Senin, 09 Februari 2009

DRUG METABOLISM

DRUG METEBOLISM
All organism are exposed :
- To foreign chemical compounds
- In the air, water, and food
Pharmacologically active foreign chemicals
Endogenous substances
Metabolic pathways :
- To alter their activity & their susceptibility to excretion

THE NEED FOR DRUG METABOLISM
Portals for entry of external molecules into the body (pulmonary alveoli, intestinal epithelium) contain transporter molecules of the P-glycoprotein family → expel undersired molecules immediately after absorption.
Some foreign molecules are absorbed : toxic
Require mechanisms biotransformation :
- Mechanism by which the body terminates the action of some drugs
- It serves to activate prodrugs
More drugs : relatively lipid soluble
- Favorable to absorption across membranes
- Very slow removal from the body because the molecule would also be reabsorbed from the urine in renal tubule

A. PHASE I REACTIONS
• Oxidation
• Reduction
• Deamination
• Hydrolysis
B. PHASE II REACTIONS
• Are synthetic reactions
• Addition (conjugation) of subgroups to-OH, -NH2, and –SH functions
• The subgroups hat are added include glucuronate, acetate, glutathione, glycine, sulfate, and methyl groups.
• Relatively polar →less lipid soluble

SITE OF DRUG METABOLISM
• Liver
• Kidneys
• Blood
• Intestinal wall

DETERMINANTS OF BIOTRANSFORMATION RATE
• Vary markedly among different individuals
• Genetic
• Drug-induced
• Age
• Disease-related
• Gender

BIOTRANSFORMATION RATE
• Rate of biotransformation → the primary determinant of clearance
• Variations in drug metabolism must be considered carefully when designing a dosage regimen
• Smoking → enzyme induction in the liver & lung → ↑ the metabolism drugs

GENETIC FACTORS
• Hydrolysis of esters
• Acetylation of amines
• Oxidation

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