2. Dose Response Curves/Relationships
• The interaction between the drug and the receptor can be described
by dose response curve.
• It depends on the dose of the drug and affinity of the drug to the
receptor
• There are two types of dose response relationships
Graded dose response relationship
Quantal dose response relationship
3. Graded dose-response Curve
• A graded response describes a drug effect which increases in
proportion to increasing drug dose.
• Graded dose-response graphs plot the response to a drug
against its concentration
• Two important things can be found by graded dose response curve
• Efficacy or maximal effect
• Potency
4. Efficacy and EC50
• EFFICACY
• The maximum response that can be achieved with maximum
tolerable dose of a drug is called efficacy
• EC50
• It is the concentration of drug required to produce half of the
maximum effect
6. POTENCY
• POTENCY
• Amount of a drug required to produce a desired effect is called
potency
• E.g. drug A produces effect at dose of 50 mg and drug B produces
same effect at a dose of 500mg. So drug A is more potent
7.
8. FULL AGONIST
• If a drug binds to a receptor and produces maximum response, it is
known as a full agonist
• A full agonist has affinity for the receptor as well as intrinsic activity
• E.g. Epinephrine at adrenergic receptor
9. PARTIAL AGONIST
• Partial agonist has affinity for the receptor but produces less
response as compared to a full agonist
• E.g.
• Pindolol
10.
11. ANTAGONIST
• An antagonist has affinity for the receptor but no intrinsic activity. It
produces no response when it binds to the receptor.
• Eg. Propanalol at adrenergic receptor
12. QUANTAL DOSE–RESPONSE RELATIONSHIPS
• A quantal response to a drug is observed in a population, and is
either present or absent in any single individual.
• Quantal dose-response graphs plot the rate of an outcome
occurrence in a population against the drug dose
• They help us to calculate
• Effective dose ED50 dose at which 50% of individuals exhibit the
specified therapeutic effect
• Toxic dose TD50 dose required to produce a defined toxic effect in
50% of subjects
• Lethal dose LD50 dose required to kill 50% of animals.
13.
14. therapeutic index and therapeutic window
• The therapeutic index or ratio is the ratio of the TD50 to the ED50 , a
parameter which reflects the selectivity of a drug to elicit a desired
effect rather than toxicity.
• The larger the value, the safer the drug.
• Drugs with a narrow TI , Digoxin
• Therapeutic Index= TD50
• ED50
15. Therapeutic window
• The therapeutic window or range is the range between the minimum
toxic dose and the minimum therapeutic dose
• Drugs with narrow therapeutic window
• Theophylline
16.
17. Clearance
• Unit volume of blood “cleared” of drug per unit time
• Rate of elimination of drug/Plasma drug concentration
• Unit = ml / min
• Eg if body has 5 liter blood and 5 mg of a drug and 1mg of that drug
is excreted It will be said that clearance is 1L/m Because 1 liter of
blood has been cleared of drug
18. Clearance
• Mostly occurs via liver or kidneys
• Liver Clearance
• Biotransformation of drug to metabolites. Excretion of drug into bile
• Renal Clearance
• Excretion of drug into urine
• In liver or kidney disease clearance may fall .Drug concentration may
rise . Toxicity may occur and dose may need to be decreased
• Liver and kidney are the most important organs , other organs may
be involved in clearance
19. Half-Life
• The half-life of a drug is the time in which the plasma concentration
of the drug decreases to half of its initial level after the peak has been
achieved.
• Depends on Vd (volume of distribution) and Clearance
• t1/2= 0.7 Vd /CL
• It takes about 5 half-lives for a drug to be roughly 97% eliminated.
20. First order elimination
• First order elimination kinetics:
• When a constant fraction of drug is eliminated per unit
time,depending upon the plasma concentration, it is called first order
elimination kinetics
• Most drugs follow first order elimination
21. Zero order elimination kinetics
• Zero order elimination kinetics:
• When a constant amount of drug is eliminated per unit time
• Zero order elimination is independent of plasma concentration.
• E.g
• ethanol
• phenytoin
• aspirin
22.
23. Steady state
• Steady-state concentration (Css) occurs when the amount of a drug
being absorbed is the same amount that's being cleared from the
body
• Drugs with short half life reach steady state fast and Drugs with long
half life reach steady state slowly.
• About 5 half lives are required to reach steady state
25. Loading dose
• For drugs with long half life it may take a long time to reach steady state, in such
cases a single large first dose can be given to achieve steady state. This dose is
called loading dose
• Loading dose =
• Desired peak concentration (mg/L) × Vd (L) / Bioavailability. (BA)
26. Maintenance dose
• After the loading dose is given and steady state is achieved another dose can be
given to maintain steady state. This dose is called maintenance dose
• Maintenance dose =
• Desired peak concentration (mg/L) × CL / Bioavailability(BA)
