DONE Pharmacodynamics

Question 1

Intrinsic efficacy

Answer 1

Ability of ligand to generate the active form of the receptor (R*)

Question 2

Efficacy

Answer 2

Cause a measurable biological response

Question 3

Potency

Answer 3

Concentration of a drug that evokes 50% of its maximal response (EC50)
Lower EC50 = more potent drug/ligand

Combines affinity + efficacy

Question 4

Full agonist

Answer 4

Tends to be endogenous ligand (e.g. ACh)
Spare receptors
EC50 = or less than Kd

Question 5

What is a partial agonist?

Answer 5

Ligand that evoke responses that are lower than the maximal response of a full agonist = lower Emax values + lower intrinsic efficacy
No spare receptors
EC50 = Kd

Question 6

What are the 3 types of drug antagonism?

Answer 6

1. Reversible competitive = at same binding site as endogenous ligand (orthosteric site),weak bonding = inhibition is surmountable by addition of more agonist than antagonist
2. Irreversible competitive = at same binding site as endogenous ligand, high affinity with slow dissociation (covalent bonding possible) = non-surmountable (antagonist binds irreversibly)
3. Non-competitive = bonding at allosteric site (no competition), high or low affinity and covalent/non-covalent bonding

Question 7

Agonists have both … but antagonists have only …

Answer 7

Intrinsic efficacy + efficacy

Affinity

Question 8

Problems with salbutamol

Answer 8

Treats asthma (Beta 2 adrenoceptor = open up airways)
Angina = beta 1 adrenoceptor = increase HR
NOT SELECTIVE AS TARGETS MORE THAN 1 RECEPTOR

Question 9

Spare receptors

Answer 9

Less than 100% receptor occupancy = 100% response
Due to signal amplification
Increase sensitivity = influence potency, allow responses @ low conc. of agonist
Allow lower conc of agonist (I.e. at Kd of drug)

Question 10

What does maximal response indicate?

Answer 10

Intrinsic activity

Question 11

What is clinical efficacy?

Answer 11

Measure of how well a treatment succeeds in achieving its aim

Question 12

What is the dissociation constant, Kd?

Answer 12

Conc. of ligand required to occupy 50% of the available receptors

Lower value = higher affinity
(Affinity low + Kd high = need higher conc. of ligand to occupy 50% of available receptors)

Question 13

What is maximal response, Emax?

Answer 13

100% of the measured response in the experimental subject

Question 14

Define concentration and dose

Answer 14

Conc. = known conc. of drug @ site of action
Dose = conc. @ site of action unknown

Question 15

What is the difference between selectivity and specificity?

Answer 15

Selectivity = drug shows preference for 1 molecular target, interacts with other targets 
Specificity = interacts with 1 receptor type