PHARMACODYNAMICS

Dr Jatin Dhanani

Dosage

Plasma Site of
Concen. Action

Pharmacokinetics

Effects

Pharmacodynamics

The study of biochemical & physiological

effects of drugs on the body & their
mechanisms of action

Principles of Drug Action

Stimulation

Depression

Irritation

Replacement

Cytotoxic action

Mechanism of Drug Action

Physical action
Adsorption
Physical mass
Osmolality
Demulcent
Astringent
Enzymes
Radioactivity
Radio-opacity

Chemical action

Action through
Biomolecule

Neutralization, alkalization, acidification

Chelation
Ion exchange
Oxidation
Antioxidant
action
Ion channels
Transporters

Receptors

RECEPTORS
Definition
macromolecule or binding site, located on the
surface or inside the effector cell, that serves to
recognize the signal molecule/drug and initiate
the response to it, but itself has no other
function.

Structure protein in nature (quaternary)

Ligand
any molecule which attaches selectively to
particular receptor or sites

Drug Receptor binding

Van

der wall force

Hydrogen bond
Ionic bond
Covalent bond

Drug Receptor interaction

Agonist
Partial agonist
antagonist
Inverse agonist

Lock & Key Theorem

A ligand acts as a "key bind to specific receptors
"lock and "unlocks" the cell's response

Many drugs work by mimicking a naturally occurring

hormone or Neurotransmitter (agonist)

Some drugs bind to the receptor, but do not produce

any response. They just occupy the receptor site
(antagonists)

Receptor Occupation Theory

D + R DR E
Occupation of receptors only not sufficient to produce
effect.Activation of the receptors is necessary
Several ligand just occupy the receptors - antagonist

D + R DR ~ S E

Clarks equation

Concept of affinity and intrinsic activity (efficacy)

Agonist high affinity and maximum

intrinsic activity (IA=1)

Competitive antagonist high affinity but

no intrinsic activity (IA=0)

Partial agonist high affinity but

submaximal intrinsic activity (IA=0 to 1)

Inverse agonist high affinity but activity

in opposite direction (IA= -1 to 0 )

Two state receptor model

RECEPTOR TYPES
&
TRANSDUCER MECHANISM

Receptors

Enzyme linked
Ion channels

GPCR
Nuclear receptors

Enzymes
Active Enzyme

Substrate

Product

Cellular Function
Bound Enzyme
stimulator (Drug)

Increased Cellular
Function

Inactive Enzyme

Substrate
Bound Enzyme
Inhibitor (Drug)

Drugs stimulate the enz

Pyridoxine

Decarboxylase activity

Adrenaline (through beta receptor)

Glycogen phosphorylate

Drugs inhibits the enz

Physostigmine

Acetylcholinesterase

Captopril

Angiotensin Converting Enz

Simvastatin/ Lovastatin

HMG-CoA reductase

Zidovudine

Reverse transcriptase

Aspirin

Thromboxane A2

Allopurinol

Xanthine oxidase

Digoxin

Na K ATPase

Ion Channels

Examples
Quinidine

blocks
myocardial Na+ channels
Nifedipine blocks L-type
voltage gated Ca+
channels
Amioderone blocks
myocardial K+channels
Phenytoin modulate
voltage sensitive Na+
channels

Transporters

Drugs

Transporters

Desipramine, Cocaine

Norepinephrine transporter(NET)

Fluoxetine

Serotonin transporter (SERT)

Furosemide

Na K 2Cl co-transporter

G-Protein Coupled Receptor

(GPCR)

Numbers of G proteins are identified

Gs:

adenylyl cyclase, Ca +2 channel

Gi: adenylyl cyclase, Ca +2 channel
Gq: phospholipase
Go: Ca +2 channel
G13: Na + /H + exchange
Gn, Gk, Gt

G-protein coupled receptors

Receptors with
Enzymatic Activity
Intrinsic enzyme receptors
JAK-STAT-kinase binding receptors

Insulin, EGF, NGF receptors

Receptors regulating
gene expression

Receptor Regulation
Prolonged deprivation of agonist results in
supersensitivity of the receptor
Mechanism up regulation of the
receptors or amplification of transducer
mechanism
Eg. sudden discontinuation of
propranolol in angina pectoris

Desensitization continued/intense
receptor stimulation causes less response
on next stimulation
Mechanism masking/internalization of
the receptors or decreased
synthesis/increase destruction (down
regulation) of receptors

DOSE RESPONSE
RELATIONSHIP
7
6

Quantal DRC

5
Graded
DRC
4
3
2
1
0

0.5

16

32

64

Graded Dose-Response Curve

Potency: amount of drug to produce certain

response
Efficacy: ability of a drug to illicit required
response

Quantal Dose-Response Curve

Therapeutic Index

Therapeutic index - the ratio of the dose that

produces toxicity to the dose that produces
a clinically desired or effective response
in a population of individual

Therapeutic Window Phenomenon

Optimal therapeutic effect seen only over a narrow range of the plasma
conc. Both above and bellow the therapeutic effect is suboptimal or
toxic effect starts appearing

COMBINED EFFECT OF
DRUGS
SYNERGISM

ANTAGONISM

Synergism
Additive
(A+B=AB)

Examples
1.

2.

Ibuprofen +
Paracetamol
(combiflam)
Amlodipine +
atenolol

Supraadditive
(A+B<AB)

Examples
1.
2.
3.

Levodopa + Carbidopa
Ach + Physistigmine
Sulfmethoxazole +
trimethoprime

Antagonism
Receptor
antagonists

Active site
binding

Reversible

Competitive
antagonist

Nonreceptor
antagonists

allosteric site
binding

Irreversible

Reversible

Noncompetitive
antagonist

Irreversible

Chemical
Physiological

Physical

Difference b/w competitive and

noncompetitive antagonism

Factors Modifying The Drug

Actions

Body size
According

to Body Weight:
or
According to surface area: individual dose is
=

Age
Youngs formula: child dose =
Dillings formula: child dose =

Sex: smaller body size, hormonal

difference, pregnancy and lactation

Species and race

Ex.

black & white difference for pupilary

reaction to atropine and adrenaline

Genetics
Ex.

Acetylation of drugs, G6PD def.,

Malignant Hyperthermia, atypical
pseudochlinesterase

Diet and environment

Ex.

tetracycline with calcium, polycyclic

hydrocarbon of cigarette smoke

Route of administration
MgSO4

by oral or iv route

Disease states
GIT

diseases, Liver diseases, Kidney disease,

CHF

Psychological factors
Placebo

Presence of other drug

Repeated dosing

Cumulation
Tolerance
Tachyphylaxis

Thank You