Drug Metabolism

Drug Metabolism

 Drug metabolism is transforming drugs, so they can be excreted from the body. They can interact with other drugs and foods, . Interactions can lessen or magnify the desired therapeutic effect of a drug, or may cause unwanted  side effects. There are thousands of possible drug-to-drug and drug-to-food interactions, and many medications and supplements are contraindicated  under certain conditions or in patients with specific diseases and disorders. This is why it is important that patients told their physician fully informed about all drugs and dietary supplements including herbal remedies they are taking.
Most drugs are treated by the body like foreign substances, also known as xenobiotics. Humans have evolved a complex system for xenobiotic metabolism. It is thought that exposure to the many toxic compounds in plants has facilitated the development of enzyme systems to detoxify foreign substances. Occasionally, though, the enzymes make an intermediate more toxic than the parent compound. This can happen with some of the compounds in cigarette smoke.
The metabolism of drug depend on many factors
 Physiological factors
AGE
in neonates & infants ==>LMEs (liver microbial enzymes) are immature meaning not well-developed
in geriatric ==>LMEs are impaired meaning their activity decrease
SO we can say that we must adjust drug dose for pediatrics & geriatrics carefully
sex
males have higher activity of LMEs than females WHY
because male sex hormones are microsomal enzyme inducers but female  sex hormones are microsomal enzyme inhibitors.

NUTRITION

malnutrition decreases activity of LME

Genetic factors
due to species & individual differences

Environmental factors
STRESS
leads to increased metabolism HOW
stress increases blood level of glucocorticoids which are LME inducers
FOREIGN COMPOUNDS
as insecticides & preservatives ==> LME inducers
DRUGS
  some drugs are LME inhibitors but most drugs are LME inducers.

Drug metabolism usually consists of two phases.

 Phase 1 

non synthetic reactions
for all types of drugs
involve metabolic modifications which may give more active compounds than original
EX
Oxidation : methyl alc. is oxidized to formic acid==> toxic
phenacetin is oxidized to paracetamol
tremorine is oxidized to oxotremorine==>tremor inducing drug
Reduction : trichloroethanol is reduced to chloral hydrate
Hydrolysis : Acetyl salicylate is hydrolyzed to acetate & salicylate

Phase 2

 synthetic reactions
for only some drugs
involve conjugation to give water sol. subs. easily to be excreted
Conjugation is done with glucoronic acid (mainly) ,acetic acid ,glycine ,or sulphate
Ex
Benzoic acid + Glycine =====> Hippuric acid