Term | Definition |
pharmacodynamics | relationship between the drug concentration at the site of action and pharmacologic response including biochemical and physiologic effect that influence interaction of drug molecule with the receptor- this interaction causes a pharmacologic response |
affinity | occupation of drug to receptor
the tendency of a drug to bind to its receptor |
efficacy | activation of drug via receptor
the tendency of bound drug to elicit response |
occupation theory | drug molecule interacts with a receptor with a single binding site to produce a pharmacologic response |
rate theory | pharmacologic response depends on the rate of association of the drug and receptor complex |
according to rate theory what will an agonist do? | an agonist with associate rapidly to form a receptor complex, which dissociated rapidly to produce a response |
according to rate theory an antagonist will | associate rapidly to form drug-receptor complex and dissociate SLOWLY to maintain antagonist response |
spare receptors | unoccupied receptors are assumed to be present at the site of action, because a maximal pharmacologic response may be obtained when only a small fraction of the receptors are occupied by drug receptors |
potency | drug concentration needed to obtain specific pharmacologic effect |
classes of drug antagonism | pk, reversibe, irreversible, chemical, physiological |
pharmacokinetic antagonism | when an antagonist effectively reduces the concentration of active drug at its site of action by altering its rate of absorption or metabolic degradation or excretion |
reversible antagonism | response still reaches max |
irreversible antagonism | maximal response is not reached |
chmical antagonism | when two substances combine that results in a loss of activity of drug substance |
physiological antagonism | interaction of two drugs whose opposing actions in the body tend to cancel each other |
drug tolerance | quantitative change in the sensitivity of the drug to the receptor site |
how is drug tolerance demonstrated | demonstrated by a decrease in pharmacodynamic effect after repeated exposure to the same drug |
two mechanisms of drug tolerance | pharmacokinetic tolerance, pharmacodynamic tolerance |
pharmacokinetic tolerance | changes in drug disposition due to altered metabolism or elimination |
pharmacodynamic tolerance | change or loss of receptors, exhaustion of mediators |
tachyphylaxis | the rapid development of tolerance after administration of a single or few doses of the drug- acute desensitization |
physical dependency | demonstrated by the appearance of withdrawal symptoms after cessation of the drug use |
factors that affect drug dependency | amount, duration, and total dose of drug used |
adverse drug response | hypersensitivity and allergic responses- not full explained by pd or pk |
pd models | express the relationship between pharmacologic effect and dose in mathematical equations- rate of change |
Maximum effect model | empirical (hyperbolic) model that relates pharmacologic response to drug concentrations, incorporated the law of diminishing returns |
Sigmoid Emax model | describes pharmacologic response to drug concentration curves that are s-shaped- extension of max effect model |
hysteresis loop | plasma verse pharmacologic response relationship is complex- identical plasma drug concentrations can result significantly different responses depending on the time due to tolerance metabolite deactivation, reduced response or translocation of receptors |
pk-pd models | related pharmacological effects to the plasma drug concentration close to the receptor site |
what do pk-pd models predict | dose-response curve for onset, magnitude, and duration of effect and help to estimate therapeutic dosage regimens |
what do pk-pd models combine | combine a pk model describing drug concentration vs time relation with pd model that describes concentration vs effect with a statistical model describing inter and intra-individual variation |
ultimately pk-pd models predict | predict time-course and variability of effect vs time |
types of pk-pd models | pk-pd models at steady state, and non-stead state and time-dependent pk-pd modles |
pk-pd models at steady state | when concentrations of drug at the site of action are constant and the pd parameters are time-invariant, the system is kinetically at steady state |
non-steady state and time depended pk-pd models | when the concentrations of drug and pd parameters are changing with time, the system is not at a steady state |
types of pk-pd models at steady state | fixed effect, linear, log-linear, Emax, sigmoid Emax models |
fixed effect model | relates drug concentration with statistical likelihood of one or several effects to be present or absent "quantal effect model" |
linear model | assumes direct proportionality between drug concentration and drug effect |
log-linear model | when concentration-effect relationship is hyperbolic |
Emax model | based on classical receptor theory, sigmoidal Emax model is extension |
non-steady state and time-dependent pk-pd models | effect compartment, physiological indirect response models |
effect compartment model | it includes a hypothetical effect compartment as an additional compartment of pk compartment model and represents the active drug concentration at the effect site- the rate constant for the transfer between central and effect compartment is negligible |
physiological indirect response model | for drugs whose mechanism of action consists of either inhibition or stimulation of a physiological process involved in the elaboration of clinical expression of the observed effect |