antagonists

Question 1

antagonist definition and types

Answer 1

def: inhibit/block the effects of an agonist

Types:
Chemical: actually combine w/ agonist
Physiological: activate opposing phys. input
Pharmacological: blocks the effect of an agonist of a R

Question 2

Competitive pharmacological antagonists (A)

Answer 2

Act at the same binding site as the agonist (D). Occupies the site and occludes the binding of endogenous agonist . Competitive antagonists have an intrinsic activity of 0
Receptors only signal when they are in the DR state

When you add antagonist the EC50 increases (aka you need more agonist to get half the max effect)-> EC50’

EC50’= EC50 (1 + ([antagonist]/KI))

Ki is the Kd of the antagonsist

Question 3

Non equilibrium/ irreversible competitive antagonists

Answer 3

Once the receptor is bound they can never be activated by agonist again, reducing the available receptor pool

Emax will start to decrease when spare receptors are all taken (and EC50 does not change)

new receptor synthesis is the only way to overcome the effects of the antagonist, cant overcome by agonist

Question 4

non competitive antagonist

Answer 4

blocks the effects of agonist activation of a receptor at a site other than the binding site

it is independent of the agonist concentration, can be used to inhibit signaling of several receptors that act on the same effector

Will lower the E max regardless of spare receptors

Question 5

partial agonist/antagonist

Answer 5

ligands with affinity for the receptor and intrinsic activities between 0 and 1, when a partial agonist is present alone it produces and agonist-like effect

when a partial agonist is present with an agonist it produces an antagonist-like effect

inverse agonist: ligands that hold receptor in inactive state

Question 6

potency

Answer 6

the relationship of the amount of drug administered and its effect

ED50 value is inversely related to potency (determined by affinity for site of action, and ability to reach the site of action)

Question 7

Efficacy

Answer 7

the maximal effect that is produced by a drug

Determined by (intrinsic activity, characteristics of the effector, limitations on the amount of drug that can administered

When effect is only dependent on law of mass action, 3 log units of drug dose are needed to cover the range from 0->100%

Question 8

Reasons for variation in response among individuals

Answer 8

1. Difference in pharmacokinetics
2. Variation in the amount endogenous agonist
3. changes in the number of function of target
4. differences in a component distal to the target

hyperreactive at the lower end
hyporeactive at the upper end

Question 9

idiosyncratic dose response

Answer 9

unexpected based upon mechanism

Question 10

hypersensitivity

Answer 10

allergic or inflammatory response

Question 11

tolerance

Answer 11

slowly developing resistance to drug

Question 12

tachyphylaxis

Answer 12

rapidly developing resistance to drug