Introduction to Pharmacodynamics

Question 1

What are the different phases of clinical drug trials?

Answer 1

Phase 1 = a small number of healthy human volunteers is given the drug to determine safety and tolerability.
Phase 2 = a small number of patients is given the drug to determine efficacy and dose.
Phase 3 = a full scale double blinded RCT compares the drug against established therapy.
Phase 4 = post-marketing surveillance to detect any rare or long-term adverse effects.

Question 2

What are the 4 main drug targets?

Answer 2

Receptors
Carriers
Ion channels
Enzymes

Question 3

What are the 4 main types of receptor?

Answer 3

Ligand-gated ion channels
G protein coupled receptors
Tyrosine kinase linked receptors
Nuclear receptors

Question 4

What is the effect of a drug that is an agonist?

Answer 4

Agonists are drugs that bind to receptors and cause their activation.

Question 5

What is the effect of a drug that is an antagonist?

Answer 5

Antagonists are drugs that bind to receptors and do not cause their activation, but instead block the effect of agonists.

Question 6

What is the difference between competitive and non-competitive antagonists?

Answer 6

Competitive antagonists bind to the ligand-binding site; they can be overcome by adding more agonist. Non-competitive antagonists bind to a different site than the ligand-binding site; they cannot be overcome by adding more agonist.

Question 7

What is an inverse agonist?

Answer 7

Some receptors are constitutively active. In this situation, if a ligand reduces the level of constitutive activation, it is referred to as an inverse agonist.

Question 8

What are the possible mechanisms that cause drug tolerance?

Answer 8

The most common cause of development of tolerance to a drug is a decrease in the expression of a receptor. Other possible causes are:
Changes in the receptor (such as phosphorylation); exhaustion of mediators; increase in metabolic degradation of the drug; physiological adaptation; active extrusion of the drug from cells.

Question 9

What is the therapeutic index?

Answer 9

The TI = median lethal dose/median effective dose. A high TI drug is safer than a low TI drug because there is a greater difference between the effective dose and the lethal dose.