2. Drug-receptor Interaction - Antagonists (2) Flashcards
What is an antagonist drug?
Any drug which reduces the response to another drug
What are the different types of antagonist drugs?
Competitive antagonist Non-competitive antagonist Physiological antagonists Pharmacokinetic antagonists Chemical antagonists
What are the two types of competitive antagonists?
Competitive reversible
Competitive irreversible
What do competitive antagonist do?
Compete with chemical mediator or agonist drug for binding to similar or overlapping binding site on the same receptor but without initiating a cellular response
What is the intrinsic efficacy of competitive agonists?
0
What is an example of a competitive antagonist?
atenolol- beta blocker
What does atenolol do?
Competes with agonist for binding site but cant cause shape change needed to initiate a signal transduction
Muscle will not contract
Will attenuate the binding and action of noradrenaline and adrenaline on heart
noradrenaline-induced increase in cardiac work and oxygen demand is blunted by atenolol
How do you classify competitive antagonists?
Classified by how long they remain associated with receptor
What is the effect of a competitive reversible antagonist on the agonist log conc response relationship?
Rightward shift for agonist in presence of antagonist
Parallel shift without reduction in max response to agonist look at slide 7
What are irreversible competitive antagonists?
Often covalent bonds
effects of the antagonist cannot be reversed unless new receptor proteins are made
What is the effect of competitive irreversible antagonists
on agonist log concentration-response curve
Progressive reduction in max response to agonist without a rightward parallel shift in agonist log conc response curve
What is a non-competitive antagonist?
Affects action of agonist at some point in chain leading to response but does not compete with agonist for binding to same site on receptor
What does binding to an allosteric site cause?
Conformational change - alters agonist binding elsewhere/intiation of signal transduction
How else does a non-competitive antagonist work?
Involves interferenec with a component of signal transduction pathway downstream from receptor
What does a physiological antagonist do?
Has an opposite effect to the agonist but achieves its results by acting as an agonist on separate cells or tissues or on different population of receptors in the same cell
Examples of functional agonists
Noradrenaline
Acetylcholine
What is a pharmacokinetic antagonist?
One drug decreases the conc of another drug by interfering with its absorption, distribution, metabolism or excretion
What does the antibiotic rifapicin do?
induces expression of liver enzymes which metabolise anti-coagulant drug warfarin
How is the division of the receptor families based upon?
which chemical mediator receptor responds to
What is the division of family members based upon?
Comparing potency of endogenous mediators at receptors for that mediators in different tissues
Selective stimulation by agonist drugs
Selective blockade by competitive antagonist drugs
What is the division of family members based upon?
Comparing potency of endogenous mediators at receptors for that mediators in different tissues
Selective stimulation by agonist drugs
Selective blockade by competitive antagonist drugs
What is the molecular biological approach to receptor classification based on?
Molecular structure of receptor protein - amino acid sequence -2yr and 3yr structure -location of antagonist binding sites Signal transduction mechanism -ion flux -enzyme activity -gene expression
What are the 4 superfamilies of receptors?
- Ligand-gated ion channels
- G-protein-coupled receptors
- kinase-linked receptors
- Nuclear receptors
What are the simlarites within superfamily 2 (G-protein coupled receptors)?
Possess basic molecular structure and functional properties of that superfamily
DIFFERENCES
Encoded by different genes and differ in region of receptor that forms agonist binding site
Each family responds to a specific agonist mediator
