Lecture 2 - Pharmacokinetics

Define pharmacokinetics and contrast it with pharmacodynamics

Pharmacokinetics - effect of body on drug

Pharmacodynamics - effect of drug on body

Define absorption, distribution, metabolism, and elimination

Absorption: drugs cross membranes

Distribution: drugs into tissues

Metabolism: inactivation of drug by enzymes in the body

Excretion: removal of metabolites or the unchanged active drug from the body

Understand basic principles determining passage of drugs across biological membranes

• few drugs are carried by carriers or endocytosis

• partition coefficient determines absorption

Define pKa and understand how it can be used to predict the percentage of a weak acid that will be ionized or non-ionized

• pH = pKa when 50% of the weak acid is ionized

• when pH > pKa… less ionized

• when pH < pKa… mostly ionized

Understand examples of weak acid/base diffusion across biological membranes in the kidney (how to enhance aspirin excretion) and GI tract

Define bioavailability and how it varies with different routes of administration

Distinguish between enteral and parenteral routes of drug administration

Describe the first pass effect and define bioavailability in terms of first pass metabolism

Describe drug distribution and the factors that influence it

Describe how the blood brain barrier can determine the CNS effects of drugs

Describe the renal and biliary excretion of drugs

Define half life and use half life to calculate drug elimination over time.

Define biotransformation and its fundamental purpose

Describe and distinguish between phase 1 and phase 2 reaction and recognize various types of reactions as being phase 1 or 2

Define a prodrug and describe when it may be necessary to develop a prodrug

Understand the principles of drug dosing and what is meant by the term therapeutic window

Describe how changes in pharmacokinetics can influence dosing for active drug and prodrugs and drug efficacy/safety

Distinguish between intrinsic and idiosyncratic drug toxicity

Understand how induction/inhibition of metabolic enzymes can alter drug effects

Know that CYP3A4 is the metabolic enzyme most commonly involved in drug interaction

Define the term genetic polymorphism and describe how a genetic polymorphism can effect drug metabolism

Define the term pharmacogenetics and cite the example of how genetic polymorphisms in VKORC1 and CYP2C9 can alter responsiveness to warfarin

Understand how individual attributes can induce pharmacokinetics

Understand how high doses of acetaminophen can cause hepatotoxicity due to NAPQI formation

Describe how chronic alcohol consumption can affect acetaminophen metabolism and increase the risk for hepatotoxicity

Understand the basic definition of clearance

Explain what it means for a drug to have a small or large volume of distribution