L8 - Receptor Theory - Agonist and Anatagonists II

Question 1

What is an antagonist?

Answer 1

A drug that prevents the response of an agonist

Most clinically useful drugs are antagonists

Question 2

5 classes of antagonists

Answer 2

Chemical antagonism 
Pharmacokinetic antagonism 
Physiological antagonism 
Non-competitive antagonism 
Competitive antagonism by receptor block

Question 3

Chemical antagonism

Answer 3

Substances combine in solution so that the effects of the active dug is lost
The agonist is chemically altered by the antagonism

Question 4

Chemical antagonism example

Answer 4

E.g. inactivation of heavy metals whose toxicity is reduced with the addition of a chelating agent

Question 5

Pharmacokinetic antagonism

Answer 5

Reduction in amount of drug absorbed

Change in drug metabolism

Question 6

Pharmacokinetic antagonism examples

Answer 6

E.g. decreased absorption from the GI tract
E.g. opiates will reduce absorption by oral route
E.g. for patients taking warfarin (anti-coagulant that thins blood reducing risk of heart attack) have to be careful with antibiotics as they may stimulate metabolism of warfarin

Question 7

Physiological antagonism

Answer 7

The interaction of two drugs with opposing actions in the body
Used when describing the actions through separate cells or different transduction/receptor systems

Question 8

Physiological antagonism example

Answer 8

E.g. noradrenaline raises arterial BP by action on the heart and peripheral vessels. Histamine lowers arterial BP by causing vasodilation

Question 9

Non-competitive antagonism

Answer 9

Blocks some step in the process between receptor activation and response
It does not compete with the agonist for the receptor site

Question 10

Competitive antagonism

Answer 10

Competes with the agonist for occupancy of the receptor

Increased agonist concentrations can then replace the antagonists on the receptors

Question 11

Reversible competitive antagonism

Answer 11

With increasing antagonist concentration parallel rightward shift in the concentration-response curve
- Higher agonist concentration needed for the same response
No change in maximum response

Question 12

Reversible competitive antagonism example

Answer 12

E.g. the effects of atropine on response to acetylcholine for ileum

Question 13

Dose ratio

Answer 13

How many more times agonist is needed in the presence of an antagonist
Conc of agonist in presence of antagonist/conc of agonist in absence of antagonist

Question 14

The dose ratio increases with?

Answer 14

Antagonist concentration

Question 15

For a competitive antagonists a plot of Dose-Ratio versus [Antagonist] is?

Answer 15

Linear

Slope of the line is proportional to the affinity of the antagonist for its receptor

Question 16

What is Schild analysis used for?

Answer 16

Measures antagonist affinity

Question 17

Schild analysis equation

Answer 17

Dose ratio = [Xb] +1      
                         KD  
Xb = concentration of antagonist 
KD = Antagonist Affinity Constant
pA2 = -log10 (molar concentration of antagonist that gives a dose ratio of 2)

Question 18

Irreversible competitive antagonists

Answer 18

Antagonism that cannot be reversed by washing the tissue
Irreversible antagonism is time-dependent
Overtime the maximum response decreases

Question 19

Irreversible competitive antagonists example

Answer 19

E.g. the effects of the alkylating drug dibenamine on histamine responses in ileum

Question 20

What is desensitisation and tachyphylaxis?

Answer 20

The effect of a drug may decline over time when given continuously or repeatedly

Question 21

Why does desensitisation occur?

Answer 21

Loss of receptors from cell surface
- Internalization by endocytosis
- Followed by recycling or degradation
- Known as tolerance 
Change in receptor itself
- Pphosphorylation 
- Decreased coupling of receptor to effectors
Exhaustion of mediators
Increased metabolic degradation or extrusion of the drug
Physiological adaptation