PCL201H1 Lecture 16: Lecture 16 Biotransformation I
Document Summary
Drug metabolizing enzymes are like the immune system: can protect the host organisms from foreign substances, dme: small molecules, immune system: large substances (viruses, bacteria, can harm host organism if not properly regulated and balanced. Drug biotransformation stable or reactive: produce stable metabolites, lower pk activity (inactivation) b, retention of pharmacological activity. Increase pk activity (prodrug activation: produce reactive metabolites, covalent binding to cellular macromolecules. Toxic consequences: cell injury or death, carcinogenicity, teratogenicity: reactive metabolites undesirable, electrophillic. Acetaminophen is active, but when metabolized by sult or ugt, becomes inactive. Sult transfers sulfer group from paps to acetaminophen. Inactive: decreased potency, more h20 soluble; side groups s, g governs duration of effect in body. With the action of xanthine oxidase, it is biotransformed to oxypurinol, an active metabolite with increased potency and half life. Decreased h2) solubility (contrary to what normally happens), and increased half life. Both are anti-arrhythmic drugs, both are active, have slightly different target selectivity, both potent.
