1. Pharmacodynamics (dynamics – power): study of
drugs in respect to their mechanism of action,
pharmacological action and side effects.
Or
what the drug does to the body.
The drug actions are:
• 1. Stimulation: drug increases the activity of
specialized cells.
Eg. adrenaline stimulates the heart
2. • 2. Depression: drug decreases the activity of
specialized cells.
eg. general anaesthetics depress central nervous
system.
• 3.Irritation: drugs on local application irritates
less specialized cells (Epithelial, connective tissue)
stimulate the associated function.
Strong irritation may result in inflammation, corrosion
and necrosis of cells.
eg. bitters increase salivary secretion.
Counter irritant increases blood flow to the site of
application.
Methyl salicylate, turpentine liniment.
3. • 4. Replacement: the deficiency of endogenous
hormone or substance corrected by hormonal
preparations or drugs.
• eg. insulin, thyroid hormone, levo-dopa.
• 5. Cytotoxic action: drugs or antibiotics produced
toxic action against infecting micro-organism or
malignant cells.
• eg. anticancer drugs, ciprofloxacin.
4. Mechanism of drug action.
1.Physical action: based on physical property of drug.
eg. Adsorption - activated charcoal (poisoning)
Osmotic effect - 20 % Mannitol ( cerebral oedema)
Radioactivity - I 131 (hyperthyroidism)
Demulcent effect - lozenges (cough)
2. Chemical action: based on chemical reaction or
interaction.
eg. Antacids - peptic ulcer (Gelusil)
Chelating agent - heavy metal poisoning
(d-penicillamine in copper toxicity)
Oxidizing agent – potassium permanganate (germicidal)
Acidification or alkalization of urine (poisoning)
5. 3. Through enzymes: drugs can increase or decrease
the rate of enzymatic reactions.
a) Enzyme stimulation: drug increases the enzymatic
activity.
eg. Adrenaline stimulate adenylyl cyclase
b) Enzyme inhibition: drug inhibiting the enzymatic
activity.
• It may be non specific or specific.
Non specific: many enzymes get inhibited by single
drug. eg. Phenol, formaldehyde
6. Specific : single or particular enzyme is inhibited.
eg. Enalapril - Angiotensin converting enzyme (ACE)
inhibitor. (HTN)
Aspirin - inhibits cyclo-oxygenase (analgesics)
Neostigmine – inhibits acetyl cholinesterase (myasthenia
gravis)
Allopurinol – inhibits xanthine oxidase (Gout)
4. Through ion channels: some drugs bind to ionic
channels and alter the movement of ions.
Calcium channel blockers. eg. verapamil
Potassium channel openers. eg. Nicorandil
7. 5. Through antibody production: vaccines increase
antibody production.
eg. BCG vaccine (tuberculosis)
Oral polio vaccine (Polio)
6.Transporter inhibitors: drugs bind to the transporters
and block reuptake of neurotransmitters.
(SSRIs)
8. 7. Through receptors: it is a macro component of cell
with which drug interacts and gives pharmacological
response.
• For pharmacological response, drugs have to have
affinity and intrinsic activity.
• Affinity: is the ability of drug to combine with
receptors.
• Intrinsic activity: is the ability of drug to produce a
response after combining with receptor.
9. • Agonist: drug combines with receptor and produce
pharmacological response. eg. Morphine
• (it has both affinity and intrinsic activity IA= 1)
• Antagonist: drug combines with receptor and
doesn’t produce pharmacological response. Or
Drug combines with receptor and prevents the
action of agonist on the receptor. eg. Naloxone
• (it has affinity but no intrinsic activity IA= 0)
10. • Partial agonist: drug combines with receptor and
produce sub maximal response. eg. Pentazocine
• (it has affinity and less intrinsic activity IA <1)
• Inverse agonist: drug combines with receptor and
produce exactly opposite response to that of an
agonist.
eg. β carboline (Benzodiazepine receptor)
(it has affinity and negative intrinsic activity. i.e IA -1)
• Ligand : a molecule which binds selectively to a
specific receptors (May be endogenous eg. hormone
/ drug)
• Types of receptors:
• They are classified into five types
11. 1) G protein coupled receptors (GPCR): are
cell membrane receptor linked to the
effector through G proteins for response.
• G proteins consist of three subunits: α, β, and γ.
Ligand / Drug binds to a receptor and thus activates
G proteins for the response.
• Gs: adenylyl cyclase activation (AC), ↑ ca++ entry.
• Gi: adenylyl cyclase inhibition,↑ K+ entry
• GO: ↓ ca++ entry
• Gq: Phospholipase C activation.
12. • GPCRs function through following pathways.
i) Activation AC pathway: results in the formation &
accumulation of cAMP. It acts through protein
kinases. Protein kinases phosphorylate various
proteins and regulate cellular activity.
• eg. Contraction / relaxation of smooth muscle,
glycogenolysis, lipolysis, and hormone synthesis.
ii) Phospholipase C / IP3 – DAG pathway :
hydrolyses the membrane phospholipids and
generate second messengers IP3 & DAG
• IP3 – mobilizes Ca++ from intracellular depots
(endoplasmic reticular)
• DAG – activates protein kinases
13. iii) Channel regulation: activation of G (Gs, Gi,
Go) protein causes opening or closing ionic
channel. eg. depolarization / hyperpolarization
• maintains responses like inotrophic,
chronotrophic, transmitter release.
• 2) Ion channel receptor / ligand gated ion
channels: The ionic channel present on the
inner side of cell membrane. Its activation
opens ionic channel. eg. GABAA, NM,NN &
NMDA. These receptors are fastest acting
(in milliseconds).
14. • 3) Enzymatic receptors / kinase linked receptor:
have binding site on the extra cellular surface and
catalytic site present at intracellular site. These sites
connected by peptide chain. They are protein
kinases. e.g. insulin receptor, leptin , epidermal
growth factor
• 4) Transmembrane JAK –STAT binding
receptors : agonist increases its affinity for a
cytosolic tyrosine protein kinase JAK. Its activation
causes phosphorylation tyrosine residue and free
moving protein STAT .
• Phoshorylated STAT binds to nucleus to regulate
gene transcription and maintains biological
response.
• e.g. cytokines, growth hormone , interferons
15. • 5) Receptors regulating gene expression:
agonist activates intracellular receptors. This
agonist - receptor complex migrates towards
nucleus and interacts with DNA, regulate gene
transcription and thus directs synthesis of specific
proteins to regulate cellular activity.
• e.g. steroidal hormones, thyroid hormones,
Vit D & Vit A.
16. Receptor regulation :
• Up regulation: The number of receptor & their
sensitivity is increase after prolonged use of
antagonist.
• eg. Propranolol after sudden discontinuation
in angina pectoris pts increase risk of attack /
MI
• Down regulation: The number of receptor &
their sensitivity is decrease after prolong use
of agonist.
• eg. Salbutamol after prolong use reduces
bronchodilatory effect in asthma pts.
