Fundamentals of Pharmacology

• Principles, Mechanisms & Applications

• For BAMS 2nd Professional Students
• By
• DR NARESH KUMAR GARG
 Definition of Pharmacology
• Pharmacology is the science that deals with the study of drugs, their sources, properties, effects, and
therapeutic applications.

• Etymology:
• Pharmacon (Greek) = Drug/Medicine
• Logos (Greek) = Study/Science

• Scope:
• - Drug discovery and development
• - Drug-body interactions
• - Therapeutic applications
• - Adverse effects and toxicity
 Principles of General Pharmacology
• 1. Dose-Response Relationship – Response proportional to drug concentration at site of action.
• 2. Receptor Theory – Drugs act via specific molecular targets (receptors).
• 3. Selectivity – Target tissues affected with minimal side effects.
• 4. Therapeutic Index – Ratio between toxic dose and therapeutic dose.
 Drug Definition & Classification
• Definition: Any chemical substance producing a biological effect, used for diagnosis, treatment, or
prevention.

• Based on Origin:
• - Natural (Plant, Animal, Mineral)
• - Semi-synthetic
• - Synthetic

• Based on Action:
• - Therapeutic
• - Diagnostic
• - Prophylactic

• Based on Prescription:
• - Prescription drugs
• - OTC
• - Controlled substances
 Drug Dosage Forms
• Solid – Tablets, Capsules, Pills, Powders, Granules
• Liquid – Solutions, Suspensions, Emulsions, Syrups, Elixirs
• Semi-solid – Ointments, Creams, Gels, Pastes
• Gaseous – Inhalations, Aerosols, Sprays
 Routes of Drug Administration
• Enteral – Oral, Sublingual, Buccal, Rectal
• Parenteral – IV, IM, SC, ID
• Topical – Dermal, Transdermal, Ophthalmic, Nasal
• Inhalation – Pulmonary, Nasal inhalation, Oral inhalation
 Pharmacokinetics (ADME)
• Study of what the body does to the drug.
• A – Absorption
• D – Distribution
• M – Metabolism
• E – Excretion
 ADME Process Detailed
• Absorption – From administration site to circulation (passive diffusion, active transport, facilitated
diffusion, pinocytosis)
• Distribution – Drug movement to tissues (blood flow, protein binding, tissue binding, BBB)
• Metabolism – Drug transformation (Phase I – oxidation/reduction; Phase II – conjugation; hepatic
metabolism; first-pass effect)
• Excretion – Removal (renal, biliary, pulmonary, others)
 Pharmacodynamics
• Study of what the drug does to the body.

• Key Concepts – Receptor binding, Affinity, Efficacy, Potency

• Types of Drug Action – Agonists, Antagonists, Partial agonists, Inverse agonists
 Drug Dose
• Types – Loading, Maintenance, Therapeutic, Toxic, Lethal
• Calculation – Dose = (Desired plasma level × Clearance) / Bioavailability
• Considerations – Weight, Age, Kidney/Liver function
• Intervals – OD, BD, TID, QID, PRN
 Principles of Drug Action
• 1. Receptor-Mediated – GPCR, ion channel, enzyme-linked, nuclear receptors
• 2. Non-Receptor Mediated – Enzyme inhibition, physical action, chemical action, membrane effects
• 3. Dose-Response Curve – Threshold dose, linear phase, Emax, ED50
 Mechanism of Drug Action
• Molecular – Lock & Key, Induced Fit, Allosteric, Covalent
• Signal Transduction – Second messengers, phosphorylation, gene expression, ion channel modulation
• Cellular Responses – Metabolic, secretory, contractile, electrical changes
 Bioavailability
• Definition – Fraction of drug reaching systemic circulation unchanged.

• Factors – Route, first-pass metabolism, formulation, pH, food, solubility

• By Route – IV: 100%, IM: 75–90%, Oral: 10–90%, Sublingual: 50–80%, Rectal: 30–70%, Topical: <5%

• Formula: F = (AUC oral × Dose IV) / (AUC IV × Dose oral)

 Clinical Examples
• Aspirin – Inhibits COX; Oral; Small intestine absorption; Hydrolysis metabolism; Renal excretion
• Insulin – Binds insulin receptors; SC injection; Rapid distribution; Proteolytic degradation; 100%
bioavailability
 Pharmacokinetics (PK)

• "What the body does to the drug"

• Pharmacokinetics is the study of the
movement of drugs within the body, including
absorption, distribution, metabolism, and
elimination.
 The Four Main Processes (ADME):

• Absorption
• Drug entry into systemic circulation
• Distribution
• Drug dispersal throughout body tissues
• Metabolism
• Chemical transformation of the drug
• Elimination
• Removal of drug from the body
 Drug Absorption

• The process by which a drug moves from its site of administration

into the systemic circulation.
• Routes of Administration:
• Enteral: Oral, sublingual, rectal
• Parenteral: IV, IM, SC, inhalation
• Topical: Dermal, transdermal patches
• Factors Affecting Absorption:
• Drug formulation and particle size
• pH and gastric emptying time
• Blood flow to absorption site
• Surface area available for absorption
• First-pass metabolism
 Bioavailability
• subcategory of absorption and is the fraction
of an administered drug that reaches the
systemic circulation. By definition, when a
medication is administered intravenously, its
bioavailability is 100%.
 Drug Distribution

• The process by which a drug is transported from the systemic circulation to

various tissues and organs throughout the body.
• Key Concepts:
• Volume of Distribution (Vd): Apparent volume in which the drug is
distributed
• Protein Binding: Binding to plasma proteins (albumin)
• Tissue Binding: Drug accumulation in specific tissues
• Blood-Brain Barrier: Selective permeability to CNS
• Volume of Distribution (Vd) = Total Amount of Drug in Body / Plasma Drug
Concentration
• Factors Affecting Distribution:
• Blood flow to tissues
• Capillary permeability
• Tissue binding affinity
• Plasma protein binding
• Lipophilicity of the drug
 • The biochemical transformation of
drugs into metabolites through
enzymatic processes.
• Primary Site:
• Liver - Contains the highest
concentration of drug-metabolizing
enzymes
• Phases of Metabolism:

Drug •
•
Phase I Reactions
Oxidation, Reduction, Hydrolysis
• Primarily by Cytochrome P450
Metabolism •
enzymes
Phase II Reactions
• Conjugation Reactions
• Glucuronidation, Sulfation,
Acetylation
• Important Enzyme Systems:
• CYP450 family (CYP3A4, CYP2D6,
CYP2C9)
• UDP-glucuronosyltransferases (UGTs)
• Sulfotransferases (SULTs)
• N-acetyltransferases (NATs)
 • The removal of drugs and their
metabolites from the body.
• Routes of Elimination:
• Renal: Kidney excretion (most common)
• Biliary: Liver to bile to feces
• Pulmonary: Lungs (volatile compounds)
Drug • Other: Sweat, saliva, breast milk
• Important Parameters:
Elimination • Half-life (t½)
• Time required for plasma concentration
to decrease by 50%
• Clearance (Cl)
• Volume of plasma cleared of drug per
unit time
• t½ = 0.693 × Vd / Cl
 Pharmacodynamics (PD)

• Pharmacodynamics is the study of the

biochemical and physiological effects of drugs and
their mechanisms of action.
• Key Concepts:
• Drug-Receptor Interactions
• Dose-Response Relationships
• Drug Efficacy and Potency
• Therapeutic Index
• Tolerance and Dependence
 Drug-Receptor Interactions

• Types of Drug Targets:

• Receptors: Protein molecules that bind drugs specifically
• Enzymes: Proteins that catalyze biochemical reactions
• Ion Channels: Membrane proteins controlling ion flow
• Transport Proteins: Carriers for specific molecules
• Types of Drug Action:
• Agonist
• Binds and activates receptor
• Produces biological response
• Antagonist
• Binds but doesn't activate receptor
• Blocks agonist action
• Partial Agonist
• Binds and partially activates
• Submaximal response
 Dose-Response Relationships

• Key Parameters:
• ED50: Dose producing 50% of maximum response
• LD50: Dose lethal to 50% of test subjects
• Potency: Amount of drug needed to produce effect
• Efficacy: Maximum response a drug can produce
• Therapeutic Index (TI) = LD50 / ED50
• Clinical Implications:
• Higher TI = Safer drug
• Lower TI = Requires careful monitoring
• Individual variation in response
• Importance of personalized medicine
 Factors Affecting Drug Action

• Patient Factors:
• Age: Pediatric and geriatric considerations
• Weight and Body Composition
• Gender: Hormonal influences
• Genetic Polymorphisms: Pharmacogenomics
• Disease States: Liver/kidney dysfunction
• Pregnancy and Lactation
 Drug Factors

• Route of administration
• Drug formulation
• Drug interactions
• Timing of administration
• Food interactions
 Therapeutic Drug Monitoring (TDM):

• Narrow therapeutic index drugs

• Individual dose optimization
• Monitoring compliance
• Detecting drug interactions
• Examples of TDM Drugs:
• Digoxin
• Cardiac glycoside