receptors, safety indexes, inhibition

Question 1

nicotinic acetylcholine receptor type?

Answer 1

ligand-gated sodium channel with receptor and conformational change allowing sodium to pass through

Question 2

what is GR?

Answer 2

cytosolic hormone receptor, has DNA binding domain, translocates to nucleus

Question 3

discuss the nature of chemical bonding of ligand to receptor

Answer 3

• most are H bond or van der waals
• antagonists are often covalent
• all non-covalents eventually dissociate and this marks the end of drug action

Question 4

the magnitude of a drug response is a function of:

Answer 4

concentration of drug-receptor complexes

Question 5

explain the two types of dose response curve

Answer 5

1) quantal - all or none, LD50 and ED50, population not individual, sigmoidal
2) continual/graded - individual only, also usually sigmoidal,

Question 6

what are ED, TD, and LD?

Answer 6

• ED - effective dose
• TD - toxic dose
• LD - lethal dose

Question 7

what is the therapeutic index (TI) and what should we know about it?

Answer 7

• LD50/ED50
• should be greater than 1 and the bigger the better
• limited because it looks at midpoint so you can’t tell from it if there is an LD/ED overlap

Question 8

what is the margin of safety index (MI) and what should we know about it?

Answer 8

• LD1/ED99
• conservative, compares extremes
• should be greater than 1 and bigger is better

Question 9

what is the protective index (PI) and what should we know about it?

Answer 9

• ED50 undesirable / ED50 desirable
• should be greater than 1 and bigger is better
• used to separate desired from undesired effects

Question 10

what is the chronicity index (CI) and what should we know about it?

Answer 10

• one-dose LD50 / ninety-dose LD50
• 1 is best (total clearance), 90 is worst (no clearance)
• ## measuring cumulative toxicity

Question 11

what is a threshold dose?

Answer 11

an apparent all or none phenomenon at the physiological level when administering progressively higher doses

Question 12

what is the difference between potency and intrinsic activity?

Answer 12

• higher potency means reaching desired effect at lower dose

- intrinsic activity means the highest desired effect a drug can obtain regardless of dose

Question 13

affinity vs efficacy

Answer 13

affinity is measured by the k1/k2, association and dissociation of ligand with receptor, whereas efficacy is measured by k3, the rate of effect of the ligand-receptor complex on the body

Question 14

what is chemical antagonism?

Answer 14

direct interaction of the agonist and antagonist

Question 15

what is functional antagonism?

Answer 15

two agonists act independently but have opposite effects, best example is SANS vs PANS

Question 16

what is competitive antagonism and what are the two types of competitive antagonists?

Answer 16

• antagonist binds to receptor but elicits no response (high affinity but no efficacy)
  1) equilibrium - reversible
  2) non-equilibrium - irreversible

Question 17

what happens to dose response curve of agonist in the presence of increasing equilibrium antagonist?

Answer 17

shifts to the right but stays the same shape

Question 18

what happens to dose response curve of agonist in the presence of increasing non-equilibrium antagonist?

Answer 18

curve flattens out

Question 19

what is non-competitive antagonism?

Answer 19

antagonist acts at site other than where agonist binds

Question 20

what happens to the dose response curve of agonist in the presence of non-competitive antagonist?

Answer 20

curve flattens - same as non-equilibrium antagonist

Question 21

what is a partial agonist?

Answer 21

• has low intrinsic activity

- in combination with an agonist it can act as either an agonist or antagonist

Question 22

additivity

Answer 22

• effects of two drugs are additive

Question 23

synergy

Answer 23

• effect of combined drugs is higher than their two individual effects added together.

Question 24

simple synergy vs potentiation

Answer 24

• simple synergy is as previous described, potentiation is when one drug that seemingly does very little on its own can dramatically affect another drug