PHARMACODYNAMICS (II)

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

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

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

EFFICACY

The magnitude of the response after

occupation of the receptors.

GRADED DOSE RESPONSE CURVES

CBA

THERAPEUTIC INDEX

The ratio between LD50 and ED50 .

LD50 : A dose which is lethal in 50% of

the experimental animals.

ED50: A dose which produces a desired

therapeutic effect in 50% of the

experimental animals

THERAPEUTIC INDEX:LD50

ED50

THERAPEUTIC INDEX

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

THERAPEUTIC INDEX:

TD50

ED50

ED50 = EC50

THERAPEUTIC INDEX

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

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

CHEMICAL ANTAGONISM

DIMERCAPROL

ANTACIDS

PROTAMINE

DEFEROXAMINE

HEAVY METALS

HCl (stomach)

HEPARIN

IRON

Chemical interaction

PHYSIOLOGICAL ANTAGONISM

HISTAMINE:H1 ADRENALINE:ß2

HISTAMINE: BRONCHOSPASM

ADRENALINE: BRONCHODILATION

Adrenaline Antagonizes Histamine

(Anaphylactic Shock)

AGONIST ANTAGONIST

Histamine

Acetylcholine

Epinephrine

Norepinephrine

Chlorpheniramine

Atropine

Propranolol

Tolazoline

The agonist and antagonist compete for the same receptors

PHARMACOLOGICALANTAGONISM

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

TOLAZOLINE DIBENAMINE

BIOCHEMICAL ANTAGONISM

ENZYME INDUCERS

DRUGS DRUGS AFFECTED

Rifampin

Phenytoin

Griseofulvin

Warfarin

Oral contraceptives

Cortisol

Warfarin

Phenobarbital

The factors affecting drug actions:

Drug preparations, route of

administration, interaction,

individual difference, allergic

reaction, physiologic and pathologic

status, drug-resistance and

environmental factors.

IMPORTANT DEFINITIONS

1. TOLERANCE: Responsiveness

decreases as a consequence of

continued drug administration.

Morphine; Opium

2. TACHYPHYLAXIS: Rapidly developing

tolerance. Ephedrine

Ο Ο Ο Ο Ο

DOG’s BLOOD PRESSURE: EPHEDRINE, THE SAME DOSE REPEATED AFTER SHORT

INTERVALS

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

5. HYPER REACTIVITY: When the intensity

of the effect of a drug is increased in

comparison to most individuals

Epinephrine → Thyrotoxicosis

6. HYPO REACTIVITY: When the intensity

of the effect of a drug is decreased in

comparison to most individuals

Epinephrine → Myxoedeme

TOLERANCE, REFARACTORINESS, RESISTANCE

CAUSES:

o Changes in the sensitivity of receptors

o Exhaustion of mediators

o Increased metabolic degradation

o Increased elimination

QUESTIONS

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

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

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

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