Introduction to pharmacology

Introduction

• Pharmacology is a core subject in medical and health sciences.

• It explains how drugs act, how they move inside the body, and how they are used safely.

• It helps in:

  • Rational drug therapy

  • Safe prescribing

  • Prevention of adverse drug reactions

  • Understanding modern drug development

 

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Pharmacology (Definition)

• Pharmacology is the science that deals with:

  • Study of drugs

  • Their sources

  • Their properties

  • Their actions on living organisms

  • Their uses in diagnosis, prevention, and treatment of diseases

  • Their adverse effects and toxicity

 

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Branches of Pharmacology

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• Pharmacology is divided into the following major branches:

General Pharmacology

• Deals with basic principles of drugs.

• Includes:

  • Pharmacodynamics

  • Pharmacokinetics

  • Receptors

  • Dose-response relationship

Systemic Pharmacology

• Study of drugs acting on different body systems.

• Includes:

  • Cardiovascular drugs

  • CNS drugs

  • Respiratory drugs

  • Gastrointestinal drugs

  • Endocrine drugs

Clinical Pharmacology

• Study of drugs in humans.

• Focuses on:

  • Drug therapy

  • Safe prescribing

  • Drug interactions

  • Adverse drug reactions

Chemotherapy

• Study of drugs used to treat:

  • Bacterial infections

  • Viral infections

  • Fungal infections

  • Parasitic infections

  • Cancer

Toxicology

• Study of harmful effects of drugs and chemicals.

• Includes:

  • Poisoning

  • Toxic dose

  • Antidotes

  • Drug-induced organ damage

Pharmacogenetics / Pharmacogenomics

• Study of genetic factors affecting drug response.

• Explains:

  • Variation in drug metabolism

  • Drug resistance

  • Adverse reactions

Pharmacovigilance

• Monitoring and prevention of adverse drug reactions.

• Includes:

  • ADR reporting

  • Post-marketing surveillance

  • Drug safety evaluation

Experimental Pharmacology

• Study of drugs in laboratory and animal models.

• Used for:

  • Screening new drugs

  • Preclinical testing

 

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Pharmacodynamics

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Definition

• Pharmacodynamics is the study of:

  • Mechanism of drug action

  • Drug receptor interactions

  • Dose-response relationship

  • Therapeutic and adverse effects

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Principles of Pharmacodynamics

• Drugs produce effects by acting on:

  • Receptors

  • Enzymes

  • Ion channels

  • Transporters

  • DNA / gene expression

  • Structural proteins

 

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Mechanisms of Drug Action

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• Mechanism of drug action means how a drug produces its effect in the body.

• Drugs act by interacting with specific biological targets such as:

  • Receptors

  • Enzymes

  • Ion channels

  • Transporters

  • DNA / RNA

  • Structural proteins

• Some drugs also act by physical or chemical mechanisms without receptors.

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Main Targets of Drugs

• Receptors

• Enzymes

• Ion channels

• Transporters (carrier proteins)

• Nucleic acids (DNA/RNA)

• Microbial structures

• Physical and chemical substances

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Table: Major Mechanisms of Drug Action 

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Action Through Receptors 

• Most drugs act by binding to specific receptors.

• Receptors are proteins present in:

  • Cell membrane

  • Cytoplasm

  • Nucleus

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Table: Types of Receptors and Their Mechanism

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Action on Enzymes

• Drugs may act by:

  • Inhibiting enzymes

  • Activating enzymes

• Enzyme inhibition is one of the most common drug mechanisms.

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Table: Drug Action on Enzymes

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Action on Ion Channels

• Ion channels control movement of ions like:

  • Sodium (Na⁺)

  • Potassium (K⁺)

  • Calcium (Ca²⁺)

  • Chloride (Cl⁻)

• Drugs may block or open these channels.

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Table: Drugs Acting on Ion Channels

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Action on Transporters (Carrier Proteins)

• Transporters move substances across membranes.

• Drugs can block transporters to produce therapeutic effects.

Table: Drugs Acting on Transporters

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Action on DNA / RNA (Genetic Level)

• Some drugs act by affecting:

  • DNA replication

  • RNA transcription

  • Protein synthesis

• These drugs are commonly used in:

  • Cancer

  • Viral infections

  • Severe bacterial infections

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Table: Drugs Acting on DNA/RNA

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Action on Microorganisms (Selective Toxicity)

• Some drugs act on structures present in microbes but absent in humans.

• This is called selective toxicity.

Table: Antimicrobial Drug Targets

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Physical Action (Non-Receptor Mechanism)

• Some drugs act by physical properties rather than receptor binding.

Examples

• Activated charcoal:

  • Adsorbs toxins in poisoning

• Bulk laxatives (psyllium husk):

  • Increase stool bulk and bowel movement

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Chemical Action

• Some drugs act by chemical neutralization or binding.

Examples

• Antacids:

  • Neutralize gastric acid

• Chelating agents (EDTA, dimercaprol):

  • Bind heavy metals and remove them

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Osmotic Action

• Some drugs act by drawing water using osmotic pressure.

Examples

• Mannitol:

  • Osmotic diuretic

• Lactulose:

  • Osmotic laxative

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Replacement Therapy

• Some drugs replace substances that are deficient in the body.

Examples

• Insulin in diabetes mellitus

• Thyroxine in hypothyroidism

• Vitamin B12 in pernicious anemia

• Iron in iron deficiency anemia

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Immunological Mechanism

• Some drugs act through immune system modulation.

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Examples

• Vaccines:

  • Stimulate immunity

• Corticosteroids:

  • Suppress inflammation and immunity

• Monoclonal antibodies:

  • Target specific immune pathways

 

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Types of Receptors

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Ligand-Gated Ion Channel Receptors

• Drug binding opens or closes ion channels.

• Action is rapid.

• Example:

  • Nicotinic acetylcholine receptor

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G-Protein Coupled Receptors (GPCRs)

• Drug binding activates G-proteins.

• Produces second messengers like:

  • cAMP

  • IP3

  • DAG

• Example:

  • Adrenaline receptors

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Enzyme-Linked Receptors

• Drug binding activates enzyme activity.

• Example:

  • Insulin receptor

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Intracellular (Nuclear) Receptors

• Drug enters cell and binds to receptor inside.

• Action is slow but long-lasting.

• Example:

  • Steroid hormones

 

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Drug-Receptor Interaction

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• Drug–receptor interaction refers to the process in which a drug binds to a specific receptor and produces a biological effect.

• Most drugs act by interacting with receptors present on:

  • Cell membrane

  • Cytoplasm

  • Nucleus

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What is a Receptor?

• A receptor is a macromolecule (mainly protein) that:

  • Recognizes a drug

  • Binds with the drug

  • Initiates a response inside the cell

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Key Points

• Receptors are highly specific.

• Drug action depends on:

  • Drug concentration

  • Receptor number

  • Binding strength

  • Type of receptor

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Steps in Drug–Receptor Interaction

• Drug approaches the receptor.

• Drug binds to receptor at a specific site.

• Drug–receptor complex is formed.

• Signal is generated inside the cell.

• Biological response occurs.

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Important Properties of Drug–Receptor Binding

Affinity

• Affinity means the ability of a drug to bind to a receptor.

• Higher affinity = stronger binding.

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Intrinsic Activity (Efficacy)

• Intrinsic activity means the ability of a drug to:

  • Produce a response after binding

• A drug may bind but may or may not produce response.

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Types of Drugs Based on Receptor Interaction

Agonist

• A drug that:

  • Binds to receptor

  • Activates receptor

  • Produces full response

• Example:

  • Salbutamol (β2 agonist)

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Partial Agonist

• A drug that:

  • Binds to receptor

  • Produces response

  • But response is less than full agonist

• Example:

  • Buprenorphine

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Antagonist

• A drug that:

  • Binds to receptor

  • Does not activate it

  • Blocks action of agonist

• Example:

  • Propranolol (β blocker)

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Inverse Agonist

• A drug that:

  • Binds to receptor

  • Produces opposite effect of agonist

• Example:

  • Some antihistamines

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Types of Antagonism (Very Important)

Competitive Antagonism

• Antagonist competes with agonist for same receptor site.

• Effect can be overcome by increasing agonist dose.

• Example:

  • Naloxone vs morphine

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Non-Competitive Antagonism

• Antagonist binds to a different site or irreversibly binds to receptor.

• Effect cannot be reversed by increasing agonist dose.

• Example:

  • Phenoxybenzamine (α blocker)

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Physiological Antagonism

• Two drugs act on different receptors producing opposite effects.

• Example:

  • Histamine causes bronchoconstriction

  • Adrenaline causes bronchodilation

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Chemical Antagonism

• Two substances react chemically and neutralize each other.

• Example:

  • Antacids neutralize gastric acid

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Receptor Regulation

Upregulation

• Increase in number of receptors.

• Occurs when receptors are blocked for long time.

• Example:

  • Long-term beta blocker use

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Downregulation

• Decrease in receptor number.

• Occurs when receptors are continuously stimulated.

• Example:

  • Long-term salbutamol overuse

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Clinical Importance of Drug–Receptor Interaction

• Helps in:

  • Choosing correct drug

  • Understanding dose-response

  • Predicting drug interactions

  • Explaining side effects

  • Designing new drugs

 

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Dose-Response Relationship

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Types of Dose–Response Relationship

Graded Dose–Response

• Response is measured in a single individual.

• Effect increases gradually with dose.

• Example:

  • Increase in heart rate with increasing dose of adrenaline

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Quantal Dose–Response

• Response is measured in a population.

• Shows the percentage of people showing a particular effect.

• Example:

  • Percentage of patients who fall asleep after sedative dose

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Dose–Response Curve

• A dose–response curve is a graph showing:

  • Drug dose on X-axis

  • Drug response on Y-axis

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Important Terms in Dose–Response Relationship

Potency

• Potency means:

  • The amount of drug required to produce a given effect.

• More potent drug:

  • Produces effect at lower dose.

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Efficacy

• Efficacy means:

  • The maximum effect a drug can produce.

• Drug with higher efficacy:

  • Produces greater maximum response.

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ED50

• ED50 means:

  • Effective dose that produces 50% of maximum response.

• Used to compare drug potency.

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Emax

• Emax means:

  • Maximum effect produced by the drug.

• Used to compare drug efficacy.

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Therapeutic Index (Drug Safety)

• Therapeutic index indicates the safety of a drug.

• It is defined as:

  • Ratio between toxic dose and effective dose.

Formula

• Therapeutic Index (TI) = TD50 / ED50

Key Point

• Higher TI = safer drug

• Lower TI = more toxic drug

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Clinical Importance of Dose–Response Relationship

• Helps in:

  • Selecting correct drug dose

  • Understanding drug effectiveness

  • Predicting side effects

  • Comparing two drugs

  • Determining safe therapeutic range

 

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Pharmacokinetics

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Definition

• Pharmacokinetics is the study of:

  • Absorption

  • Distribution

  • Metabolism

  • Excretion

• It explains how drug concentration changes in the body over time.

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Absorption

• Absorption is the process by which a drug enters the bloodstream from the site of administration.

Factors Affecting Absorption

• Route of administration

• Drug solubility (lipid or water soluble)

• pH of drug and body fluids

• Blood flow at site

• Surface area

• Presence of food

• Gastric emptying time

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Distribution

• Distribution is the transport of drug from blood to tissues and organs.

Factors Affecting Distribution

• Blood flow to organs

• Plasma protein binding (albumin)

• Tissue binding

• Lipid solubility

• Blood-brain barrier

• Placental barrier

 

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Metabolism

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• Metabolism is the chemical alteration of drug in the body.

• Mainly occurs in:

  • Liver

• Purpose:

  • Convert drugs into more water-soluble forms for excretion.

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Phases of Drug Metabolism

Phase I Reactions

• Includes:

  • Oxidation

  • Reduction

  • Hydrolysis

• Usually produces:

  • Active or inactive metabolites

• Mostly performed by:

  • Cytochrome P450 enzymes

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Phase II Reactions

• Includes conjugation with:

  • Glucuronic acid

  • Sulfate

  • Glycine

• Makes drug:

  • Highly water-soluble

  • Easier to excrete

 

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Excretion

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• Excretion is the removal of drugs from the body.

Major Routes of Excretion

• Kidney (urine) – most common

• Bile and feces

• Lungs (volatile anesthetics)

• Sweat

• Saliva

• Breast milk

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Bioavailability

• Bioavailability is defined as:

  • The fraction (percentage) of administered drug that reaches systemic circulation in active form.

Key Points

• IV route has:

  • 100% bioavailability

• Oral route has lower bioavailability due to:

  • Incomplete absorption

  • First-pass metabolism

 

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First-Pass Metabolism

• It refers to metabolism of orally administered drugs in:

  • Intestinal wall

  • Liver

• This reduces the amount of drug reaching circulation.

 

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Routes of Drug Administration

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Definition

• Route of administration is the path by which a drug is introduced into the body to produce its effect.

Classification of Routes of Drug Administration

• Routes are broadly classified into:

  • Enteral routes (through gastrointestinal tract)

  • Parenteral routes (injections; bypass GIT)

  • Inhalational route

  • Topical and transdermal routes

  • Special routes (intrathecal, intra-articular, etc.)

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Enteral Routes (Through GIT)

Table: Enteral Routes of Drug Administration

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Parenteral Routes (Injection Routes)

Table: Parenteral Routes of Drug Administration

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Inhalational Route

Table: Inhalational Route

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Topical and Transdermal Routes

Table: Topical and Transdermal Routes

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Special Routes of Drug Administration

Table: Special Routes

 

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Classification of Routes of Drug Administration

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Enteral Routes (Through GIT)

Oral Route

• Most common route.

• Advantages:

  • Safe

  • Convenient

  • Economical

• Disadvantages:

  • Slow onset

  • First-pass metabolism

  • Not suitable in vomiting or unconscious patients

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Sublingual Route

• Drug placed under tongue.

• Advantages:

  • Rapid absorption

  • No first-pass metabolism

• Example:

  • Nitroglycerin

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Rectal Route

• Drug administered through rectum.

• Advantages:

  • Useful in vomiting/unconscious patients

  • Partially avoids first-pass metabolism

• Disadvantages:

  • Irregular absorption

  • Patient discomfort

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Parenteral Routes (Injection Routes)

Intravenous (IV)

• Drug injected directly into blood.

• Advantages:

  • Immediate action

  • 100% bioavailability

• Disadvantages:

  • Risk of infection

  • Requires skilled person

  • Cannot be reversed easily

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Intramuscular (IM)

• Drug injected into muscle.

• Advantages:

  • Faster than oral

  • Suitable for depot preparations

• Disadvantages:

  • Painful

  • Risk of nerve injury

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Subcutaneous (SC)

• Drug injected under skin.

• Advantages:

  • Slow, sustained absorption

• Example:

  • Insulin

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Intradermal

• Drug injected into dermis.

• Mainly used for:

  • Allergy testing

  • Tuberculin test

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Inhalational Route

• Drug inhaled into lungs.

• Advantages:

  • Rapid action

  • Useful for local effect in asthma

• Example:

  • Salbutamol inhaler

  • Anesthetic gases

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Topical Route

• Drug applied on skin or mucous membrane.

• Used for local action.

• Example:

  • Antifungal creams

  • Antibiotic ointments

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Transdermal Route

• Drug absorbed through skin using patch.

• Advantages:

  • Sustained release

  • Avoids first-pass metabolism

• Example:

  • Nicotine patch

  • Nitroglycerin patch

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Other Special Routes

• Intrathecal (into CSF)

• Intra-articular (into joint)

• Intranasal (nasal spray)

• Vaginal route