PH1.5 Describe general principles of mechanism of drug action.

1. Understanding
Pharmacodynamics
Dr. Pankaj Kumar Gupta,
Assistant Professor,
Department of Pharmacology,
ESIC Medical College & Hospital, Faridabad

2. Pharmacon = Drug
Dynamics = Action/Power
(In Greek)
“What a drug does to the body”

3. Objectives
• Definition
• Site of drug action
• Types of drug action
• Mechanism of action of drugs
• Receptor mediated action
– Receptor function
– Drug receptor interaction
– Receptor subtypes
– Receptor families
• Non-receptor mediated action
• Factors modifying drug action

4. Site of Drug Action
1 Extra cellular
2 Cellular
3 Intracellular

5. Site of Drug Action
1 Extra cellular •Antacids neutralizing gastric acidity.
•Chelating agents forming complexes with heavy
metals.
•MgSo4 acting as purgative by retaining the fluid inside
the lumen of intestine.
2 Cellular •Ach on Nicotinic receptors of motor end plate, leading
to contraction of skeletal muscle.
•Adrenaline on heart muscle and blood vessels.
3 Intracellular •Folic acid synthesis inhibitors (Trimethoprim and sulfa
drug) - folic acid which is intracellular component
essential for synthesis of proteins.

6. Types of Drug Action
1 Stimulation
2 Inhibition/
Depression
3 Replacement
4 Irritation
5 Cytotoxic

7. Types of Drug Action
1 Stimulation Some of drug act by increasing the activity of specialized cells.
Eg: Adrenaline stimulate the Heart rate & Force of contraction
2 Inhibition/
Depression
Some drug act by decreasing the activity of specialized cells.
Eg: Alcohol, Barbiturates, General anesthetic these drug depress
the CNS system.
3 Replacement When there is a deficiency of endogenous substances, they can
replaced by drugs.
Eg: Insulin in Diabetes mellitus, Throxine in cretinism and
myxedema
4 Irritation Certain drugs on topical application cause irritation of the skin and
adjacent tissues. These drugs are used for counter irritant.
Eg: Eucalyptus oil, methyl salicylates (Used in sprains, joint pain,
myalgia)
5 Cytotoxic Treatment of infectious disease/cancer with drugs that are
selectively toxic for infecting organism/cancer cells
Eg: Anticancer drugs, All Antibiotics

8. Mechanism of Action of Drugs
• Chemical interaction between drug & tissue.
• Drug acts by (HOW)
Through functional/regulatory
proteins
Through other mechanisms
(Physical/Chemical properties)
MOA
•Enzyme
•Transmembrane Ion Channel
•Transporter
•Receptor
•Adsorption
•Physical Mass
•Osmolarity
•Taste
•Demulcent
•Astringent
•Surface tension
•Chelation

9. TARGETS OF DRUG ACTION

10. Functional/Regulatory Proteins
Proteins Properties
1 Enzyme •Stimulation
•Induction (synthesis of more enzyme proteins)
•Inhibition (Competitive/Non-competitive)
2 Transmembrane Ion
Channel
Participate in transmembrane signaling and
regulate intracellular ionic composition.
They can be:
1.ligand gated channels
2.voltage operated
3 Transporter •Many drug produce their action by directly
interacting with the transporter proteins to inhibit
the ongoing transport of the metabolite/ ion.
4 Receptor •Drug produce their effect through interacting
with some chemical compartment of living
organism c/s Receptor.

11. Receptor Mediated action
• Receptor is defined as a 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.
• Receptors are macromolecules.
• Most are proteins.
• Present either on the cell surface, cytoplasm or
in the nucleus.

12. Receptor Functions: Two essential functions
1. Recognization of specific ligand molecule (Ligand
binding domain)
2. Transduction of signal into response (Effector domain)
Ligand binding
domain
Transduction of
signal into response

13. DRUG RECEPTOR INTERACTIONS
Drug(D) +Receptor® Drug receptor complex Response

14. DRUG RECEPTOR INTERACTIONS
•Selectivity - Degree to which a drug acts on a given
site relative to other sites. Relatively nonselective
drugs affect many different tissues or organs.
Ex:- Salbutamol selectivity for ß2 Receptors as
compared to ß1 receptors.
•Affinity - Ability of drug to get bound to the receptor.
•Intrinsic activity (IA) or Efficacy - Ability of drug to
produce a pharmacological response after making
the drug receptor complex.

15. DRUG RECEPTOR INTERACTIONS
•Agonist - An agent which activates a receptor to
produce an effect similar to that of the physiological
signal molecule. (Affinity + IA=1)
•Inverse agonist - An agent which activates a
receptor to produce an effect in the opposite
direction to that of the agonist.
•Antagonist - An agent which prevents the action of
an agonist on a receptor or the subsequent
response, but does not have any effect of its own.

16. • Partial agonist - An agent which activates a receptor to
produce submaximal effect.
• Ligand (Latin: ligare- to bind) - Any molecule which
attaches selectively to particular receptors or sites. The
term only indicates affinity or ability to bind without
regard to functional change. Agonists and competitive
antagonists are both ligands of the same receptor.
DRUG RECEPTOR INTERACTIONS

17. Receptor Families
Five types of receptors families (Transducer mechanisms)
1. G-protien coupled receptor (Metabotropic receptors)
1. Adenylyl cyclase: cAMP pathway
2. Phospholipase C: IP3-DAG pathway
3. Channel regulation
2. Ligand-gated ion channels (inotropic receptors)
3. Enzymatic receptors (tyrosine kinase)
4. Transmembrane JAK-STAT binding receptors
5. Receptor regulating gene expression (transcription factors/
Steroid)

23. Characteristics of receptor families
Ligand
gated
G-protein
coupled
Enzymatic Nuclear
Location Membrane Membrane Membrane Intracellular
Effector Ion channel Ion Channel
or enzyme
Enzyme Gene
coupling Direct G-protein Direct Via DNA
Example Nicotinic Muscarinic Insulin Steroid ,
hormone

24. Non receptor mediated action
• All drug actions are not mediated by receptors or
other regulatory proteins. Some of drugs may
act through chemical action or physical action or
other modes.
»Physical action
»False incorporation
»Protoplasmic poison
»Formation of antibody (Vaccines)
»Targeting specific genetic changes
»Chemical action

25. Non receptor mediated action
1. Physical action •Adsorption: Kaolin absorbs bacterilal toxin and thus acts as antidiarrhoeal
agent.
•Protectives:- Various dusting powders.
•Osmosis:- MgSo4 acts as a purgative by exerting osmotic effect
•Astringents:- They precipitate the surface proteins and protect the mucosa
Ex: tannic acid in gum patients
•Demulcent:- These drugs coat the inflamed mucus membrane and provide
soothing effect. Ex: Menthol
2. False
incorporation
•Bacteria synthesis folic acid from PABA (Para Amino Benzoic Acid), for
growth sand development.
•Sulfa drugs resemble PABA, therefore falsely enter into the synthesis
process of PABA, cause nonfunctional production and no utility for bacterial
growth.
3. Protoplasmic
poison
•Germicides and antiseptics like phenol and formaldehyde act as non
specifically as protoplasmic poison causing the death of bacteria
4. Formation of
antibodies
•Vaccines produce their effect by inducing the formation of antibodies and
thus stimulate the defense mechanism of the body- eg:- Vaccines against
COVID19.
5. Targeting specific
genetic changes
•Anti cancer drugs that specifically target genetic changes.
•Inhibitors of specific tyrosine kinase that that block the activity of oncogenic
kinases.
6. Chemical action •Ion Exchanges:-Anticoagulant effect of heparin(-ve charge) antagonized by
protamine (+ve charged) protein.
•Neutralization:- Excessive gastric acid is neutralized by antacids.
•Chelation:-These are trap the heavy metals. Ex:-EDTA, BAL.

26. Factors modifying drug action

27. Factors modifying drug action
Factors Drug Action
1 Body weight/size •It influences the concentration of drug attained at the site of
action.
•The average adult dose refers to individuals of medium built
(70 KG).
•For exceptionally obese or lean individuals and for children
dose may be calculated on body weight basis.
•BSA=BW(Kg)0.425 x Height(cm)0.725 x 0.007184
dose
adult
Average
x
70
(kg)
BW
dose
Individual 
dose
adult
Average
x
1.7
(m2)
BSA
dose
Individual 

28. Factors modifying drug action
Factors Drug Action
2 Age •In elderly, renal function progressively declines (intact nephron loss) and drug
doses have to be reduced.
•Infants and children are have important physiological differences
• Higher proportion of water
• Lower plasma protein levels
• More available drug
• Immature liver/kidneys
• Liver often metabolizes more slowly
• Kidneys may excrete more slowly
formula)
s
Young'
.........(
dose
adult
x
12
Age
Age
dose
Child


formula)
s
g'
...(Dillin
dose......
adult
x
20
Age
dose
Child 

29. Factors modifying drug action
Factors Drug Action
3 Gender •Females have smaller body size, and so require doses of drugs on
the lower side of the dose range
4 Pregnancy •Profound physiological changes which may affect drug responses:
•GI motility reduced –delayed absorption of orally administered
drugs
•Plasma and ECF volume expands
•Albumin level falls
•Renal blood flow increases markedly
•Hepatic microsomal enzyme induction
5 Food •Delays gastric emptying, delays absorption (ampicillin)
•Calcium in milk –interferes with absorption of tetracyclines and iron
by chelation

30. Factors modifying drug action
Factors Drug Action
6 Species & race Afro-americans require higher Mongols require lower concentrations of
atropine and ephedrine to dilate their pupil
7 ROA I.V route dose smaller than oral route
8 Biorhythm •Hypnotics –taken at night
•Corticosteroid –taken at a single morning dose
9 Psychological state •Efficacy of drugs can be effected by patients beliefs, attitudes and
expectations particularly applicable to centrally acting drugs
10 Presence of
diseases/pathological
states
Hepatic/renal disease may slow drug metabolism
11 Cumulation Any drug will cumulate in the body if rate of administration is more than the
rate of elimination-eg: digitalis, heavy metals etc.
12 Genetic Factors Lack of specific enzymes, lower metabolic rate-eg: Acetylation, Plasma
cholinesterase (Atypical pseudo cholinesterase), G-6PD, Glucuronide
conjugation
13 Tolerance Requirement of a higher dose of the drug to produce an effect, which is
ordinarily produced by normal therapeutic dose of the drug

32. Thank You