Question

1. How are drugs chemically converted in drug metabolism (generally speaking)?
2. What are cytochrome P450 enzymes and how do they relate to drug metabolism?
3. How does the number of genes that code for cytochrome P450 relate to drug variation?
4. How can drug combinations affect metabolic rate?

Answer 1

Drugs: A substance used to treat an illness , relieve a symptom or modify a chemical process in the body for a specific purpose , is called a drug.

Metabolism: The complete set of chemical reactions that occur in living cells , is called Metabolism.

Drugs and its metabolism

The primary site of drug metabolism is liver. So usually all drugs should have to pass through liver via blood stream. Oral medications also absorbed by blood in the small intestine, then carried to liver. During drug metabolism, any pro-drugs present, become active and active drugs become pro- active by the help of enzymes. Also active drugs metabolites converts into inactive form for further elimination through urine or bile.

Cytochrome P 450

The main enzymes used in drug metabolism is a group of Cytochrome P 450 enzymes. These enzyme react with drugs and make inactive pro- drug forms into active forms to produce its effect or mechanism of action, there by achieving therapeutic effect. Also this enzyme helps in the metabolism of already metabolized drug products ( metabolites) to act again. Cytochrome P 450 also makes active metabolites of drugs into inactive form and helps in its excretion through urine or bile. These enzymes helps in the metabolism of toxic compounds and thus its elimination through urine or bile .

Drug variation and the number of Genes code for the enzymes:

Cytochrome P 450 enzymes are coded differently by gene coding, that is identified by the Human Genome project. Difference in the numbers of Gene coding for the Enzyme Cytochrome P 450 affects the metabolism of dugs or it causes variation in drug metabolism. The activity level of "clearance of drug ' by inactivating the excess drug compounds or bioactivating the certain drug compounds are varied according to the gene coding.

For example : Antifungal drugs are metabolized differently : CY P 3A4/S ,metabolizes 36% , Whereas CY P 2D6 metabolizes only 19 % of drug.

Drug Combination and Metabolic rate:

Certain drug interfers with the CY P 450 enzyme , some drugs increases the activity of the enzyme through enzyme induction ( biosynthesis of an isozyme) or by enzyme inhibitions ( inhibiting the CYP enzyme activity). Certain drug combination affects the metabolic rate of drugs by CY P enzymes. If one drug in the combination interfers the Enzymes activity of another drug , results in the decreased metabolism of second drug, affecting the clearance of drugs from the body. It inturn increases the accumulation of drug metabolite and increases the toxic effects or adverse effect of second drug. So the Drug Combination should be cautious or need dosage adjustments when combining two drugs together.