lec7 pharmacodynamics Flashcards
categories of drug effects
therapeutic
nontherapeutic
placebo
dose intensity curves measures
how much effect
dose frequency curves measures
hoe many affected
application of the law of mass action to the kinetics of the binding of drug and receptor creates the equation
drug + receptor bound-receptor –> effect
dissociation constant (Kd) for the drug from the receptor is measured by (2 equations for it)
=Kr/Kf
K reverse / K forward
or
= drug + receptor / bound-receptor
the curve for durg conc v fraction of bound receptors (i.e. bound / total receptors) is what shape
hyperbolic
the conc at which half of the receptors are bound is the
Kd = dissociation constant
Bmax is the
totality of the receptors bound by the drug
why are semilogarithmic plots used instead of linear (hyperbola)
linear plots at point near zero, the effect changes rapidly
semi log curve has large middle portion close to EC50 which is linear and easier to work with so easier to make accurate determination
Emax =
maximum effect
what is used as a measure of Kd
EC50
lower EC50 means what to the affinity for binding to the receptor
lower EC50 –> lower Kd –> higher affinity for binding to the receptor
drug conc producing an effect that’s 50% of the max effect
EC50
EC50 provides what important characteristic of drugs
potency
Emax provides what important characteristic of drugs
efficacy
define efficacy
max effect of a drug achieveable at a high dose
lower EC50 = ____ potency
higher
lower Emax = ____ efficacy
lower
when comparing 2 drugs you want the one with the lower or higher Emax
higher
how well the drug binds the receptor
potency
how well the drug produces the effect
efficacy
t/f potency and efficacy are related
f: unrelated
potency is ___ related to EC50
inversely
lower potency = higher EC50
ability of a drug to affect one tissue or receptor in prefereance to another
selectivity
a highly selective drug is one which
affects only a receptor or tissue without affecting others
what curve is needed to measure selectivity
concentration - response
what type of agonist:
drug that has efficacy greater than zero but less than a full agonist
partial agonist
what type of agonist:
drug that binds to a receptor and produces max bio response
full agonist
what type of agonist:
drug that induces pharm response opposite of agonist
inverse agonist
what is a neutral antagonist
drug that does NOT induce a bio response and reduces/blocks response induced by agonist
order the 3 agonists from highest emax to lowest
full > partial > inverse
process where a drug decr or opposes action of another drug or endogenous ligand
antagonism
what are the 4 types of antagonisms
chemical
pharmacokinetic
physiological
pharmacological
type of antagonism where antagonist accelerates the metabolism or the elimination of the agonist
pharmacokinetic
type of antagonism where antagonist binds directly to agonistto make it inactive
chemical
type of antagonism where theres 3 types
reversible competitive, noncompetitive, irreversible
pharmacological
type of antagonismwhere antagonist activates a diff mechanism that opposes the effects of the agonist
physiological
what happens to potency and efficacy in reversible competitive
right shift of dose-response curve
higher EC50 –> lower potency
no change in efficacy
competitive antagonism can be overcome by
incr the conc of agonist to achieve the same effect as before
can a noncompetitive antagonism be overcome
no cant restory to original response by incr conc of agonist
what happens to potency and efficacy in noncompetitive
lower emax –> decr efficacy
unchanged potency
what happens to potency and efficacy in irreversible competitive
lower emax –> decr effcacy
no change potency
joint effect of 2 drugs is the sum of their individual effects
summation
joint effect of 2 drugs is greater than sum of their effects
synergism
inert drug enhances the effect of another drug
potentiation
drug effect loss over time
tolerance
mechanism for decreased effect (includes tachyphylaxis)
desensitization
what curve is all or nothing i.e. their effect is scored on whether present or absent
quantal dose-response curves
diff bn incremental and cumulative quantal curves
incremental - as dose incr, number responders incr (bell curve)
cumulative - as dose incr, number responders adds up
which curve has more variability?
shallow, wider
taller, narrow
shallow, wide
dose producing effect in 50% of subject
ED50
dose making death in 50% of subjects
LD 50 = lethal dose
what do different slopes in quantal curves imply
diff sources of variability, suggesting diff in route or mechanism of action
therapeutic index equation
LD50 / ED50
the higher the therapeutic index
the safer the drug
why is pop variability important in quantal curves
bc can have same therapeutic index but different risk
standardized safety margin equation
(LD1-ED99) / ED99 * 100
the more positive the ED99 or the greater the diff bn LD1 and ED99 , the ___ the drug
safer
