Physiology and Pharmacology 2: (Evans)

Question 1

Langmuir equation?

Answer 1

Xa / (Xa + Kd)

Multiply by Bmax to fit real biological data (as long as it obeys law of mass action)

Question 2

What can you estimate with Kd?

Answer 2

Kd is an estimate of affinity
low Kd = high affinity
high Kd = low affinity

Question 3

What is EC50? What is it a measure of?

Answer 3

Effective concentration of agonist evoking 50% of the maximum response

• Measure of drug potency

Question 4

Why is EC50 nearly always lower than Kd?

Answer 4

Because of receptor reserve

i.e not all receptors must be occupied to produce a maximum response

Question 5

Model Equation for ‘response’ with respect to EC50? Explain terms

Answer 5

Xa = conc. of agonist
n = slope factor
EC50 = conc. of agonist evoking 50% max response
max = max response amplitude 

max.[Xa]^n / ([Xa]^n + [EC50]^n)

Question 6

Which is the hill slope indicative of?

Answer 6

The number of molecules that bind to each receptor

hill slope > 1 indicates multiple molecules needed to bind

Question 7

What is indicated by 2 curves, One with 100% Bmax, one with 70%, but with the same EC50?

Answer 7

One of them is a partial agonist (70%) (can never achieve 100% maximum response

Question 8

What is efficacy?

Answer 8

The measure of a single agonist-receptor complex’s ability to generate a response, 0 -> 1

1 = full agonist

0 = binding to receptor, no response

Question 9

What is an antagonist? Classes on antagonism?

Answer 9

A drug that prevents the response of an agonist

• chemical antagonism
• pharmicokinetic antagonism
• physiological antagonism
• non-competitive antagonism
• competitive antagonism by receptor block

Question 10

What is chemical antagonism? Examples?

Answer 10

Agonist is chemically altered by the antagonism -> substances combine in solution such that the effect of the agonist is lost

e. g. treatment of heavy metal poisoning via chelating agents
e. g. cytokine inactivation by injecting neutralising antibodies

Question 11

What is pharmacokinetic antagonism? Examples?

Answer 11

Reduction in the amount of drug absorbs
e.g. decrease in absorption via the GI tract
or
Change in the rate of renal excretion of an agonist
e.g. aspirin reduces rate of renal excretion
or
Change in drug metabolism

Question 12

What is physiological antagonism? Examples?

Answer 12

The interaction of 2 drugs with opposing actions in the body

e.g. noradrenaline raises arterial blood pressure by acting on the heart and peripheral blood vessels, while histamine lowers arterial pressure by causing vasodilation

Question 13

What is non-competitive antagonism? examples?

Answer 13

Blocks some step in the process between receptor activation and response i.e it does not compete with the agonist for the receptor site

e.g. metabolic inhibitors

Question 14

What is competitive antagonism? Sub-divisions?

Answer 14

COmpete with the agonist for occupancy of the receptor
(binds to receptor, 0 response)

Reversible or Irreversible