PHARMACOLOGY

 MICROSOMAL ENZYMES ::

Microsomal enzymes are the mixed function oxidases and requires nicotinamide adenine dinucleotide phosphate (NADP) and molecular oxygen The principle steps involved are shown in (1) Mixed function oxidase have a terminal protein cytochrome p-450 where a drug binds to form the complex (2) This complex gets reduced by flavoproteins and NADPH cytochrome with reductase system (3) The reduced p.450-drug complex then gets oxidized by the addition of molecular oxygen (4) The oxidized complex gives off the oxidized drug and the enzyme p.450 is regenerated 

Enzyme induction and enzyme inhibition ::

Miccrosomal enzymes are of great importance since a large number of drugs are metabolized by these enzymes microsomal enzymes act on compounds of high lipid solubility Various microsomal enzymes are mixed function oxidases reductases esterases and UDP glucuronic acid transferase etc 

    Various drugs inhibit the activity of these enzymes and hence retard the biotransformation of their own as well as other drugs This is enzyme inhibition Drugs like ether ethanol chloralhydrate chloralose meprobamate phenytoin etc produce slight depression Others like iproniazid morphine estrogen porgesterone etc cause marked depression Tolbutamide carbutamide SKF 525 A etc produce marked depression of microsomal enzymes but recovary is also equally fast Mechanisms of enzyme inhibition are (a) inhibition of cytochrome p-450 (b) prevention of the penetration of drug into microsomes (c) inhibiton of the binding of the drug with cytochrome P-450 

    Certain drugs activate the microsomal enzymes by either increasing the formation of these enzymes i.e. protein synthesis or by inducing synthesis of cytochrome c reductase This activation is called enzyme induction Such drugs not only enhance their own metabolism but also that of others Enzyme induction hence may be one of the mechanisms of drug tolerance Drugs which are reported to cause enzyme induction are many but barbiturates are of great significance other drugs are chloroform nitrous oxide chlorbutanol chlorpromazine methadione nikethemide pethidine phenylbutazone diphenhydramine and androgens polycyclic hydrocarbons like DDT also produce enzyme induction