pharmacodynamics (1)

PHARMACODYNAMICS PHARMACODYNAMICS (I)(I)

AIMS AND OBJECTIVES

Pharmacodynamics can be defined as the

study of the pharmacological effects of drugs

and their mechanism of action.

The objectives of the analysis of drug action

are to understand the interactions between

drug and target cells, and to characterize the

full sequence and scope of action of each

drug.

Such a complete analysis provides the

basis for both the rational therapeutic

use of a drug, and the development of

new and better therapeutic agents.

RECEPTORS

Specialized target macromolecules

present on the CELL SURFACE or

INTRACELLULARLY.

They are the specific molecules in a

biological system with which drugs

interact to produce changes in the

function of the system.

RECEPTORS

Among the most important drug

receptors are the cellular proteins

whose normal function is to act as

receptors for endogenous regulatory

ligands i.e. Hormones,

Neurotransmitters.

RECEPTORS

Two functional domains with in the receptors:

1. Ligand binding domain

2. Effector domain

Drug + Receptor Drug Receptor

Complex

Biological Effect

RECEPTORS

1. LIGAND GATED ION CHANNELS

The ligand gated trans membrane ion

channels that are responsible for the

regulation of flow of ions across cell

membrane.

Changes in membrane potential or ion

concentration with-in cell Effects

EXAMPLES:

NICOTONIC receptors

GABA receptors

1. LIGAND GATED ION CHANNELS

2. G-PROTEIN COUPLED RECEPTORS

Binding of the ligand to extra cellular

surface of the trans membrane receptor

activates Gs protein.

The sub unit of Gs protein dissociates

and activates ADENYLYL CYCLASE.

This results in the production of

cAMP, the second messenger, that

regulates protein phosphorylation

and produces biological activity.

2. G-PROTEIN COUPLED RECEPTORS

3. ENZYME LINKED RECEPTORS

The receptor has two hetrodimers each

containing an subunit and a ß

subunit.

subunit is extra cellular and

constitutes the recognition site.

ß subunit spans the membrane and

contains a Tysosine kinase.

When insulin binds to the subunit,

Tyrosine Kinase activity in the ß subunit

is stimulated.

This causes phosphorylation (activation)

of IRS.

This phosphorylation triggers different

actions of insulin.

IRS: Insulin receptor substrate (1-6)


Though ß dimeric form is capable of

binding insulin, it has lower affinity than

ß ß tetrameric form.


4. INTRA CELLULAR RECEPTOR

The receptor is entirely intra cellular.

The ligand (lipid soluble) crosses the

cell membrane and combines with the

receptor.

The activated receptor then enters the

nucleus where it binds to specific DNA

sequences Effects.

The response is obtained after about 30

minutes and the duration of the response

(hours to days) is much greater than that

of other receptor families.

4. INTRA CELLULAR RECEPTOR

DRUGS WHICH ACT INDEPENDETLY OF RECEPTORS

• ANTACIDS

• CHELATING AGENTS

• OSMOTICALLY ACTIVE DRUGS

Diuretics (Mannitol)

Cathartics (Methyl Cellulose)

• VOLATILE GENERAL ANAESTHETICS

OTHER CLASSES OF PROTEINS THAT HAVE BEEN CLEARLY IDENTIFIED AS RECEPTORS

1. ENZYMES

Drugs inhibit the enzymes and

produce effects.

Dihydrofolate reductase is the

receptor for METHOTREXATE

2. TRANSPORT PROTEINS

Na+ / K+ ATPase

The membrane receptor for

cardioactive Digitalis Glycosides.


3. STRUCTURAL PROTEINS

Tubulin: The receptor for

Cholchicine, a drug used in the

treatment of GOUT.


AGONIST

DRUGS RECEPTORS

Phenylephrine

Histamine

Acetylcholine

Morphine

1

H1, H2

M, N

Opioid

A drug which activates the receptors and

elicits maximum response

ANTAGONISTA drug which occupies the receptors, but instead of activation the receptors are blocked

DRUGS RECEPTORS

Atropine

Prazosin

Dimetane

Ranitidine

Naloxone

M

1

H1

H2

OPIOID

Agonists as drugs; Antagonists as drugs

PARTIAL AGONIST

A partial agonist has EFFICACY greater than

zero, but less than the full agonist.

Partial agonist: Elicits sub maximal response

Full agonist: Elicits maximal response

The tendency of a drug to bind to the

receptors is governed by its AFFINITY, but

the tendency for it to activate the receptors,

after binding with the receptors, is denoted

by its EFFICACY.

PARTIAL AGONIST

A partial agonist will produce sub maximal

response even if 100% of the receptors are

occupied.

A partial agonist may act as an antagonist

of the full agonist.

PARTIAL AGONIST

Example:

The beta blockers: Pindolol, Acebutolol

ß1 and ß2 receptors are partially activated, but

are unable to respond to the agonist

Epinephrine.

PARTIAL AGONIST

QUESTIONS

1. Binding of GABA to its receptors

opens channels for: -

a) Cl-

b) Na+

c) K+

d) Ca+2

e) H+

2. Binding of Acetylcholine to its receptors opens channels for: -

a) Cl-

b) Na+

c) K+

d) Ca+2

e) H+

3. A drug which produces its effects by the stimulation of specific receptors: -

a) Antacid

b) Mannitol

c) Methyl cellulose

d) Morphine

e) A chelating agent

4. A drug which produces its effects

(antagonism) by the blockade of

specific receptors: -

a) Phenylephrine

b) Histamine

c) Atropine

d) Mannitol

e) Acetylcholine

pharmacodynamics (1)

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