Dr.U.P.

Rathnakar
MD.DIH.PGDHM
PHARMACODYNAMICS
 What the drug does to the body.

Study of drug effects. How? And What?

Pharmacodynamics deals with the study of

biochemical and physiological effects of drugs and
their mechanisms of action.
 Dose
Absorption
Distribution
Metabolism
Pharmacokinetics
Excretion

Drug in the plasma

Drug at the site of action

Pharmacodynamics
PRINCIPLES [Types] OF DRUG ACTION
1. Stimulation
 Adrenaline
4. Replacement
• Insulin
 Pilocarpine
• Iron
2. Depression
• Levodopa
 Quinidine
5. Cytotoxic action
 Morphine
•Penicillin,
 Barbiturates
•Chloroquine
3. Irritation • cyclophosphamide
 Bitters
6. Modification of
 Counter
immune status
irritants •Vaccines
•Sera
Action
Non-receptor mediated Receptor mediated

Physical Receptor
Chemical s on the
Enzymes cell
membran
Antibody
e
Placebo Receptor
Mediated

Physical Examples
Osmosis 20% Mannitol in
Glaucoma
Activated
Adsorption
charcoal in
poisoning
Demulcent Soothing effect
of cough lozenges
I131 in
Radioactivity
Hyperthyroidism
Mediated

Chemical Examples
Antacids Neutralize acid
in stomach
Chelation BAL in As
poisoning
Mediated

Enzymes Examples
Enzyme ACE inhibitors
inhibition in HTN

Disulfiram in
chronic
alcoholism
Enzyme
activation Pralidoxime in
OP poisoning
Mechanism of Drug Action -
Non-receptor Mediated

Antibody production Examples

Stimulation of
BCG against TB,
AB production in Polio vaccine
body against Polio
 Mechanism of Drug Action - Non-receptor
Mediated-Placebo effect
Placebo
 Dummy medicine without Pharmacological
effect
Uses
4.Relief of subjective symptoms- Eg .Anxiety
5.In Clinical trials to reduce bias
Factors affecting
7.Pt factors-With neurotic symptoms
8.Drug factor-Injection, Capsules
9.Doctor factor-Personality, Fame, Dr - Pt
relationship
 Mechanism of Drug Action - Receptor
Mediated
Eg.Adrenergic,
Receptor: Receptors,Muscarinic receptors
 Protein macromolecules
 Present on cell wall or
 Inside the cell
 To which drug binds, interacts, produces action
Drug[D]+Receptor[R]↔D-R-Complex→Action

r
D
ug
Dr
ug
 D-R
Binding

Drug

Effect

Receptor

Second messengers

RECEPTOR MEDIATED DRUG ACTION

Receptor Mediated- Terms
Affinity: Ability of the drug to
bind to receptor
Intrinsic activity: Ability of drug to produce
pharmacological activity after binding
Agonist: Drug which binds and
Affinity+Intrinsic activity
produces pharmacological action Eg. Morphine,
Adrenaline
Antagonist: Binds but no action. Affinity + NO
Int.activity
But blocks receptors Eg. Naloxone,
Partial agonist: Binds
Atropine BUT Affinity +
LESS intrinsic
less Action
Inverse agonist:Binds BUT activity-
Pindolol
Affinity + opp
Produces action opp.of agonist
endocrine and the sensory systems.
Receptor Super

 
Families

                                                                                                            

References:

Ligand gated ion channels

G-Protein coupled[GPCR]

Nuclear receptors
Enzymatic receptors
 Receptor Super
Families
MEMBRANE BOUND RECEPTORS
GPCR: Eg. Muscarinic, Adrenergic receptors

Ligand gated Ion channel: Eg. Nicotinic receptors

Enzymatic: Eg. Insulin receptor

 INTRACELLULAR RECEPTORS
Nuclear Receptors: Eg. Steroid, Thyroid hormone
Receptor Regulation
Downregulatio
Upregulation
n
Prolonged use of Prolonged use of
agonists antagonists
[Salbutamol] [Propranolol]
 ↓  ↓
Receptor no. and Receptor no. and
sensitivity [β2 sensitivity [β2
receptors] ↓ ↓ receptors] ↑↑
↓ ↓
Drug effect  [Sudden withdrawal →
↓↓ Increased sensitivity of
[Decreased effect on adrenoreceptors→Angina
chronic use]
Dose response
Dose-Response relationship: Relationship between
Pharmacological effect and dose [Concn.of drug at
site of action]
Graded or quantitative: As the dose
administered in a single sub or tissue is
increased, response increases in a graded fashion
Graded Quantal

Quantal or all or none: frequency with which any

drug evokes a all or none response in a population
Therapeutic index [TI]
Index of drug safety [TI]
 Median lethal dose[LD50] = TI
Median effective dose[ED50]
LD50=Dose which kills 50% of sample population
ED50=Dose which produces desired effect in 50%
of sample population
Margin of safety=LD1/ED99
LD1=Lethaldose for 1% population
ED1=Effective dose for 99% of population
Wider the TI-More safe the drug
Eg.Penicillin -wide TI , Digoxin narrow TI
 TI=10/5=2 TI=100/5=20

100→

TI TI WIDE
Narrow
50% ED50 LD50
→

0 →
Drug potency: QUANTITY
of a drug required to
produce a response
Lower the dose more
potent
Drug efficacy: Maximum
effect of the drug.
Morphine more efficacious
Therapeutic window: Effect is
seen only during the narrow
range of plasma concn. Both
below and above the range
beneficial effect not seen. Eg.
TCA

Therapeutic range: Range

between dose which produces
minimal Th.effect and
Max.acceptable adverse effect
Combined effect of drugs
When 2 drugs are administered together:-

They may be Indifferent to each other

One may increase the action of the other-

Synergism

Action may be decreased or abolished

Antagonism
Indifferent Synergism Antagonism

Physical

One facilitates Chemical

One opposes the
Additive the action of
action of other
other Physiological

Supra-additive Receptor
[Potentiation]

Competitive Non-competitive
 SYNERGISM
Two drugs → One increases or facilitates
the action of the other
Supra-additive
Additive (Potentiation)
1 + 1 = 2
1 + 1 = 3 OR 1 + 0 = 2
 Drug A + Drug B
Effect of combination is
= Effect of A+B
more than individual effect
 Advantage:
of 2 drugs
 Side effect may not add up
One drug may be inactive
 Dose of both can be reduced
Levodopa+Carbidopa[Inactive
 Eg.
alone]
 Aspirin+Paracetamol
Sulfamethaoxazole+Trimeth
 Nitrous oxide +Halothane
oprim[Both active]
 Amlodipine+Atenolol
Antagonism
[Effect of one drug is decreased]
Physical – Charcoal adsorbs alkaloids
Chemical – KMno4 oxidizes Alkaloids
- BAL chelates arsenic
- Protamine neutralizes
Heparin
- Na.Thiopentone+
Succinylcholine
3. Physiological – Histamine and Adrenaline
[Functional] - Glucagon and Insulin
- Hydrochlorothiazide
andTriamterene
4. Receptor:
 Antagonism [RECEPTOR]
One[Antagonist] blocks the receptor action of the
other[Agonist]
Competitive[Surmounta Noncompetitive[Unsurmount
ble] able]
1. Binds with the same 1. Binds to another site or
site on the receptor same site covalently
2. Resembles the agonist 2. No resemblance
3. Surmountable by Not surmountable
incresing the concn. Of
agonist Flattening of DRC
4. Rightward shift of DRC
Eg.
5. Eg. Diazepam –Bicuculline
Ach – atropine Phenoxybenzamine-
Morphine - Naloxone Noradrenaline
Action
Patient
Drug Factors
Route of administration Age Factors
Presence of other drugs Body Wt.
Cumulation Sex
Placebo Drug dependence
Diseases[Pathological
state]
Environment
Emotional factors
Genetic factor
Tolerance
 Factors Modifying Drug Action: ‘Drug Factors’
1. Route:
 Quantitative- Oral dose more than i.v. dose
 Qualitative
 Mgso4 Locally- Reduces edema
 Mgso4 orally - Purgative
 Mgso4 i.v. - CNS depressant
2. Presence of other drugs- ‘Combined effect’
3. Cumulation: When elimination is slower may
accumulate and produce toxic effect- Digoxin
4. Placebo
 Factors Modifying Drug Action:
‘Patient Factors’
5. Age:
Infants:
 Low GFR and immature tubular transport
Penicillin G is given BID
Inadequate hepatic metabolizing system
Chloramphenicol – gray baby syndrome
Blood brain barrier is more permeable
-kernicterus
Skin is more permeable
Factors Modifying Drug Action:
‘Patient Factors’
Age:
Elderly:
- decline in renal function
-reduced hepatic activity
-reduced intestinal motility
-altered volume of distribution
-drug interactions
-prostatic hypertrophy - urinary retention
ADE effects more
Dose to be lowered- AG
Body Wt. And Surface Area
6. Body weight:
Individual = Body weight (kg) X Adult dose

Dose 70

BSA
Individual dose = ------x Average adult dose
1.7
‘Patient Factors’
1. Sex:
Morphine and Barbiturates paradoxical response of
excitement in females. Use of hormones
3. Environment:
Pollutants like DDT, Cigarette smoke, Insecticides,
Alcohol-Enzyme inducers- Affects OCP
9. Genetic factors
6. Emotional:
Personality of the Doctor[Placebo] and Pt[Neurotics
require higher dose of diazepam
‘Patient Factors’
11. Pathological states;
 Gastrointestinal diseases:
Malabsorption syndrome:
Achlorhydria: Decreases aspirin absorption
 Liver disease:
↓First pass metabolism
B.A of Lidocaine, Propranalol
 Kidney disease
↓Clearance of drugs that are excreted in unchanged
form.
Aminoglycosides
12.Tolerance
Tolerance occurs when the person no longer
responds to the drug in the way that person initially
responded.

A state in which higher dose is required to achieve

the same effect
Eg.
 Nitrates in Angina
 Morphine in pain relief
 Types of Tolerance
Natur Toleranc Acquire
d
al e
•On
repeate
SPECIE RACE d
S In Afro – exposur
Rabbits Carribea e
are ns
resista β •May be
Morphine
nt to blockers Not to
only to
Atropin Less Constipatio some
e effective n and effects
Mydriatic
actions
of a
drug
Tolerance: Mechanism
Pharmacokinetic:
Increased Metabolism, reduced
absorption
Pharmacodynamic
Cells of the target organ become
less sensitive
Morphine, Barbiturates,
Nitrates, Alcohol
Tachyphylaxis (acute tolerance):
Rapid development of tolerance
Amphetamine, Nicotine

Cross tolerance:
Development of tolerance to pharmacologically
related drugs
Eg.
 Alcohol and Barbiturates
 Morphine and Barbiturates
 Morphine and Pethidine
12. Drug Interactions
Two drugs Combined: Synergism, Antagonism Etc.
 Pharmacokinetic:
Delivery of a drug to its site of action is altered by
a second drug
Eg. Antacids and tetracyclines

Pharmacodynamic:
Response of a drug target is modified by a second
drug
Eg. NSAIDs and ACE inhibitors
Nitrates and Sildenafil