G.D , Q.D & CLINICAL DOSE RESPONSE Flashcards
T or F: The intensity of drug effect (response) on animal is generally proportional to
the dose of the drug.
TRUE
Factors which affect the amount of drug that finally gets to the receptor
sites
- Physicochemical properties of the drug including rate of dissolution and
lipid solubility - Blood flow through the site of absorption (less blood flow, less drug
absorbed).
the elicited response could be measured in continuous scale.
GRADED DOSE RESPONSE
also termed quantal response, an individual unit of a
biological system responds to a drug dose either maximally or not at all.
ALL or NONE RESPONSE
the smallest dose at which death occurs.
Threshold dose or minimal lethal of effective dose
– the differences in the susceptibility to chemicals among
individuals.
Biologic variation
Two important Factors to consider during the drug test
- EFFECTIVE DOSE
- LETHAL or TOXIC DOSE
may also be used to refer to any unwanted effects other then death.
LETHAL DOSE
can be constructed for responses that are measured on a
continuous scale, eg, heart rate. It also relate the
intensity of response to the size of the dose, and hence are useful for characterizing the actions of drugs.
Graded dose- response-curve
can be constructed for drugs that elicit an all-or-non response, eg, presence or absence of epileptic seizures.
Quantal dose-responsive-curve
When these data are plotted as a cumulative frequency distribution, a _______________________ is generated.
sigmoidal dose-response curve
This is a measure of how tightly a drug binds to its receptor.
Equilibrium Dissociation Constant (K D)
two rate constants
- (forward reaction, k1)
- (reverse reaction, k2)
reaction between the drug and receptor and the drug-receptor complex.
Forward reaction, K1
is the ratio of rate constants for the reverse
Reverse reaction, k2
drug with _______dissiociate rapidly from receptors;
high KD (low affinity)
Examples of specific drugs
- atropine (a muscarinic antagonist)
- salbutamol (a β 2 -adrenoceptor agonist)
- phenoxybenzamine (an a-alergic blocking agent) 4.cimetidine drug effects
a muscarinic antagonist
ATROPINE
a β 2 -adrenoceptor agonist
SALBUTAMOL
an a-alergic blocking agent
PHENOXYBENZAMINE
causes blockade of D 2 -dopamine receptors, a-adrenergic receptors, and muscarinic receptors.
PHENOTHIAZINE
is the ration of the dose that results in an
undesired effect to that which results in a desired effect.
Therapeutic index
The therapeutic index of a drug is usually defined as the ratio of__________which indicates how
selective the drug is in resulting in its desired effect.
LD50 to ED50,
LD5O & ED ED50 are derived from ?
quantal dose-response curves
The maximal efficacy of the drug-receptor complex to result in a graded effect is _____ on a graded dose-response curve.
Emax
plotting plasma concentrations of a drug (abscissa) versus therapeutic effect
(ordinate) in chronologic order displays the data as a loop. This phenomenon
is referred to as
hysteresis
A counterclockwise hysteresis loop is observed of a drug such as?
Digoxin
The extent and duration of action of a competitive antagonist depends on its concentration in the?
Plasma
may occur as a result of continual stimulation by an agonist, and manifests as the development of tachyphylaxis, which demonstrates a clockwise hysteresis loop in the concentration-effect relationship,
Down-reuglation of receptors
The ____ of drug for a receptor describe how avidly the drug binds to the receptor (ie, the K D ).
AFFINITY
refers to the concentration (EC 50 ) or dose (ED 50 ) of a drug required to produce 50% of the drug’s maximal effect.
POTENCY
Potency depends on both the?
affinity & efficacy
(also referred to as intrinsic activity) of a drug is the ability of the drug to elicit a response when it binds to the receptor.
EFFICACY
is the concentration of an antagonist that reduces a specified response to 50% of the maximal possible
effect.
median inhibitory concentration or IC 50
refers to a drug’s ability to preferentially produce a particular effect and is related to the structural specificity of drug binding to receptors.
SELECTIVITY
binds equally well to 1 -adrenoceptors;
propranol (a β-blocker)
β-agonist used for treating asthma binds selectively to β 2 -adrenoceptors.
SALBUTAMOL
selectivity of salbutamol may be further enhanced by
administering it directly to the?
LUNGS
drugs with a ________dissociate slowly from receptors.
low K D (high affinity)
obtained from either graded or quantal dose-response curves is used to
determine the dose that should be administered.
drug’s potency
provides information concerning the dose range over which a drug elicits its effect.
The slope of the graded
dose-response curve
indication of the ability of drugs to reach the receptor is obtained from _______ _______that characterize the absorption, distribution, and
clearance of a drug.
pharmacokinetics parameters
