Obstetric History Taking: HOPI for Any Complaint

const {
  Document, Packer, Paragraph, TextRun, HeadingLevel, AlignmentType,
  TableOfContents, PageBreak, NumberingFormat, convertInchesToTwip,
  BorderStyle, Table, TableRow, TableCell, WidthType, ShadingType,
  UnderlineType
} = require('docx');
const fs = require('fs');

// ─── STYLING HELPERS ────────────────────────────────────────────────────────

const H1 = (text) => new Paragraph({
  text,
  heading: HeadingLevel.HEADING_1,
  spacing: { before: 400, after: 200 },
});

const H2 = (text) => new Paragraph({
  text,
  heading: HeadingLevel.HEADING_2,
  spacing: { before: 300, after: 150 },
});

const H3 = (text) => new Paragraph({
  text,
  heading: HeadingLevel.HEADING_3,
  spacing: { before: 240, after: 120 },
});

const bold = (text, size = 22) => new TextRun({ text, bold: true, size });
const normal = (text, size = 22) => new TextRun({ text, size });
const italic = (text, size = 22) => new TextRun({ text, italics: true, size });

const para = (text, opts = {}) => new Paragraph({
  children: [new TextRun({ text, size: 22, ...opts })],
  spacing: { after: 100 },
  ...(opts.paragraphOpts || {}),
});

const answerPara = (text) => new Paragraph({
  children: [new TextRun({ text: `Answer: ${text}`, size: 20, color: '1F5C8B', bold: true })],
  spacing: { after: 200 },
  indent: { left: convertInchesToTwip(0.25) },
});

const pageBreakPara = () => new Paragraph({ children: [new PageBreak()] });

const divider = () => new Paragraph({
  border: { bottom: { style: BorderStyle.SINGLE, size: 6, color: 'AAAAAA' } },
  spacing: { after: 150 },
  children: [],
});

const numbered = (num, text) => new Paragraph({
  children: [bold(`${num}. `, 22), normal(text, 22)],
  spacing: { after: 80 },
});

const option = (letter, text, correct = false) => new Paragraph({
  children: correct
    ? [new TextRun({ text: `     ${letter}) ${text}`, size: 21, bold: true, color: '1F5C8B' })]
    : [new TextRun({ text: `     ${letter}) ${text}`, size: 21 })],
  spacing: { after: 60 },
});

const saqQ = (num, text) => new Paragraph({
  children: [bold(`${num}. `, 22), normal(text, 22)],
  spacing: { after: 60 },
});

const saqA = (text) => new Paragraph({
  children: [new TextRun({ text: `   ${text}`, size: 20, color: '2E7D32' })],
  spacing: { after: 180 },
  indent: { left: convertInchesToTwip(0.3) },
});

const laqQ = (num, text) => new Paragraph({
  children: [bold(`${num}. `, 23), new TextRun({ text, size: 23, bold: false })],
  spacing: { before: 120, after: 80 },
});

const bullet = (text) => new Paragraph({
  children: [new TextRun({ text: `• ${text}`, size: 21 })],
  spacing: { after: 60 },
  indent: { left: convertInchesToTwip(0.4) },
});

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

const children = [];

// ── TITLE PAGE ──
children.push(
  new Paragraph({
    children: [new TextRun({ text: 'CARDIOVASCULAR PHARMACOLOGY', size: 52, bold: true, color: '1B2A4A' })],
    alignment: AlignmentType.CENTER,
    spacing: { before: 1000, after: 200 },
  }),
  new Paragraph({
    children: [new TextRun({ text: 'Question Bank', size: 40, bold: true, color: '2C5F8A' })],
    alignment: AlignmentType.CENTER,
    spacing: { after: 200 },
  }),
  new Paragraph({
    children: [new TextRun({ text: 'Antihypertensives  |  Heart Failure Drugs  |  Hematinics', size: 26, italics: true, color: '555555' })],
    alignment: AlignmentType.CENTER,
    spacing: { after: 200 },
  }),
  new Paragraph({
    children: [new TextRun({ text: 'MCQs  •  SAQs  •  LAQs', size: 28, bold: true, color: '444444' })],
    alignment: AlignmentType.CENTER,
    spacing: { after: 200 },
  }),
  new Paragraph({
    children: [new TextRun({ text: 'Undergraduate Medical Student Level', size: 22, italics: true, color: '888888' })],
    alignment: AlignmentType.CENTER,
    spacing: { after: 800 },
  }),
  pageBreakPara(),
);

// ════════════════════════════════════════════════════════════
// SECTION 1 — ANTIHYPERTENSIVES
// ════════════════════════════════════════════════════════════

children.push(H1('SECTION 1: ANTIHYPERTENSIVE DRUGS'));
children.push(divider());

// ── MCQs ──
children.push(H2('Part A: Multiple Choice Questions (MCQs)'));
children.push(para('Choose the single best answer for each question.', { italics: true }));

const antihtnMCQs = [
  {
    q: 'Which class of antihypertensive drugs acts primarily by blocking the renin–angiotensin–aldosterone system at the level of the converting enzyme?',
    opts: ['Beta-blockers', 'ACE inhibitors', 'Calcium channel blockers', 'Thiazide diuretics'],
    ans: 'B',
    exp: 'ACE inhibitors (e.g. enalapril, lisinopril) block the conversion of angiotensin I to angiotensin II by inhibiting angiotensin-converting enzyme.',
  },
  {
    q: 'A 55-year-old patient on enalapril develops a persistent dry cough. What is the most appropriate next step?',
    opts: ['Add codeine for symptom relief', 'Switch to an ARB such as losartan', 'Increase the dose of enalapril', 'Add a beta-blocker'],
    ans: 'B',
    exp: 'ACE-inhibitor-induced cough results from bradykinin accumulation. Switching to an ARB (which does not affect bradykinin) resolves the cough.',
  },
  {
    q: 'Which antihypertensive is the drug of choice in a pregnant woman with severe hypertension?',
    opts: ['Enalapril', 'Losartan', 'Methyldopa', 'Atenolol'],
    ans: 'C',
    exp: 'Methyldopa is the first-line antihypertensive in pregnancy. ACE inhibitors and ARBs are teratogenic (category D/X).',
  },
  {
    q: 'The mechanism of action of thiazide diuretics as antihypertensives involves:',
    opts: ['Inhibition of Na+/K+/2Cl− cotransporter in the thick ascending limb', 'Inhibition of Na+/Cl− cotransporter in the distal convoluted tubule', 'Blockade of aldosterone receptors', 'Inhibition of carbonic anhydrase'],
    ans: 'B',
    exp: 'Thiazides inhibit the Na+/Cl− cotransporter (NCC) in the distal convoluted tubule, reducing sodium and water reabsorption.',
  },
  {
    q: 'Which calcium channel blocker is most selective for vascular smooth muscle and preferred for hypertension without significant cardiac effects?',
    opts: ['Verapamil', 'Diltiazem', 'Amlodipine', 'Nifedipine (immediate release)'],
    ans: 'C',
    exp: 'Amlodipine is a dihydropyridine CCB highly selective for vascular smooth muscle. It is long-acting and widely used for hypertension.',
  },
  {
    q: 'A patient with hypertension and bronchial asthma should NOT receive:',
    opts: ['Amlodipine', 'Atenolol', 'Losartan', 'Hydralazine'],
    ans: 'B',
    exp: 'Beta-blockers (including cardioselective ones like atenolol) are contraindicated in asthma due to risk of bronchospasm.',
  },
  {
    q: 'Which of the following antihypertensive drugs causes reflex tachycardia as a notable side effect?',
    opts: ['Propranolol', 'Metoprolol', 'Hydralazine', 'Losartan'],
    ans: 'C',
    exp: 'Hydralazine directly dilates arterioles, triggering baroreceptor-mediated reflex tachycardia and sympathetic activation.',
  },
  {
    q: 'Spironolactone is classified as which type of antihypertensive/diuretic?',
    opts: ['Loop diuretic', 'Thiazide diuretic', 'Potassium-sparing diuretic (aldosterone antagonist)', 'Osmotic diuretic'],
    ans: 'C',
    exp: 'Spironolactone is a competitive aldosterone antagonist (potassium-sparing diuretic) acting at the collecting duct.',
  },
  {
    q: 'The JNC 8 guideline recommends initiating antihypertensive therapy in the general non-Black population with which of the following drug classes? (Select ALL that apply — choose the answer that includes the most complete set)',
    opts: ['ACE inhibitor or ARB, and thiazide or CCB', 'Beta-blocker only', 'Loop diuretic only', 'Alpha-blocker and direct vasodilator'],
    ans: 'A',
    exp: 'JNC 8 recommends thiazide diuretics, CCBs, ACEi, or ARBs as first-line options for non-Black patients.',
  },
  {
    q: 'Which antihypertensive acts as a centrally acting alpha-2 agonist, reducing sympathetic outflow?',
    opts: ['Prazosin', 'Clonidine', 'Labetalol', 'Nifedipine'],
    ans: 'B',
    exp: 'Clonidine is a central alpha-2 agonist that reduces sympathetic outflow from the CNS, lowering heart rate and blood pressure.',
  },
  {
    q: 'A patient with hypertension and diabetic nephropathy benefits most from which drug class due to its renoprotective effect?',
    opts: ['Thiazide diuretics', 'Beta-blockers', 'ACE inhibitors / ARBs', 'Calcium channel blockers'],
    ans: 'C',
    exp: 'ACEi/ARBs reduce intraglomerular pressure by dilating the efferent arteriole, slowing progression of diabetic nephropathy.',
  },
  {
    q: 'The drug labetalol is unique among antihypertensives because it:',
    opts: ['Is a pure alpha-1 blocker', 'Combines alpha-1 and beta receptor blockade', 'Acts only on central receptors', 'Is a direct renin inhibitor'],
    ans: 'B',
    exp: 'Labetalol blocks both alpha-1 and beta receptors, making it useful in hypertensive emergencies and pregnancy-related hypertension.',
  },
  {
    q: 'Which antihypertensive class is most associated with the side effect of ankle oedema?',
    opts: ['ACE inhibitors', 'Beta-blockers', 'Dihydropyridine CCBs', 'Thiazide diuretics'],
    ans: 'C',
    exp: 'Dihydropyridine CCBs (e.g. amlodipine) cause preferential arterial vasodilation, leading to dependent ankle oedema.',
  },
  {
    q: 'Aliskiren is an antihypertensive that works by:',
    opts: ['Blocking AT1 receptors', 'Inhibiting ACE', 'Directly inhibiting renin', 'Blocking aldosterone receptors'],
    ans: 'C',
    exp: 'Aliskiren is a direct renin inhibitor — the first in its class — blocking the RAAS at its very first step.',
  },
  {
    q: 'What is a major contraindication to the use of ACE inhibitors?',
    opts: ['Diabetes mellitus', 'Bilateral renal artery stenosis', 'Chronic heart failure', 'Proteinuric nephropathy'],
    ans: 'B',
    exp: 'In bilateral renal artery stenosis, ACEi/ARBs can cause acute renal failure by removing the angiotensin II-mediated efferent constriction that maintains GFR.',
  },
];

antihtnMCQs.forEach((item, i) => {
  children.push(numbered(i + 1, item.q));
  ['A','B','C','D'].forEach((l, j) => children.push(option(l, item.opts[j], l === item.ans)));
  children.push(answerPara(`${item.ans}) ${item.exp}`));
});

// ── SAQs ──
children.push(pageBreakPara());
children.push(H2('Part B: Short Answer Questions (SAQs)'));
children.push(para('Answer each question in 3–6 lines.', { italics: true }));

const antihtnSAQs = [
  { q: '1. List FOUR classes of antihypertensive drugs with ONE example drug from each class.', a: 'ACE inhibitors (enalapril), ARBs (losartan), CCBs (amlodipine), Thiazide diuretics (hydrochlorothiazide). Others: Beta-blockers (atenolol), alpha-2 agonists (clonidine), direct vasodilators (hydralazine), aldosterone antagonists (spironolactone).' },
  { q: '2. State the mechanism of action of ACE inhibitors and describe TWO of their clinical uses beyond hypertension.', a: 'ACEi block the conversion of angiotensin I → II, reducing vasoconstriction and aldosterone release. Additional uses: (1) Heart failure with reduced EF — reduce preload and afterload. (2) Diabetic nephropathy — renoprotection by reducing intraglomerular pressure.' },
  { q: '3. Why are ACE inhibitors and ARBs contraindicated in pregnancy?', a: 'They are teratogenic (FDA category D/X). Use in the 2nd and 3rd trimesters is associated with fetal renal dysplasia, oligohydramnios, skull ossification defects, intrauterine growth restriction, and neonatal renal failure.' },
  { q: '4. Explain why beta-blockers can worsen asthma and what alternative should be used for hypertension in an asthmatic.', a: 'Beta-2 receptors in bronchial smooth muscle mediate bronchodilation. Beta-blockers (even cardioselective ones at high doses) can block these receptors, causing bronchoconstriction. Alternatives: CCBs (e.g. amlodipine) or ACEi/ARBs are safe in asthma.' },
  { q: '5. What is the "J-curve" phenomenon in antihypertensive therapy?', a: 'The J-curve describes the observation that excessively lowering diastolic blood pressure (below ~70 mmHg) may paradoxically increase cardiovascular events, particularly myocardial infarction. This is because coronary perfusion occurs predominantly in diastole and depends on adequate diastolic pressure.' },
  { q: '6. Differentiate between thiazide and loop diuretics in terms of site of action, potency, and clinical use.', a: 'Thiazides act on the DCT (NCC transporter), moderate potency, used for hypertension and mild oedema. Loop diuretics (furosemide) act on the thick ascending limb (Na+/K+/2Cl−), highly potent, used in acute pulmonary oedema, heart failure, and severe hypertension. Loop diuretics cause greater fluid loss.' },
  { q: '7. What is hypertensive urgency vs. hypertensive emergency? Name two drugs used in hypertensive emergency.', a: 'Urgency: severely elevated BP (>180/120 mmHg) without acute end-organ damage. Emergency: severely elevated BP WITH acute end-organ damage (stroke, AKI, aortic dissection, pulmonary oedema). IV agents: sodium nitroprusside, IV labetalol, IV nicardipine, IV hydralazine, IV enalaprilat.' },
  { q: '8. State the mechanism of action of dihydropyridine calcium channel blockers and explain their selectivity for vessels over the heart.', a: 'Dihydropyridines (e.g. amlodipine, nifedipine) block L-type voltage-gated Ca²⁺ channels. They have much greater selectivity for vascular smooth muscle than cardiac tissue (due to pharmacokinetic differences in tissue binding), causing vasodilation with minimal negative chronotropy or inotropy.' },
];

antihtnSAQs.forEach(item => {
  children.push(saqQ('', item.q));
  children.push(saqA('Answer: ' + item.a));
});

// ── LAQs ──
children.push(pageBreakPara());
children.push(H2('Part C: Long Answer Questions (LAQs)'));
children.push(para('Answer each question comprehensively. Marks as indicated.', { italics: true }));

children.push(laqQ(1, 'Classify antihypertensive drugs with examples. Discuss the pharmacology of ACE inhibitors in detail including mechanism, indications, side effects, contraindications, and drug interactions. (20 marks)'));
const laq1Points = [
  'Classification: ACEi, ARBs, CCBs, Thiazides, Beta-blockers, Alpha-blockers, Central agonists, Direct vasodilators, Renin inhibitors',
  'Mechanism: Inhibits ACE → ↓ Ang II → vasodilation + ↓ aldosterone → ↓ Na/water retention + ↑ bradykinin (cough)',
  'Indications: Hypertension, Heart failure (HFrEF), Post-MI, Diabetic nephropathy, CKD with proteinuria',
  'Side effects: Dry cough (bradykinin), Hyperkalemia, Acute renal impairment, Angioedema (rare but serious), First-dose hypotension, Teratogenicity',
  'Contraindications: Pregnancy, Bilateral renal artery stenosis, Previous angioedema from ACEi, Severe aortic stenosis',
  'Drug interactions: NSAIDs reduce efficacy and increase nephrotoxicity; K+-sparing diuretics → hyperkalemia; Lithium toxicity increased; Antacids may reduce absorption',
  'Monitoring: Renal function (U&E, creatinine) and potassium checked 1–2 weeks after initiation and after each dose increase',
];
laq1Points.forEach(p => children.push(bullet(p)));
children.push(para(''));

children.push(laqQ(2, 'Describe the renin–angiotensin–aldosterone system (RAAS) and explain how different drug classes interrupt it at different points to lower blood pressure. (15 marks)'));
const laq2Points = [
  'Renin: released from JGA in response to low BP, low Na+, or sympathetic activation → cleaves angiotensinogen → Ang I',
  'ACE: converts Ang I → Ang II (primarily in pulmonary endothelium)',
  'Ang II effects: AT1 receptor → vasoconstriction, aldosterone release, ADH release, sympathetic stimulation, cardiac hypertrophy',
  'Aldosterone: acts on collecting duct → Na+ reabsorption, K+ excretion → volume expansion',
  'Drug interruption points: Renin inhibitors (aliskiren) block renin; ACEi block conversion; ARBs block AT1 receptor; Aldosterone antagonists (spironolactone, eplerenone) block aldosterone; Beta-blockers reduce renin release',
  'Clinical significance: Combined RAAS blockade (ACEi + ARB or ACEi + spironolactone) can provide greater BP and organ protection in selected patients',
];
laq2Points.forEach(p => children.push(bullet(p)));
children.push(para(''));

children.push(laqQ(3, 'A 60-year-old man with hypertension, type 2 diabetes, CKD stage 3, and a history of myocardial infarction presents for review. Discuss the most appropriate antihypertensive regimen for him, with pharmacological justification. (15 marks)'));
const laq3Points = [
  'ACEi or ARB: First-line — renoprotection in diabetic nephropathy, cardioprotection post-MI, reduces mortality in CKD with proteinuria',
  'Beta-blocker (cardioselective e.g. metoprolol): Post-MI survival benefit, reduces sympathetic overactivity; avoid high-dose in diabetes (masks hypoglycaemia)',
  'CCB (amlodipine): Additive BP control; combination ACEi + CCB (ACCOMPLISH trial) superior to ACEi + thiazide in reducing CV events',
  'Thiazide: Use with caution in CKD (less effective when eGFR <30); may worsen glucose tolerance',
  'Avoid: NSAIDs (nephrotoxic, reduce antihypertensive efficacy), Aldosterone antagonists if K+ already high or eGFR <30',
  'BP target: <130/80 mmHg in diabetes per ADA/ESC guidelines',
  'Monitor: Renal function, electrolytes, glucose, HR, lipid profile',
];
laq3Points.forEach(p => children.push(bullet(p)));

children.push(pageBreakPara());

// ════════════════════════════════════════════════════════════
// SECTION 2 — HEART FAILURE DRUGS
// ════════════════════════════════════════════════════════════

children.push(H1('SECTION 2: DRUGS USED IN HEART FAILURE'));
children.push(divider());

children.push(H2('Part A: Multiple Choice Questions (MCQs)'));
children.push(para('Choose the single best answer for each question.', { italics: true }));

const hfMCQs = [
  {
    q: 'Which drug class is the cornerstone of therapy for heart failure with reduced ejection fraction (HFrEF) and has proven mortality benefit?',
    opts: ['Loop diuretics', 'Digoxin', 'ACE inhibitors / ARBs', 'Calcium channel blockers'],
    ans: 'C',
    exp: 'ACEi/ARBs (and ARNi sacubitril/valsartan) are core therapies in HFrEF, shown in landmark trials (CONSENSUS, SOLVD) to reduce mortality by ~25–30%.',
  },
  {
    q: 'The "four pillars" of medical therapy for HFrEF include all of the following EXCEPT:',
    opts: ['ACEi/ARBs or ARNi (sacubitril/valsartan)', 'Beta-blockers', 'Dihydropyridine CCBs', 'MRA (e.g. spironolactone/eplerenone)'],
    ans: 'C',
    exp: 'The four pillars of HFrEF are ACEi/ARNi, beta-blocker, MRA, and SGLT2 inhibitor. Dihydropyridine CCBs are NOT recommended in HFrEF as they may worsen outcomes.',
  },
  {
    q: 'Which beta-blocker is specifically licensed for use in heart failure?',
    opts: ['Atenolol', 'Metoprolol succinate (extended release)', 'Propranolol', 'Timolol'],
    ans: 'B',
    exp: 'Metoprolol succinate (MERIT-HF trial), carvedilol, and bisoprolol are the three beta-blockers with proven mortality benefit in HFrEF.',
  },
  {
    q: 'Digoxin exerts its positive inotropic effect by:',
    opts: ['Activating beta-1 receptors', 'Inhibiting Na+/K+ ATPase pump', 'Blocking L-type calcium channels', 'Inhibiting phosphodiesterase'],
    ans: 'B',
    exp: 'Digoxin inhibits Na+/K+ ATPase → ↑ intracellular Na+ → ↓ Na+/Ca²+ exchanger activity → ↑ intracellular Ca²+ → enhanced contractility.',
  },
  {
    q: 'A patient with HFrEF and NYHA class II-III symptoms should be started on spironolactone. What is the PRIMARY mechanism of benefit?',
    opts: ['Diuresis and volume reduction', 'Aldosterone blockade reducing cardiac fibrosis and remodelling', 'Peripheral vasodilation', 'Positive inotropy'],
    ans: 'B',
    exp: 'While spironolactone does have diuretic effects, in heart failure the primary benefit is aldosterone blockade, reducing myocardial and vascular fibrosis and harmful cardiac remodelling (RALES trial — 30% mortality reduction).',
  },
  {
    q: 'Sacubitril/valsartan (Entresto) is superior to enalapril in HFrEF because sacubitril:',
    opts: ['Is a more potent ACE inhibitor', 'Inhibits neprilysin, increasing natriuretic peptides (BNP, ANP)', 'Blocks AT2 receptors', 'Directly activates cardiac beta-1 receptors'],
    ans: 'B',
    exp: 'Sacubitril inhibits neprilysin (neutral endopeptidase), preventing degradation of natriuretic peptides → vasodilation, natriuresis, reduced fibrosis. In PARADIGM-HF trial, it reduced mortality vs enalapril by 20%.',
  },
  {
    q: 'SGLT2 inhibitors (e.g. dapagliflozin, empagliflozin) are now part of HFrEF therapy. Their primary mechanism is:',
    opts: ['Positive inotropic effect on myocardium', 'Renal glucose excretion reducing cardiac workload and volume overload', 'Beta-1 receptor blockade', 'Inhibition of ACE'],
    ans: 'B',
    exp: 'SGLT2 inhibitors promote glycosuria/natriuresis reducing preload, may have direct cardiac metabolic effects, and reduce hospitalisation and mortality in HFrEF (DAPA-HF, EMPEROR-Reduced trials).',
  },
  {
    q: 'Which of the following is a sign of digoxin toxicity?',
    opts: ['Tachycardia with QRS widening', 'Xanthopsia (yellow-green vision), bradycardia, AV block', 'Dry cough and hyperkalemia', 'Ankle oedema and weight gain'],
    ans: 'B',
    exp: 'Digoxin toxicity presents with GI symptoms (nausea, vomiting), visual disturbances (xanthopsia — yellow-green vision), cardiac arrhythmias (bradycardia, heart block, ventricular ectopics/VT), and neurological effects.',
  },
  {
    q: 'Loop diuretics such as furosemide are used in heart failure primarily to:',
    opts: ['Reduce mortality', 'Relieve symptoms of congestion (dyspnoea, oedema)', 'Improve cardiac contractility', 'Reduce cardiac remodelling'],
    ans: 'B',
    exp: 'Loop diuretics relieve symptomatic congestion. They have NOT been shown to reduce mortality in HF trials. Disease-modifying benefit comes from ACEi, beta-blockers, MRAs, and SGLT2i.',
  },
  {
    q: 'Ivabradine is used in HFrEF when the patient is in sinus rhythm with HR ≥70 bpm despite maximum beta-blocker therapy. Its mechanism is:',
    opts: ['Beta-1 receptor antagonism', 'L-type calcium channel blockade', 'Selective If (funny current) channel inhibition in the SA node', 'Muscarinic (M2) receptor agonism'],
    ans: 'C',
    exp: 'Ivabradine selectively inhibits the If (funny) current in the SA node, slowing heart rate without affecting inotropy or BP.',
  },
  {
    q: 'Which condition is an absolute contraindication to the use of hydralazine–isosorbide dinitrate in heart failure?',
    opts: ['Renal failure', 'Use of phosphodiesterase-5 inhibitors (e.g. sildenafil)', 'Systolic BP of 100 mmHg', 'Atrial fibrillation'],
    ans: 'B',
    exp: 'Concurrent use of hydralazine-isosorbide dinitrate (a nitrate source) with PDE5 inhibitors causes severe hypotension due to synergistic cGMP-mediated vasodilation.',
  },
  {
    q: 'The neprilysin inhibitor in sacubitril/valsartan increases the risk of which side effect that also occurs with ACE inhibitors?',
    opts: ['Hyperkalemia', 'Angioedema', 'Dry cough', 'Peripheral oedema'],
    ans: 'B',
    exp: 'Neprilysin also degrades bradykinin. Inhibiting neprilysin raises bradykinin, which — combined with ACEi use — greatly increases angioedema risk. Hence ACEi must be stopped 36 hours before starting sacubitril/valsartan.',
  },
  {
    q: 'Tolvaptan is used in heart failure complicated by hyponatraemia. Its mechanism is:',
    opts: ['Aldosterone antagonism', 'Selective V2-vasopressin receptor antagonism (aquaretic)', 'Inhibition of sodium-chloride cotransporter', 'Blockade of AT1 receptor'],
    ans: 'B',
    exp: 'Tolvaptan is a selective vasopressin V2 receptor antagonist ("vaptans"), blocking ADH action in the collecting duct, causing electrolyte-free water excretion (aquaresis) and raising serum sodium.',
  },
  {
    q: 'In acute decompensated heart failure, which drug combination is used to provide both afterload and preload reduction intravenously?',
    opts: ['Furosemide + digoxin', 'Sodium nitroprusside + furosemide', 'Metoprolol + amlodipine', 'Dobutamine + spironolactone'],
    ans: 'B',
    exp: 'Sodium nitroprusside causes both arterial (afterload ↓) and venous (preload ↓) dilation. Furosemide adds diuresis to reduce congestion. Together they rapidly improve haemodynamics in ADHF.',
  },
  {
    q: 'Dobutamine is used in cardiogenic shock. Its mechanism is:',
    opts: ['Selective beta-1 agonist providing positive inotropy with mild chronotropy', 'Alpha-1 agonist causing vasoconstriction', 'Phosphodiesterase inhibitor', 'Vasopressin analogue'],
    ans: 'A',
    exp: 'Dobutamine is primarily a beta-1 adrenergic agonist with mild beta-2 effects, increasing cardiac contractility (inotropy) with less increase in heart rate compared to adrenaline.',
  },
];

hfMCQs.forEach((item, i) => {
  children.push(numbered(i + 1, item.q));
  ['A','B','C','D'].forEach((l, j) => children.push(option(l, item.opts[j], l === item.ans)));
  children.push(answerPara(`${item.ans}) ${item.exp}`));
});

// ── HF SAQs ──
children.push(pageBreakPara());
children.push(H2('Part B: Short Answer Questions (SAQs)'));
children.push(para('Answer each question in 3–6 lines.', { italics: true }));

const hfSAQs = [
  { q: '1. Name the four pharmacological "pillars" of HFrEF therapy with an example drug from each class.', a: '(1) ACEi/ARNi: enalapril / sacubitril-valsartan. (2) Beta-blocker: bisoprolol or carvedilol. (3) Mineralocorticoid receptor antagonist (MRA): spironolactone or eplerenone. (4) SGLT2 inhibitor: dapagliflozin or empagliflozin. All have proven mortality benefit in major RCTs.' },
  { q: '2. Explain why beta-blockers are beneficial in heart failure despite their negative inotropic effect.', a: 'Chronic sympathetic overactivity in HF causes beta-1 receptor downregulation, myocyte apoptosis, and arrhythmias. Beta-blockers counteract this neurohormonal activation, prevent adverse remodelling, reduce arrhythmia-related sudden death, and improve long-term EF and survival — despite short-term reduction in contractility.' },
  { q: '3. What is the NYHA classification for heart failure? State which classes benefit from drug therapy.', a: 'Class I: No symptoms with ordinary activity. Class II: Slight limitation. Class III: Marked limitation. Class IV: Symptoms at rest/unable to perform activity. ACEi/ARBs and beta-blockers indicated from Class II onwards. Digoxin and hydralazine-nitrate used in Classes III–IV.' },
  { q: '4. Why must an ACE inhibitor be discontinued 36 hours before starting sacubitril/valsartan?', a: 'Both ACEi and neprilysin inhibition (sacubitril) raise bradykinin levels. Concurrent use causes dangerously elevated bradykinin → severe, potentially life-threatening angioedema. A washout period of at least 36 hours (or 5 half-lives for enalapril) is mandatory between stopping ACEi and starting sacubitril/valsartan.' },
  { q: '5. State three signs/symptoms of digoxin toxicity and how it is managed.', a: 'Toxicity signs: (1) GI — nausea, vomiting, anorexia; (2) Cardiac — bradycardia, heart block, VT/VF; (3) Visual — xanthopsia (yellow vision); (4) Neurological — confusion, delirium. Management: Stop digoxin, correct hypokalemia/hypomagnesemia, cardiac monitoring, temporary pacing if bradycardia, digoxin-specific antibody fragments (Digibind/DigiFab) for severe toxicity.' },
  { q: '6. What is cardiac remodelling and which drug classes reduce it in heart failure?', a: 'Cardiac remodelling: maladaptive changes in cardiac architecture — ventricular dilatation, hypertrophy, and fibrosis — driven by neurohormonal activation (Ang II, aldosterone, catecholamines). ACEi/ARBs and ARNi, beta-blockers, and MRAs (spironolactone/eplerenone) all reduce or reverse remodelling, improving EF and prognosis.' },
  { q: '7. Outline the haemodynamic goals of therapy in acute decompensated heart failure.', a: 'Goals: (1) Reduce pulmonary congestion (preload reduction — diuretics, nitrates); (2) Improve cardiac output (inotropes if cardiogenic shock — dobutamine, milrinone); (3) Reduce afterload (vasodilators — nitroprusside, nitroglycerin); (4) Optimise fluid balance; (5) Maintain BP and renal perfusion; (6) Address precipitating cause (e.g. arrhythmia, infection, ischaemia).' },
  { q: '8. How does spironolactone differ from eplerenone in the context of heart failure therapy?', a: 'Both are MRAs with similar cardiac benefit. Differences: Spironolactone is non-selective — also blocks androgen and progesterone receptors causing gynaecomastia, breast tenderness, and menstrual irregularities. Eplerenone is selective for mineralocorticoid receptors, has fewer sex hormone side effects, but is more expensive. Eplerenone is preferred post-MI (EPHESUS trial) and in men with gynaecomastia from spironolactone.' },
];

hfSAQs.forEach(item => {
  children.push(saqQ('', item.q));
  children.push(saqA('Answer: ' + item.a));
});

// ── HF LAQs ──
children.push(pageBreakPara());
children.push(H2('Part C: Long Answer Questions (LAQs)'));
children.push(para('Answer each question comprehensively. Marks as indicated.', { italics: true }));

children.push(laqQ(1, 'Discuss the pathophysiology of heart failure and how pharmacological therapy targets each pathophysiological mechanism. Include a discussion of the four evidence-based drug pillars with their mechanisms, clinical trial evidence, and key side effects. (25 marks)'));
[
  'Pathophysiology: Reduced CO → compensatory neurohormonal activation (RAAS + SNS) → cardiac remodelling (fibrosis, hypertrophy, dilation) → worsening pump function — a vicious cycle',
  'ACEi/ARNi: Block RAAS at converting enzyme or AT1 receptor / augment natriuretic peptides; CONSENSUS trial — enalapril ↓ mortality 40%; PARADIGM-HF — sacubitril/valsartan superior to enalapril, ↓ CV death/HF hospitalisation by 20%',
  'Beta-blockers: Block catecholamine toxicity; MERIT-HF (metoprolol), CIBIS-II (bisoprolol), COPERNICUS (carvedilol) — each showed 34–35% mortality reduction',
  'MRA (spironolactone/eplerenone): Block aldosterone-mediated fibrosis; RALES trial — spironolactone ↓ mortality 30% in severe HF; EPHESUS — eplerenone ↓ mortality post-MI + LV dysfunction',
  'SGLT2 inhibitors: DAPA-HF (dapagliflozin) and EMPEROR-Reduced (empagliflozin) — each reduced CV death + HF hospitalisation by ~25%, even in non-diabetics',
  'Loop diuretics: Symptom relief only (no mortality benefit) — furosemide; used to reduce congestion',
  'Digoxin: Rate control in AF + HF; modest reduction in hospitalisation (DIG trial) but no mortality benefit; narrow therapeutic index',
  'Ivabradine: SHIFT trial — added to beta-blocker, ↓ CV death/hospitalisation in SR + HR ≥70',
  'Side effects summary: ACEi — cough, AKI, angioedema; beta-blockers — initiate low, avoid in acute decompensation; MRA — hyperkalemia, gynaecomastia; SGLT2i — UTI, DKA; digoxin — narrow TI, toxicity',
].forEach(p => children.push(bullet(p)));

children.push(para(''));

children.push(laqQ(2, 'A 65-year-old woman with HFrEF (EF 30%), NYHA class III, in sinus rhythm with HR 85 bpm, is currently on furosemide. Design a complete pharmacological management plan, providing justification for each drug added. (20 marks)'));
[
  'Step 1 — Start ACEi: Ramipril 2.5 mg BD titrated up; or if tolerates, upgrade to sacubitril/valsartan (after 36h washout) — PARADIGM-HF superior outcomes',
  'Step 2 — Add beta-blocker: Start bisoprolol 1.25 mg once symptoms stable (not in acute decompensation); titrate to target dose — reverses remodelling, reduces SCD',
  'Step 3 — Add MRA: Spironolactone 25 mg (monitor K+ and creatinine); RALES trial — 30% mortality reduction; NYHA III–IV benefits most',
  'Step 4 — Add SGLT2i: Dapagliflozin 10 mg OD — DAPA-HF: ↓ CV death/HF hospitalisation; additional benefit regardless of diabetes status',
  'Step 5 — Ivabradine: If HR remains ≥70 in SR after maximising beta-blocker — SHIFT trial benefit',
  'Continue furosemide: For symptom relief; titrate to achieve euvolemia',
  'Consider hydralazine + isosorbide dinitrate: If ACEi/ARB/ARNi not tolerated; particularly beneficial in self-identified Black patients (A-HeFT trial)',
  'Patient education: Salt/fluid restriction, daily weights, medication adherence, exacerbation plan',
  'Monitoring: U&E, creatinine, BP, HR, echocardiography at 3–6 months',
].forEach(p => children.push(bullet(p)));

children.push(pageBreakPara());

// ════════════════════════════════════════════════════════════
// SECTION 3 — HEMATINICS
// ════════════════════════════════════════════════════════════

children.push(H1('SECTION 3: HEMATINICS'));
children.push(para('(Iron, Folic Acid, Vitamin B12, Erythropoietin, and related agents)', { italics: true }));
children.push(divider());

children.push(H2('Part A: Multiple Choice Questions (MCQs)'));
children.push(para('Choose the single best answer for each question.', { italics: true }));

const hemMCQs = [
  {
    q: 'Hematinics are agents that promote blood formation. Which of the following is NOT a haematinic?',
    opts: ['Ferrous sulphate', 'Folic acid', 'Cyanocobalamin (Vitamin B12)', 'Warfarin'],
    ans: 'D',
    exp: 'Warfarin is an anticoagulant, not a haematinic. Hematinics include iron salts, folic acid, vitamin B12, and erythropoietin.',
  },
  {
    q: 'A 30-year-old woman presents with fatigue, pallor, and glossitis. Blood film shows microcytic hypochromic anaemia. Serum ferritin is low. What is the first-line treatment?',
    opts: ['Intramuscular vitamin B12', 'Oral ferrous sulphate 200 mg TDS', 'Blood transfusion', 'Folic acid 5 mg daily'],
    ans: 'B',
    exp: 'Iron deficiency anaemia (microcytic, hypochromic) is treated with oral ferrous sulphate 200 mg TDS (65 mg elemental iron per tablet). Treatment continues for 3 months after haemoglobin normalisation to replenish stores.',
  },
  {
    q: 'Which form of dietary iron is most efficiently absorbed in the gastrointestinal tract?',
    opts: ['Non-haem (Fe³+ plant sources)', 'Haem iron (Fe²+ from meat)', 'Ferric iron (Fe³+) in supplements', 'Enteric-coated iron tablets'],
    ans: 'B',
    exp: 'Haem iron (from meat, Fe²+ form) is absorbed more efficiently (~25%) than non-haem iron (Fe³+ from plants, ~5% absorption). Vitamin C (ascorbic acid) enhances non-haem iron absorption by keeping it in the ferrous (Fe²+) state.',
  },
  {
    q: 'A pregnant woman is prescribed ferrous sulphate. What is the most common side effect that may affect compliance?',
    opts: ['Haemolytic anaemia', 'Constipation, nausea, and epigastric discomfort', 'Peripheral neuropathy', 'Megaloblastic anaemia'],
    ans: 'B',
    exp: 'GI side effects of oral iron — constipation, nausea, abdominal cramps, dark stools — are the most common cause of non-compliance. Ferrous gluconate has fewer GI side effects than ferrous sulphate.',
  },
  {
    q: 'Megaloblastic anaemia with neurological symptoms (subacute combined degeneration of the spinal cord) is characteristic of deficiency of:',
    opts: ['Iron', 'Folic acid', 'Vitamin B12 (cobalamin)', 'Vitamin C'],
    ans: 'C',
    exp: 'Vitamin B12 deficiency causes megaloblastic anaemia AND neurological demyelination (subacute combined degeneration — affecting posterior and lateral columns). Folate deficiency causes megaloblastic anaemia without neurological features.',
  },
  {
    q: 'What is the primary role of folic acid in erythropoiesis?',
    opts: ['Required for haem synthesis', 'Required for DNA synthesis (thymidylate production via one-carbon transfer)', 'Required for iron absorption', 'Required for vitamin B12 activation'],
    ans: 'B',
    exp: 'Folate (as THF/MTHF) is essential for one-carbon transfer reactions required for thymidylate (dTMP) and purine synthesis — critical for DNA replication in rapidly dividing erythroid precursors.',
  },
  {
    q: 'Parenteral iron therapy is indicated in which of the following situations?',
    opts: ['Patient with mild iron deficiency anaemia who can swallow tablets', 'Patient with IBD and malabsorption, or intolerance to oral iron', 'Patient with B12 deficiency', 'Patient who refuses any medication'],
    ans: 'B',
    exp: 'IV/IM iron (e.g. iron sucrose, ferric carboxymaltose) is indicated when oral iron is not tolerated, is ineffective (malabsorption), there is ongoing blood loss exceeding oral supplementation, or rapid repletion is needed (e.g. pre-surgery).',
  },
  {
    q: 'Why must vitamin B12 deficiency be treated BEFORE or alongside folic acid supplementation?',
    opts: ['Folic acid is ineffective without B12', 'Folic acid can correct the anaemia but not the neurological damage of B12 deficiency, masking it and allowing irreversible neurological deterioration', 'Folic acid causes B12 deficiency', 'They must always be given together due to pharmacokinetic interactions'],
    ans: 'B',
    exp: 'High-dose folic acid corrects the haematological abnormality (megaloblastic anaemia) of B12 deficiency, masking its diagnosis. The neurological damage (subacute combined degeneration) continues silently and becomes irreversible if B12 deficiency goes untreated.',
  },
  {
    q: 'Which of the following is the intrinsic factor required for vitamin B12 absorption?',
    opts: ['Produced in the stomach by chief cells', 'Produced in the stomach by parietal cells', 'Produced in the duodenum by enterocytes', 'Produced in the ileum by Paneth cells'],
    ans: 'B',
    exp: 'Intrinsic factor (IF) is a glycoprotein produced by gastric parietal cells. It binds vitamin B12 in the stomach; the IF-B12 complex is absorbed in the terminal ileum via specific receptors.',
  },
  {
    q: 'A gastrectomy patient develops megaloblastic anaemia 3 years post-surgery. What is the underlying mechanism?',
    opts: ['Reduced gastric acid → impaired iron absorption', 'Loss of intrinsic factor → B12 malabsorption → B12 deficiency anaemia', 'Loss of pepsin → protein malabsorption', 'Folate deficiency due to rapid gut transit'],
    ans: 'B',
    exp: 'Gastrectomy removes the parietal cells responsible for intrinsic factor production. Without IF, B12 cannot be absorbed in the terminal ileum. Body stores last 3–5 years, explaining the delayed presentation.',
  },
  {
    q: 'Erythropoietin (EPO) is used in anaemia of chronic kidney disease. Its mechanism of action is:',
    opts: ['Increases dietary iron absorption', 'Stimulates erythroid colony-forming units (CFU-E) in bone marrow via JAK2-STAT5 pathway', 'Provides iron for haem synthesis', 'Inhibits hepcidin to release stored iron'],
    ans: 'B',
    exp: 'Recombinant erythropoietin (epoetin alfa, darbepoetin) binds EPO receptors on erythroid progenitors → JAK2/STAT5 signalling → proliferation and differentiation of red cell precursors.',
  },
  {
    q: 'Which of the following drugs can CAUSE folate deficiency megaloblastic anaemia?',
    opts: ['Methotrexate and trimethoprim', 'Penicillin', 'Gentamicin', 'Omeprazole'],
    ans: 'A',
    exp: 'Methotrexate (and to a lesser extent trimethoprim) inhibit dihydrofolate reductase (DHFR), reducing conversion of dietary folate to its active form (THF), causing functional folate deficiency and megaloblastic anaemia.',
  },
  {
    q: 'The recommended dose of folic acid for prevention of neural tube defects in women planning pregnancy is:',
    opts: ['0.1 mg daily', '0.4 mg (400 micrograms) daily', '5 mg daily', '10 mg daily'],
    ans: 'B',
    exp: '400 micrograms (0.4 mg) folic acid daily from at least 12 weeks before conception until 12 weeks gestation. Women at high risk (previous NTD, anticonvulsant use, diabetes) should take 5 mg daily.',
  },
  {
    q: 'What is the preferred route of B12 supplementation in a patient with pernicious anaemia?',
    opts: ['Oral cyanocobalamin (since oral absorption is sufficient)', 'Intramuscular hydroxocobalamin (bypasses IF requirement)', 'Sublingual methylcobalamin only', 'Intravenous folic acid'],
    ans: 'B',
    exp: 'Pernicious anaemia is caused by anti-intrinsic factor antibodies. Since IF-mediated absorption is lost, oral B12 cannot be absorbed (except very small amounts via passive diffusion at very high doses). IM hydroxocobalamin is standard — given loading doses then monthly maintenance.',
  },
  {
    q: 'A patient receiving iron therapy develops black, tarry stools. What is the most appropriate initial interpretation?',
    opts: ['Iron therapy is causing GI bleeding — stop immediately', 'This is a normal expected side effect of oral iron supplementation', 'This indicates iron toxicity requiring chelation therapy', 'The patient has developed haemolytic anaemia'],
    ans: 'B',
    exp: 'Oral iron commonly turns stools dark black — this is a well-known, harmless side effect due to unabsorbed iron in the stool forming iron sulphide. It should be distinguished from melaena (tarry stools from GI bleeding) by clinical context.',
  },
];

hemMCQs.forEach((item, i) => {
  children.push(numbered(i + 1, item.q));
  ['A','B','C','D'].forEach((l, j) => children.push(option(l, item.opts[j], l === item.ans)));
  children.push(answerPara(`${item.ans}) ${item.exp}`));
});

// ── Hematinics SAQs ──
children.push(pageBreakPara());
children.push(H2('Part B: Short Answer Questions (SAQs)'));
children.push(para('Answer each question in 3–6 lines.', { italics: true }));

const hemSAQs = [
  { q: '1. List the main hematinics and the type of anaemia each treats.', a: '(1) Iron (ferrous sulphate/gluconate/fumarate) — iron deficiency anaemia (microcytic, hypochromic). (2) Folic acid — megaloblastic anaemia due to folate deficiency (macrocytic). (3) Vitamin B12 (cyanocobalamin/hydroxocobalamin) — megaloblastic anaemia + neurological deficiency. (4) Erythropoietin (epoetin alfa) — anaemia of CKD. (5) Darbepoetin alfa — longer-acting EPO analogue for CKD anaemia.' },
  { q: '2. Describe the absorption of iron in the gastrointestinal tract and the factors that enhance or inhibit it.', a: 'Iron absorbed mainly in the duodenum and proximal jejunum. Fe³+ reduced to Fe²+ by ferric reductase (Dcytb). Fe²+ enters enterocytes via DMT1. Enhancers: vitamin C (ascorbic acid), acidic environment (HCl), haem iron (meat). Inhibitors: phytates (cereals), polyphenols (tea, coffee), calcium (dairy), antacids/PPIs, H. pylori infection. Regulatory hormone hepcidin (liver) controls ferroportin to regulate systemic iron export.' },
  { q: '3. A patient with pernicious anaemia requires B12 therapy. Why is it given intramuscularly rather than orally? What monitoring is required?', a: 'Pernicious anaemia results from autoimmune destruction of gastric parietal cells → loss of intrinsic factor → B12 malabsorption. IM hydroxocobalamin (1000 mcg) is given daily for 1 week, then weekly for 4 weeks, then every 3 months for life. Monitoring: FBC (haemoglobin, MCV), serum B12 levels, watch for hypokalemia as new RBCs consume potassium during recovery (treatment may precipitate hypokalemia).' },
  { q: '4. What is the role of hepcidin in iron homeostasis, and how does chronic disease cause anaemia?', a: 'Hepcidin (liver-derived antimicrobial peptide): binds ferroportin → its internalisation and degradation → blocks iron export from enterocytes and macrophages into plasma → functional iron deficiency despite adequate stores. In chronic disease (infection, inflammation, malignancy): IL-6 → ↑ hepcidin → iron sequestration in stores → reduced erythropoiesis → normocytic (or mildly microcytic) anaemia of chronic disease.' },
  { q: '5. Outline the differences between iron deficiency anaemia and anaemia of chronic disease in terms of investigations.', a: 'Iron deficiency anaemia: ↓ serum ferritin, ↓ serum iron, ↑ TIBC, ↓ transferrin saturation, low reticulocytes, microcytic hypochromic film. Anaemia of chronic disease: normal/↑ ferritin (acute phase protein), ↓ serum iron, ↓ TIBC, normal/↓ transferrin saturation, normocytic (usually), elevated inflammatory markers (ESR, CRP). Key: ferritin is normal or raised in ACD even though functional iron is reduced.' },
  { q: '6. State the indications and precautions for intravenous iron therapy.', a: 'Indications: intolerance to oral iron, malabsorption (IBD, coeliac, post-gastrectomy), ongoing blood loss > oral replacement, pre-operative anaemia requiring rapid correction, renal anaemia on EPO. Precautions: anaphylaxis risk — resuscitation facilities must be available; administer as slow infusion under monitoring; avoid in active systemic infection; use caution in atopy/allergy history. Options: iron sucrose, ferric carboxymaltose (single large dose), low-molecular-weight iron dextran.' },
  { q: '7. How does erythropoietin therapy differ from iron therapy in managing anaemia of chronic kidney disease?', a: 'Iron therapy: replenishes iron stores depleted by dialysis-related blood loss and EPO-driven erythropoiesis. EPO therapy: directly stimulates BM erythroid progenitors to produce more RBCs. Both are often required together — EPO is ineffective if iron stores are insufficient (functional iron deficiency). Target Hb in CKD: 10–12 g/dL; over-correction (Hb >13) associated with increased CV events (TREAT trial).' },
  { q: '8. A pregnant woman at 16 weeks gestation is found to have Hb 9.2 g/dL, MCV 72 fL, and ferritin 8 ng/mL. Outline your management.', a: 'Diagnosis: iron deficiency anaemia in pregnancy. Management: oral ferrous sulphate 200 mg TDS (taken between meals with vitamin C for absorption; away from calcium, tea). Also ensure adequate folic acid (5 mg/day if risk factors). Review in 4–6 weeks — expect reticulocytosis first (day 5–10), then rise in Hb (~1 g/dL per week). Continue iron for 3 months post-normalisation. If oral iron not tolerated or not responding → consider IV ferric carboxymaltose. Check for and treat any cause of blood loss.' },
];

hemSAQs.forEach(item => {
  children.push(saqQ('', item.q));
  children.push(saqA('Answer: ' + item.a));
});

// ── Hematinics LAQs ──
children.push(pageBreakPara());
children.push(H2('Part C: Long Answer Questions (LAQs)'));
children.push(para('Answer each question comprehensively. Marks as indicated.', { italics: true }));

children.push(laqQ(1, 'Classify the hematinics and discuss in detail the pharmacology of iron compounds including: sources, daily requirements, absorption, mechanism of action, indications, dosage, adverse effects, drug interactions, and treatment monitoring. (25 marks)'));
[
  'Classification: Iron salts (oral/parenteral), Folic acid, Vitamin B12, Erythropoietin/darbepoetin, Intrinsic factor co-factor',
  'Dietary sources: haem iron (meat, fish — 25% absorbed); non-haem (leafy vegetables, legumes, fortified cereals — 5–10% absorbed)',
  'Daily requirements: adult male 8 mg/day, adult female 18 mg/day, pregnancy 27 mg/day',
  'Absorption: duodenum/proximal jejunum; Fe³+ → Fe²+ (Dcytb); Fe²+ → enterocyte (DMT1); storage as ferritin; export via ferroportin (regulated by hepcidin); transferrin transports Fe in blood',
  'MOA: Fe²+ incorporated into haem (protoporphyrin IX + Fe) → haemoglobin; also in myoglobin, cytochromes, catalase, other enzymes',
  'Oral preparations: ferrous sulphate 200 mg (65 mg elemental Fe), ferrous gluconate 300 mg (35 mg elemental Fe — better tolerated), ferrous fumarate 200 mg (65 mg elemental Fe)',
  'Indications: IDA (therapeutic); prophylactic in pregnancy, prematurity, malabsorption, heavy menstrual bleeding, CKD on EPO',
  'Adverse effects: Constipation (most common), nausea, vomiting, epigastric pain, dark stools, diarrhoea. IV iron: anaphylaxis, hypotension, local reactions. Acute toxicity (children): nausea/vomiting/haemorrhagic gastroenteritis → shock → liver necrosis → strictures',
  'Drug interactions: Antacids/PPIs ↓ absorption; tetracyclines/quinolones chelated by iron (take 2h apart); calcium salts, zinc compete for DMT1; levothyroxine absorption reduced',
  'Monitoring: Reticulocyte count rises in 5–10 days; Hb rises ~1g/dL/week; continue 3 months post-correction; serum ferritin to confirm stores replenished',
  'Parenteral iron (IV/IM): ferric carboxymaltose, iron sucrose, iron dextran; indicated when oral fails or not tolerated; anaphylaxis precautions required',
].forEach(p => children.push(bullet(p)));

children.push(para(''));

children.push(laqQ(2, 'Compare and contrast folic acid deficiency and vitamin B12 deficiency — causes, clinical features, pathophysiology, investigations, and management. (20 marks)'));
[
  'CAUSES — Folate: poor diet (alcoholism, elderly), malabsorption (coeliac), drugs (methotrexate, trimethoprim, phenytoin), pregnancy/haemolytic states (increased demand)',
  'CAUSES — B12: pernicious anaemia (anti-IF antibodies), gastrectomy, terminal ileal disease (Crohn\'s), vegan diet, fish tapeworm',
  'BLOOD FILM: Both cause macrocytic (megaloblastic) anaemia; hypersegmented neutrophils; giant metamyelocytes in BM',
  'PATHOPHYSIOLOGY — Folate: THF deficiency → impaired thymidylate synthesis → defective DNA replication in dividing cells',
  'PATHOPHYSIOLOGY — B12: Required for methionine synthesis (via methyl-THF); also required for methylmalonyl-CoA conversion (neurological pathway); deficiency causes demyelination',
  'NEUROLOGICAL: Folate — none (no spinal cord demyelination). B12 — subacute combined degeneration (posterior column: proprioception/vibration; lateral corticospinal tract: UMN signs) + peripheral neuropathy + neuropsychiatric features',
  'INVESTIGATIONS: B12 and folate levels; FBC (MCV, platelets, WBC); blood film; methylmalonic acid + homocysteine (↑ in B12 def); anti-IF antibodies; Schilling test (historical)',
  'MANAGEMENT — Folate: folic acid 5 mg OD for 4 months (or lifetime if cause persists); B12 MUST be excluded/treated first',
  'MANAGEMENT — B12: IM hydroxocobalamin 1000 mcg: loading (6 doses over 2 weeks) then every 3 months for life (pernicious anaemia); identify and treat cause',
  'KEY CLINICAL PEARL: Never give folic acid alone in mixed/uncertain deficiency — masks B12 deficiency neurologically',
].forEach(p => children.push(bullet(p)));

children.push(para(''));

children.push(laqQ(3, 'A 55-year-old vegetarian woman presents with fatigue, tingling in her feet, and memory difficulties. Investigations show Hb 8.4 g/dL, MCV 112 fL, hypersegmented neutrophils, serum B12 60 pg/mL (normal 200–900 pg/mL), and serum folate normal. Discuss the diagnosis, complications if untreated, and full management plan. (15 marks)'));
[
  'Diagnosis: Vitamin B12 deficiency megaloblastic anaemia — likely dietary (vegan) or early pernicious anaemia',
  'Key features: macrocytic anaemia (MCV 112), hypersegmented neutrophils, neurological symptoms (tingling feet = peripheral neuropathy, memory difficulties = neuropsychiatric manifestation of B12 deficiency)',
  'Investigations: Serum B12 (confirmed low), anti-parietal cell antibodies and anti-IF antibodies (to exclude pernicious anaemia), methylmalonic acid (↑ confirms functional B12 deficiency), homocysteine (↑), FBC, reticulocytes, LFTs, TFTs (thyroid disease can cause macrocytosis)',
  'Complications if untreated: Irreversible subacute combined degeneration of the spinal cord (posterior column loss → ataxia; lateral column loss → spastic paraparesis); dementia, psychosis; pancytopenia; increased homocysteine → thrombotic risk',
  'Treatment: If dietary — high-dose oral cyanocobalamin 1000 mcg OD (passive absorption bypasses IF); OR IM hydroxocobalamin 1000 mcg loading doses × 6 over 2 weeks, then every 3 months',
  'If pernicious anaemia confirmed: lifelong IM hydroxocobalamin; monitor B12 levels annually',
  'Address diet: B12 found only in animal products; advise supplementation or fortified foods for vegetarians/vegans',
  'Monitoring: FBC at 4–6 weeks (reticulocyte count rises first, Hb normalises over 6–8 weeks); neurological recovery slower and may be incomplete if long-standing; serum B12; repeat neurological assessment',
  'Caution: Watch for hypokalemia in first week of treatment — ↑ RBC production consumes K+',
].forEach(p => children.push(bullet(p)));

// ─── BUILD DOCUMENT ──────────────────────────────────────────────────────────

const doc = new Document({
  styles: {
    default: {
      document: {
        run: { font: 'Calibri', size: 22 },
      },
    },
    paragraphStyles: [
      {
        id: 'Heading1',
        name: 'Heading 1',
        run: { bold: true, size: 32, color: '1B2A4A' },
        paragraph: { spacing: { before: 400, after: 200 } },
      },
      {
        id: 'Heading2',
        name: 'Heading 2',
        run: { bold: true, size: 26, color: '2C5F8A' },
        paragraph: { spacing: { before: 300, after: 150 } },
      },
      {
        id: 'Heading3',
        name: 'Heading 3',
        run: { bold: true, size: 23, color: '2E7D32' },
        paragraph: { spacing: { before: 200, after: 100 } },
      },
    ],
  },
  sections: [{
    properties: {
      page: {
        margin: {
          top: convertInchesToTwip(1),
          bottom: convertInchesToTwip(1),
          left: convertInchesToTwip(1.2),
          right: convertInchesToTwip(1.2),
        },
      },
    },
    children,
  }],
});

Packer.toBuffer(doc).then(buffer => {
  fs.writeFileSync('/home/daytona/workspace/cardio-pharmacology-questions/Cardiovascular_Pharmacology_Question_Bank.docx', buffer);
  console.log('SUCCESS: Document written.');
});