This document discusses pharmacodynamics concepts including graded dose response curves, potency, efficacy, therapeutic index, and types of antagonism. Graded dose response curves plot the magnitude of drug responses against increasing doses to determine efficacy, potency, and therapeutic index. Potency refers to the amount of drug needed to produce an effect, while efficacy refers to the magnitude of response. Therapeutic index is the ratio of lethal dose 50 (LD50) to effective dose 50 (ED50), and indicates a drug's safety margin. Antagonism can be chemical, physiological, pharmacological (competitive or noncompetitive), or biochemical in nature.

1. PHARMACODYNAMICS
(II)

2. AIMS AND OBJECTIVES
The topics discussed in this lecture: -
i. Graded dose response curves
ii. Potency and Efficacy
iii.Therapeutic index
iv.Types of antagonism
v. Important definitions

3. GRADED DOSE RESPONSE
CURVES
The response to a drug is a graded effect.
Here the magnitude of responses are
plotted against the graded doses.
Determination of :
Efficacy, Potency ,Therapeutic index

7. Potency and Efficacy
Two important properties which can be
determined by graded doze response
curves.
POTENCY: A measure of the amount of
drug necessary to produce an effect of a
given magnitude.
GRADED DOSE RESPONSE
CURVES

8. EFFICACY
The magnitude of the response after
occupation of the receptors.
GRADED DOSE RESPONSE
CURVES

9. CBA

11. THERAPEUTIC INDEX
The ratio between LD50 and ED50 .
LD50 : A dose which is lethal in 50% of
the experimental animals.

12. ED50: A dose which produces a desired
therapeutic effect in 50% of the
experimental animals
THERAPEUTIC INDEX:
LD50
ED50
THERAPEUTIC INDEX

14. HUMAN BEINGS
Ratio between TD50 and ED50
TD50:A drug dose which produces toxic
effect in 50% of the population
ED50:A drug dose which produces a desired
therapeutic response in 50% of the
population
THERAPEUTIC INDEX

15. THERAPEUTIC INDEX:
TD50
ED50
ED50 = EC50
THERAPEUTIC INDEX

16. Therapeutic index is a measure of the drug
safety.
A large value indicates that there is a wide
margin between doses that are effective and
doses that are toxic ie the drug is safe
EXAMPLE: PENICILLIN
THERAPEUTIC INDEX

18. A small value indicates that the margin
between the toxic and effective doses is
small.
The drug can produce toxic effects with
slight increase in the dose
EXAMPLE: WARFARIN
THERAPEUTIC INDEX

20. CHEMICAL
ANTAGONISM
DIMERCAPROL
ANTACIDS
PROTAMINE
DEFEROXAMINE
HEAVY METALS
HCl (stomach)
HEPARIN
IRON
Chemical interaction

21. PHYSIOLOGICAL
ANTAGONISM
HISTAMINE:H1 ADRENALINE:ß2
HISTAMINE: BRONCHOSPASM
ADRENALINE: BRONCHODILATION
Adrenaline Antagonizes Histamine
(Anaphylactic Shock)

22. AGONIST ANTAGONIST
Histamine
Acetylcholine
Epinephrine
Norepinephrine
Chlorpheniramine
Atropine
Propranolol
Tolazoline
The agonist and antagonist compete
for the same receptors
PHARMACOLOGICA
L
ANTAGONISM

23. PHARMACOLOGICAL
ANTAGONISM
Competitive: Maximum effect can be
obtained in the presence of Antagonist
NE TOLAZOLINE
Non competitive: Maximum effect can not
be obtained
NE  DIBENAMINE

24. TOLAZOLINE DIBENAMINE

25. BIOCHEMICAL
ANTAGONISM
ENZYME INDUCERS
DRUGS DRUGS AFFECTED
Rifampin
Phenytoin
Griseofulvin
Warfarin
Oral contraceptives
Cortisol
Warfarin
Phenobarbital

26. The factors affecting drug actions:
Drug preparations, route of
administration, interaction,
individual difference, allergic
reaction, physiologic and pathologic
status, drug-resistance and
environmental factors.

27. IMPORTANT
DEFINITIONS
1. TOLERANCE: Responsiveness
decreases as a consequence of
continued drug administration.
Morphine; Opium
2. TACHYPHYLAXIS: Rapidly developing
tolerance. Ephedrine

28. Ο Ο Ο Ο Ο
DOG’s BLOOD PRESSURE: EPHEDRINE, THE
SAME DOSE REPEATED AFTER SHORT
INTERVALS

29. 3. IDIOSYNCRASY: Abnormal responses to
drugs due to genetic abnormalities
4. HYPERSENSITIVITY: Allergic
(immunological) responses to drugs
Drug acts as an antigen; TYPE I, II, III, IV

30. 5. HYPER REACTIVITY: When the intensity
of the effect of a drug is increased in
comparison to most individuals
Epinephrine → Thyrotoxicosis

31. 6. HYPO REACTIVITY: When the intensity
of the effect of a drug is decreased in
comparison to most individuals
Epinephrine → Myxoedeme

32. TOLERANCE,
REFARACTORINESS,
RESISTANCE
CAUSES:
o Changes in the sensitivity of receptors
o Exhaustion of mediators
o Increased metabolic degradation
o Increased elimination

33. QUESTIONS

34. 1. The following are the values of the
therapeutic index of five different
drugs. Which one of these drugs is
most toxic: -
a) 2.5
b) 3.0
c) 3.5
d) 4.0
e) 5.0

35. 2. In human beings, the value of
Therapeutic index is expressed by
the ration: -
a) LD50 / ED50
b) ED50 / LD50
c) TD50 / ED50
d) ED50 / TD50
e) TD50 / LD50

36. 3. The mechanism of action of antagonism of
Heparin by Protamine is similar to the
mechanism involved in the antagonism of : -
a) Iron by Deferoxamine
b) Histamine by Omeprazole
c) Acetylcholine by Atropine
d) Histamine by Epinephrine
e) Norepinephrine by Tolazoline

37. 4. The antagonism of NE by Tolazoline
is an example of: -
a) Noncompetitive antagonism
b) Competitive antagonism
c) Chemical antagonism
d) Biochemical antagonism
e) Physiological antagonism