general principles lect 1

Question 1

pharmacodynamics

Answer 1

biochemical and physiological effects and mechanisms (what drugs do to the body)

Question 2

pharmacokinetics

Answer 2

absorption, distribution, metabolism, and elimination of drugs (what body does to drugs)

Question 3

measures the ability of a drug to bind to a receptora

Answer 3

affinity

Question 4

Kd

Answer 4

equilibrium dissociation constant: concentration of free drug when binding is at 50%

Question 5

relationship between Kd and affinity

Answer 5

the lower the Kd, the higher the affinity

Question 6

efficacy (intrinsic activity)

Answer 6

measure of biological response resulting from binding of a drug - determines maximal response that can be obtained with a drug

Question 7

potency

Answer 7

dose (amount of drug) required to produce a desired effect

Question 8

EC50

Answer 8

concentration required for half-maximal effect

Question 9

relationship between EC50 and potency

Answer 9

lower the EC50 the more potent the drug

Question 10

binds to receptor and initiates a response

Answer 10

agonist (full vs partial)

Question 11

binds to receptor but does not initiate a response

Answer 11

antagonist (inhibits response to an agonist) -competitive vs non-competitive

Question 12

binds to different receptor site than agonist and alters the reponse to agonist

Answer 12

allosteric activators and inhibitors

Question 13

interaction between drug and receptor is reversible unless they are bound by what kind of bond

Answer 13

covalent

Question 14

at drug-receptor equilibrium, how many receptors are bound?

Answer 14

half of the receptors are bound; half are free

Question 15

efficacy (alpha; intrinsic activity) is the ability of a drug to initiate a response; if there is a 100% response, Alpha = ?; if there is a 0% reponse, alpha = ?

Answer 15

1; 0

Question 16

what type of agonist have affinity and intrinsic activity (alpha = 1)

Answer 16

full agonist

Question 17

what type of agonist have affinity but no intrinsic activity (alpha = 0)

Answer 17

antagonist

Question 18

what type of agonist have affinity but lower intrinsic activity (0

Answer 18

partial agonist

Question 19

What Emax?

Answer 19

Emax: response produced will increase with increasing drug concentration until a maximal response is reached

Question 20

what is Emax a function of

Answer 20

• amt of drug - ability to evoke a response - the number of available receptors

Question 21

plotting %biological effect vs log[drug] gives what types of curve. what effect does this have on theraputic effect and toxicity

Answer 21

sigmoid curve - expands the scale at low concentrations where the response increases rapidly (theraputic effect) and contracts at high concentrations where the response is not changing as quickly (toxicity)

Question 22

in graded dose-response curves, what does the slope of the curve indicate

Answer 22

how rapidly the response changes when the dose in increased. Steep slopes are risky (small theraputic window)

Question 23

What do quantal dose-response curves measure

Answer 23

frequency with which a response will occur to a given dose within a population - “all or none effect” - frequency of response is measured - determines doses that produce therapeutic and lethal effects

Question 24

How is therapeutic ratio measured in humans

Answer 24

TD50 (toxic dose)/ED50: (LD50= dose that is toxic in 50% of population that recieves the drug). ex: if TR = 4 and 100mg is effective in 50% of population; then 400mg is lethal in 50% of population

* animal studies can use LD50: lethal dose

Question 25

Margin of safety

Answer 25

= LD1/ED99 - higher the margin of safety, safer the drug

Question 26

how does number of receptors affect sensitivity of a cell to a drug

Answer 26

the more receptors, the more sensitive a cell is to a drug

Question 27

when do spare receptors exist

Answer 27

when it is possible to elicit a maximum biological response without occupying all of the available receptors

Question 28

when spare receptors exist, the concentration-response curve (ED50) is shifted to what side

Answer 28

shifted to smaller concentrations-> to the left

Question 29

what is the relationship between EC50 and Kd when there are spare receptors

Answer 29

EC50 is lower than Kd * maximal response still produced due to amplification of the cell signaling mechanism

Question 30

clinical implications of spare receptors

Answer 30

use a lower dose

Question 31

how is potency determined on a dose response curve

Answer 31

postion along the x-axis; a drug is more potent if a curve is located near the left side of the x-axis; a drug is less potent is a curve is located near the right side of the x-axis

ex: Drug X is more potent than Drug Y

Question 32

Drug + receptor -> [DR]; what is the rate constant for DR association

Answer 32

K1

Question 33

[DR] -> Drug + receptor; what is the rate constant for DR dissociation

Answer 33

K2

Question 34

What is Kd in terms of K1 and K2

Answer 34

Kd=K2/K1; if Kd is low; dissociation is slow and binding affinity is high and vice versa

Question 35

in most cases, ED50 and Kd are the same; name a case in which they aren’t

Answer 35

spare receptors; ED50 is lower than Kd

Question 36

drugs that act on the same receptor but have a lower affinity for the receptor will show what ED50 compared to a drug that has a high affinity for a receptor

Answer 36

lower ED50

Question 37

threshold dose

Answer 37

dose below which no response is observed

Question 38

what is theraputic ratio

Answer 38

range of concentrations in which likelihood of efficacy is high and the probability of adverse effects is low