ls -la /home/daytona/workspace/ && ls /home/daytona/skills/docx/

ls /home/daytona/workspace/cardio-pharmacology-questions/

ls /home/daytona/workspace/ && ls /home/daytona/skills/docx/scripts/office/

~/cardio-pharmacology-questions/generate.js

const {
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  AlignmentType, PageNumber, Header, Footer,
  BorderStyle, UnderlineType, PageBreak
} = require('docx');
const fs = require('fs');

// ─── HELPERS ────────────────────────────────────────────────────────────────

function heading1(text) {
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function pageBreak() {
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}

function mcqBlock(num, question, options, answer) {
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  options.forEach(o => items.push(para(`    ${o}`)));
  items.push(answerPara(`Answer: ${answer}`));
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function saqBlock(num, question, answer) {
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function laqBlock(num, question, answerPoints) {
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}

// ─── CONTENT ─────────────────────────────────────────────────────────────────

const children = [];

// ── TITLE PAGE ───────────────────────────────────────────────────────────────
children.push(
  new Paragraph({
    children: [new TextRun({ text: 'PHARMACOLOGY', bold: true, size: 48, color: '1F4E79', font: 'Calibri' })],
    alignment: AlignmentType.CENTER,
    spacing: { before: 1200, after: 200 },
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  new Paragraph({
    children: [new TextRun({ text: 'Exam-Oriented Question Bank', size: 32, color: '2E75B6', font: 'Calibri' })],
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  new Paragraph({
    children: [new TextRun({ text: 'Antihypertensives  |  Heart Failure  |  Angina  |  Hematinics', size: 26, italics: true, color: '555555', font: 'Calibri' })],
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    spacing: { before: 100, after: 600 },
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  new Paragraph({
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    spacing: { before: 200, after: 1200 },
  }),
  pageBreak()
);

// ════════════════════════════════════════════════════════════════════════════
// SECTION 1 – ANTIHYPERTENSIVES
// ════════════════════════════════════════════════════════════════════════════
children.push(heading1('SECTION 1: ANTIHYPERTENSIVE DRUGS'));

// --- MCQs ---
children.push(heading2('MULTIPLE CHOICE QUESTIONS (MCQs)'));

const ahMCQs = [
  { q: 'Which antihypertensive drug acts by blocking angiotensin-converting enzyme (ACE)?', opts: ['A. Losartan', 'B. Enalapril', 'C. Amlodipine', 'D. Metoprolol'], ans: 'B. Enalapril' },
  { q: 'The drug of choice for hypertension in a patient with bilateral renal artery stenosis is:', opts: ['A. Enalapril', 'B. Losartan', 'C. Amlodipine', 'D. Ramipril'], ans: 'C. Amlodipine (CCBs are safe; ACE inhibitors/ARBs are contraindicated)' },
  { q: 'Which class of antihypertensives is the first-line drug in diabetic hypertensive patients with proteinuria?', opts: ['A. Beta-blockers', 'B. Calcium channel blockers', 'C. ACE inhibitors / ARBs', 'D. Thiazide diuretics'], ans: 'C. ACE inhibitors / ARBs' },
  { q: 'Mechanism of action of thiazide diuretics in hypertension:', opts: ['A. Block Na+/K+/2Cl- transporter in loop of Henle', 'B. Block Na+/Cl- transporter in distal tubule', 'C. Block aldosterone receptors', 'D. Block Na+ channels in collecting duct'], ans: 'B. Block Na+/Cl- transporter in distal tubule' },
  { q: 'Dry cough as a side effect is associated with:', opts: ['A. Losartan', 'B. Amlodipine', 'C. Enalapril', 'D. Atenolol'], ans: 'C. Enalapril (due to accumulation of bradykinin)' },
  { q: 'Which antihypertensive causes reflex tachycardia and fluid retention?', opts: ['A. Atenolol', 'B. Hydralazine', 'C. Methyldopa', 'D. Clonidine'], ans: 'B. Hydralazine' },
  { q: 'Drug of choice for hypertension in pregnancy:', opts: ['A. Enalapril', 'B. Methyldopa', 'C. Losartan', 'D. Atenolol'], ans: 'B. Methyldopa' },
  { q: 'Calcium channel blockers used specifically for hypertension (dihydropyridines):', opts: ['A. Verapamil and Diltiazem', 'B. Amlodipine and Nifedipine', 'C. Verapamil and Nifedipine', 'D. Diltiazem and Amlodipine'], ans: 'B. Amlodipine and Nifedipine' },
  { q: 'Clonidine acts on which receptor to lower blood pressure?', opts: ['A. Alpha-1 adrenoceptor', 'B. Beta-1 adrenoceptor', 'C. Alpha-2 adrenoceptor (central)', 'D. Imidazoline receptor only'], ans: 'C. Alpha-2 adrenoceptor (central)' },
  { q: 'Spironolactone lowers blood pressure by:', opts: ['A. Blocking renin release', 'B. Blocking aldosterone receptors in collecting duct', 'C. Inhibiting ACE', 'D. Blocking calcium channels'], ans: 'B. Blocking aldosterone receptors in collecting duct' },
  { q: 'Which beta-blocker has intrinsic sympathomimetic activity (ISA)?', opts: ['A. Atenolol', 'B. Propranolol', 'C. Pindolol', 'D. Metoprolol'], ans: 'C. Pindolol' },
  { q: 'First-dose hypotension is a characteristic side effect of:', opts: ['A. Prazosin', 'B. Atenolol', 'C. Amlodipine', 'D. Hydrochlorothiazide'], ans: 'A. Prazosin' },
  { q: 'Which drug is used for hypertensive emergency causing cyanide toxicity?', opts: ['A. Labetalol', 'B. Hydralazine', 'C. Sodium nitroprusside', 'D. Fenoldopam'], ans: 'C. Sodium nitroprusside' },
  { q: 'ACE inhibitors are contraindicated in:', opts: ['A. Diabetes mellitus', 'B. Pregnancy', 'C. Heart failure', 'D. Post-MI'], ans: 'B. Pregnancy (teratogenic - fetopathy)' },
  { q: 'The antihypertensive effect of beta-blockers is due to:', opts: ['A. Decreased peripheral vascular resistance', 'B. Decreased cardiac output and renin secretion', 'C. Vasodilation of arterioles', 'D. Increased natriuresis'], ans: 'B. Decreased cardiac output and renin secretion' },
];

ahMCQs.forEach((item, i) => mcqBlock(i + 1, item.q, item.opts, item.ans).forEach(p => children.push(p)));

// --- SAQs ---
children.push(pageBreak());
children.push(heading2('SHORT ANSWER QUESTIONS (SAQs)'));

const ahSAQs = [
  {
    q: 'Write a note on the mechanism and adverse effects of ACE inhibitors.',
    ans: [
      'Mechanism: Inhibit angiotensin-converting enzyme → prevent conversion of Ang I → Ang II.',
      '→ Reduced aldosterone secretion → natriuresis, reduced preload and afterload.',
      '→ Bradykinin accumulation → vasodilation (also causes cough).',
      'Uses: Hypertension, heart failure, diabetic nephropathy, post-MI.',
      'Adverse effects:',
      '  • Dry cough (most common, due to bradykinin)',
      '  • Angioedema (rare but serious)',
      '  • Hyperkalemia',
      '  • First-dose hypotension',
      '  • Teratogenicity (contraindicated in pregnancy)',
      '  • Renal impairment in bilateral renal artery stenosis',
    ],
  },
  {
    q: 'Classify antihypertensive drugs with one example each.',
    ans: [
      '1. Diuretics: Hydrochlorothiazide, Furosemide, Spironolactone',
      '2. Beta-blockers: Atenolol, Metoprolol, Propranolol',
      '3. Calcium channel blockers: Amlodipine (DHP), Verapamil (non-DHP)',
      '4. ACE inhibitors: Enalapril, Ramipril, Lisinopril',
      '5. ARBs (AT1 blockers): Losartan, Telmisartan',
      '6. Alpha-1 blockers: Prazosin, Doxazosin',
      '7. Central sympatholytics: Clonidine, Methyldopa',
      '8. Vasodilators: Hydralazine, Minoxidil, Sodium nitroprusside',
      '9. Renin inhibitors: Aliskiren',
    ],
  },
  {
    q: 'What is the treatment of hypertensive emergency? Name drugs used.',
    ans: [
      'Definition: Severe hypertension (>180/120 mmHg) with acute end-organ damage.',
      'Drugs used (IV/parenteral):',
      '  • Sodium nitroprusside - arterial and venous dilator; risk of cyanide toxicity',
      '  • Labetalol (alpha+beta blocker) - drug of choice in most emergencies',
      '  • Nitroglycerin - preferred in hypertension with cardiac ischemia',
      '  • Hydralazine - preferred in eclampsia/pregnancy',
      '  • Fenoldopam - dopamine D1 agonist; preserves renal function',
      '  • Nicardipine - CCB; used in stroke, perioperative hypertension',
      'Goal: Reduce MAP by not more than 25% in first hour.',
    ],
  },
  {
    q: 'Enumerate antihypertensives used in pregnancy and explain why some drugs are contraindicated.',
    ans: [
      'SAFE in pregnancy: Methyldopa (first choice), Labetalol, Nifedipine, Hydralazine',
      'CONTRAINDICATED:',
      '  • ACE inhibitors: Cause fetal renal tubular dysplasia, oligohydramnios, neonatal renal failure, skull ossification defects',
      '  • ARBs: Same teratogenic profile as ACE inhibitors',
      '  • Atenolol: Associated with fetal growth restriction',
      '  • Diuretics: Reduce plasma volume, worsen uteroplacental perfusion',
    ],
  },
];

ahSAQs.forEach((item, i) => saqBlock(i + 1, item.q, item.ans).forEach(p => children.push(p)));

// --- LAQs ---
children.push(pageBreak());
children.push(heading2('LONG ANSWER QUESTIONS (LAQs)'));

const ahLAQs = [
  {
    q: 'Classify antihypertensive drugs. Describe in detail the pharmacology of calcium channel blockers. Add a note on their clinical uses and adverse effects.',
    ans: [
      'CLASSIFICATION: (as above - 9 classes)',
      '',
      'CALCIUM CHANNEL BLOCKERS (CCBs):',
      'Classification:',
      '  1. Dihydropyridines (DHP): Amlodipine, Nifedipine, Felodipine, Nicardipine',
      '     → Selective for vascular smooth muscle',
      '  2. Non-dihydropyridines:',
      '     • Phenylalkylamines: Verapamil → cardiac selective',
      '     • Benzothiazepines: Diltiazem → intermediate',
      '',
      'Mechanism of Action:',
      '  • Block L-type voltage-gated calcium channels',
      '  • Reduce intracellular Ca²⁺ in vascular smooth muscle → vasodilation → ↓ BP',
      '  • In SA and AV nodes (verapamil, diltiazem): reduce heart rate and AV conduction',
      '',
      'Pharmacokinetics:',
      '  • All well absorbed orally; high first-pass metabolism',
      '  • Amlodipine: long half-life (~35-50 hrs), once daily dosing',
      '  • Verapamil: multiple daily doses required',
      '',
      'Clinical Uses:',
      '  • Hypertension (especially DHP types)',
      '  • Angina (stable and vasospastic/Prinzmetal)',
      '  • Supraventricular tachycardias (verapamil, diltiazem)',
      '  • Raynaud phenomenon',
      '  • Safe in COPD, asthma, diabetes, peripheral vascular disease',
      '  • Preferred in elderly, isolated systolic hypertension, Afro-Caribbean patients',
      '',
      'Adverse Effects:',
      '  • DHP: Peripheral edema (most common), flushing, headache, reflex tachycardia',
      '  • Verapamil: Constipation, bradycardia, AV block, negative inotropy',
      '  • Diltiazem: Bradycardia, edema (intermediate profile)',
      '  • Gingival hyperplasia (especially nifedipine)',
      '',
      'Contraindications:',
      '  • Verapamil/Diltiazem: Sick sinus syndrome, heart block, decompensated HF',
      '  • DHP: No major cardiac contraindications',
    ],
  },
  {
    q: 'Discuss the Renin-Angiotensin-Aldosterone System (RAAS) and the pharmacology of drugs acting on it. What are their clinical uses and adverse effects?',
    ans: [
      'THE RAAS:',
      '  Renin (juxtaglomerular cells) → cleaves Angiotensinogen → Ang I',
      '  Ang I + ACE (lung/vascular endothelium) → Ang II',
      '  Ang II: vasoconstriction, aldosterone release, Na/water retention, hypertrophy',
      '',
      'DRUGS ACTING ON RAAS:',
      '',
      '1. ACE INHIBITORS (-pril):',
      '   Examples: Enalapril, Ramipril, Lisinopril, Captopril',
      '   Mechanism: Inhibit ACE → ↓ Ang II → vasodilation + ↓ aldosterone',
      '   Also ↑ bradykinin → vasodilation + cough',
      '   Uses: Hypertension, HF, diabetic nephropathy, post-MI, CKD with proteinuria',
      '   AEs: Cough, angioedema, hyperkalemia, teratogenicity, renal impairment',
      '',
      '2. ARBs (Angiotensin Receptor Blockers) (-sartan):',
      '   Examples: Losartan, Telmisartan, Valsartan, Candesartan',
      '   Mechanism: Block AT1 receptors selectively → ↓ vasoconstriction + ↓ aldosterone',
      '   NO bradykinin effect → no cough; angioedema rare',
      '   Uses: Same as ACE inhibitors; used when ACE inhibitor cough occurs',
      '   AEs: Hyperkalemia, teratogenicity; NO cough',
      '',
      '3. RENIN INHIBITORS:',
      '   Aliskiren: Direct renin inhibitor → ↓ Ang I and Ang II',
      '   Uses: Hypertension (add-on therapy)',
      '   AEs: Diarrhea, hyperkalemia; contraindicated with ACE-I/ARBs in diabetics (renal risk)',
      '',
      '4. ALDOSTERONE ANTAGONISTS:',
      '   Spironolactone, Eplerenone',
      '   Mechanism: Competitive aldosterone receptor blockade → natriuresis, K+ retention',
      '   Uses: Resistant hypertension, HF, primary aldosteronism',
      '   AEs: Hyperkalemia, gynecomastia (spironolactone)',
      '',
      'COMBINATION THERAPY:',
      '  ACE-I + ARB + Aliskiren together are CONTRAINDICATED (excessive RAAS blockade → AKI, hyperkalemia)',
    ],
  },
];

ahLAQs.forEach((item, i) => laqBlock(i + 1, item.q, item.ans).forEach(p => children.push(p)));

// ════════════════════════════════════════════════════════════════════════════
// SECTION 2 – HEART FAILURE
// ════════════════════════════════════════════════════════════════════════════
children.push(pageBreak());
children.push(heading1('SECTION 2: DRUGS USED IN HEART FAILURE'));

// --- MCQs ---
children.push(heading2('MULTIPLE CHOICE QUESTIONS (MCQs)'));

const hfMCQs = [
  { q: 'The first-line drug combination for chronic heart failure with reduced ejection fraction (HFrEF) is:', opts: ['A. Digoxin + Furosemide', 'B. ACE inhibitor + Beta-blocker + Spironolactone', 'C. Amlodipine + Atenolol', 'D. Hydralazine + Nifedipine'], ans: 'B. ACE inhibitor + Beta-blocker + Spironolactone' },
  { q: 'Mechanism of action of digoxin in heart failure:', opts: ['A. Inhibits Na+/K+ ATPase → increased intracellular Ca²⁺', 'B. Activates adenylyl cyclase → increased cAMP', 'C. Blocks beta-1 receptors', 'D. Activates BNP receptors'], ans: 'A. Inhibits Na+/K+ ATPase → increased intracellular Ca²⁺' },
  { q: 'Which drug is used in acute decompensated heart failure as an IV inotrope?', opts: ['A. Carvedilol', 'B. Dobutamine', 'C. Ramipril', 'D. Furosemide'], ans: 'B. Dobutamine' },
  { q: 'Sacubitril (in Sacubitril/Valsartan) acts by:', opts: ['A. Inhibiting ACE', 'B. Inhibiting neprilysin → increased natriuretic peptides', 'C. Blocking AT1 receptor', 'D. Inhibiting aldosterone'], ans: 'B. Inhibiting neprilysin → increased natriuretic peptides' },
  { q: 'Which drug reduces mortality in HFrEF by blocking neurohormonal activation?', opts: ['A. Furosemide', 'B. Digoxin', 'C. Carvedilol', 'D. Dobutamine'], ans: 'C. Carvedilol (beta-blocker with alpha-blocking activity)' },
  { q: 'Digoxin toxicity is precipitated by:', opts: ['A. Hyperkalemia', 'B. Hypokalemia', 'C. Hypernatremia', 'D. Metabolic acidosis'], ans: 'B. Hypokalemia (K+ and digoxin compete for Na+/K+ ATPase binding)' },
  { q: 'SGLT2 inhibitors (e.g. Empagliflozin) in heart failure work by:', opts: ['A. Increasing aldosterone', 'B. Osmotic diuresis, reducing preload, direct cardiac effects', 'C. Increasing cardiac contractility', 'D. Inhibiting ACE'], ans: 'B. Osmotic diuresis, reducing preload, direct cardiac effects' },
  { q: 'Which diuretic is preferred in acute pulmonary edema?', opts: ['A. Hydrochlorothiazide', 'B. Spironolactone', 'C. Furosemide (IV)', 'D. Acetazolamide'], ans: 'C. Furosemide (IV) - rapid diuresis and venodilation' },
  { q: 'Beta-blockers approved for HFrEF include:', opts: ['A. Atenolol, Propranolol', 'B. Carvedilol, Bisoprolol, Metoprolol succinate', 'C. Metoprolol tartrate, Pindolol', 'D. Labetalol, Nebivolol'], ans: 'B. Carvedilol, Bisoprolol, Metoprolol succinate' },
  { q: 'The antidote for digoxin toxicity is:', opts: ['A. Naloxone', 'B. Atropine', 'C. Digoxin-specific antibody fragments (Fab)', 'D. Calcium gluconate'], ans: 'C. Digoxin-specific antibody fragments (Fab)' },
  { q: 'Milrinone acts by:', opts: ['A. Beta-1 agonism', 'B. Inhibiting phosphodiesterase III → increased cAMP', 'C. Blocking adenosine receptors', 'D. Inhibiting Na+/K+ ATPase'], ans: 'B. Inhibiting phosphodiesterase III → increased cAMP' },
  { q: 'Hydralazine + Nitrate combination in heart failure is recommended in:', opts: ['A. All HFrEF patients', 'B. Patients intolerant to ACE inhibitors AND ARBs', 'C. Patients with HFpEF', 'D. Acute heart failure only'], ans: 'B. Patients intolerant to ACE inhibitors AND ARBs (especially self-identified African Americans)' },
  { q: 'Which NYHA class is contraindicated for starting beta-blockers in HF?', opts: ['A. Class I', 'B. Class II', 'C. Class IV (decompensated/wet)', 'D. Class III'], ans: 'C. Class IV (decompensated/wet) - initiate only when patient is stabilized' },
  { q: 'Ivabradine in heart failure acts by:', opts: ['A. Blocking beta receptors', 'B. Inhibiting funny (If) current in SA node → reduces HR', 'C. Inhibiting calcium channels', 'D. Increasing vagal tone'], ans: 'B. Inhibiting funny (If) current in SA node → reduces HR' },
  { q: 'BNP (B-type natriuretic peptide) levels in heart failure are:', opts: ['A. Decreased', 'B. Unchanged', 'C. Elevated (marker of ventricular stress)', 'D. Elevated only in right heart failure'], ans: 'C. Elevated (marker of ventricular stress)' },
];

hfMCQs.forEach((item, i) => mcqBlock(i + 1, item.q, item.opts, item.ans).forEach(p => children.push(p)));

// --- SAQs ---
children.push(pageBreak());
children.push(heading2('SHORT ANSWER QUESTIONS (SAQs)'));

const hfSAQs = [
  {
    q: 'Write a short note on the pharmacology of digoxin.',
    ans: [
      'Source: Digitalis purpurea and D. lanata (foxglove)',
      'Mechanism: Inhibits Na+/K+ ATPase pump → ↑ intracellular Na+ → ↑ intracellular Ca²⁺ via Na+/Ca²⁺ exchanger → positive inotropy',
      'Also: Increases vagal tone → ↓ HR (negative chronotropy), slows AV conduction',
      'Uses: HFrEF (symptom relief), atrial fibrillation (rate control)',
      'Pharmacokinetics: Oral bioavailability 75%; renally excreted; narrow therapeutic index',
      'Toxicity (therapeutic range: 0.5-0.9 ng/mL):',
      '  • GI: Anorexia, nausea, vomiting (earliest signs)',
      '  • CNS: Xanthopsia (yellow vision), confusion',
      '  • Cardiac: Bradycardia, heart block, ventricular arrhythmias',
      'Precipitants of toxicity: Hypokalemia, hypomagnesemia, renal failure, hypothyroidism',
      'Treatment of toxicity: Digoxin-specific Fab antibody fragments',
    ],
  },
  {
    q: 'Describe the role of RAAS inhibitors in heart failure.',
    ans: [
      'In HF: RAAS is chronically activated → Ang II → vasoconstriction, aldosterone → Na/water retention → increased preload/afterload → worsening HF',
      '',
      'ACE Inhibitors (e.g. Enalapril, Ramipril):',
      '  • Reduce Ang II → ↓ afterload + ↓ aldosterone → ↓ preload',
      '  • Reduce cardiac remodeling',
      '  • Proven mortality benefit in HFrEF (CONSENSUS, SOLVD trials)',
      '',
      'ARBs (e.g. Valsartan, Candesartan):',
      '  • Used when ACE inhibitor not tolerated (dry cough)',
      '  • Similar mortality benefit (Val-HeFT, CHARM trials)',
      '',
      'Aldosterone Antagonists (Spironolactone, Eplerenone):',
      '  • Block aldosterone → reduce fibrosis, Na retention',
      '  • Proven mortality benefit in NYHA class III-IV (RALES trial)',
      '  • Monitor K+ levels (risk of hyperkalemia)',
      '',
      'ARNI (Sacubitril/Valsartan):',
      '  • Replaces ACE-I in HFrEF; superior to enalapril (PARADIGM-HF trial)',
      '  • 36-hour washout required before switching from ACE-I',
    ],
  },
  {
    q: 'What are SGLT2 inhibitors? Describe their role in heart failure.',
    ans: [
      'Examples: Empagliflozin (EMPEROR-Reduced trial), Dapagliflozin (DAPA-HF trial)',
      'Primary action: Block SGLT2 in proximal tubule → glucosuria + natriuresis',
      '',
      'Benefits in HF:',
      '  • Reduce hospitalizations for HF and CV mortality',
      '  • Osmotic diuresis → reduces preload',
      '  • Reduce sympathetic activation',
      '  • Direct cardiac effects: reduce myocardial Na+/H+ exchange, reduce cardiac fibrosis',
      '  • Beneficial in both HFrEF and HFpEF',
      '',
      'Side effects: Genitourinary infections, DKA (rare), volume depletion',
      'Now part of "Fantastic Four" of HFrEF: ACE-I/ARB/ARNI + Beta-blocker + MRA + SGLT2i',
    ],
  },
];

hfSAQs.forEach((item, i) => saqBlock(i + 1, item.q, item.ans).forEach(p => children.push(p)));

// --- LAQs ---
children.push(pageBreak());
children.push(heading2('LONG ANSWER QUESTIONS (LAQs)'));

const hfLAQs = [
  {
    q: 'Classify drugs used in chronic heart failure. Discuss the pharmacology, mechanism, clinical uses and adverse effects of drugs that reduce mortality in HFrEF.',
    ans: [
      'CLASSIFICATION OF DRUGS IN HEART FAILURE:',
      '',
      'A. Drugs that reduce mortality (disease-modifying):',
      '   1. ACE inhibitors / ARBs / ARNI',
      '   2. Beta-blockers (Carvedilol, Bisoprolol, Metoprolol succinate)',
      '   3. Mineralocorticoid receptor antagonists (Spironolactone, Eplerenone)',
      '   4. SGLT2 inhibitors (Empagliflozin, Dapagliflozin)',
      '',
      'B. Drugs that relieve symptoms:',
      '   1. Diuretics: Furosemide, Hydrochlorothiazide, Spironolactone',
      '   2. Digoxin',
      '   3. Ivabradine',
      '   4. Hydralazine + Nitrates',
      '',
      'C. Drugs for acute decompensated HF:',
      '   1. IV diuretics (Furosemide)',
      '   2. Inotropes: Dobutamine, Milrinone, Levosimendan',
      '   3. Vasopressors: Norepinephrine (if hypotension)',
      '   4. Nesiritide (recombinant BNP)',
      '',
      'BETA-BLOCKERS IN HFrEF (Detailed):',
      '',
      'Approved agents: Carvedilol (α1+β1+β2), Bisoprolol (β1 selective), Metoprolol succinate (β1 selective)',
      '',
      'Mechanism:',
      '  • Block excessive sympathetic activation in HF → ↓ tachycardia, ↓ arrhythmias',
      '  • ↓ myocardial O2 demand',
      '  • Reduce cardiac remodeling (↑ EF over months)',
      '  • Anti-apoptotic effects on cardiomyocytes',
      '  • Improve beta-receptor density (upregulation)',
      '',
      'Clinical evidence:',
      '  • COPERNICUS (carvedilol): 35% mortality reduction in severe HF',
      '  • CIBIS-II (bisoprolol): 34% mortality reduction',
      '  • MERIT-HF (metoprolol): 34% mortality reduction',
      '',
      'Important note: Start at LOW dose; do NOT start in decompensated/fluid-overloaded patient',
      '  Titrate up slowly over weeks to months',
      '',
      'Adverse effects: Bradycardia, fatigue, hypotension, worsening HF (initial), bronchospasm (non-selective)',
      '',
      'SACUBITRIL/VALSARTAN (ARNI):',
      '',
      'Mechanism:',
      '  • Valsartan: AT1 blocker → reduces Ang II effects',
      '  • Sacubitril: Neprilysin inhibitor → ↑ ANP, BNP, bradykinin → vasodilation + natriuresis',
      '  • Dual action: reduces neurohormonal activation + increases natriuretic peptides',
      '',
      'Clinical use: Replaces ACE-I in HFrEF patients (EF ≤40%) who remain symptomatic',
      'Evidence: PARADIGM-HF trial → 20% reduction in CV death vs enalapril',
      '',
      'Key precaution: 36-hour washout period required when switching from ACE-I (risk of angioedema)',
      'Contraindicated with ACE-I (do not use together)',
      '',
      'Adverse effects: Hypotension, hyperkalemia, angioedema, renal impairment',
    ],
  },
];

hfLAQs.forEach((item, i) => laqBlock(i + 1, item.q, item.ans).forEach(p => children.push(p)));

// ════════════════════════════════════════════════════════════════════════════
// SECTION 3 – ANGINA
// ════════════════════════════════════════════════════════════════════════════
children.push(pageBreak());
children.push(heading1('SECTION 3: DRUGS USED IN ANGINA'));

// --- MCQs ---
children.push(heading2('MULTIPLE CHOICE QUESTIONS (MCQs)'));

const anginaMCQs = [
  { q: 'Drug of choice for acute attack of stable angina:', opts: ['A. Isosorbide mononitrate (oral)', 'B. Sublingual nitroglycerin', 'C. Atenolol', 'D. Amlodipine'], ans: 'B. Sublingual nitroglycerin (rapid onset, 1-3 minutes)' },
  { q: 'Mechanism of antianginal action of nitrates:', opts: ['A. Reduce heart rate', 'B. Release NO → activate guanylyl cyclase → ↑ cGMP → venodilation → ↓ preload', 'C. Block calcium channels', 'D. Reduce renin secretion'], ans: 'B. Release NO → activate guanylyl cyclase → ↑ cGMP → venodilation → ↓ preload' },
  { q: 'Drug of choice for Prinzmetal (vasospastic) angina:', opts: ['A. Beta-blockers', 'B. Digoxin', 'C. Calcium channel blockers (Nifedipine/Amlodipine)', 'D. Aspirin alone'], ans: 'C. Calcium channel blockers (Nifedipine/Amlodipine)' },
  { q: 'Nitrate tolerance is prevented by:', opts: ['A. Using long-acting nitrates continuously', 'B. Providing nitrate-free interval of 8-12 hours', 'C. Combining with verapamil', 'D. Using IV route only'], ans: 'B. Providing nitrate-free interval of 8-12 hours' },
  { q: 'Beta-blockers reduce anginal attacks by:', opts: ['A. Coronary vasodilation', 'B. Decreasing HR, contractility, and afterload → ↓ myocardial O2 demand', 'C. Increasing coronary blood flow', 'D. Dilating peripheral veins'], ans: 'B. Decreasing HR, contractility, and afterload → ↓ myocardial O2 demand' },
  { q: 'Ranolazine is a newer antianginal drug that acts by:', opts: ['A. Blocking L-type calcium channels', 'B. Blocking late sodium current (INa) → ↓ diastolic Ca²⁺ overload', 'C. Opening potassium channels', 'D. Inhibiting phosphodiesterase'], ans: 'B. Blocking late sodium current (INa) → ↓ diastolic Ca²⁺ overload' },
  { q: 'Nitroglycerin is stored in tightly closed glass containers because:', opts: ['A. It reacts with plastic due to volatility and adsorption', 'B. It is light sensitive', 'C. It reacts with atmospheric oxygen', 'D. It is water sensitive'], ans: 'A. It reacts with plastic due to volatility and adsorption' },
  { q: 'Which antianginal drug is contraindicated in Prinzmetal angina?', opts: ['A. Amlodipine', 'B. Nifedipine', 'C. Non-selective beta-blockers (e.g. Propranolol)', 'D. Diltiazem'], ans: 'C. Non-selective beta-blockers (e.g. Propranolol) - may worsen coronary spasm' },
  { q: 'The mechanism by which beta-blockers increase exercise tolerance in angina:', opts: ['A. Dilate coronary arteries directly', 'B. ↓ HR and contractility → ↓ O2 demand, allowing more work before ischemia threshold', 'C. Increase collateral circulation', 'D. Reduce platelet aggregation'], ans: 'B. ↓ HR and contractility → ↓ O2 demand, allowing more work before ischemia threshold' },
  { q: 'Amlodipine is preferred over verapamil in angina in patients with:',  opts: ['A. Atrial fibrillation', 'B. Supraventricular tachycardia', 'C. Heart failure (HFrEF)', 'D. Raynaud syndrome'], ans: 'C. Heart failure (HFrEF) - verapamil is negatively inotropic and contraindicated' },
  { q: 'Oral bioavailability of nitroglycerin is low (<10%) due to:', opts: ['A. Poor intestinal absorption', 'B. High first-pass hepatic metabolism (organic nitrate reductase)', 'C. Extensive protein binding', 'D. Renal excretion before systemic circulation'], ans: 'B. High first-pass hepatic metabolism (organic nitrate reductase)' },
  { q: 'Which combination is NOT appropriate in angina?', opts: ['A. Beta-blocker + long-acting nitrate', 'B. Beta-blocker + amlodipine', 'C. Verapamil + beta-blocker', 'D. Nitroglycerin + amlodipine'], ans: 'C. Verapamil + beta-blocker (both reduce HR and AV conduction → risk of complete heart block)' },
  { q: 'Trimetazidine in angina acts by:', opts: ['A. Vasodilation of coronary arteries', 'B. Inhibiting fatty acid oxidation → shifts metabolism to glucose oxidation (more efficient)', 'C. Reducing heart rate', 'D. Blocking calcium channels'], ans: 'B. Inhibiting fatty acid oxidation → shifts metabolism to glucose oxidation (more efficient)' },
  { q: 'Isosorbide mononitrate (ISMN) compared to isosorbide dinitrate (ISDN):', opts: ['A. Requires hepatic activation; less bioavailable', 'B. Does not require hepatic activation; 100% bioavailability', 'C. Only available as sublingual formulation', 'D. Has shorter duration of action'], ans: 'B. Does not require hepatic activation; 100% bioavailability' },
  { q: 'Sildenafil is absolutely contraindicated with nitrates because:', opts: ['A. Both cause tachycardia', 'B. Both inhibit PDE5 causing excessive cGMP accumulation → severe hypotension', 'C. Combined they cause renal failure', 'D. They cause serotonin syndrome'], ans: 'B. Both inhibit PDE5 causing excessive cGMP accumulation → severe hypotension' },
];

anginaMCQs.forEach((item, i) => mcqBlock(i + 1, item.q, item.opts, item.ans).forEach(p => children.push(p)));

// --- SAQs ---
children.push(pageBreak());
children.push(heading2('SHORT ANSWER QUESTIONS (SAQs)'));

const anginaSAQs = [
  {
    q: 'Write the mechanism of action, uses, and adverse effects of organic nitrates.',
    ans: [
      'Examples: Nitroglycerin (GTN), Isosorbide dinitrate (ISDN), Isosorbide mononitrate (ISMN), Amyl nitrite',
      '',
      'Mechanism:',
      '  • Denitration in vascular smooth muscle → release of nitric oxide (NO)',
      '  • NO activates soluble guanylyl cyclase → ↑ cGMP → activation of cGMP-dependent kinase',
      '  • Phosphorylation of myosin light chain kinase → smooth muscle relaxation',
      '  • At lower doses: primarily venodilation → ↓ preload (↓ LVEDP)',
      '  • At higher doses: arterial dilation → ↓ afterload',
      '  • In coronary arteries: dilate large epicardial vessels + collateral vessels',
      '',
      'Uses:',
      '  • Acute anginal attack (SL nitroglycerin)',
      '  • Prophylaxis of angina (long-acting nitrates)',
      '  • Acute MI (IV nitroglycerin)',
      '  • Acute LVF / pulmonary edema',
      '  • Esophageal spasm',
      '  • Anal fissure (topical GTN 0.2%)',
      '',
      'Adverse effects:',
      '  • Headache (most common - due to meningeal vessel dilation)',
      '  • Postural hypotension, dizziness, flushing',
      '  • Reflex tachycardia',
      '  • Tolerance (with continuous use; prevented by nitrate-free interval)',
      '  • Methemoglobinemia (high doses, especially amyl nitrite)',
      '',
      'Contraindication: Concurrent use of PDE5 inhibitors (sildenafil, tadalafil) - risk of severe hypotension',
    ],
  },
  {
    q: 'Classify antianginal drugs. What is the treatment of stable angina?',
    ans: [
      'CLASSIFICATION:',
      '1. Nitrates: GTN (sublingual, transdermal, IV), ISDN, ISMN, Amyl nitrite',
      '2. Beta-blockers: Atenolol, Metoprolol, Propranolol, Carvedilol',
      '3. Calcium channel blockers: Amlodipine, Nifedipine, Verapamil, Diltiazem',
      '4. Newer antianginals: Ranolazine, Trimetazidine, Ivabradine, Nicorandil',
      '5. Anti-platelet/Anti-ischemic: Aspirin, Statins (for underlying CAD)',
      '',
      'TREATMENT OF STABLE ANGINA:',
      'Acute attack: Sublingual nitroglycerin 0.3-0.6 mg (repeat every 5 min, max 3 doses)',
      '',
      'Prophylaxis:',
      '  • First line: Beta-blocker (atenolol/metoprolol) + low-dose aspirin + statin',
      '  • Add long-acting nitrate (ISMN) or CCB if not controlled',
      '  • If beta-blocker contraindicated: use CCB (amlodipine or diltiazem)',
      '  • Ranolazine: add-on if still symptomatic',
      '',
      'Modify risk factors: Treat hypertension, diabetes, dyslipidemia, smoking cessation',
    ],
  },
];

anginaSAQs.forEach((item, i) => saqBlock(i + 1, item.q, item.ans).forEach(p => children.push(p)));

// --- LAQs ---
children.push(pageBreak());
children.push(heading2('LONG ANSWER QUESTIONS (LAQs)'));

const anginaLAQs = [
  {
    q: 'Classify antianginal drugs. Describe in detail the pharmacology of beta-blockers in angina. Compare the three types of angina and their drug management.',
    ans: [
      'CLASSIFICATION OF ANTIANGINAL DRUGS: (see SAQ above)',
      '',
      'BETA-BLOCKERS IN ANGINA:',
      '',
      'Mechanism:',
      '  • Competitive blockade of beta-1 (and beta-2 for non-selective) receptors',
      '  • ↓ HR (chronotropy) → more time for diastolic coronary perfusion',
      '  • ↓ Contractility (inotropy) → ↓ myocardial O2 consumption',
      '  • ↓ BP (afterload) → ↓ wall tension → ↓ O2 demand',
      '  • Increase diastolic filling time → better subendocardial perfusion',
      '',
      'Examples in angina:',
      '  • Atenolol 25-100 mg OD (cardioselective)',
      '  • Metoprolol 25-100 mg BD (cardioselective)',
      '  • Propranolol (non-selective; also useful in hypertensive heart disease)',
      '',
      'Contraindications in angina:',
      '  • Asthma / COPD (use cardioselective with caution)',
      '  • Prinzmetal angina (may worsen vasospasm via unopposed alpha stimulation)',
      '  • Significant bradycardia, high-degree AV block',
      '  • Severe peripheral arterial disease',
      '',
      '─────────────────────────────────────────────────────────────',
      'COMPARISON: THREE TYPES OF ANGINA',
      '─────────────────────────────────────────────────────────────',
      '',
      '1. STABLE ANGINA (Effort angina):',
      '   Pathophysiology: Fixed atherosclerotic plaque → demand ischemia on exertion',
      '   Trigger: Physical exertion, cold, emotional stress',
      '   ECG: ST depression during attack (subendocardial ischemia)',
      '   Treatment:',
      '     Acute: SL nitroglycerin',
      '     Prophylaxis: Beta-blocker (1st choice) + aspirin + statin',
      '     Add-on: Long-acting nitrate or CCB; Ranolazine if refractory',
      '',
      '2. UNSTABLE ANGINA (ACS):',
      '   Pathophysiology: Plaque rupture → partial thrombosis → dynamic obstruction',
      '   Trigger: At rest or minimal exertion',
      '   ECG: ST depression or T-wave changes at rest',
      '   Treatment:',
      '     Anti-thrombotic: Aspirin + P2Y12 inhibitor (Clopidogrel/Ticagrelor)',
      '     Anticoagulant: Heparin (LMWH/UFH)',
      '     Anti-ischemic: Beta-blocker + SL nitroglycerin + statin',
      '     Revascularization (PCI) for high-risk features',
      '',
      '3. PRINZMETAL (Vasospastic) ANGINA:',
      '   Pathophysiology: Focal coronary artery spasm → transmural ischemia',
      '   Trigger: At rest, early morning; may be induced by smoking, cocaine',
      '   ECG: ST elevation during attack (transmural ischemia)',
      '   Treatment:',
      '     First choice: Calcium channel blockers (Amlodipine, Diltiazem, Verapamil)',
      '     Second: Long-acting nitrates',
      '     AVOID: Beta-blockers (non-selective block → unopposed alpha → ↑ spasm)',
      '     AVOID: Aspirin (high dose aspirin may inhibit prostacyclin → spasm)',
    ],
  },
];

anginaLAQs.forEach((item, i) => laqBlock(i + 1, item.q, item.ans).forEach(p => children.push(p)));

// ════════════════════════════════════════════════════════════════════════════
// SECTION 4 – HEMATINICS
// ════════════════════════════════════════════════════════════════════════════
children.push(pageBreak());
children.push(heading1('SECTION 4: HEMATINICS'));

// --- MCQs ---
children.push(heading2('MULTIPLE CHOICE QUESTIONS (MCQs)'));

const hemMCQs = [
  { q: 'Iron is primarily absorbed in which part of the GI tract?', opts: ['A. Stomach', 'B. Duodenum and proximal jejunum', 'C. Ileum', 'D. Colon'], ans: 'B. Duodenum and proximal jejunum' },
  { q: 'The form of iron absorbed by intestinal enterocytes is:', opts: ['A. Ferric (Fe³⁺)', 'B. Ferrous (Fe²⁺)', 'C. Transferrin-bound iron', 'D. Heme iron directly as ferric'], ans: 'B. Ferrous (Fe²⁺) - via DMT-1 (divalent metal transporter 1)' },
  { q: 'Vitamin C enhances iron absorption by:', opts: ['A. Forming chelates with iron', 'B. Reducing Fe³⁺ to Fe²⁺ and preventing iron precipitation', 'C. Increasing gastric pH', 'D. Stimulating erythropoietin'], ans: 'B. Reducing Fe³⁺ to Fe²⁺ and preventing iron precipitation' },
  { q: 'The most common cause of iron deficiency anemia in women of reproductive age:', opts: ['A. Poor dietary intake only', 'B. Chronic blood loss (menstruation)', 'C. Malabsorption syndrome', 'D. Chronic inflammation'], ans: 'B. Chronic blood loss (menstruation)' },
  { q: 'Expected rise in hemoglobin with oral iron therapy:', opts: ['A. 0.1-0.2 g/dL/week', 'B. 1-2 g/dL/week', 'C. 0.5-1 g/dL/day', 'D. 2-3 g/dL/week'], ans: 'A. 1-2 g/dL per week (approximately)' },
  { q: 'Which preparation is used for IV iron therapy?', opts: ['A. Ferrous sulfate', 'B. Ferrous gluconate', 'C. Iron sucrose / Ferric carboxymaltose', 'D. Carbonyl iron'], ans: 'C. Iron sucrose / Ferric carboxymaltose' },
  { q: 'The characteristic blood picture in folic acid deficiency is:', opts: ['A. Microcytic hypochromic anemia', 'B. Normocytic normochromic anemia', 'C. Macrocytic megaloblastic anemia', 'D. Hemolytic anemia with spherocytes'], ans: 'C. Macrocytic megaloblastic anemia' },
  { q: 'Folic acid is converted to its active form by:', opts: ['A. Vitamin B12-dependent methionine synthase', 'B. Dihydrofolate reductase (DHFR) → tetrahydrofolate (THF)', 'C. Thymidylate synthase', 'D. Intrinsic factor'], ans: 'B. Dihydrofolate reductase (DHFR) → tetrahydrofolate (THF)' },
  { q: 'Intrinsic factor (IF) is secreted by:', opts: ['A. Chief cells of stomach', 'B. Parietal cells of stomach', 'C. Brunner glands of duodenum', 'D. Goblet cells of ileum'], ans: 'B. Parietal cells of stomach' },
  { q: 'Vitamin B12 deficiency causes subacute combined degeneration of spinal cord because B12 is needed for:', opts: ['A. DNA synthesis in neurons', 'B. Myelin synthesis (via methylmalonyl-CoA → succinyl-CoA conversion)', 'C. Heme synthesis', 'D. Iron absorption'], ans: 'B. Myelin synthesis (via methylmalonyl-CoA → succinyl-CoA conversion)' },
  { q: 'Treatment of pernicious anemia requires:', opts: ['A. Oral folic acid', 'B. IM injection of cyanocobalamin (Vitamin B12) lifelong', 'C. Oral ferrous sulfate', 'D. IV iron therapy'], ans: 'B. IM injection of cyanocobalamin (Vitamin B12) lifelong (as IF is absent, oral B12 not absorbed)' },
  { q: 'Erythropoietin is used in anemia associated with:', opts: ['A. Iron deficiency', 'B. Vitamin B12 deficiency', 'C. Chronic kidney disease', 'D. Thalassemia'], ans: 'C. Chronic kidney disease (deficient EPO production)' },
  { q: 'Folic acid supplementation is recommended before and during early pregnancy to prevent:', opts: ['A. Iron deficiency anemia', 'B. Neural tube defects (spina bifida, anencephaly)', 'C. Pernicious anemia', 'D. Sickle cell crisis'], ans: 'B. Neural tube defects (spina bifida, anencephaly)' },
  { q: 'Acute iron poisoning treatment includes:', opts: ['A. Naloxone', 'B. Desferrioxamine (chelation therapy)', 'C. Dimercaprol (BAL)', 'D. Sodium bicarbonate'], ans: 'B. Desferrioxamine (chelation therapy)' },
  { q: 'Which drug inhibits folic acid synthesis and is used as a chemotherapeutic/antifolate?', opts: ['A. Metformin', 'B. Methotrexate (DHFR inhibitor)', 'C. Mesalazine', 'D. Methyldopa'], ans: 'B. Methotrexate (DHFR inhibitor) - can cause megaloblastic anemia' },
];

hemMCQs.forEach((item, i) => mcqBlock(i + 1, item.q, item.opts, item.ans).forEach(p => children.push(p)));

// --- SAQs ---
children.push(pageBreak());
children.push(heading2('SHORT ANSWER QUESTIONS (SAQs)'));

const hemSAQs = [
  {
    q: 'Describe the pharmacokinetics and therapeutic use of iron in iron deficiency anemia.',
    ans: [
      'PREPARATIONS:',
      '  Oral: Ferrous sulfate (most common), Ferrous gluconate, Ferrous fumarate, Carbonyl iron',
      '  Parenteral: Iron sucrose, Ferric carboxymaltose, Iron dextran',
      '',
      'PHARMACOKINETICS:',
      '  Absorption:',
      '    • Ferrous (Fe²⁺) form absorbed via DMT-1 in duodenum/jejunum',
      '    • Heme iron (meat) absorbed separately, more efficiently (~25%)',
      '    • Non-heme iron absorption: 5-10%',
      '    • Enhanced by: Vitamin C, acidic pH, meat, fasting state',
      '    • Reduced by: Phytates, tannins (tea/coffee), antacids, calcium, H2-blockers, tetracyclines',
      '  Distribution:',
      '    • Absorbed into blood → bound to transferrin → transported to bone marrow',
      '    • Stored as ferritin and hemosiderin (liver, spleen, bone marrow)',
      '  Excretion: No active excretion; lost only through blood loss, exfoliation of cells',
      '',
      'THERAPEUTIC USE:',
      '  Dose: Ferrous sulfate 325 mg (65 mg elemental iron) 2-3 times daily',
      '  Duration: 3-6 months (3 months to correct anemia + 3 months to replenish stores)',
      '  Monitor: Hb rise ~1-2 g/dL/week; reticulocytosis within 7-10 days',
      '',
      'ADVERSE EFFECTS (oral iron):',
      '  • GI: Nausea, constipation, dark stools, epigastric pain (most common)',
      '  • Take after meals to reduce GI side effects (but reduces absorption)',
      '  • Liquid iron: may stain teeth (use straw)',
      '',
      'PARENTERAL IRON:',
      '  Indications: Malabsorption, intolerance to oral iron, rapid repletion needed, IBD',
      '  Risk: Anaphylaxis (especially iron dextran); test dose required',
    ],
  },
  {
    q: 'Write a note on Vitamin B12 (Cyanocobalamin): sources, absorption, deficiency, and treatment.',
    ans: [
      'SOURCES: Animal products (meat, fish, eggs, dairy); absent in strict vegan diet',
      '',
      'ABSORPTION:',
      '  • B12 released from food by gastric acid and pepsin',
      '  • Binds to Intrinsic Factor (IF) secreted by gastric parietal cells',
      '  • B12-IF complex absorbed in terminal ileum via cubilin receptors',
      '  • Stored in liver (up to 3-5 year supply)',
      '',
      'FUNCTION:',
      '  • Cofactor for Methionine synthase: Homocysteine → Methionine (requires methylcobalamin)',
      '    - Also regenerates THF from methylTHF → needed for DNA synthesis',
      '  • Cofactor for Methylmalonyl-CoA mutase: Methylmalonyl-CoA → Succinyl-CoA',
      '    - Deficiency → methylmalonyl-CoA accumulates → abnormal myelin → SACD',
      '',
      'DEFICIENCY CAUSES:',
      '  • Pernicious anemia (autoimmune destruction of parietal cells → ↓ IF)',
      '  • Strict vegetarian/vegan diet',
      '  • Gastrectomy, terminal ileum resection, Crohn disease',
      '  • Metformin (impairs absorption), Prolonged PPI use',
      '  • Fish tapeworm (Diphyllobothrium latum)',
      '',
      'CLINICAL FEATURES:',
      '  • Megaloblastic anemia (macrocytic, hypersegmented neutrophils)',
      '  • Glossitis, angular stomatitis',
      '  • Subacute Combined Degeneration of Spinal Cord (SACD):',
      '    - Posterior columns (loss of vibration/proprioception)',
      '    - Lateral corticospinal tracts (upper motor neuron signs)',
      '  • Dementia, psychiatric changes',
      '  • Note: Folic acid deficiency does NOT cause SACD',
      '',
      'TREATMENT:',
      '  • Pernicious anemia: IM cyanocobalamin 1000 mcg daily for 7 days, then weekly for 4 weeks, then monthly LIFELONG',
      '  • Dietary deficiency: Oral cyanocobalamin 1000-2000 mcg daily (high-dose oral can achieve passive absorption)',
      '  • Important: Correct B12 BEFORE giving folic acid (treating with folate alone may worsen SACD)',
    ],
  },
  {
    q: 'Write a note on folic acid: its role, deficiency, and uses in clinical practice.',
    ans: [
      'SOURCES: Green leafy vegetables, legumes, liver, cereals (dietary folate)',
      '  Body stores: 5-10 mg (lasts only 3-4 months)',
      '',
      'ABSORPTION: Proximal small intestine (jejunum); converted to methyltetrahydrofolate in blood',
      '',
      'ACTIVE FORM: Tetrahydrofolate (THF) - generated by dihydrofolate reductase (DHFR)',
      '',
      'FUNCTIONS:',
      '  • DNA synthesis: THF donates one-carbon units for purine and thymidylate synthesis',
      '  • Amino acid metabolism: Homocysteine → Methionine (with B12)',
      '  • Neural tube development in embryo',
      '',
      'DEFICIENCY CAUSES:',
      '  • Poor dietary intake (most common)',
      '  • Malabsorption (celiac disease)',
      '  • Drugs: Methotrexate, Trimethoprim, Phenytoin (impair DHFR or absorption)',
      '  • Increased demand: Pregnancy, hemolytic anemia, dialysis',
      '',
      'CLINICAL FEATURES:',
      '  • Megaloblastic anemia (identical blood picture to B12 deficiency)',
      '  • Glossitis',
      '  • Neural tube defects in fetus (if deficient periconceptionally)',
      '  • No neurological deficits (unlike B12 deficiency)',
      '',
      'USES:',
      '  • Prevention of NTDs: 400-800 mcg daily starting 1 month before conception and through first trimester',
      '    (High-risk women - previous NTD, on antiepileptics: 5 mg/day)',
      '  • Treatment of megaloblastic anemia (5 mg OD for 4 months)',
      '  • Leucovorin (folinic acid): used to rescue normal cells from methotrexate toxicity',
    ],
  },
];

hemSAQs.forEach((item, i) => saqBlock(i + 1, item.q, item.ans).forEach(p => children.push(p)));

// --- LAQs ---
children.push(pageBreak());
children.push(heading2('LONG ANSWER QUESTIONS (LAQs)'));

const hemLAQs = [
  {
    q: 'Classify hematinics. Discuss in detail the pharmacology of iron: mechanism of absorption, oral and parenteral preparations, adverse effects, and treatment of iron toxicity.',
    ans: [
      'CLASSIFICATION OF HEMATINICS:',
      '',
      '1. Iron preparations:',
      '   Oral: Ferrous sulfate, Ferrous gluconate, Ferrous fumarate, Carbonyl iron',
      '   Parenteral: Iron sucrose, Ferric carboxymaltose, Iron dextran, Ferumoxytol',
      '',
      '2. Vitamin B12 (Cyanocobalamin, Hydroxocobalamin)',
      '',
      '3. Folic acid (Folate, Folinic acid/Leucovorin)',
      '',
      '4. Erythropoiesis-stimulating agents:',
      '   Erythropoietin (EPO), Darbepoetin alfa, Epoetin alfa',
      '',
      '5. Others: Pyridoxine (sideroblastic anemia), Hydroxycarbamide (sickle cell)',
      '',
      '─────────────────────────────────────────────────────────────',
      'IRON - DETAILED PHARMACOLOGY:',
      '─────────────────────────────────────────────────────────────',
      '',
      'MECHANISM OF ABSORPTION:',
      '',
      'Step 1 – Luminal reduction:',
      '  • Dietary ferric iron (Fe³⁺) → reduced to Fe²⁺ by ferrireductase (Dcytb) at brush border',
      '  • Vitamin C and gastric acid facilitate this reduction',
      '',
      'Step 2 – Enterocyte uptake:',
      '  • Fe²⁺ enters enterocyte via DMT-1 (Divalent Metal Transporter 1)',
      '  • Heme iron: absorbed via heme carrier protein (HCP-1) → haem oxygenase releases Fe inside cell',
      '',
      'Step 3 – Intracellular storage or export:',
      '  • Stored as ferritin (mucosal block - lost when enterocyte exfoliates)',
      '  • Exported to blood via ferroportin (basolateral transporter)',
      '',
      'Step 4 – Oxidation and binding in plasma:',
      '  • Fe²⁺ → Fe³⁺ by hephaestin/ceruloplasmin',
      '  • Fe³⁺ binds to transferrin (plasma carrier) → delivered to bone marrow',
      '',
      'Regulation: Hepcidin (liver peptide) degrades ferroportin → reduces iron absorption in iron-replete states',
      '',
      'FACTORS AFFECTING ABSORPTION:',
      '  Enhance:',
      '    • Ascorbic acid (Vitamin C) - reduces Fe³⁺ to Fe²⁺',
      '    • Meat (heme iron - 25% absorbed)',
      '    • Fasting, iron deficiency state, increased erythropoiesis',
      '    • Acidic pH (gastric acid)',
      '  Inhibit:',
      '    • Phytates (cereals, legumes), oxalates, tannins (tea, coffee)',
      '    • Calcium, phosphates',
      '    • Antacids, H2 blockers, PPIs (↑ pH)',
      '    • Tetracyclines, quinolones (chelation in gut)',
      '    • Hepcidin (iron overload states)',
      '',
      'ORAL PREPARATIONS:',
      '  • Ferrous sulfate: 60-65 mg elemental iron per 325 mg tablet; cheapest and most widely used',
      '  • Ferrous gluconate: 35-37 mg elemental iron per 325 mg; better tolerated',
      '  • Ferrous fumarate: 106 mg elemental iron per 325 mg; high elemental iron content',
      '  • Carbonyl iron: slow release; lower risk of acute toxicity',
      '',
      '  Standard adult dose: 150-200 mg elemental iron/day in divided doses',
      '  Best absorbed: Empty stomach (1 hour before or 2 hours after food)',
      '  Duration: 3 months to correct anemia + 3 months to replenish stores = minimum 6 months',
      '  Monitoring: Reticulocytosis in 5-10 days; Hb rise 1-2 g/dL/week',
      '',
      'PARENTERAL IRON:',
      '  Indications:',
      '    • Malabsorption (celiac, Crohn disease)',
      '    • Intolerance to oral iron',
      '    • Non-compliance with oral therapy',
      '    • Severe iron deficiency requiring rapid repletion',
      '    • Functional iron deficiency in CKD with EPO therapy',
      '    • IBD (oral iron may worsen symptoms)',
      '',
      '  Preparations and routes:',
      '    • Iron sucrose (IV only): Low risk of anaphylaxis; preferred in CKD',
      '    • Ferric carboxymaltose (IV): Can give large doses (up to 1000 mg) at once; safe',
      '    • Iron dextran (IV or IM): Highest anaphylaxis risk; test dose mandatory',
      '    • Ferumoxytol (IV): Approved in USA for CKD',
      '',
      '  Adverse effects of parenteral iron:',
      '    • Anaphylaxis / hypersensitivity (especially iron dextran)',
      '    • Flushing, headache, myalgia, fever (infusion reaction)',
      '    • Hypotension',
      '    • Local pain, skin staining with IM injection (Z-track technique used)',
      '    • Hemosiderosis with overtreatment',
      '',
      'ADVERSE EFFECTS OF ORAL IRON:',
      '  • Nausea, vomiting, epigastric discomfort (most common)',
      '  • Constipation (dark tarry stools → may mask melena)',
      '  • Diarrhea (occasionally)',
      '  • Liquid iron stains teeth (use straw, rinse mouth)',
      '',
      '─────────────────────────────────────────────────────────────',
      'ACUTE IRON TOXICITY (OVERDOSE):',
      '─────────────────────────────────────────────────────────────',
      '',
      'Common in children ingesting adult iron tablets',
      '',
      'Stages:',
      '  Stage 1 (0.5-6 hrs): GI - nausea, vomiting, abdominal pain, hematemesis, bloody diarrhea',
      '  Stage 2 (6-24 hrs): Apparent recovery (may miss this stage clinically)',
      '  Stage 3 (12-48 hrs): Systemic toxicity - metabolic acidosis, shock, coma, hepatic failure',
      '  Stage 4 (2-6 wks): GI scarring - pyloric stenosis, bowel obstruction',
      '',
      'Treatment:',
      '  1. Gastric lavage (if recent ingestion)',
      '  2. Desferrioxamine (Deferoxamine) IV - chelates free iron → ferrioxamine excreted in urine (orange-red "vin rose" urine)',
      '     Dose: 15 mg/kg/hr IV',
      '  3. Supportive: IV fluids, correct acidosis',
      '  4. Oral deferiprone or subcutaneous deferoxamine: for chronic iron overload (thalassemia)',
      '',
      'CHRONIC IRON OVERLOAD (Hemochromatosis):',
      '  • Primary: HFE gene mutation',
      '  • Secondary: Repeated transfusions (thalassemia, sickle cell)',
      '  • Treatment: Phlebotomy (primary), Iron chelators (desferrioxamine, deferasirox, deferiprone)',
    ],
  },
];

hemLAQs.forEach((item, i) => laqBlock(i + 1, item.q, item.ans).forEach(p => children.push(p)));

// ─── FOOTER NOTE ────────────────────────────────────────────────────────────
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const revisionTable = [
  '► GTN (Nitroglycerin): Releases NO → ↑ cGMP → venodilation. Route: Sublingual (avoids first-pass). Use: Acute angina.',
  '► ACE Inhibitors: Inhibit ACE → ↓ Ang II → vasodilation + ↓ aldosterone. SE: Cough (bradykinin), Angioedema, Teratogenic.',
  '► ARBs: Block AT1 receptor. No cough. Same as ACE-I but NO bradykinin effect.',
  '► Amlodipine (CCB): Blocks L-Ca²⁺ channels in vascular SM → vasodilation. Safe in asthma, diabetes, pregnancy (not 1st trimester).',
  '► Digoxin: Inhibits Na+/K+ ATPase → ↑ intracellular Ca²⁺ → +ve inotropy. Toxicity precipitated by hypokalemia. Antidote: Fab antibody.',
  '► Furosemide: Loop diuretic → blocks Na+/K+/2Cl- in LOH. IV for acute pulmonary edema.',
  '► Spironolactone: Aldosterone antagonist → reduces cardiac fibrosis. Mortality benefit in HF (RALES trial). Monitor K+.',
  '► Sacubitril/Valsartan (ARNI): Neprilysin inhibitor + AT1 blocker → ↑ natriuretic peptides. Superior to ACE-I in HFrEF.',
  '► SGLT2 inhibitors: Osmotic diuresis, ↓ preload, direct cardiac benefit. Used in HFrEF and HFpEF.',
  '► Ferrous Sulfate: Oral iron. Absorbed as Fe²⁺ via DMT-1. Enhanced by Vit C. SE: Constipation, dark stools.',
  '► Desferrioxamine: Iron chelator. Treatment of acute iron poisoning and chronic iron overload.',
  '► Vitamin B12 (Cyanocobalamin): Required for myelin synthesis. Pernicious anemia → IM injections lifelong.',
  '► Folic Acid: Required for DNA synthesis. Prevents NTDs. Deficiency → Megaloblastic anemia (no SACD). Drug: Methotrexate inhibits DHFR → folic acid deficiency.',
  '► Methyldopa: Central alpha-2 agonist. Drug of choice for hypertension in pregnancy.',
  '► Hydralazine: Arteriolar dilator. SE: Reflex tachycardia, lupus-like syndrome. Used in hypertensive emergencies in pregnancy.',
];

revisionTable.forEach(line => children.push(para(line)));

// ─── DOCUMENT CREATION ───────────────────────────────────────────────────────
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~/cardio-pharmacology-questions/generate.js

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/cardio-pharmacology-questions/generate.js'

ls /home/daytona/workspace/ && node --version && ls /home/daytona/skills/docx/sc…

ls /home/daytona/workspace/ && ls /home/daytona/skills/pptx/

mkdir -p /home/daytona/workspace/autocoids-pptx && ls /home/daytona/workspace/au…

~/autocoids-pptx/generate.js

"use strict";
const pptxgen = require("pptxgenjs");
const pres = new pptxgen();
pres.layout = "LAYOUT_WIDE"; // 13.3 x 7.5 inches
pres.title = "Autocoids – Comprehensive Pharmacology Notes";
pres.author = "Pharmacology";

// ─── THEME ───────────────────────────────────────────────────────────────────
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// ─── HELPERS ─────────────────────────────────────────────────────────────────
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// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 1 – TITLE
// ═══════════════════════════════════════════════════════════════════════════
titleSlide("AUTOCOIDS", "Histamine  •  Serotonin  •  Eicosanoids  •  Kinins  •  Nitric Oxide");

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 2 – OVERVIEW
// ═══════════════════════════════════════════════════════════════════════════
contentSlide("What are Autocoids?", sl => {
  sl.addText([
    { text: "Autacoid", options:{bold:true, color:C.teal, fontSize:16} },
    { text: ' = from Greek ', options:{fontSize:15} },
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    { label:"EICOSANOIDS",fill:C.teal,  sub:"PGs / TXA2 / LTs" },
    { label:"KININS",     fill:C.navy,  sub:"Bradykinin" },
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// ═══════════════════════════════════════════════════════════════════════════
// SECTION 1 – HISTAMINE
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider(1, "HISTAMINE", "Chemistry • Synthesis • Storage • Receptors • Clinical Uses");

// SLIDE 3 – Histamine: Synthesis & Storage
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// SLIDE 4 – Histamine Receptors
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    { h:"H2", loc:"Gastric parietal cells\nHeart\nVascular SM", mech:"Gs → adenylyl cyclase → ↑cAMP", eff:"↑ Gastric acid secretion\n↑ HR (direct)\nVasodilatation", drug:"Ranitidine, Famotidine\nCimetidine (now less used)", col:C.teal },
    { h:"H3", loc:"CNS (presynaptic autoreceptors)\nPeripheral nerves", mech:"Gi → ↓cAMP", eff:"Inhibits histamine release\n(auto-feedback)\nInhibits other transmitters", drug:"Pitolisant (narcolepsy)", col:C.navy },
    { h:"H4", loc:"Immune cells\nEosinophils, mast cells\nBasophils", mech:"Gi → ↓cAMP", eff:"Chemotaxis of immune cells\nInflammatory signalling", drug:"Under investigation", col:"7B2D8B" },
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// SLIDE 5 – H1 Antihistamines
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    { text:"Diphenhydramine (Benadryl)", bold:false },
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    { text:"Promethazine (also antiemetic)", bold:false },
    { text:"Hydroxyzine (anti-anxiety)", bold:false },
    { text:"Cyproheptadine (also anti-serotonin, appetite stimulant)", bold:false },
    { text:"Meclizine / Dimenhydrinate (motion sickness)", bold:false },
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    { text:"Loratadine (Claritin)", bold:false },
    { text:"Desloratadine (active metabolite)", bold:false },
    { text:"Fexofenadine (Allegra) – no cardiac effects", bold:false },
    { text:"Rupatadine (also PAF antagonist)", bold:false },
    { text:"Bilastine, Azelastine (nasal spray)", bold:false },
    { text:"ADVANTAGES:", bold:true, color:C.navy, size:13 },
    { text:"Once daily dosing, safe for driving", bold:false, color:C.subtext },
    { text:"Terfenadine/Astemizole (withdrawn – QT prolongation / Torsades)", bold:true, color:C.red },
  ], 7.0, 1.6, 6.0, 5.0, 13, C.text);
});

// SLIDE 6 – Uses of Antihistamines
contentSlide("Clinical Uses of H1 Antihistamines", sl => {
  const uses = [
    { title:"Allergic Conditions", items:["Allergic rhinitis (seasonal & perennial)", "Urticaria, angioedema", "Atopic dermatitis (itching)","Conjunctivitis"], col:C.red },
    { title:"Anaphylaxis", items:["Adjunct to epinephrine (NEVER replace epinephrine)","Controls urticaria & pruritus component","Given IM/IV in anaphylaxis"], col:"C0392B" },
    { title:"Motion Sickness\n& Vomiting", items:["Meclizine, dimenhydrinate, promethazine","Prevent nausea/vomiting of motion sickness","Post-op N&V (promethazine)"], col:C.teal },
    { title:"Sleep Aid", items:["Diphenhydramine – short-term insomnia","NOT recommended for chronic use","Tolerance develops quickly"], col:C.navy },
    { title:"Pruritus", items:["Topical diphenhydramine for local itch","Hydroxyzine – severe pruritus","Cholestatic pruritus"], col:"7B2D8B" },
    { title:"Cold Remedies", items:["Chlorpheniramine in OTC cold combinations","Dries up secretions (anticholinergic effect)","Limited evidence of benefit"], col:C.green },
  ];
  uses.forEach((u,i) => {
    const col = i % 3, row = Math.floor(i/3);
    const x = 0.4 + col*4.3, y = 1.2 + row*3.0;
    sl.addShape(pres.ShapeType.rect, { x, y, w:4.1, h:2.7, fill:{color:u.col}, line:{color:"FFFFFF", width:0.5} });
    sl.addText(u.title, { x:x+0.1, y:y+0.1, w:3.9, h:0.5, fontSize:13.5, color:C.gold, bold:true, fontFace:FONT, wrap:true });
    sl.addShape(pres.ShapeType.rect, { x:x+0.1, y:y+0.65, w:3.9, h:0.03, fill:{color:"FFFFFF"}, transparency:50 });
    u.items.forEach((it,ii) => {
      sl.addText("• "+it, { x:x+0.1, y:y+0.72+ii*0.55, w:3.9, h:0.5, fontSize:11, color:C.white, fontFace:FONT, wrap:true });
    });
  });
});

// SLIDE 7 – H2 Antagonists
contentSlide("H2-Receptor Antagonists", sl => {
  sl.addText([
    {text:"Mechanism: ", options:{bold:true, color:C.teal, fontSize:15}},
    {text:"Competitively block H2 receptors on gastric parietal cells → ↓ histamine-stimulated gastric acid secretion\nAlso reduce acid secreted in response to gastrin and acetylcholine (indirect effect)\nReduce both basal (nocturnal) and meal-stimulated acid output", options:{fontSize:14, color:C.text}},
  ], {x:0.5, y:1.15, w:12.3, h:1.3, fontFace:FONT, wrap:true});

  const drugs = [
    { name:"Cimetidine", note:"Prototype; inhibits CYP450 → many drug interactions; anti-androgenic (gynaecomastia)", col:C.teal },
    { name:"Ranitidine", note:"More potent; fewer interactions; WITHDRAWN (NDMA contamination concerns)", col:C.navy },
    { name:"Famotidine", note:"Most potent H2 blocker; no CYP450 inhibition; preferred currently", col:C.green },
    { name:"Nizatidine", note:"Similar to ranitidine; good oral bioavailability", col:"7B2D8B" },
  ];
  drugs.forEach((d,i) => {
    const x = 0.4 + (i%2)*6.45, y = 2.55 + Math.floor(i/2)*1.45;
    sl.addShape(pres.ShapeType.roundRect, {x, y, w:6.2, h:1.3, fill:{color:d.col}, rectRadius:0.1});
    sl.addText(d.name, {x:x+0.12, y:y+0.08, w:2.2, h:0.5, fontSize:15, color:C.gold, bold:true, fontFace:FONT});
    sl.addText(d.note, {x:x+0.12, y:y+0.55, w:6.0, h:0.65, fontSize:12, color:C.white, fontFace:FONT, wrap:true});
  });

  sl.addText("Clinical Uses", {x:0.5, y:5.5, w:5.8, h:0.4, fontSize:15, color:C.teal, bold:true, fontFace:FONT});
  bullets(sl, [
    "Peptic ulcer disease (PUD) – duodenal > gastric",
    "Gastro-oesophageal reflux disease (GERD)",
    "Zollinger-Ellison syndrome (PPIs now preferred)",
    "Prevention of stress ulcers in ICU patients",
    "Urticaria (H1 + H2 combination for refractory cases)",
  ], 0.5, 5.9, 6.2, 1.4, 12.5, C.text);

  sl.addText("Adverse Effects", {x:7.0, y:5.5, w:5.8, h:0.4, fontSize:15, color:C.red, bold:true, fontFace:FONT});
  bullets(sl, [
    "Generally well tolerated",
    "Cimetidine: gynaecomastia, impotence (anti-androgenic), confusion in elderly",
    "Headache, dizziness, constipation/diarrhoea",
    "↑ risk of C. difficile and pneumonia (all acid suppressants)",
  ], 7.0, 5.9, 6.0, 1.4, 12.5, C.text);
});

// ═══════════════════════════════════════════════════════════════════════════
// SECTION 2 – SEROTONIN (5-HT)
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider(2, "SEROTONIN (5-HT)", "5-Hydroxytryptamine • Receptors • Agonists • Antagonists");

// SLIDE 8 – Serotonin basics
contentSlide("Serotonin – Synthesis, Distribution & Metabolism", sl => {
  sl.addText("5-Hydroxytryptamine (5-HT) = Serotonin", { x:0.5, y:1.12, w:12, h:0.45, fontSize:17, color:C.navy, bold:true, fontFace:FONT });

  sl.addText("Synthesis", {x:0.5, y:1.65, w:5.8, h:0.38, fontSize:15, color:C.teal, bold:true, fontFace:FONT});
  bullets(sl, [
    "L-Tryptophan → 5-hydroxytryptophan (rate-limiting step: tryptophan hydroxylase-1)",
    "5-HTP → 5-HT (by aromatic L-amino acid decarboxylase)",
    "Rate-limiting enzyme blocked by: p-chlorophenylalanine (PCPA / fenclonine)",
    "Telotristat ethyl: tryptophan hydroxylase inhibitor approved for carcinoid diarrhoea",
  ], 0.5, 2.08, 6.2, 2.0, 13, C.text);

  sl.addText("Distribution", {x:0.5, y:4.15, w:5.8, h:0.38, fontSize:15, color:C.teal, bold:true, fontFace:FONT});
  bullets(sl, [
    ">90% in enterochromaffin (EC) cells of GI tract",
    "~8% in platelets (concentrate via SERT – serotonin transporter)",
    "~1-2% in CNS (raphe nuclei of brainstem)",
    "Stored in vesicles; depleted by reserpine",
  ], 0.5, 4.55, 6.2, 2.6, 13, C.text);

  sl.addText("Metabolism & Inactivation", {x:7.0, y:1.65, w:5.8, h:0.38, fontSize:15, color:C.teal, bold:true, fontFace:FONT});
  bullets(sl, [
    "Primarily by MAO (monoamine oxidase) → 5-hydroxy-indoleacetic acid (5-HIAA)",
    "5-HIAA excreted in urine (↑ in carcinoid syndrome – diagnostic marker)",
    "Uptake back into neurons/platelets via SERT (blocked by SSRIs, TCAs)",
    "Reserpine depletes vesicular storage of 5-HT",
  ], 7.0, 2.08, 6.0, 2.0, 13, C.text);

  sl.addText("CNS Functions of Serotonin", {x:7.0, y:4.15, w:5.8, h:0.38, fontSize:15, color:C.teal, bold:true, fontFace:FONT});
  bullets(sl, [
    "Mood regulation (depression, anxiety)",
    "Sleep-wake cycle (promotes sleep initiation)",
    "Appetite suppression",
    "Temperature regulation",
    "Pain modulation (descending inhibition)",
    "Vomiting (via 5-HT3 in CTZ)",
  ], 7.0, 4.55, 6.0, 2.5, 13, C.text);
});

// SLIDE 9 – 5-HT Receptors
contentSlide("5-HT Receptors – Classification & Actions", sl => {
  const receptors = [
    { r:"5-HT1", mech:"Gi → ↓cAMP", loc:"CNS, blood vessels", effect:"Vasoconstriction (cerebral)\nInhibits NT release\nAnxiolysis", drug:"Sumatriptan (agonist – migraine)\nBuspirone (5-HT1A partial agonist)", col:C.navy },
    { r:"5-HT2", mech:"Gq → ↑IP3/DAG", loc:"Platelets, smooth muscle,\nCNS (cortex)", effect:"Platelet aggregation\nVasoconstriction / bronchoconstriction\nHallucinogenic effects", drug:"Clozapine, Ketanserin (antagonists)\nCyproheptadine", col:C.red },
    { r:"5-HT3", mech:"Ligand-gated\nNa+/K+ channel", loc:"CTZ, GI tract,\nvagal afferents", effect:"Nausea and vomiting\nGI motility\nPain signalling", drug:"Ondansetron, Granisetron\n(antagonists – antiemetics)", col:C.teal },
    { r:"5-HT4", mech:"Gs → ↑cAMP", loc:"GI tract,\nheart", effect:"↑ GI motility\n(prokinetic)", drug:"Metoclopramide (partial)\nMosapride, Prucalopride\n(agonists – IBS/constipation)", col:C.green },
  ];
  receptors.forEach((r,i) => {
    const x = 0.3 + i*3.2;
    sl.addShape(pres.ShapeType.rect, {x, y:1.1, w:3.1, h:5.9, fill:{color:r.col}});
    sl.addText(r.r + " Receptor", {x, y:1.15, w:3.1, h:0.45, fontSize:16, color:C.gold, bold:true, fontFace:FONT, align:"center"});
    sl.addShape(pres.ShapeType.rect, {x:x+0.08, y:1.62, w:2.94, h:0.04, fill:{color:"FFFFFF"}, transparency:50});
    [
      {label:"Mechanism", val:r.mech},
      {label:"Location", val:r.loc},
      {label:"Effects", val:r.effect},
      {label:"Key Drugs", val:r.drug},
    ].forEach((f,fi) => {
      const yy = 1.72 + fi*1.3;
      sl.addText(f.label.toUpperCase(), {x:x+0.1, y:yy, w:2.9, h:0.28, fontSize:9, color:C.gold, bold:true, fontFace:FONT, charSpacing:2});
      sl.addText(f.val, {x:x+0.1, y:yy+0.28, w:2.9, h:0.95, fontSize:11.5, color:C.white, fontFace:FONT, wrap:true});
    });
  });
});

// SLIDE 10 – Serotonin Clinical Applications
contentSlide("Serotonin: Clinical Pharmacology", sl => {
  sl.addText("KEY CLINICAL APPLICATIONS", {x:0.5, y:1.1, w:12.3, h:0.38, fontSize:15, color:C.gold, bold:true, charSpacing:5, fontFace:FONT});

  const apps = [
    { title:"MIGRAINE\n(Triptans)", body:"Sumatriptan, Zolmitriptan, Rizatriptan\n5-HT1B/1D agonists → cranial vasoconstriction\n→ inhibit neuropeptide release\nPO/SC/nasal; use within 1hr of headache\nContra: ischaemic heart disease, uncontrolled HTN", col:C.navy },
    { title:"CARCINOID\nSYNDROME", body:"Carcinoid tumour (enterochromaffin cells) secretes excess 5-HT\nFeatures: flushing, diarrhoea, bronchoconstriction, tricuspid disease\n↑ urinary 5-HIAA (diagnostic marker)\nTreatment: Octreotide, Telotristat\nSerotonin antagonists: Cyproheptadine, Ketanserin", col:"7B2D8B" },
    { title:"ANTI-EMETICS\n(5-HT3 Blockers)", body:"Ondansetron, Granisetron, Palonosetron\nBlock 5-HT3 in CTZ and GI vagal afferents\nPost-chemo N&V, post-op N&V\nSafe in pregnancy (ondansetron)\nAEs: Headache, constipation, QT prolongation", col:C.teal },
    { title:"DEPRESSION\n(SERT Blockers)", body:"SSRIs block SERT → ↑ synaptic 5-HT\nFluoxetine, Escitalopram, Sertraline\nSerotonin Syndrome: hyperthermia, clonus, agitation, tachycardia\n(due to excess 5-HT – drug-drug interaction)\nTreatment of syndrome: Cyproheptadine + supportive", col:C.red },
    { title:"IBS / CONSTIPATION\n(5-HT4 Agonists)", body:"Prucalopride → potent 5-HT4 agonist\nUsed in chronic constipation, IBS-C\nIncreases colonic motility\nMosapride: 5-HT4 agonist + weak 5-HT3 antagonist\nDoes NOT cross BBB – no CNS effects", col:C.green },
    { title:"ANXIETY / DEPRESSION\n(5-HT1A Partial Agonist)", body:"Buspirone: 5-HT1A partial agonist\nUsed in Generalised Anxiety Disorder (GAD)\nNon-benzodiazepine, non-addictive\nOnset: 2-4 weeks (no acute anxiolysis)\nNo sedation, no dependence, no withdrawal", col:"B7950B" },
  ];
  apps.forEach((a,i) => {
    const col = i%3, row = Math.floor(i/3);
    const x = 0.3 + col*4.35, y = 1.55 + row*2.85;
    sl.addShape(pres.ShapeType.roundRect, {x, y, w:4.15, h:2.7, fill:{color:a.col}, rectRadius:0.12});
    sl.addText(a.title, {x:x+0.1, y:y+0.08, w:3.95, h:0.6, fontSize:13, color:C.gold, bold:true, fontFace:FONT, wrap:true});
    sl.addText(a.body, {x:x+0.1, y:y+0.72, w:3.95, h:1.88, fontSize:11, color:C.white, fontFace:FONT, wrap:true});
  });
});

// ═══════════════════════════════════════════════════════════════════════════
// SECTION 3 – EICOSANOIDS
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider(3, "EICOSANOIDS", "Prostaglandins • Thromboxanes • Leukotrienes • Lipoxins");

// SLIDE 11 – Eicosanoid synthesis overview
contentSlide("Eicosanoids – Synthesis Pathways", sl => {
  sl.addText("All eicosanoids are derived from 20-carbon polyunsaturated fatty acids (mainly Arachidonic Acid)", {x:0.5, y:1.12, w:12.3, h:0.5, fontSize:14, color:C.subtext, italic:true, fontFace:FONT, wrap:true});

  // Cascade boxes
  pill(sl, 0.5, 1.75, 12.3, 0.55, C.navy, "MEMBRANE PHOSPHOLIPIDS", C.white, 15);
  sl.addShape(pres.ShapeType.rect, {x:6.4, y:2.32, w:0.08, h:0.5, fill:{color:C.teal}});
  pill(sl, 2.0, 2.82, 3.5, 0.52, C.teal, "PHOSPHOLIPASE A2", C.white, 13);
  sl.addText("(blocked by glucocorticoids via lipocortin)", {x:5.7, y:2.88, w:4.5, h:0.42, fontSize:11.5, color:C.subtext, italic:true, fontFace:FONT});
  sl.addShape(pres.ShapeType.rect, {x:6.4, y:3.37, w:0.08, h:0.5, fill:{color:C.teal}});
  pill(sl, 2.5, 3.87, 8.3, 0.52, C.navy, "ARACHIDONIC ACID  (from membrane phospholipids)", C.white, 14);
  sl.addShape(pres.ShapeType.rect, {x:2.8, y:4.42, w:0.08, h:0.5, fill:{color:C.red}});
  sl.addShape(pres.ShapeType.rect, {x:9.7, y:4.42, w:0.08, h:0.5, fill:{color:C.teal}});

  // COX pathway
  sl.addShape(pres.ShapeType.rect, {x:0.3, y:4.92, w:5.7, h:2.45, fill:{color:"FEF0F0"}, line:{color:C.red, width:1}});
  sl.addText("COX PATHWAY (Cyclooxygenase)", {x:0.35, y:4.97, w:5.6, h:0.42, fontSize:13.5, color:C.red, bold:true, fontFace:FONT, align:"center"});
  sl.addText("Enzymes: COX-1 (constitutive) & COX-2 (inducible)\nBlocked by: NSAIDs (non-selective), Aspirin (irreversible)\nCelecoxib, Rofecoxib (COX-2 selective)\n\nProducts:\n  PGE2 – pain, fever, vasodilation, cytoprotection\n  PGI2 (Prostacyclin) – vasodilation, ↓ platelet aggregation\n  TXA2 (Thromboxane A2) – vasoconstriction, ↑ platelet aggregation", {x:0.4, y:5.42, w:5.55, h:1.88, fontSize:11, color:C.text, fontFace:FONT, wrap:true});

  // LOX pathway
  sl.addShape(pres.ShapeType.rect, {x:7.3, y:4.92, w:5.7, h:2.45, fill:{color:"EEF8F0"}, line:{color:C.teal, width:1}});
  sl.addText("LOX PATHWAY (Lipoxygenase)", {x:7.35, y:4.97, w:5.6, h:0.42, fontSize:13.5, color:C.green, bold:true, fontFace:FONT, align:"center"});
  sl.addText("Enzyme: 5-Lipoxygenase (5-LOX)\nBlocked by: Zileuton (5-LOX inhibitor)\n\nProducts:\n  LTB4 – chemotaxis of neutrophils, PMN\n  LTC4, LTD4, LTE4 – cysteinyl leukotrienes\n    (slow reacting substances of anaphylaxis – SRS-A)\n    → bronchoconstriction, ↑ mucus, vascular permeability\n  Blocked by: Montelukast, Zafirlukast (LT receptor antagonists)", {x:7.4, y:5.42, w:5.55, h:1.88, fontSize:11, color:C.text, fontFace:FONT, wrap:true});
});

// SLIDE 12 – Prostaglandins
contentSlide("Prostaglandins – Receptors, Effects & Clinical Uses", sl => {
  const pgs = [
    { pg:"PGE2", rec:"EP1–EP4", effect:"Vasodilation, pain sensitisation, fever (hypothalamus), uterine contraction (EP3 in late pregnancy), bronchodilation (EP2)", use:"Misoprostol (EP3/EP1 agonist): cervical ripening, labour induction, PPH prevention, peptic ulcer", col:C.red },
    { pg:"PGI2\n(Prostacyclin)", rec:"IP", effect:"Potent vasodilation, inhibits platelet aggregation (↑cAMP in platelets), reduces pulmonary hypertension", use:"Epoprostenol, Iloprost, Treprostinil: pulmonary arterial hypertension (PAH)", col:C.teal },
    { pg:"PGF2α", rec:"FP", effect:"Uterine contraction, vasoconstriction, bronchoconstriction, ↑ IOP reduction", use:"Carboprost (15-methyl PGF2α): refractory PPH\nLatanoprost, Bimatoprost: glaucoma (↓ IOP)", col:C.navy },
    { pg:"TXA2", rec:"TP", effect:"Potent vasoconstriction, platelet aggregation, bronchoconstriction\nShort half-life (30 seconds)", use:"Aspirin: irreversibly inhibits TXA2 synthesis (antiplatelet)\nTP receptor blocked by Ramatroban", col:"7B2D8B" },
  ];
  pgs.forEach((p,i) => {
    const x = 0.3 + (i%2)*6.55, y = 1.1 + Math.floor(i/2)*3.05;
    sl.addShape(pres.ShapeType.rect, {x, y, w:6.3, h:2.9, fill:{color:p.col}, line:{color:"FFFFFF", width:0.5}});
    sl.addText(p.pg, {x:x+0.1, y:y+0.08, w:2.2, h:0.55, fontSize:18, color:C.gold, bold:true, fontFace:FONT});
    sl.addText("Receptor: "+p.rec, {x:x+2.4, y:y+0.18, w:3.8, h:0.38, fontSize:12, color:C.gold, fontFace:FONT});
    sl.addShape(pres.ShapeType.rect, {x:x+0.1, y:y+0.68, w:6.1, h:0.04, fill:{color:"FFFFFF"}, transparency:60});
    sl.addText("Effects: "+p.effect, {x:x+0.1, y:y+0.75, w:6.1, h:1.05, fontSize:11, color:C.white, fontFace:FONT, wrap:true});
    sl.addText("Uses: "+p.use, {x:x+0.1, y:y+1.85, w:6.1, h:0.95, fontSize:11, color:C.gold, fontFace:FONT, wrap:true});
  });
});

// SLIDE 13 – Leukotrienes & NSAIDs
contentSlide("Leukotrienes & Anti-Eicosanoid Drugs", sl => {
  sl.addText("LEUKOTRIENES", {x:0.5, y:1.1, w:5.8, h:0.4, fontSize:16, color:C.red, bold:true, fontFace:FONT});
  bullets(sl, [
    { text:"LTB4: potent neutrophil chemoattractant (inflammatory bowel disease, psoriasis)", bold:false },
    { text:"Cysteinyl-LTs (LTC4, LTD4, LTE4):", bold:true, color:C.teal },
    { text:"= Slow Reacting Substances of Anaphylaxis (SRS-A)", bold:false, color:C.subtext },
    { text:"Bronchoconstriction (more potent than histamine)", bold:true, color:C.red },
    { text:"↑ Mucus secretion, mucosal oedema", bold:false },
    { text:"↑ Vascular permeability", bold:false },
    { text:"Key role in ASTHMA, URTICARIA, ALLERGIC RHINITIS", bold:true, color:C.navy },
  ], 0.5, 1.55, 6.0, 3.5, 13, C.text);

  sl.addShape(pres.ShapeType.line, {x:6.75, y:1.1, w:0, h:6.2, line:{color:C.navy, width:1.5}});

  sl.addText("ANTI-LEUKOTRIENE DRUGS", {x:7.0, y:1.1, w:5.8, h:0.4, fontSize:16, color:C.teal, bold:true, fontFace:FONT});
  const antiLT = [
    { drug:"Zileuton", mech:"5-LOX inhibitor → blocks ALL leukotriene synthesis", use:"Asthma (oral, 4x/day)", ae:"Hepatotoxicity (monitor LFTs)" },
    { drug:"Montelukast", mech:"Cys-LT1 receptor antagonist (blocks LTC4/LTD4/LTE4)", use:"Asthma prophylaxis, allergic rhinitis, exercise-induced bronchoconstriction", ae:"Neuropsychiatric (depression, suicidal ideation – FDA warning)" },
    { drug:"Zafirlukast", mech:"Cys-LT1 receptor antagonist", use:"Asthma prophylaxis (adults)", ae:"Hepatitis (monitor LFTs)" },
  ];
  antiLT.forEach((d,i) => {
    sl.addShape(pres.ShapeType.roundRect, {x:7.05, y:1.55+i*1.85, w:5.9, h:1.7, fill:{color:i===0?C.navy:i===1?C.teal:C.green}, rectRadius:0.1});
    sl.addText(d.drug, {x:7.15, y:1.6+i*1.85, w:2.5, h:0.42, fontSize:15, color:C.gold, bold:true, fontFace:FONT});
    sl.addText("MOA: "+d.mech, {x:7.15, y:2.02+i*1.85, w:5.7, h:0.42, fontSize:11.5, color:C.white, fontFace:FONT, wrap:true});
    sl.addText("Use: "+d.use, {x:7.15, y:2.44+i*1.85, w:5.7, h:0.38, fontSize:11, color:"CCEEFF", fontFace:FONT, wrap:true});
    sl.addText("AE: "+d.ae, {x:7.15, y:2.82+i*1.85, w:5.7, h:0.32, fontSize:10.5, color:C.gold, fontFace:FONT, wrap:true});
  });

  sl.addText("NSAIDs: Mechanism Summary", {x:0.5, y:5.15, w:6.0, h:0.4, fontSize:14, color:C.navy, bold:true, fontFace:FONT});
  sl.addText("Inhibit COX-1 and/or COX-2 → ↓ PG synthesis → antipyretic, analgesic, anti-inflammatory effects\nAspirin: IRREVERSIBLE COX inhibition → used as antiplatelet (75-325mg/day)\nNon-selective NSAIDs (Ibuprofen, Diclofenac): reversible; GI adverse effects (↓ PGE2 cytoprotection)\nCOX-2 selective (Celecoxib): fewer GI effects; ↑ cardiovascular risk (↓ PGI2, TXA2 unopposed)\nParacetamol: weak COX inhibition; antipyretic-analgesic; safe GI profile; hepatotoxic in overdose", {x:0.5, y:5.6, w:6.0, h:1.7, fontSize:11.5, color:C.text, fontFace:FONT, wrap:true});
});

// ═══════════════════════════════════════════════════════════════════════════
// SECTION 4 – KININS
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider(4, "KININS (BRADYKININ)", "The Kallikrein-Kinin System");

// SLIDE 14 – Bradykinin
contentSlide("Bradykinin – Synthesis, Effects & Clinical Relevance", sl => {
  // Synthesis cascade
  sl.addText("SYNTHESIS CASCADE", {x:0.5, y:1.12, w:12.3, h:0.38, fontSize:14, color:C.gold, bold:true, charSpacing:5, fontFace:FONT});
  const steps = [
    { label:"Kininogens\n(HMW & LMW)\nin plasma/tissues", col:C.navy },
    { label:"Kallikreins\n(tissue & plasma)\n[serine proteases]", col:C.teal },
    { label:"BRADYKININ\n(nonapeptide)", col:C.red },
    { label:"Inactive fragments\nby ACE (kininase II)\nby NEP (neprilysin)", col:C.subtext },
  ];
  steps.forEach((s,i) => {
    sl.addShape(pres.ShapeType.roundRect, {x:0.4+i*3.25, y:1.6, w:3.0, h:1.0, fill:{color:s.col}, rectRadius:0.1});
    sl.addText(s.label, {x:0.4+i*3.25, y:1.62, w:3.0, h:0.96, fontSize:11.5, color:C.white, bold:false, fontFace:FONT, align:"center", valign:"middle", wrap:true});
    if(i<3) sl.addText("→", {x:3.38+i*3.25, y:1.88, w:0.25, h:0.45, fontSize:20, color:C.navy, bold:true, fontFace:FONT, align:"center"});
  });

  sl.addText("Receptors: B1 (inducible, inflammation) and B2 (constitutive, mediates most effects)", {x:0.5, y:2.7, w:12.3, h:0.45, fontSize:13.5, color:C.navy, bold:true, fontFace:FONT});

  sl.addText("Pharmacological Effects", {x:0.5, y:3.25, w:5.8, h:0.38, fontSize:15, color:C.teal, bold:true, fontFace:FONT});
  bullets(sl, [
    { text:"Vasodilation (endothelial NO and PGI2 release) → ↓ BP", bold:true, color:C.teal },
    { text:"↑ Vascular permeability → oedema, wheal", bold:false },
    { text:"Pain and hyperalgesia (sensitises nociceptors)", bold:true, color:C.red },
    { text:"Bronchoconstriction (asthma – less potent than histamine)", bold:false },
    { text:"Stimulates sensory nerve endings → cough", bold:true, color:C.red },
    { text:"Stimulates uterine smooth muscle", bold:false },
    { text:"↑ Renal blood flow, natriuresis", bold:false },
  ], 0.5, 3.68, 6.0, 3.4, 13, C.text);

  sl.addText("Clinical Relevance", {x:7.0, y:3.25, w:5.8, h:0.38, fontSize:15, color:C.teal, bold:true, fontFace:FONT});
  bullets(sl, [
    { text:"ACE Inhibitor Cough:", bold:true, color:C.red },
    { text:"ACE (= kininase II) degrades bradykinin → ACE-I blocks this → bradykinin accumulates → cough + angioedema", bold:false, color:C.subtext },
    { text:"ACE Inhibitor Angioedema:", bold:true, color:C.red },
    { text:"Bradykinin-mediated; does not respond to antihistamines/corticosteroids; treat with icatibant (B2 antagonist) or C1-esterase inhibitor", bold:false, color:C.subtext },
    { text:"ARBs (Losartan):", bold:true, color:C.navy },
    { text:"Do NOT inhibit ACE → bradykinin levels unchanged → NO cough", bold:false, color:C.subtext },
    { text:"Icatibant: Selective B2 receptor antagonist – hereditary angioedema", bold:true, color:C.green },
    { text:"Berotralstat: Plasma kallikrein inhibitor – prophylaxis of hereditary angioedema", bold:false },
  ], 7.0, 3.68, 6.0, 3.4, 13, C.text);
});

// ═══════════════════════════════════════════════════════════════════════════
// SECTION 5 – NITRIC OXIDE
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider(5, "NITRIC OXIDE (NO)", "Endogenous Vasodilator & Signalling Molecule");

// SLIDE 15 – Nitric Oxide
contentSlide("Nitric Oxide – Synthesis, Mechanism & Clinical Uses", sl => {
  sl.addText("SYNTHESIS:", {x:0.5, y:1.12, w:2.2, h:0.4, fontSize:14, color:C.teal, bold:true, fontFace:FONT});
  sl.addText("L-Arginine + O₂ → NO + L-Citrulline   (enzyme: Nitric Oxide Synthase – NOS)", {x:2.7, y:1.12, w:10.0, h:0.4, fontSize:14, color:C.text, fontFace:FONT});

  const nos = [
    {name:"nNOS\n(NOS-1)", loc:"Neurons", const:"Constitutive", func:"Neurotransmission\nLong-term potentiation", col:C.navy},
    {name:"iNOS\n(NOS-2)", loc:"Macrophages, immune cells", const:"Inducible", func:"Large amounts of NO\nAntimicrobial, septic shock", col:C.red},
    {name:"eNOS\n(NOS-3)", loc:"Vascular endothelium", const:"Constitutive", func:"Vasodilation, ↓ BP\nAntiplatelet, antithrombotic", col:C.teal},
  ];
  nos.forEach((n,i) => {
    const x = 0.5 + i*4.25;
    sl.addShape(pres.ShapeType.roundRect, {x, y:1.62, w:4.0, h:2.2, fill:{color:n.col}, rectRadius:0.12});
    sl.addText(n.name, {x:x+0.1, y:1.68, w:3.8, h:0.55, fontSize:17, color:C.gold, bold:true, fontFace:FONT, align:"center"});
    sl.addText("Location: "+n.loc, {x:x+0.1, y:2.28, w:3.8, h:0.38, fontSize:11.5, color:C.white, fontFace:FONT});
    sl.addText(n.const, {x:x+0.1, y:2.65, w:3.8, h:0.3, fontSize:11, color:C.gold, italic:true, fontFace:FONT});
    sl.addText(n.func, {x:x+0.1, y:2.98, w:3.8, h:0.75, fontSize:11.5, color:C.white, fontFace:FONT, wrap:true});
  });

  sl.addText("MECHANISM OF ACTION", {x:0.5, y:3.95, w:5.8, h:0.4, fontSize:14, color:C.gold, bold:true, fontFace:FONT});
  bullets(sl, [
    "NO activates soluble guanylyl cyclase (sGC) in smooth muscle",
    "↑ cGMP → activates cGMP-dependent protein kinase (PKG)",
    "PKG phosphorylates myosin light chain kinase → ↓ Ca²⁺ → smooth muscle relaxation",
    "→ VASODILATION (especially venous/arterial at higher doses)",
    "cGMP degraded by PDE5 (inhibited by sildenafil → ↑ NO effect)",
  ], 0.5, 4.38, 6.0, 2.85, 13, C.text);

  sl.addText("CLINICAL APPLICATIONS", {x:7.0, y:3.95, w:5.8, h:0.4, fontSize:14, color:C.gold, bold:true, fontFace:FONT});
  bullets(sl, [
    { text:"Nitrates (GTN, Isosorbide dinitrate): donate NO → angina, acute LVF", bold:true, color:C.teal },
    { text:"Inhaled NO: pulmonary hypertension in newborns (PPHN)", bold:true, color:C.teal },
    { text:"Sildenafil (PDE5 inhibitor): erectile dysfunction, PAH; CONTRAINDICATED with nitrates → severe hypotension", bold:true, color:C.red },
    { text:"Sodium nitroprusside: releases NO → arterial+venous dilation → hypertensive emergency; cyanide toxicity at high doses", bold:false },
    { text:"Septic shock: iNOS overactivation → massive NO → refractory vasodilation (treated with NOS inhibitors in trials)", bold:false },
  ], 7.0, 4.38, 6.0, 2.85, 13, C.text);
});

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 16 – COMPARISON SUMMARY TABLE
// ═══════════════════════════════════════════════════════════════════════════
contentSlide("Autocoids – Comparison at a Glance", sl => {
  const headers = ["AUTOCOID", "SOURCE", "KEY RECEPTOR", "MAIN EFFECT", "KEY DRUG / ANTAGONIST"];
  const rows = [
    ["Histamine", "Mast cells, Basophils, ECL cells", "H1, H2, H3, H4", "Allergy, bronchoconstriction, acid secretion, vasodilation", "Cetirizine (H1), Famotidine (H2), Pitolisant (H3)"],
    ["Serotonin (5-HT)", "EC cells (GIT), Platelets, Raphe nuclei", "5-HT1 to 5-HT7", "Mood, vasoconstriction, GI motility, vomiting, platelet aggregation", "Sumatriptan, Ondansetron, SSRIs, Buspirone"],
    ["PGE2", "All tissues (COX-1/2 from AA)", "EP1–EP4", "Pain, fever, vasodilation, uterine contraction", "Misoprostol (agonist); NSAIDs (↓ synthesis)"],
    ["PGI2", "Vascular endothelium", "IP", "Vasodilation, ↓ platelet aggregation", "Epoprostenol (agonist – PAH)"],
    ["TXA2", "Platelets", "TP", "Vasoconstriction, ↑ platelet aggregation", "Aspirin (irreversible COX block)"],
    ["LTC4/D4/E4", "Mast cells, eosinophils (5-LOX)", "CysLT1", "Bronchoconstriction, ↑ mucus, oedema", "Montelukast (antagonist); Zileuton (↓ synthesis)"],
    ["Bradykinin", "Kininogens via Kallikrein", "B1, B2", "Vasodilation, pain, ↑ permeability, cough", "Icatibant (B2 antagonist)"],
    ["Nitric Oxide", "Endothelium, neurons, macrophages", "sGC → ↑ cGMP", "Vasodilation, neurotransmission, antimicrobial", "Nitrates (NO donors); Sildenafil (↑ cGMP)"],
  ];
  const colW = [1.8, 2.3, 2.0, 3.5, 2.95];
  const startX = 0.25;
  let x = startX;
  headers.forEach((h,i) => {
    sl.addShape(pres.ShapeType.rect, {x, y:1.1, w:colW[i], h:0.52, fill:{color:C.navy}});
    sl.addText(h, {x:x+0.04, y:1.12, w:colW[i]-0.08, h:0.48, fontSize:11, color:C.gold, bold:true, fontFace:FONT, align:"center", valign:"middle", wrap:true});
    x += colW[i];
  });
  rows.forEach((row, ri) => {
    let rx = startX;
    const bgColor = ri%2===0 ? "EEF3FB" : C.white;
    row.forEach((cell, ci) => {
      sl.addShape(pres.ShapeType.rect, {x:rx, y:1.62+ri*0.73, w:colW[ci], h:0.71, fill:{color:bgColor}, line:{color:"CCCCCC", width:0.3}});
      sl.addText(cell, {x:rx+0.04, y:1.64+ri*0.73, w:colW[ci]-0.08, h:0.67, fontSize:10, color:ci===0?C.navy:C.text, bold:ci===0, fontFace:FONT, valign:"middle", wrap:true});
      rx += colW[ci];
    });
  });
});

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 17 – HIGH-YIELD EXAM FACTS
// ═══════════════════════════════════════════════════════════════════════════
contentSlide("HIGH-YIELD EXAM FACTS – Autocoids", sl => {
  sl.addShape(pres.ShapeType.rect, {x:0, y:0, w:13.3, h:7.5, fill:{color:C.navy}});
  sl.addShape(pres.ShapeType.rect, {x:0, y:0, w:0.35, h:7.5, fill:{color:C.gold}});
  sl.addShape(pres.ShapeType.rect, {x:0, y:1.0, w:13.3, h:0.07, fill:{color:C.teal}});
  sl.addText("HIGH-YIELD EXAM FACTS", {x:0.55, y:0.1, w:12.5, h:0.8, fontSize:22, color:C.white, bold:true, fontFace:FONT, valign:"middle"});

  const facts = [
    { t:"Histamine + Gastric acid:", d:"ECL cells release histamine → H2 receptors on parietal cells → ↑ acid. Blocked by H2 antagonists (Famotidine) and PPIs." },
    { t:"ACE inhibitor cough:", d:"Due to bradykinin accumulation (ACE = kininase II). Switch to ARB (no cough). Angioedema: treat with Icatibant." },
    { t:"Serotonin Syndrome:", d:"Excess 5-HT → hyperthermia, clonus, agitation. Treat with Cyproheptadine (5-HT2 antagonist). Can occur with SSRIs + MAOIs, Linezolid, Tramadol." },
    { t:"Aspirin paradox:", d:"Low dose aspirin: ↓ TXA2 (platelets, irreversible) > ↓ PGI2 (endothelium) → net antiplatelet. High dose: blocks both → may REDUCE antiplatelet benefit." },
    { t:"Montelukast warning:", d:"FDA black box – neuropsychiatric effects (suicidal ideation, depression). Use caution especially in children." },
    { t:"Sildenafil + Nitrates:", d:"ABSOLUTELY CONTRAINDICATED. Both ↑ cGMP → synergistic hypotension → fatal." },
    { t:"Triple whammy in asthma:", d:"Histamine (H1) + Leukotrienes (CysLT1) + Prostanoids (TXA2) all cause bronchoconstriction. Treatment targets each pathway." },
    { t:"Carcinoid syndrome markers:", d:"↑ urinary 5-HIAA (serotonin metabolite). Flushing + diarrhoea + tricuspid disease. Octreotide for symptom control." },
    { t:"Glucocorticoids:", d:"Inhibit Phospholipase A2 (via lipocortin/annexin-A1) → block ALL eicosanoid synthesis (PGs + LTs). Broadest anti-inflammatory action." },
    { t:"PAH treatment options:", d:"Prostacyclin analogues (Epoprostenol, Iloprost), PDE5 inhibitors (Sildenafil), Endothelin antagonists (Bosentan), inhaled NO." },
  ];

  const col1 = facts.slice(0,5), col2 = facts.slice(5);
  col1.forEach((f,i) => {
    sl.addText([
      {text:"► "+f.t+" ", options:{bold:true, color:C.gold, fontSize:12.5}},
      {text:f.d, options:{color:"CCDDFF", fontSize:12}},
    ], {x:0.55, y:1.2+i*1.2, w:6.2, h:1.1, fontFace:FONT, wrap:true});
  });
  col2.forEach((f,i) => {
    sl.addText([
      {text:"► "+f.t+" ", options:{bold:true, color:C.gold, fontSize:12.5}},
      {text:f.d, options:{color:"CCDDFF", fontSize:12}},
    ], {x:7.1, y:1.2+i*1.2, w:6.0, h:1.1, fontFace:FONT, wrap:true});
  });
});

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 18 – IMPORTANT DRUG LIST (Quick Revision)
// ═══════════════════════════════════════════════════════════════════════════
contentSlide("Important Drugs – Autocoids Quick Revision", sl => {
  const cats = [
    { cat:"H1 BLOCKERS", col:C.red, drugs:"1st Gen: Diphenhydramine, Chlorpheniramine, Promethazine, Cyproheptadine, Meclizine\n2nd Gen: Cetirizine, Levocetirizine, Loratadine, Desloratadine, Fexofenadine\n⚠ Withdrawn: Terfenadine, Astemizole (QT prolongation)" },
    { cat:"H2 BLOCKERS", col:C.teal, drugs:"Famotidine (preferred), Cimetidine (CYP450 inhibitor, anti-androgenic), Ranitidine (withdrawn – NDMA), Nizatidine\nUse: PUD, GERD, stress ulcers" },
    { cat:"5-HT AGONISTS", col:"7B2D8B", drugs:"Triptans (Sumatriptan, Zolmitriptan): migraine – 5-HT1B/1D agonists\nProkinetics (Prucalopride, Mosapride): IBS-C – 5-HT4 agonists\nBuspirone: GAD – 5-HT1A partial agonist" },
    { cat:"5-HT ANTAGONISTS", col:C.navy, drugs:"Ondansetron/Granisetron: 5-HT3 antagonists – antiemetics\nCyproheptadine: H1 + 5-HT2 blocker – carcinoid, serotonin syndrome\nMetoclopramide: partial 5-HT4 agonist + D2 blocker – prokinetic" },
    { cat:"ANTI-EICOSANOIDS", col:C.green, drugs:"NSAIDs (Ibuprofen, Diclofenac): COX-1 + COX-2 inhibitors\nCelecoxib: COX-2 selective (↓ GI SE, ↑ CV risk)\nAspirin: irreversible COX inhibition (antiplatelet)\nMontelukast/Zafirlukast: CysLT1 antagonists (asthma)\nZileuton: 5-LOX inhibitor" },
    { cat:"EICOSANOID AGONISTS", col:"B7950B", drugs:"Misoprostol (PGE1 analogue): PUD, cervical ripening, PPH prevention\nCarboprost (PGF2α): refractory PPH\nLatanoprost (PGF2α): glaucoma\nEpoprostenol/Treprostinil (PGI2): PAH\nAlprostadil (PGE1): erectile dysfunction, ductus arteriosus" },
  ];
  cats.forEach((c,i) => {
    const col = i%2, row = Math.floor(i/2);
    const x = 0.3 + col*6.6, y = 1.1 + row*2.05;
    sl.addShape(pres.ShapeType.rect, {x, y, w:6.4, h:1.95, fill:{color:c.col}});
    sl.addText(c.cat, {x:x+0.1, y:y+0.08, w:6.2, h:0.38, fontSize:13, color:C.gold, bold:true, fontFace:FONT, charSpacing:4});
    sl.addText(c.drugs, {x:x+0.1, y:y+0.52, w:6.2, h:1.38, fontSize:11, color:C.white, fontFace:FONT, wrap:true});
  });
  sl.addShape(pres.ShapeType.rect, {x:0.3, y:7.2, w:12.7, h:0.22, fill:{color:C.teal}});
  sl.addText("Ref: Katzung BG. Basic & Clinical Pharmacology, 16th ed. | Goodman & Gilman's Pharmacological Basis of Therapeutics, 14th ed.", {x:0.5, y:7.22, w:12.3, h:0.2, fontSize:9, color:C.white, fontFace:FONT, align:"center"});
});

// ─── WRITE FILE ──────────────────────────────────────────────────────────────
const OUT = "/home/daytona/workspace/autocoids-pptx/Autocoids_Pharmacology.pptx";
pres.writeFile({ fileName: OUT })
  .then(() => console.log("SUCCESS: " + OUT))
  .catch(err => { console.error("ERROR:", err); process.exit(1); });

cd /home/daytona/workspace/autocoids-pptx && node generate.js 2>&1

python /home/daytona/skills/docx/scripts/office/validate.py /home/daytona/worksp…

python3 -c "import zipfile; z=zipfile.ZipFile('/home/daytona/workspace/autocoids…