II - Pharmacodynamics Flashcards
Specific molecules in a biologic system with which drugs interact to produce changes in the function of the system
receptors
Receptors must be _____ in their ligand-binding characteristics.
selective
Receptors must be _____ when they bind an agonist to bring about functional change.
modified
Most receptors are
proteins
Specific binding region of the macromolecules, high and selective affinity for the corresponding drug molecule
receptor/recognition site
Translate the drug-receptor interaction into a change in cellular activity
effectors
Some receptors are also
effectors
Response of a particular receptor-effector system measured against increasing drug concentrations
Graded Dose-Response Curve
Dose-Response Curve yields a _____ if plotted on a semilogarithmic axis.
sigmoid curve
Efficacy (Emax) and potency (EC50) are derived from
Graded Dose-Response Curve
Fraction of receptors bound by a drug plotted against the log of the drug concentration
Binding Affinity
Concentration required to bind 50% of the receptors
Kd
The smaller the Kd, the _____ the affinity of a drug for its receptor.
smaller Kd = greater affinity
Maximal effect achievable with increasing concentration of the drug
Emax (Efficacy)
Concentration of the drug wherein half of the maximal effect is achieved
EC50 (Potency)
Maximum percentage of receptors with increasing concentration of a drug
Bmax (Efficacy)
Concentration wherein 50% of receptors are occupied
Kd (Potency)
Fraction of the population that responds at each dose against the log of the dose administered
Quantum Dose-Response Curve
Median effective (ED50), median toxic (TD50) and median lethal (LD50) doses are derived from
Quantum Dose-Response Curve
Therapeutic Index
TD50/ED50
Maximal effect an agonist can produce if the dose is taken at very high levels
Efficacy
Efficacy is determined by
the nature of the receptor and its associated effector system
Efficacy is measured by
Graded Dose-Response Curve
Denotes the amount of drug needed to produce a given effect
Potency
Potency is determined by
the affinity of the receptor for the drug
Capable of fully activating the effector system when it binds to the receptor
full agonist
High affinity for the activated receptor conformation
full agonist
Sufficiently high concentration result in all the receptors achieving the activated state
full agonist
Produces less than the full effect even when it has saturated the receptors
partial agonist
In the presence of a full agonist a _____ acts as an inhibitor.
partial agonist
Do not provoke a biological response by themselves upon binding to a receptor
antagonist
Blocks or dampens drug response in the presence of an agonist
antagonist
Binds to receptors in a reversible way without activating the effector system
competitive antagonist
Shifts the dose-response curve to the right (increased ED50) but same maximal effect is reached
competitive antagonist
Effects are overcome by adding more agonist
competitive antagonist
Binds to receptors in an irreversible way without activating the effector system
non-competitive antagonist
Shifts the dose-response curve to downwards (decreased EC50)
non-competitive antagonist
Binds to a different receptor producing an effect opposite to that produced by the drug it’s antagonizing
physiologic antagonist
Interact directly with the drug being antagonized to remove it or to prevent it from reaching its target
chemical antagonist
Responsiveness diminishes rapidly after administration of a drug
Tachyphylaxis
Frequent or continuous exposure to agonists often results in short-term diminution of the receptor response
Tachyphylaxis
Drugs that Exhibit Tachyphylaxis
dobutamine, ephedrine, LSD, metoclopramide, calcitonin, nitroglycerin, nicotine, hydralazine, desmopressin
Continuous activation may lead to depletion of essential substrates, reversed by repletion of missing substrates
Tolerance
Response that is infrequently observed in most patients
Idiosyncratic Drug Response
