Pharmacodynamics Flashcards
Receptors?
Proteins that recognise + bind to endogenous signal (ligand)
What happens when ligand binds with receptor?
Initiates cascade of chemical reactions
Results in biological response
Describe an agonist
Binds to + activates receptor
Adds to effect of normal endogenous ligand
Describe an antagonist
Binds to but does not activate receptors
When bound prevents an endogenous ligand from binding
Inhibits / reduces effect of endogenous signal
Therapeutic Window?
Range of drug doses that give desired effects without toxic side effects
Therapeutic Index (Defintion + Equation)
D: Measure of difference between an effective dose + toxic dose
E: minimum toxic dose in 50% of population DIVIDED BY minimum effective dose in 50% of population
Higher therapeutic index =
safer drug
Safest drugs have… (3)
1) Have a wide therapeutic window
2) Have no overlap between therapeutic + toxic dose-response curves
3) Have high therapeutic index
Side effects of drugs can be due to…
can be due to off-target binding (drug can bind to other receptors that have a similar binding site)
Non-selective beta blockers
block B1 + B2 adrenoreceptors equally (cause bronchoconstriction and reduction in heart rate
Cardio-selective beta blocker
More effect on B1 adrenoreceptors
Characteristics of completive antagonist
Prevents A from binding when Ant is bound to receptor
Dynamic (can bind + unbind)
(Overcoming inhibition) If Antagonist has a higher affinity than Agonist…
even more A needed to overcome inhibition
Increasing [A] overcomes inhibition by reversible antagonist
Inhibition of biological effects depends on… (4)
1) Relative conc of A and Ant
2) Relative affinities for receptor
3) Rate of dissociation of Ant from receptor
4) Relationship between receptor occupancy + biological effect
What makes an antagonist irreversible?
Dissociation occurs at VERY LOW rate (or NOT AT ALL)
May be covalently bonded
Describe the irreversible and competitive elements of irreversible competitive inhibitors
1) Higher [A] may prevent Ant from binding (competitive) 2)…but once bound it cant be displaced (irreversible)
(so further increasing [A] cannot reverse effects)
