High-Yield MCQs: RAAS Inhibitors Pharmacology

const pptxgen = require("pptxgenjs");
const pres = new pptxgen();
pres.layout = "LAYOUT_WIDE";
pres.title = "RAAS Inhibitors Pharmacology";
pres.author = "Orris Medical";

// ── PALETTE ──────────────────────────────────────────────────────────────────
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  gold:    "E8A020",   // highlight / warning
  red:     "C0392B",   // danger / contraindication
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// ── HELPERS ──────────────────────────────────────────────────────────────────
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// ── SLIDE 1 – TITLE ──────────────────────────────────────────────────────────
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  s.addText("RAAS Inhibitors", { x:0.8, y:1.1, w:11.7, h:1.3, fontSize:52, bold:true, color:C.white, align:"center", fontFace:"Calibri" });
  s.addText("Pharmacology", { x:0.8, y:2.4, w:11.7, h:0.9, fontSize:42, bold:false, color:C.gold, align:"center", fontFace:"Calibri" });
  s.addText("Mechanism • Drug Classes • Clinical Uses • High-Yield MCQs", {
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  s.addText("References: Goodman & Gilman 14e  •  Katzung 16e  •  KD Tripathi", {
    x:0.8, y:6.1, w:11.7, h:0.5, fontSize:13, color:C.white, align:"center", fontFace:"Calibri"
  });
}

// ── SLIDE 2 – OVERVIEW / AGENDA ─────────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "Contents at a Glance", pres);
  const items = [
    ["1", "Classical RAAS Cascade",        C.blue],
    ["2", "Sites of Drug Action (Diagram)", C.teal],
    ["3", "ACE Inhibitors",                 C.sky],
    ["4", "ARBs – Angiotensin Receptor Blockers", C.lilac],
    ["5", "Direct Renin Inhibitor – Aliskiren",   C.orange],
    ["6", "ARNi – Sacubitril/Valsartan",    C.green],
    ["7", "Comparison Table – All Classes", C.gold],
    ["8", "Adverse Effects & Contraindications", C.red],
    ["9", "Special Clinical Scenarios",     C.navy],
    ["10","High-Yield Memory Tricks",        C.teal],
  ];
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}

// ── SLIDE 3 – CLASSICAL RAAS CASCADE ─────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "Classical RAAS Cascade", pres);

  // Title note
  s.addText("Rate-limiting step = Renin → Angiotensin I (the committed, irreversible step)", {
    x:0.4, y:0.82, w:12.5, h:0.38, fontSize:12, italic:true, color:C.mid_gray, fontFace:"Calibri"
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  // Cascade boxes
  const steps = [
    { label:"Angiotensinogen\n(α2-globulin, made in liver)", fill:C.sky,    tc:C.white },
    { label:"Angiotensin I\n(decapeptide)", fill:C.blue,   tc:C.white },
    { label:"Angiotensin II\n(octapeptide – ACTIVE)", fill:C.navy,  tc:C.white },
  ];
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    box(s, pres, startX + i*stepX, by, bw, bh, st.fill, st.label, st.tc, 13, true);
    if (i < 2) {
      arrowRight(s, pres, startX + i*stepX + bw + 0.05, by + 0.24, 0.72, C.gold);
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  // Enzyme labels
  s.addText("RENIN\n(JG cells → rate-limiting)", { x:4.0, y:1.15, w:2.0, h:0.55, fontSize:11, bold:true, color:C.gold, align:"center", fontFace:"Calibri" });
  s.addText("ACE\n(lung endothelium)", { x:8.4, y:1.15, w:2.0, h:0.55, fontSize:11, bold:true, color:C.teal, align:"center", fontFace:"Calibri" });
  s.addText("Also: chymase, cathepsin G\n(non-ACE pathways → why ACEi incomplete)", { x:8.2, y:2.5, w:3.2, h:0.6, fontSize:10, italic:true, color:C.red, align:"left", fontFace:"Calibri" });

  // AT1 / AT2 effects
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  // AT1
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  s.addText("AT1 Receptor Effects", { x:0.3, y:2.85, w:5.8, h:0.45, fontSize:14, bold:true, color:C.blue, align:"center", valign:"middle", fontFace:"Calibri" });
  const at1 = ["Vasoconstriction (↑ SVR)", "↑ Aldosterone secretion → Na⁺/H₂O retention", "Cardiac & vascular hypertrophy/remodeling", "↑ Sympathetic tone (NE release)", "ADH (AVP) release → water reabsorption", "↓ Renin (negative feedback)"];
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  s.addText("AT2 Receptor Effects (counter-regulatory)", { x:7.1, y:2.85, w:5.8, h:0.45, fontSize:14, bold:true, color:C.green, align:"center", valign:"middle", fontFace:"Calibri" });
  const at2 = ["Vasodilation (↑ NO, ↑ cGMP)", "Anti-proliferative / anti-fibrotic", "↑ Bradykinin → further vasodilation", "Upregulated when AT1 blocked (by ARBs)", "Counter-balances AT1 effects", "Cardioprotective in disease states"];
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  // arrow from Ang II to AT1 and AT2
  s.addText("↙ AT1", { x:4.8, y:2.52, w:1.2, h:0.35, fontSize:12, bold:true, color:C.blue, fontFace:"Calibri" });
  s.addText("AT2 ↘", { x:7.3, y:2.52, w:1.2, h:0.35, fontSize:12, bold:true, color:C.green, fontFace:"Calibri" });
}

// ── SLIDE 4 – SITES OF DRUG ACTION ──────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "Sites of Drug Action on RAAS", pres);

  // Central flow column
  const flow = [
    { label:"Angiotensinogen", fill:C.lt_gray, tc:C.dark, y:1.0 },
    { label:"Angiotensin I",   fill:C.sky,     tc:C.white, y:2.1 },
    { label:"Angiotensin II",  fill:C.blue,    tc:C.white, y:3.2 },
    { label:"AT1 Receptor",    fill:C.navy,    tc:C.white, y:4.3 },
  ];
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  // down arrows
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  // enzyme labels on arrows
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  s.addText("ACE", { x:fx+fw+0.1, y:2.88, w:1.5, h:0.4, fontSize:11, bold:true, color:C.teal, fontFace:"Calibri" });

  // Drug intervention boxes – LEFT
  // β-blockers
  box(s, pres, 0.3, 1.0, 3.5, 0.75, C.mid_gray, "β-Blockers\n(↓ Renin release from JG cells)", C.white, 11, false);
  // Aliskiren
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  // ACE inhibitors
  box(s, pres, 0.3, 2.85, 3.5, 0.75, C.teal, "ACE Inhibitors\nCaptopril, Enalapril, Lisinopril…", C.white, 11, true);

  // arrows from drug boxes to flow
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    s.addText("✖", { x:ax+0.6, y:ay-0.22, w:0.4, h:0.4, fontSize:13, bold:true, color:C.red, fontFace:"Calibri" });
  });

  // Drug boxes – RIGHT
  // ARBs
  box(s, pres, 9.5, 4.05, 3.5, 0.85, C.lilac, "ARBs\nLosartan, Valsartan, Candesartan…", C.white, 11, true);
  // Aldosterone antagonists
  box(s, pres, 9.5, 5.2, 3.5, 0.85, C.green, "Aldosterone Antagonists\nSpironolactone, Eplerenone", C.white, 11, true);

  // right-side arrows
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  s.addText("✖", { x:8.6, y:4.45, w:0.4, h:0.4, fontSize:13, bold:true, color:C.red, fontFace:"Calibri" });

  // Aldosterone below AT1
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  arrowDown(s, pres, fx + fw/2 - 0.16, 5.1, C.gold);
  s.addShape(pres.shapes.LINE, { x:9.5, y:5.6, w:-1.62, h:0, line:{ color:C.red, width:2, dashType:"sysDot" } });
  s.addText("✖", { x:7.7, y:5.45, w:0.4, h:0.4, fontSize:13, bold:true, color:C.red, fontFace:"Calibri" });

  // ARNi callout
  box(s, pres, 0.3, 5.2, 3.5, 0.85, C.sky, "ARNi – Sacubitril/Valsartan\n(Neprilysin inhib + AT1 block)", C.white, 11, true);
  s.addText("Bradykinin / BNP\n↑ preserved by ARNi", { x:0.3, y:6.2, w:3.5, h:0.7, fontSize:10, italic:true, color:C.teal, fontFace:"Calibri", align:"center" });

  // Legend
  s.addShape(pres.shapes.RECTANGLE, { x:0.3, y:6.98, w:0.35, h:0.2, fill:{ color:C.red } });
  s.addText("= Block/Inhibit", { x:0.7, y:6.95, w:2.0, h:0.28, fontSize:10, color:C.dark, fontFace:"Calibri" });
}

// ── SLIDE 5 – ACE INHIBITORS ─────────────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "ACE Inhibitors – Mechanism & Pharmacology", pres);

  // Mechanism box
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  s.addText([
    { text:"Mechanism: ", options:{ bold:true, color:C.navy, fontSize:13 } },
    { text:"Inhibit ACE (kininase II = peptidyl dipeptidase) → ", options:{ color:C.dark, fontSize:13 } },
    { text:"(1) ↓ Ang I → Ang II  ", options:{ bold:true, color:C.blue, fontSize:13 } },
    { text:"AND  ", options:{ color:C.dark, fontSize:13 } },
    { text:"(2) ↑ Bradykinin + Substance P", options:{ bold:true, color:C.teal, fontSize:13 } },
    { text:"  (because kininase II normally degrades them). Dual vasodilation via reduced AngII + NO/prostacyclin from bradykinin.", options:{ color:C.dark, fontSize:12 } },
  ], { x:0.5, y:0.94, w:12.3, h:1.12, fontFace:"Calibri", valign:"middle", margin:6 });

  // Prodrug table
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  const pdRows = [
    ["Drug", "Prodrug?", "Active Form", "Clearance"],
    ["Captopril", "NO (–SH)", "Captopril", "Renal"],
    ["Lisinopril", "NO (lysine)", "Lisinopril", "Renal"],
    ["Enalapril", "YES", "Enalaprilat (IV only)", "Renal"],
    ["Ramipril", "YES", "Ramiprilat", "Renal"],
    ["Fosinopril", "YES", "Fosinoprilat", "Hepatic ✔"],
    ["Moexipril", "YES", "Moexiprilat", "Hepatic ✔"],
  ];
  pdRows.forEach((row, ri) => {
    row.forEach((cell, ci) => {
      const isHeader = ri === 0;
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      const y = 2.75 + ri * 0.45;
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        fill:{ color: isHeader ? C.navy : (ri%2===0 ? C.offwht : C.white) },
        line:{ color: C.lt_gray, width: 0.5 }
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        bold:isHeader, color: isHeader?C.white:(cell.includes("✔")?C.green:C.dark),
        align:"center", valign:"middle", fontFace:"Calibri" });
    });
  });

  // Indications
  s.addText("Key Indications", { x:6.6, y:2.3, w:6.4, h:0.4, fontSize:14, bold:true, color:C.navy, fontFace:"Calibri" });
  const indics = [
    ["Hypertension", C.sky],
    ["Heart Failure (HFrEF) – 1st line", C.blue],
    ["Post-MI (↓ remodeling, ↓ mortality)", C.blue],
    ["Diabetic nephropathy (↓ proteinuria)", C.green],
    ["CKD – non-diabetic (↓ progression)", C.green],
    ["Prevention of DM in high CV-risk pts", C.teal],
  ];
  indics.forEach(([txt, color], i) => {
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:6.6, y:2.75 + i*0.45, w:6.3, h:0.41, fill:{ color }, rectRadius:0.06 });
    s.addText("✔  " + txt, { x:6.6, y:2.75 + i*0.45, w:6.3, h:0.41, fontSize:11.5, color:C.white, fontFace:"Calibri", valign:"middle", margin:8 });
  });

  // Hemodynamic effects
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:0.3, y:5.8, w:12.7, h:1.35, fill:{ color:"F0FFF4" }, line:{ color:C.green, width:1.5 }, rectRadius:0.08 });
  s.addText("Hemodynamic Profile", { x:0.5, y:5.82, w:4, h:0.36, fontSize:13, bold:true, color:C.green, fontFace:"Calibri" });
  const hemo = [
    ["Heart Rate", "↔ (no reflex tachycardia ✓)"],
    ["Cardiac Output", "↔"],
    ["Total Peripheral Resistance", "↓ (main BP effect)"],
    ["Plasma Volume", "↔"],
    ["Plasma Renin Activity", "↑ (compensatory)"],
    ["Aldosterone", "↓"],
  ];
  hemo.forEach(([k,v], i) => {
    const x = 0.4 + (i < 3 ? 0 : 6.4);
    const y = 6.23 + (i < 3 ? i : i-3) * 0.28;
    s.addText(k + ":  ", { x, y, w:2.8, h:0.27, fontSize:10.5, bold:true, color:C.dark, fontFace:"Calibri", margin:0 });
    s.addText(v, { x:x+2.8, y, w:3.2, h:0.27, fontSize:10.5, color:(v.includes("↔"))?C.mid_gray:(v.includes("↓")?C.teal:C.orange), fontFace:"Calibri", margin:0 });
  });
}

// ── SLIDE 6 – ACE INHIBITOR ADVERSE EFFECTS ─────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "ACE Inhibitors – Adverse Effects & Contraindications", pres);

  // AE boxes
  const aes = [
    { title:"Dry Cough (5-20%)", body:"Bradykinin + Substance P accumulation in lungs\n→ C-fiber irritation. More common in women + Asians.\nFix: Switch to ARB", color:C.orange },
    { title:"Angioedema (rare, dangerous)", body:"Bradykinin-mediated. Can be life-threatening\nlaryngeal swelling. Occurs even after years of use.\nFix: STOP; use icatibant; switch to ARB", color:C.red },
    { title:"Hyperkalemia", body:"↓ Aldosterone → ↓ K⁺ excretion\nRisk ↑ with: renal failure, DM, K⁺ supplements,\nK⁺-sparing diuretics, NSAIDs, heparin", color:C.gold },
    { title:"Acute Renal Failure", body:"In bilateral RAS or solitary kidney RAS:\nLoss of efferent arteriolar AngII tone\n→ GFR collapses. Monitor creatinine.", color:C.red },
    { title:"First-dose Hypotension", body:"Risk if volume-depleted (diuretics, fluid loss).\nStart LOW dose; hold diuretic 24h before.\nEspecially captopril (short-acting).", color:C.blue },
    { title:"Fetal Toxicity", body:"2nd & 3rd trimester: hypotension, oliguria,\nrenal failure, malformations, fetal death.\nCONTRAINDICATED in pregnancy", color:C.navy },
  ];
  aes.forEach((ae, i) => {
    const col = i % 3, row = Math.floor(i/3);
    const x = 0.3 + col * 4.3, y = 1.0 + row * 2.95;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x, y, w:4.1, h:2.75, fill:{ color: ae.color }, rectRadius:0.1,
      shadow:{ type:"outer", color:"000000", blur:6, offset:2, angle:135, opacity:0.15 } });
    s.addText(ae.title, { x, y:y+0.05, w:4.1, h:0.55, fontSize:13.5, bold:true, color:C.white, align:"center", valign:"middle", fontFace:"Calibri" });
    s.addShape(pres.shapes.RECTANGLE, { x, y:y+0.58, w:4.1, h:0.05, fill:{ color:C.white } });
    s.addText(ae.body, { x:x+0.1, y:y+0.65, w:3.9, h:2.0, fontSize:11, color:C.white, fontFace:"Calibri", valign:"top" });
  });

  // Contraindication table
  s.addShape(pres.shapes.RECTANGLE, { x:0.3, y:6.85, w:12.7, h:0.5, fill:{ color:C.navy } });
  s.addText("COMPELLING CONTRAINDICATIONS: Pregnancy • Bilateral RAS • Hyperkalemia • Angioedema history  |  PRECAUTION: Childbearing potential",
    { x:0.3, y:6.85, w:12.7, h:0.5, fontSize:11.5, bold:true, color:C.gold, align:"center", valign:"middle", fontFace:"Calibri" });
}

// ── SLIDE 7 – ARBs ──────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "Angiotensin Receptor Blockers (ARBs)", pres);

  // Mechanism
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:0.3, y:0.9, w:12.7, h:1.0, fill:{ color:"F3F0FF" }, line:{ color:C.lilac, width:2 }, rectRadius:0.08 });
  s.addText([
    { text:"Mechanism: ", options:{ bold:true, color:C.navy, fontSize:13 } },
    { text:"Selective competitive antagonism at AT1 receptors. Unlike ACEi, they do NOT inhibit bradykinin degradation → ", options:{ color:C.dark, fontSize:13 } },
    { text:"no cough, less angioedema.", options:{ bold:true, color:C.lilac, fontSize:13 } },
    { text:"  Blocked AT1 → AngII floods AT2 → additional NO-mediated vasodilation (bonus).", options:{ color:C.dark, fontSize:12 } },
  ], { x:0.5, y:0.93, w:12.3, h:0.92, fontFace:"Calibri", valign:"middle", margin:6 });

  // Drug list
  s.addText("Members", { x:0.3, y:2.05, w:4.0, h:0.38, fontSize:14, bold:true, color:C.lilac, fontFace:"Calibri" });
  const arbs = [
    ["Losartan","First ARB; active metabolite EXP-3174; uricosuric (blocks URAT-1) → use in gout + HTN","★★★"],
    ["Valsartan","HFrEF + HTN; in Sacubitril/Valsartan (ARNi)","★★★"],
    ["Candesartan","Prodrug; long duration; HFrEF benefit","★★"],
    ["Irbesartan","No active metabolite; DM nephropathy (IDNT trial)","★★"],
    ["Telmisartan","Longest t½ (~24h); PPAR-γ agonism; once daily","★★"],
    ["Olmesartan","Potent; sprue-like enteropathy (rare)","★"],
    ["Azilsartan","Newest; strongest BP lowering","★"],
    ["Eprosartan","Non-biphenyl tetrazole","★"],
  ];
  arbs.forEach((r, i) => {
    const isH = false;
    const y = 2.5 + i * 0.52;
    s.addShape(pres.shapes.RECTANGLE, { x:0.3, y, w:2.2, h:0.49, fill:{ color: i%2===0?C.lilac:C.offwht }, line:{ color:C.lt_gray, width:0.5 } });
    s.addText(r[0], { x:0.3, y, w:2.2, h:0.49, fontSize:11.5, bold:true, color: i%2===0?C.white:C.lilac, align:"center", valign:"middle", fontFace:"Calibri" });
    s.addShape(pres.shapes.RECTANGLE, { x:2.52, y, w:6.8, h:0.49, fill:{ color: i%2===0?"F3F0FF":C.white }, line:{ color:C.lt_gray, width:0.5 } });
    s.addText(r[1], { x:2.55, y, w:6.7, h:0.49, fontSize:10.5, color:C.dark, valign:"middle", fontFace:"Calibri", margin:4 });
    s.addShape(pres.shapes.RECTANGLE, { x:9.34, y, w:0.8, h:0.49, fill:{ color: i%2===0?"F3F0FF":C.white }, line:{ color:C.lt_gray, width:0.5 } });
    s.addText(r[2], { x:9.34, y, w:0.8, h:0.49, fontSize:11, color:C.gold, align:"center", valign:"middle", fontFace:"Calibri" });
  });

  // Losartan key fact
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:10.2, y:2.05, w:2.85, h:5.0, fill:{ color:"FFF9E6" }, line:{ color:C.gold, width:2 }, rectRadius:0.1 });
  s.addText("★ LOSARTAN\nHigh-Yield Facts", { x:10.2, y:2.1, w:2.85, h:0.7, fontSize:12, bold:true, color:C.gold, align:"center", valign:"middle", fontFace:"Calibri" });
  const lFacts = ["Only ARB with uricosuric effect","Active metabolite EXP-3174","Shortest t½ (~6-9h)","Prototype / first ARB","Use in gout + HTN","LIFE trial: ↓ stroke vs atenolol"];
  lFacts.forEach((f,i) => s.addText("• " + f, { x:10.25, y:2.85+i*0.52, w:2.75, h:0.5, fontSize:10.5, color:C.dark, fontFace:"Calibri" }));

  // Hemodynamics footer note
  s.addShape(pres.shapes.RECTANGLE, { x:0.3, y:6.85, w:9.7, h:0.5, fill:{ color:"EDE9FE" }, line:{ color:C.lilac, width:1 } });
  s.addText("Hemodynamics: Heart rate ↔ • CO ↔ • TPR ↓ • PRA ↑ (same as ACEi)  |  Plasma Ang II ↑ (AT1 blocked) → AT2 stimulated",
    { x:0.3, y:6.85, w:9.7, h:0.5, fontSize:11, color:C.navy, align:"center", valign:"middle", fontFace:"Calibri" });
}

// ── SLIDE 8 – ACEi vs ARB COMPARISON ────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "ACE Inhibitors vs ARBs – Head-to-Head", pres);

  const headers = ["Feature", "ACE Inhibitors", "ARBs"];
  const rows = [
    ["Target enzyme/receptor", "ACE (kininase II)", "AT1 receptor"],
    ["Bradykinin", "↑↑ (prevents degradation)", "Unchanged"],
    ["Substance P", "↑ (prevents degradation)", "Unchanged"],
    ["Cough", "5–20% (common AE)", "Rare (<1%)"],
    ["Angioedema", "0.1–0.7%", "~0.1% (less)"],
    ["Plasma Ang II", "↓ (less formed)", "↑ (AT1 blocked, backs up)"],
    ["Plasma Renin Activity", "↑ (loss of feedback)", "↑ (loss of feedback)"],
    ["AT2 stimulation", "Unchanged", "↑↑ (Ang II floods AT2)"],
    ["Aldosterone", "↓", "↓"],
    ["Hyperkalemia", "Yes", "Yes (similar risk)"],
    ["Fetal safety", "Contraindicated (2nd/3rd tri)", "Contraindicated"],
    ["Cardiac outcomes (HF)", "First-line (ACEi preferred)", "Non-inferior; use if ACEi intolerant"],
    ["Diabetic nephropathy", "1st-line (captopril trial)", "1st-line (IDNT, RENAAL)"],
    ["Unique feature", "Lisinopril/captopril not prodrugs", "Losartan uricosuric"],
  ];

  const colW = [3.2, 4.3, 5.5], colX = [0.15, 3.4, 7.75];
  const rh = 0.41;
  // header row
  headers.forEach((h,ci) => {
    s.addShape(pres.shapes.RECTANGLE, { x:colX[ci], y:0.85, w:colW[ci]-0.08, h:rh, fill:{ color: ci===0?C.navy:(ci===1?C.teal:C.lilac) }, line:{ color:C.lt_gray, width:0.5 } });
    s.addText(h, { x:colX[ci], y:0.85, w:colW[ci]-0.08, h:rh, fontSize:13, bold:true, color:C.white, align:"center", valign:"middle", fontFace:"Calibri" });
  });
  rows.forEach((row, ri) => {
    const bg = ri%2===0 ? C.offwht : C.white;
    row.forEach((cell, ci) => {
      const y = 1.3 + ri * rh;
      s.addShape(pres.shapes.RECTANGLE, { x:colX[ci], y, w:colW[ci]-0.08, h:rh-0.01, fill:{ color: ci===0?"EEF2FF":bg }, line:{ color:C.lt_gray, width:0.5 } });
      const textColor = cell.includes("Rare") || cell.includes("less") || cell.includes("preferred") ? C.green
        : cell.includes("5–20") || cell.includes("0.1–0.7") || cell.includes("intolerant") ? C.orange
        : cell.includes("Contra") ? C.red : C.dark;
      s.addText(cell, { x:colX[ci]+0.05, y:1.3+ri*rh, w:colW[ci]-0.18, h:rh-0.01, fontSize:10.5, color:textColor, valign:"middle", fontFace:"Calibri", margin:3 });
    });
  });
}

// ── SLIDE 9 – ALISKIREN ──────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "Direct Renin Inhibitor – Aliskiren", pres);

  // Hero box
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:0.3, y:0.9, w:12.7, h:0.95, fill:{ color: C.orange }, rectRadius:0.1 });
  s.addText("Aliskiren – First orally active direct renin inhibitor (DRI) approved for hypertension", {
    x:0.5, y:0.92, w:12.3, h:0.88, fontSize:15, bold:true, color:C.white, align:"center", valign:"middle", fontFace:"Calibri"
  });

  // 3 column info
  const cols = [
    {
      title:"Mechanism",
      color: C.orange,
      items:[
        "Binds directly to renin's active site",
        "Blocks cleavage of angiotensinogen → Ang I",
        "Attacks RATE-LIMITING step of cascade",
        "↓ Plasma renin ACTIVITY (PRA)",
        "↑ Plasma renin CONCENTRATION (PRC) – feedback",
        "Also blocks rise in PRA caused by ACEi/ARBs",
        "Does NOT affect bradykinin levels",
        "→ No cough, no angioedema",
      ]
    },
    {
      title:"Pharmacokinetics",
      color: C.blue,
      items:[
        "Oral bioavailability ~3% (F = 0.03)",
        "Classic example: low-F drug still works",
        "High-fat meal ↓ absorption by 85%",
        "t½ ~ 24 hours (once daily dosing)",
        "Mainly excreted unchanged in feces",
        "NOT a prodrug",
        "P-glycoprotein substrate (drug interactions)",
        "Minimal hepatic metabolism",
      ]
    },
    {
      title:"Adverse Effects / Contraindications",
      color: C.red,
      items:[
        "Hyperkalemia (same RAAS mechanism)",
        "Hypotension (first-dose)",
        "Diarrhea (distinct from ACEi/ARBs)",
        "Renal impairment in susceptible pts",
        "PREGNANCY – contraindicated",
        "Avoid with: ACEi/ARB combination → ↑ AEs",
        "Combination with ACEi/ARB contraindicated",
        "No proven mortality benefit (no CV outcomes)",
      ]
    },
  ];

  cols.forEach((col, ci) => {
    const x = 0.3 + ci * 4.35;
    s.addShape(pres.shapes.RECTANGLE, { x, y:2.0, w:4.1, h:0.5, fill:{ color: col.color }, line:{ color:col.color, width:0 } });
    s.addText(col.title, { x, y:2.0, w:4.1, h:0.5, fontSize:13, bold:true, color:C.white, align:"center", valign:"middle", fontFace:"Calibri" });
    col.items.forEach((item, ii) => {
      const bg = ii%2===0 ? (ci===0?"FFF3E6":(ci===1?"EFF6FF":"FFF0F0")) : C.white;
      s.addShape(pres.shapes.RECTANGLE, { x, y:2.52+ii*0.56, w:4.1, h:0.53, fill:{ color:bg }, line:{ color:C.lt_gray, width:0.5 } });
      const tc = item.includes("contraind") || item.includes("PREG") ? C.red : C.dark;
      s.addText("• " + item, { x:x+0.08, y:2.52+ii*0.56, w:3.98, h:0.53, fontSize:10.5, color:tc, valign:"middle", fontFace:"Calibri", margin:3 });
    });
  });

  // PRA comparison
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:0.3, y:7.0, w:12.7, h:0.38, fill:{ color:"EFF6FF" }, line:{ color:C.blue, width:1 }, rectRadius:0.06 });
  s.addText("PRA Effect Comparison: ACEi ↑PRA  |  ARBs ↑PRA  |  Aliskiren ↓PRA (unique) – eliminates compensatory renin rise caused by ACEi, ARBs, diuretics",
    { x:0.3, y:7.0, w:12.7, h:0.38, fontSize:10.5, color:C.blue, align:"center", valign:"middle", fontFace:"Calibri" });
}

// ── SLIDE 10 – ARNi ──────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "ARNi – Sacubitril/Valsartan (Entresto)", pres);

  // Mechanism diagram
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:0.3, y:0.9, w:12.7, h:4.7, fill:{ color:"F0F9FF" }, line:{ color:C.sky, width:2 }, rectRadius:0.1 });
  s.addText("Dual Mechanism", { x:0.5, y:0.95, w:4, h:0.4, fontSize:14, bold:true, color:C.sky, fontFace:"Calibri" });

  // Left – Sacubitril arm
  box(s, pres, 0.5, 1.48, 3.5, 0.7, C.sky, "Sacubitril (prodrug)", C.white, 13, true);
  arrowDown(s, pres, 0.5+1.59, 2.22, C.sky);
  box(s, pres, 0.5, 2.68, 3.5, 0.7, C.blue, "LBQ657 (active)\nNeprilysin Inhibitor", C.white, 12, true);
  arrowDown(s, pres, 0.5+1.59, 3.42, C.blue);
  box(s, pres, 0.5, 3.88, 3.5, 0.7, C.teal, "↑ ANP, BNP, Bradykinin\n(less breakdown by neprilysin)", C.white, 12, false);
  arrowDown(s, pres, 0.5+1.59, 4.62, C.teal);
  box(s, pres, 0.5, 5.08, 3.5, 0.65, C.green, "Vasodilation, Natriuresis\n↓ Cardiac Fibrosis, ↓ Hypertrophy", C.white, 11.5, false);

  // Right – Valsartan arm
  box(s, pres, 9.3, 1.48, 3.5, 0.7, C.lilac, "Valsartan (ARB)", C.white, 13, true);
  arrowDown(s, pres, 9.3+1.59, 2.22, C.lilac);
  box(s, pres, 9.3, 2.68, 3.5, 0.7, C.lilac, "AT1 Receptor Blockade", C.white, 13, true);
  arrowDown(s, pres, 9.3+1.59, 3.42, C.lilac);
  box(s, pres, 9.3, 3.88, 3.5, 0.7, C.navy, "↓ AngII effects\n↑ AT2 stimulation", C.white, 12, false);
  arrowDown(s, pres, 9.3+1.59, 4.62, C.navy);
  box(s, pres, 9.3, 5.08, 3.5, 0.65, C.green, "Vasodilation, ↓ Aldosterone\n↓ Remodeling, ↓ Afterload", C.white, 11.5, false);

  // Center – combined effect
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:4.5, y:2.0, w:4.3, h:3.8, fill:{ color:C.green }, rectRadius:0.12,
    shadow:{ type:"outer", color:"000000", blur:8, offset:3, angle:135, opacity:0.18 } });
  s.addText("Combined\nBenefit", { x:4.5, y:2.05, w:4.3, h:0.7, fontSize:15, bold:true, color:C.white, align:"center", valign:"middle", fontFace:"Calibri" });
  const comb = ["↓ Mortality (PARADIGM-HF)", "↓ HF hospitalizations", "↓ Cardiac fibrosis", "↓ LV remodeling", "↑ Quality of life", "↑ Exercise tolerance"];
  comb.forEach((c, i) => s.addText("✔  " + c, { x:4.6, y:2.82+i*0.5, w:4.0, h:0.46, fontSize:12, color:C.white, fontFace:"Calibri", valign:"middle" }));

  // Bottom notes
  s.addShape(pres.shapes.RECTANGLE, { x:0.3, y:5.9, w:12.7, h:1.45, fill:{ color:C.navy } });
  const notes = [
    "INDICATION: HFrEF (EF ≤40%) – superior to enalapril (PARADIGM-HF). NOT approved for hypertension alone.",
    "WARNING: NEVER combine with ACE inhibitor → dual bradykinin ↑ → severe angioedema. Require 36-hour washout after last ACEi dose.",
    "Contraindicated in pregnancy. Check potassium + renal function regularly.",
  ];
  notes.forEach((n,i) => s.addText((i===1?"⚠️  ":"• ") + n, { x:0.5, y:5.95+i*0.45, w:12.3, h:0.42, fontSize:10.5, color: i===1?C.gold:C.lt_gray, fontFace:"Calibri", valign:"middle" }));
}

// ── SLIDE 11 – MASTER COMPARISON TABLE ──────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "Master Comparison – All RAAS Drug Classes", pres);

  const headers2 = ["Feature", "ACE Inhibitors", "ARBs", "Aliskiren (DRI)", "ARNi (Sacubitril/Val)"];
  const colWs = [2.4, 2.6, 2.35, 2.35, 3.4];
  const colXs = [0.15, 2.6, 5.22, 7.6, 9.98];
  const hColors = [C.navy, C.teal, C.lilac, C.orange, C.sky];

  headers2.forEach((h,ci) => {
    s.addShape(pres.shapes.RECTANGLE, { x:colXs[ci], y:0.82, w:colWs[ci]-0.06, h:0.52, fill:{ color:hColors[ci] }, line:{ color:C.lt_gray, width:0.5 } });
    s.addText(h, { x:colXs[ci], y:0.82, w:colWs[ci]-0.06, h:0.52, fontSize:11.5, bold:true, color:C.white, align:"center", valign:"middle", fontFace:"Calibri" });
  });

  const mRows = [
    ["Target", "ACE (kininase II)", "AT1 receptor", "Renin (active site)", "Neprilysin + AT1"],
    ["Bradykinin", "↑↑", "Unchanged", "Unchanged", "↑ (neprilysin block)"],
    ["Cough", "5–20% (bradykinin)", "Rare (<1%)", "None", "Possible"],
    ["Angioedema", "0.1–0.7%", "Very rare", "None", "Rare (avoid with ACEi)"],
    ["PRA (plasma renin)", "↑ (reflex)", "↑ (reflex)", "↓ (direct block)", "↑"],
    ["Plasma Ang II", "↓", "↑ (AT1 blocked)", "↓", "↑ (valsartan blocks it)"],
    ["Aldosterone", "↓", "↓", "↓", "↓"],
    ["K⁺ (hyperkalemia)", "Risk yes", "Risk yes", "Risk yes", "Risk yes"],
    ["Pregnancy", "CI (2nd/3rd tri)", "CI", "CI", "CI"],
    ["Primary use", "HTN, HF, DM nephropathy", "HTN, HF (ACEi intol)", "HTN only", "HFrEF (NOT HTN alone)"],
    ["Unique fact", "Captopril/Lisinopril not prodrugs", "Losartan uricosuric", "Lowest F (~3%)", "36h washout from ACEi"],
  ];

  const rh2 = 0.5;
  mRows.forEach((row, ri) => {
    row.forEach((cell, ci) => {
      const y = 1.38 + ri * rh2;
      const bg = ci===0 ? "EEF2FF" : (ri%2===0?C.offwht:C.white);
      s.addShape(pres.shapes.RECTANGLE, { x:colXs[ci], y, w:colWs[ci]-0.06, h:rh2-0.02, fill:{ color:bg }, line:{ color:C.lt_gray, width:0.5 } });
      const tc = (cell.includes("CI") || cell.includes("risk")) ? C.red
        : (cell.includes("Rare") || cell.includes("None") || cell.includes("not prodrug")) ? C.green
        : (cell.includes("↑↑") || cell.includes("5–20")) ? C.orange
        : C.dark;
      s.addText(cell, { x:colXs[ci]+0.05, y, w:colWs[ci]-0.16, h:rh2-0.02, fontSize:10, color:tc, valign:"middle", fontFace:"Calibri", margin:3 });
    });
  });
}

// ── SLIDE 12 – RENAL PHYSIOLOGY SCENARIOS ───────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "High-Yield Renal Scenarios – Why & How RAAS Drugs Work", pres);

  // Scenario 1 – Normal kidney
  const scenarios = [
    {
      title:"Diabetic Nephropathy",
      subtitle:"ACEi / ARB: PREFERRED",
      color: C.green,
      path:["↑ Intraglomerular pressure (AngII constricts efferent arteriole)", "→ Hyperfiltration → Proteinuria → Glomerulosclerosis"],
      rx:["ACEi/ARB dilates EFFERENT arteriole", "↓ Intraglomerular pressure", "↓ Proteinuria (even without ↓ BP)", "↓ Progression to ESRD", "Recommended even if NORMOTENSIVE"],
    },
    {
      title:"Bilateral Renal Artery Stenosis",
      subtitle:"ACEi / ARB: CONTRAINDICATED",
      color: C.red,
      path:["Low flow to both kidneys", "AngII REQUIRED to constrict efferent arteriole", "→ Maintains GFR under low perfusion pressure"],
      rx:["ACEi/ARB removes efferent AngII constriction", "GFR collapses → Acute renal failure", "Creatinine rises sharply after starting drug", "Contraindicated in bilateral RAS"],
    },
    {
      title:"Heart Failure",
      subtitle:"ACEi / ARB / ARNi: CORE THERAPY",
      color: C.blue,
      path:["↓ CO → AngII activation (compensatory)", "↑ Afterload, ↑ preload, cardiac remodeling", "Short-term survival ↑ but long-term cardiac death ↑"],
      rx:["ACEi → ↓ AngII → ↓ afterload + preload", "↓ Aldosterone → ↓ Na/H₂O retention", "↓ Cardiac remodeling, ↓ hypertrophy", "ARNi (sacubitril/valsartan) > enalapril (PARADIGM-HF)"],
    },
  ];

  scenarios.forEach((sc, i) => {
    const x = 0.25 + i * 4.35;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x, y:0.85, w:4.1, h:6.45, fill:{ color:sc.color }, rectRadius:0.1,
      shadow:{ type:"outer", color:"000000", blur:6, offset:2, angle:135, opacity:0.15 } });
    s.addText(sc.title, { x, y:0.9, w:4.1, h:0.5, fontSize:13, bold:true, color:C.white, align:"center", valign:"middle", fontFace:"Calibri" });
    s.addText(sc.subtitle, { x, y:1.43, w:4.1, h:0.38, fontSize:11, bold:true, color: sc.color===C.red?C.gold:C.white, align:"center", valign:"middle", fontFace:"Calibri", italic:true });
    s.addShape(pres.shapes.RECTANGLE, { x, y:1.84, w:4.1, h:0.05, fill:{ color:C.white } });
    s.addText("Pathophysiology:", { x:x+0.1, y:1.92, w:3.9, h:0.35, fontSize:11, bold:true, color:C.white, fontFace:"Calibri" });
    sc.path.forEach((p,pi) => s.addText("▸ " + p, { x:x+0.1, y:2.3+pi*0.48, w:3.9, h:0.45, fontSize:10, color:C.white, fontFace:"Calibri" }));
    s.addShape(pres.shapes.RECTANGLE, { x, y:3.72, w:4.1, h:0.04, fill:{ color:C.white } });
    s.addText("Drug Effect:", { x:x+0.1, y:3.78, w:3.9, h:0.35, fontSize:11, bold:true, color:C.white, fontFace:"Calibri" });
    sc.rx.forEach((r,ri) => s.addText("✔ " + r, { x:x+0.1, y:4.18+ri*0.56, w:3.9, h:0.52, fontSize:10.5, color:C.white, fontFace:"Calibri", valign:"top" }));
  });
}

// ── SLIDE 13 – DRUG INTERACTIONS ────────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "Clinically Important Drug Interactions", pres);

  const interactions = [
    { drug:"ACEi + K⁺-sparing diuretics\n(Spironolactone, Amiloride)", effect:"Severe Hyperkalemia", mech:"Both reduce K⁺ excretion. Additive effect.", severity:"DANGER", color:C.red },
    { drug:"ACEi + NSAIDs", effect:"↓ Antihypertensive effect + AKI risk", mech:"NSAIDs block prostaglandin vasodilation in kidney; reduce kinin effects", severity:"CAUTION", color:C.orange },
    { drug:"ACEi + Potassium supplements", effect:"Hyperkalemia", mech:"Direct K⁺ loading + reduced renal excretion", severity:"CAUTION", color:C.orange },
    { drug:"ACEi + Thiazides (LOW dose)", effect:"Enhanced BP lowering (beneficial)", mech:"ACEi blocks aldosterone counter-regulation; potentiates diuresis", severity:"SYNERGY", color:C.green },
    { drug:"ACEi + Thiazides (HIGH dose)", effect:"Severe hypotension / volume depletion", mech:"Excessive natriuresis without aldosterone compensation", severity:"CAUTION", color:C.orange },
    { drug:"ARNi + ACE Inhibitor", effect:"Life-threatening angioedema", mech:"Double bradykinin accumulation (neprilysin + ACE both blocked)", severity:"ABSOLUTE CI", color:C.red },
    { drug:"Aliskiren + ACEi or ARB", effect:"No benefit + ↑ AEs (hypotension, K⁺, AKI)", mech:"Dual RAAS blockade; no outcome benefit proven", severity:"CONTRAINDICATED", color:C.red },
    { drug:"ACEi + Lithium", effect:"Lithium toxicity", mech:"ACEi reduce renal Li⁺ clearance → toxicity", severity:"CAUTION", color:C.orange },
  ];

  const cols = ["Drug Combination", "Effect", "Mechanism", "Risk Level"];
  const cw = [3.1, 2.6, 4.8, 2.5], cx = [0.15, 3.3, 5.95, 10.8];
  cols.forEach((h,ci) => {
    s.addShape(pres.shapes.RECTANGLE, { x:cx[ci], y:0.85, w:cw[ci]-0.06, h:0.46, fill:{ color:C.navy }, line:{ color:C.lt_gray, width:0.5 } });
    s.addText(h, { x:cx[ci], y:0.85, w:cw[ci]-0.06, h:0.46, fontSize:12, bold:true, color:C.white, align:"center", valign:"middle", fontFace:"Calibri" });
  });

  interactions.forEach((row, ri) => {
    const y = 1.35 + ri * 0.72;
    const vals = [row.drug, row.effect, row.mech, row.severity];
    vals.forEach((v, ci) => {
      const bg = ri%2===0 ? C.offwht : C.white;
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    });
  });
}

// ── SLIDE 14 – HIGH-YIELD MNEMONICS ─────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "High-Yield Memory Tricks & Exam Tips", pres);

  // ACEi side effects mnemonic
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  s.addText("ACEi Side Effects: CAPTOPRIL", { x:0.4, y:0.95, w:5.9, h:0.5, fontSize:14, bold:true, color:C.navy, fontFace:"Calibri" });
  const acro = [
    ["C","Cough (bradykinin/substance P)"],
    ["A","Angioedema (life-threatening)"],
    ["P","Potassium ↑ (hyperkalemia)"],
    ["T","Taste disturbance / Teratogenic"],
    ["O","hOrrible for Bilateral RAS"],
    ["P","Proteinuria in renal pts (rare)"],
    ["R","Renal failure (1st dose, volume depleted)"],
    ["I","Induced hypotension (1st dose)"],
    ["L","Liver: prodrugs need hepatic conversion"],
  ];
  acro.forEach(([letter, meaning], i) => {
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    s.addText(letter, { x:0.4, y:1.52+i*0.32, w:0.35, h:0.29, fontSize:12, bold:true, color:C.white, align:"center", valign:"middle", fontFace:"Calibri" });
    s.addText(meaning, { x:0.8, y:1.52+i*0.32, w:5.5, h:0.29, fontSize:11, color:C.dark, valign:"middle", fontFace:"Calibri" });
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    ["L","Losartan (prototype, uricosuric)"],
    ["A","Azilsartan (newest)"],
    ["V","Valsartan (in ARNi)"],
    ["E","Eprosartan"],
    ["C","Candesartan (prodrug, HFrEF)"],
    ["I","Irbesartan (DM nephropathy)"],
    ["T","Telmisartan (longest t½)"],
    ["O","Olmesartan (sprue-like enteropathy)"],
  ];
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  const pearls = [
    "Only ACEi that is NOT a prodrug and has –SH group → Captopril (also used IV emergencies? No – Enalaprilat is IV)",
    "Only ARB with uricosuric effect → Losartan (also has active metabolite EXP-3174)",
    "Only DRI approved for HTN → Aliskiren (does NOT cause cough, does NOT improve CV outcomes)",
    "ARNi is contraindicated WITH ACEi (36-hr washout needed) – double bradykinin = angioedema",
    "First-dose hypotension risk highest with Captopril in volume-depleted patients (short-acting)",
    "ACEi preferred post-MI with LV dysfunction; reduce remodeling, mortality (SAVE, HOPE trials)",
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      line:{ color:C.lt_gray, width:0.5 }
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}

// ── SLIDE 15 – MCQ SUMMARY ───────────────────────────────────────────────────
{
  const s = pres.addSlide();
  slideTitle(s, "Top 5 Must-Know MCQ Concepts", pres);

  const mcqs = [
    {
      q:"Q1. Which drug causes cough by accumulating bradykinin + substance P?",
      a:"ACE Inhibitor (NOT ARBs, NOT Aliskiren)",
      color: C.teal,
    },
    {
      q:"Q2. Which ACE inhibitor is NOT a prodrug AND has a sulfhydryl (–SH) group?",
      a:"Captopril (Lisinopril is also not a prodrug, but has no –SH group)",
      color: C.blue,
    },
    {
      q:"Q3. ACE inhibitor is contraindicated in bilateral RAS because...",
      a:"Removes efferent arteriolar AngII tone → GFR collapses → Acute Renal Failure",
      color: C.red,
    },
    {
      q:"Q4. What is the unique property of Losartan among ARBs?",
      a:"Uricosuric effect (blocks URAT-1) → drug of choice in HTN + Gout",
      color: C.lilac,
    },
    {
      q:"Q5. Sacubitril/valsartan (ARNi) must NEVER be combined with...",
      a:"ACE Inhibitors (36-hr washout required). Risk: severe angioedema from dual bradykinin potentiation",
      color: C.orange,
    },
  ];
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    s.addShape(pres.shapes.RECTANGLE, { x:0.3, y:y+0.55, w:12.7, h:0.04, fill:{ color:C.white } });
    s.addText("→ " + mcq.a, { x:0.45, y:y+0.62, w:12.35, h:0.48, fontSize:12, color:C.white, fontFace:"Calibri", valign:"middle", italic:true });
  });
}

// ── SLIDE 16 – CLOSING ───────────────────────────────────────────────────────
{
  const s = pres.addSlide();
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  s.addShape(pres.shapes.RECTANGLE, { x:0, y:5.78, w:13.3, h:0.08, fill:{ color:C.gold } });
  s.addText("Key Takeaways", { x:1, y:0.8, w:11.3, h:0.9, fontSize:38, bold:true, color:C.gold, align:"center", fontFace:"Calibri" });
  const takes = [
    "ACEi: Dual action (↓AngII + ↑bradykinin). Cough/angioedema = bradykinin side effects.",
    "ARBs: Selective AT1 block. No cough. Redirect AngII to AT2 (bonus vasodilation).",
    "Aliskiren: Attacks rate-limiting step. Only DRI. ↓PRA (unique). No CV outcome benefit proven.",
    "ARNi: Neprilysin + AT1 block. Superior to enalapril in HFrEF. 36-hr washout from ACEi.",
    "Bilateral RAS + ACEi/ARB = Acute renal failure (loss of efferent arteriolar tone).",
    "Dual RAAS blockade (ACEi + ARB or + Aliskiren) = No additional benefit + ↑ adverse effects.",
  ];
  takes.forEach((t,i) => {
    s.addText("• " + t, { x:1, y:1.85+i*0.63, w:11.3, h:0.6, fontSize:14, color:C.white, fontFace:"Calibri", valign:"middle" });
  });
  s.addText("References: Goodman & Gilman 14e  •  Katzung Basic & Clinical Pharmacology 16e  •  KD Tripathi Essentials of Medical Pharmacology",
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}

pres.writeFile({ fileName: "/home/daytona/workspace/raas-pptx/RAAS_Inhibitors_Pharmacology.pptx" })
  .then(() => console.log("SUCCESS: RAAS_Inhibitors_Pharmacology.pptx written"))
  .catch(e => { console.error("ERROR:", e); process.exit(1); });

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<body>

<!-- TOP NAV -->
<div class="top-nav">
  <button class="nav-btn" id="prevBtn" onclick="changeSlide(-1)" disabled>◀ Prev</button>
  <h1>RAAS Inhibitors</h1>
  <span class="slide-counter" id="counter">1 / 16</span>
  <button class="nav-btn" id="nextBtn" onclick="changeSlide(1)">Next ▶</button>
</div>

<div class="slides-wrap">

<!-- ═══════════════════════════════════════════════════════ SLIDE 1 – TITLE -->
<div class="slide active" id="slide-1">
  <div class="title-slide">
    <div style="font-size:48px; margin-bottom:10px;">💊</div>
    <h1>RAAS Inhibitors</h1>
    <div class="gold">Pharmacology</div>
    <div class="sub">Mechanism • Drug Classes • Clinical Uses • High-Yield Exam Tips</div>
    <div style="margin-top: 28px; display:flex; gap:10px; flex-wrap:wrap; justify-content:center;">
      <span class="badge badge-blue">ACE Inhibitors</span>
      <span class="badge badge-blue" style="background:#7C3AED">ARBs</span>
      <span class="badge badge-orange">Aliskiren</span>
      <span class="badge badge-blue" style="background:#0D7C7C">ARNi</span>
    </div>
    <div class="refs">📚 References: Goodman &amp; Gilman 14e &nbsp;•&nbsp; Katzung Basic &amp; Clinical Pharmacology 16e &nbsp;•&nbsp; KD Tripathi Essentials of Medical Pharmacology</div>
  </div>
</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 2 – CONTENTS -->
<div class="slide" id="slide-2">
  <div class="slide-header"><h2>📋 Contents at a Glance</h2><div class="subtitle">Tap any topic to jump to it</div></div>
  <div class="slide-body">
    <div class="contents-item" onclick="goToSlide(3)" style="border-color:#3B8EC8"><div class="contents-num" style="background:#3B8EC8">1</div><div class="contents-text">Classical RAAS Cascade</div></div>
    <div class="contents-item" onclick="goToSlide(4)" style="border-color:#0D7C7C"><div class="contents-num" style="background:#0D7C7C">2</div><div class="contents-text">Sites of Drug Action (Diagram)</div></div>
    <div class="contents-item" onclick="goToSlide(5)" style="border-color:#1A3E8C"><div class="contents-num" style="background:#1A3E8C">3</div><div class="contents-text">ACE Inhibitors – Mechanism &amp; Pharmacology</div></div>
    <div class="contents-item" onclick="goToSlide(6)" style="border-color:#C0392B"><div class="contents-num" style="background:#C0392B">4</div><div class="contents-text">ACE Inhibitors – Adverse Effects &amp; Contraindications</div></div>
    <div class="contents-item" onclick="goToSlide(7)" style="border-color:#7C3AED"><div class="contents-num" style="background:#7C3AED">5</div><div class="contents-text">ARBs – Angiotensin Receptor Blockers</div></div>
    <div class="contents-item" onclick="goToSlide(8)" style="border-color:#0B1F4B"><div class="contents-num" style="background:#0B1F4B">6</div><div class="contents-text">ACEi vs ARBs – Head-to-Head</div></div>
    <div class="contents-item" onclick="goToSlide(9)" style="border-color:#E06C2A"><div class="contents-num" style="background:#E06C2A">7</div><div class="contents-text">Direct Renin Inhibitor – Aliskiren</div></div>
    <div class="contents-item" onclick="goToSlide(10)" style="border-color:#1D7A4E"><div class="contents-num" style="background:#1D7A4E">8</div><div class="contents-text">ARNi – Sacubitril/Valsartan</div></div>
    <div class="contents-item" onclick="goToSlide(11)" style="border-color:#E8A020"><div class="contents-num" style="background:#E8A020; color:#1E293B">9</div><div class="contents-text">Master Comparison – All 4 Classes</div></div>
    <div class="contents-item" onclick="goToSlide(12)" style="border-color:#3B8EC8"><div class="contents-num" style="background:#3B8EC8">10</div><div class="contents-text">Clinical Scenarios – Renal Physiology</div></div>
    <div class="contents-item" onclick="goToSlide(13)" style="border-color:#C0392B"><div class="contents-num" style="background:#C0392B">11</div><div class="contents-text">Drug Interactions</div></div>
    <div class="contents-item" onclick="goToSlide(14)" style="border-color:#1D7A4E"><div class="contents-num" style="background:#1D7A4E">12</div><div class="contents-text">Mnemonics &amp; Exam Pearls</div></div>
    <div class="contents-item" onclick="goToSlide(15)" style="border-color:#7C3AED"><div class="contents-num" style="background:#7C3AED">13</div><div class="contents-text">Top 5 MCQ Concepts</div></div>
    <div class="contents-item" onclick="goToSlide(16)" style="border-color:#0D7C7C"><div class="contents-num" style="background:#0D7C7C">14</div><div class="contents-text">Key Takeaways</div></div>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 3 – RAAS CASCADE -->
<div class="slide" id="slide-3">
  <div class="slide-header"><h2>🔄 Classical RAAS Cascade</h2><div class="subtitle">Rate-limiting step = Renin → Angiotensin I</div></div>
  <div class="slide-body">
    <div class="mech-diagram">
      <div class="mech-label">Liver</div>
      <div class="flow">
        <div class="flow-box" style="background:#64748B">Angiotensinogen (α₂-globulin)</div>
        <div class="flow-arrow"><span style="font-size:10px; color:#E06C2A; position:absolute; right:10px;">⭐ RENIN (JG cells – rate-limiting)</span></div>
        <div class="flow-box">Angiotensin I (decapeptide)</div>
        <div class="flow-arrow"><span style="font-size:10px; color:#0D7C7C; position:absolute; right:10px;">ACE (lung endothelium)</span></div>
        <div class="flow-box ang2">Angiotensin II (octapeptide – ACTIVE)</div>
        <div class="flow-arrow"></div>
        <div style="display:grid; grid-template-columns:1fr 1fr; gap:8px; width:100%;">
          <div class="flow-box at1" style="border-radius:8px; font-size:11px;">AT₁ Receptor</div>
          <div class="flow-box" style="background:#1D7A4E; border-radius:8px; font-size:11px;">AT₂ Receptor</div>
        </div>
      </div>
      <div class="highlight" style="margin-top:10px; font-size:11.5px;">⚠️ Non-ACE pathways (chymase, cathepsin G) also make Ang II — explains why ACEi blockade is never 100% complete</div>
    </div>

    <div class="receptor-grid">
      <div class="card card-red">
        <div class="card-title">AT₁ Effects (Harmful)</div>
        <ul style="font-size:12px; padding-left:16px; line-height:1.7;">
          <li>Vasoconstriction ↑ SVR</li>
          <li>Aldosterone secretion → Na⁺/H₂O retention</li>
          <li>Cardiac & vascular hypertrophy</li>
          <li>↑ Sympathetic tone (NE release)</li>
          <li>ADH release → water reabsorption</li>
          <li>↓ Renin (negative feedback)</li>
        </ul>
      </div>
      <div class="card card-green">
        <div class="card-title">AT₂ Effects (Protective)</div>
        <ul style="font-size:12px; padding-left:16px; line-height:1.7;">
          <li>Vasodilation (↑ NO, ↑ cGMP)</li>
          <li>Anti-proliferative / anti-fibrotic</li>
          <li>↑ Bradykinin → vasodilation</li>
          <li>Upregulated when AT₁ blocked</li>
          <li>Counter-balances AT₁ effects</li>
          <li>Cardioprotective in disease</li>
        </ul>
      </div>
    </div>

    <div class="highlight blue">
      💡 <strong>Key Concept:</strong> ARBs block AT₁ → Ang II floods AT₂ → bonus vasodilation + anti-fibrotic effect. This is one pharmacological advantage ARBs have over ACEi.
    </div>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 4 – DRUG ACTION SITES -->
<div class="slide" id="slide-4">
  <div class="slide-header"><h2>🎯 Sites of Drug Action on RAAS</h2></div>
  <div class="slide-body">
    <div class="mech-diagram">
      <div class="flow" style="position:relative;">

        <div style="display:grid; grid-template-columns:1fr auto 1fr; gap:8px; width:100%; align-items:center; margin-bottom:4px;">
          <div class="card card-navy" style="padding:8px; font-size:11px; border-radius:8px; text-align:center;">
            <strong>β-Blockers</strong><br><span style="font-size:10px; color:#94a3b8">↓ Renin release from JG cells</span>
          </div>
          <div class="mech-arrow">→</div>
          <div class="flow-box" style="background:#64748B; font-size:12px;">Angiotensinogen</div>
        </div>

        <div style="display:grid; grid-template-columns:1fr auto 1fr; gap:8px; width:100%; align-items:center; margin-bottom:4px;">
          <div class="card card-orange" style="padding:8px; font-size:11px; border-radius:8px; text-align:center;">
            <strong>Aliskiren (DRI)</strong><br><span style="font-size:10px;">Direct renin inhibitor</span>
          </div>
          <div style="color:#C0392B; font-size:20px;">✖</div>
          <div>
            <div class="flow-box" style="font-size:12px;">Angiotensin I</div>
            <div style="text-align:center; font-size:10px; color:#E06C2A; font-weight:700; margin:2px 0;">⬇ RENIN (rate-limiting)</div>
          </div>
        </div>

        <div style="display:grid; grid-template-columns:1fr auto 1fr; gap:8px; width:100%; align-items:center; margin-bottom:4px;">
          <div class="card card-teal" style="padding:8px; font-size:11px; border-radius:8px; text-align:center;">
            <strong>ACE Inhibitors</strong><br><span style="font-size:10px;">Captopril, Enalapril, Lisinopril…</span>
          </div>
          <div style="color:#C0392B; font-size:20px;">✖</div>
          <div>
            <div class="flow-box ang2" style="font-size:12px;">Angiotensin II</div>
            <div style="text-align:center; font-size:10px; color:#0D7C7C; font-weight:700; margin:2px 0;">⬇ ACE (lung)</div>
          </div>
        </div>

        <div style="display:grid; grid-template-columns:1fr auto 1fr; gap:8px; width:100%; align-items:center; margin-bottom:4px;">
          <div class="card card-lilac" style="padding:8px; font-size:11px; border-radius:8px; text-align:center;">
            <strong>ARBs</strong><br><span style="font-size:10px;">Losartan, Valsartan…</span>
          </div>
          <div style="color:#C0392B; font-size:20px;">✖</div>
          <div class="flow-box at1" style="font-size:12px;">AT₁ Receptor</div>
        </div>

        <div style="display:grid; grid-template-columns:1fr auto 1fr; gap:8px; width:100%; align-items:center; margin-bottom:4px;">
          <div class="card card-green" style="padding:8px; font-size:11px; border-radius:8px; text-align:center;">
            <strong>Aldosterone Antagonists</strong><br><span style="font-size:10px;">Spironolactone, Eplerenone</span>
          </div>
          <div style="color:#C0392B; font-size:20px;">✖</div>
          <div class="flow-box" style="background:#E8A020; color:#1E293B; font-size:12px;">Aldosterone (adrenal cortex)</div>
        </div>

      </div>
    </div>

    <div class="card card-sky" style="margin-top:10px;">
      <div class="card-title">ARNi – Sacubitril/Valsartan</div>
      <p style="font-size:12px;">Blocks <strong>neprilysin</strong> (↑ ANP/BNP/bradykinin) + blocks <strong>AT₁</strong> (valsartan). Dual action for heart failure.</p>
    </div>

    <div class="highlight red">
      <strong>Remember:</strong> Only ACEi also ↑ bradykinin (kininase II block). ARBs, aliskiren, and aldosterone antagonists do NOT affect bradykinin.
    </div>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 5 – ACEi MECHANISM -->
<div class="slide" id="slide-5">
  <div class="slide-header"><h2>💊 ACE Inhibitors – Mechanism &amp; Pharmacology</h2></div>
  <div class="slide-body">

    <div class="card card-light-blue">
      <div class="card-title" style="color:#0B1F4B;">⚙️ Mechanism (Dual Action)</div>
      <div style="display:grid; grid-template-columns:1fr 1fr; gap:8px; margin-top:6px;">
        <div style="background:#1A3E8C; border-radius:8px; padding:10px; text-align:center;">
          <div style="font-size:11px; font-weight:700; color:#E8A020;">Action 1</div>
          <div style="font-size:12px; color:#fff; margin-top:4px;">↓ Ang I → Ang II<br><span style="font-size:10px; color:#cbd5e1;">(blocks ACE/kininase II)</span></div>
        </div>
        <div style="background:#0D7C7C; border-radius:8px; padding:10px; text-align:center;">
          <div style="font-size:11px; font-weight:700; color:#E8A020;">Action 2</div>
          <div style="font-size:12px; color:#fff; margin-top:4px;">↑ Bradykinin + Substance P<br><span style="font-size:10px; color:#cbd5e1;">(prevents degradation)</span></div>
        </div>
      </div>
      <p style="font-size:11.5px; margin-top:8px; color:#334155;">→ Vasodilation via: reduced AngII <strong>AND</strong> NO/prostacyclin from bradykinin. Proven by: icatibant (bradykinin antagonist) blunts captopril's BP effect.</p>
    </div>

    <div class="card-title" style="margin:12px 0 6px; font-size:14px;">🧬 Prodrug Status (High-Yield)</div>
    <table class="tbl">
      <tr><th>Drug</th><th>Prodrug?</th><th>Active Form</th><th>Clearance</th></tr>
      <tr><td><strong>Captopril</strong></td><td class="good">NO (–SH)</td><td>Captopril</td><td>Renal</td></tr>
      <tr><td><strong>Lisinopril</strong></td><td class="good">NO (lysine)</td><td>Lisinopril</td><td>Renal</td></tr>
      <tr><td>Enalapril</td><td class="warn">YES</td><td>Enalaprilat (IV only)</td><td>Renal</td></tr>
      <tr><td>Ramipril</td><td class="warn">YES</td><td>Ramiprilat</td><td>Renal</td></tr>
      <tr><td>Fosinopril</td><td class="warn">YES</td><td>Fosinoprilat</td><td class="good">Hepatic ★</td></tr>
      <tr><td>Moexipril</td><td class="warn">YES</td><td>Moexiprilat</td><td class="good">Hepatic ★</td></tr>
      <tr><td>Benazepril, Quinapril, Perindopril, Trandolapril</td><td class="warn">YES</td><td>Active acid</td><td>Renal</td></tr>
    </table>
    <div class="highlight" style="font-size:11.5px; margin-top:8px;">★ Fosinopril &amp; Moexipril — hepatic clearance. Safer in renal failure.</div>

    <div class="card-title" style="margin:12px 0 6px; font-size:14px;">✅ Key Indications</div>
    <div class="grid-2">
      <div class="card card-blue" style="padding:10px;"><p style="font-size:12px; line-height:1.7;">• Hypertension (1st line)<br>• Heart Failure (HFrEF)<br>• Post-MI (↓ remodeling, ↓ mortality)</p></div>
      <div class="card card-green" style="padding:10px;"><p style="font-size:12px; line-height:1.7;">• Diabetic nephropathy<br>• CKD (↓ proteinuria)<br>• Prevention of DM in high CV-risk</p></div>
    </div>

    <div class="card-title" style="margin:12px 0 6px; font-size:14px;">📊 Hemodynamic Profile</div>
    <table class="tbl">
      <tr><th>Parameter</th><th>Effect</th></tr>
      <tr><td>Heart Rate</td><td class="good">↔ (no reflex tachycardia ✓)</td></tr>
      <tr><td>Cardiac Output</td><td>↔</td></tr>
      <tr><td>Total Peripheral Resistance</td><td class="good">↓ (main BP effect)</td></tr>
      <tr><td>Plasma Renin Activity (PRA)</td><td class="warn">↑ (compensatory reflex)</td></tr>
      <tr><td>Aldosterone</td><td class="good">↓</td></tr>
    </table>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 6 – ACEi ADVERSE EFFECTS -->
<div class="slide" id="slide-6">
  <div class="slide-header"><h2>⚠️ ACEi – Adverse Effects &amp; Contraindications</h2></div>
  <div class="slide-body">

    <div class="grid-2">
      <div class="card card-orange" style="padding:12px;">
        <div class="card-title">😤 Dry Cough (5–20%)</div>
        <p style="font-size:12px; line-height:1.6;">Bradykinin + Substance P accumulate in lungs → C-fiber stimulation.<br><br>More common in: women, Asians.<br><br><strong>Fix:</strong> Switch to ARB (no bradykinin effect).</p>
      </div>
      <div class="card card-red" style="padding:12px;">
        <div class="card-title">🚨 Angioedema (rare but dangerous)</div>
        <p style="font-size:12px; line-height:1.6;">Bradykinin-mediated. Life-threatening laryngeal swelling. Can occur after years of use.<br><br><strong>Fix:</strong> STOP ACEi; give icatibant; switch to ARB.</p>
      </div>
      <div class="card card-gold" style="padding:12px;">
        <div class="card-title">🔋 Hyperkalemia</div>
        <p style="font-size:12px; line-height:1.6;">↓ Aldosterone → ↓ K⁺ excretion.<br><br>Risk ↑ with: CKD, DM, K⁺ supplements, K⁺-sparing diuretics, NSAIDs, heparin.</p>
      </div>
      <div class="card card-red" style="padding:12px;">
        <div class="card-title">🫘 Acute Renal Failure</div>
        <p style="font-size:12px; line-height:1.6;">Bilateral RAS or solitary kidney RAS: removes efferent arteriolar AngII tone → GFR collapses.<br><br>Monitor creatinine after starting.</p>
      </div>
      <div class="card card-blue" style="padding:12px;">
        <div class="card-title">📉 First-Dose Hypotension</div>
        <p style="font-size:12px; line-height:1.6;">Risk if volume-depleted (diuretics, vomiting). Start LOW dose. Hold diuretic 24h before first dose (esp. captopril).</p>
      </div>
      <div class="card card-navy" style="padding:12px;">
        <div class="card-title">🤰 Fetal Toxicity</div>
        <p style="font-size:12px; line-height:1.6;">2nd &amp; 3rd trimester: fetal hypotension, oliguria, renal failure, malformations, death.<br><br><span style="color:#C0392B; font-weight:700;">CONTRAINDICATED IN PREGNANCY</span></p>
      </div>
    </div>

    <div class="card" style="margin-top:12px; background:#0B1F4B; border-left:4px solid #C0392B;">
      <div class="card-title" style="color:#E8A020;">🚫 Compelling Contraindications</div>
      <div style="display:flex; flex-wrap:wrap; gap:6px; margin-top:6px;">
        <span class="badge badge-red">Pregnancy (2nd/3rd tri)</span>
        <span class="badge badge-red">Bilateral RAS</span>
        <span class="badge badge-red">Hyperkalemia</span>
        <span class="badge badge-red">Angioedema history</span>
        <span class="badge badge-orange">Women of childbearing potential (caution)</span>
      </div>
    </div>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 7 – ARBs -->
<div class="slide" id="slide-7">
  <div class="slide-header"><h2>🔵 ARBs – Angiotensin Receptor Blockers</h2></div>
  <div class="slide-body">

    <div class="card card-light-purple">
      <div class="card-title" style="color:#7C3AED;">⚙️ Mechanism</div>
      <p style="font-size:13px;">Selective competitive antagonism at <strong>AT₁ receptors</strong>. Do NOT inhibit ACE → <strong>no cough, no angioedema</strong> (bradykinin unchanged). Blocked AT₁ → AngII accumulates → floods AT₂ → extra NO-mediated vasodilation (bonus).</p>
    </div>

    <div class="card-title" style="margin:12px 0 6px; font-size:14px;">Members – Mnemonic: <span style="color:#7C3AED; font-weight:800;">LAVE CITO</span></div>
    <table class="tbl">
      <tr><th>Drug</th><th>Key Feature</th></tr>
      <tr><td><strong style="color:#7C3AED;">L</strong>osartan</td><td><span class="badge badge-gold">★ Uricosuric</span> – blocks URAT-1. Active metabolite EXP-3174. Prototype ARB. LIFE trial.</td></tr>
      <tr><td><strong style="color:#7C3AED;">A</strong>zilsartan</td><td>Newest; strongest BP lowering</td></tr>
      <tr><td><strong style="color:#7C3AED;">V</strong>alsartan</td><td>HFrEF + HTN; component of ARNi (Sacubitril/Valsartan)</td></tr>
      <tr><td><strong style="color:#7C3AED;">E</strong>prosartan</td><td>Non-biphenyl tetrazole structure</td></tr>
      <tr><td><strong style="color:#7C3AED;">C</strong>andesartan</td><td>Prodrug; long duration; HFrEF benefit</td></tr>
      <tr><td><strong style="color:#7C3AED;">I</strong>rbesartan</td><td>No active metabolite; DM nephropathy (IDNT trial)</td></tr>
      <tr><td><strong style="color:#7C3AED;">T</strong>elmisartan</td><td>Longest t½ (~24h); PPAR-γ agonism; once daily</td></tr>
      <tr><td><strong style="color:#7C3AED;">O</strong>lmesartan</td><td>Potent; rare sprue-like enteropathy</td></tr>
    </table>

    <div class="highlight" style="margin-top:10px;">
      <strong>★ Losartan High-Yield:</strong> Only ARB with uricosuric effect (blocks URAT-1 in proximal tubule) → drug of choice in <strong>hypertension + gout/hyperuricemia</strong>. Active metabolite EXP-3174 is 10–40× more potent.
    </div>

    <div class="card card-light-blue" style="margin-top:10px;">
      <div class="card-title" style="color:#0B1F4B;">📊 Hemodynamic Profile</div>
      <p style="font-size:12px; line-height:1.8;">HR ↔ &nbsp;|&nbsp; CO ↔ &nbsp;|&nbsp; TPR <span style="color:#1D7A4E; font-weight:700;">↓</span> &nbsp;|&nbsp; PRA <span style="color:#E06C2A; font-weight:700;">↑</span> (loss of AngII feedback) &nbsp;|&nbsp; Plasma Ang II <span style="color:#E06C2A; font-weight:700;">↑</span> (AT₁ blocked) → stimulates AT₂</p>
    </div>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 8 – ACEi vs ARB -->
<div class="slide" id="slide-8">
  <div class="slide-header"><h2>⚖️ ACEi vs ARBs – Head-to-Head</h2></div>
  <div class="slide-body">
    <div style="overflow-x:auto;">
      <table class="tbl" style="min-width:500px;">
        <tr>
          <th style="background:#0B1F4B; width:32%;">Feature</th>
          <th style="background:#0D7C7C; width:34%;">ACE Inhibitors</th>
          <th style="background:#7C3AED; width:34%;">ARBs</th>
        </tr>
        <tr><td class="col-head">Target</td><td>ACE (kininase II)</td><td>AT₁ receptor</td></tr>
        <tr><td class="col-head">Bradykinin</td><td class="warn">↑↑ (prevents degradation)</td><td class="good">Unchanged</td></tr>
        <tr><td class="col-head">Substance P</td><td class="warn">↑</td><td class="good">Unchanged</td></tr>
        <tr><td class="col-head">Cough</td><td class="danger">5–20% (common)</td><td class="good">Rare (&lt;1%)</td></tr>
        <tr><td class="col-head">Angioedema</td><td class="danger">0.1–0.7%</td><td class="good">~0.1% (less)</td></tr>
        <tr><td class="col-head">Plasma Ang II</td><td>↓</td><td class="warn">↑ (AT₁ blocked)</td></tr>
        <tr><td class="col-head">PRA</td><td class="warn">↑ (reflex)</td><td class="warn">↑ (reflex)</td></tr>
        <tr><td class="col-head">AT₂ stimulation</td><td>Unchanged</td><td class="good">↑↑ (bonus)</td></tr>
        <tr><td class="col-head">Aldosterone</td><td class="good">↓</td><td class="good">↓</td></tr>
        <tr><td class="col-head">Hyperkalemia</td><td class="danger">Yes</td><td class="danger">Yes (similar)</td></tr>
        <tr><td class="col-head">Pregnancy</td><td class="danger">CI (2nd/3rd tri)</td><td class="danger">CI</td></tr>
        <tr><td class="col-head">HF outcomes</td><td class="good">1st-line preferred</td><td>Non-inferior; use if ACEi intolerant</td></tr>
        <tr><td class="col-head">DM nephropathy</td><td class="good">1st-line</td><td class="good">1st-line (IDNT, RENAAL)</td></tr>
        <tr><td class="col-head">Unique feature</td><td>Captopril/Lisinopril not prodrugs</td><td class="warn">Losartan uricosuric</td></tr>
      </table>
    </div>
    <div class="highlight green" style="margin-top:10px;">
      <strong>Bottom line:</strong> Initial hopes for ARB superiority over ACEi were NOT fulfilled (ONTARGET). In HFrEF, ACEi remain first-line. ARBs are used when ACEi are not tolerated (usually because of cough).
    </div>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 9 – ALISKIREN -->
<div class="slide" id="slide-9">
  <div class="slide-header"><h2>🧪 Direct Renin Inhibitor – Aliskiren</h2><div class="subtitle">First orally active DRI approved for hypertension</div></div>
  <div class="slide-body">

    <div class="card card-orange" style="text-align:center; padding:10px;">
      <div style="font-size:13px; font-weight:700;">Aliskiren — attacks the RATE-LIMITING step of RAAS (renin's active site)</div>
    </div>

    <div class="card card-light" style="margin-top:10px;">
      <div class="card-title" style="color:#E06C2A;">⚙️ Mechanism</div>
      <ul style="font-size:12.5px; padding-left:18px; line-height:1.7;">
        <li>Binds directly to renin's active site → blocks angiotensinogen cleavage</li>
        <li>↓ Plasma Renin Activity (PRA) <strong>and</strong> ↓ Ang I, ↓ Ang II, ↓ Aldosterone</li>
        <li>Plasma Renin Concentration (PRC) ↑ (compensatory feedback)</li>
        <li>Eliminates the PRA rise caused by ACEi, ARBs, and diuretics</li>
        <li>Does <strong>NOT</strong> affect bradykinin → No cough, No angioedema</li>
      </ul>
    </div>

    <div class="highlight blue" style="margin:10px 0; font-size:12px;">
      <strong>Unique PRA Effect:</strong> ACEi ↑PRA &nbsp;|&nbsp; ARBs ↑PRA &nbsp;|&nbsp; Aliskiren <span style="color:#1D7A4E; font-weight:700;">↓PRA</span> (only one that truly suppresses renin activity)
    </div>

    <div class="grid-2">
      <div class="card card-light-blue">
        <div class="card-title" style="color:#1A3E8C;">🧪 Pharmacokinetics</div>
        <ul style="font-size:12px; padding-left:16px; line-height:1.7;">
          <li>Oral bioavailability <strong>~3%</strong> (F = 0.03)</li>
          <li>Classic example: very low-F drug still works</li>
          <li>High-fat meal ↓ absorption by 85%</li>
          <li>t½ ~24h (once daily dosing)</li>
          <li>Excreted unchanged in feces</li>
          <li>NOT a prodrug</li>
          <li>P-glycoprotein substrate</li>
        </ul>
      </div>
      <div class="card" style="background:#FFF0F0;">
        <div class="card-title" style="color:#C0392B;">⚠️ Adverse Effects / Contraindications</div>
        <ul style="font-size:12px; padding-left:16px; line-height:1.7;">
          <li>Hyperkalemia</li>
          <li>First-dose hypotension</li>
          <li>Diarrhea (unique to DRI)</li>
          <li class="danger"><strong>PREGNANCY – CI</strong></li>
          <li class="danger"><strong>Avoid ACEi/ARB combo</strong> (↑ AEs)</li>
          <li>No proven mortality benefit</li>
          <li>No CV outcomes data (unlike ACEi)</li>
        </ul>
      </div>
    </div>

    <div class="highlight red" style="margin-top:10px;">
      ⚠️ <strong>Dual RAAS blockade (Aliskiren + ACEi or ARB) is CONTRAINDICATED</strong> — no additional benefit + increased adverse effects (hypotension, hyperkalemia, AKI). [Goodman &amp; Gilman 14e]
    </div>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 10 – ARNi -->
<div class="slide" id="slide-10">
  <div class="slide-header"><h2>💙 ARNi – Sacubitril/Valsartan (Entresto)</h2></div>
  <div class="slide-body">

    <div class="card card-sky" style="text-align:center; padding:10px; margin-bottom:12px;">
      <div style="font-size:13px; font-weight:700;">Angiotensin Receptor–Neprilysin Inhibitor (ARNi)</div>
      <div style="font-size:11.5px; margin-top:4px; color:#fff; opacity:0.9;">Co-crystal of Sacubitril (neprilysin inhibitor prodrug) + Valsartan (AT₁ blocker)</div>
    </div>

    <div class="grid-2">
      <div>
        <div class="card card-sky" style="padding:10px; margin-bottom:8px; text-align:center;">
          <div style="font-size:12px; font-weight:700;">SACUBITRIL (prodrug)</div>
          <div style="font-size:20px; color:#E8A020;">↓</div>
          <div style="font-size:11px;">LBQ657 (active) — Neprilysin Inhibitor</div>
          <div style="font-size:20px; color:#E8A020;">↓</div>
          <div style="font-size:11px;">↑ ANP, BNP, Bradykinin<br>(less neprilysin breakdown)</div>
          <div style="font-size:20px; color:#E8A020;">↓</div>
          <div style="font-size:11px; font-weight:700; color:#E8A020;">Vasodilation + Natriuresis<br>↓ Cardiac fibrosis</div>
        </div>
      </div>
      <div>
        <div class="card card-lilac" style="padding:10px; margin-bottom:8px; text-align:center;">
          <div style="font-size:12px; font-weight:700;">VALSARTAN (ARB)</div>
          <div style="font-size:20px; color:#E8A020;">↓</div>
          <div style="font-size:11px;">AT₁ Receptor Blockade</div>
          <div style="font-size:20px; color:#E8A020;">↓</div>
          <div style="font-size:11px;">↓ AngII effects<br>↑ AT₂ stimulation</div>
          <div style="font-size:20px; color:#E8A020;">↓</div>
          <div style="font-size:11px; font-weight:700; color:#E8A020;">↓ Afterload &amp; preload<br>↓ Remodeling</div>
        </div>
      </div>
    </div>

    <div class="card card-green" style="padding:12px; margin-bottom:10px;">
      <div class="card-title">✅ Combined Benefit (PARADIGM-HF Trial)</div>
      <div class="grid-2" style="margin-top:6px; gap:6px;">
        <p style="font-size:12px; line-height:1.7; color:#fff;">• ↓ Mortality vs enalapril<br>• ↓ HF hospitalizations<br>• ↓ Cardiac fibrosis &amp; LV remodeling</p>
        <p style="font-size:12px; line-height:1.7; color:#fff;">• ↑ Quality of life<br>• ↑ Exercise tolerance<br>• Superior to ACEi in HFrEF</p>
      </div>
    </div>

    <div class="card" style="background:#FFF0F0; border-left:4px solid #C0392B; padding:12px;">
      <div class="card-title" style="color:#C0392B;">⚠️ Critical Warnings</div>
      <ul style="font-size:12.5px; padding-left:16px; line-height:1.8;">
        <li><strong>Indication:</strong> HFrEF (EF ≤40%) — NOT approved for hypertension alone</li>
        <li class="danger"><strong>NEVER combine with ACE inhibitor</strong> → dual bradykinin accumulation → life-threatening angioedema</li>
        <li><strong>Washout:</strong> Must wait <strong>36 hours</strong> after stopping ACEi before starting ARNi</li>
        <li class="danger"><strong>Pregnancy — CONTRAINDICATED</strong></li>
        <li>Monitor K⁺ and renal function regularly</li>
      </ul>
    </div>
  </div>
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<!-- ═══════════════════════════════════════════════════ SLIDE 11 – MASTER TABLE -->
<div class="slide" id="slide-11">
  <div class="slide-header"><h2>📊 Master Comparison – All 4 RAAS Classes</h2></div>
  <div class="slide-body">
    <div style="overflow-x:auto;">
      <table class="tbl" style="min-width:620px; font-size:10.5px;">
        <tr>
          <th style="background:#0B1F4B; width:18%;">Feature</th>
          <th style="background:#0D7C7C; width:22%;">ACE Inhibitors</th>
          <th style="background:#7C3AED; width:20%;">ARBs</th>
          <th style="background:#E06C2A; width:20%;">Aliskiren (DRI)</th>
          <th style="background:#3B8EC8; width:20%;">ARNi (Sacubitril/Val)</th>
        </tr>
        <tr><td class="col-head">Target</td><td>ACE (kininase II)</td><td>AT₁ receptor</td><td>Renin active site</td><td>Neprilysin + AT₁</td></tr>
        <tr><td class="col-head">Bradykinin</td><td class="warn">↑↑</td><td>Unchanged</td><td>Unchanged</td><td class="warn">↑ (neprilysin)</td></tr>
        <tr><td class="col-head">Cough</td><td class="danger">5–20%</td><td class="good">Rare (&lt;1%)</td><td class="good">None</td><td>Possible</td></tr>
        <tr><td class="col-head">Angioedema</td><td class="danger">0.1–0.7%</td><td class="good">Very rare</td><td class="good">None</td><td>Rare (not with ACEi)</td></tr>
        <tr><td class="col-head">PRA</td><td class="warn">↑ (reflex)</td><td class="warn">↑ (reflex)</td><td class="good">↓ (unique!)</td><td class="warn">↑</td></tr>
        <tr><td class="col-head">Plasma Ang II</td><td class="good">↓</td><td class="warn">↑ (blocked AT₁)</td><td class="good">↓</td><td class="warn">↑ (valsartan blocks)</td></tr>
        <tr><td class="col-head">Aldosterone</td><td class="good">↓</td><td class="good">↓</td><td class="good">↓</td><td class="good">↓</td></tr>
        <tr><td class="col-head">Hyperkalemia</td><td class="danger">Risk ✓</td><td class="danger">Risk ✓</td><td class="danger">Risk ✓</td><td class="danger">Risk ✓</td></tr>
        <tr><td class="col-head">Pregnancy</td><td class="danger">CI</td><td class="danger">CI</td><td class="danger">CI</td><td class="danger">CI</td></tr>
        <tr><td class="col-head">Primary use</td><td>HTN, HF, DM nephropathy</td><td>HTN, HF (ACEi intol)</td><td>HTN only</td><td>HFrEF (NOT HTN alone)</td></tr>
        <tr><td class="col-head">Unique fact</td><td>Captopril/Lisinopril = not prodrugs</td><td class="good">Losartan uricosuric</td><td>Lowest F (~3%)</td><td>36h washout from ACEi</td></tr>
      </table>
    </div>

    <div class="highlight red" style="margin-top:12px; font-size:12px;">
      <strong>Dual RAAS blockade rule:</strong> ACEi + ARB = No added benefit + ↑ AEs (ONTARGET trial). ACEi/ARB + Aliskiren = CONTRAINDICATED. ARNi + ACEi = CONTRAINDICATED (angioedema risk).
    </div>
  </div>
  <div class="spacer"></div>
</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 12 – CLINICAL SCENARIOS -->
<div class="slide" id="slide-12">
  <div class="slide-header"><h2>🏥 Clinical Scenarios – Renal Physiology</h2></div>
  <div class="slide-body">

    <div class="scenario" style="background:#1D7A4E;">
      <h3>🟢 Diabetic Nephropathy</h3>
      <span class="badge-label">ACEi / ARB — PREFERRED even if normotensive</span>
      <div class="section">
        <div class="section-title">Pathophysiology</div>
        <p>↑ Intraglomerular pressure (AngII constricts efferent arteriole) → hyperfiltration → proteinuria → glomerulosclerosis → ESRD</p>
      </div>
      <div class="section">
        <div class="section-title">Drug Effect</div>
        <ul><li>Dilates efferent arteriole → ↓ intraglomerular pressure</li><li>↓ Proteinuria (even without lowering BP)</li><li>↓ Progression to ESRD</li><li>Recommended even in normotensive diabetics</li></ul>
      </div>
    </div>

    <div class="scenario" style="background:#C0392B;">
      <h3>🔴 Bilateral Renal Artery Stenosis</h3>
      <span class="badge-label">ACEi / ARB — CONTRAINDICATED</span>
      <div class="section">
        <div class="section-title">Pathophysiology</div>
        <p>Low flow to both kidneys → AngII REQUIRED to constrict efferent arteriole to maintain GFR under low perfusion pressure</p>
      </div>
      <div class="section">
        <div class="section-title">Why Drug Causes Harm</div>
        <ul><li>ACEi/ARB removes efferent AngII constriction</li><li>GFR collapses → Acute renal failure</li><li>Creatinine rises sharply after starting drug</li><li>Monitor creatinine 1–2 weeks after starting any RAAS drug</li></ul>
      </div>
    </div>

    <div class="scenario" style="background:#1A3E8C;">
      <h3>🔵 Heart Failure (HFrEF)</h3>
      <span class="badge-label">ACEi / ARB / ARNi — Core Therapy</span>
      <div class="section">
        <div class="section-title">Drug Effect</div>
        <ul><li>ACEi → ↓ AngII → ↓ afterload + preload</li><li>↓ Aldosterone → ↓ Na/H₂O retention</li><li>↓ Cardiac remodeling + hypertrophy</li><li>ARNi (sacubitril/valsartan) superior to enalapril in HFrEF (PARADIGM-HF)</li></ul>
      </div>
    </div>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 13 – DRUG INTERACTIONS -->
<div class="slide" id="slide-13">
  <div class="slide-header"><h2>💊 Drug Interactions</h2></div>
  <div class="slide-body">
    <div style="overflow-x:auto;">
      <table class="tbl" style="min-width:500px;">
        <tr><th>Combination</th><th>Effect</th><th>Risk</th></tr>
        <tr>
          <td>ACEi + K⁺-sparing diuretics (Spironolactone)</td>
          <td>Severe Hyperkalemia</td>
          <td><span class="badge badge-red">DANGER</span></td>
        </tr>
        <tr>
          <td>ACEi + NSAIDs</td>
          <td>↓ Antihypertensive effect + AKI risk</td>
          <td><span class="badge badge-orange">CAUTION</span></td>
        </tr>
        <tr>
          <td>ACEi + K⁺ supplements</td>
          <td>Hyperkalemia</td>
          <td><span class="badge badge-orange">CAUTION</span></td>
        </tr>
        <tr>
          <td>ACEi + Thiazide (LOW dose)</td>
          <td>Enhanced BP lowering (synergistic)</td>
          <td><span class="badge badge-green">BENEFIT</span></td>
        </tr>
        <tr>
          <td>ACEi + Thiazide (HIGH dose)</td>
          <td>Severe hypotension, volume depletion</td>
          <td><span class="badge badge-orange">CAUTION</span></td>
        </tr>
        <tr>
          <td>ARNi + ACE Inhibitor</td>
          <td>Life-threatening angioedema</td>
          <td><span class="badge badge-red">ABSOLUTE CI</span></td>
        </tr>
        <tr>
          <td>Aliskiren + ACEi or ARB</td>
          <td>No benefit + ↑ AEs (hypotension, K⁺, AKI)</td>
          <td><span class="badge badge-red">CONTRAINDICATED</span></td>
        </tr>
        <tr>
          <td>ACEi + Lithium</td>
          <td>Lithium toxicity (↓ renal Li⁺ clearance)</td>
          <td><span class="badge badge-orange">CAUTION</span></td>
        </tr>
      </table>
    </div>

    <div class="card card-navy" style="margin-top:12px; padding:12px;">
      <div class="card-title" style="color:#E8A020;">💡 Why ACEi + Thiazide is Synergistic</div>
      <p style="font-size:12.5px; color:#fff; line-height:1.6;">Normally, diuretic-induced Na⁺ loss → ↑ aldosterone (counter-regulatory escape). ACEi blunts this aldosterone rise → diuretic effect is maintained &amp; potentiated. Even very small thiazide doses greatly improve ACEi efficacy. Conversely, high diuretic doses + ACEi = excessive volume depletion → hypotension/AKI.</p>
    </div>
  </div>
  <div class="spacer"></div>
</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 14 – MNEMONICS -->
<div class="slide" id="slide-14">
  <div class="slide-header"><h2>🧠 Mnemonics &amp; Exam Pearls</h2></div>
  <div class="slide-body">

    <div class="card card-light">
      <div class="card-title" style="color:#0B1F4B;">ACEi Side Effects: <span style="color:#E8A020; font-size:16px; font-weight:800;">CAPTOPRIL</span></div>
      <table class="tbl" style="margin-top:6px;">
        <tr><th style="width:36px; background:#E8A020; color:#1E293B;">C</th><td><strong>C</strong>ough (bradykinin + substance P accumulation)</td></tr>
        <tr><th style="background:#E8A020; color:#1E293B;">A</th><td><strong>A</strong>ngioedema (life-threatening, bradykinin-mediated)</td></tr>
        <tr><th style="background:#E8A020; color:#1E293B;">P</th><td><strong>P</strong>otassium ↑ (hyperkalemia)</td></tr>
        <tr><th style="background:#E8A020; color:#1E293B;">T</th><td><strong>T</strong>eratogenic (CI pregnancy) / Taste disturbance</td></tr>
        <tr><th style="background:#E8A020; color:#1E293B;">O</th><td>h<strong>O</strong>rrible for bilateral RAS (AKI)</td></tr>
        <tr><th style="background:#E8A020; color:#1E293B;">P</th><td><strong>P</strong>rodrug (most are) / Proteinuria reduced</td></tr>
        <tr><th style="background:#E8A020; color:#1E293B;">R</th><td><strong>R</strong>enal failure (bilateral RAS, volume depletion)</td></tr>
        <tr><th style="background:#E8A020; color:#1E293B;">I</th><td><strong>I</strong>nduced hypotension (1st dose)</td></tr>
        <tr><th style="background:#E8A020; color:#1E293B;">L</th><td><strong>L</strong>iver converts prodrugs (except lisinopril/captopril)</td></tr>
      </table>
    </div>

    <div class="card card-light-purple" style="margin-top:10px;">
      <div class="card-title" style="color:#7C3AED;">ARB Members: <span style="color:#7C3AED; font-size:16px; font-weight:800;">LAVE CITO</span></div>
      <p style="font-size:12.5px; color:#4B5563; margin-top:4px; line-height:1.8;"><strong>L</strong>osartan &nbsp;•&nbsp; <strong>A</strong>zilsartan &nbsp;•&nbsp; <strong>V</strong>alsartan &nbsp;•&nbsp; <strong>E</strong>prosartan &nbsp;•&nbsp; <strong>C</strong>andesartan &nbsp;•&nbsp; <strong>I</strong>rbesartan &nbsp;•&nbsp; <strong>T</strong>elmisartan &nbsp;•&nbsp; <strong>O</strong>lmesartan</p>
    </div>

    <div style="margin-top:10px;">
      <div class="card-title" style="font-size:14px; margin-bottom:8px;">⚡ Must-Know Exam Pearls</div>
      <div class="highlight" style="margin-bottom:6px; font-size:12px;"><span class="star">★</span> ACEi that is NOT a prodrug AND has –SH group → <strong>Captopril</strong> (Lisinopril also not a prodrug but no –SH)</div>
      <div class="highlight" style="margin-bottom:6px; font-size:12px;"><span class="star">★</span> Only ARB with uricosuric effect → <strong>Losartan</strong> (use in HTN + gout)</div>
      <div class="highlight" style="margin-bottom:6px; font-size:12px;"><span class="star">★</span> Only DRI approved for HTN → <strong>Aliskiren</strong> (no CV outcome benefit proven, no cough)</div>
      <div class="highlight" style="margin-bottom:6px; font-size:12px;"><span class="star">★</span> ARNi contraindicated WITH ACEi — 36-hour washout needed (double bradykinin = angioedema)</div>
      <div class="highlight" style="margin-bottom:6px; font-size:12px;"><span class="star">★</span> ACEi available IV only → <strong>Enalaprilat</strong> (active form of enalapril, for hypertensive emergencies)</div>
      <div class="highlight" style="font-size:12px;"><span class="star">★</span> ARB with longest t½ (~24h) + PPAR-γ activity → <strong>Telmisartan</strong></div>
    </div>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 15 – MCQs -->
<div class="slide" id="slide-15">
  <div class="slide-header"><h2>📝 Top 5 Must-Know MCQ Concepts</h2></div>
  <div class="slide-body">

    <div class="mcq-card" style="background:#0D7C7C;">
      <div class="mcq-q">Q1. Which drug causes cough by accumulating bradykinin + substance P?</div>
      <div class="mcq-a">→ <strong>ACE Inhibitor</strong> (NOT ARBs, NOT Aliskiren, NOT ARNi-alone). Bradykinin normally degraded by ACE (kininase II). ACEi prevents this → C-fiber stimulation → cough.</div>
    </div>

    <div class="mcq-card" style="background:#1A3E8C;">
      <div class="mcq-q">Q2. Which ACEi is NOT a prodrug AND has a sulfhydryl (–SH) group?</div>
      <div class="mcq-a">→ <strong>Captopril</strong>. Lisinopril is also NOT a prodrug (lysine derivative) but has no –SH group. All others (enalapril, ramipril, etc.) are prodrugs converted in liver.</div>
    </div>

    <div class="mcq-card" style="background:#C0392B;">
      <div class="mcq-q">Q3. ACEi is contraindicated in bilateral RAS because…</div>
      <div class="mcq-a">→ Removes efferent arteriolar AngII constriction → <strong>GFR collapses → Acute Renal Failure</strong>. AngII is needed to maintain filtration pressure when both renal arteries are stenosed.</div>
    </div>

    <div class="mcq-card" style="background:#7C3AED;">
      <div class="mcq-q">Q4. What is the unique property of Losartan among all ARBs?</div>
      <div class="mcq-a">→ <strong>Uricosuric effect</strong> (blocks URAT-1 transporter in proximal tubule → ↓ uric acid reabsorption). Drug of choice in hypertension + gout/hyperuricemia.</div>
    </div>

    <div class="mcq-card" style="background:#E06C2A;">
      <div class="mcq-q">Q5. Sacubitril/valsartan (ARNi) must NEVER be combined with…</div>
      <div class="mcq-a">→ <strong>ACE Inhibitors</strong>. Require 36-hour washout period after stopping ACEi. Reason: neprilysin inhibition + ACE inhibition = double bradykinin accumulation = <strong>life-threatening angioedema</strong>.</div>
    </div>

    <div class="highlight" style="font-size:12px;">
      <strong>Bonus Q:</strong> Which RAAS drug has the lowest oral bioavailability (~3%) yet is clinically effective? → <strong>Aliskiren</strong> (classic pharmacokinetics example in Goodman &amp; Gilman Ch 2).
    </div>
  </div>
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</div>

<!-- ═══════════════════════════════════════════════════ SLIDE 16 – TAKEAWAYS -->
<div class="slide" id="slide-16">
  <div class="slide-header" style="background: linear-gradient(135deg, #0B1F4B, #0D7C7C); border-bottom-color:#E8A020;"><h2 style="color:#E8A020;">🎯 Key Takeaways</h2></div>
  <div class="slide-body">

    <div class="card card-navy" style="margin-bottom:8px; padding:12px; border-left:4px solid #0D7C7C;">
      <div class="card-title" style="color:#0D7C7C;">ACE Inhibitors</div>
      <p style="font-size:12.5px; color:#fff; line-height:1.6;">Dual action: ↓AngII + ↑bradykinin. Cough &amp; angioedema = bradykinin side effects. Not prodrug: captopril (–SH), lisinopril (lysine). IV-only: enalaprilat. 1st-line: HTN, HFrEF, DM nephropathy, post-MI.</p>
    </div>

    <div class="card card-navy" style="margin-bottom:8px; padding:12px; border-left:4px solid #7C3AED;">
      <div class="card-title" style="color:#7C3AED;">ARBs</div>
      <p style="font-size:12.5px; color:#fff; line-height:1.6;">Selective AT₁ block. No cough. Redirect AngII to AT₂ (bonus vasodilation). Losartan = only uricosuric ARB. Not superior to ACEi in outcomes. Use when ACEi intolerant (cough).</p>
    </div>

    <div class="card card-navy" style="margin-bottom:8px; padding:12px; border-left:4px solid #E06C2A;">
      <div class="card-title" style="color:#E06C2A;">Aliskiren (DRI)</div>
      <p style="font-size:12.5px; color:#fff; line-height:1.6;">Attacks rate-limiting step. ↓PRA (unique). F = 3% (lowest of all). No cough. No proven CV outcome benefit. Combination with ACEi/ARB CONTRAINDICATED.</p>
    </div>

    <div class="card card-navy" style="margin-bottom:8px; padding:12px; border-left:4px solid #3B8EC8;">
      <div class="card-title" style="color:#3B8EC8;">ARNi (Sacubitril/Valsartan)</div>
      <p style="font-size:12.5px; color:#fff; line-height:1.6;">Neprilysin + AT₁ block. Superior to enalapril in HFrEF (PARADIGM-HF). NOT approved for HTN alone. 36-hour washout from ACEi. NEVER combine with ACEi (angioedema).</p>
    </div>

    <div class="card" style="background:#C0392B; margin-bottom:8px; padding:12px;">
      <div class="card-title" style="color:#E8A020;">⚠️ Critical Rules</div>
      <ul style="font-size:12px; color:#fff; padding-left:16px; line-height:1.8;">
        <li>Bilateral RAS + ACEi/ARB = <strong>Acute Renal Failure</strong> (efferent tone loss)</li>
        <li>Dual RAAS blockade = No benefit + ↑ adverse effects (ONTARGET)</li>
        <li>All RAAS drugs CONTRAINDICATED in pregnancy</li>
        <li>ACEi + K⁺-sparing diuretic = severe hyperkalemia risk</li>
      </ul>
    </div>

    <div class="card card-light" style="text-align:center; padding:10px;">
      <div style="font-size:11px; color:#64748B;">📚 References: Goodman &amp; Gilman 14e • Katzung Basic &amp; Clinical Pharmacology 16e • KD Tripathi Essentials of Medical Pharmacology</div>
    </div>
  </div>
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</div>

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  function showSlide(n) {
    document.querySelectorAll('.slide').forEach(s => s.classList.remove('active'));
    document.getElementById('slide-' + n).classList.add('active');
    document.getElementById('counter').textContent = n + ' / ' + total;
    document.getElementById('prevBtn').disabled = (n === 1);
    document.getElementById('nextBtn').disabled = (n === total);
    window.scrollTo(0, 0);
    current = n;
  }

  function changeSlide(dir) {
    const next = current + dir;
    if (next >= 1 && next <= total) showSlide(next);
  }

  function goToSlide(n) { showSlide(n); }

  // Swipe support
  let touchStartX = 0;
  document.addEventListener('touchstart', e => { touchStartX = e.touches[0].clientX; });
  document.addEventListener('touchend', e => {
    const diff = touchStartX - e.changedTouches[0].clientX;
    if (Math.abs(diff) > 50) changeSlide(diff > 0 ? 1 : -1);
  });
</script>
</body>
</html>