Pharmacodynamics Flashcards
pharmacodynamics
the study of the relationship between the concentration of a drug and the response obtained in a patient
*how the drug affects the body
receptor
the component of a cell or organism that interacts with a drug and initiates the chain of events leading to the drug’s observed effects
ligand
a substance that binds to a receptor
agonist
a drug that binds to and ACTIVATES a receptor
antagonist
a drug that attenuates the effect of an agonist
5 basic mechanisms of transmembrane signaling
1) a lipid-soluble chemical signal crosses the plasma membrane and acts on an intracellular receptor
2) the signal binds to the extracellular domain of a transmembrane protein, thereby activating an enzymatic activity of its cytoplasmic domain
3) the signal binds to the extracellular domain of a transmembrane receptor bound to a separate protein tyrosine kinase, which it activates
4) the signal binds to and directly regulates the opening of an ion channel
5) the signal binds to a cell-surface receptor linked to an effector enzyme by a G protein
EC50
drug concentration producing HALF-maximal effect
*used in drug concentration-effect relationship curve
Emax
maximal effect of a drug
*used in drug concentration-effect relationship curve
Bmax
total concentration of receptor sites
*used in curve for relationship of receptor binding & drug concentration
Kd
equilibrium dissociation constant
*represents concentration of free drug at which HALF-maximal BINDING is observed
*used in curve for relationship of receptor binding & drug concentration
relationship between Kd and affinity
INVERSE
**Kd characterizes the receptor’s affinity for the drug
**if Kd is high, affinity is low
competitive antagonists
*bind the SAME receptor at the agonist
*increases EC50 (shift right) but does not affect Emax
*can be overcome by increasing dose of agonist
noncompetitive antagonist
*usually bind in irreversible fashion
*decreases Emax; EC50 unchanged
*effects can NOT be overcome by increasing dose of agonist
spare receptors
*in reality, maximal biologic response occurs at a concentration of agonist that does NOT occupy all receptors
*demonstrated by adding an increasing concentration of irreversible antagonist
negative allosteric modulators
bind to a different site that alters the agonist binding site
*similar effect to non-competitive antagonists
alternative nomenclatures for non-competitive antagonists
1) non-competitive antagonist - orthosteric
2) competitive antagonist - irreversible
3)irreversible antagonist (& insurmountable)
alternative nomenclatures for negative allosteric modifiers
1) non-competitive antagonist - negative allosteric modifiers
2) non-competitive antagonist (& insurmountable)
partial agonists
*drugs that bind to the receptor, but cause LESS THAN MAXIMAL activation
*concentration-effect curve looks like agonist in presence of irreversible antagonist
*“mixed agonist-antagonist”
inverse agonists
*bind to a receptor and produce the OPPOSITE pharmacological effect that would be produced by an agonist or by the natural ligand
*DECREASE receptor activity (less than constitutive activity)
potency
*concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect
*depends on affinity (Kd) of drug for receptors AND efficiency of drug:receptor interaction
relationship between potency and EC50
potency INCREASES as EC50 decreases
*inverse relationship
efficacy
the maximal response that the drug can produce
*whichever curve has the highest Emax is the drug with the highest efficacy
ED50
dose that causes a therapeutic effect in 50% of the population
LD50
dose that causes death in 50% of the population
median lethal dose
TD50
median toxic dose
therapeutic dose
RATIO between TD50 and ED50
= TD50 / ED50
therapeutic window
RANGE of doses that produce a therapeutic effect without causing significant toxic effects
do you prefer a high or a low therapeutic index
prefer a HIGH therapeutic index (can give a lot of drug without toxicity)
idiosyncratic response
infrequently observed; sometimes makes no sense
hyporeactive response
drug’s effect at a given dose are decreased compared to most people
hyperreactive response
drug’s effect at a given dose are increased compared to most people
tolerance
decreased responsiveness to a drug as a result of continued administration (need to give more of the drug to get the same effect)
tachyphylaxis
desensitization (decreased effect) that occurs rapidly with subsequent doses
*rapidly occurring tolerance
