occurs following frequent or continuous exposure of the receptor to the agonist over a short period of time (seconds to minutes)
densensitization
desensitization is a rapid and _______ process that desensitizes the tissue to further receptor-agonist interaction for only a few minutes
reversible
of receptor molecules occurs following frequent or continuous exposure of the receptor to the agonist over a relatively short period of tie (minutes to hours)
internalization
during internalization, receptor molecules are _______ intact to the plasma membrane via endocytic vesicles.
recycled
process that regulates receptor-mediated repsonses. it occurs only after prolonged or repeated exposure of cells to the agonist over a long period of time (hours to days)
down-regulation
down-regulation _____ the number of receptor molecules present in the cell or tissue
decreases
down-regulation involves ________ of receptor molecules present in the cell and requires the biosynthesis of new receptor molecules for recovery
degradation
down-regulation may cause relative _________ to the effects of a drug agonist int he some patients
tolerance
refers to a decrease in the intensity of the response to a given dose of a drug as a consequence of continued drug administration over an extended period of time
tolerance
tolerance may also occur as a result of _________ of essential substrates required for downstream effects in the signal transduction pathway following continuous activation of the receptor-effector system
depletion
of the receptor occurs when receptor activation is blocked for prolonged periods of time (usually several days) by pharmacologic antagonists or by denervation.
up-regulation
refers to the ability of the drug to accomplish a specified effect
efficacy
reflects the amount of drug required to cause an effect (EC50)
potency
a drug may have ____ efficacy but _____ potency or vice versa
high;low
refers to the concentration (EC50) or dose (ED50) of the drug required to produce 50% of its maximal therapeutic efficacy
potency
potency of a drug depends on the ______ (KD) of the drug for binding tot he receptor and the efficiency of the occupancy-response coupling process
affinity
of a drug depends on its maximal therapeutic efficacy (Emax) and its ability to reach its site of action (not on its pharmacologic potency)
clinical effectiveness
in selecting on of two drugs to administer to a patient, one must make that selection based on the relative ______ rather than the relative ______ of the two drugs
effectiveness;potency
pharmacologic potency is going to largely determine the administered ______ of the selected drug.
dose
is the upper limit of the dose-response relationship on the response axis of the graph
maximal efficacy
in a patient may be determined by the mode of interactions of the drug with the receptor or by the characteristics of the receptor-effector system
drug efficacy
in a patient also depends on a host of other factors
therapeutic efficacy
the practical clinical efficacy of drug of a drug may in some cases be limited by the drug’s tendency to cause a _______ effect, even if the drug can otherwise exert a greater therapeutic effect
toxic
a quantal dose response curve represents the _____ of individuals under study who exhibit a specified drug effect plotted as a function of drug
percentage
illustrates the potential variability of responsiveness to the drug among individuals in a given human population
quantal dose response curve
the drug dose at which 50% of individuals exhibit the specified quantal effect
median effictive dose (ED50)
drug dose required to produce a particular toxic effect in 50% of individuals or lab animals
median toxic dose (TD50)
if the toxic effect is death it is defined as ______
median lethal dose (LD50)
of a drug relates the dose of the drug required to produce a desired effect to the dose of the drug which produces an undesirable effect
therapeutic index TD50/ED50
represents an estimate of the safety of a drug
therapeutic index TD50/ED50
of a drug is a more clinically useful index of safety
therapeutic window (therapeutic range)