Pharmacodynamics

Question 1

What is pharmacodynamics?

Answer 1

study of the biochemical and physiological effects of drugs, their mechanisms of action, and how the drugs interact with the body

Question 2

Define affinity

Answer 2

measure of how tightly or strongly a drug binds to a receptor

Question 3

Define intrinsic activity

Answer 3

ability of a drug to evoke a response or effect in a target by altering some activity in the target (second messenger)

Question 4

Define efficacy

Answer 4

the strength of a single drug receptor interaction that evokes a response

Question 5

Define agonists

Answer 5

drugs that bind to receptors and produce some effect similar to the response produced by endogenous agents
*POSSESS INTRINSIC ACTIVITY

Question 6

Define antagonists

Answer 6

drugs that bind to receptors but do NOT produce an effect

*POSSESS NO INTRINSIC ACTIVITY

Question 7

What are the 4 targets for drug action?

Answer 7

1. receptors
2. ion channels
3. enzymes
4. carrier molecules

Question 8

What two factors affect drug-receptor interactions?

Answer 8

1. binding forces

2. structure activity relationships

Question 9

What 3 things can chemical structure of a drug affect?

Answer 9

1. affinity
2. intrinsic activity
3. efficacy

Question 10

How can you quantify drug responses to provide meaningful information about the effects of a drug and its usefulness?

Answer 10

create a Dose-Response (D-R) Curve which allows measurement of physiological response
*D-R curve cannot measure affinity

Question 11

What fact leads to the conclusion of the presence of spare receptors?

Answer 11

the fact that the maximum response of a receptor system is often evoked at a low percent of receptor occupancy

Question 12

What are spare receptors? What does their presence mean/entail?

Answer 12

they are receptors which exist in excess of those required to produce a full effect

this means you cannot directly correlate physiological responses to binding

Question 13

What 3 factors alter drug concentration at a receptor ?

Answer 13

1. metabolism/degradation
2. uptake into tissue
3. diffusion from the site of action

Question 14

When talking about response curves, what are the differences between quantal relationships and graded responses?

Answer 14

1. quantal relationships - based on ALL or NONE responses; provides estimate of percent of subjects who respond to any given dose
2. graded responses - based on data from single subjects; provides info about potency and efficacy

Question 15

Define competitive antagonist. Effect on D-R curve?

Answer 15

an antagonist (exhibits affinity but does not have intrinsic activity) that binds to the receptor in a reversible mass-action manner; blocks binding of agonist;
can be overcome by increasing agonist concentration; maximal response of agonist is NOT decreased; D-R curve is displaced to the right

Question 16

Define (pseudo) irreversible antagonism. Effect on D-R curve?

Answer 16

antagonist binds very tightly to the same site as an agonist; receptor irreversibly inactive and cannot be overcome with increasing agonist concentration; shifts the D-R curve to the right and depresses maximal responsiveness

Question 17

Define partial antagonists.

Answer 17

are agonists that evoke a response that is less than maximal; can diminish the response of full agonists when administered prior to administration of the full agonist; maximum response is diminished

Question 18

Define non-competitive (allosteric) interactions

Answer 18

antagonist does not bind to the same site as the agonist but rather binds somewhere else in the transaction system that leads to the physiological response

Question 19

What is an inverse agonist?

Answer 19

binds to same location as agonist but produces an opposite response; they are in a constitutively active state

Question 20

What are 2 changes ins receptor sensitivity that can occur? Explain both.

Answer 20

1. desensitization = diminish the response to a given dose drug; usually due to increased receptor exposure to ligand causing altered binding of the drug to receptor and decreased coupling of the drug-receptor complex to the signaling mechanism
2. supersensitivity - enhance the response to a given dose of a drug; usually due to decreased receptor exposure to a ligand; can be drug induced or pathophysiological

Question 21

Define tachyphylaxis

Answer 21

acute rapid decrease in response to a drug after increasing frequency of dosage

Question 22

Describe the process of receptor down-regulation

Answer 22

1. ligand binds to receptor and increases cAMP production activated protein kinase
2. protein kinase phosphorylates receptor and desensitizes it allowing arresting to bind
3. phosphorylated receptor is internalized
4. dephosphorylated receptor is recycled to membrane

Question 23

Name the 4 superfamilies of receptors and give their relevant response time scale.

Answer 23

1. channel-linked receptors (inotropic) = milliseconds
2. G-protein coupled receptors (metabotropic) = seconds
3. kinase-linked receptors = minutes
4. nuclear receptors (gene transcription) = hours