Ch.5: Principals of Drug-Receptor Interactions

Question 1

drugs do/do not initiate new processes**

Answer 1

do NOT. They speed up or slow down already occurring processes.

Question 2

endogenous substance*

Answer 2

substance naturally occurring in the body

Question 3

Receptors are usually coupled to:*

Answer 3

an effector (transducer) or ion channel. Includes enzymes and receptor-gated ion channels

Question 4

receptor “down regulation”*

Answer 4

excessive receptor stimulation –> decreased receptor density

Question 5

receptor “up regulation”*

Answer 5

decreased receptor stimulation –> increased receptor density

Question 6

effect of stopping long-term atenolol therapy?*

Answer 6

Will result in intense cardiac stimulation. Atenolol had been chronically blocking beta-1 receptors, leading to up-regulation of beta-1 receptors. If therapy is suddenly stopped, circulating EP will bind with these up-regulated beta-1 receptors, resulting in CV stimulation.

Question 7

T/F there are variable life-times for different receptors*

Answer 7

T

Question 8

There are an abundance of which receptors in vessel of skeletal muscle?*

Answer 8

beta-2 receptors

Question 9

There are an abundance of which receptors in vessel of cutaneous skin?*

Answer 9

alpha-1

Question 10

beta-2 receptor stimulation relaxes/constricts vascular smooth m.*

Answer 10

relax

Question 11

What would be expected effect of EP on systemic blood pressure inthe presence of an agent that blocks alpha adrenergic receptors?***

Answer 11

drop in BP

Question 12

T/F a drug with alpha-adrenergic blocking ability can stimulate the animal?*

Answer 12

T (i.e. acepromazine)

Question 13

alpha-1 receptor stimulation relaxes/constricts vascular smooth muscle?

Answer 13

constrict

Question 14

4 broad categories of receptors for drugs

Answer 14

1) ion channels
2) G-protein coupled receptors (GPCR)
3) receptor tyrosine kinase (TRK)
4) intracellular receptors

Question 15

receptors that are coupled to G proteins and ion channels are common therapeutic agents*

Answer 15

:)

Question 16

G protein coupled receptor types

Answer 16

adrenergic
cholinergic
dopaminergic
histamine
opiate
serotonergic

Question 17

ion channel coupled receptors

Answer 17

nicotinic receptor gated Na+ channels
GABA receptor gated Cl- channels
Glutamate-coupled cation channels

Question 18

T/F: a drug may have different actions on different classes of receptors*

Answer 18

T

Question 19

What percent stimulation do full agonists have?*

Answer 19

100%

Question 20

What percent stimulation do partial agonists have?*

Answer 20

1-99%

Question 21

Competitive antagonists have reversible or irreversible binding?*

Answer 21

reversible

Question 22

Non-competitive antagonists have reversible or irreversible binding?*

Answer 22

irreversible

Question 23

Properties of Receptor Agonists (6)*

Answer 23

• bind rapidly
• response dissipates quickly after dissociating from receptor
• prolonged stim. of receptors leads to diminished response
• 2 or more agonists are no more effective than 1 at max. conc.
• produce changes independent of other ligands
• full agonist produces a complete or maximal effect

Question 24

Properties of Receptor Antagonists (5)*

Answer 24

• bind to receptor to prevent agonist binding
• have zero efficacy*
• usually bind and dissociate more slowly than agonists
• reversible or irreversible
• unable to elicit cellular or physiological actions when given alone

Question 25

3 major types of antagonists used clinically. Which most common?*

Answer 25

-competitive, noncompetitive, irreversible. Competitive most common

Question 26

competitive antagonist*

Answer 26

antagonist that binds REVERSIBLY to a receptor. Mutually competitive with agonist, and one can override the other when present in excess.

Question 27

non-competitive antagonist*

Answer 27

antagonist that bind IRREVERSIBLY or bind to an alternate site on a receptor at which agonists do not compete.

• extent of blockage proportional to dose of antagonist
• cannot be overcome by raising conc. of agonist

Question 28

How to remedy overdose of pancuronium, a paralytic agent that acts a competitive antagonist at nicotinic cholinergic receptors?*

Answer 28

use a short-acting AChE inhibitor, such as edrophonium

Question 29

AChE works primarily on which receptors?*

Answer 29

nicotinic

Question 30

AChE agents work how?*

Answer 30

(muscle relaxants). block nicotinic receptors and block AChE ability to bind

Question 31

How to remedy overdose of non-competitive antagonist at nicotinic cholinergic receptor*

Answer 31

Can’t. be careful!

Question 32

dissociation constant (Kd)*

Answer 32

mathematical relationship that predicts the relative conc. of the drug-receptor complex at any conc. of drug

• the drug conc. at which half of the receptors are occupied by drug
• independent from cellular response

Question 33

high affinity has low or high Kd?*

Answer 33

low

Question 34

low affinity has low or high Kd?*

Answer 34

high

Question 35

Why might a drug with high affinity not necessarily also have high potency?*

Answer 35

drug could have poor bioavailability, poor access to receptor site, etc.

Question 36

Specificity (selectivity)*

Answer 36

measure of a drug’s ability to produce one effect (desirable) relative to its ability to produce another effect (undesirable). The dose that creates an undesirable response in 50% of patients relative to dose that creates desirable response in 50% of patients

Question 37

Drug has high (good) specificity if: *

Answer 37

ED50 (undesirable)&raquo_space;> ED50 (desirable) (Want a large separation between desirable and undesirable effects)

Question 38

drug safety is most commonly determined by:*

Answer 38

comparing drug doses that produce a desired effect (ED) relative to doses that are lethal (LD)
-a lot of species variation**