PHARMACODYNAMICS · PHARMACODYNAMICS Presented by Dr. Sannithi Nagarjuna Coordinator for RIPER-GPAT Cell, Hyderabad Academy & Online GPAT Academy 7899107907 9885784793 [email protected]

PHARMACODYNAMICS

Presented by

Dr. Sannithi Nagarjuna

Coordinator for RIPER-GPAT Cell,

Hyderabad Academy &

Online GPAT Academy

7899107907

9885784793

[email protected]

It is a branch of pharmacology deals with the study of mechanism of

action, pharmacological actions and uses of drugs.

(What the drug does to the body)

(OR)

It is defined as the response of the body to the drug. It refers to the

relationship between drug concentration at the site of action and

resulting effect.

(OR)

It is the study of biochemical, physiological and molecular effects of

drugs on the body.

Most of the drugs produce their mechanism

of action by binding to the receptors.

DEFINITIONS

1. RECEPTORS → defined as specific binding sites for drug

molecules/ ligands and chemically they are protein in nature.

All receptors are proteins but all proteins are not receptors.

2. LIGAND → defined as a substance that selectively attaches to

the receptors, activates the receptors and produces maximum

pharmacological action.

Both receptors and ligand are highly specific.

Receptors Ligand

Muscarinic and Nicotinic

receptors (Cholinergic)

Acetylcholine

Adrenergic receptors Noradrenaline

Histamine receptors Histamine

Dopamine receptors Dopamine

5-HT receptors 5-HT (Serotonin)

GABA receptors GABA

3. AFFINITY →

ability of an agent to bind with the receptors

4. INTRINSIC ACTIVITY ( EFFICACY)→

ability of an agent to activate the receptors and produces

pharmacological action

5. AGONIST : Affinity + Maximum Intrinsic activity (IA= + 1)

Agonist and ligand both are same, the only difference is agonist is

exogenous and ligand is endogenous.

Agonist produces actions similar to ligand

or

Agonist increases the actions of ligand

6. ANTAGONIST: Affinity + No Intrinsic activity (IA= 0)

Antagonist blocks or stops the actions of ligand hence it is otherwise

called as blocker.

Source : Google

Source : Google

Ligand Agonist Antagonist

Acetylcholine Carbachol,

Bethanechol

Atropine

Noradrenaline Dobutamine Propranolol

Histamine 2-methyl histamine Diphenhydramine

TYPES OF RECEPTORS

❖ Receptors will not exist as alone and they are

always present in attached manner

(Coupled manner)

❖ Based upon the coupled substance receptors

are classified into 4 types

1. G-Protein Coupled Receptors ( Receptors coupled to

G-Protein )

2. Ionotropic receptors ( Receptors coupled to Ion

channels )

3. Enzyme linked receptors ( Receptors coupled to

Enzymes)

4. Nuclear receptors ( Receptors coupled to nucleus)

G-Protein Coupled Receptors

( Receptors coupled to G-Protein )

❖ Receptors located across/on/within the cell

membrane

❖ Hence called as transcellular receptors

❖ Here there are two parts one is G-protein and

another one is Receptor

Receptor consist of

7 transcellular helical structures

3 loops

-NH2 group present on extracellular side

-COOH group present on intracellular side

G-protein is trimeric in nature consist of 3 subunits called

as α, β, and γ and these three subunits attached to GDP.

binding of ligand with the receptors

GDP replaces with GTP

G-Protein dissociated into 2 complexes

Interacts with the pathways

Release of substances called as secondary messengers

Produces pharmacological actions

GTP α β γ

Source : Google

Source : Google

PATHWAYS

1. ADENYL CYCLASE PATHWAY

ATP -------------→ cAMP -----------→ Inactive

❖ cAMP acts as a second messenger

❖ Enzyme Phosphodiesterase involved in the inactivation

of cAMP

Source : Google

ACTIONS OF CAMP

In cardiac muscle/Heart --

Increases force of contraction, Increases cardiac output, Increases blood pressure, Increases heart rate.

In smooth muscles (GIT, Bronchi, Uterus) –

Smooth muscle relaxation

In Liver –

Glycogenolysis

In adipose tissue

Lipolysis

In Platelets

Decreases platelet aggregation

2. PHOSPHOLIPASE PATHWAY

Stimulation of this pathway results in the breakdown of

cell membrane phospholipids.

Cell membrane phospholipids upon breakdown will

release Inositol-1,4,5- triphosphate (IP3)and Diacylglycerol

(DAG) which act as second messengers.

IP3 & DAG always produce stimulation.

ACTIONS OF IP3

AND DAG

Location Action

Cardiac muscles Contraction

Smooth muscles Contraction

Skeletal muscles Contraction

Glands Increase in secretions

CNS CNS Stimulation

GS → Increased levels of cAMP

Gi → Decreased levels of cAMP

Gq →Increased levels of IP3 and DAG

EXAMPLES:

1.Muscarinic receptors (M1- M5)

2. Adrenergic receptors (α1- α2 & β1- β3)

3.Histamine receptors (H1-H3)

4.Dopamine receptors (D1-D5)

5.5-HT receptors (5-HT1 to 5-HT 7 except 5-HT 3)

6.Opiod receptors

7.GABAB receptors

MUSCARINIC RECEPTORS(M1 - M

5)

Gq Gi

M1 M2

M3 M4

M5

Type of

receptor

Second

Messenger

Location Pharmacological actions

M1 Gq ❖ Gastric Parietal Cells

❖ Ciliary Muscles of Iris

M3 Gq ❖ Smooth muscles like

Bronchi, Uterus, GIT

❖ Glands like sweat

glands, salivary

glands & lacrimal

glands

M5 Gq CNS

Type of

receptor

Second

Messenger


M1 Gq ❖ Gastric Parietal Cells

❖ Ciliary Muscles of Iris

❖ Increase in acid

secretion

❖ Contraction of Ciliary

Muscles of Iris (Miosis)

M3 Gq ❖ Smooth muscles like


❖ Glands like sweat

glands, salivary glands

& lacrimal glands

❖ Smooth muscle

contraction like

Bronchoconstriction,

Uterus constriction,

Contraction of GIT,

Increase in motility of GIT

❖ Increase in secretions

like sweating,

salivation and

lacrimation

M5 GqCNS ❖ CNS stimulation

Type of

receptor

Second

Messenger

Location Pharmacological

actions

M2 Gi Heart

M4 Gi CNS

Type of receptor Second

Messenger

Location Pharmacological

actions

M2 Gi Heart Decrease in

force of

contraction,

Decrease in

cardiac output,

Decrease in

blood pressure,

Decrease in

heart rate

M4 Gi CNS No action

Source: Google

PHARMACOLOGICAL ACTIONS OF ACETYLCHOLINE


Heart Decrease in force of contraction,

Decrease in cardiac output, Decrease

in blood pressure, Decrease in heart

rate

Smooth muscles like


Smooth muscle contraction like

Bronchoconstriction,

Uterus constriction,

Contraction of GIT, Increase in

motility of GIT

Gastric Parietal Cells Increase in acid secretion

Ciliary Muscles of Iris Contraction of Ciliary Muscles of Iris

(Miosis)

Glands like sweat glands, salivary

glands & lacrimal glands

Increase in secretions like sweating,

salivation and lacrimation

CNS CNS stimulation

ADRENERGIC RECEPTORS {α1 – α2 & β1- β3}

Gq Gi GS

α1 α2 β1

β2

β3

Type of

receptor

Second

Messenger


α1 Gq ❖ Blood vessels

α2 Gi ❖ CNS

Type of

receptor

Second

Messenger


α1 Gq ❖ Blood vesselsVasoconstriction,

increase in blood

pressure

α2 Gi ❖ CNSNo Action

Type of

receptor

Second

Messenger


β1 GS ❖ Heart

β2 GS ❖ Smooth muscles

❖ Bronchi

❖ Liver

β3 GS ❖ Adipose tissue

Type of

receptor

Second

Messenger


β1 GS ❖ HeartIncrease in force of

contraction,

Increase in cardiac output,

Increase in blood

pressure,

Increase in heart rate

β2 GS ❖ Smooth muscles

❖ Bronchi

❖ Liver

❖ Smooth muscle

relaxation

❖ Bronchodilation

❖ Glycogenolysis

β3 GS ❖ Adipose tissue❖ Lipolysis

PHARMACOLOGICAL ACTIONS OF NORADRENALINE


Heart Increase in force of contraction,

Increase in cardiac output,

Increase in blood pressure,


Smooth muscles

Bronchi

Smooth muscle relaxation

Bronchodilation

Blood vessels Vasoconstriction, increase in blood

pressure

Metabolic effects Glycogenolysis & Lipolysis

IONOTROPIC RECEPTORS

(RECEPTORS COUPLED TO ION

CHANNELS )

❖ Receptors coupled to ion channels

❖ Receptors located across/on/within the cell membrane

❖ These are also transcellular receptors

❖ Also called as ligand gated ion channels

Ligand binds to the receptors

Opening of ion channels will take place

Result in either influx or efflux of ions depending upon

concentration gradient

Result in pharmacological actions which may be stimulation or

inhibition

O

p

Source : Google

Sodium, Calcium & Chloride ions present extracellularly

so when these ion channels get opened that result in

influx of ions.

Potassium ions present intracellularly so when these ion

channels get opened that result in efflux of ions.

Ligand binds

to the receptors → Sodium channels → Influx of sodium ions→

Ligand binds

to the receptors → Calcium channels → Influx of Calcium ions→

Ligand binds

to the receptors → Chloride channels → Influx of chloride ions→

Ligand binds

to the receptors → Potassium channels → Efflux of potassium ions →

Ligand binds

to the receptors →Sodium channels → Influx of sodium ions→ Stimulation

Ligand binds

to the receptors → Calcium channels → Influx of Calcium ions→ Stimulation

Ligand binds

to the receptors → Chloride channels → Influx of chloride ions→ Inhibition

Ligand binds

to the receptors → Potassium channels → Efflux of potassium ions →Inhibition

Location Stimulation Inhibition

Cardiac

muscle/Heart

Contraction,

Increase in force of

contraction,

Increase in cardiac

output,

Increase in blood

pressure,


Relaxation,

Decrease in force of

contraction,

Decrease in cardiac

output,

Decrease in blood

pressure,

Decrease in heart rate

Smooth muscles Contraction Relaxation

Skeletal muscles Contraction Relaxation

Glands Increase in secretions Decrease in secretions

CNS CNS Stimulation CNS depression

EXAMPLES:

1. Nicotinic receptors (NM & NN receptors)

2. 5-HT3 receptors

3. GABAA receptors

4. NMDA receptors

Type of

receptor

Type of ion

channel

attached


NM Sodium ❖ Skeletal muscles

NN Sodium ❖ Autonomic ganglia

5-HT3 Sodium ❖ CTZ

GABAA Chloride ❖ CNS

NMDA Calcium ❖ CNS

Type of

receptor

Type of ion

channel

attached


NM Sodium ❖ Skeletal musclesSkeletal muscle contraction

NN Sodium ❖ Autonomic gangliaGanglionic stimulation

5-HT3 Sodium ❖ CTZNausea and vomiting

GABAA Chloride ❖ CNSCNS depression

NMDA Calcium ❖ CNSCNS stimulation

Type of

receptor

Pharmacological

actions

Category Therapeutic

Uses

NMSkeletal muscle

contraction

Skeletal

Muscle

relaxants

NM receptor

blockers

NNGanglionic stimulation Ganglionic

blockers

NN receptor

blockers

5-HT3Nausea and vomiting Antiemetics 5-HT3

antagonists

GABAACNS depression CNS

depressants

GABAA

receptor

agonists

NMDA CNS stimulation CNS

depressants

NMDA

receptor

blockers

ENZYME LINKED RECEPTORS

(RECEPTORS COUPLED TO ENZYMES)

❖ Receptors coupled to enzymes

❖ Receptors located across/on/within the cell

membrane

❖ These are also transcellular receptors


Enzymes automatically undergo

phosphorylation (Autophosphorylation)

Responsible for mediating the pharmacological

actions

Most of the enzymatic receptors are

coupled to the enzyme

Tyrosine Kinase

EXAMPLES:

1. Insulin receptors (Tyrosine Kinase)

2. Epidermal growth factor receptors (Tyrosine Kinase)

3. Natriuretic peptide receptors (Guanyl cyclase)

❖ Receptors coupled directly to nucleus

❖ Receptors located inside the cell

❖ These are also called as intracellular receptors

❖ Otherwise called as steroidal receptors

NUCLEAR RECEPTORS

( RECEPTORS COUPLED TO NUCLEUS)


Direct change in gene expression

Synthesis of specific mRNA

Synthesis of specific proteins

Responsible for mediating pharmacological actions

Source: Google

EXAMPLES:

1. Glucocorticoid receptors

2. Mineralocorticoid receptors (Aldosterone receptors)

3. Estrogen receptors

4. Progesterone receptors

5. Androgen receptors (Testosterone receptors)

6. Vitamin A & Vitamin D receptors

7. Thyroid hormone receptors

Source: Google

Source : Google

SIGNAL TRANSDUCTION

Ligand after binding to the receptors a sequence of

events/steps taking place in order to produce

pharmacological actions.

Fastest acting receptors

Most intensifying action

observed in case of

Fastest acting receptors Ionotropic receptors

Most intensifying action

observed in case of

Nuclear receptors

Transcellular

receptors

Intracellular receptors

Ligand binding site

Reactions

Examples

Transcellular

receptors

Intracellular receptors

Ligand binding site Extracellular Intracellular

Reactions Intracellular Intracellular

Examples GPCR, Ionotropic

receptors, Enzyme

linked receptors

Nuclear receptors

Presented by

Dr. Sannithi Nagarjuna

Coordinator for RIPER-GPAT Cell,

Hyderabad Academy &

Online GPAT Academy

7899107907

9885784793

[email protected]

Documents

PHARMACODYNAMICS · PHARMACODYNAMICS Presented by Dr. Sannithi Nagarjuna Coordinator for RIPER-GPAT Cell, Hyderabad Academy & Online GPAT Academy 7899107907 9885784793 [email protected]