What is pharmacokinetics?
What the body does to the drug
What is pharmacodynamics?
The study of the biochemical and physiological effects of drugs on the body
What are modulators?
Drugs that inhibit or induce an enzyme involved in the clearance of a drug
What are the three avenues of thought that should be used to determine a drug interaction?
- Why is the drug doing too little?
- Why is the drug doing to much?
- The Syx are strange
In a patient where pharmacologic effect is not seen, what could be two causes?
- Pharmacodynamic (NSAID doing the opposite of an ACEI)
- Pharmacokinetic (Induction of enzymes)
What is the pharmacodynamic example resulting in inadequate effect of the drug?
ACEI and NSAIDS. ACEI used to decrease BP, but the NSAIDS caused constriction of the afferent arterioles and increase in BP thru RAAS.
Itraconozole is used to treat onchomycosis, but a concurrent PPI is used decreasing the absorption of the itraconozole. What type of drug interaction is this?
Pharmacokinetic. The itraconazole needs an acidic environment to be bioavailable. The PPI makes the stomach more basic, decreasing the bioavailability of the itraconazole
What are the two basic pharmacokinetic scenarios that a drug is not having its desired effect?
Either the bioavailability is decreased, or there is enzyme induction
What is the MOA of pharmacokinetic inducers and inhibitors?
- Inducers increase enzyme through transcription
- Inhibitors compete by binding to the receptor and preventing access to the substrate
What is a pharmacokinetic example of inhibition between metoprolol and propoxyphene?
Propoxyphene is a potent inhibitor of Cytochrome P450. Metoprolol cannot be degraded. Therefore, regular doses of metoprolol can cause life-threatening bradycardia
What is the cytochrome P450 group?
Group of oxidase enzymes
What two general processes can the CP450s perform?
- Inactivation: Active Drug --> CP450 --> Inactive drug
- Activation: Inactive Prodrug --> CP450 --> Active drug
What is significant about P450 polymorphisms?
Because P450 enzymes are polymorphic, amounts of an enzyme vary between a population and therefore, inactivation/activation of drugs can differ