Pharmacology and

Therapeutics
Course Code: PHM-412, 4 (3-1)

Faculty:
Zulfia Hussain
AHP - GCUF
Introduction
Introduction
Pharmacodynamics is the study of the
biochemical cellular and physiological effects of
drugs and their mechanisms of action
Pharmacodynamics:
What drugs do?
• Effects
How drugs do it?
• Mechanism
Components of
Pharmacodynamics
5 Principles of Drug action

Stimulation:
Selective enhancement of the level of
activity of specialized cells
 Acetylcholine on salivary glands
• Increases secretion of saliva
Principles of Drug action
Depression:
Selective diminution of the level of activity of
specialized cells
Salbutamol on uterine muscles
• Contraction of uterus decreased
Principles of Drug action
Irritation:
Non-selective, often noxious effect on less
specialized cells
• Capsaicin in herpetic neuralgia
Strong irritation  inflammation, necrosis,
morphological damage
• Local alcohol injection in refractory
neuralgia
Principles of Drug action
Replacement:
Use of natural metabolites, hormones, or
their congeners in deficiency states
• Iron supplementation in Iron deficiency
anaemia
• Insulin in Diabetes mellitus
Principles of Drug action
Cytotoxic Action:
Selective cytotoxic action on invading
microbes
• Penicillin, cephalosporins
 Selective cytotoxic action on cancer
cells
• Methotrexate, Cisplatin
Mechanism of Action of Drugs
By virtue of physical property:
 Isaphgula Laxatives
 Dimethicone Ulcer dressing
 Para-amino benzoic acid
Sunscreen
Activated charcoal Drug overdose
 131 I radioisotopes Hyperthyroidism
Mechanism of Action of Drugs
By virtue of chemical property:
Antacids Hyper-
acidity
Potassium permanganate Antibacterial
Chelating agents Heavy metal poisoning

Cholestyramine Hypercholesterolemia
Mechanism of Action of Drugs
By interacting with protein molecules:
Colchicine
Vinca alkaloids
Taxanes
By interacting with nucleic acids:
Alkylating agents
Sulfonamides
Mechanism of Action of Drugs
By interacting with macromolecular functional
proteins: (RICE)
Ion channels
Transporters (Carriers) RIC
Enzymes E
Receptors
Drug targets
Cellular macromolecule or macromolecular
complex with which the drug interacts to elicit a
cellular or systemic response.
Drug Targets- Ion channels
Drug Targets- Ion channels
 Ion channels-

Modify the intracellular ionic composition of cells

Drugs can be used to modify their

conductance
 Can be:
Ligand gated
Receptors
G-protein gated
Voltage gated
Drug Targets- Ion channels

Drug Ion channel Use

Myocardial Na+
Quinidine Arrhythmia
channels

Myocardial K+ Arrhythmia
Amiodarone channels
Sulfonylurea Pancreatic K+
Diabetes
channels
Neuronal Na+ Epilepsy
Phenytoin
channels
Drug Targets- Transporters
(Carriers)
Drug Targets- Transporters
Carrier Blockers
Transports Noradrenaline Desipramine,
Norepinephrine
transporters (Norepinephrine) Cocaine
Gamma butyric
acid GABA Tiagabin
transporter e
Na+(GAT1)
- K+ - 2Cl-
Na+, K+, Cl- Furosemide
co-transporter
Serotonin
Serotonin Fluoxetine
Transporte
Drug Targets- Enzymes
Enzymes:
Optimises the rate of chemical reaction in
our body
 Can be stimulated or inhibited using
drugs
Increase in activity can also occur by
enzyme induction
Drug Targets- Enzymes

Enzyme stimulation:
Thiamine, Pyridoxine: increase decarboxylase
activity
• Metabolism of formaldehyde, formic acid
enhanced
Adrenaline: increases hepatic glycogen
phosphorylase
• Increased glycogen breakdown
Drug Targets- Enzymes
Enzyme inhibition:
 Nonselective inhibition
• Denature proteins
• Heavy metal salts, strong acids and alkalis
 Selective inhibition
• Competitive (equilibrium, non-equilibrium
type)
• Non-competitive
Drug Targets- Receptors
Receptors:
Are the macromolecule or binding site
located on the surface or inside the effector
cell
that serves to recognise the signal
molecule/drug, and
initiate a response to it,
but itself has no other function
Drug Targets- Receptors
Has two sites
Ligand binding domain
• Recognition of physiological molecules/
drugs
Effector domain
• Undergoes functional conformational
changes
Drug Targets- Receptors

Site 1

Site 2
Drug Targets- Receptors
Types (Based on intracellular signalling
molecules)
G-protein Coupled receptors
Ion channel receptors
Transmembrane-enzyme linked
receptors
Transmembrane JAK-STAT binding
receptors
Drug Targets- Receptors
G-protein coupled receptors (GPCRs)
Examples: α, β receptors, muscarinic
receptors
 Consists of 7 transmembrane helices
 Linked to various effectors
 Action seen in seconds
 Coupled to G-protein ( α, β and γ)
•
Drug Targets- Receptors
 G-protein coupled receptors (GPCRs)
 Coupled to different transducer mechanisms
• Gs  cAMP, Gi  cAMP
• Gq  Phospholipase C, Go  Ca2+ channel
 β and γ subunits:
• As chaperone
• Receptor
operated K+
channels
• Voltage gated
Drug Targets- Receptors

β G
Gα γ

cAMP K+, Ca2+ channel

Phospholipase C Ca2+ channels

Drug Targets- Receptors
Ion channel receptors
Examples: nicotinic ACh receptors, GABAA
receptors
Two types:
• G-protein gated
• Ligand gated
Encloses ion selective channels within their
molecules
Drug Targets- Receptors

Agonist Na+, K+, Ca2+, Cl-

binding Site

α
Drug Targets- Receptors
Transmembrane enzyme-linked receptors
Examples: insulin, epidermal growth factors
(EGF), transforming growth factors (TGF)
Extracellular and intracellular subunits
connected with single transmembrane helix
Intracellular subunit has enzymatic activity
• Tyrosine, serine/threonine
Response seen in minutes to hours
Drug Targets- Receptors

Agonist
binding site

Intracellular
subunit having
enzymatic
activity
Drug Targets- Receptors
Transmembrane JAK-STAT binding receptors
Examples: cytokines, growth factors,
prolactin
Extracellular and intracellular subunits
connected with single transmembrane helix
Intracellular subunit has no enzymatic
activity
• On activation, binds to cytosolic protein
Janus Kinase (has enzymatic activity)
Drug Targets- Receptors

Agonist
binding site

Intracellular
subunit with NO
enzymatic
activity
Drug Targets- Receptors
Intracellular receptors
Examples: glucocorticoids, androgens,
thyroxine, vitamin D
Can be present in cytoplasm or within
nucleus
Ligand binding domain- carboxy
terminus
Effector domain – N-terminus
Drug Targets- Receptors

Ligand

binding

domain

Effector
Conclusion
Pharmacodynamics:
What drug does, How it does and
modification of drug action by another drug
(Drug interactions)
Five principles of drug action
Drug Targets: mainly proteins (RICE)
Other drug targets do exists