Lecture 1

Pharmacodynamics is what drugs do to the body, the physiology involved

Pharmacokinetics is what the body does to drugs, the ADME principle

• Absorption

• Distribution

• Metabolism

• Elimination

Terfenadine

• Marketed as a nondrowsy antihistamine

• It is a prodrug

• H1 receptor antagonist, it 

• Metabolized in the liver into its active form fexofenadine

• Terfenadine in its inactive form can cause unwanted issues, it blocks the potassium ion channels affecting the electrical activity and beating of the heart

• Creates an off target effect leading to potentially lethal effects

• The liver enzyme used to metabolize terfenadine was CYP3A4

Prodrug - compound activated by some metabolic step

Receptor - the molecular target of a drug

Off Target Effects - drugs are not specific to one receptor and can influence other receptors

Adverse Effects - undesirable drug effects

On-Target Effects - related to the mechanism of the drug

Pharmacogenetics - genetic backgrounds can affect drug response

Receptor Theory

1. Receptors have a high affinity for its endogenous (ligand)

2. The ligand binds and has an early recognizable chemical event

3. Receptors must be structurally specific for a ligand

4. Receptors are saturable and finite (limited binding and inhibition)

• The majority of drugs bind reversibly to proteins, forming an equilibrium between bound and unbound proteins

• Only bound drugs can have an effect on the receptors

• Drugs bind through electrostatic interactions (reversible) or covalent bonds (irreversible) 

• More complementary interactions allow for better drug binding

• A tighter binding drug requires lower doses to reach the desired therapeutic effect

• Receptors are selective, not specific

• Drug effect is the function of the total amount of receptors, how much drug is bound to the receptors and the affinity