Quantifying drug action

Question 1

depending on the way they act, which 2 categories can drugs be split into?

Answer 1

1. agonists - activates a receptor
2. antagonist - blocks against an action

Question 2

describe the drug-receptor interactions of agonists

Answer 2

• drug reversibly binds to G-protein coupled receptor to form a reversible drug-receptor complex
• response can be meaured from cellular level to whole body level
• response is dose dependant

Question 3

define ‘EC50’

Answer 3

concentration of a drug that will bring about half the maximum response

Question 4

what is the ‘occupation theory’?

Answer 4

the drug effect is proportional to the number of receptors occupied

Question 5

define ‘partial agonist’

Answer 5

drugs that induce a response but the response is non-maximal.

even if conc. was increased, partial agonist would never induce a full response

Question 6

what can cause alterations in drug receptor activity?

Answer 6

• change/loss of receptor
• exhaustion of mediator
• increased metabolic degradation
• physiological adaptation
• active extrusion of drug from cell

Question 7

what can alterations in drug receptor activity cause?

Answer 7

• desensitisation/tachyphylaxis
• tolerance
• refractoriness
• resistance

Question 8

define ‘antagonist’

Answer 8

a drug with zero efficacy, although it has affinity for the receptor and they won’t bring about a biological response

Question 9

define ‘competitive antagonism’

Answer 9

binding of the antagonist to receptor inhibits binding of agonist. can be reversible or irreversible

Question 10

draw a sigmoid graph of reversible competitive antagonism

Answer 10

Question 11

draw a sigmoid graph of irreversible antagonism

Answer 11

Question 12

define a ‘non-competitive antagonist’

Answer 12

antagonist binds to a site on the receptor other than the agonist binding site. can change the effect the agonist has on the cell/tissue

Question 13

what are 3 other forms of antagonism?

Answer 13

1. physiological - opposing action of both drugs cancels each other out
2. chemical - when 2 substances combine in solution
3. pharmacokinetic - can increase microsomal enzymes, reduce GI absorption, alter renal excretion

Question 14

define ‘therapeutic index’

Answer 14

LD50

ED50

LD50 - lethal dose in 50% of population

ED50 - effective dose in 50% of population

Question 15

when are compartment models needed?

Answer 15

when working out dosing regimes

Question 16

describe a single compartment model

Answer 16

• simplified model in which the animal is a single, well stirred compartment into which a drug is introduced and from which it is eliminated

Question 17

what are the consequences of a steady state?

Answer 17

• duration of action more dependant on dose
• lead to accumulation of drug
• relationship between dose and steady state of [plasma] is steep and unpredictable

Question 18

describe a 2 compartment model

Answer 18

• drug is administered IV to a central compartment from there it distributes to peripheral compartment (fast a phase)
• elimination from plasma is slow B-phase