This document discusses key concepts related to drug dose-response relationships and curves. It begins by explaining that the dose-response relationship has two components: the dose-plasma concentration relationship determined by pharmacokinetics and the plasma concentration-response relationship. It then defines terms like potency, efficacy, therapeutic index and discusses factors that influence dose-response curves like drug selectivity. The document illustrates concepts like additive and synergistic drug interactions through examples.

1. Sarita Sharma
Assistant professor
of pharmacology
Mumbai

2.  When a Drug administered systemically the dose-response
relationship has 2 components:
 Dose-plasma concentration relationship (determined by
pharmacokinetic properties)
 Plasma concentration (dose)-response relationship
 Intensity of response increases with increase in dose /
concentration at the receptor
 Drug-receptor interaction obeys law of mass action

3. Emax × [D]
E=
KD +[D]
E- observed effect
D- dose
Emax- maximal response
Kd- dissociation constant of the drug-receptor complex

4. E =
Emax X [D]
Kd + [D]
Dose-response and log dose-response
curves

5.  Response is proportional to the dose.
 Advantages:
- A wide range of drug doses can be easily displayed on a
graph
- Comparison between agonists and study of antagonists
becomes easier

6. • Potency: amount of drug required to produce a certain response
DRC positioned rightward indicates a lower potency
Relative potency is more meaningful than absolute potency
Relative potency: comparing the dose of two agonists at which they elicit half
maximal response (EC50)
Ex: 10mg of morphine= 100 mg pethidine as analgesic , morphine is potent
• Potency for therapeutic effect increase over the potency for adverse effects.
• Potency of a drug important to choose a dose

7. • Efficacy:
Maximal response that can be elicited by the drug
Ex: morphine produces analgesia not reached with any dose of
aspirin. Morphine is more efficacious than aspirin.
Efficacy is an important factor in the choice of a drug

8. Illustration of drug potency and drug efficacy.
Dose-response curve of four drugs producing the same
qualitative effect
Potency and efficacy
1.Compare drug A&B
2.A&C
3.D vs A,B,C

9. Note:
Drug B is less potent but equally efficacious as drug A.
Drug C is less potent and less efficacious than drug A
Drug D is more potent than drugs A, B, & C, but less
efficacious

10. • Aspirin is less potent as well as less efficacious than Morphine
• Pethidine is less potent analgesic than Morphine but equally
efficacious
• Diazepam is more potent but less efficacious than pentobarbitone
• Furosemide is less potent but more efficacious than metolazone
• Depending on the type of drug, both higher efficacy or lower
efficacy could be clinically advantageous.

11.  Steep slope – moderate increase in dose markedly increase the response (dose needs
individualization)
 Flat DRC – little increase in response occurs in wide range of doses (standard dose can
be given to most patients)
 Example: Hydralazine and Hydrochlorothiazide DRC in
Hypertension
Steep and flat dose-response curves illustrated
by antihypertensive effect of hydralazine and
hydrochlorothiazide

12. • Depends on
- Relative potency and efficacy
- Pharmacokinetic variables
- Pathophysiological variables
• Expressed in terms of
a. Degree of benefit/ relief afforded by the drug or
b. Success rate in achieving a defined therapeutic end point
Ex: a drug which makes a higher percentage of epileptic patients
totally seizure free than drug is the more therapeutically effective
antiepileptic.

13. • Some drugs may produce different actions
• DRCs for different effects of drug may be different
• Extent of separation of DRCs of a drug for different effects is a
measure of its selectivity
Ex: Isoprenaline vs salbutamol

14. Illustration of drug selectivity.
Log dose-response curves of salbutamol for bronchodilatation
(A) and cardiac stimulation (D)
Log dose-response curves of isoprenaline for bronchodilatation
(B) and cardiac stimulation (C)

15. Gap between the therapeutic effect DRC and adverse effect
DRC
Median lethal dose(LD50)- dose which
kills 50% of the recipients
Median effective dose(ED50)- - dose
which produces the Specified effect in
50% individuals

17. • Bounded by the dose which produces minimal therapeutic
effect and the dose which produces maximal acceptable
adverse effect
• Individual variability: effective dose may be toxic for others
• Defining the therapeutic range is difficult
• Few drugs higher therapeutic response and adverse effects in
higher doses
Ex: Prednisolone in Asthma

18. Illustrative dose-response curves for
therapeutic
effect and adverse effect of the same
drug

19.  Judgment between estimated harm and the expected advantages
 Estimated harms:
- Adverse effects
- Cost
- Inconvenience
 Expected advantages:
- Relief of symptoms
- Cure
- Reduction in complications/mortality
- Improvement in quality of life
-
 Prescribe when benefit is more than risks
 Difficult to measure accurately

20. • Refers to range of actions produced by a drug
• Drugs may show –
- One / limited number of actions
- Widespread effects on many organs of the body
• Depends on:
a. Whether drug acts on single/many receptors/targets and
b. How widely the target is distributed in the body
Ex:
Omeprazole- highly selective
Chlorpromazine- D2, muscarinic cholinergic, H1, 5-HT
Dexamathasone- involves many organs due to receptors widespread in the
body

22. • If two/ more drugs given simultaneously/ in quick succession,
they may be either indifferent to each other or exhibit
synergism/ antagonism.
• Interaction may take place at
- Pharmacokinetic level
- Pharmacodynamic level

23.  Action of one drug is facilitated or increased by the other
 In a synergetic pair
- Both drugs can have action in same direction or
- One may be inactive and enhancing the effect of other
 Two types
- Additive
- Supraadditive/ potentiation

24. • Effect of two drugs in same direction and simply adds up
Effect of drug A+ effect of drug B = Effects of drugs A+B
1+1=2
Side effects do not add up

25. • Effect of combination is greater than the individual effects
Effects of drug A+B > effect of drug A+ effect of
drug B
1+1=3
Eg: sulfamethoxazole and
Trimethoprim bacteriostatic individually but
Bacteriocidal in combination.