Basic Principles of Pharmacology I & II

Question 1

Difference between drug action vs. drug effect

Answer 1

Drug action: molecular effect. INVISIBLE.

Drug effect: pharmacologic effect. VISIBLE response.

Question 2

What is selectivity?

Answer 2

A property of a drug to cause a specific effect. Few drugs produce a single effect.

Primary effect –> desired
Secondary effect –> “side effects”, may or may not be desirable

Question 3

What are pharmacokinetics?

Answer 3

The time course of drug absorption, actions, and elimination

Question 4

What are pharmacodynamics?

Answer 4

The types of drug actions. Can be physiochemical (simple chemical interactions that are nonspecific like antacids, antiseptics) or receptor interactions (drug interacts with physiologic receptors)

Question 5

Which drug-receptor bonds are reversible, irreversible?

Answer 5

Reversible – ionic, van der waals, hydrogen

Irreversible – covalent

Question 6

What do second messengers do?

Answer 6

Produce amplification of the drug-receptor interaction

- Converts an event that happens outside the cell into a change that happens inside the cell

Question 7

Relationship between structure and activity

Answer 7

The better the drug fits in the receptor, the better the stimulation

Question 8

Michaelis-Menten equation

Answer 8

Effect = (Emax *[D])/(Kd+[D]) where Kd = dissociation constant = EC 50
- it’s a little different than enzyme kinetics. The drug is not consumed as a substrate, and the macromolecule is one of the reactants, not simply a catalyst.

Question 9

threshold (log dose response curve characteristic)

Answer 9

the beginning of the curve. The dose of agonist at which a response begins. May relate to the affinity of the agonist for the receptor.

Question 10

slope (log dose response curve characteristic)

Answer 10

rate of rise of the response on the steep portion of the curve, also relates to affinity

Question 11

maximal asymptote (log dose response curve characteristic)

Answer 11

the top of the curve, represents Emax for that particular agonist

Question 12

Receptor occupancy

Answer 12

Intensity of response is proportional to the fraction of the receptors occupied

Question 13

Intrinsic activity ***

Answer 13

ability to stimulate the receptor once bound. Relates to structure and influences efficacy and potency.

Greater intrinsic activity = greater efficacy

Question 14

Spare receptors

Answer 14

Not all receptors need to be occupied to achieve Emax. Less efficacious agonists may need to occupy more receptors than highly efficacious agonists.

Question 15

Secondary receptors

Answer 15

Receptors outside of the target tissue. May mediate other effects of the drug, aka “side effects”.

Question 16

How does the cell regulate receptors?

Answer 16

The cell can up or down-regulate a population of receptors by changing the total number of receptors or their sensitivity.
Ex: desensitization: can occur with down-regulation of the receptor, or fatigue or depletion of the intracellular or tissue mechanisms

Question 17

Agonist drugs

Answer 17

These drugs bind to the receptor and produce a pharmacologic effect. There are 2 important events:

1. Binding to the receptor
2. Activating the receptor after binding

• a better fit to the receptor from a more specific structure of the molecule results in more drug-receptor interaction and effect at lower doses

Question 18

Relationship between structure and activity

Answer 18

There is a difference between the binding site of the receptor and the effector portion of the receptor. The better a drug fits both of these, the greater the response. A drug that only fits the binding site and not the effector site will have no effect.

Question 19

Agonists with the same intrinsic activity

Answer 19

Agonists will differ by binding but not in activating the receptor (all can achieve Emax, therefore have the same intrinsic activity)

Question 20

Agonists with different intrinsic activity

Answer 20

Agonists will bind to the receptor in the same way but will differ in activating the receptor

Question 21

Agonists with different intrinsic activity AND different affinity

Answer 21

Agonists will have different affinities to the receptors AND also different intrinsic activities

Question 22

Efficacy

Answer 22

The ability of the drug to activate the effector portion of the receptor once the drug is bound to the receptor. Depends upon the STRUCTURE of the drug. VERTICAL relationship.

Question 23

Potency

Answer 23

Relates to the AMOUNT of drug needed for effect. Depends on the biologic system (receptor density, efficiency of stimulus-response mechanism of tissue) as well as interaction of the drug with the receptor (affinity, efficacy). HORIZONTAL effect.

Question 24

Competitive antagonists

Answer 24

Antagonist effect can be overcome by increasing dose of agonist.
Simple competitive antagonism: a simultaneous equilibrium exists for agonist and antagonist. Binding of antagonist to the receptor is weak and easily reversed.

Question 25

Noncompetitive antagonists

Answer 25

Can’t be overcome by increasing doses of agonist. Receptors remain occupied by antagonist because binding of the antagonist to receptor is strong (like covalent) and not easily reversed. The inhibitor can change the effector OR the binding site.