Nursing Pharmacology Chapter 2: General Principles: Pharmacokinetics
Drug Metabolism: Phase I and Phase II Metabolism
Lipophilic drug properties that promote passage through biological membranes and facilitate reaching site to drug action inhibit drug excretion.
Note: renal excretion of unchanged drug contributes only slightly to elimination, since the unchanged, lipophilic drug is easily reabsorbed through renal tubular membranes.
Biotransformation of drugs to more hydrophilic molecules is required for elimination from the body
Biotransformation reactions produces more polar, hydrophilic, biologically inactive molecules -- that are more readily excreted.
Sometimes metabolites retain biological activity and may be toxic.
Drug biotransformation mechanisms are described as either phase I or phase II reaction types.
Parent drug is altered by introducing or exposing a functional group (-OH,-NH2, -SH)
Drugs transformed by phase I reactions usually lose pharmacological activity
Inactive, prodrugs are converted by phase I reactions to biologically-active metabolites
Phase I reaction products may:
Be directly excreted in the urine
React with endogenous compounds to form water soluble conjugates.
Parent drug participates in conjugation reactions that:
form covalent linkage between a parent compound functional group and:
Conjugates are highly polar, and generally biologically inactive.
One exception to this rule is a morphine metabolite, morphine glucuronide which is a more potent analgesic compared to the parent compound.
Conjugates tend to be rapidly excreted in the urine.
High molecular weight conjugates are more likely excreted in the bile.
The conjugate bond may be cleaved by intestinal flora with the parent compound released back to the systemic circulation.
This process, "enterohepatic recirculation" results in delayed parent drug elimination and a prolongation of drug effects.