Antagonists Flashcards
Antagonist Def
A substance close enough in shape to an agonist to bind to a receptor but not close enough to produce an effect
Relationship between endogenous ligands and drug agonists
Drug agonists are designed to be identical in shape to the endogenous ligands the body naturally produces to produce the same effect when binding to a receptor
Pharmacological Antagonism Def
Binding to a receptor, blocking agonist binding. Mainly what we discuss
Physiological Antagonism Def
2 agents bind to different receptors producing changes that each cancel out the other. Eg histamine and epinephrine on blood pressure
Chemical Antagonism Def
2 substances interacting before binding, where 1 binds to the other leaving agonist unable to bind to receptors. Eg chelating agents and heavy metal ions
Pharmacokinetic Antagonism
Metabolism of 1 substance decreases the concentration of another (the agonist). Eg barbituitz has P450 metabolism
Surmountable/Reversible anatgonist relationship to agonist
As agonist conc increases, antagonist dissociates allowing for agonist to bind in it’s place
Insurmountable/Irreversible Antagonist relationship to agonist
As agonist conc increases antagonists don’t dissociate. Agonists can not replace it
Competitive Reversible Antagonists Outline
Temporarily bind to binding site of receptor = increase EC50 = shift to right of graph. As agonist conc increases, it replaces antagonist causing EC50 to decease again (move back left)
Example of competitive reversible antagonism
Opioids are displaced from their receptors by naloxone (as naloxone has the higher affinity). This reduces the effects of an overdose (eg respiratory depression)
Competitive Irreversible Antagonist Outline
Antagonists permanently bind to receptors binding sites = decreased % emax = graph shifting down. Increasing agonist conc causes no change (% emax stays low)
Example of an irreversible competitive antagonist
Clopidogrel binds to platlette P2Y12 receptors. This prevents thrombus formation by intercepting ADP pathway
Non-competitive antagonists Outline
Bind to site on receptor other then binding site = reduce Emax and Bmax = graph shifts down. Has no association with agonist conc
Eg of Allosteric Inhibition
Ketamine binds to NDMA (Glutamate) receptors decreasing receptor-drug affinity. reducing Glutamates maximum excittaory response (eg epilepsy treatment)
Eg allosteric activator
Benzodiazapine increases GABAa receptor affinity for GABA. Thus increasing GABAs effects of hyperpolarisation
EC50 Outline
Agonist conc at 50% Emax. The greater the agonist affinity = lower EC50
IC50 Outline
Antagonist conc when Emax is reduced by 50%. The greater the antagonist affinity = lower IC50
Quantal Dose Response Curves Outline
Measures the effect of an agonist in a population in relation to it’s concentration. There has to be a defined endpoint of drug action eg sleep, death. Sometimes can only be marked all (symptom did occur) or nothing (symptom did not occur)
Graded Dose Response Curve Outline
Measures the effect of a drug in an individual in relation to it’s concentration. Continuos spectrum
ED50/EC50 in Quantal Dose Outline
Dose required for atherapuetic response in 50% of the population
TD50 Outline
Dose required for a toxic response in 50% of population. Used in animal and human testing
LD50 Outline
Dose required for a lethal response in 50% of the population. Used in animal testing only
Therapuetic Index outline
Ratio: TD50/ED50. The larger the therapuetric index the safer the drug is (more stable, less likely to interact with other drug/ other body tissues). Narrow TI results in a need for defined risk and benefit
Therapuetic Window Outline
Range between minimum effective dose in population and minimum toxic dose
Eg of drug with a high TI
Benadryl and Valium
Eg of drugs with low TI
Digoxin and lithium
