01 Pharmacodynamics

Question 1

Types of drug mechanisms

Answer 1

1. Ligand-receptor
2. Enzyme inhibitors–ACE inhibitors
3. transporter inhibitors–Cocaine (DA uptake carrier)
4. Ion channel inhibitor–Glibenclamide blocks K-ATP channel
5. Other–ex. Heparin binds thrombin

Question 2

Kd effect on affinity

Answer 2

Low Kd–high affinity

High Kd–low affinity

Question 3

Types of Binding forces between ligand and receptor

Answer 3

1. Ionic–major determinate of k1
2. H bonds
3. Van der Waals (major determinant of k2)

Question 4

EC50

Answer 4

Ligand concentration to produce 50% of drug effect

Question 5

Kact

Answer 5

aka EC50: ligand concentration to produce 50% of drug effect

Question 6

Intrinsic activity

Answer 6

(designated alpha)
Each drug’s fraction of Emax that it can illicit:

• Agonist: 1
• Antagonist: 0
• Partial agonist: 0-1
• inverse agonist: <0

Question 7

What happens when you reduce spare receptors?

Answer 7

Initially, EC50 is increased while Emax remains the same. Eventually, EC50 stays constant but Emax decreases.

Question 8

Types of antagonists

Answer 8

1. Chemical–binds to agonist
2. Physiological–activate opposing physiological input
3. Pharmacological–blocks receptor

Question 9

What happens when you increase competitive antagonist?

Answer 9

EC50 is increased, but Emax stays same because antagonist can be ‘outcompeted’

Question 10

What happens when you increase irreversible competitive antagonist with no spare receptors? with spare receptors?

Answer 10

No spare receptors: EC50 remains same, but Emax decreases permanently.
With spare receptors–EC50 increases and Emax stays same until no more spare receptors.

Question 11

What happens when you increase noncompetitive antagonist?

Answer 11

EC50 stays same, Emax decreases.

Question 12

Potency vs Efficacy

Answer 12

Potency–ED50
Efficacy–Emax

Efficacy matters more clinically.

Question 13

Quantal Dose-Response Curve

aka ?

Answer 13

• aka Cumulative Frequency Distribution.
• curve shows when at what dose that 50% of population receives a specific response to that dose. Shows variation of response within a population.

Question 14

tachyphylaxis

Answer 14

rapidly developing resistance to a drug

Question 15

Therapeutic Index (TI)

Answer 15

TI= TD50/ED50

Used to measure safety range of dosing. TD50 is dose at which 50% of people receive toxic response. ED50 is dose at which 50% of people receive drug effect.

Question 16

Rt

Answer 16

-total # of receptors
Rt = LR + R

(sum of bound and unbound receptors)

Question 17

Kd

Answer 17

equilibrium dissociation constant
Ligand + Receptor –> LR complex
k1 —>
k2 <—

Kd = k2/k1

Question 18

hypo/hyper reactive

Answer 18

at the tails of the dose response curve

Question 19

hypersensitivity

Answer 19

allergic or inflammatory response