Dr.

Johnson Segment 2 Lecture Notes

Learning Objective 1: Basics of pharmacology
-Define pharmacokinetics
-Discuss absorption, distribution, metabolism, and excretion
-Define pharmacodynamics
-Why do different people respond differently to drugs?
-What happens when you take a drug?
It gets taken up (absorbed) by your gut and is distributed by the blood around your body,
ultimately it must be eliminated somehow or the concentration would keep on increasing
with every dose.

Amount of drug in the blood changes over time

What processes are involved in drug uptake and elimination?

The details depend on the properties of the drug and the route of administration
1) Drug uptake from the gut
2) Absorption
3) Passive diffusion, alone or with other molecules
4) Active transport
Barriers to absorption
1) Conditions in the gut, motility, pH, gut contents etc
2) Efflux pumps
Distribution of drugs around the body and uptake by the target organs
-Distribution around the body is impacted by many things
-Differences in blood flow to organs and tissues
-Differences in drug solubility in fatty versus lean parts of tissues
-Binding to specific transport proteins and non-specific binding
Uptake into cells
-Passive diffusion
-Active transport
Drug metabolism

-Drugs are metabolized by the body to make them easier to excrete.

-Involves enzyme-mediated chemical modification and typically occurs in two phases:
Phase I: Cleavage of the compound, or addition or modification of functional groups by
hydrolysis, oxidation, or reduction reactions.
Phase II: Conjugation with compounds such as glucuronic acid, glycine and sulfate which
make the drugs more soluble.
-The most important enzymes for phase I metabolism are ten members of the cytochrome
P-450 super family which metabolize a vast array of drugs.
CYPs 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, 3A5, 3A7
-Many phase II enzymes are transferases, such as UDP-glucuronosyltransferases
The consequences of drug metabolism
-Some drugs must be metabolized to become active or more active (pro-drugs).
-Metabolism can produce active metabolites that we want, and toxic metabolites that
cause problems.
-Many drugs can be metabolized by several different enzymes resulting in the generation
of many different metabolites with different properties
-Metabolism is a key step in the elimination of many drugs
Drug excretion
-The majority of drugs are excreted in the urine
-Drugs and their metabolites are filtered out along with the water and electrolytes, but are
not reabsorbed if they are polar.
-Many drugs are actively secreted by the proximal tubule.
-Drugs are also excreted into the gut in the bile and exit the body in the feces
-This involves the active transport mechanisms.
-Different mechanisms for different drugs
-Important for large drug conjugates
Pharmacokinetics The study of how drugs move in the body
What the body does to the drug
Why do different people respond differently to drugs?
Many things can explain how different people taking the same dose of a drug can have a
very different outcome:
-Physiology: (Size and shape, Age, Gender)
-Health & wellbeing (Kidney function, Liver function, Heart disease, Lung disease)
Why do different people respond differently to drugs?
Many things can explain how different people taking the same dose of a drug can have a
very different outcome:
-Lifestyle and environment: (Smoking history, Alcohol use, Nutrition and diet, Other
medications, Environmental toxins, Exercise)
-Genetics