PED1003/L03 Antagonists Flashcards
Define an antagonist. (2)
A drug which blocks the response to an agonist
Do not by themselves cause any action by binding
Describe the action of propanolol. (3)
Binds to B-adrenoceptor
Propanolol-B-adrenoceptor complex
Decreased blood pressure
Give the 3 classes of antagonist.
Chemical
Physiological
Pharmacological
What is a chemical antagonist? Use an example.
Binding of two agents to render drug inactive
AKA chelating agents
E.g., protamine binds heparin
What is a physiological antagonist? Use an example.
Two agents with opposite effects cancel each other out
E.g., glucocorticoids and insulin
What is a pharmacological antagonist?
Binds to receptor and blocks normal action of an agonist on receptor responses
What 2 classes can active site binding antagonists be put into?
Reversible - competitive
Irreversible - non-competitive active site
What are allosteric binding antagonists called?
Non-competitive
Describe the agonist-response curve in the presence of a competitive antagonist.
Parallel shift to right
Can be overcome by increasing [agonist]
Describe the agonist-response curve in the presence of an irreversible antagonist. (2)
Parallel shift to right
Reduced maximal asymptote
Describe the agonist-response curve in the presence of a non-competitive antagonist
Reduced slope and maximum of dose response curve
(signal transduction rather than effector)
What is the dose ratio?
Agonist plus increasing concentrations of competitive antagonist
(Agonist + antagonist EC50)/Agonist EC50
What is the Schild Equation?
r-1 = [B]/Kb
What is plotted on the x and y axis in a competitive antagonist Schild plot?
x = log(antagonist conc)
y = log(r-1)
What is a pA2 value? Give the equation.
Describes the activity of a receptor antagonist in simple numbers
pA2 = -log(Kb)
What conditions must follow for calculation of a pA2 value? (2)
Must have a linear relationship
Schild plot slope = 1 (competitive antagonist)
What does the extent of antagonist inhibition depend on? (2)
Concentration of competing agonist
Concentration of antagonist
Why do irreversible antagonists a) do not have the same form and b) have a reduced maximal response on a dose-response curve?
a) bind irreversibly with receptor
b) cannot be overcome with increased concentration of agonist
What happens to EC50 in the presence of an irreversible antagonist?
Increases
What allows a parallel shift to the right at lower concentrations with an irreversible antagonist?
Receptor reserves
Give an example of a competitive antagonist.
Cimetidine at H2 receptor
Tamoxifen at oestrogen receptor
Give an example of irreversible antagonism.
Phenoxybenzamine at a1 receptor
Give an example of a non-competitive antagonist.
Nifedipine blocks Ca2+ influx
What effect does a non-competitive antagonist have on a dose-response curve? (2)
Reduces slope and maximal effect
