Enzymes drugs interacting with

Interactions with Cytochrome 450 Enzymes. Drug interactions with opioid analgesics can also result from their interaction withcyctochromep450 (CYP) isozymes, specifically 3A4 and 2D6 (Table 7.5) (50). 

Ethic variations in medication responses include differences in therapeutic responses and susceptibility to adverse effects. Such differences are attributable mostly to two aspects, the variation of enzyme activities for the metabolism of medications, and variations of the drugs interactions with target binding sites. 

Drugs interact with enzymes and receptors mainly through van der Waals forces and hydrogen bonding they need the correct shapes and sizes to fit into the active sites of the targets. 

As described for receptor interactions, enantioselectivity may also be manifested in drug interactions with enzymes and transport proteins. Enantiomers may display different affinities and reaction velocities. 

Levy RH et al. Metabolic Drug Interactions. With information on drug metabolising enzymes, inhibitors and inducers. 

By now you will be comfortable with the idea that the body treats drugs as just another set of chemicals to cope with, and also the idea that drugs interact with many molecules in many sites - with gastric acid, with chemicals in food, with enzymes in the gut and others in the gut wall and liver, with plasma proteins in the blood, and (often transiently) with their tissue receptor once they have got that far. 

Rifabutin appears as effective as rifampin in the treatment of drug-susceptible tuberculosis and is used in the treatment of latent tuberculosis infection either alone or in combination with pyrazinamide. Clinical use of rifabutin has increased in recent years, especially in the treatment of HIV infection. It is a less potent inducer of cytochrome 450 enzymes pathways than rifampin and results in less drug interaction with the protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Rifabutin is therefore commonly substituted for rifampin in the treatment of tuberculosis in HIV-infected patients. Another important use of rifabutin in the HIV-infected population is prevention and treatment of disseminated MAC. 

Flavonoids, as food components or potential drugs, interact with a wide range of proteins by distinct mechanisms weak and rather unspecific binding of tannins to proline-rich or histi-dine-rich random coils leading to protein precipitation, specific enzyme inhibition, and... 

Research on drug interactions with zolpidem and zaleplon is limited, but any drug with CNS depressant effects could potentially enhance the CNS depressant effects of zolpidem and zaleplon through pharmacodynamic interactions. In addition, zolpidem is primarily metabolized by CYP 3A3/4, and zaleplon is partially metabolized by CYP 3A3/4. Thus, inhibitors of these enzymes may increase blood levels and the toxicity of zolpidem. 

Drug interactions The label states that no pharmacokinetic-based drug-drug interaction studies have been conducted with Synarel. However, because nafarelin acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes, drug interactions would not be expected to occur. 

Because of its substantial inhibition of CYP 3A3/4, this antidepressant is prone to pharmacokinetic drug-drug interactions with substrates for this enzyme ( Table 7-30). That is important because CYP 3A3/4 is responsible for approximately 50% of all known drug metabolism. Thus, there are a number of medications that either... 

Studies in recent years have revealed a number of remarkable drug interactions with irreversible or mechanism-based inhibitors of CYP3A, many of which can be attributed to inhibition of sequential intestinal and hepatic first-pass metabolism. Mechanism-based inhibition involves the metabolism of an inhibitor to a reactive metabolite, which either forms a slowly reversible metabolic-intermediate (MI) complex with the heme moiety or inactivates the enzyme irreversibly via covalent binding to the enzyme catalyzing the last step in the bioactivation sequence. As a result, mechanism-based inhibition is both... 

Iatsimirskaia E, Tulebaev S, Storozhuk E, et al. Metabolism of rifabutin in human enterocyte and liver microsomes kinetic paramters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents. Clin Pharmacol Ther 1997 61 554-562. 

---