyme Inhibition

Perpetrators of Drag-Drug Interactions Enzyme Inhibition 169... 

Perpetrators of Drug-Drug Interactions Enzyme Inhibition... 

Although significant interactions for specific drugs will be addressed in subsequent chapters, case 10 illustrates the most frequently encountered of all drug interactions, enzyme inhibition (Hansten and Horn 1990). This interaction occurs when... 

As with carbamazepine, the historical use of valproate for anxiety is not supported by robust clinical trials. A randomised study showed efficacy in panic disorder (Lum et al. 1991) and benefit has been reported in open studies in OCD and PTSD. The major side-effects are tremor, nausea, ataxia and weight gain and there is the potential for drug interactions via inhibition of hepatic enzymes. 

Drug Interactions. Felbamate inhibits the clearance and increases the serum concentration of phenytoin, valproic acid, and phenobar-bital. The concentration of carbamazepine decreases in patients on concmrent therapy with felbamate secondary to enzyme induction however, the concentration of the 10,11 -epoxide metabolite increases. It is recommended that the dose of phenytoin, carbamazepine, and valproic acid be decreased by about 30% when felbamate is added. Felbamate does not appear to interact with either gabapentin or 1am-otrigine. Phenytoin and carbamazepine are enzyme inducers and have been shown to increase the clearance of felbamate. Interactions with warfarin also have been reported. ... 

Following concurrent administration of two drugs, especially when they are metabolized by the same enzyme in the liver or small intestine, the metabolism of one or both drugs can be inhibited, which may lead to elevated plasma concentrations of the dtug(s), and increased pharmacological effects. The types of enzyme inhibition include reversible inhibition, such as competitive or non-competitive inhibition, and irreversible inhibition, such as mechanism-based inhibition. The clinically important examples of drug interactions involving the inhibition of metabolic enzymes are listed in Table 1 [1,4]. 

Drug Interactions. Table 1 Examples of clinically important drug interactions due to enzyme inhibition... 

Use of zileuton is uncommon due to the need for dosing four times a day, potential drug interactions, and the potential for hepatotoxicity with the resulting need for frequent monitoring of liver enzymes. In patients started on zileuton, serum alanine aminotransferase concentrations should be monitored before treatment begins, monthly for the first 3 months, every 2 to 3 months for the remainder of the first year, and then periodically thereafter for as long as the patient continues to receive the medication. Zileuton also inhibits the cytochrome P-450 (CYP) mixed function enzyme system and has been shown to decrease the clearance of theophylline, R-warfarin and propranolol.34... 

Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P-450 (CYP)3A4 or 2D6. Whether or not donepezil has the potential for enzyme induction is not known. No interactions with theophylline, cimeti-dine, warfarin, digoxin, or ketoconazole have been documented. In vitro studies show that inhibitors of CYP3A4 and 2D6 have the potential to inhibit the metabolism of donepezil. The clinical relevance of this is unknown. However, monitoring for possible increased peripheral side effects is advised... 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Keto con azole Inhibits several 200 mg twice reactions develops with continued use. Hematologic disturbances and hypothyroidism also seen. Generally well High potential for drug interactions due to potent induction of hepatic enzymes. Effective in a majority of causes ... 

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