Lecture 9 Flashcards
Receptor theory III
Inverse agonists
Some receptors show spontaneous constitutive activity
Are a drug that when bound stabilises the resting state of the receptor - reducing any constitutive activity
Antagonists
A drug that prevents the response of an agonist, of which there are many classes
Majority of clinically useful drugs
Chemical antagonists
Substances which combine in solution to chemically alter the agonist so that the effects of the active drug are lost
Pharmacokinetic antagonists
Causes a change in the rate of excretion, metabolism and absorption of the drug
Physiological antagonists
Two drugs that have opposing effects within the body
Describing actions through separate cells/separate signalling machinery
Non-competitive antagonists
Causes a block between the receptor activation and a response, but does not compete for the binding site
Competitive antagonists
Directly compete with the agonist for receptor occupancy
Can be reversibe or non-reversible
Reversible competitive antagonists
Increasing antagonist conc. would result in parallel rightward shift of the curve
But no change in max response
Slope unaffected
Schild analysis measures
Affinity of the antagonist
Dose ratio for schild anaysis equation
= [Xb]/KD + 1
Xb in schild analysis
Conc. of antagonist
PA2
=-log10(molar conc. of antagonist that gives dose ratio of 2)
Irreversible competitive antagonists
Cannot be reversed by washing the tissue
Is time dependent
Desensitisation
Effect of a drug may decline over time if given repeatedly or continuously
Desensitisation causes
Loss of receptors from cell surface Change in receptors Exhaustion of mediators Increased metabolic degradation/extrusion of the drug Physiological adaptation
