Pharmacodynamic lecture

Question 1

What is a drug?

Answer 1

Any substance that brings about a change in biological function through its chemical actions.

Question 2

What is the common size of a drug and why?

Answer 2

Small (MW>10) to very large (MW > 10,000)
Vast majority between 100-1,000

Too small—> high interaction = high toxicity
Too large –> low interaction = below therapeutic dose.

Question 3

3 types of receptors?

Answer 3

DNA, RNA, Lipids

Question 4

Agonist

Answer 4

mimic actions of endogenous compounds

-interacts with receptor = response

Question 5

partial agonist

Answer 5

Bind to receptor and produce only a partial response.

Question 6

Antagonist

Answer 6

interferes with the action of an agonist by binding to receptors

Question 7

Relationship of dose and response depends on these two things:

Answer 7

1. number of receptors

2. Affinity of the receptors for the drug

Question 8

Affinity vs. Specificity

Answer 8

Affinity: how tightly does a drug bind to the receptor

Specificity: how tight a drug binds to receptor A vs. receptor B.
-molecular size, shape, and charge

Question 9

Potency

Answer 9

measure of how much drug is required to elicit a response.

EC50 value

Question 10

Potency ratio

Answer 10

Difference in potency between two drugs:

EC50 Drug A / EC50 Drug B

Question 11

Efficacy

Answer 11

measure of the degree of a response a drug is capable of.

Emax determines efficacy of drug

Question 12

Drug selection in terms of efficacy and potency?

Answer 12

Drug is selected on efficacy and potential side effects.

Dose of drug to be administered is determined by the potency of the selected drug

Question 13

Therapeutic advantage vs. disadvantage of a noncompetitive antagonist

Answer 13

1. Irreversibly binds = Antagonist will maintain blockade when the concentration of endogenous agonist episodically increases

Disadvantage:
-If overdose occurs, the antagonist-induced blockade will be difficult to overcome

Question 14

Mechanisms of Antagonism (other than competitive vs. noncompetitive)

Answer 14

Chemical Antagonism:
-one drug antagonizes another drug by binding to and inactivating a second drug.

Physiological Antagonism:
-a drug can be antagonized by endogenous compounds. Ex. glucocorticoids lead to an increase in blood sugar – antagonized by insulin.

Pharmacokinetic Antagonism
-a drug induces the metabolism of another drug.

Question 15

Spare receptors

Answer 15

a maximal response in a tissue can occur without drug binding to all of the available receptors.

Increase likelihood of drug being bound to have a maximal response
= Increase Tissue Sensitivity to drug

Question 16

Limitations of a graded dose-response curve?

Answer 16

E. vs. Log [D]

1. difficult to construct when pharmacological response is quantal (either or event).
   ex. prevention of convulsions or arrhythmia.
2. Quantitative dose-response relationship in a single individual may have limited applicability to others (due to inter-invididual variability)

Question 17

What is a quantal dose-response curve?

Answer 17

Cumulative % of individuals responding vs. log [dose].

-Clinical trials
ED50
-provide a convenient way for comparing the potencies of drugs in a clinical setting.

Question 18

Therapeutic index

Answer 18

TD50/ ED50

Toxic dose/ Effective dose