GENERAL PHARMACOLOGY

General Pharmacology is the core biomedical science that explores the interaction between chemical substances (drugs) and living systems. It provides the essential framework for understanding how medications enter the body, produce therapeutic effects, and undergo clearance.The Two Pillars of PharmacologyThe discipline is fundamentally divided into two complementary halves:1. Pharmacokinetics (PK) — What the body does to the drug:Absorption: Transfer of the drug from the site of administration into systemic circulation (governed by bioavailability, $F$).Distribution: Reversible movement of the drug between blood plasma and tissues (quantified by the Apparent Volume of Distribution, $V_d$).Metabolism (Biotransformation): Enzymatic alteration (chiefly in the liver) converting lipophilic compounds into polar metabolites via Phase I (functionalization) and Phase II (conjugation) reactions.Excretion: Irreversible removal of unchanged drug or metabolites from the body, primarily through renal filtration and biliary secretion.2. Pharmacodynamics (PD) — What the drug does to the body:Investigates the biochemical and physiological effects of drugs and their underlying mechanisms of action.Focuses on drug-target interactions, primarily mediated through:Receptors: Ligand-gated ion channels, GPCRs, kinase-linked receptors, and nuclear receptors.Enzymes: Enzyme induction or competitive/non-competitive inhibition.Ion Channels & Transporters: Blocking or modulating voltage/ligand channels and carrier proteins.Non-specific Mechanisms: Physical actions (osmotic diuretics) and chemical neutralization (antacids).

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1. GENERAL PHARMACOLOGY PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
2. INTRODUCTION TO PHARMACOLOGY Definition: Pharmacology is the science of drugs. Derived from Greek words: Pharmacon = drug, and logos = discourse in / study. It is the study of drugs and their interactions with living systems (specifically how externally administered chemical molecules interact with the body).
3. BRANCHES AND KEY TERMINOLOGIES Pharmacy: The art and science of compounding, dispensing, and preparing suitable dosage forms to administer to humans or animals. Pharmacokinetics (What the body does to the drug): Covers Absorption, Distribution, Metabolism, and Excretion (ADME). Pharmacodynamics (What the drug does to the body): Studies the mechanism of action and the pharmacological effects of the drug. Pharmacoeconomics: Evaluates the cost and economic aspects of therapeutic drug use. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
4. BRANCHES AND KEY TERMINOLOGIES Pharmacogenetics / Pharmacogenomics: Explores the genetic basis causing variations in drug responses. Pharmacovigilance: Science involving the detection, assessment, understanding, and prevention of adverse effects. Toxicology: Study of adverse drug effects, as well as the detection, prevention, and treatment of poisonings. Chemotherapy: Use of natural or synthetic chemicals/drugs to treat infections or selectively destroy cancerous cells. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
5. BRANCHES AND KEY TERMINOLOGIES Therapeutics: The branch of medicine concerned with treating disease and determining proper therapeutic doses. Clinical Pharmacology: Applying pharmacological principles and quantitative methods to clinical human drug use. Behavioural Pharmacology: Studies drug effects on behavior and drug-behavior interactions. Cardiovascular Pharmacology: Studies drug effects on the heart and circulatory system. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
6. BRANCHES AND KEY TERMINOLOGIES Neuropharmacology: Studies drug actions on the nervous system. Biochemical Pharmacology: Focuses on the biochemical mechanisms behind drug actions. Molecular & Cellular Pharmacology: Uses biology, chemistry, and physics techniques to study drug actions at the cellular and molecular levels. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
7. TYPES OF DRUGS & CLASSIFICATIONS Orphan Drugs: Lifesaving drugs intended for the prevention or treatment of rare diseases. Examples: Digoxin, Levothyroxine, Sumatriptan, Fomepizole, Nitrates, Amphotericin B. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
8. TYPES OF DRUGS & CLASSIFICATIONS 1 2 3 4 Essential Medicines: Drugs satisfying priority healthcare needs of the majority of the population. They should be available at all times in adequate amounts and proper dosage forms. First WHO model list was created in 1977. The 23rd WHO Model List (July 2023) contains 591 drugs and 103 therapeutic equivalents. Examples: Atenolol, Cetrimide, Capreomycin, Dimercaprol. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
9. TYPES OF DRUGS & CLASSIFICATIONS Prescription Drugs: Legally require a licensed medical prescription for dispensing. Examples: Metformin, Simvastatin, Amlodipine, Metoprolol, Acetaminophen, Isoniazid, Rifampicin. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
10. TYPES OF DRUGS & CLASSIFICATIONS Non-Prescription / Over-TheCounter (OTC) Drugs: Can be purchased without a prescription. Examples: ENO, Paracetamol, Aspirin, Aceclofenac. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
11. TYPES OF DRUGS & CLASSIFICATIONS Drug Definition: Any substance used internally or externally for diagnosis, treatment, mitigation, or prevention of diseases in humans or animals, including insect repellents (e.g., mosquito repellents). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
12. SOURCES OF DRUGS Source Origin / Class • Alkaloids Morphine, Atropine, Quinine Natural: Plants • Glycosides Digoxin, Ouabain Natural: Animals • Oils / Herbs Organ extracts Natural: Minerals Inorganic salts Opium, Belladonna, Castor oil Insulin, Heparin Iron salts, Calcium, Magnesium sulphate • Fungi Natural: Microbes • Bacteria • Actinomycetes Key Examples Penicillin, Griseofulvin Polymyxin B, Bacitracin Tetracycline, Gentamicin Natural: Human Blood & glands Immunoglobulins, Growth Hormone Synthetic Chemical synthesis Aspirin, Omeprazole, Neostigmine Biotechnology Recombinant DNA Human Insulin (Humulin), Rituximab PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
13. ROUTES OF DRUG ADMINISTRATION PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
14. ROUTES OF DRUG ADMINISTRATION Factors Influencing Route Selection: Drug characteristics Emergency vs. routine situation Local vs. systemic site of action Patient condition (unconscious, vomiting, diarrhea) Patient age Stability in gastric pH, digestive enzymes, and first-pass metabolism PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
15. A. LOCAL ROUTES Delivers high drug concentrations to a specific area with minimal systemic absorption. Topical: Applied to skin or mucous membranes (nasal, ocular, ear, anal, vaginal) via creams, ointments, lotions, or gels (e.g., Iodine, Lidocaine, Salbutamol, Cromolyn Sodium, GTN ointment). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
16. A. LOCAL ROUTES Deeper Tissues: Intra-articular: Injected into joints (e.g., Hydrocortisone for knee joint). Intrathecal: Retrobulbar: Injected into Injected behind the eyeballs spinal/subarachnoid space (e.g., Hydrocortisone (e.g., Lidocaine for spinal acetate). anesthesia/chemotherapy). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
17. B. SYSTEMIC ROUTES: ENTERAL Advantage: Oral Route: Oldest, safest, common, non-invasive, inexpensive, selfadministered. Disadvantage: Slow onset; unsuitable for emergencies; bioavailability varies due to intestinal absorption and first-pass hepatic metabolism. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
18. SUBLINGUAL ROUTE: Placed under the tongue to dissolve and absorb across sublingual mucosa (e.g., Nitroglycerin for acute angina). Disadvantage: Ineffective for bitter/unpalatable drugs; only few drugs are absorbed. Advantage: Fast onset; avoids first-pass metabolism. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
19. RECTAL ROUTE: Solid or liquid delivery into the rectum (e.g., Suppositories like Indomethacin; Enemas like Diazepam for pediatric status epilepticus). Advantage: Useful in vomiting, unconsciousness, and children. Disadvantage: Irritation/inflammation of rectal mucosa; erratic absorption. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
20. CUTANEOUS: Highly lipid-soluble drugs rubbed over skin for slow, prolonged systemic absorption (enhanced with oily base/occlusive dressing). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
21. C. SYSTEMIC ROUTES: PARENTERAL Derived from Greek words: Par = beyond, Enterone = outside the intestine. Requires sterile liquid formulations administered via needle/catheter. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
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23. C. SYSTEMIC ROUTES: PARENTERAL Route Intravenous (I.V.) Intramuscular (I.M.) Insertion Angle 25° 90° Injection Site Key Features / Examples Veins 100% Bioavailability; instant action; ideal for emergencies. Cons: Cannot be recalled once injected; risk of phlebitis. Large muscles (Deltoid, Gluteus maximus, Vastus lateralis) Faster than oral; allows mild irritants; volume 5–10 mL (e.g., Paracetamol, Diclofenac). Cons: Painful; risk of abscess; requires aseptic care. Subcutaneous (S.C.) 45° Subcutaneous tissue (thigh, abdomen, arm) Enables self-administration; allows depot/implants (e.g., Insulin, Adrenaline, Norplant). Cons: Slow absorption; suitable only for non-irritants. Intradermal (I.D.) 10°–15° Dermis (below epidermis) Very small volumes (e.g., BCG vaccination, drug sensitivity testing). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
24. OTHER PARENTERAL ROUTES: Transdermal: Dermal patches/ointments delivering drug through skin into systemic circulation (e.g., Scopolamine for motion sickness, Nitroglycerin for angina, Estrogen HRT). Inhalation: Volatile liquids and gases administered via lungs (e.g., General anesthetics). Fast onset, adjustable dosage, low systemic toxicity, but may cause bronchospasm. Intranasal: Drug absorbed by nasal mucosa; bypasses liver and gastric degradation (e.g., GnRH agonists, Calcitonin, Desmopressin). Intrathecal (Systemic/Central): Drug injected into subarachnoid space (e.g., Lignocaine, Antibiotics, Amphotericin B). Intra-articular: Injected directly into joint spaces (e.g., Hydrocortisone for rheumatoid arthritis; requires strict asepsis to prevent cartilage damage). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
25. 1. PHARMACOKINETICS PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
26. 1. PHARMACOKINETICS Definition: Derived from Greek word Kinesis (movement). It is "What the body does to the drug"—the quantitative study of drug movement in, through, and out of the body. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
27. CORE STAGES (ADME): Excretion: Elimination via urine, feces, bile, sweat, or saliva. Absorption: Entry into circulation. Metabolism (Biotransformation): Breakdown of the drug into metabolites. Distribution: Movement from blood to various tissues/sites of action. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
28. DRUG ABSORPTION & MEMBRANE TRANSPORT Site-Specific Absorption: Absorption: Movement of a drug from its administration site into systemic circulation/bloodstream. • Oral Route: The primary barrier is the lipoidal epithelial lining of the GI tract. Acidic drugs remain mostly unionized in acidic gastric juice and get absorbed from the stomach; basic drugs ionize in the stomach and absorb mainly in the duodenum. However, small intestine absorption is generally faster due to large surface area (villi). • Non-ionized lipid-soluble drug: Ethanol (rapidly absorbed from stomach). • Water partition coefficient acidic drugs: Salicylates, Barbiturates. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
29. DRUG ABSORPTION & MEMBRANE TRANSPORT Subcutaneous & Intramuscular: Deposited near capillaries. Lipid-soluble drugs easily pass capillary endothelium. SC absorption is slower than IM, but both are faster/more consistent than oral. Topical Sites (Skin, Cornea, Mucous Membrane): Systemic absorption depends mainly on lipid solubility. Applied for local action; systemic absorption here is often unintended. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
30. TRANSPORT MECHANISMS ACROSS CELL MEMBRANES: 1. Passive Transport (No energy required): Diffusion: Molecules move from higher to lower concentration. Lipid-soluble drugs diffuse through lipids; water-soluble drugs pass through aqueous channels. Filtration: Solute flow driven by hydrostatic/osmotic pressure gradients. Facilitated Transport: High molecular weight drugs (e.g., glucose, amino acids) bind to carrier proteins that change shape to transport them across without energy. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
31. TRANSPORT MECHANISMS ACROSS CELL MEMBRANES: 2. Active Transport (Requires energy/ATP): Moves against gradients using specialized transporters (Symporter, Antiporter, Uniporter) and carrier proteins (e.g., Iron, Amino acids, Levodopa). 3. Pinocytosis / Vesicular Transport (For macromolecules/proteins): Endocytosis: Cell membrane engulfs droplets to form internal vesicles (e.g., Vitamin 𝐵12 in the gut). cap B sub 12 Exocytosis: Vesicles fuse with the outer membrane to secrete substances (e.g., Neurotransmitters at nerve endings). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
32. BIOAVAILABILITY & DISTRIBUTION Bioavailability: The fraction/percentage of an administered drug that reaches the systemic circulation in an unchanged chemical form. Example: If 100 mg is taken orally and 70 mg reaches systemic circulation unchanged, bioavailability is 70% (0.7). For IV injection, it is 100%. 0.7 Formula: AUC (Oral) Bioavailability (%) = × 100 AUC (IV) Bioavailability (%) equals AUC , open paren Oral close paren over AUC , open paren IV close paren times 100 PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
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34. BIOAVAILABILITY & DISTRIBUTION Administered Dose: 100 mg administered orally. 100 mg Fraction Reaching Systemic Circulation: 70 mgenters the bloodstream in chemically unchanged active form. 70 mg Oral Bioavailability (𝐹): start equation cap F Bioavailability equals 70 , mg over 100 , mg equals 0.7 open paren 70% , close paren Bioavailability = 70 mg = 0.7 100 mg 70% Intravenous (IV) Bioavailability: 100%(𝐹 = 1.0), because the full dose is introduced directly into venous blood, completely bypassing the gastrointestinal barrier and hepatic first-pass metabolism. 100% cap F equals 1.0 PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
35. FACTORS INFLUENCING DRUG ABSORPTION Pharmaceutical Factors: Disintegration time, dissolution time, formulation particle size. Drug Factors: Lipid solubility, pH, and degree of ionization. Biological Factors: Absorptive surface area/vascularity, GI motility, presence of food, diseases, first-pass metabolism. Drug Distribution: Transfer of drug from bloodstream into tissues driven by concentration gradients. Apparent Volume of Distribution (𝑉𝑑 ): Hypothetical volume of fluid needed to contain the total drug in the body at the same concentration found in plasma. cap V sub d Total amount of drug in the body Concentration of the drug in plasma cap V sub d equals Total , amount , of , drug , in , the , body over Concentration , of , the , drug , in , plasma 𝑉𝑑 = PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
36. BIOTRANSFORMATION (METABOLISM) Goal: Converts nonpolar (lipid-soluble) drugs into polar (water-soluble/lipidinsoluble) forms to prevent renal tubular reabsorption and accelerate excretion. Primary Site: Liver (secondary sites include kidneys, intestine, lungs, and plasma). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
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39. METABOLIC REACTIONS: Phase I (Non-synthetic / Functionalization): Introduces or unmasks polar functional groups (−OH, −COOH, −CHO, −NH2 , − SH). minus OH minus COOH minus CHO minus subscript base , NH , end base , sub 2 minus SH Oxidation: Addition of oxygen/negative radicals or removal of hydrogen/positive radicals via Cytochrome P450 enzymes. Reduction: Opposite of oxidation (e.g., Alcohols, Aldehydes, Quinones). Hydrolysis: Cleavage of drug molecules by taking up water. Cyclization: Ring formation from a straight chain (e.g., Proguanil to Cycloguanil). Decyclization: Opening of cyclic ring structures (e.g., Barbiturates, Phenytoin). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
40. METABOLIC REACTIONS: Phase II (Synthetic / Conjugation): Conjugates drug or Phase I metabolite with an endogenous molecule (carbohydrate/amino acid) to produce a polar, ionized molecule easily excreted. Glucuronide Conjugation: Most important pathway; catalyzed by UDP-Glucuronosyl Transferases (UGTs). Acetylation: Conjugation of amino/hydrazine groups using acetyl-CoA (e.g., Sulphonamides, Isoniazid, PAS, Dapsone, Hydralazine, Clonazepam, Procainamide). Methylation: Methylation of amines/phenols via methyltransferases using methionine/cysteine (e.g., Adrenaline, Histamine, Nicotinic acid, Methyldopa, Captopril, Mercaptopurine). Sulphate Conjugation: Phenolic/steroid conjugation via sulfotransferases (SULTs) (e.g., Chloramphenicol, Methyldopa, Adrenal & Sex steroids). Glycine Conjugation: Minor pathway for salicylates and nicotinic acid. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
41. DRUG EXCRETION Definition: Irreversible transfer of systemically absorbed drugs/metabolites from internal tissues to the external environment via renal (urine) or nonrenal (bile, feces, sweat, saliva) routes. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
42. 2. PHARMACODYNAMIC PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
43. PHARMACODYNAMIC Definition: Derived from Greek dynamis (power). It is "What the drug does to the body"—the study of drug actions, mechanisms, and physiological effects. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
44. FUNDAMENTAL MECHANISMS OF DRUG ACTION Receptors: Macromolecules that bind specific drugs to trigger cellular responses. Enzymes & Pumps: Drugs activate or inhibit enzymes (Enzyme induction or inhibition). Ion Channels: • Voltage-gated: e.g., Local anesthetics blocking voltage-sensitive Na+ channels. superscript base , Na , end base , to the plus • Ligand-gated: e.g., Nicotinic receptors. • G-protein regulated: e.g., Cardiac 𝛽1 -adrenergic receptor activating Ca2+ channels. beta sub 1 PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P. superscript base , Ca , end base , to the , 2 plus end superscript
45. FUNDAMENTAL MECHANISMS OF DRUG ACTION Transporters & Symporters: Blocking or activating carrier-mediated movement. Physical Actions: Osmotic effects (mannitol), adsorption (charcoal), mass, radioactivity, radio-opacity. Chemical Reactions: Neutralization or chelation (e.g., Antacids, Oxidizing agents, Chelating agents). Altering Metabolic Processes: Disrupting cellular pathways. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
46. RECEPTOR PHARMACOLOGY & MAJOR RECEPTOR FAMILIES Receptor: A macromolecule /binding site on the cell surface or inside the effector cell that recognizes a ligand/drug and initiates a response. Two Functions: 1. Recognition and binding of ligand 2. Propagation of the signal via effector domain. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P. Receptors are the cellular "doorbells" and "locks" of the body. A drug or hormone acts like a key (ligand). When the key enters the lock, a specific biochemical reaction is triggered inside the room (cell). The 4 major receptor superfamilies differ by where they sit, how many middlemen they use, and how fast they work.
47. RECEPTOR PHARMACOLOGY & MAJOR RECEPTOR FAMILIES Receptor Family Location / Subunits Effector Mechanism / Second Messenger Time Scale Examples 1. Ligand-Gated Ion Channels (Ionotropic) Membrane-bound Direct opening/closing of ion channels →Hyperpolarization or Depolarization Milliseconds Nicotinic ACh receptor 2. G-Protein Coupled Receptors (GPCRs / Metabotropic / Serpentine) 7-transmembrane; Heterotrimeric G-protein (𝛼, 𝛽, 𝛾 subunits) Second messengers (cAMP via Adenylyl cyclase, IP3 /DAGvia Phospholipase C, Ca2+release) Seconds Adrenergic, Muscarinic receptors 3. Enzymatic / Kinase-Linked Receptors Transmembrane protein (extracellular ligand site + intracellular catalytic domain) Protein phosphorylation →Gene transcription & Protein synthesis Hours Insulin receptor, Growth factor receptors 4. Nuclear Receptors Intracellular (Cytoplasm or Nucleus); requires lipidsoluble drugs Binds to DNA →Regulates Transcription, Translation, and Replication PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P. Cytoplasmic: Glucocorticoids, Mineralocorticoids, Progestins Hours Nuclear: T3 /T4(Thyroid), Estrogen, Vitamin A, Vitamin D
48. 1. LIGAND-GATED ION CHANNELS (IONOTROPIC RECEPTORS) The Core Concept: Think of this as an Automatic Electric Door. The receptor and the door (ion channel) are the exact same physical structure. When the key turns the lock, the door swings open immediately and ions rush in. Location & Architecture: Embedded directly in the cell membrane. It is a protein tube with a central pore that stays shut until a drug binds to its external surface. Effector Mechanism: • As soon as the ligand binds, the gate snaps open or shut. • Charged ions (Na+ , K+ , Ca2+ , or Cl− ) flow directly across the cell membrane down their gradient. superscript base , Na , end base , to the plus K to the plus superscript base , Ca , end base , to the , 2 plus end superscript superscript base , Cl , end base , to the minus • This alters the electrical charge across the membrane, causing either depolarization (activation/excitation) or hyperpolarization (inhibition/calming down). Speed (Time Scale): Milliseconds (10−3 s). Because there is zero middleman or enzymatic step, it is the fastest signaling mechanism in the human body. 10 to the , minus 3 end superscript , s Classic Example: Nicotinic Acetylcholine (nACh) Receptor (found at neuromuscular junctions where motor nerves signal muscles to twitch instantly). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
49. 2. G-PROTEIN COUPLED RECEPTORS (GPCRS / METABOTROPIC / SERPENTINE) The Core Concept: Think of this as a Manager Relaying Orders to a Team. The receptor does not perform the action itself; instead, it taps a helper protein inside the cell (the G-protein), which then triggers internal messengers. Location & Architecture: • Embedded in the cell membrane, snaking back and forth through the lipid bilayer 7 times (which is why they are called serpentine or 7-transmembrane receptors). • Attached inside to a three-part molecular switch: a heterotrimeric G-protein made of 𝛼, 𝛽, and 𝛾subunits. start equation alpha start equation beta start equation gamma Effector Mechanism: • When a drug binds externally, the G-protein wakes up and splits apart. • The active subunit slides along the inner membrane to activate enzymes like Adenylyl Cyclase (which generates the second messenger cAMP) or Phospholipase C (which generates IP3 and DAG, releasing stored Ca2+ ). subscript base , IP , end base , sub 3 DAG superscript base , Ca , end base , to the , 2 plus end superscript • These second messengers then amplify the signal throughout the cell. Speed (Time Scale): Seconds. It requires a few molecular handshakes before the cellular change happens. Classic Examples: Adrenergic Receptors (𝛼 and 𝛽receptors for adrenaline/noradrenaline) and Muscarinic Receptors (for acetylcholine in cardiac and smooth muscle). start equation alpha start equation beta PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
50. 3. ENZYMATIC / KINASE-LINKED RECEPTORS (CATALYTIC RECEPTORS) The Core Concept: Think of this as a Direct Power Switch with Built-in Tools. The outside part catches the hormone, and the inside part is an active chemical factory (enzyme) that immediately begins tagging cellular machinery to turn it on. Location & Architecture: Spans across the cell membrane once. It consists of an extracellular binding site (for the hormone) directly connected across the membrane to an intracellular catalytic domain (usually a tyrosine kinase enzyme). Effector Mechanism: • Binding of the ligand causes two receptor pieces to clamp together (dimerize). • The internal kinase domain activates and performs protein phosphorylation (attaching phosphate groups to target proteins). • This initiates a phosphorylation cascade that migrates into the nucleus to turn on specific genes for protein synthesis, tissue growth, and cell metabolism. Speed (Time Scale): Hours. Phosphorylating proteins, changing gene expression, and building new cellular enzymes takes time. Classic Examples: Insulin Receptor (regulates glucose uptake and glycogen storage) and Growth Factor Receptors (EGF, PDGF promoting cell growth and repair). PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
51. 4. NUCLEAR / INTRACELLULAR RECEPTORS The Core Concept: Think of this as a Guest with a VIP Master Key. Most drugs cannot enter cells on their own, but these drugs are lipid-soluble, so they slip right through the fatty cell membrane without needing any surface receptor, walking straight into the control room (the nucleus). Location & Architecture: •These are not on the cell membrane. •They reside entirely inside the cell—either free-floating in the cytoplasm or already stationed directly inside the nucleus. •They require lipid-soluble (lipophilic) drugs that can dissolve across the phospholipid bilayer. Effector Mechanism: •The drug enters the cell and locks directly onto the intracellular receptor. •The drug-receptor complex migrates onto the cell's DNA. •It binds to specific promoter sequences (Hormone Response Elements) and directly governs transcription (DNA →mRNA), translation (mRNA →Protein), and replication. start equation goes to start equation goes to Speed (Time Scale): Hours to Days. Transcribing new DNA and synthesizing completely new structural or enzymatic proteins is the slowest of all mechanisms, but its effects often last the longest. Subclasses & Examples: •Cytoplasmic Receptors: Receptors sit in the cytoplasm until bound, then travel to the nucleus (e.g., Glucocorticoids, Mineralocorticoids, Progestins). •Pure Nuclear Receptors: Receptors sit permanently inside the nucleus waiting for their ligand (e.g., Thyroid hormones T3 /T4 , Estrogen, Vitamin A, Vitamin D). T sub 3 over T sub 4 PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
52. SPEED & COMPLEXITY AT A GLANCE Ligand−Gated Channels ⟶ 𝐌𝐢𝐥𝐥𝐢𝐬𝐞𝐜𝐨𝐧𝐝𝐬 (Direct pore, zero intermediary) G−Protein Receptors ⟶ 𝐒𝐞𝐜𝐨𝐧𝐝𝐬 (G−protein + second messenger cascade) Kinase−Linked Receptors ⟶ 𝐇𝐨𝐮𝐫𝐬 (Enzymatic cascade altering gene readout) Nuclear Receptors ⟶ 𝐇𝐨𝐮𝐫𝐬/𝐃𝐚𝐲𝐬 (Direct genomic transcription inside DNA) PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
53. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
54. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
55. PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.
56. THANK YOU PAWAN KUMAR SAHU LECTURER AT RUDAULI COLLEGE OF PHARMACY, AYODHYA U.P.