Graded dose and quantal dose response Flashcards
as the dose increases, more drug molecules are delivered into
receptor sites
Factors which affect the amount of drug that finally gets to the receptor
sites
- Physicochemical properties of drug
- Blood flow through the site of absorption
If the entire administered drug dose is absorbed, there is still no assurance to
obtain a maximal response because of the following factors;
- non specific binding of the drug with tissue and plasma proteins
- biotransformation or metabolism of drug in tissues (liver, kidney) and
plasma - excretion of drug before it reaches the biophase
- initial drug effect on the effector system
- local and systematic contra – regulation of the response
intensity or drug
effect can increases as the drug dose is increased
graded dose-response
responsible for induction of drug effect
drug molecules in the biophase
individual unit of a biological system responds to a drug dose either maximally or not at all
all-or-none response, also termed quantal response
smallest dose at
which death occurs
threshold dose or minimal lethal effective dose
differences in the susceptibility to chemicals among
individuals
biologic variation
can be constructed for responses that are measured on a continuous scale, eg, heart rate
graded dose-response curve
ratio of rate constants for the reverse (k2) and forward (k1) reaction
between the drug and receptor and the drug-receptor complex
KD
dissociate rapidly from receptors
high KD (low affinity)
dissociate slowly from receptors
low KD (high affinity)
β2-adrenoceptor agonist
salbutamol
a-alergic blocking agent
phenoxybenzamine
ration of the dose that results in an
undesired effect to that which results in a desired effect
therapeutic index of a drug
usually defined as the ratio of LD50 to ED50, which indicates how
selective the drug is in resulting in its desired effect
therapeutic index
describe how avidly the drug binds to the receptor (ie, the KD)
affinity
refers to the concentration (EC50) or dose (ED50) of a drug required to
produce 50% of the drug’s maximal effect
potency
ability of the drug
to elicit a response when it binds to the receptor
efficacy
concentration of an
antagonist that reduces a specified response to 50% of the maximal possible
effect
median inhibitory concentration or IC50
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
primary determinants of a drug’s clinical
effectiveness
- drug concentration at the receptor
- efficacy of the drug-receptor complex
derived from a quantitive dose-response relationship for a single animal and varies among individuals
Emax (maximum effect)
used to determine the dose that should be administered
drug’s potency
required before a drug can produce an
observable effect
threshold dose
drug concentration at which receptor occupancy is half of maximum
KD
causes blockade of D2-dopamine receptors, a-adrenergic receptors, and
muscarinic receptors
phenothiazine
When quantal effects are being considered information concerning
pharmacologic potency, selectivity of drug action, the margin of safety, and the
potential variability of responsiveness among individuals is obtained from
quantal dose-response curves
demonstrates a clockwise hysteresis loop in the concentration-effect relationship
tachyphylaxis
