cd /home/daytona/workspace/attachments/d8b2103a-d081-4709-a119-bb880fd0603f && python3 -c " from pypdf import PdfReader reader = PdfReader('Pharmacology_Paper_1.pdf') print(f'Total pages: {len(reader.pages)}') text = '' for i, page in enumerate(reader.pages): text += f'\n--- PAGE {i+1} ---\n' text += page.extract_text() or '' print(text) " 2>&1 | head -300

cd /home/daytona/workspace/attachments/d8b2103a-d081-4709-a119-bb880fd0603f && python3 -c " from pypdf import PdfReader reader = PdfReader('Pharmacology_Paper_1.pdf') for i in range(6, len(reader.pages)): print(f'\n--- PAGE {i+1} ---') print(reader.pages[i].extract_text() or '') "

python3 -c " from pypdf import PdfReader reader = PdfReader('/home/daytona/workspace/attachments/d8b2103a-d081-4709-a119-bb880fd0603f/Pharmacology_Paper_1 (1).pdf') print(f'Pages: {len(reader.pages)}') for i, page in enumerate(reader.pages): print(f'\n=== PAGE {i+1} ===') print(page.extract_text() or '') "

python3 -c " from pypdf import PdfReader reader = PdfReader('/home/daytona/workspace/attachments/d8b2103a-d081-4709-a119-bb880fd0603f/kome-default.pdf') print(f'Total pages: {len(reader.pages)}') # Print first 5 pages to understand content for i in range(min(5, len(reader.pages))): print(f'\n=== PAGE {i+1} ===') print(reader.pages[i].extract_text() or '[no text]') " 2>&1

python3 -c " from pypdf import PdfReader reader = PdfReader('/home/daytona/workspace/attachments/d8b2103a-d081-4709-a119-bb880fd0603f/kome-default.pdf') full_text = '' for i, page in enumerate(reader.pages): full_text += page.extract_text() or '' # Save to file with open('/home/daytona/workspace/pharma_full.txt', 'w') as f: f.write(full_text) print(f'Done. Characters: {len(full_text)}') " 2>&1

mkdir -p /home/daytona/workspace/pharma-revision && ls /home/daytona/workspace/pharma-revision/

mkdir -p /home/daytona/workspace/pharma-revision && node -e " const { Document, Packer, Paragraph, TextRun, HeadingLevel, AlignmentType, BorderStyle, Table, TableRow, TableCell, WidthType } = require('docx'); const fs = require('fs'); const H1 = (text) => new Paragraph({ text, heading: HeadingLevel.HEADING_1, spacing: { before: 300, after: 100 } }); const H2 = (text) => new Paragraph({ text, heading: HeadingLevel.HEADING_2, spacing: { before: 200, after: 80 } }); const H3 = (text) => new Paragraph({ text, heading: HeadingLevel.HEADING_3, spacing: { before: 150, after: 60 } }); const P = (text) => new Paragraph({ children: [new TextRun({ text, size: 20 })], spacing: { after: 60 } }); const B = (label, val) => new Paragraph({ children: [new TextRun({ text: label, bold: true, size: 20 }), new TextRun({ text: val || '', size: 20 })], spacing: { after: 50 } }); const bullet = (text) => new Paragraph({ bullet: { level: 0 }, children: [new TextRun({ text, size: 20 })], spacing: { after: 40 } }); const sub = (text) => new Paragraph({ bullet: { level: 1 }, children: [new TextRun({ text, size: 18 })], spacing: { after: 30 } }); const HR = () => new Paragraph({ border: { bottom: { style: BorderStyle.SINGLE, size: 6, color: '4472C4' } }, text: '' }); const children = [ // TITLE new Paragraph({ children: [new TextRun({ text: 'PHARMACOLOGY PAPER I', bold: true, size: 52, color: '1F3864' })], alignment: AlignmentType.CENTER, spacing: { after: 100 } }), new Paragraph({ children: [new TextRun({ text: 'QUICK REVISION NOTES', bold: true, size: 36, color: '2F5496' })], alignment: AlignmentType.CENTER, spacing: { after: 60 } }), new Paragraph({ children: [new TextRun({ text: 'Based on Shanbhag\\'s Review of Pharmacology', italics: true, size: 22, color: '595959' })], alignment: AlignmentType.CENTER, spacing: { after: 300 } }), // ===================== SECTION 1 ===================== H1('1. GENERAL PHARMACOLOGY — ROUTES OF DRUG ADMINISTRATION'), H2('Factors Governing Choice of Route'), bullet('Nature of drug — insulin destroyed orally → parenteral; nitroglycerin → sublingual'), bullet('Nature of illness — emergencies → IV; chronic → oral'), bullet('Desired onset — IV = immediate; depot = prolonged'), bullet('Patient condition — unconscious/vomiting → parenteral'), bullet('First-pass metabolism — high FPM drugs (propranolol, GTN) avoid oral'), bullet('Local vs systemic — topical for local; systemic for general effect'), bullet('Cost/compliance — oral cheapest and most convenient'), H2('Transdermal Therapeutic Systems (TTS)'), bullet('Patch delivers drug through skin at constant rate → bypasses first-pass'), bullet('Advantages: constant blood levels, easy removal, improved compliance'), bullet('Disadvantages: expensive, skin irritation, only lipophilic low-MW low-dose drugs'), bullet('Examples: GTN patch (angina), Fentanyl (pain), Nicotine (cessation), Scopolamine (motion sickness)'), H2('Routes — Quick Table'), B('Oral: ','Aspirin | Sublingual: GTN | Rectal: Diazepam | IV: Furosemide'), B('IM: ','Penicillin G | SC: Insulin | Inhalation: Salbutamol | Intrathecal: Bupivacaine'), H2('Subcutaneous Route'), bullet('Advantages: self-administration, slow sustained absorption, avoids FPM, depot possible'), bullet('Disadvantages: small volumes only (≤2 mL), slow (not for emergencies), irritants cause necrosis'), bullet('Examples: Insulin, heparin, morphine, adrenaline'), H2('IV Route — 4 drugs: Furosemide, Digoxin, Dopamine, Heparin'), bullet('Advantages: 100% bioavailability, immediate effect, accurate titration, large volumes'), bullet('Disadvantages: irreversible, thrombophlebitis, air embolism, requires sterile technique'), H2('Kinetics of Drug Administration'), bullet('IV bolus → instant peak, exponential decline'), bullet('Oral/IM → absorption + elimination phases (rise and fall curve)'), bullet('IV infusion → plateau (steady state) after 4-5 half-lives'), bullet('First-order kinetics: constant fraction eliminated/time (most drugs); t½ constant'), bullet('Zero-order: constant amount/time (phenytoin, alcohol, aspirin high dose); t½ increases with dose'), HR(), // ===================== SECTION 2 ===================== H1('2. PHARMACOKINETICS'), H2('Bioavailability (F)'), B('Definition: ','Fraction of administered drug reaching systemic circulation unchanged. IV = 100%.'), B('Formula: ','F = AUC(oral)/AUC(IV) × 100'), H3('Factors Affecting Bioavailability'), bullet('First-pass metabolism — propranolol (F=26%), morphine (25%), GTN (<10%), lignocaine (3%)'), bullet('Dissolution/solubility — griseofulvin (micronised = better)'), bullet('GI instability — penicillin G (acid-labile), insulin (proteolytic)'), bullet('GI motility — metoclopramide ↑ paracetamol absorption'), bullet('Food — ↓ ampicillin, tetracycline; ↑ griseofulvin, fat-soluble vitamins'), bullet('Drug interactions — antacids chelate tetracycline/fluoroquinolones'), bullet('Disease — liver disease ↑ bioavailability of high-extraction drugs; malabsorption ↓'), bullet('Age — neonates: higher gastric pH; elderly: ↓ motility'), B('Bioequivalence: ','Two products equivalent if AUC, Cmax, Tmax same. Generic = innovator within 80-125% CI'), H2('Biotransformation (Drug Metabolism)'), B('Definition: ','Enzymatic conversion of drug to metabolite; converts lipophilic → hydrophilic for renal excretion'), B('Site: ','Liver (microsomal CYP450) primarily; also kidney, gut wall, plasma'), H3('Phase 1 Reactions (Functionalization) — CYP450'), bullet('Oxidation (most common): Phenobarbitone → hydroxyphenobarbitone'), bullet('Reduction: Chloramphenicol → arylamine'), bullet('Hydrolysis: Procaine → PABA + diethylaminoethanol'), bullet('Products may be active, inactive, or toxic'), H3('Phase 2 Reactions (Conjugation) — synthetic, add polar groups'), bullet('Glucuronidation (most common): Morphine → morphine-6-glucuronide (active)'), bullet('Acetylation: INH, dapsone, hydralazine (slow/fast acetylators)'), bullet('Sulphation: Paracetamol, steroids'), bullet('Methylation: Noradrenaline → adrenaline (COMT)'), bullet('Glycine conjugation: Salicylate → salicyluric acid'), H3('Factors Affecting Biotransformation'), bullet('Age: Neonates — immature CYP → grey baby syndrome (chloramphenicol)'), bullet('Genetics: Slow acetylators (50% Indians) — INH toxicity; CYP2D6 PM — codeine no effect'), bullet('Liver disease: ↓ metabolism → ↑ drug levels'), bullet('Enzyme Induction: Rifampicin, phenobarbitone, phenytoin, carbamazepine, alcohol (chronic)'), sub('Consequences: ↓ effect of OCP (rifampicin → OCP failure), warfarin, corticosteroids'), bullet('Enzyme Inhibition: Cimetidine, ketoconazole, erythromycin, grapefruit juice, ciprofloxacin'), sub('Consequences: ↑ drug levels → toxicity (cimetidine + theophylline → theophylline toxicity)'), H2('Prodrug'), B('Definition: ','Inactive compound converted to active drug in body'), bullet('Advantages: Better oral absorption (enalapril → enalaprilat), reduced toxicity, targeted delivery, improved stability'), bullet('Examples: Enalapril → enalaprilat; Levodopa → dopamine; Codeine → morphine; Azathioprine → 6-MP; Prednisone → prednisolone; Sulphasalazine → 5-ASA'), H2('Plasma Half-Life (t½)'), B('Definition: ','Time for plasma concentration to fall to half its value after distribution equilibrium'), bullet('Short: Penicillin G (30 min), aspirin (15 min)'), bullet('Medium: Propranolol (4 hr), paracetamol (2-3 hr)'), bullet('Long: Amlodipine (35-50 hr), digoxin (36-48 hr), amiodarone (weeks)'), bullet('Clinical uses: Determines dosing frequency; predicts time to steady state (4-5 × t½); guides overdose management'), H2('Therapeutic Drug Monitoring (TDM)'), B('Definition: ','Measurement of drug plasma levels to optimise therapy'), B('Significance: ','NTI drugs, variable PK, toxicity assessment, compliance monitoring'), bullet('Narrow TI drugs (TDM needed): Digoxin (0.5-2 ng/mL), Phenytoin (10-20 mcg/mL), Lithium (0.6-1.2 mEq/L), Theophylline (10-20 mcg/mL)'), bullet('Others: Aminoglycosides, carbamazepine, cyclosporine, warfarin'), H2('Prolongation of Drug Action'), bullet('1. Sustained-release formulations: Diltiazem SR, Metformin SR, Nifedipine GITS'), bullet('2. Depot injections: Fluphenazine decanoate (2-4 wk), Benzathine penicillin (monthly), DMPA (3 months)'), bullet('3. Implants: Levonorgestrel (Norplant, 5 yr), etonogestrel'), bullet('4. Protein binding: Warfarin 99% bound → prolonged effect'), bullet('5. Enzyme inhibitors: Probenecid + penicillin; Carbidopa + levodopa'), HR(), // ===================== SECTION 3 ===================== H1('3. PHARMACODYNAMICS'), H2('Mechanisms of Drug Action'), bullet('1. Receptor-mediated: Agonist/antagonist at GPCRs, ion channels, RTK, nuclear receptors'), bullet('2. Enzyme inhibition: Aspirin (COX), ACE inhibitors, statins (HMG-CoA reductase), neostigmine (AChE)'), bullet('3. Ion channel blockade: Local anaesthetics (Na⁺), CCBs (Ca²⁺), antiarrhythmics'), bullet('4. Carrier/transporter interference: Thiazides (Na-Cl cotransporter), furosemide (Na-K-2Cl), TCAs (noradrenaline reuptake)'), bullet('5. Physical/chemical: Antacids (acid neutralisation), mannitol (osmosis), chelating agents'), bullet('6. Membrane action: Amphotericin B (ergosterol binding)'), H2('Drug Antagonism'), B('Competitive (reversible): ','Antagonist competes at same receptor; effect overcome by ↑ agonist dose; parallel rightward shift of dose-response curve; Emax unchanged. Ex: Atropine vs ACh; naloxone vs morphine; propranolol vs adrenaline'), B('Non-competitive (irreversible): ','Antagonist binds irreversibly or at different site; Emax reduced; not overcome by ↑ agonist. Ex: Phenoxybenzamine; aspirin (irreversible COX)'), B('Physiological antagonism: ','Two drugs produce opposite effects through different receptors. Ex: Adrenaline vs histamine in anaphylaxis; insulin vs glucagon'), B('Chemical antagonism: ','Direct chemical inactivation. Ex: Protamine + heparin; DMSA + heavy metals'), B('Pharmacokinetic antagonism: ','One drug reduces levels of another. Ex: Rifampicin ↓ OCP levels'), H2('Drug Interactions — Classification'), H3('Pharmacokinetic Interactions'), bullet('Absorption: Antacids ↓ tetracycline (chelation); metoclopramide ↑ paracetamol absorption'), bullet('Distribution: Aspirin displaces warfarin from albumin → ↑ bleeding'), bullet('Metabolism: Rifampicin (inducer) ↓ OCP; cimetidine (inhibitor) ↑ theophylline/warfarin'), bullet('Excretion: Probenecid ↓ penicillin secretion; alkaline urine ↑ phenobarbitone excretion'), H3('Pharmacodynamic Interactions'), bullet('Synergism: Co-trimoxazole (trimethoprim + sulphamethoxazole); β-lactam + aminoglycoside'), bullet('Potentiation: Alcohol + CNS depressants'), bullet('Antagonism: Naloxone + morphine'), H3('Beneficial Drug Interactions'), bullet('Co-trimoxazole — sequential blockade of folate synthesis → synergism'), bullet('Carbidopa + levodopa — carbidopa prevents peripheral conversion → more levodopa reaches brain'), bullet('Probenecid + ampicillin — probenecid blocks tubular secretion → prolonged ampicillin'), bullet('Adrenaline + lignocaine — vasoconstriction reduces absorption of LA, prolongs effect'), H3('4 Mechanisms Altering Absorption'), bullet('1. Chelation: Antacids/milk + tetracycline → insoluble chelate'), bullet('2. Adsorption: Cholestyramine + digoxin/warfarin → ↓ absorption'), bullet('3. Altered GI motility: Metoclopramide ↑ gastric emptying → ↑ paracetamol absorption'), bullet('4. Altered GI pH: Antacids → ↑ pH → altered ionisation of weak acid/base drugs'), HR(), // ===================== SECTION 4 ===================== H1('4. PHARMACOTHERAPY'), H2('Tachyphylaxis vs Tolerance'), bullet('Tachyphylaxis: Rapidly developing tolerance to a drug on repeated dosing within short time (minutes-hours)'), bullet('Mechanism: Receptor desensitisation (downregulation), depletion of mediator (indirectly acting sympathomimetics e.g. ephedrine), ion channel inactivation'), bullet('Examples: Ephedrine (tachyphylaxis), Nitrates (develops in 24 hr), LSD'), B('3 Differences — Tachyphylaxis vs Tolerance:',''), sub('Tachyphylaxis: rapid onset (minutes-hours) | Tolerance: develops over days-weeks'), sub('Tachyphylaxis: non-immunological | Tolerance may involve neuroadaptation'), sub('Tachyphylaxis: often mediator depletion | Tolerance: receptor/enzyme changes'), H2('Drug Tolerance'), bullet('Types: Pharmacokinetic (enzyme induction — alcohol → CYP2E1), Pharmacodynamic (receptor downregulation — morphine), Physiological (compensation — antihypertensives → baroreflex), Behavioural'), bullet('Mechanism: Receptor uncoupling, downregulation, altered signal transduction'), bullet('Examples: Morphine (rapid to analgesia/sedation; slow to constipation/miosis), Barbiturates, Nitrates'), H2('Factors Affecting Drug Action'), bullet('Age: Neonates (immature enzymes → grey baby, kernicterus); Elderly (↓ renal/hepatic function → digoxin toxicity)'), bullet('Body weight: Dose in mg/kg; lean body weight for aminoglycosides'), bullet('Sex: Women — higher CYP3A4; different Vd due to body composition'), bullet('Genetics: Slow acetylators (INH neurotoxicity); G6PD deficiency (primaquine → haemolysis); CYP2D6 PM (codeine ineffective)'), bullet('Route & time of administration, disease states (liver/renal/cardiac)'), bullet('Drug interactions (see above)'), H2('Fixed Dose Combinations (FDC)'), H3('Advantages'), bullet('Improved compliance (fewer tablets); synergism (co-trimoxazole); reduced resistance (anti-TB — HRZE); reduced cost'), H3('Disadvantages'), bullet('Cannot adjust individual drug doses; one drug may not be needed; adverse effects of both even if one causes them; irrational combinations promoted commercially'), bullet('Examples of rational FDC: Levodopa + carbidopa; co-trimoxazole; ORS; Anti-TB (HRZE)'), HR(), // ===================== SECTION 5 ===================== H1('5. ADVERSE DRUG REACTIONS & PHARMACOVIGILANCE'), H2('Classification of ADRs (Rawlins & Thompson)'), B('Type A (Augmented/Predictable): ','Dose-related, pharmacological, predictable, common. Ex: Bleeding with warfarin, hypoglycaemia with insulin, dry mouth with atropine'), B('Type B (Bizarre/Unpredictable): ','Not dose-related, immunological or idiosyncratic. Ex: Penicillin anaphylaxis, halothane hepatitis, malignant hyperthermia'), B('Type C (Chronic): ','Long-term use. Ex: Adrenal suppression with corticosteroids, tardive dyskinesia with antipsychotics'), B('Type D (Delayed): ','Teratogenicity (thalidomide), carcinogenicity (cyclophosphamide → bladder cancer)'), B('Type E (End of use/Withdrawal): ','Rebound hypertension (clonidine), seizures (benzodiazepine withdrawal), adrenal crisis (steroid withdrawal)'), H3('Specific ADR Types'), bullet('Toxic effect: Paracetamol → hepatotoxicity; aminoglycosides → nephrotoxicity'), bullet('Side effect: Atropine → dry mouth (when used for bradycardia)'), bullet('Idiosyncratic: Primaquine → haemolysis in G6PD def'), bullet('Hypersensitivity: Type I (penicillin → anaphylaxis), Type IV (contact dermatitis)'), bullet('Drug dependence: Morphine, benzodiazepines'), bullet('Teratogenicity: Thalidomide (phocomelia), warfarin (nasal hypoplasia), valproate (NTD)'), bullet('Carcinogenicity: Cyclophosphamide (bladder), DES (vaginal adenocarcinoma)'), bullet('Photosensitivity: Tetracycline, sulphonamides, amiodarone'), H2('Pharmacovigilance'), B('Definition: ','Science of detecting, assessing, understanding, and preventing adverse effects of drugs (WHO)'), bullet('Objectives: Detect new ADRs, quantify risk, identify risk factors, communicate safety information'), bullet('Methods: Spontaneous reporting (yellow card/vigibase), PMS, cohort studies, case-control studies'), bullet('India: PvPI (Pharmacovigilance Programme of India) — CDSCO/IPC Ghaziabad'), HR(), // ===================== SECTION 6 ===================== H1('6. AUTONOMIC NERVOUS SYSTEM — CHOLINERGIC DRUGS'), H2('Classification of Cholinergic Drugs'), B('Direct-acting: ','Acetylcholine, Carbachol, Bethanechol (muscarinic), Pilocarpine (muscarinic), Nicotine'), B('Indirect-acting (Anticholinesterases): ',''), bullet('Reversible: Physostigmine, Neostigmine, Pyridostigmine, Edrophonium, Rivastigmine'), bullet('Irreversible: Organophosphates — Malathion, Parathion, TEPP, Nerve agents (sarin, tabun), Echothiophate'), H2('Neostigmine'), B('MOA: ','Reversibly inhibits AChE → ↑ ACh at all cholinergic junctions (muscarinic + nicotinic)'), H3('Actions'), bullet('Skeletal muscle: ↑ NMJ ACh → improves muscle contraction (useful in MG)'), bullet('GI: ↑ peristalsis, ↑ secretions'), bullet('CVS: Bradycardia, ↓ BP'), bullet('Eye: Miosis, ↓ IOP'), H3('Clinical Uses'), bullet('Myasthenia gravis (diagnosis and treatment)'), bullet('Reversal of non-depolarising NM blockade (after surgery with atropine pre-treatment)'), bullet('Post-operative ileus, urinary retention'), bullet('Diagnosis of MG (edrophonium = Tensilon test — short acting)'), H2('Rationale: Atropine with Neostigmine'), bullet('Neostigmine ↑ ACh at ALL sites — muscarinic (bradycardia, bronchospasm, excessive secretions) + nicotinic (desired: ↑ muscle power)'), bullet('Atropine blocks only muscarinic side effects, preserving nicotinic (NMJ) effects'), bullet('Atropine given first (3-5 min before neostigmine) to prevent dangerous bradycardia/bronchospasm'), H2('Reversible vs Irreversible Anticholinesterases'), bullet('Reversible: Bind AChE at esteratic site → released in hours. Clinical use: MG, glaucoma, reversal of NMB, Alzheimer\'s (rivastigmine, donepezil)'), bullet('Irreversible: Phosphorylate AChE serine-OH → permanent (aging occurs in 24-48 hr). Clinical use: Echothiophate in glaucoma; toxicology (OP poisoning)'), H2('Treatment of Myasthenia Gravis'), bullet('Anticholinesterases: Pyridostigmine (drug of choice — longer acting than neostigmine)'), bullet('Immunosuppressants: Prednisolone, azathioprine'), bullet('Thymectomy (if thymoma present)'), bullet('Crisis: IV neostigmine or edrophonium; plasmapheresis; IVIG'), H2('Organophosphate Poisoning — Management'), H3('Features (SLUDGE + KILLER Bs)'), bullet('Muscarinic: Salivation, Lacrimation, Urination, Diarrhoea, GI cramps, Emesis (SLUDGE)'), bullet('Bronchospasm, Bradycardia, Miosis, ↓BP, Sweating'), bullet('Nicotinic: Muscle fasciculations → weakness → paralysis (respiratory failure)'), bullet('CNS: Anxiety, seizures, coma'), H3('Treatment'), bullet('1. Remove from exposure, remove contaminated clothing, wash skin'), bullet('2. Maintain airway, O₂, suction secretions'), bullet('3. Atropine: 2-4 mg IV every 5-10 min until secretions dry (end point = atropinisation) — NO fixed dose'), bullet('4. Pralidoxime (2-PAM): 1-2 g IV over 15-30 min — reactivates AChE if given EARLY (before aging)'), bullet('5. Diazepam: for seizures'), bullet('6. NO morphine, aminophylline, phenothiazines'), HR(), // ===================== SECTION 7 ===================== H1('7. ANTICHOLINERGIC DRUGS'), H2('Atropine — 4 Clinical Uses'), bullet('1. Organophosphate poisoning (blocks muscarinic effects)'), bullet('2. Preoperative medication (↓ secretions, bronchodilation, ↓ vagal tone)'), bullet('3. Bradycardia (sinus bradycardia, AV block — IV 0.5-1 mg)'), bullet('4. Antispasmodic (biliary/renal colic — with opioid)'), bullet('Other: Mydriasis for eye examination, reversal of NMB (with neostigmine)'), H2('Atropine vs Tropicamide as Mydriatics'), bullet('Atropine: Duration 7-10 days (long-acting), mydriasis + cycloplegia; used for uveitis, refraction in children; risk of glaucoma precipitation'), bullet('Tropicamide: Duration 4-6 hours (short-acting); mydriasis + mild cycloplegia; preferred for fundoscopy and ophthalmic examination'), H2('Atropine Substitutes — Uses'), bullet('Hyoscine (scopolamine): Motion sickness (patch), premedication, sedation — crosses BBB'), bullet('Ipratropium: COPD/asthma (inhaled bronchodilator) — does NOT cross BBB'), bullet('Tiotropium: COPD (once daily inhaled) — long-acting'), bullet('Glycopyrrolate: Premedication, hyperhidrosis — does NOT cross BBB, no sedation'), bullet('Propantheline: Peptic ulcer, irritable bowel, urinary incontinence'), bullet('Homatropine: Mydriasis (shorter than atropine, 1-3 days)'), bullet('Pirenzepine: M1 blocker — peptic ulcer'), HR(), // ===================== SECTION 8 ===================== H1('8. ADRENERGIC DRUGS'), H2('Classification of Adrenergic Drugs'), B('Direct-acting: ','Adrenaline (α+β), Noradrenaline (α1,α2,β1), Isoprenaline (β1+β2), Dopamine (D1,β1,α1), Dobutamine (β1), Salbutamol (β2), Phenylephrine (α1), Clonidine (α2)'), B('Indirect-acting: ','Ephedrine, amphetamine (release NE)'), B('Mixed: ','Ephedrine'), H2('Catecholamines vs Non-Catecholamines'), bullet('Catecholamines (have catechol ring): Adrenaline, Noradrenaline, Dopamine, Dobutamine, Isoprenaline'), sub('Not effective orally (COMT/MAO destroyed), rapid onset, short duration, CNS — do not cross BBB'), bullet('Non-catecholamines: Salbutamol, Ephedrine, Phenylephrine, Clonidine, Amphetamine'), sub('Effective orally, longer duration (resistant to COMT), many cross BBB'), H2('Adrenaline (Epinephrine) — Complete'), H3('Pharmacological Actions'), bullet('CVS: ↑ HR (β1), ↑ force (β1), ↑ CO; vasodilation of skeletal/coronary vessels (β2), vasoconstriction of skin/viscera (α1) → ↑ SBP, ↓ DBP, ↑ pulse pressure'), bullet('Bronchi: Bronchodilation (β2) — most potent bronchodilator'), bullet('Eye: Mydriasis (α1), ↓ IOP (↓ aqueous production β2, ↑ outflow α)'), bullet('Metabolic: ↑ glycogenolysis (β2) → hyperglycaemia; ↑ lipolysis; ↑ O₂ consumption'), bullet('CNS: Anxiety, tremor, headache (does not cross BBB significantly)'), H3('Therapeutic Uses + Pharmacological Basis'), bullet('1. Anaphylactic shock (1st line): α1 → ↑ BP + vasoconstriction; β2 → bronchodilation; ↓ mast cell degranulation. Dose: 0.5 mg IM (1:1000)'), bullet('2. Cardiac arrest: β1 → restores cardiac rhythm. IV/intracardiac'), bullet('3. With local anaesthetics: α1 vasoconstriction → ↓ absorption of LA, prolonged effect, ↓ systemic toxicity'), bullet('4. Acute severe asthma: β2 bronchodilation (now replaced by selective β2 agonists)'), bullet('5. Open-angle glaucoma: ↓ aqueous humour production (β2), ↑ outflow (α)'), H3('Why Adrenaline Contraindicated in Hypotensive Shock (other than anaphylaxis)'), bullet('Adrenaline causes intense peripheral vasoconstriction (α1) → further ↓ tissue perfusion'), bullet('Also causes ↑ HR and arrhythmias → worsens cardiac output'), bullet('Preferred agent: Noradrenaline (α > β, pure vasoconstriction) or Dopamine'), H3('Adverse Effects'), bullet('Hypertensive crisis, palpitations, arrhythmias (VF)'), bullet('Angina, MI (↑ O₂ demand)'), bullet('Contraindicated with halothane (sensitises myocardium to arrhythmias)'), H3('Vasopressor Agents (4)'), bullet('1. Noradrenaline — ↑ SVR, ↑ BP; vasodilatory/septic shock'), bullet('2. Dopamine — low dose (D1 → renal/splanchnic vasodilation); medium (β1 → ↑CO); high (α1 → vasoconstriction)'), bullet('3. Dobutamine — β1 selective → ↑ CO; cardiogenic shock'), bullet('4. Phenylephrine — α1 only → pure vasoconstriction; spinal hypotension'), HR(), // ===================== SECTION 9 ===================== H1('9. ANTIADRENERGIC DRUGS & DRUGS FOR GLAUCOMA'), H2('Beta Blockers — Classification'), B('Non-selective (β1+β2): ','Propranolol, Timolol, Nadolol, Sotalol'), B('Cardioselective (β1): ','Atenolol, Metoprolol, Bisoprolol, Esmolol (ultra-short)'), B('With ISA: ','Pindolol, Acebutolol'), B('With α-blocking: ','Labetalol, Carvedilol'), H2('Propranolol vs Atenolol — 8 Differences'), bullet('1. Selectivity: Propranolol = non-selective (β1+β2); Atenolol = cardioselective (β1)'), bullet('2. Lipid solubility: Propranolol = high (crosses BBB → CNS effects); Atenolol = low (no CNS effects)'), bullet('3. Oral bioavailability: Propranolol = 26% (high FPM); Atenolol = 50%'), bullet('4. Half-life: Propranolol = 4 hr; Atenolol = 6-9 hr'), bullet('5. Route of elimination: Propranolol = hepatic; Atenolol = renal (dose adjust in renal failure)'), bullet('6. Asthma use: Propranolol CONTRAINDICATED (β2 block → bronchospasm); Atenolol relatively safer'), bullet('7. Diabetes: Propranolol masks hypoglycaemia symptoms (β2 block); Atenolol safer'), bullet('8. Membrane stabilising activity (MSA): Propranolol has MSA; Atenolol does not'), H2('Beta Blockers — Therapeutic Uses'), H3('Cardiovascular'), bullet('Hypertension, Angina pectoris, Arrhythmias (AF, SVT, VT), MI (↓ mortality), CCF (carvedilol, bisoprolol, metoprolol CR in stable CCF)'), H3('Non-Cardiovascular'), bullet('Hyperthyroidism (propranolol — blocks peripheral conversion T4→T3, controls tachycardia)'), bullet('Migraine prophylaxis (propranolol)'), bullet('Anxiety/tremor/performance anxiety (propranolol)'), bullet('Phaeochromocytoma (after α-blockade)'), bullet('Glaucoma (timolol eye drops — ↓ aqueous production)'), bullet('Portal hypertension (propranolol — ↓ portal pressure)'), H2('Alpha Adrenergic Blockers'), B('Selective α1: ','Prazosin, Terazosin, Doxazosin — hypertension, BPH'), B('Non-selective: ','Phenoxybenzamine (irreversible), Phentolamine — phaeochromocytoma'), bullet('Adverse effects: First-dose hypotension (prazosin), reflex tachycardia, postural hypotension, nasal congestion'), H2('Drugs Used in Glaucoma'), H3('Classification + MOA'), bullet('1. β-blockers (Timolol 0.5%, Betaxolol): ↓ aqueous humour production — first-line for open-angle glaucoma'), bullet('2. Prostaglandin analogues (Latanoprost, Bimatoprost): ↑ uveoscleral outflow — most effective IOP reduction'), bullet('3. α2 agonists (Brimonidine): ↓ aqueous production + ↑ uveoscleral outflow'), bullet('4. Carbonic anhydrase inhibitors (Dorzolamide eye drops; Acetazolamide oral): ↓ aqueous production by ↓ HCO₃⁻ secretion'), bullet('5. Miotics (Pilocarpine): ↑ conventional outflow by ciliary muscle contraction → opens trabecular meshwork; also used in acute angle-closure glaucoma'), bullet('6. Sympathomimetics (Dipivefrine, Adrenaline): ↓ production + ↑ outflow'), HR(), // ===================== SECTION 10 ===================== H1('10. SKELETAL MUSCLE RELAXANTS'), H2('Classification by MOA'), B('1. Competitive (non-depolarising) NM blockers: ','Tubocurarine, Pancuronium, Vecuronium, Atracurium, Rocuronium, Mivacurium'), B('2. Depolarising NM blockers: ','Succinylcholine (Suxamethonium) only used clinically'), B('3. Centrally acting: ','Diazepam, Baclofen, Tizanidine'), B('4. Direct acting: ','Dantrolene sodium'), H2('Succinylcholine (Suxamethonium)'), B('MOA: ','Depolarising NMJ blocker — mimics ACh at nicotinic receptor, causes persistent depolarisation → Phase 1 block (flaccid paralysis); prolonged use → Phase 2 block (desensitisation)'), H3('Adverse Effects'), bullet('Muscle fasciculations (before paralysis) → post-op myalgia'), bullet('Hyperkalaemia (↑ K⁺ by 0.5-1 mEq/L) — dangerous in burns, spinal injury, crush injury'), bullet('Malignant hyperthermia (rare, genetic, with halothane) — treat with dantrolene'), bullet('Prolonged apnoea in pseudocholinesterase deficiency (dibucaine number test)'), bullet('↑ IOP, ↑ intragastric pressure, ↑ ICP'), bullet('Bradycardia (2nd dose), hypersalivation'), H3('Therapeutic Uses'), bullet('Rapid sequence induction/intubation (fastest onset: 60 sec)'), bullet('Electroconvulsive therapy (ECT)'), bullet('Laryngoscopy, endoscopy (short procedures)'), H2('Non-depolarising Blockers (Curare/d-Tubocurarine)'), bullet('MOA: Competitive antagonism at nAChR — no depolarisation; reversed by neostigmine + atropine'), bullet('Uses: Surgical muscle relaxation, mechanical ventilation, tetanus (prevent spasms)'), bullet('d-Tubocurarine: releases histamine → bronchospasm; causes ganglionic blockade → hypotension'), HR(), // ===================== SECTION 11 ===================== H1('11. CARDIOVASCULAR — RAAS DRUGS & ACE INHIBITORS'), H2('Drugs Acting on RAAS'), bullet('ACE Inhibitors: Captopril, Enalapril, Lisinopril, Ramipril, Perindopril'), bullet('ARBs: Losartan, Valsartan, Candesartan, Telmisartan, Irbesartan'), bullet('Direct Renin Inhibitor: Aliskiren'), bullet('Aldosterone antagonists: Spironolactone, Eplerenone'), H2('ACE Inhibitors — Complete'), B('MOA: ','Block conversion of Ang I → Ang II (by ACE/kininase II); ↓ Ang II effects (vasoconstriction, aldosterone, SNS); ↑ bradykinin (vasodilator, but causes cough)'), H3('Therapeutic Uses'), bullet('Hypertension (1st line, especially diabetics with nephropathy)'), bullet('CCF (↓ preload + afterload, ↓ aldosterone → ↓ Na/water retention, ↓ ventricular remodelling)'), bullet('Post-MI (↓ mortality, prevent remodelling)'), bullet('Diabetic nephropathy (↓ GFR and reduce proteinuria — renoprotective)'), bullet('Asymptomatic LV dysfunction'), bullet('Scleroderma renal crisis (captopril)'), H3('Adverse Effects'), bullet('Dry cough (most common — bradykinin accumulation; 10-15% patients) → switch to ARB'), bullet('First-dose hypotension (volume-depleted patients)'), bullet('Hyperkalaemia (↓ aldosterone)'), bullet('Acute renal failure (bilateral renal artery stenosis — dependent on Ang II for GFR)'), bullet('Angioedema (rare but life-threatening — bradykinin)'), bullet('Teratogenic (2nd & 3rd trimester) — avoid in pregnancy'), bullet('Neutropenia, proteinuria (captopril — sulphydryl group)'), H3('Contraindications'), bullet('Bilateral RAS, pregnancy, hyperkalaemia, angioedema history'), H2('Enalapril vs Losartan'), bullet('Enalapril: Prodrug (→ enalaprilat active); blocks ACE; causes cough + angioedema; bradykinin ↑'), bullet('Losartan: ARB — direct AT1 receptor block; NO cough (no bradykinin); uricosuric (unique); first ARB approved; metabolite EXP3174 (active)'), bullet('Both used for: HTN, CCF, diabetic nephropathy, post-MI'), bullet('Losartan preferred when: ACE inhibitor cough; history of angioedema'), H2('Rationale for ACE Inhibitors in CCF'), bullet('↓ Ang II → venous dilation (↓ preload) + arteriolar dilation (↓ afterload) → ↓ cardiac work'), bullet('↓ Aldosterone → ↓ Na/water retention → ↓ oedema'), bullet('↓ Ventricular remodelling (hypertrophy/fibrosis) → slows CCF progression'), bullet('↑ Cardiac output, ↑ exercise tolerance'), H2('Spironolactone in CHF — Rationale'), bullet('Aldosterone ↑ in CHF → Na retention, K loss, cardiac fibrosis → remodelling'), bullet('Spironolactone blocks aldosterone receptors → K-sparing diuresis, ↓ fibrosis, ↓ remodelling'), bullet('RALES trial: ↓ mortality 30% in severe CHF'), bullet('Drug interactions: ACE inhibitors + spironolactone → ↑ risk of hyperkalaemia (monitor K⁺)'), HR(), // ===================== SECTION 12 ===================== H1('12. CARDIAC GLYCOSIDES & CHF'), H2('Digoxin — MOA'), bullet('Inhibits Na⁺/K⁺-ATPase pump → ↑ intracellular Na⁺ → ↑ intracellular Ca²⁺ (via Na/Ca exchanger) → positive inotropy (↑ contractility)'), bullet('Also: Vagal stimulation → ↓ HR, ↓ AV conduction (↑ PR interval)'), H2('Digoxin in CHF — Pharmacological Basis'), bullet('↑ Cardiac contractility (positive inotrope) → ↑ stroke volume, ↑ CO → relieves symptoms'), bullet('↓ Heart rate → more time for diastolic filling'), bullet('↓ Sympathetic activity (indirect — improved CO) → ↓ oedema'), bullet('Indicated in: Systolic CHF + AF (controls ventricular rate)'), H2('Digitalis Toxicity — Treatment'), bullet('GI: Nausea, vomiting, anorexia (earliest)'), bullet('Visual: Yellow-green vision (xanthopsia), halos'), bullet('Cardiac: Any arrhythmia — PAT with block, VT, VF; bradycardia; bigeminy'), bullet('Treatment: Stop digoxin; correct hypokalaemia (K⁺ IV); Lignocaine/phenytoin for VT; Atropine for bradycardia; Digoxin-specific antibody fragments (Digibind/DigiFab) for severe toxicity'), H2('Treatment of CHF — Complete'), H3('Objectives'), bullet('Relieve symptoms (dyspnoea, oedema), improve exercise tolerance, ↓ hospitalisations, ↓ mortality, slow progression'), H3('Drug Groups'), bullet('1. ACE Inhibitors/ARBs: ↓ afterload + preload; ↓ remodelling — backbone of therapy'), bullet('2. Beta blockers (Carvedilol, Bisoprolol, Metoprolol CR): ↓ SNS activation, ↓ remodelling — ↓ mortality'), bullet('3. Diuretics (Furosemide, Spironolactone): Symptomatic relief of congestion; spiro ↓ mortality'), bullet('4. Digoxin: Symptom control in systolic CHF + AF; does NOT ↓ mortality'), bullet('5. Hydralazine + Isosorbide dinitrate: Alternative to ACEI (if intolerant)'), bullet('6. ARNI (Sacubitril + Valsartan): Superior to enalapril (PARADIGM-HF)'), bullet('7. SGLT2 inhibitors (Empagliflozin, Dapagliflozin): ↓ HF hospitalisations + mortality'), HR(), // ===================== SECTION 13 ===================== H1('13. ANTIARRHYTHMIC DRUGS'), H2('Classification (Vaughan-Williams)'), B('Class I (Na⁺ channel blockers): ','IA: Quinidine, Procainamide, Disopyramide | IB: Lignocaine, Mexiletine, Phenytoin | IC: Flecainide, Propafenone'), B('Class II (β-blockers): ','Propranolol, Atenolol, Metoprolol, Esmolol'), B('Class III (K⁺ channel blockers): ','Amiodarone, Sotalol, Ibutilide'), B('Class IV (Ca²⁺ channel blockers): ','Verapamil, Diltiazem'), B('Others: ','Adenosine (SVT), Digoxin (AF rate control)'), H2('Propranolol — Antiarrhythmic Effects'), bullet('Class II: ↓ automaticity of SA/AV nodes; ↓ conduction velocity; ↑ refractory period'), bullet('Reduces sympathetic-triggered arrhythmias'), bullet('Uses: SVT, AF/flutter (rate control), VT (sympathetic), HOCM, peri-operative arrhythmias'), HR(), // ===================== SECTION 14 ===================== H1('14. ANTIANGINAL DRUGS'), H2('Nitrates — MOA'), bullet('Converted to NO (nitric oxide) → activates guanylyl cyclase → ↑ cGMP → ↓ intracellular Ca²⁺ → smooth muscle relaxation → vasodilation'), bullet('Predominantly venodilation (↓ preload = main effect) + arteriolar dilation at high doses (↓ afterload)'), bullet('↓ Ventricular wall tension, ↓ O₂ demand; also dilates coronary collaterals'), H2('Nitroglycerin (GTN)'), bullet('Therapeutic uses: Acute angina (SL, rapid 2-3 min), angina prophylaxis (patch, oral SR), acute MI (IV), acute LVF (IV), oesophageal spasm'), bullet('Routes: Sublingual (0.3-0.6 mg, onset 2-3 min), Transdermal patch (12-14 hr on, 10-12 hr off), IV infusion, Oral SR (capsules), Buccal'), bullet('Adverse effects: Headache (most common — meningeal vessel dilation), postural hypotension, reflex tachycardia, flushing; Tolerance (nitrate-free period)'), H2('Calcium Channel Blockers (CCBs)'), B('MOA in Angina: ','Block L-type voltage-gated Ca²⁺ channels → ↓ Ca²⁺ influx → coronary vasodilation (↑ supply) + ↓ myocardial contractility + ↓ HR (non-DHP) + peripheral vasodilation (↓ afterload)'), H3('Classification'), bullet('Dihydropyridines (DHP) — vascular selective: Nifedipine (short), Amlodipine (long), Felodipine, Nicardipine'), bullet('Non-DHP — cardiac selective: Verapamil (phenylalkylamine), Diltiazem (benzothiazepine)'), H3('Nifedipine vs Verapamil'), bullet('Nifedipine: Vascular selective, vasodilation → reflex tachycardia, NO AV block, used in angina/HTN; headache, flushing, ankle oedema'), bullet('Verapamil: Cardiac selective, ↓ HR, ↓ AV conduction, NO reflex tachycardia, negative inotrope; constipation (most characteristic); used in angina/SVT/HTN; AVOID in CHF, heart block, with beta blockers'), H3('Therapeutic Uses of CCBs'), bullet('Angina (all types including vasospastic/Prinzmetal — CCBs DOC), Hypertension, Arrhythmias (SVT — verapamil), Raynaud\'s phenomenon, Hypertrophic obstructive cardiomyopathy (verapamil)'), H2('Coronary Steal Phenomenon'), bullet('Phenomenon where vasodilators (e.g. dipyridamole) cause preferential dilation of normal coronary vessels → blood "stolen" from ischaemic areas (which are already maximally dilated)'), bullet('Clinical significance: Dipyridamole-thallium stress test uses this; can worsen ischaemia; nifedipine less likely than dipyridamole to cause it'), H2('Management of Myocardial Infarction'), bullet('Immediate: Aspirin 300 mg + Clopidogrel (DAPT); Thrombolysis (streptokinase/alteplase) or primary PCI'), bullet('Nitrates IV (pain + LV failure); Morphine (pain, anxiolysis, venodilation); O₂ (if SaO₂ <94%)'), bullet('Beta blocker (metoprolol/atenolol) — early if no contraindication, ↓ mortality, ↓ infarct size'), bullet('Heparin (UFH or LMWH) — anticoagulation'), bullet('ACE inhibitor (within 24 hr) — ↓ remodelling; Statin (high-dose atorvastatin)'), bullet('Long-term: DAPT (12 months), Beta blocker (lifelong), ACEI, Statin, Aldosterone antagonist if LV dysfunction'), HR(), // ===================== SECTION 15 ===================== H1('15. ANTIHYPERTENSIVE DRUGS'), H2('Classification'), B('Diuretics: ','Thiazides (HCTZ, Chlorthalidone), Loop (Furosemide), K-sparing (Spironolactone, Amiloride)'), B('Beta blockers: ','Atenolol, Metoprolol, Bisoprolol, Labetalol'), B('ACE inhibitors: ','Enalapril, Ramipril, Lisinopril'), B('ARBs: ','Losartan, Valsartan, Telmisartan'), B('CCBs: ','Amlodipine (DHP), Verapamil, Diltiazem'), B('Alpha blockers: ','Prazosin, Doxazosin (also for BPH)'), B('Central agents: ','Clonidine (α2 agonist), Methyldopa (DOC in pregnancy)'), B('Vasodilators: ','Hydralazine (arteriolar), Sodium nitroprusside (arterio + venous)'), H2('Thiazide Diuretics — MOA'), bullet('Inhibit Na⁺-Cl⁻ cotransporter in early DCT → ↑ Na⁺ and water excretion → ↓ plasma volume → ↓ BP'), bullet('Long-term: ↓ peripheral vascular resistance (exact mechanism unclear)'), bullet('Adverse effects: Hypokalaemia, hyponatraemia, hyperuricaemia (gout), hyperglycaemia (diabetes), hyperlipidaemia, hypercalcaemia, impotence'), H2('Combination Therapy in Hypertension'), bullet('Rationale: Different MOA, additive effects, allow lower doses of each (↓ side effects), overcome compensatory mechanisms'), bullet('Preferred combinations: ACEI/ARB + CCB; ACEI/ARB + Thiazide; CCB + Beta blocker'), bullet('Avoid: ACEI + ARB (dual RAAS blockade = ↑ adverse effects); two beta blockers; Non-DHP CCB + Beta blocker (heart block)'), H2('Hypertensive Emergencies vs Urgencies'), bullet('Emergency: BP >180/120 + end-organ damage (encephalopathy, MI, AKI, aortic dissection, papilloedema) → IV drugs, lower BP by 20-25% in 1 hr'), bullet('Urgency: Severe BP elevation without acute end-organ damage → oral drugs, lower BP over 24-48 hr'), H3('Drugs for Hypertensive Emergency (IV)'), bullet('Sodium nitroprusside (SNP): Most rapid; arterial + venous dilator; risk of cyanide toxicity (prolonged use)'), bullet('Labetalol (α+β blocker): Safe in most emergencies including aortic dissection'), bullet('Nicardipine/Clevidipine: DHP CCBs; preferred in perioperative, neurological'), bullet('Hydralazine: Used in pregnancy-induced hypertension'), bullet('Nitroglycerin: Acute coronary syndromes with HTN'), bullet('Esmolol: Aortic dissection (with SNP)'), HR(), // ===================== SECTION 16 ===================== H1('16. DIURETICS'), H2('Classification by Mechanism/Site'), bullet('1. Osmotic: Mannitol (PCT, loop, collecting) — ↓ ICP, ↑ urine output, glaucoma'), bullet('2. CAIs: Acetazolamide (PCT) — glaucoma (DOC for acute angle-closure), altitude sickness, alkalinise urine'), bullet('3. Loop/High-ceiling: Furosemide, Bumetanide, Ethacrynic acid (Henle loop, thick ascending) — most potent'), bullet('4. Thiazides: HCTZ, Chlorthalidone (early DCT) — HTN, mild-mod CCF, diabetes insipidus (paradoxical)'), bullet('5. K-sparing: Spironolactone (aldosterone antagonist), Amiloride, Triamterene (Na channel block, late DCT) — CCF, hyperaldosteronism'), H2('Furosemide — Complete'), B('MOA: ','Inhibits Na⁺-K⁺-2Cl⁻ cotransporter in thick ascending limb of Loop of Henle → ↑ Na⁺, K⁺, Cl⁻, H₂O excretion; ↑ Ca²⁺, Mg²⁺ excretion; ↑ renal blood flow (PGE₂)'), H3('Therapeutic Uses'), bullet('Pulmonary oedema/LVF (IV furosemide — rapid venodilation + diuresis)'), bullet('Hypertension (refractory/with CKD)'), bullet('Oedema (CCF, cirrhosis, nephrotic syndrome)'), bullet('Hypercalcaemia (with IV saline)'), bullet('Hyperkalaemia, SIADH'), H3('Adverse Effects'), bullet('Hypokalaemia (most common) → cardiac arrhythmias, potentiates digoxin toxicity'), bullet('Hyponatraemia, hypomagnesaemia, hypocalcaemia'), bullet('Hyperuricaemia (gout) — competes with urate for tubular secretion'), bullet('Ototoxicity (high dose IV, especially with aminoglycosides)'), bullet('Hyperglycaemia, hyperlipidaemia (less than thiazides)'), bullet('Metabolic alkalosis (H⁺ and K⁺ loss)'), H2('Furosemide in LVF — Pharmacological Basis'), bullet('1. Immediate (within minutes): Venodilation (PGE₂-mediated) → ↓ preload → ↓ pulmonary congestion'), bullet('2. Later: Diuresis → ↓ blood volume → ↓ preload + afterload → ↓ pulmonary oedema'), bullet('3. ↓ Cardiac work and O₂ demand'), HR(), // ===================== SECTION 17 ===================== H1('17. DRUGS AFFECTING BLOOD — HAEMATINICS'), H2('Iron Preparations'), H3('Oral Iron'), bullet('Ferrous sulphate (most common), Ferrous gluconate, Ferrous fumarate, Carbonyl iron, Ferrous succinate'), bullet('Ferrous (Fe²⁺) better absorbed than ferric (Fe³⁺); absorption in proximal duodenum; better on empty stomach'), H3('Adverse Effects of Oral Iron'), bullet('GI: Nausea, vomiting, epigastric discomfort, constipation (most common), diarrhoea, black stools'), bullet('Reduce by: Taking with food (but ↓ absorption), using enteric-coated, starting low dose'), H3('Parenteral Iron'), bullet('Iron sucrose (most common, safest), Iron dextran (risk of anaphylaxis), Ferric carboxymaltose (low anaphylaxis, high dose single infusion), Sodium ferric gluconate'), H3('Indications for Parenteral Iron'), bullet('Oral intolerance/non-compliance, malabsorption (IBD, post-gastrectomy), continued blood loss > oral replacement, severe deficiency needing rapid replenishment, pre-op optimisation, CKD patients on erythropoietin'), H3('Iron Poisoning — Treatment'), bullet('Antidote: Desferrioxamine (chelates Fe³⁺) — IV/IM in severe poisoning'), bullet('Gastric lavage (if early), sodium bicarbonate (to form insoluble ferrous carbonate)'), bullet('Supportive: IV fluids, treat acidosis, haemodynamic support'), H2('Iron Deficiency Anaemia — Treatment'), bullet('Oral ferrous sulphate 200 mg (60 mg elemental Fe) TDS × 3-6 months'), bullet('Continue 3 months after Hb normalises to replenish stores'), bullet('Reticulocyte response: peaks at 7-10 days; Hb rises ~1 g/dL/week'), H2('Folic Acid (1st Trimester) vs Iron (2nd Trimester) in Pregnancy'), bullet('Folic acid from 1st trimester: Neural tube forms in first 28 days (4 wks) of pregnancy; folate deficiency → NTD (anencephaly, spina bifida); started ideally pre-conception + 1st trimester'), bullet('Iron from 2nd trimester: Fetal demand for iron peaks in 2nd/3rd trimester; early pregnancy — maternal iron stores sufficient; iron not needed for neural tube development; GI side effects of iron worsen 1st trimester nausea'), HR(), // ===================== SECTION 18 ===================== H1('18. ANTICOAGULANTS & THROMBOLYTICS'), H2('Heparin (Unfractionated) vs LMWH'), bullet('UFH: MW 15,000-20,000; inhibits IIa (thrombin) + Xa via antithrombin III; IV/SC; monitored by APTT; reversed by protamine 1:1; risk of HIT'), bullet('LMWH (Enoxaparin, Dalteparin): MW 4,000-6,000; mainly inhibits Xa; SC only; no monitoring needed (anti-Xa if needed); less HIT; partially reversed by protamine'), H3('LMWH Advantages over UFH'), bullet('Predictable PK → fixed weight-based dosing; no routine monitoring; outpatient use; less HIT; once/twice daily SC'), H2('Warfarin'), B('MOA: ','Inhibits vitamin K epoxide reductase → ↓ synthesis of Vit K-dependent factors II, VII, IX, X (and protein C, S)'), bullet('Onset: 2-3 days (time for existing factors to deplete); monitored by PT/INR'), bullet('Therapeutic uses: DVT/PE treatment + prophylaxis, AF (stroke prevention), mechanical heart valves, post-MI'), bullet('Reversal: Withhold warfarin; Vit K (oral/IV); FFP (immediate reversal); PCC (prothrombin complex concentrate)'), bullet('Interactions: Rifampicin (↓ warfarin effect via induction); amiodarone (↑ effect via inhibition); aspirin (↑ bleeding)'), H2('Streptokinase vs Alteplase'), bullet('Streptokinase: Non-fibrin selective; systemic thrombolysis; antigenic (antibodies, fever, anaphylaxis); cheaper; 1.5 MU IV over 60 min for MI; contraindicated if prior use within 5 yr or recent streptococcal infection'), bullet('Alteplase (tPA): Fibrin-selective (plasminogen on clot); non-antigenic; expensive; shorter half-life; less systemic bleeding; DOC for ischaemic stroke (within 4.5 hr), massive PE; used in MI'), H2('Anti-Platelet Drugs'), bullet('Aspirin: Irreversibly inhibits COX → ↓ TXA₂ → ↓ platelet aggregation; use: ACS, post-MI, post-stroke, AF, PCI'), bullet('Clopidogrel/Ticagrelor/Prasugrel: ADP (P2Y12) receptor blockers; used with aspirin (DAPT) in ACS/PCI'), bullet('Dipyridamole: ↑ cAMP by ↑ adenosine; combined with aspirin for secondary stroke prevention'), bullet('GPIIb/IIIa inhibitors: Abciximab, Eptifibatide — IV, for high-risk PCI'), H2('Thrombolytics (Fibrinolytics)'), bullet('Drugs: Streptokinase, Alteplase (tPA), Reteplase, Tenecteplase, Urokinase'), bullet('MOA: Convert plasminogen to plasmin → fibrin clot dissolution'), bullet('Alteplase indications: AMI (failed PCI/thrombolysis alternative), Ischaemic stroke (≤4.5 hr), Massive PE with haemodynamic instability, Occluded central venous catheters'), bullet('Contraindications: Active internal bleeding, stroke (haemorrhagic or recent), recent surgery (<10 days), severe hypertension, intracranial tumour'), HR(), // ===================== SECTION 19 ===================== H1('19. HYPOLIPIDAEMIC DRUGS & PLASMA EXPANDERS'), H2('Statins (HMG-CoA Reductase Inhibitors)'), bullet('Drugs: Simvastatin, Atorvastatin (most widely used), Rosuvastatin (most potent), Pravastatin, Fluvastatin, Lovastatin'), B('MOA: ','Competitively inhibit HMG-CoA reductase (rate-limiting step in cholesterol synthesis) → ↓ intracellular cholesterol → ↑ LDL receptor expression → ↑ LDL clearance from blood → ↓ LDL-C 30-55%'), H3('Therapeutic Effects (beyond lipid lowering — Pleiotropic)'), bullet('↓ LDL-C (primary), ↑ HDL-C (modest), ↓ TG (modest), ↓ CRP (anti-inflammatory), plaque stabilisation, ↑ endothelial NO production'), bullet('Uses: Primary + secondary prevention of CVD; ACS (high-dose early); Familial hypercholesterolaemia; Diabetic dyslipidaemia'), H3('Adverse Effects'), bullet('Myopathy/Myalgia (most common) → Rhabdomyolysis (rare — ↑ CK >10× ULN; risk ↑ with fibrates/cyclosporine/macrolides)'), bullet('Hepatotoxicity (↑ transaminases — monitor LFTs); Contraindicated in active liver disease'), bullet('Teratogenic — avoid in pregnancy'), bullet('New-onset diabetes (modest risk)'), H2('Plasma Expanders'), B('Definition: ','Solutions given IV to expand plasma volume (maintain oncotic pressure); used when blood unavailable'), bullet('Natural: Albumin (5%, 25%), FFP'), bullet('Synthetic: Dextran-40, Dextran-70 (risk of anaphylaxis, interfere with crossmatch), Hydroxylethyl starch (HES — risk of AKI, avoid in sepsis), Gelatin (Haemaccel, Gelofusine)'), bullet('Uses: Hypovolaemic shock, burns, surgery, plasmapheresis, micro-circulation improvement (Dextran-40)'), HR(), // ===================== SECTION 20 ===================== H1('20. GASTROINTESTINAL — PEPTIC ULCER DRUGS'), H2('Classification'), bullet('1. Antacids: Mg(OH)₂, Al(OH)₃, CaCO₃, Sodium bicarbonate'), bullet('2. H2 Receptor blockers: Ranitidine, Famotidine, Cimetidine'), bullet('3. Proton Pump Inhibitors (PPIs): Omeprazole, Pantoprazole, Lansoprazole, Rabeprazole, Esomeprazole'), bullet('4. Cytoprotectives: Sucralfate (coats ulcer), Misoprostol (PGE₁ analogue), Bismuth compounds'), bullet('5. Anti-H. pylori: Triple/quadruple regimens'), H2('Omeprazole — MOA'), bullet('Prodrug — activated in acidic environment of parietal cell canaliculus → sulphenamide → irreversibly inhibits H⁺/K⁺-ATPase (proton pump) → blocks ALL acid secretion (basal + stimulated)'), bullet('Most potent acid suppressant; onset 1-2 hr; effect lasts 24 hr (irreversible); take 30 min before meal'), bullet('Uses: PUD, GERD, Zollinger-Ellison syndrome, H. pylori (in triple/quad therapy), NSAID gastropathy'), bullet('Zollinger-Ellison: Gastrin-secreting tumour → massive acid hypersecretion → multiple ulcers; omeprazole → suppresses acid regardless of stimulus (irreversible pump blockade)'), H2('Ranitidine (H2 Blocker)'), bullet('MOA: Competitively blocks H2 receptors on parietal cells → ↓ cAMP → ↓ acid secretion'), bullet('Uses: PUD, GERD, Zollinger-Ellison (high doses), stress ulcer prophylaxis, urticaria'), bullet('Adverse effects: Few; headache, dizziness; Cimetidine: gynaecomastia (anti-androgen), impotence, inhibits CYP450 → drug interactions (warfarin, theophylline toxicity)'), bullet('Note: Ranitidine withdrawn in many countries due to NDMA contamination'), H2('H. pylori Treatment Regimens'), bullet('Triple therapy (14 days): PPI (omeprazole) + Clarithromycin + Amoxicillin (OR Metronidazole)'), bullet('Quadruple therapy (10-14 days): PPI + Bismuth + Metronidazole + Tetracycline (if clarithromycin resistance)'), HR(), // ===================== SECTION 21 ===================== H1('21. ANTIEMETICS & LAXATIVES'), H2('Metoclopramide'), B('MOA: ','D2 receptor antagonist (also 5-HT4 agonist + 5-HT3 antagonist at high doses); acts at CTZ + peripherally'), bullet('Actions: Antiemetic (blocks CTZ); prokinetic (↑ gastric emptying, ↑ LOS tone, ↑ peristalsis)'), bullet('Uses: Nausea/vomiting (chemotherapy, post-op), gastroparesis, GERD (adjunct), pre-procedural (↑ gastric emptying)'), bullet('Adverse effects: Extrapyramidal effects (dystonia, Parkinsonism, tardive dyskinesia — due to D2 block), galactorrhoea (↑ prolactin), drowsiness'), H2('Prokinetic Agents'), bullet('Definition: Drugs that enhance coordinated GI propulsive motility without stimulating secretion'), bullet('Examples: Metoclopramide (D2/5-HT4), Domperidone (D2, does NOT cross BBB — less EPS), Cisapride (5-HT4 — withdrawn: QT prolongation), Mosapride (5-HT4), Erythromycin (motilin receptor agonist — short-term gastroparesis)'), bullet('Uses: Gastroparesis (diabetic), GERD, post-op ileus, chronic intestinal pseudo-obstruction, nausea'), H2('Laxatives — Classification + MOA'), H3('1. Bulk-forming'), bullet('Drugs: Ispaghula (psyllium), Methylcellulose, Sterculia'), bullet('MOA: Absorb water, increase faecal bulk → stimulate peristalsis; safe, physiological'), bullet('Uses: Constipation (1st line), IBS, diverticular disease, hyperlipidaemia (ispaghula)'), H3('2. Osmotic Laxatives'), bullet('Saline: Mg sulphate (acute constipation, bowel prep), Mg hydroxide'), bullet('Lactulose: Synthetic disaccharide → not absorbed → osmotic effect in colon; also metabolised by bacteria → acidic environment → traps NH₄⁺ in colon → used in hepatic encephalopathy'), bullet('PEG (polyethylene glycol): Bowel prep, chronic constipation'), H3('3. Stimulant Laxatives'), bullet('Senna (anthraquinone), Bisacodyl, Castor oil, Cascara'), bullet('MOA: Stimulate enteric nervous system + directly irritate mucosa → ↑ peristalsis + ↓ water absorption'), bullet('Adverse effects: Cramping, electrolyte imbalance, melanosis coli (senna), laxative dependence'), H3('4. Lubricant/Emollient'), bullet('Liquid paraffin: Coats and softens stool; risk of aspiration pneumonia (elderly), malabsorption of fat-soluble vitamins, anal leakage'), bullet('Docusate: Stool softener (detergent effect)'), H3('Contraindications of Laxatives'), bullet('Intestinal obstruction, undiagnosed abdominal pain, appendicitis, acute inflammatory bowel'), bullet('Stimulants: Avoid in pregnancy (uterine stimulation), prolonged use'), HR(), // ===================== SECTION 22 ===================== H1('22. CHELATING AGENTS'), H2('Desferrioxamine'), bullet('MOA: Chelates Fe³⁺ (and Al³⁺) → ferrioxamine complex → excreted in urine (red-brown colour) and bile'), bullet('Uses: Acute iron poisoning (IV/IM), Chronic iron overload (thalassaemia, sickle cell), Aluminium toxicity in dialysis patients'), bullet('Adverse effects: Pain at injection site, hypotension (rapid IV), allergic reactions, ototoxicity, retinal damage (chronic use)'), H2('Dimercaprol (BAL — British Anti-Lewisite)'), bullet('MOA: Dithiol compound; chelates arsenic, mercury, gold, lead, bismuth, antimony by competitive binding'), bullet('Uses: Arsenic poisoning (DOC), Mercury poisoning, Gold toxicity, Lead encephalopathy (with EDTA), Copper (Wilson\'s disease — with penicillamine)'), bullet('Adverse effects: Pain at injection site, nausea, vomiting, salivation, headache, hypertension; contraindicated in hepatic failure (except arsenical jaundice); oil-based — only IM'), H2('Chelating Agents — List + Uses'), bullet('EDTA (Calcium disodium): Lead poisoning (drug of choice), digitalis toxicity (hypercalcaemia)'), bullet('Penicillamine: Wilson\'s disease (Cu), Rheumatoid arthritis, Cystinuria, Lead poisoning'), bullet('DMSA (Succimer): Lead/Mercury/Arsenic — oral, safer, preferred in children'), bullet('DMPS: Mercury, arsenic'), bullet('Deferoxamine: Fe³⁺, Al³⁺'), bullet('Deferiprone: Oral iron chelator — thalassaemia (when deferoxamine intolerant)'), HR(), // ===================== SECTION 23 ===================== H1('23. VITAMINS'), H2('Antioxidant Vitamins'), bullet('Vitamin E (tocopherol): Neutralises free radicals (lipid peroxidation); protects cell membranes; uses: premature infants (haemolytic anaemia), retrolental fibroplasia, possible CVD prevention'), bullet('Vitamin C (ascorbic acid): Water-soluble antioxidant; co-factor for collagen synthesis; enhances iron absorption; treats scurvy; pharmacological doses: wound healing, UTI (acidifies urine)'), bullet('Beta-carotene (provitamin A): Antioxidant; no proven cardiovascular benefit; excess may ↑ lung cancer in smokers'), bullet('Selenium: Component of glutathione peroxidase (antioxidant enzyme)'), H2('Vitamin A (Retinol)'), bullet('Daily requirement: 750 mcg retinol equivalents (adult); 3000 IU; pregnancy: 770 mcg; lactation: 1300 mcg'), H3('Therapeutic Uses'), bullet('Vitamin A deficiency: Night blindness (1st sign), xerophthalmia, Bitot\'s spots → keratomalacia → blindness; supplement 200,000 IU oral × 2 doses'), bullet('Measles (WHO recommendation in endemic areas) — reduces severity and mortality'), bullet('Acne (13-cis retinoic acid = isotretinoin) — severe nodulocystic acne; teratogenic'), bullet('Psoriasis (acitretin), skin disorders, leukoplakia'), bullet('Acute promyelocytic leukaemia (ATRA = all-trans-retinoic acid) — induces differentiation'), bullet('Toxicity: Acute: headache, vomiting, bulging fontanelle | Chronic: pseudotumour cerebri, hepatotoxicity, bone abnormalities, alopecia, teratogenic'), H2('Drug Use in Children — General Principles'), bullet('Dose calculation: Clark\'s rule (body weight in lbs/150 × adult dose), Body surface area method (most accurate)'), bullet('Physiological differences: Neonates — immature liver enzymes (↑ t½ of drugs); immature renal function; higher total body water (↑ Vd for water-soluble drugs); permeable BBB; lower plasma proteins'), bullet('Specific cautions: Chloramphenicol → grey baby syndrome; Tetracycline → dental discolouration/bone (avoid <8 yr); Aspirin → Reye\'s syndrome (avoid <12 yr); Sulphonamides → kernicterus in neonates; Fluoroquinolones → cartilage damage (avoid in children); Corticosteroids → growth retardation'), ]; const doc = new Document({ styles: { default: { document: { run: { font: 'Calibri', size: 20 } } } }, sections: [{ properties: { page: { margin: { top: 720, bottom: 720, left: 900, right: 900 } } }, children }] }); const fs = require('fs'); Packer.toBuffer(doc).then(buf => { fs.writeFileSync('/home/daytona/workspace/pharma-revision/Pharmacology_Quick_Revision.docx', buf); console.log('Done!'); }).catch(e => console.error(e)); " 2>&1

mkdir -p /home/daytona/workspace/pharma-revision && python3 << 'PYEOF' from reportlab.lib.pagesizes import A4 from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle from reportlab.lib.units import cm from reportlab.lib import colors from reportlab.platypus import SimpleDocTemplate, Paragraph, Spacer, HRFlowable, Table, TableStyle from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY from reportlab.platypus import KeepTogether doc = SimpleDocTemplate( '/home/daytona/workspace/pharma-revision/Pharmacology_Quick_Revision.pdf', pagesize=A4, rightMargin=1.8*cm, leftMargin=1.8*cm, topMargin=1.8*cm, bottomMargin=1.8*cm ) W = A4[0] - 3.6*cm # ── Styles ────────────────────────────────────────────────────────── styles = getSampleStyleSheet() title_s = ParagraphStyle('title_s', fontName='Helvetica-Bold', fontSize=22, textColor=colors.HexColor('#1F3864'), alignment=TA_CENTER, spaceAfter=4) sub_s = ParagraphStyle('sub_s', fontName='Helvetica-Bold', fontSize=14, textColor=colors.HexColor('#2F5496'), alignment=TA_CENTER, spaceAfter=2) auth_s = ParagraphStyle('auth_s', fontName='Helvetica-Oblique',fontSize=10, textColor=colors.HexColor('#595959'), alignment=TA_CENTER, spaceAfter=16) h1_s = ParagraphStyle('h1_s', fontName='Helvetica-Bold', fontSize=13, textColor=colors.white, backColor=colors.HexColor('#1F3864'), borderPad=4, leftIndent=0, spaceAfter=6, spaceBefore=14) h2_s = ParagraphStyle('h2_s', fontName='Helvetica-Bold', fontSize=11, textColor=colors.HexColor('#1F3864'), spaceBefore=8, spaceAfter=4, borderPad=2, borderWidth=0, leftIndent=0) h3_s = ParagraphStyle('h3_s', fontName='Helvetica-Bold', fontSize=10, textColor=colors.HexColor('#2F5496'), spaceBefore=6, spaceAfter=3) body_s = ParagraphStyle('body_s', fontName='Helvetica', fontSize=9, leading=13, spaceAfter=2, leftIndent=0) bullet_s = ParagraphStyle('bullet_s', fontName='Helvetica', fontSize=9, leading=13, spaceAfter=2, leftIndent=12, bulletIndent=0, bulletFontName='Helvetica') sub_b_s = ParagraphStyle('sub_b_s', fontName='Helvetica', fontSize=8.5,leading=12, spaceAfter=1, leftIndent=24, textColor=colors.HexColor('#444444')) bold_s = ParagraphStyle('bold_s', fontName='Helvetica-Bold', fontSize=9, leading=13, spaceAfter=2) kv_s = ParagraphStyle('kv_s', fontName='Helvetica', fontSize=9, leading=13, spaceAfter=2, leftIndent=12) def H1(t): return Paragraph(f' {t}', h1_s) def H2(t): return Paragraph(t, h2_s) def H3(t): return Paragraph(t, h3_s) def P(t): return Paragraph(t, body_s) def B(lbl, val=''): return Paragraph(f'<b>{lbl}</b>{val}', kv_s) def BUL(t):return Paragraph(f'• {t}', bullet_s) def SUB(t):return Paragraph(f' – {t}', sub_b_s) def HR(): return HRFlowable(width='100%', thickness=1, color=colors.HexColor('#4472C4'), spaceAfter=6, spaceBefore=4) def SP(n=4): return Spacer(1, n) story = [] # ── TITLE ──────────────────────────────────────────────────────────── story += [ SP(10), Paragraph('PHARMACOLOGY PAPER I', title_s), Paragraph('QUICK REVISION NOTES', sub_s), Paragraph('Based on Shanbhag\'s Review of Pharmacology', auth_s), HR(), SP(6) ] # ═══════════════════════════════════════════════════════════════════ # 1. GENERAL PHARMACOLOGY # ═══════════════════════════════════════════════════════════════════ story += [H1('1. GENERAL PHARMACOLOGY — ROUTES OF DRUG ADMINISTRATION'), SP(4)] story += [H2('Factors Governing Choice of Route'), BUL('Nature of drug — insulin destroyed orally → parenteral; GTN → sublingual (high FPM)'), BUL('Nature of illness — emergencies → IV; chronic conditions → oral'), BUL('First-pass metabolism — propranolol (F=26%), GTN (<10%) avoid oral'), BUL('Patient condition — unconscious/vomiting → parenteral route'), BUL('Local vs systemic — topical for local; systemic for general effect'), BUL('Cost/compliance — oral cheapest and most convenient'), SP(4)] story += [H2('Transdermal Therapeutic Systems (TTS)'), BUL('Drug in reservoir/matrix patch → diffuses through skin at constant rate → bypasses first-pass'), BUL('Advantages: constant blood levels, easy removal, improved compliance'), BUL('Disadvantages: expensive, skin irritation, only lipophilic low-MW low-dose drugs'), BUL('Examples: GTN patch (angina), Fentanyl (pain), Nicotine (cessation), Scopolamine (motion sickness)'), SP(4)] # Routes table story += [H2('Routes of Administration — Quick Reference')] tdata = [ ['Route','Example','Route','Example'], ['Oral (PO)','Aspirin','Sublingual (SL)','GTN'], ['Intravenous (IV)','Furosemide','Intramuscular (IM)','Penicillin G'], ['Subcutaneous (SC)','Insulin','Inhalation','Salbutamol'], ['Transdermal','GTN patch','Intrathecal','Bupivacaine'], ['Rectal','Diazepam suppository','Intranasal','Desmopressin'], ] t = Table(tdata, colWidths=[W/4, W/4, W/4, W/4]) t.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')), ('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'), ('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [t, SP(4)] story += [H2('Subcutaneous Route'), BUL('Advantages: self-administration (insulin), slow sustained absorption, depot possible, avoids FPM'), BUL('Disadvantages: small volumes (≤2 mL), slow (not for emergencies), irritants → necrosis'), BUL('Examples: Insulin, heparin, morphine, adrenaline'), SP(4)] story += [H2('IV Route — 4 drugs: Furosemide, Digoxin, Dopamine, Heparin'), BUL('Advantages: 100% bioavailability, immediate effect, accurate titration, large volumes possible'), BUL('Disadvantages: irreversible, thrombophlebitis, air embolism, requires sterile technique'), SP(4)] story += [H2('Kinetics of Drug Administration'), BUL('IV bolus → instant peak, exponential decline'), BUL('Oral/IM → absorption + elimination phases (rise and fall curve)'), BUL('IV infusion → steady state plateau after 4-5 half-lives'), BUL('First-order kinetics: constant fraction eliminated/time (most drugs); t½ constant'), BUL('Zero-order: constant amount/time (phenytoin, alcohol, high-dose aspirin); t½ increases with dose'), HR()] # ═══════════════════════════════════════════════════════════════════ # 2. PHARMACOKINETICS # ═══════════════════════════════════════════════════════════════════ story += [H1('2. PHARMACOKINETICS'), SP(4)] story += [H2('Bioavailability (F)'), B('Definition: ','Fraction of administered drug reaching systemic circulation unchanged. IV = 100%.'), B('Formula: ','F = AUC(oral) / AUC(IV) × 100'), H3('Factors Affecting Bioavailability'), BUL('First-pass metabolism — propranolol (F=26%), morphine (25%), GTN (<10%), lignocaine (3%)'), BUL('Dissolution/solubility — griseofulvin micronised form = better bioavailability'), BUL('GI instability — penicillin G (acid-labile), insulin (proteolytic destruction)'), BUL('GI motility — metoclopramide ↑ paracetamol absorption'), BUL('Food — ↓ ampicillin, tetracycline; ↑ griseofulvin, fat-soluble vitamins'), BUL('Drug interactions — antacids chelate tetracycline/fluoroquinolones → ↓ absorption'), BUL('Liver disease — ↑ bioavailability of high-extraction drugs (propranolol)'), B('Bioequivalence: ','Two products equivalent if AUC, Cmax, Tmax same within 80–125% CI. Basis for generic approval.'), SP(4)] story += [H2('Biotransformation (Drug Metabolism)'), B('Definition: ','Enzymatic conversion of drug → metabolite; lipophilic → hydrophilic for renal excretion'), B('Site: ','Liver (CYP450/SER) primarily; also kidney, gut wall, plasma'), H3('Phase 1 Reactions (CYP450) — Functionalization'), BUL('Oxidation (most common): Phenobarbitone → hydroxyphenobarbitone'), BUL('Reduction: Chloramphenicol → arylamine'), BUL('Hydrolysis: Procaine → PABA + diethylaminoethanol'), BUL('Products may be active, inactive, or toxic (paracetamol → NAPQI — toxic)'), H3('Phase 2 Reactions — Conjugation (synthetic)'), BUL('Glucuronidation (most common): Morphine → morphine-6-glucuronide (active)'), BUL('Acetylation: INH, dapsone, hydralazine (slow vs fast acetylators — genetic)'), BUL('Sulphation: Paracetamol, steroids | Methylation: NA → Adrenaline (COMT)'), H3('Enzyme Induction vs Inhibition'), BUL('Inducers: Rifampicin, phenobarbitone, phenytoin, carbamazepine, chronic alcohol'), SUB('Consequences: ↓ OCP effect (rifampicin → OCP failure), ↓ warfarin, ↓ corticosteroids'), BUL('Inhibitors: Cimetidine, ketoconazole, erythromycin, ciprofloxacin, grapefruit juice'), SUB('Consequences: ↑ theophylline (cimetidine → toxicity), ↑ warfarin → bleeding'), SP(4)] story += [H2('Prodrug'), B('Definition: ','Inactive compound converted to active drug in the body by enzymatic/chemical reactions'), BUL('Advantages: Better oral absorption, reduced toxicity, site-specific delivery, improved stability'), BUL('Examples: Enalapril → enalaprilat; Levodopa → dopamine; Codeine → morphine; Azathioprine → 6-MP; Prednisone → prednisolone; Sulphasalazine → 5-ASA'), SP(4)] story += [H2('Plasma Half-Life (t½)'), B('Definition: ','Time for plasma concentration to fall to half after distribution equilibrium'), BUL('Short: Penicillin G (30 min), aspirin (15 min)'), BUL('Medium: Propranolol (4 hr), paracetamol (2-3 hr)'), BUL('Long: Amlodipine (35-50 hr), digoxin (36-48 hr), amiodarone (weeks)'), BUL('Clinical uses: Dosing frequency, time to steady state (4-5 × t½), overdose prediction'), SP(4)] story += [H2('TDM — Narrow Therapeutic Index Drugs'), B('NTI drugs: ','Digoxin (0.5-2 ng/mL), Phenytoin (10-20 mcg/mL), Lithium (0.6-1.2 mEq/L), Theophylline (10-20 mcg/mL)'), BUL('Others: Aminoglycosides, carbamazepine, cyclosporine, warfarin'), SP(4)] story += [H2('Prolongation of Drug Action (4 methods)'), BUL('1. Sustained-release formulations: Diltiazem SR, Metformin SR, Nifedipine GITS'), BUL('2. Depot injections: Fluphenazine decanoate (2-4 wk), Benzathine penicillin (monthly), DMPA (3 months)'), BUL('3. Protein binding: Warfarin 99% bound → prolonged effect'), BUL('4. Enzyme inhibitors: Probenecid + penicillin (↓ tubular secretion); Carbidopa + levodopa'), HR()] # ═══════════════════════════════════════════════════════════════════ # 3. PHARMACODYNAMICS # ═══════════════════════════════════════════════════════════════════ story += [H1('3. PHARMACODYNAMICS'), SP(4)] story += [H2('Mechanisms of Drug Action'), BUL('1. Receptor-mediated: Agonist/antagonist at GPCRs, ion channels, RTK, nuclear receptors'), BUL('2. Enzyme inhibition: Aspirin (COX), ACEi, statins (HMG-CoA), neostigmine (AChE)'), BUL('3. Ion channel blockade: LAs (Na⁺), CCBs (Ca²⁺), antiarrhythmics'), BUL('4. Transporter interference: Thiazides (Na-Cl), furosemide (Na-K-2Cl), TCAs (NA reuptake)'), BUL('5. Physical/chemical: Antacids (neutralisation), mannitol (osmosis), chelating agents'), SP(4)] story += [H2('Drug Antagonism — Types'), B('Competitive (reversible): ','Same receptor; Emax unchanged; overcome by ↑ agonist; parallel rightward shift. Ex: Atropine vs ACh; naloxone vs morphine; propranolol vs adrenaline'), B('Non-competitive (irreversible): ','Different/same site; ↓ Emax; not overcome by ↑ agonist. Ex: Phenoxybenzamine, aspirin (COX)'), B('Physiological: ','Opposite effects via different receptors. Ex: Adrenaline vs histamine (anaphylaxis), insulin vs glucagon'), B('Chemical: ','Direct inactivation. Ex: Protamine + heparin; DMSA + heavy metals'), B('Pharmacokinetic: ','One drug ↓ levels of another. Ex: Rifampicin ↓ OCP'), SP(4)] story += [H2('Drug Interactions'), H3('Pharmacokinetic'), BUL('Absorption: Antacids ↓ tetracycline (chelation); metoclopramide ↑ paracetamol'), BUL('Distribution: Aspirin displaces warfarin from albumin → ↑ bleeding risk'), BUL('Metabolism: Rifampicin (inducer) ↓ OCP; cimetidine (inhibitor) ↑ theophylline'), BUL('Excretion: Probenecid ↓ penicillin tubular secretion → prolongs effect'), H3('Beneficial Drug Interactions'), BUL('Co-trimoxazole: Sequential blockade of folate synthesis → synergism'), BUL('Carbidopa + levodopa: Prevents peripheral conversion; ↑ brain dopamine'), BUL('Adrenaline + lignocaine: Vasoconstriction → prolongs LA, ↓ systemic toxicity'), BUL('Probenecid + ampicillin: ↑ penicillin levels → enhanced antibacterial effect'), HR()] # ═══════════════════════════════════════════════════════════════════ # 4. PHARMACOTHERAPY # ═══════════════════════════════════════════════════════════════════ story += [H1('4. PHARMACOTHERAPY — TOLERANCE, FACTORS AFFECTING DRUG ACTION, FDC'), SP(4)] story += [H2('Tachyphylaxis vs Tolerance'), B('Tachyphylaxis: ','Rapid (minutes-hours) decrease in response; mediator depletion (ephedrine), receptor desensitisation (nitrates in 24 hr), ion channel inactivation. Ex: Ephedrine, LSD, nitrates'), B('Tolerance: ','Gradual (days-weeks) ↓ response. Types: PK (enzyme induction), PD (receptor downregulation), Physiological (compensatory), Behavioural'), H3('3 Differences'), BUL('1. Speed: Tachyphylaxis rapid (min-hr) vs Tolerance slow (days-weeks)'), BUL('2. Mechanism: Tachyphylaxis = mediator depletion/desensitisation vs Tolerance = receptor/enzyme adaptation'), BUL('3. Examples: Tachyphylaxis — ephedrine, nitrates vs Tolerance — morphine, barbiturates, alcohol'), SP(4)] story += [H2('Factors Affecting Drug Action'), BUL('Age: Neonates — immature CYP450 → grey baby (chloramphenicol), kernicterus; Elderly — ↓ renal/hepatic function → digoxin toxicity'), BUL('Genetics: Slow acetylators (50% Indians) — INH neurotoxicity; G6PD def — primaquine haemolysis; CYP2D6 PM — codeine ineffective'), BUL('Body weight: mg/kg dosing; lean body weight for aminoglycosides'), BUL('Sex: Women — higher CYP3A4; different Vd (higher body fat %)'), BUL('Disease: Liver disease ↓ metabolism ↑ drug levels; Renal disease ↓ excretion; CHF ↓ hepatic blood flow'), BUL('Route & time of administration, drug interactions'), SP(4)] story += [H2('Fixed Dose Combinations (FDC)'), H3('Advantages'), BUL('Improved compliance (fewer tablets), synergism (co-trimoxazole), ↓ resistance (anti-TB: HRZE), ↓ cost'), H3('Disadvantages'), BUL('Cannot adjust individual doses, adverse effects of both, irrational combinations promoted commercially'), B('Examples of rational FDC: ','Levodopa + carbidopa; Co-trimoxazole; ORS; Anti-TB (HRZE); Lopinavir + ritonavir'), HR()] # ═══════════════════════════════════════════════════════════════════ # 5. ADVERSE DRUG REACTIONS & PHARMACOVIGILANCE # ═══════════════════════════════════════════════════════════════════ story += [H1('5. ADVERSE DRUG REACTIONS & PHARMACOVIGILANCE'), SP(4)] story += [H2('Classification (Rawlins & Thompson)')] adr_data = [ ['Type','Name','Features','Examples'], ['A','Augmented\n(Predictable)','Dose-related, pharmacological,\ncommon, preventable','Warfarin → bleeding\nInsulin → hypoglycaemia\nAtropine → dry mouth'], ['B','Bizarre\n(Unpredictable)','Not dose-related, immune/\nidiosyncratic, rare, serious','Penicillin → anaphylaxis\nHalothane → hepatitis\nMalignant hyperthermia'], ['C','Chronic','Long-term use','Corticosteroids → adrenal\nsuppression; Tardive dyskinesia'], ['D','Delayed','Teratogenicity,\ncarcinogenicity','Thalidomide → phocomelia\nCyclophosphamide → bladder Ca'], ['E','End of use\n(Withdrawal)','On stopping drug','Clonidine → rebound HTN\nBDZ → seizures\nSteroids → adrenal crisis'], ] at = Table(adr_data, colWidths=[W*0.06, W*0.16, W*0.38, W*0.40]) at.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')), ('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'), ('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('VALIGN',(0,0),(-1,-1),'TOP'), ('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [at, SP(6)] story += [H2('Pharmacovigilance'), B('Definition (WHO): ','Science of detecting, assessing, understanding, and preventing adverse effects of drugs'), BUL('Objectives: Detect new ADRs, quantify risk, identify risk factors, communicate drug safety information'), BUL('Methods: Spontaneous reporting (yellow card/VigiBase), PMS, cohort studies, case-control studies'), B('India: ','PvPI (Pharmacovigilance Programme of India) — under CDSCO/IPC Ghaziabad'), HR()] # ═══════════════════════════════════════════════════════════════════ # 6. ANS — CHOLINERGIC # ═══════════════════════════════════════════════════════════════════ story += [H1('6. CHOLINERGIC SYSTEM & DRUGS'), SP(4)] story += [H2('Classification'), B('Direct-acting: ','ACh, Carbachol, Bethanechol (muscarinic), Pilocarpine (muscarinic), Nicotine'), B('Reversible anticholinesterases: ','Physostigmine, Neostigmine, Pyridostigmine, Edrophonium, Rivastigmine, Donepezil'), B('Irreversible anticholinesterases: ','Organophosphates — Malathion, Parathion, TEPP, Sarin (nerve agent), Echothiophate'), SP(4)] story += [H2('Neostigmine'), B('MOA: ','Reversibly inhibits AChE → ↑ ACh at muscarinic + nicotinic junctions'), BUL('Actions: ↑ muscle contraction (NMJ), ↑ GI peristalsis, bradycardia, miosis, ↓ IOP'), H3('Clinical Uses'), BUL('Myasthenia gravis (treatment — pyridostigmine preferred)'), BUL('Reversal of non-depolarising NM blockade (with atropine pre-treatment)'), BUL('Post-operative ileus and urinary retention'), BUL('Diagnosis of MG: Edrophonium (Tensilon test) — very short acting'), SP(4)] story += [H2('Rationale: Atropine Given WITH Neostigmine'), BUL('Neostigmine ↑ ACh at ALL cholinergic sites (muscarinic + nicotinic)'), BUL('Muscarinic side effects: bradycardia, bronchospasm, excessive secretions (dangerous)'), BUL('Nicotinic (desired) effect: ↑ NMJ transmission → reversal of NMB'), BUL('Atropine blocks ONLY muscarinic side effects; does NOT block nicotinic (NMJ) effect'), BUL('Given 3-5 min BEFORE neostigmine to prevent dangerous bradycardia/bronchospasm'), SP(4)] story += [H2('Reversible vs Irreversible Anticholinesterases'), BUL('Reversible: Bind esteratic site; released in hours; used for MG, glaucoma, reversal of NMB, Alzheimer\'s (rivastigmine)'), BUL('Irreversible: Phosphorylate AChE serine-OH → permanent; "aging" in 24-48 hr; used as insecticides/nerve agents; echothiophate for glaucoma'), SP(4)] story += [H2('Organophosphate Poisoning — Management'), H3('Features — SLUDGE + Bs'), BUL('Muscarinic: Salivation, Lacrimation, Urination, Defecation, GI cramps, Emesis'), BUL('Bronchospasm, Bradycardia, Miosis, ↓BP, Sweating'), BUL('Nicotinic: Muscle fasciculations → weakness → paralysis → RESPIRATORY FAILURE (cause of death)'), BUL('CNS: Anxiety, seizures, coma'), H3('Treatment'), BUL('1. Remove from exposure; wash skin; remove contaminated clothing'), BUL('2. Airway maintenance, O₂, suction secretions'), BUL('3. Atropine 2-4 mg IV q5-10 min until secretions dry (atropinisation = end point)'), BUL('4. Pralidoxime (2-PAM) 1-2 g IV — reactivates AChE if given EARLY (before "aging" in 24-48 hr)'), BUL('5. Diazepam for seizures'), BUL('AVOID: Morphine, aminophylline, phenothiazines'), HR()] # ═══════════════════════════════════════════════════════════════════ # 7. ANTICHOLINERGIC DRUGS # ═══════════════════════════════════════════════════════════════════ story += [H1('7. ANTICHOLINERGIC DRUGS'), SP(4)] story += [H2('Atropine — 4 Clinical Uses'), BUL('1. Organophosphate poisoning (blocks muscarinic effects — dry secretions, ↑ HR, bronchodilation)'), BUL('2. Preoperative medication (↓ secretions, bronchodilation, ↓ vagal tone during surgery)'), BUL('3. Bradycardia/AV block (IV 0.5-1 mg)'), BUL('4. Antispasmodic (biliary/renal colic, IBS — with opioid for colic)'), BUL('Also: Mydriasis for fundoscopy, reversal of NMB (with neostigmine)'), SP(4)] story += [H2('Atropine vs Tropicamide as Mydriatics')] comp1 = Table([ ['Feature','Atropine','Tropicamide'], ['Duration','7-10 days','4-6 hours'], ['Cycloplegia','Marked','Mild'], ['Uses','Uveitis, refraction in children','Fundoscopy, retinal examination'], ['Risk','Glaucoma precipitation','Minimal'], ], colWidths=[W*0.28, W*0.36, W*0.36]) comp1.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [comp1, SP(6)] story += [H2('Atropine Substitutes — Uses'), BUL('Hyoscine/Scopolamine: Motion sickness (patch), premedication, sedation — CROSSES BBB'), BUL('Ipratropium: COPD/asthma (inhaled bronchodilator) — does NOT cross BBB'), BUL('Tiotropium: COPD (once daily inhaled, long-acting)'), BUL('Glycopyrrolate: Premedication, hyperhidrosis — does NOT cross BBB, no sedation'), BUL('Propantheline: Peptic ulcer, IBS, urinary incontinence'), BUL('Pirenzepine: M1 blocker — peptic ulcer (selective)'), HR()] # ═══════════════════════════════════════════════════════════════════ # 8. ADRENERGIC DRUGS # ═══════════════════════════════════════════════════════════════════ story += [H1('8. ADRENERGIC SYSTEM & DRUGS'), SP(4)] story += [H2('Classification'), B('Direct α+β: ','Adrenaline (α1,α2,β1,β2)'), B('Direct α: ','Noradrenaline (α1,α2,β1), Phenylephrine (α1), Clonidine (α2)'), B('Direct β: ','Isoprenaline (β1+β2), Dobutamine (β1 selective), Salbutamol (β2 selective)'), B('Dopaminergic: ','Dopamine (D1,β1,α1 dose-dependent)'), B('Indirect-acting: ','Amphetamine, Tyramine (release NE)'), B('Mixed: ','Ephedrine (direct + indirect)'), SP(4)] story += [H2('Catecholamines vs Non-Catecholamines')] cat_data = [ ['Feature','Catecholamines','Non-Catecholamines'], ['Examples','Adrenaline, NA, Dopamine, Isoprenaline, Dobutamine','Salbutamol, Ephedrine, Phenylephrine, Clonidine'], ['Oral activity','No (COMT/MAO destroys)','Yes (resistant to COMT)'], ['Duration','Short','Longer'], ['CNS penetration','Minimal (except dopamine CNS pathways)','Many cross BBB (ephedrine, clonidine)'], ] catt = Table(cat_data, colWidths=[W*0.22, W*0.39, W*0.39]) catt.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('VALIGN',(0,0),(-1,-1),'TOP'),('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [catt, SP(6)] story += [H2('Adrenaline — Complete'), H3('Pharmacological Actions'), BUL('CVS: ↑ HR (β1), ↑ contractility (β1) → ↑ CO; vasodilation skeletal/coronary (β2), vasoconstriction skin/viscera (α1) → ↑ SBP, ↓ DBP, ↑ pulse pressure'), BUL('Bronchi: Bronchodilation (β2) — most potent bronchodilator'), BUL('Eye: Mydriasis (α1), ↓ IOP'), BUL('Metabolic: ↑ glycogenolysis → hyperglycaemia, ↑ lipolysis, ↑ O₂ consumption'), H3('Therapeutic Uses + Rationale'), BUL('1. Anaphylactic shock (1st line, IM 0.5 mg 1:1000): α1 → ↑ BP; β2 → bronchodilation; ↓ mast cell degranulation'), BUL('2. Cardiac arrest: β1 → restores rhythm (IV 1 mg 1:10,000)'), BUL('3. With local anaesthetics: α1 vasoconstriction → ↓ LA absorption, prolongs effect, ↓ systemic toxicity'), BUL('4. Acute severe asthma: β2 bronchodilation'), BUL('5. Open-angle glaucoma: ↓ aqueous production (β2), ↑ outflow (α)'), H3('Why Adrenaline Contraindicated in Hypotensive Shock (non-anaphylactic)'), BUL('Intense peripheral vasoconstriction (α1) → further ↓ tissue perfusion → worsens shock'), BUL('↑ HR + arrhythmias → ↓ cardiac output'), BUL('Preferred: Noradrenaline (↑ SVR), Dopamine (dose-dependent), Dobutamine (cardiogenic)'), H3('Vasopressor Agents'), BUL('Noradrenaline: ↑ SVR → vasodilatory/septic shock'), BUL('Dopamine: Low (renal/splanchnic D1), Medium (β1 → ↑ CO), High (α1 → vasoconstriction)'), BUL('Dobutamine: β1 selective → ↑ CO (cardiogenic shock)'), BUL('Phenylephrine: Pure α1 → vasoconstriction (spinal hypotension)'), HR()] # ═══════════════════════════════════════════════════════════════════ # 9. ANTIADRENERGIC & GLAUCOMA # ═══════════════════════════════════════════════════════════════════ story += [H1('9. BETA BLOCKERS & DRUGS FOR GLAUCOMA'), SP(4)] story += [H2('Beta Blockers — Classification'), B('Non-selective (β1+β2): ','Propranolol, Timolol, Nadolol, Sotalol'), B('Cardioselective (β1): ','Atenolol, Metoprolol, Bisoprolol, Esmolol (ultra-short)'), B('With ISA: ','Pindolol, Acebutolol'), B('With α-blocking: ','Labetalol (IV HTN emergency), Carvedilol (CCF)'), SP(4)] story += [H2('Propranolol vs Atenolol — 8 Differences')] pa_data = [ ['Feature','Propranolol','Atenolol'], ['Selectivity','Non-selective (β1+β2)','Cardioselective (β1)'], ['Lipid solubility','High → crosses BBB','Low → no CNS effects'], ['Bioavailability','~26% (high FPM)','~50%'], ['Half-life','4 hr','6-9 hr'], ['Elimination','Hepatic','Renal (dose adjust in RF)'], ['Asthma','Contraindicated','Relatively safer'], ['Diabetes','Masks hypoglycaemia (β2)','Safer'], ['MSA','Yes','No'], ] pat = Table(pa_data, colWidths=[W*0.28, W*0.36, W*0.36]) pat.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [pat, SP(6)] story += [H2('Beta Blockers — Therapeutic Uses'), B('Cardiovascular: ','Hypertension, Angina, Arrhythmias (AF/SVT/VT), MI (↓ mortality), CCF (carvedilol/bisoprolol/metoprolol CR in stable CCF)'), B('Non-cardiovascular: ','Hyperthyroidism (propranolol), Migraine prophylaxis (propranolol), Anxiety/tremor/performance anxiety, Phaeochromocytoma (after α-blockade), Glaucoma (timolol drops), Portal hypertension (propranolol)'), SP(4)] story += [H2('Alpha Adrenergic Blockers'), B('Selective α1: ','Prazosin, Terazosin, Doxazosin — hypertension, BPH'), B('Non-selective: ','Phenoxybenzamine (irreversible), Phentolamine — phaeochromocytoma'), BUL('Adverse effects: First-dose hypotension, reflex tachycardia, postural hypotension, nasal congestion'), SP(4)] story += [H2('Drugs Used in Glaucoma')] glau_data = [ ['Drug/Class','MOA','Notes'], ['β-blockers\n(Timolol, Betaxolol)','↓ aqueous humour production','1st line; Betaxolol = cardioselective, safer in asthma'], ['Prostaglandin analogues\n(Latanoprost, Bimatoprost)','↑ uveoscleral outflow','Most effective IOP ↓; once daily at night; SE: iris pigmentation'], ['α2 agonists\n(Brimonidine)','↓ aqueous production +\n↑ uveoscleral outflow','Neuroprotective; avoid in children'], ['CAIs\n(Dorzolamide, Acetazolamide)','↓ aqueous production\n(↓ HCO₃⁻ secretion)','Oral acetazolamide for acute angle-closure; SE: ↓ K⁺, stones'], ['Miotics\n(Pilocarpine)','↑ conventional outflow\n(ciliary muscle contraction)','Acute angle-closure; miosis (limited driving); SE: brow ache'], ] gt = Table(glau_data, colWidths=[W*0.26, W*0.36, W*0.38]) gt.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('VALIGN',(0,0),(-1,-1),'TOP'),('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [gt, HR()] # ═══════════════════════════════════════════════════════════════════ # 10. SKELETAL MUSCLE RELAXANTS # ═══════════════════════════════════════════════════════════════════ story += [H1('10. SKELETAL MUSCLE RELAXANTS'), SP(4)] story += [H2('Classification by MOA'), B('Non-depolarising (Competitive): ','Tubocurarine, Pancuronium, Vecuronium, Atracurium, Rocuronium — reversed by neostigmine+atropine'), B('Depolarising: ','Succinylcholine (suxamethonium) — only one used clinically'), B('Centrally acting: ','Diazepam, Baclofen, Tizanidine'), B('Directly acting: ','Dantrolene sodium (malignant hyperthermia)'), SP(4)] story += [H2('Succinylcholine'), B('MOA: ','Persistent depolarisation of NMJ → Phase 1 block (flaccid paralysis); prolonged use → Phase 2 (desensitisation block)'), H3('Adverse Effects'), BUL('Muscle fasciculations → post-op myalgia'), BUL('Hyperkalaemia (↑ K⁺ 0.5-1 mEq/L) — dangerous in burns, spinal injury, crush injury'), BUL('Malignant hyperthermia (with halothane, genetic) — treat with dantrolene'), BUL('Prolonged apnoea in pseudocholinesterase deficiency'), BUL('↑ IOP, ↑ intragastric pressure, bradycardia (2nd dose)'), H3('Therapeutic Uses'), BUL('Rapid sequence intubation (fastest onset ~60 sec)'), BUL('Electroconvulsive therapy (ECT)'), BUL('Short procedures: laryngoscopy, endoscopy'), SP(4)] story += [H2('Non-Depolarising (Curare) — Uses'), BUL('Surgical muscle relaxation, mechanical ventilation, tetanus (prevent spasms)'), BUL('d-Tubocurarine: releases histamine → bronchospasm; ganglionic blockade → hypotension'), HR()] # ═══════════════════════════════════════════════════════════════════ # 11. CVS — RAAS & ACE INHIBITORS # ═══════════════════════════════════════════════════════════════════ story += [H1('11. CARDIOVASCULAR — RAAS, ACE INHIBITORS & ARBs'), SP(4)] story += [H2('ACE Inhibitors — Complete'), B('Drugs: ','Captopril, Enalapril (prodrug), Lisinopril, Ramipril, Perindopril'), B('MOA: ','Block ACE → ↓ Ang II → vasodilation + ↓ aldosterone + ↑ bradykinin'), H3('Therapeutic Uses'), BUL('Hypertension (1st line in diabetics with nephropathy)'), BUL('CCF (↓ preload + afterload, ↓ ventricular remodelling)'), BUL('Post-MI (↓ mortality, prevent remodelling)'), BUL('Diabetic nephropathy (renoprotective — ↓ glomerular pressure, ↓ proteinuria)'), BUL('Asymptomatic LV dysfunction; Scleroderma renal crisis (captopril)'), H3('Adverse Effects'), BUL('Dry cough (10-15%) — bradykinin accumulation; switch to ARB if intolerant'), BUL('First-dose hypotension; Hyperkalaemia (↓ aldosterone)'), BUL('Acute renal failure (bilateral RAS — dependent on Ang II to maintain GFR)'), BUL('Angioedema (rare, life-threatening — bradykinin); Teratogenic (2nd/3rd trimester)'), B('Contraindications: ','Bilateral RAS, pregnancy, hyperkalaemia, history of angioedema'), SP(4)] story += [H2('Enalapril vs Losartan')] el_data = [ ['Feature','Enalapril (ACEi)','Losartan (ARB)'], ['MOA','Blocks ACE enzyme','Blocks AT1 receptor directly'], ['Cough','Yes (10-15%) — bradykinin','No cough'], ['Angioedema','Yes (rare)','Rare (less than ACEi)'], ['Unique property','—','Uricosuric (lowers uric acid)'], ['Prodrug','Yes (→ enalaprilat)','No (but active metabolite EXP3174)'], ['Uses','HTN, CCF, Diabetic nephropathy','Same; preferred if ACEi cough'], ] elt = Table(el_data, colWidths=[W*0.28, W*0.36, W*0.36]) elt.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [elt, HR()] # ═══════════════════════════════════════════════════════════════════ # 12. CARDIAC GLYCOSIDES & CHF # ═══════════════════════════════════════════════════════════════════ story += [H1('12. CARDIAC GLYCOSIDES & TREATMENT OF CCF'), SP(4)] story += [H2('Digoxin — MOA'), BUL('Inhibits Na⁺/K⁺-ATPase → ↑ intracellular Na⁺ → ↑ intracellular Ca²⁺ (Na/Ca exchanger) → ↑ contractility'), BUL('Vagal stimulation → ↓ HR, ↓ AV conduction (↑ PR interval)'), BUL('Indicated in: Systolic CCF + AF (controls ventricular rate)'), SP(4)] story += [H2('Digitalis Toxicity — Treatment'), BUL('Early signs: Nausea, vomiting, anorexia, yellow-green vision (xanthopsia)'), BUL('Cardiac: Any arrhythmia — PAT with block, bigeminy, VT, VF; bradycardia'), BUL('Precipitated by: Hypokalaemia (diuretics → ↓ K⁺ → ↑ digoxin toxicity)'), BUL('Treatment: Stop digoxin; correct hypokalaemia (IV K⁺); Lignocaine/Phenytoin (VT); Atropine (bradycardia); Digibind/DigiFab (severe toxicity — digoxin-specific Fab fragments)'), SP(4)] story += [H2('Treatment of CHF — Complete'), H3('Drugs Used'), BUL('1. ACE Inhibitors/ARBs: ↓ afterload + preload; ↓ remodelling — backbone of therapy'), BUL('2. Beta blockers (Carvedilol, Bisoprolol, Metoprolol CR): ↓ SNS activation; ↓ mortality'), BUL('3. Diuretics: Furosemide (symptomatic relief); Spironolactone (↓ mortality — RALES trial)'), BUL('4. Digoxin: Symptom control in systolic CCF + AF; does NOT ↓ mortality'), BUL('5. ARNI (Sacubitril+Valsartan): Superior to enalapril — PARADIGM-HF trial'), BUL('6. SGLT2 inhibitors (Empagliflozin, Dapagliflozin): ↓ HF hospitalisations + mortality'), BUL('7. Hydralazine + ISDN: Alternative if ACEI/ARB intolerant'), B('Spironolactone rationale: ','Aldosterone ↑ in CHF → Na retention, K loss, cardiac fibrosis; Spiro blocks → K-sparing diuresis + ↓ remodelling. Caution: ↑ K⁺ with ACEi'), HR()] # ═══════════════════════════════════════════════════════════════════ # 13. ANTIARRHYTHMICS # ═══════════════════════════════════════════════════════════════════ story += [H1('13. ANTIARRHYTHMIC DRUGS'), SP(4)] story += [H2('Vaughan-Williams Classification'), B('Class IA (Na⁺ block + K⁺ block): ','Quinidine, Procainamide, Disopyramide'), B('Class IB (Na⁺ block, shorten APD): ','Lignocaine, Mexiletine, Phenytoin'), B('Class IC (Na⁺ block, no APD change): ','Flecainide, Propafenone'), B('Class II (β-blockers): ','Propranolol, Atenolol, Metoprolol, Esmolol'), B('Class III (K⁺ channel block): ','Amiodarone, Sotalol, Ibutilide'), B('Class IV (Ca²⁺ channel block): ','Verapamil, Diltiazem'), B('Others: ','Adenosine (SVT — DOC), Digoxin (AF rate control)'), H2('Propranolol — Antiarrhythmic Effects'), BUL('↓ Automaticity SA/AV nodes; ↓ conduction velocity; ↑ refractory period (AV node)'), BUL('Uses: SVT, AF/flutter (rate control), VT (sympathetic), peri-operative arrhythmias, HOCM'), HR()] # ═══════════════════════════════════════════════════════════════════ # 14. ANTIANGINAL DRUGS # ═══════════════════════════════════════════════════════════════════ story += [H1('14. ANTIANGINAL DRUGS'), SP(4)] story += [H2('Nitrates — MOA'), BUL('GTN → NO (nitric oxide) → ↑ cGMP → ↓ intracellular Ca²⁺ → smooth muscle relaxation'), BUL('Predominantly venodilation (↓ preload) ± arteriolar dilation (↓ afterload) at high doses'), BUL('↓ Ventricular wall tension, ↓ O₂ demand; dilates coronary collaterals'), H2('Nitroglycerin (GTN)'), BUL('Uses: Acute angina (SL onset 2-3 min), prophylaxis (patch), acute MI (IV), acute LVF (IV), oesophageal spasm'), BUL('Routes: SL (0.3-0.6 mg), Transdermal patch (12-14 hr on + 10-12 hr off), IV infusion, Oral SR, Buccal'), BUL('AEs: Headache (most common), postural hypotension, reflex tachycardia, nitrate tolerance (nitrate-free period)'), SP(4)] story += [H2('Calcium Channel Blockers')] ccb_data = [ ['Feature','Nifedipine (DHP)','Verapamil (non-DHP)'], ['Selectivity','Vascular >> cardiac','Cardiac > vascular'], ['Heart rate','↑ (reflex tachycardia)','↓ (direct SA/AV node)'], ['AV conduction','No effect','↓ (useful in SVT)'], ['Negative inotropy','Mild','Marked'], ['Uses','Angina, HTN, Vasospastic','Angina, HTN, SVT, HOCM'], ['Key adverse effect','Headache, flushing, ankle oedema','Constipation, bradycardia, heart block'], ['Caution','—','Avoid: CCF, heart block, + β-blocker'], ] ccbt = Table(ccb_data, colWidths=[W*0.28, W*0.36, W*0.36]) ccbt.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('VALIGN',(0,0),(-1,-1),'TOP'),('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [ccbt, SP(6)] story += [H2('Coronary Steal Phenomenon'), BUL('Vasodilators (e.g. dipyridamole) preferentially dilate NORMAL vessels → blood "stolen" from ischaemic areas (already maximally dilated) → worsen ischaemia'), BUL('Clinical: Dipyridamole-thallium stress test; avoid non-selective vasodilators in ischaemia'), SP(4)] story += [H2('MI — Drug Management'), BUL('Immediate: Aspirin 300 mg + Clopidogrel (DAPT); Thrombolysis or Primary PCI'), BUL('Nitrates IV (pain + LVF); Morphine (pain/anxiolysis); O₂ (SaO₂ <94%)'), BUL('Beta blocker (early — ↓ mortality, infarct size); Heparin (UFH or LMWH)'), BUL('ACE inhibitor (within 24 hr — ↓ remodelling); Statin (high-dose atorvastatin)'), BUL('Long-term: DAPT ×12 months, Beta blocker + ACEi + Statin (lifelong), Aldosterone antagonist if LV dysfunction'), HR()] # ═══════════════════════════════════════════════════════════════════ # 15. ANTIHYPERTENSIVE DRUGS # ═══════════════════════════════════════════════════════════════════ story += [H1('15. ANTIHYPERTENSIVE DRUGS'), SP(4)] story += [H2('Classification'), B('Diuretics: ','Thiazides (HCTZ, Chlorthalidone), Loop (Furosemide), K-sparing (Spironolactone)'), B('Beta blockers: ','Atenolol, Metoprolol, Labetalol (HTN emergency IV)'), B('ACE inhibitors: ','Enalapril, Ramipril, Lisinopril'), B('ARBs: ','Losartan, Valsartan, Telmisartan'), B('CCBs: ','Amlodipine (DHP), Verapamil, Diltiazem'), B('Alpha blockers: ','Prazosin, Doxazosin (also BPH)'), B('Central agents: ','Clonidine (α2 agonist), Methyldopa (DOC in pregnancy)'), B('Vasodilators: ','Hydralazine (arteriolar), Sodium nitroprusside (IV — emergency)'), SP(4)] story += [H2('Thiazide Diuretics — MOA'), BUL('Inhibit Na⁺-Cl⁻ cotransporter in early DCT → ↑ Na⁺/water excretion → ↓ plasma volume'), BUL('Long-term: ↓ peripheral vascular resistance'), BUL('AEs: Hypokalaemia, hyponatraemia, hyperuricaemia (gout), hyperglycaemia, hyperlipidaemia, hypercalcaemia'), SP(4)] story += [H2('Hypertensive Emergency vs Urgency')] hte_data = [ ['Feature','Emergency','Urgency'], ['Definition','BP >180/120 + END-ORGAN damage','Severe BP elevation WITHOUT acute end-organ damage'], ['Target','↓ BP 20-25% in 1 hr (not normalise)','↓ BP over 24-48 hr'], ['Route','IV drugs','Oral drugs'], ['Drugs','SNP, Labetalol, Nicardipine,\nHydralazine, Esmolol, GTN IV','Amlodipine, Labetalol oral,\nClonidine, Captopril'], ] htt = Table(hte_data, colWidths=[W*0.22, W*0.39, W*0.39]) htt.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('VALIGN',(0,0),(-1,-1),'TOP'),('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [htt, HR()] # ═══════════════════════════════════════════════════════════════════ # 16. DIURETICS # ═══════════════════════════════════════════════════════════════════ story += [H1('16. DIURETICS'), SP(4)] story += [H2('Furosemide — Complete'), B('MOA: ','Inhibits Na⁺-K⁺-2Cl⁻ cotransporter in thick ascending LOH → ↑ Na⁺, K⁺, Cl⁻, H₂O, Ca²⁺, Mg²⁺ excretion'), H3('Therapeutic Uses'), BUL('Pulmonary oedema/LVF (IV — immediate venodilation PGE₂ + diuresis)'), BUL('CCF oedema, cirrhosis, nephrotic syndrome'), BUL('Hypertension (with CKD/refractory), Hypercalcaemia (with IV saline), Hyperkalaemia'), H3('Adverse Effects'), BUL('Hypokalaemia (most common) → arrhythmias, potentiates digoxin toxicity'), BUL('Hyponatraemia, hypomagnesaemia, hypocalcaemia'), BUL('Hyperuricaemia (gout); Ototoxicity (high IV dose — esp. with aminoglycosides)'), BUL('Metabolic alkalosis (H⁺ + K⁺ loss)'), H2('Furosemide in LVF — Rationale'), BUL('1. Immediate (minutes): Venodilation (PGE₂) → ↓ preload → ↓ pulmonary congestion'), BUL('2. Delayed: Diuresis → ↓ blood volume → ↓ preload + afterload'), BUL('3. ↓ Cardiac work and O₂ demand'), HR()] # ═══════════════════════════════════════════════════════════════════ # 17. HAEMATINICS # ═══════════════════════════════════════════════════════════════════ story += [H1('17. DRUGS AFFECTING BLOOD — HAEMATINICS'), SP(4)] story += [H2('Iron Preparations'), H3('Oral Iron'), BUL('Drugs: Ferrous sulphate (most common), Ferrous gluconate, Ferrous fumarate, Carbonyl iron'), BUL('Ferrous (Fe²⁺) better absorbed than ferric; absorbed in proximal duodenum; best on empty stomach'), BUL('AEs: Nausea, vomiting, constipation (most common), epigastric discomfort, black stools'), H3('Parenteral Iron — Indications'), BUL('Oral intolerance/non-compliance, malabsorption (IBD, post-gastrectomy), continued blood loss > oral replacement, severe deficiency, CKD on erythropoietin'), B('Drugs: ','Iron sucrose (safest), Ferric carboxymaltose (high-dose single infusion), Iron dextran (anaphylaxis risk), Sodium ferric gluconate'), H3('Iron Poisoning — Antidote: Desferrioxamine (chelates Fe³⁺ → excreted)'), SP(4)] story += [H2('Folic Acid (1st trimester) vs Iron (2nd trimester)'), BUL('Folic acid from 1st trimester: Neural tube closes in first 28 days → folate deficiency → NTD (spina bifida, anencephaly); start ideally pre-conception'), BUL('Iron from 2nd trimester: Fetal iron demand peaks in 2nd/3rd trimester; early maternal stores sufficient; iron does NOT prevent NTD; GI side effects worse 1st trimester nausea'), HR()] # ═══════════════════════════════════════════════════════════════════ # 18. ANTICOAGULANTS & THROMBOLYTICS # ═══════════════════════════════════════════════════════════════════ story += [H1('18. ANTICOAGULANTS, ANTIPLATELETS & THROMBOLYTICS'), SP(4)] story += [H2('UFH vs LMWH')] hep_data = [ ['Feature','UFH','LMWH (Enoxaparin)'], ['MW','15,000-20,000 Da','4,000-6,000 Da'], ['Mechanism','Inhibits IIa + Xa (via AT-III)','Mainly inhibits Xa'], ['Route','IV or SC','SC only'], ['Monitoring','APTT (target 60-80 sec)','Not routinely needed'], ['Reversal','Protamine 1:1','Partial (50%) with protamine'], ['HIT risk','Higher','Lower'], ['Renal failure','Preferred (not renal)','Use UFH; dose adjust needed'], ] hept = Table(hep_data, colWidths=[W*0.28, W*0.36, W*0.36]) hept.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('VALIGN',(0,0),(-1,-1),'TOP'),('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [hept, SP(6)] story += [H2('Warfarin'), B('MOA: ','Inhibits Vit K epoxide reductase → ↓ factors II, VII, IX, X (+ protein C, S)'), BUL('Onset: 2-3 days; monitored by PT/INR; therapeutic INR 2-3 (2.5-3.5 for mechanical valves)'), BUL('Uses: DVT/PE, AF (stroke prevention), mechanical heart valves, post-MI'), BUL('Reversal: Withhold; Vit K oral/IV; FFP (immediate); PCC'), BUL('Interactions: Rifampicin ↓ warfarin (induction); amiodarone ↑ warfarin (inhibition)'), SP(4)] story += [H2('Streptokinase vs Alteplase')] sk_data = [ ['Feature','Streptokinase','Alteplase (tPA)'], ['Fibrin selectivity','Non-selective','Fibrin-selective'], ['Antigenicity','Antigenic (fever, anaphylaxis)','Non-antigenic'], ['Cost','Cheaper','Expensive'], ['Re-use','Not within 5 yr','Can be repeated'], ['Dose (MI)','1.5 MU IV over 60 min','15 mg bolus + infusion'], ['Uses','MI, DVT/PE','MI, Ischaemic stroke (≤4.5hr), PE'], ] skt = Table(sk_data, colWidths=[W*0.25, W*0.38, W*0.37]) skt.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),8), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('VALIGN',(0,0),(-1,-1),'TOP'),('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [skt, SP(6)] story += [H2('Anti-Platelet Drugs'), BUL('Aspirin: Irreversible COX inhibition → ↓ TXA₂; uses: ACS, post-MI, post-stroke'), BUL('Clopidogrel/Ticagrelor/Prasugrel: P2Y12 (ADP) receptor blockers; DAPT in ACS/PCI'), BUL('Dipyridamole: ↑ cAMP via ↑ adenosine; combined with aspirin (secondary stroke prevention)'), BUL('GPIIb/IIIa inhibitors (Abciximab, Eptifibatide): IV — high-risk PCI'), HR()] # ═══════════════════════════════════════════════════════════════════ # 19. STATINS & PLASMA EXPANDERS # ═══════════════════════════════════════════════════════════════════ story += [H1('19. HYPOLIPIDAEMIC DRUGS & PLASMA EXPANDERS'), SP(4)] story += [H2('Statins (HMG-CoA Reductase Inhibitors)'), B('Drugs: ','Atorvastatin (most used), Rosuvastatin (most potent), Simvastatin, Pravastatin'), B('MOA: ','Competitively inhibit HMG-CoA reductase (rate-limiting step) → ↓ cholesterol synthesis → ↑ LDL receptor expression → ↑ LDL clearance → ↓ LDL-C 30-55%'), BUL('Pleiotropic effects: ↓ CRP (anti-inflammatory), plaque stabilisation, ↑ endothelial NO'), BUL('Uses: Primary + secondary CVD prevention; ACS (high-dose early); FH; Diabetic dyslipidaemia'), H3('Adverse Effects'), BUL('Myopathy/Myalgia (most common) → Rhabdomyolysis (rare; ↑ risk with fibrates/cyclosporine/macrolides; check CK)'), BUL('Hepatotoxicity (↑ transaminases); Teratogenic (avoid pregnancy); New-onset diabetes'), SP(4)] story += [H2('Plasma Expanders'), B('Definition: ','IV solutions to expand plasma volume (maintain oncotic pressure) when blood unavailable'), BUL('Natural: Albumin (5%, 25%), FFP'), BUL('Synthetic: Dextran-40/70 (anaphylaxis risk; interfere with crossmatch), HES (avoid in sepsis — AKI risk), Gelatin (Haemaccel, Gelofusine)'), BUL('Uses: Hypovolaemic shock, burns, surgery, Dextran-40 (improve microcirculation)'), HR()] # ═══════════════════════════════════════════════════════════════════ # 20. GI DRUGS — PEPTIC ULCER # ═══════════════════════════════════════════════════════════════════ story += [H1('20. GASTROINTESTINAL — PEPTIC ULCER & GERD'), SP(4)] story += [H2('Classification of Anti-Ulcer Drugs'), BUL('1. Antacids: Mg(OH)₂, Al(OH)₃, CaCO₃ — neutralise gastric acid'), BUL('2. H2 Receptor Blockers: Ranitidine, Famotidine, Cimetidine — ↓ acid (basal + stimulated)'), BUL('3. PPIs: Omeprazole, Pantoprazole, Lansoprazole, Rabeprazole, Esomeprazole — most potent'), BUL('4. Cytoprotectives: Sucralfate (coats ulcer), Misoprostol (PGE₁ — ↑ mucus + bicarbonate, ↓ acid), Bismuth'), BUL('5. Anti-H. pylori: Triple/quadruple regimens'), SP(4)] story += [H2('Omeprazole — MOA'), BUL('Prodrug → activated in acidic parietal cell canaliculus → sulphenamide → IRREVERSIBLY inhibits H⁺/K⁺-ATPase (proton pump)'), BUL('Blocks ALL acid (basal + stimulated); take 30 min before meal; effect lasts 24 hr'), BUL('Zollinger-Ellison: Gastrin tumour → massive acid; omeprazole suppresses regardless of stimulus'), BUL('AEs: Generally safe; long-term → hypomagnesaemia, ↑ C. difficile, ↑ fracture risk'), SP(4)] story += [H2('H. pylori Treatment'), BUL('Triple therapy (14 days): PPI + Clarithromycin + Amoxicillin (or Metronidazole)'), BUL('Quadruple therapy (if resistance): PPI + Bismuth + Metronidazole + Tetracycline'), SP(4)] story += [H2('Ranitidine'), BUL('MOA: Competitively blocks H2 receptors → ↓ cAMP → ↓ acid secretion'), BUL('Uses: PUD, GERD, Zollinger-Ellison (high dose), stress ulcer prophylaxis'), BUL('Cimetidine AEs: Gynaecomastia (anti-androgenic), impotence, inhibits CYP450 (↑ warfarin, theophylline)'), BUL('Note: Ranitidine withdrawn in many countries — NDMA contamination'), HR()] # ═══════════════════════════════════════════════════════════════════ # 21. ANTIEMETICS & LAXATIVES # ═══════════════════════════════════════════════════════════════════ story += [H1('21. ANTIEMETICS, PROKINETICS & LAXATIVES'), SP(4)] story += [H2('Metoclopramide'), B('MOA: ','D2 antagonist (+ 5-HT4 agonist); acts at CTZ + peripheral GI'), BUL('Actions: Antiemetic (blocks CTZ); Prokinetic (↑ gastric emptying, ↑ LOS tone, ↑ peristalsis)'), BUL('Uses: Nausea/vomiting (chemo, post-op), gastroparesis, GERD'), BUL('AEs: EPS (dystonia, Parkinsonism, tardive dyskinesia — D2 block), galactorrhoea (↑ prolactin), drowsiness'), SP(4)] story += [H2('Prokinetics — Key Differences'), BUL('Domperidone (D2 block): Does NOT cross BBB → less EPS; used in gastroparesis, Parkinson\'s nausea'), BUL('Cisapride (5-HT4): Withdrawn — QT prolongation/arrhythmias'), BUL('Mosapride (5-HT4): Safer alternative; gastroparesis'), BUL('Erythromycin (motilin agonist): Short-term gastroparesis'), SP(4)] story += [H2('Laxatives — Classification + MOA')] lax_data = [ ['Class','Drugs','MOA','Uses'], ['Bulk-forming','Ispaghula, Methylcellulose','↑ faecal bulk → stimulate peristalsis','1st line constipation, IBS, diverticular disease'], ['Osmotic\n(Saline)','Lactulose, Mg sulphate,\nPEG','Draw water into colon osmotically;\nLactulose → NH₄⁺ trap in colon','Constipation; Lactulose = hepatic encephalopathy'], ['Stimulant','Senna, Bisacodyl,\nCastor oil','Stimulate ENS + ↑ peristalsis,\n↓ water absorption','Acute constipation; bowel prep'], ['Lubricant','Liquid paraffin','Coats/softens stool','Anal fissure; AVOID in elderly (aspiration)'], ['Stool softener','Docusate sodium','Detergent — ↑ water penetration','Post-surgical, haemorrhoids'], ] laxt = Table(lax_data, colWidths=[W*0.18, W*0.22, W*0.32, W*0.28]) laxt.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),7.5), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('VALIGN',(0,0),(-1,-1),'TOP'),('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [laxt, SP(4)] story += [B('Contraindications: ','Intestinal obstruction, undiagnosed abdominal pain, appendicitis, pregnancy (stimulants)'), HR()] # ═══════════════════════════════════════════════════════════════════ # 22. CHELATING AGENTS # ═══════════════════════════════════════════════════════════════════ story += [H1('22. CHELATING AGENTS'), SP(4)] chel_data = [ ['Agent','Chelates','Uses','Adverse Effects'], ['Desferrioxamine\n(Deferoxamine)','Fe³⁺, Al³⁺','Iron poisoning (IV/IM), Iron overload\n(thalassaemia), Al toxicity (dialysis)','Hypotension (rapid IV), ototoxicity,\nretinal damage, urine red-brown'], ['Dimercaprol (BAL)','As, Hg, Au, Pb, Bi','Arsenic (DOC), Mercury, Gold toxicity,\nLead encephalopathy (+ EDTA)','Pain at site, nausea, hypertension;\nonly IM (oil-based); avoid in hepatic failure'], ['EDTA (CaNa₂)','Pb, Hg','Lead poisoning (DOC), Digitalis\ntoxicity (hypercalcaemia)','Nephrotoxicity, hypocalcaemia'], ['Penicillamine','Cu, Pb, Hg','Wilson\'s disease (Cu — DOC),\nRA, Cystinuria','Rash, nephrotic syndrome, aplastic anaemia,\nLupus-like syndrome'], ['DMSA (Succimer)','Pb, Hg, As','Lead/Mercury/Arsenic; preferred\nin children (oral, safer)','Mild GI, rash'], ['Deferiprone','Fe³⁺','Oral chelator — thalassaemia\n(when deferoxamine intolerant)','Agranulocytosis (monitor WBC)'], ] ctt = Table(chel_data, colWidths=[W*0.19, W*0.14, W*0.35, W*0.32]) ctt.setStyle(TableStyle([ ('BACKGROUND',(0,0),(-1,0),colors.HexColor('#2F5496')),('TEXTCOLOR',(0,0),(-1,0),colors.white), ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,-1),7.5), ('GRID',(0,0),(-1,-1),0.5,colors.HexColor('#AAAAAA')), ('ROWBACKGROUNDS',(0,1),(-1,-1),[colors.HexColor('#EBF3FB'),colors.white]), ('VALIGN',(0,0),(-1,-1),'TOP'),('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3), ])) story += [ctt, HR()] # ═══════════════════════════════════════════════════════════════════ # 23. VITAMINS # ═══════════════════════════════════════════════════════════════════ story += [H1('23. VITAMINS'), SP(4)] story += [H2('Antioxidant Vitamins'), BUL('Vitamin E (tocopherol): Neutralises free radicals (lipid peroxidation); protects cell membranes; uses: premature infants, retrolental fibroplasia'), BUL('Vitamin C (ascorbic acid): Water-soluble antioxidant; collagen synthesis co-factor; ↑ iron absorption; treats scurvy'), BUL('Beta-carotene: Antioxidant; provitamin A; no proven CVD benefit; excess may ↑ lung cancer risk in smokers'), BUL('Selenium: Component of glutathione peroxidase (antioxidant enzyme)'), SP(4)] story += [H2('Vitamin A'), B('Daily requirement: ','750 mcg RE/day (adult); pregnancy: 770 mcg; lactation: 1300 mcg'), H3('Therapeutic Uses'), BUL('Vitamin A deficiency: Night blindness (1st sign) → xerophthalmia → keratomalacia → blindness; dose 200,000 IU × 2'), BUL('Measles (WHO — reduces severity, mortality in endemic areas)'), BUL('Acne: Isotretinoin (13-cis-retinoic acid) — severe nodulocystic acne; TERATOGENIC'), BUL('Psoriasis: Acitretin; Acute promyelocytic leukaemia: ATRA (induces differentiation)'), BUL('Toxicity — Acute: headache, vomiting, bulging fontanelle | Chronic: pseudotumour cerebri, hepatotoxicity, bone abnormalities, alopecia, teratogenic'), HR()] # ═══════════════════════════════════════════════════════════════════ # 24. DRUG USE IN CHILDREN # ═══════════════════════════════════════════════════════════════════ story += [H1('24. DRUG USE IN CHILDREN — GENERAL PRINCIPLES'), SP(4)] story += [ BUL('Dose calculation: Body surface area method (most accurate); Clark\'s rule: (weight in lb/150) × adult dose'), BUL('Higher total body water in neonates → larger Vd for water-soluble drugs'), BUL('Immature liver enzymes (CYP450, glucuronyl transferase) → ↑ t½, drug accumulation'), BUL('Immature renal function (premature/neonate) → ↓ excretion'), BUL('Permeable BBB → more CNS effects'), BUL('Lower plasma proteins → more free drug'), SP(4), H3('Specific Drug Cautions in Children'), BUL('Chloramphenicol: Grey baby syndrome (immature glucuronyl transferase → accumulation)'), BUL('Tetracycline: Dental discolouration + bone growth impairment — AVOID <8 years'), BUL('Aspirin: Reye\'s syndrome (encephalopathy + hepatic failure) — AVOID <12 years in viral illness'), BUL('Sulphonamides: Kernicterus in neonates (displace bilirubin from albumin)'), BUL('Fluoroquinolones: Cartilage/joint damage — avoid in children'), BUL('Corticosteroids: Growth retardation with chronic use'), HR(), SP(8), Paragraph('END OF QUICK REVISION NOTES', ParagraphStyle('end', fontName='Helvetica-Bold', fontSize=11, textColor=colors.HexColor('#1F3864'), alignment=TA_CENTER)), Paragraph('Pharmacology Paper I — Shanbhag\'s Review of Pharmacology', ParagraphStyle('end2', fontName='Helvetica-Oblique', fontSize=9, textColor=colors.HexColor('#595959'), alignment=TA_CENTER)), ] doc.build(story) print("PDF created successfully!") PYEOF echo "Exit: $?"