Pharmacology Principles: Mechanisms and Drug Actions

Posted on Jun 25, 2026 in Medicine

Pharmacokinetics and Drug Transport Mechanisms

Understanding Pharmacokinetics

Pharmacokinetics is the study of the movement of drugs within the body. It describes what the body does to the drug. It includes Absorption, Distribution, Metabolism, and Excretion (ADME).

Pharmacokinetics Process Flow

Drug Administration → Absorption → Distribution → Metabolism → Excretion

Mechanisms of Drug Absorption

Passive Diffusion

The drug moves from a higher concentration to a lower concentration. No energy is required.

High Concentration → Cell Membrane → Low Concentration

Facilitated Diffusion

The drug is transported with the help of carrier proteins. No energy is required.

Drug + Carrier → Transport Across Membrane → Cell Entry

Active Transport

The drug is transported with the help of carrier proteins. ATP energy is required as the drug moves against the concentration gradient.

Low Concentration → Carrier + ATP → Cell Membrane → High Concentration

Filtration (Aqueous Diffusion)

Small water-soluble drugs pass through membrane pores.

Drug → Membrane Pores → Blood

Endocytosis (Pinocytosis)

The cell membrane engulfs drug molecules and forms vesicles.

Drug → Vesicle Formation → Inside Cell

Drug Absorption and Influencing Factors

Defining Drug Absorption

Absorption is the process by which a drug passes from its site of administration into the systemic circulation (bloodstream).

Drug → Absorption → Bloodstream → Site of Action

Factors Affecting Drug Absorption

Lipid Solubility: Lipid-soluble drugs are absorbed more easily through biological membranes.
Degree of Ionization: Unionized drugs are absorbed better than ionized drugs.
pH of Medium: Acidic drugs are absorbed better in the stomach, whereas basic drugs are absorbed better in the intestine.
Blood Flow: Greater blood supply at the absorption site increases drug absorption.
Surface Area: A larger surface area results in greater absorption. The small intestine is the major site of drug absorption.
Gastric Emptying Time: Rapid gastric emptying increases the rate of absorption.
Dosage Form: The rate of absorption follows this hierarchy: Solution > Suspension > Capsule > Tablet.
Presence of Food: Food may increase or decrease drug absorption depending on the specific drug.
Drug Concentration: Higher drug concentration increases the rate of absorption.
Route of Administration: Different routes produce different rates of absorption.

Biotransformation and Plasma Protein Binding

Biotransformation

Biotransformation is the chemical conversion of a drug into more water-soluble metabolites so that it can be easily excreted from the body. It mainly occurs in the liver.

Drug → Biotransformation (Liver) → Metabolite → Excretion

Phases of Biotransformation

Phase I Reactions

Oxidation
Reduction
Hydrolysis
Result: Drug → Phase I Reaction → Polar Metabolite

Phase II Reactions

Glucuronidation
Sulfation
Acetylation
Methylation
Result: Metabolite → Phase II Reaction → Water-Soluble Product

Plasma Protein Binding

Plasma protein binding is the reversible binding of drugs with plasma proteins, such as Albumin, present in the blood.

Drug + Albumin ↔ Drug-Protein Complex

Significance of Plasma Protein Binding

Acts as a reservoir for the drug.
Prolongs the duration of action.
Decreases the rate of drug elimination.
Only free (unbound) drug is pharmacologically active.
Affects the distribution of drugs in the body.
Increases the biological half-life of drugs.
Helps maintain plasma drug concentration.
May cause drug interactions due to the displacement of one drug by another.

Routes of Drug Administration

Drug absorption occurs through different routes of administration:

1. Enteral Route

Drugs are administered through the gastrointestinal tract.

Oral Route: Mouth → Stomach → Intestine → Blood. (Convenient and economical).
Sublingual Route: Drug under the tongue → Blood. (Example: Nitroglycerin).
Rectal Route: Rectum → Blood. (Example: Suppositories).

2. Parenteral Route

Drugs are administered by injection.

Intravenous (IV): Injection → Vein → Blood. (Immediate action and 100% bioavailability).
Intramuscular (IM): Injection → Muscle → Blood. (Example: Vaccines).
Subcutaneous (SC): Injection → Skin → Blood. (Example: Insulin).

3. Topical Route

Drug Applied → Skin → Absorption. (Examples: Ointments and Creams).

4. Inhalation Route

Drug → Lungs → Blood. (Examples: Salbutamol, Anaesthetic gases).

G-Protein-Coupled Receptors (GPCR)

G-Protein-Coupled Receptors (GPCRs) are membrane receptors that transmit signals from outside the cell to the inside through G-proteins. They are the largest family of receptors and regulate many physiological functions.

GPCR Signaling Pathway

Drug (Agonist) → GPCR → G-Protein → Effector Enzyme → Second Messenger → Cellular Response

Structure of GPCR

GPCR consists of seven transmembrane alpha-helical segments and is therefore called a 7-transmembrane receptor.

Outside Cell → Receptor (7 Transmembrane Segments) → G-Protein → Inside Cell

Mechanism of Action

Drug binds to the receptor.
Receptor activates the G-protein.
GDP is replaced by GTP.
Activated G-protein stimulates the effector enzyme.
Second messengers are produced.
Cellular response occurs.

Example Pathway

Drug → GPCR → G-Protein → Adenyl Cyclase → cAMP → Response

Types of G-Proteins

Gs: Stimulates Adenyl Cyclase and increases cAMP.
Gi: Inhibits Adenyl Cyclase and decreases cAMP.
Gq: Activates Phospholipase C and produces IP3 and DAG.

Examples of GPCRs

Beta-Adrenergic Receptors
Muscarinic Receptors
Dopamine Receptors
Histamine Receptors

Signal Transducer Mechanisms

Signal transduction is the process by which a signal received by a receptor is converted into a cellular response.

Drug → Receptor → Signal Transducer → Second Messenger → Cellular Response

Various Receptor Signal Transducer Mechanisms

G-Protein-Coupled Receptors (GPCR): Drug → GPCR → G-Protein → cAMP → Response.
Ligand-Gated Ion Channel Receptors: Drug → Ion Channel Opens → Ion Movement → Response.
Enzyme-Linked Receptors: Drug → Tyrosine Kinase Activation → Response.
JAK-STAT Receptors: Drug → JAK Activation → STAT Activation → Response.

Theory of Receptors and JAK-STAT Signaling

Theory of Receptors

A receptor is a protein molecule that binds with a drug and produces a biological response.

Key Receptor Theories

Occupancy Theory: The response is directly proportional to the number of receptors occupied by the drug. (Drug + Receptor → Drug-Receptor Complex → Response).
Rate Theory: The response depends upon the rate at which the drug combines and dissociates from the receptor.
Induced Fit Theory: The drug changes the shape of the receptor after binding to produce a response.
Macromolecular Perturbation Theory: Drug interaction causes structural changes in receptors resulting in activation or inhibition.

Signal Transduction in JAK-STAT Binding Receptors

JAK-STAT receptor signaling is a mechanism in which Janus Kinases (JAK) activate Signal Transducers and Activators of Transcription (STAT) proteins to regulate gene expression.

Mechanism

Ligand binds to the receptor.
JAK enzymes become activated.
STAT proteins are phosphorylated.
STAT proteins form dimers.
STAT dimers enter the nucleus.
Gene transcription occurs.

Ligand → Receptor → JAK Activation → STAT Activation → Nucleus → Gene Transcription → Cellular Response

Examples

Growth Hormone
Erythropoietin
Interferons

Clinical Trials and Their Phases

A Clinical Trial is a systematic study conducted on human volunteers to evaluate the safety, efficacy, and quality of a new drug before it is approved for marketing.

Drug Development Timeline

Drug Discovery → Preclinical Studies (Animals) → Clinical Trials → Drug Approval → Marketing

Phases of Clinical Trials

Phase I

Conducted on 20–100 healthy volunteers. Purpose: To determine safety, tolerability, and dosage range.

Phase II

Conducted on 100–300 patients suffering from the disease. Purpose: To evaluate efficacy and identify side effects.

Phase III

Conducted on 1000–3000 patients. Purpose: To confirm safety and effectiveness on a large scale and compare with standard drugs.

Phase IV

Conducted after marketing approval. Purpose: Post-marketing surveillance to monitor long-term safety and rare adverse effects.

Parasympathomimetics and Acetylcholine

Parasympathomimetics

Parasympathomimetics are drugs that mimic the actions of the parasympathetic nervous system by stimulating cholinergic receptors.

Examples: Acetylcholine, Bethanechol, Pilocarpine, Neostigmine.
Actions: Miosis (pupil constriction), decreased heart rate, increased GIT motility, bronchoconstriction, and bladder contraction.

Pharmacology of Acetylcholine

Acetylcholine (ACh) is the natural neurotransmitter of the parasympathetic nervous system. It acts on Muscarinic and Nicotinic receptors.

Uses: Used to produce miosis during eye surgery.

Sympathomimetics and Adrenaline

Classification of Sympathomimetics

Direct Acting: Adrenaline, Noradrenaline, Dopamine, Salbutamol.
Indirect Acting: Amphetamine, Tyramine.
Mixed Acting: Ephedrine, Pseudoephedrine.

Pharmacology of Adrenaline

Adrenaline (Epinephrine) stimulates both α and β adrenergic receptors.

Actions: Increases heart rate, cardiac output, and blood pressure; produces bronchodilation and mydriasis; increases blood glucose.
Uses: Anaphylactic shock, cardiac arrest, and bronchial asthma.
Adverse Effects: Tachycardia, hypertension, anxiety, and headache.

Local Anaesthetics and Lignocaine

Local Anaesthetics

These drugs produce reversible loss of sensation in a specific area without loss of consciousness. Examples: Lignocaine (Lidocaine), Bupivacaine, Procaine.

Lignocaine (Lidocaine)

Mechanism of Action: Blocks voltage-gated sodium (Na+) channels in nerve membranes, preventing the conduction of nerve impulses.

Uses: Surface, infiltration, and nerve block anaesthesia; also used for cardiac arrhythmias.
Adverse Effects: Dizziness, drowsiness, hypotension, and allergic reactions.

Drugs for Myasthenia Gravis and Glaucoma

Myasthenia Gravis Treatment

Anticholinesterases: Neostigmine, Pyridostigmine.
Corticosteroids: Prednisolone.
Immunosuppressants: Azathioprine, Cyclosporine.
Monoclonal Antibodies: Rituximab.

Glaucoma Treatment

Cholinergics (Miotics): Pilocarpine.
Beta Blockers: Timolol.
Carbonic Anhydrase Inhibitors: Acetazolamide.
Prostaglandin Analogues: Latanoprost.
Alpha Agonists: Brimonidine.
Osmotic Agents: Mannitol.

General Anaesthetics and Nitrous Oxide

Classification

Inhalational: Nitrous Oxide, Halothane, Isoflurane.
Intravenous: Thiopentone Sodium, Propofol, Ketamine.

Stages of Anaesthesia (Guedel’s Stages)

Stage of Analgesia: Pain loss; patient conscious.
Stage of Delirium: Excitement and irregular breathing.
Stage of Surgical Anaesthesia: Unconsciousness and muscle relaxation.
Stage of Medullary Paralysis: Dangerous depression of vital centers.

Nitrous Oxide (N²O)

A gaseous inhalational anaesthetic with good analgesic action. It provides rapid induction and recovery with minimal cardiovascular effects.

Sedatives, Hypnotics, and Barbiturates

Sedatives reduce anxiety and calm the patient, while hypnotics induce and maintain sleep.

Barbiturates

Mechanism: Enhance the action of GABA, the inhibitory neurotransmitter in the CNS. Examples: Phenobarbitone, Thiopentone Sodium.

Uses: Insomnia, anxiety, epilepsy, and induction of anaesthesia.
Adverse Effects: Drowsiness, respiratory depression, and dependence.

Antiepileptic and Anti-Parkinson Drugs

Antiepileptic Drugs (AEDs)

Used to control seizures by reducing abnormal electrical activity. Examples: Phenytoin, Sodium Valproate, Carbamazepine.

Parkinson’s Disease Treatment

Caused by dopamine deficiency. Drugs aim to increase dopamine or decrease acetylcholine.

Dopamine Precursor: Levodopa.
MAO-B Inhibitors: Selegiline.
Anticholinergics: Trihexyphenidyl.

Opioid Analgesics and Morphine

Opioids relieve moderate to severe pain by acting on opioid receptors (mainly μ receptors) in the CNS.

Morphine

Actions: Powerful analgesia, euphoria, sedation, respiratory depression, and constipation.
Uses: Cancer pain, post-operative pain, and myocardial infarction.
Adverse Effects: Addiction, nausea, and respiratory depression.

Pharmacology Short Notes (2 Marks)

1. Routes of Administration

Oral, Sublingual, Rectal, IV, IM, Subcutaneous, Inhalation, and Topical.

2. Bioavailability

The amount of unchanged drug reaching systemic circulation. IV route has 100% bioavailability. Factors include first-pass metabolism and formulation.

3. Pharmacokinetics vs. Pharmacodynamics

Pharmacokinetics: What the body does to the drug (ADME).
Pharmacodynamics: What the drug does to the body (Mechanism of action).

4. Factors Affecting Absorption

Lipid solubility, blood flow, pH, route, dosage form, and surface area.

5. Mechanism of Drug Action

Receptor action, enzyme inhibition, ion channel action, and physical/chemical action.

6. Local vs. General Anaesthetics

Local: Specific area, patient conscious (e.g., Lidocaine).
General: Whole body, patient unconscious (e.g., Halothane).

7. NSAIDs Classification

Salicylates (Aspirin), Propionic acid (Ibuprofen), COX-2 inhibitors (Celecoxib).

8. Sedatives and Hypnotics

Benzodiazepines (Diazepam), Barbiturates (Phenobarbital).

9. Analgesics

Opioid: Severe pain (Morphine).
Non-opioid: Mild pain (Paracetamol).

10. Cholinergic and Anticholinergic Drugs

Cholinergic: Mimic ACh (Pilocarpine).
Anticholinergic: Block ACh (Atropine).

11. Local and General Anaesthetics (Repeated)

Local: Loss of sensation in a specific area; patient remains conscious (Example: Lidocaine).
General: Loss of sensation in the whole body; patient becomes unconscious (Example: Halothane).

12. NSAIDs with Classification (Repeated)

Salicylates – Aspirin; Propionic acid derivatives – Ibuprofen; Acetic acid derivatives – Diclofenac; Oxicams – Piroxicam; COX-2 inhibitors – Celecoxib.

13. Sedatives and Hypnotics (Repeated)

Sedatives reduce anxiety; Hypnotics produce sleep. Classification: Benzodiazepines (Diazepam), Barbiturates (Phenobarbital), Non-benzodiazepines (Zolpidem).

14. Analgesics (Repeated)

Opioid analgesics (Morphine) act on opioid receptors for severe pain. Non-opioid analgesics (Paracetamol) are for mild/moderate pain.

15. Cholinergic and Anticholinergic Drugs (Repeated)

Cholinergic drugs (Pilocarpine) stimulate receptors. Anticholinergic drugs (Atropine) block muscarinic receptors.

16. Hypertensive Drugs

Agents that increase blood pressure by increasing cardiac output or vasoconstriction. Examples: Adrenaline, Noradrenaline, Dopamine.

17. Mechanism of Action and Uses

Rifampicin: Inhibits RNA synthesis; used for Tuberculosis.
Chloroquine: Interferes with parasite metabolism; used for Malaria.
Erythromycin: Inhibits protein synthesis; used for bacterial infections.

18. Adverse Drug Reactions (ADR)

Harmful effects at normal doses, such as allergies, nausea, vomiting, and toxic effects.

19. Anti-Parkinson Drugs MOA

Increase dopamine activity or decrease acetylcholine activity (e.g., Levodopa, Carbidopa).

20. Plasma Protein Binding

Attachment to proteins like albumin; only free drug is active; affects distribution and duration.

21. Hematinic Agents

Drugs that increase blood cell formation, used for anaemia. Examples: Iron, Folic acid, Vitamin B12.

22. Bronchodilators

Relax bronchial smooth muscles to increase airflow. Examples: Salbutamol, Theophylline.

23. Laxatives and Purgatives

Laxatives: Promote bowel movement (Lactulose).
Purgatives: Strong bowel evacuation (Castor oil).

24. Sulphonamides

Antimicrobial drugs that inhibit bacterial folic acid synthesis (e.g., Sulfamethoxazole).

25. Pharmacology of Atropine and Adrenaline

Atropine: Anticholinergic; used for bradycardia.
Adrenaline: Sympathomimetic; used for anaphylaxis and cardiac arrest.