Introduction

Question 1

target of diphenhydramine

Answer 1

1. H1 R in PNS: antihistamine
2. H1 R in CNS: sedative
3. ACh R in CNS: antiemetic
4. Histamine N-methyl transferase in CNS: (enhances actions of histamine on CNS)

Question 2

atropine

Answer 2

blocks sm contraction

Question 3

nicotine

Answer 3

blocks sk contraction

Question 4

binding forces between drugs/receptors

Answer 4

covalent bond (irreversible)
coordinate covalent bonds (irreversible)
ionic bonds (electrostatic forces)
hydrogen bonds (weak electrostatic forces)
van der Waals forces (weak electrostatic forces)
hydrophobic forces (weak interactions)

Question 5

receptor occupancy theory

Answer 5

D + R —> DR

D=free drug
R=free receptor
DR=drug-receptor complex

k1 = associate rate 
k-1 = dissocation rate 

equilibrium:
k1[D][R]=k-1[DR]

Question 6

EQUILIBRIUM DISSOCIATION CONSTANT

Answer 6

Kd

[D][R] = Kd
[DR]

Question 7

V =

Answer 7

V = [D] Vmax
Kd + [D]

D=free drug
V=amount of drug bound
Vmax=maximum occupancy of R

Question 8

[R]

Answer 8

[R] = [Rt] - [DR]

R=free receptor
Rt=receptor total
DR=drug-receptor complex

Question 9

[DR]

Answer 9

[DR] = [D] [Rt]

Kd + [D]

Question 10

Kd apparent is also known as

Answer 10

EC50

E = [D] Emax
Kd ap + [D]

E = biological response

Question 11

EC50

Answer 11

is the concentration of a drug that gives the half-maximal response

Question 12

occupancy assumptions

Answer 12

1. biological response = binding of D-R
2. magnitude of response = directly porprotional to receptor occupancy
3. conc of drug measured = same as conc of free drug in eq with receptor

Question 13

advantage of log dose-response plot over arithmetic

Answer 13

expands the linear portion of curve = help determine Kd/Kd app

-draw line at 50% occupancy

Question 14

therapeutic index

Answer 14

TI = LD50/ED50
lethal dose in 50% of population
effective dose in 50% of the population

High TI =better = more dose needed to reach lethal threshold

Question 15

Scatchard

Answer 15

slope = -1/Kd
X intercept = Vmax

• drug binding with receptor
• only for binding
• not biological response
• linear curve

= reveal multiple drug binding sites ( at the top = slope larger vale = higher affinity = smaller Kd)

Question 16

double reciprocal

Answer 16

X intercept = -1/Kd
Y intercept = 1/Vmax

• used for biological response

Question 17

affinity

Answer 17

strength of binding

inversely proportional to Kd

Question 18

smaller Kd

Answer 18

higher affinity

Question 19

potency

Answer 19

ability of drug dose to elicit biological response

inversely proportional to Kd app

Question 20

partial agonist

Answer 20

an agonist cannot generate full biological response = low efficacy

Question 21

efficacy

Answer 21

the ability of drug once bound - modify the function of the receptor

Question 22

occupation governed by

Answer 22

affinity

Question 23

activation governed by

Answer 23

efficacy

Question 24

partial agonists have

Answer 24

antagonist activity when combined with full agonist

Question 25

competitive antagonist

Answer 25

binds reversibly to same site as agonist

curve shift RIGHT = less response

(same x intercept // shallower slope = larger Kd
(same y-intercept // x intercept bigger)

Question 26

KI/KB

Answer 26

equilibrium dissociation constant for a competitive antagonist

Question 27

KB and pA2

Answer 27

potency of an agonist

Question 28

pA2

Answer 28

pA2 = -logKI

negative log of the concentration of agonist that would produce a two-fold shift in the Kd apparent of the agonist

Question 29

noncompetitive antagonists

Answer 29

Binds reversibly to allosteric site or (rarely) irreversibly to same site as agonist

curve shift DOWN

(identical slope - shifted to lower value)
(x intercept = same
(y intercept = higher)

Question 30

noncompetitive antagonist, when added to an agonist

Answer 30

partial agonist activity

Question 31

inverse agonist

Answer 31

decreases the spontaneous activity of a receptor

opposite effect of an agonist
The addition of increasing amounts of a competitive antagonist will return the biological activity to the level observed in the absence of the inverse agonist

Question 32

drug desensitization

Answer 32

The response of the body to long-term treatment will often decrease over time
Multiple causes: 
conformational change in the receptor
receptor endocytosis
depletion of a mediator
increased drug metabolism
physiological adaptation