const pptxgen = require("pptxgenjs");

const pres = new pptxgen();
pres.layout = "LAYOUT_16x9";
pres.author = "Orris Medical";
pres.title = "Morphine – Comprehensive Pharmacology";

// ─── COLOUR PALETTE ────────────────────────────────────────────────────────
const DARK_BG   = "0D1B2A";   // deep navy
const MID_BG    = "1B2A3B";   // slightly lighter navy
const ACCENT    = "E8A020";   // amber gold
const ACCENT2   = "3DA5D9";   // sky blue
const WHITE     = "FFFFFF";
const LIGHT     = "D8E8F4";
const SUBTEXT   = "B0C4D8";
const RED       = "E05C5C";
const GREEN     = "5CB85C";
const HEADING_FONT = "Calibri";
const BODY_FONT    = "Calibri";

// ─── HELPERS ────────────────────────────────────────────────────────────────
function darkSlide(pres) {
  const slide = pres.addSlide();
  slide.background = { color: DARK_BG };
  return slide;
}

function midSlide(pres) {
  const slide = pres.addSlide();
  slide.background = { color: MID_BG };
  return slide;
}

function sectionBanner(slide, text) {
  slide.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: DARK_BG } });
  slide.addShape(pres.ShapeType.rect, { x: 0, y: 2.3, w: 10, h: 0.06, fill: { color: ACCENT } });
  slide.addText(text, {
    x: 0.5, y: 1.5, w: 9, h: 1.4,
    fontSize: 44, bold: true, color: WHITE,
    fontFace: HEADING_FONT, align: "center", valign: "middle"
  });
}

function slideTitle(slide, title, subtitle) {
  slide.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 1.0, fill: { color: "0A1520" } });
  slide.addShape(pres.ShapeType.rect, { x: 0, y: 0.9, w: 10, h: 0.05, fill: { color: ACCENT } });
  slide.addText(title, {
    x: 0.4, y: 0.05, w: 9.2, h: 0.85,
    fontSize: 26, bold: true, color: WHITE,
    fontFace: HEADING_FONT, margin: 0
  });
  if (subtitle) {
    slide.addText(subtitle, {
      x: 0.4, y: 0.88, w: 9.2, h: 0.2,
      fontSize: 11, color: ACCENT, fontFace: BODY_FONT, margin: 0, italic: true
    });
  }
}

function bullet(text, level) {
  return { text, options: { bullet: { code: "2022" }, indentLevel: level || 0, breakLine: true } };
}

function subBullet(text) {
  return { text, options: { bullet: { code: "2013" }, indentLevel: 1, breakLine: true, color: SUBTEXT } };
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 1 – TITLE
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  // background decorative bar
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 0.18, h: 5.625, fill: { color: ACCENT } });
  s.addShape(pres.ShapeType.rect, { x: 0.18, y: 0, w: 9.82, h: 5.625, fill: { color: DARK_BG } });
  // vertical label strip
  s.addText("PHARMACOLOGY", {
    x: -1.6, y: 4.1, w: 5.625, h: 0.18,
    fontSize: 8, bold: true, color: ACCENT, fontFace: HEADING_FONT,
    align: "center", charSpacing: 5, rotate: 270, margin: 0
  });
  // title block
  s.addText("MORPHINE", {
    x: 0.6, y: 0.5, w: 8.8, h: 2.0,
    fontSize: 72, bold: true, color: WHITE, fontFace: HEADING_FONT,
    align: "left", valign: "bottom", margin: 0
  });
  s.addShape(pres.ShapeType.rect, { x: 0.6, y: 2.5, w: 6, h: 0.05, fill: { color: ACCENT } });
  s.addText("Comprehensive Pharmacology, Dosing & Clinical Use", {
    x: 0.6, y: 2.6, w: 8.8, h: 0.55,
    fontSize: 20, color: LIGHT, fontFace: BODY_FONT, align: "left", margin: 0
  });
  s.addText("Opioid Analgesic  •  μ-Receptor Agonist  •  WHO Essential Medicine", {
    x: 0.6, y: 3.3, w: 8.8, h: 0.4,
    fontSize: 13, color: SUBTEXT, fontFace: BODY_FONT, align: "left", margin: 0, italic: true
  });
  s.addText("Sources: Goodman & Gilman 14e  •  Miller's Anesthesia 10e  •  Rosen's Emergency Medicine 9e  •  Barash Clinical Anesthesia 9e", {
    x: 0.6, y: 5.1, w: 9, h: 0.35,
    fontSize: 9, color: SUBTEXT, fontFace: BODY_FONT, align: "left", margin: 0
  });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 2 – OVERVIEW / TABLE OF CONTENTS
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Presentation Overview");
  const topics = [
    ["01", "History & Classification"],
    ["02", "Chemistry & Structure-Activity Relationships"],
    ["03", "Mechanism of Action"],
    ["04", "Pharmacokinetics (ADME)"],
    ["05", "Pharmacodynamics – CNS & Systemic Effects"],
    ["06", "Clinical Uses"],
    ["07", "Dosing – All Routes"],
    ["08", "Special Populations"],
    ["09", "Adverse Effects"],
    ["10", "Contraindications & Precautions"],
    ["11", "Drug Interactions"],
    ["12", "Overdose & Reversal"],
    ["13", "Tolerance, Dependence & Withdrawal"],
  ];
  const col1 = topics.slice(0, 7);
  const col2 = topics.slice(7);
  col1.forEach((item, i) => {
    s.addText(item[0], { x: 0.4, y: 1.15 + i * 0.6, w: 0.5, h: 0.48, fontSize: 15, bold: true, color: ACCENT, fontFace: HEADING_FONT, margin: 0 });
    s.addText(item[1], { x: 0.9, y: 1.15 + i * 0.6, w: 4.0, h: 0.48, fontSize: 14, color: WHITE, fontFace: BODY_FONT, margin: 0, valign: "middle" });
  });
  col2.forEach((item, i) => {
    s.addText(item[0], { x: 5.2, y: 1.15 + i * 0.6, w: 0.5, h: 0.48, fontSize: 15, bold: true, color: ACCENT2, fontFace: HEADING_FONT, margin: 0 });
    s.addText(item[1], { x: 5.7, y: 1.15 + i * 0.6, w: 4.1, h: 0.48, fontSize: 14, color: WHITE, fontFace: BODY_FONT, margin: 0, valign: "middle" });
  });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 3 – HISTORY & CLASSIFICATION
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = midSlide(pres);
  slideTitle(s, "History & Classification", "From opium poppy to WHO Essential Medicine");
  s.addText([
    bullet("Morphine isolated from opium (Papaver somniferum) by Friedrich Sertürner in 1804 – the first alkaloid isolated from a plant"),
    bullet("Named after Morpheus, the Greek god of dreams"),
    bullet("Commercial production began ~1827 (Merck); hypodermic needle introduced ~1853 accelerated clinical use"),
    bullet("Still considered the gold standard opioid analgesic against which all others are compared"),
  ], { x: 0.4, y: 1.05, w: 5.6, h: 2.2, fontSize: 14, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.3 });

  // Classification box
  s.addShape(pres.ShapeType.rect, { x: 6.3, y: 1.05, w: 3.5, h: 4.3, fill: { color: "0A1520" }, line: { color: ACCENT, width: 1.5 } });
  s.addText("CLASSIFICATION", { x: 6.3, y: 1.05, w: 3.5, h: 0.4, fontSize: 12, bold: true, color: ACCENT, fontFace: HEADING_FONT, align: "center", margin: 0 });
  const classItems = [
    ["Class", "Opioid analgesic"],
    ["Subclass", "Phenanthrene alkaloid"],
    ["Receptor", "μ (mu) > κ, δ agonist"],
    ["Schedule", "Schedule II (DEA)"],
    ["WHO", "Essential Medicine"],
    ["Source", "Natural (opium)"],
  ];
  classItems.forEach((item, i) => {
    s.addText(item[0] + ":", { x: 6.45, y: 1.5 + i * 0.6, w: 1.2, h: 0.45, fontSize: 11, bold: true, color: ACCENT2, fontFace: BODY_FONT, margin: 0 });
    s.addText(item[1], { x: 7.7, y: 1.5 + i * 0.6, w: 2.0, h: 0.45, fontSize: 11, color: WHITE, fontFace: BODY_FONT, margin: 0 });
  });

  s.addText([
    bullet("Other natural opioids: codeine, thebaine"),
    bullet("Semi-synthetic derivatives: heroin (3,6-diacetylmorphine), hydromorphone, oxymorphone, oxycodone, buprenorphine, naloxone, naltrexone"),
    bullet("Fully synthetic: fentanyl, methadone, meperidine, tramadol"),
  ], { x: 0.4, y: 3.15, w: 5.6, h: 2.2, fontSize: 13, color: LIGHT, fontFace: BODY_FONT, lineSpacingMultiple: 1.25 });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 4 – CHEMISTRY & STRUCTURE-ACTIVITY
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Chemistry & Structure-Activity Relationships");
  s.addText([
    bullet("Molecular formula: C₁₇H₁₉NO₃  •  MW: 285.3 Da"),
    bullet("Pentacyclic structure with two hydroxyl groups: C-3 (phenolic) and C-6 (alcoholic)"),
    bullet("The phenolic –OH at C-3 is critical for opioid receptor binding"),
    subBullet("Methylation → codeine (10× less potent); acetylation → heroin (faster CNS entry)"),
    bullet("C-6 hydroxyl: oxidation increases potency (hydromorphone ~7× morphine)"),
    bullet("Tertiary nitrogen at position 17 (N-methyl)"),
    subBullet("Replace N-methyl with allyl/cyclopropylmethyl → naloxone/naltrexone (antagonists)"),
    subBullet("Replace N-methyl with lower efficacy group → buprenorphine (partial agonist)"),
    bullet("Double bond C7–C8: reduction increases potency"),
    bullet("14-OH addition (from thebaine) → oxymorphone, oxycodone, naloxone"),
    bullet("pKa = 8.0 → at physiologic pH, only 10–20% un-ionized → slower CNS penetration vs. fentanyl"),
    bullet("Lipid solubility: LOW relative to fentanyl; accounts for slower onset and longer duration"),
  ], { x: 0.4, y: 1.05, w: 9.3, h: 4.35, fontSize: 13, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.2 });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 5 – MECHANISM OF ACTION
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = midSlide(pres);
  slideTitle(s, "Mechanism of Action", "μ-Opioid Receptor Agonist");
  // Left column
  s.addText("Receptor Binding", { x: 0.4, y: 1.1, w: 4.5, h: 0.4, fontSize: 16, bold: true, color: ACCENT, fontFace: HEADING_FONT, margin: 0 });
  s.addText([
    bullet("Binds preferentially to μ (mu) opioid receptors; also κ and δ"),
    bullet("All opioid receptors are Gi/Go-protein coupled receptors (GPCRs)"),
    subBullet("↓ adenylyl cyclase → ↓ cAMP"),
    subBullet("Opens K⁺ channels → hyperpolarization"),
    subBullet("Closes voltage-gated Ca²⁺ channels → ↓ neurotransmitter release"),
    bullet("Net effect: decreased neuronal excitability and reduced pain signal transmission"),
  ], { x: 0.4, y: 1.5, w: 4.5, h: 2.5, fontSize: 13, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.2 });

  // Right column
  s.addText("Sites of Action", { x: 5.2, y: 1.1, w: 4.5, h: 0.4, fontSize: 16, bold: true, color: ACCENT2, fontFace: HEADING_FONT, margin: 0 });
  s.addText([
    bullet("Supraspinal: periaqueductal gray (PAG), nucleus raphe magnus → descending inhibition"),
    bullet("Spinal: dorsal horn → inhibit substance P / glutamate release"),
    bullet("Peripheral: inflamed tissue sensory terminals → ↓ nociceptor sensitivity"),
    bullet("Limbic system: emotional/affective component of pain"),
  ], { x: 5.2, y: 1.5, w: 4.5, h: 2.5, fontSize: 13, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.2 });

  // Receptor effect table
  s.addShape(pres.ShapeType.rect, { x: 0.4, y: 3.95, w: 9.2, h: 1.45, fill: { color: "0A1520" }, line: { color: ACCENT, width: 1 } });
  s.addText("μ Receptor Effects at a Glance", { x: 0.5, y: 4.0, w: 9, h: 0.3, fontSize: 12, bold: true, color: ACCENT, fontFace: HEADING_FONT, margin: 0 });
  const mrfx = [
    ["Analgesia (supraspinal + spinal)", ACCENT2],
    ["Respiratory depression", RED],
    ["Euphoria / sedation", SUBTEXT],
    ["Miosis", LIGHT],
    ["Reduced GI motility / constipation", RED],
    ["Physical dependence", RED],
  ];
  mrfx.forEach((item, i) => {
    const col = i < 3 ? 0 : 1;
    const row = i < 3 ? i : i - 3;
    s.addText("• " + item[0], {
      x: 0.5 + col * 4.65, y: 4.32 + row * 0.35, w: 4.5, h: 0.33,
      fontSize: 11, color: item[1], fontFace: BODY_FONT, margin: 0
    });
  });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 6 – PHARMACOKINETICS (ADME)
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Pharmacokinetics (ADME)", "Goodman & Gilman 14e  •  Miller's Anesthesia 10e");
  const rows = [
    ["ABSORPTION", [
      "Oral bioavailability ~20–30% (extensive first-pass hepatic metabolism)",
      "IM/SC: bioavailability ~100%; peak 30–60 min",
      "IV: immediate; peak analgesia 15–20 min",
      "Rectal: ~20% bioavailability (similar to oral)",
      "Spinal/epidural: direct spinal cord effect",
    ]],
    ["DISTRIBUTION", [
      "Protein binding: ~20–40% (mainly albumin)",
      "Low lipid solubility → slow CNS penetration; pKa 8.0",
      "Only 10–20% un-ionized at pH 7.4 → slower onset vs. fentanyl",
      "Vd ~3–5 L/kg; crosses placenta and enters breast milk",
    ]],
    ["METABOLISM", [
      "Primarily hepatic conjugation (glucuronidation, UGT2B7)",
      "Morphine-3-glucuronide (M3G, ~60%): NO analgesic activity; may antagonize morphine; CNS excitatory (myoclonus, seizures) with accumulation",
      "Morphine-6-glucuronide (M6G, ~10%): MORE potent μ-agonist than morphine; major contributor to analgesia (especially oral/renal failure)",
      "Kidney contributes ~40% of morphine conjugation",
    ]],
    ["EXCRETION", [
      "Eliminated primarily as M3G by glomerular filtration",
      "~90% excreted within 24 hours",
      "Half-life (t½): 2–3 hours (parent drug); M6G longer",
      "Enterohepatic circulation → small amounts in feces/urine for days",
    ]],
  ];
  rows.forEach((row, ri) => {
    const y = 1.08 + ri * 1.1;
    s.addShape(pres.ShapeType.rect, { x: 0.3, y, w: 1.55, h: 0.9, fill: { color: ACCENT }, line: { color: ACCENT } });
    s.addText(row[0], { x: 0.3, y, w: 1.55, h: 0.9, fontSize: 10, bold: true, color: DARK_BG, fontFace: HEADING_FONT, align: "center", valign: "middle", margin: 0 });
    const items = row[1].map(t => ({ text: t, options: { bullet: { code: "2022" }, breakLine: true } }));
    s.addText(items, { x: 2.0, y: y + 0.02, w: 7.7, h: 0.88, fontSize: 11.5, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.15, valign: "top" });
  });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 7 – PK PARAMETERS TABLE
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = midSlide(pres);
  slideTitle(s, "Key Pharmacokinetic Parameters");
  const tableData = [
    [
      { text: "Parameter", options: { bold: true, color: DARK_BG, fill: ACCENT, align: "center" } },
      { text: "Value", options: { bold: true, color: DARK_BG, fill: ACCENT, align: "center" } },
      { text: "Parameter", options: { bold: true, color: DARK_BG, fill: ACCENT, align: "center" } },
      { text: "Value", options: { bold: true, color: DARK_BG, fill: ACCENT, align: "center" } },
    ],
    [{ text: "Oral bioavailability" }, { text: "20–30%" }, { text: "Half-life (t½)" }, { text: "2–3 hours" }],
    [{ text: "Protein binding" }, { text: "20–40%" }, { text: "M6G t½" }, { text: "~9 hours" }],
    [{ text: "Vd" }, { text: "3–5 L/kg" }, { text: "Onset IV" }, { text: "5 min (peak 15–20 min)" }],
    [{ text: "Onset IM/SC" }, { text: "10–15 min" }, { text: "Onset PO" }, { text: "30–45 min" }],
    [{ text: "Duration" }, { text: "3–6 hours (IR)" }, { text: "Duration ER" }, { text: "8–24 hours" }],
    [{ text: "pKa" }, { text: "8.0" }, { text: "Renal excretion" }, { text: ">90% as glucuronides" }],
    [{ text: "Metabolite M3G" }, { text: "~60% (inactive/excitatory)" }, { text: "Metabolite M6G" }, { text: "~10% (active, potent)" }],
  ];
  s.addTable(tableData, {
    x: 0.3, y: 1.1, w: 9.5, h: 4.25,
    border: { pt: 0.5, color: "2A4A6A" },
    fill: MID_BG,
    color: WHITE,
    fontSize: 13,
    fontFace: BODY_FONT,
    rowH: 0.48,
    align: "center",
    valign: "middle",
  });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 8 – PHARMACODYNAMICS: CNS EFFECTS
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Pharmacodynamics – CNS Effects");
  s.addText([
    bullet("Analgesia: effective for moderate-to-severe pain; raises pain threshold at supraspinal and spinal levels"),
    bullet("Euphoria & sedation: activation of limbic μ-receptors; basis for reward and addiction"),
    bullet("Respiratory depression: direct action on brainstem respiratory center; reduced sensitivity to CO₂; DOSE-DEPENDENT; principal cause of opioid overdose death"),
    bullet("Miosis (pinpoint pupils): stimulation of Edinger-Westphal nucleus of CN III; no tolerance develops; diagnostic sign of opioid use"),
    bullet("Antitussive: suppresses cough center in medulla"),
    bullet("Nausea/vomiting: stimulates chemoreceptor trigger zone (CTZ) in area postrema"),
    bullet("Hypothermia: reset hypothalamic thermostat"),
    bullet("Hormonal effects: ↓ LH, FSH, ACTH, TSH; ↑ prolactin, growth hormone, ADH"),
    bullet("EEG changes: high-voltage slow waves; seizures possible at very high doses"),
    bullet("Sedation: dose-related; potentiated by other CNS depressants"),
  ], { x: 0.4, y: 1.05, w: 9.3, h: 4.4, fontSize: 13, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.15 });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 9 – PHARMACODYNAMICS: SYSTEMIC EFFECTS
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = midSlide(pres);
  slideTitle(s, "Pharmacodynamics – Systemic Effects");
  const systems = [
    { label: "CARDIOVASCULAR", color: RED, items: [
      "Vasodilation → orthostatic hypotension (histamine release, ↓ sympathetic tone)",
      "Heart rate usually unchanged (may see bradycardia at high doses)",
      "Dangerous in hypovolemia / hemorrhagic shock – use with extreme caution",
    ]},
    { label: "RESPIRATORY", color: RED, items: [
      "Dose-dependent respiratory depression – main toxic effect",
      "↓ Rate, tidal volume, and hypoxic/hypercapnic drive",
      "Bronchoconstriction (histamine release) – caution in asthma",
    ]},
    { label: "GI TRACT", color: ACCENT, items: [
      "↓ Gastric emptying, ↓ propulsive motility → constipation (tolerance does NOT develop)",
      "↑ Sphincter of Oddi tone (spasm) → biliary colic worsening possible",
      "Nausea/vomiting via CTZ; ↑ nausea on ambulation",
    ]},
    { label: "GENITOURINARY", color: ACCENT2, items: [
      "↑ Urinary bladder sphincter tone → urinary retention",
      "↑ Ureteral tone and amplitude of contractions",
    ]},
    { label: "ENDOCRINE / IMMUNE", color: SUBTEXT, items: [
      "Chronic use → hypogonadotropic hypogonadism (↓ LH, FSH, testosterone, estrogen)",
      "Immunosuppression reported with chronic use",
    ]},
  ];
  systems.forEach((sys, i) => {
    const col = i < 3 ? 0 : 1;
    const row = i < 3 ? i : i - 3;
    const x = col === 0 ? 0.3 : 5.2;
    const y = 1.05 + row * 1.5;
    s.addShape(pres.ShapeType.rect, { x, y, w: 4.6, h: 0.3, fill: { color: sys.color }, line: { color: sys.color } });
    s.addText(sys.label, { x, y, w: 4.6, h: 0.3, fontSize: 11, bold: true, color: DARK_BG, fontFace: HEADING_FONT, align: "center", valign: "middle", margin: 0 });
    const items = sys.items.map(t => ({ text: t, options: { bullet: { code: "2022" }, breakLine: true } }));
    s.addText(items, { x: x + 0.1, y: y + 0.3, w: 4.5, h: 1.15, fontSize: 11, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.1, valign: "top" });
  });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 10 – CLINICAL USES
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Clinical Uses / Indications");
  const uses = [
    { title: "Acute Severe Pain", color: ACCENT, items: ["Trauma, post-operative pain", "Myocardial infarction (IV morphine for acute pulmonary edema + pain)", "Renal/biliary colic (myth of worsening disproven)", "Burns, cancer pain crisis"] },
    { title: "Chronic Cancer Pain", color: RED, items: ["WHO analgesic ladder Step 3 drug", "Oral morphine (IR + ER) is standard of care for moderate-to-severe cancer pain", "Starting dose: 5–15 mg PO q4h (IR); convert to ER after dose titration"] },
    { title: "Acute Pulmonary Edema", color: ACCENT2, items: ["IV morphine: ↓ preload/afterload via venodilation", "↓ Anxiety and dyspnea perception", "Caution: evidence questioned in recent literature"] },
    { title: "Neuraxial Analgesia", color: GREEN, items: ["Epidural/intrathecal morphine for post-op and obstetric pain", "Long duration (up to 24 h IT; 12–24 h epidural)", "Risk of delayed respiratory depression (monitor 24 h)"] },
    { title: "Palliative Care", color: SUBTEXT, items: ["Dyspnea management in terminal illness", "Pain at end of life; subcutaneous infusion acceptable"] },
    { title: "Procedural Sedation", color: ACCENT, items: ["IV titration in ED/ICU", "Paired with benzodiazepine for sedation-analgesia"] },
  ];
  uses.forEach((use, i) => {
    const col = i < 3 ? 0 : 1;
    const row = i < 3 ? i : i - 3;
    const x = col === 0 ? 0.3 : 5.2;
    const y = 1.05 + row * 1.5;
    s.addShape(pres.ShapeType.rect, { x, y, w: 4.6, h: 0.32, fill: { color: use.color }, line: { color: use.color } });
    s.addText(use.title, { x, y, w: 4.6, h: 0.32, fontSize: 12, bold: true, color: DARK_BG, fontFace: HEADING_FONT, align: "center", valign: "middle", margin: 0 });
    const items = use.items.map(t => ({ text: t, options: { bullet: { code: "2022" }, breakLine: true } }));
    s.addText(items, { x: x + 0.1, y: y + 0.32, w: 4.5, h: 1.1, fontSize: 11, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.1, valign: "top" });
  });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 11 – DOSING: ORAL
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = midSlide(pres);
  slideTitle(s, "Dosing – Oral Routes", "Immediate Release (IR) & Extended Release (ER)");
  s.addText("ORAL IMMEDIATE RELEASE (Morphine Sulfate IR)", {
    x: 0.4, y: 1.05, w: 9.2, h: 0.38, fontSize: 15, bold: true, color: ACCENT, fontFace: HEADING_FONT, margin: 0
  });
  const irData = [
    [{ text: "Population", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Dose", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Frequency", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Notes", options: { bold: true, fill: ACCENT, color: DARK_BG } }],
    [{ text: "Adults (opioid-naive)" }, { text: "5–15 mg" }, { text: "q4h" }, { text: "Titrate to effect; 30–60 mg/day starting" }],
    [{ text: "Adults (severe pain)" }, { text: "10–30 mg" }, { text: "q4h" }, { text: "Monitor respiratory rate closely" }],
    [{ text: "Elderly (≥65 yrs)" }, { text: "2.5–5 mg" }, { text: "q4–6h" }, { text: "Start low; ↑ risk ADRs" }],
    [{ text: "Pediatric (>6 mo)" }, { text: "0.2–0.5 mg/kg" }, { text: "q4–6h" }, { text: "Max 15–20 mg/dose" }],
  ];
  s.addTable(irData, { x: 0.3, y: 1.45, w: 9.4, h: 1.95, border: { pt: 0.5, color: "2A4A6A" }, fill: DARK_BG, color: WHITE, fontSize: 12, fontFace: BODY_FONT, rowH: 0.38, align: "center", valign: "middle" });

  s.addText("ORAL EXTENDED RELEASE (MS Contin, Morphine ER)", {
    x: 0.4, y: 3.45, w: 9.2, h: 0.38, fontSize: 15, bold: true, color: ACCENT2, fontFace: HEADING_FONT, margin: 0
  });
  const erData = [
    [{ text: "Population", options: { bold: true, fill: ACCENT2, color: DARK_BG } },
     { text: "Starting Dose", options: { bold: true, fill: ACCENT2, color: DARK_BG } },
     { text: "Frequency", options: { bold: true, fill: ACCENT2, color: DARK_BG } },
     { text: "Notes", options: { bold: true, fill: ACCENT2, color: DARK_BG } }],
    [{ text: "Opioid-naive adult" }, { text: "15 mg" }, { text: "q8–12h" }, { text: "Do NOT crush/chew/dissolve" }],
    [{ text: "Cancer pain (conversion)" }, { text: "Total 24-hr IR dose ÷ 2" }, { text: "q12h" }, { text: "Provide IR for breakthrough (10–15% of total daily dose)" }],
    [{ text: "Cancer pain (Swanson)" }, { text: "30–60 mg/day total" }, { text: "Divide q12h after 1 wk IR titration" }, { text: "Add breakthrough IR morphine" }],
  ];
  s.addTable(erData, { x: 0.3, y: 3.85, w: 9.4, h: 1.6, border: { pt: 0.5, color: "2A4A6A" }, fill: DARK_BG, color: WHITE, fontSize: 12, fontFace: BODY_FONT, rowH: 0.42, align: "center", valign: "middle" });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 12 – DOSING: PARENTERAL (IV / IM / SC)
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Dosing – Parenteral Routes (IV / IM / SC)", "Rosen's Emergency Medicine 9e  •  Miller's Anesthesia 10e");
  s.addText("INTRAVENOUS (IV)", { x: 0.4, y: 1.06, w: 9.2, h: 0.35, fontSize: 15, bold: true, color: ACCENT, fontFace: HEADING_FONT, margin: 0 });
  const ivData = [
    [{ text: "Indication", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Dose", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Notes", options: { bold: true, fill: ACCENT, color: DARK_BG } }],
    [{ text: "Acute severe pain (adults)" }, { text: "0.1–0.15 mg/kg IV (loading); then ~half dose q5–15 min" }, { text: "Titrate to pain relief; onset 5 min, peak 15–20 min" }],
    [{ text: "Intraoperative analgesia" }, { text: "0.05–0.2 mg/kg IV" }, { text: "Adjust for age, ASA status" }],
    [{ text: "Post-op analgesia" }, { text: "2–5 mg IV q2–4h PRN" }, { text: "PCA preferred for ongoing pain" }],
    [{ text: "ICU infusion" }, { text: "2–10 mg/h IV" }, { text: "Titrate to CPOT/NRS; ↓ dose in renal failure" }],
    [{ text: "Pediatric acute pain (>6 mo)" }, { text: "0.05–0.1 mg/kg IV; max 0.15 mg/kg" }, { text: "Repeat q2–4h; dilute; monitor SpO₂" }],
    [{ text: "Neonates (prem)" }, { text: "0.01–0.02 mg/kg q4–6h" }, { text: "↓ clearance with gestational age; caution" }],
  ];
  s.addTable(ivData, { x: 0.3, y: 1.42, w: 9.4, h: 2.45, border: { pt: 0.5, color: "2A4A6A" }, fill: MID_BG, color: WHITE, fontSize: 11.5, fontFace: BODY_FONT, rowH: 0.36, align: "center", valign: "middle" });

  s.addText("IM / SUBCUTANEOUS (SC)", { x: 0.4, y: 3.92, w: 9.2, h: 0.35, fontSize: 15, bold: true, color: ACCENT2, fontFace: HEADING_FONT, margin: 0 });
  const imData = [
    [{ text: "Route", options: { bold: true, fill: ACCENT2, color: DARK_BG } },
     { text: "Adult Dose", options: { bold: true, fill: ACCENT2, color: DARK_BG } },
     { text: "Pediatric Dose", options: { bold: true, fill: ACCENT2, color: DARK_BG } },
     { text: "Notes", options: { bold: true, fill: ACCENT2, color: DARK_BG } }],
    [{ text: "IM" }, { text: "5–20 mg q4h" }, { text: "0.1–0.2 mg/kg q4h" }, { text: "Not preferred; unpredictable absorption" }],
    [{ text: "SC" }, { text: "5–15 mg q4h" }, { text: "0.1–0.15 mg/kg q4h" }, { text: "Good for palliative care SC infusions" }],
  ];
  s.addTable(imData, { x: 0.3, y: 4.3, w: 9.4, h: 1.1, border: { pt: 0.5, color: "2A4A6A" }, fill: MID_BG, color: WHITE, fontSize: 12, fontFace: BODY_FONT, rowH: 0.35, align: "center", valign: "middle" });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 13 – DOSING: NEURAXIAL (EPIDURAL / INTRATHECAL)
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = midSlide(pres);
  slideTitle(s, "Dosing – Neuraxial Routes (Epidural / Intrathecal)", "Preservative-free morphine only");
  s.addText("EPIDURAL", { x: 0.4, y: 1.06, w: 4.5, h: 0.35, fontSize: 15, bold: true, color: ACCENT, fontFace: HEADING_FONT, margin: 0 });
  s.addText("INTRATHECAL (SPINAL)", { x: 5.2, y: 1.06, w: 4.5, h: 0.35, fontSize: 15, bold: true, color: ACCENT2, fontFace: HEADING_FONT, margin: 0 });

  const epItems = [
    "Adults (post-op): 2–5 mg epidural q12–24h",
    "Obstetric (labor analgesia): 2–3 mg epidural",
    "Cesarean section: 3–5 mg single dose epidural",
    "Cancer/chronic pain infusion: 1–10 mg/day",
    "Duration of analgesia: 12–24 hours",
    "Extended-release epidural (DepoDur): 10–20 mg single dose for C/S",
    "Monitor for delayed respiratory depression (12–24 h)",
    "Must use PRESERVATIVE-FREE preparation",
  ];
  const itItems = [
    "Adults (post-op): 0.1–0.3 mg intrathecal single dose",
    "Cesarean section: 0.1–0.2 mg IT",
    "Chronic pain pump: variable (mcg/day titrated)",
    "Duration: up to 24 hours (longer than epidural)",
    "Onset: 45–60 min (hydrophilic; slow)",
    "Risk of delayed respiratory depression: monitor 24 h",
    "IT dose ~10× less than epidural dose",
    "PRESERVATIVE-FREE preparation mandatory",
  ];
  s.addText(epItems.map(t => ({ text: t, options: { bullet: { code: "2022" }, breakLine: true } })),
    { x: 0.4, y: 1.45, w: 4.5, h: 3.9, fontSize: 12.5, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.2 });
  s.addText(itItems.map(t => ({ text: t, options: { bullet: { code: "2022" }, breakLine: true } })),
    { x: 5.2, y: 1.45, w: 4.5, h: 3.9, fontSize: 12.5, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.2 });

  s.addShape(pres.ShapeType.rect, { x: 0.3, y: 5.22, w: 9.4, h: 0.25, fill: { color: RED }, line: { color: RED } });
  s.addText("⚠ ALL neuraxial morphine requires monitoring for delayed respiratory depression for at least 12–24 h post-dose", {
    x: 0.3, y: 5.22, w: 9.4, h: 0.25, fontSize: 10, bold: true, color: WHITE, fontFace: BODY_FONT, align: "center", valign: "middle", margin: 0
  });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 14 – DOSING: PCA
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Dosing – Patient-Controlled Analgesia (PCA) & Infusions");
  s.addText("PCA – MORPHINE (IV)", { x: 0.4, y: 1.06, w: 9.2, h: 0.35, fontSize: 15, bold: true, color: ACCENT, fontFace: HEADING_FONT, margin: 0 });
  const pcaData = [
    [{ text: "Setting", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Typical Value", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Range", options: { bold: true, fill: ACCENT, color: DARK_BG } }],
    [{ text: "Demand (bolus) dose" }, { text: "1 mg" }, { text: "0.5–2.5 mg" }],
    [{ text: "Lockout interval" }, { text: "6 minutes" }, { text: "5–10 minutes" }],
    [{ text: "Basal rate" }, { text: "0 mg/h (opioid-naive)" }, { text: "0–2 mg/h (opioid-tolerant)" }],
    [{ text: "1-hour limit" }, { text: "10 mg" }, { text: "Per protocol" }],
  ];
  s.addTable(pcaData, { x: 0.3, y: 1.45, w: 9.4, h: 2.0, border: { pt: 0.5, color: "2A4A6A" }, fill: MID_BG, color: WHITE, fontSize: 13, fontFace: BODY_FONT, rowH: 0.4, align: "center", valign: "middle" });

  s.addText("CONTINUOUS IV INFUSION (ICU/Palliative)", { x: 0.4, y: 3.52, w: 9.2, h: 0.35, fontSize: 15, bold: true, color: ACCENT2, fontFace: HEADING_FONT, margin: 0 });
  s.addText([
    bullet("Adults: typically 2–10 mg/h; titrate q15–30 min to target (CPOT ≤2 or NRS ≤3)"),
    bullet("Opioid-tolerant patients may require much higher rates"),
    bullet("Pediatric: 0.01–0.03 mg/kg/h IV (neonates/infants – see special populations)"),
    bullet("Reduce by 25–50% in renal impairment (M6G accumulation risk)"),
    bullet("Syringe pump: typically 1 mg/mL concentration for adults"),
  ], { x: 0.4, y: 3.88, w: 9.3, h: 1.65, fontSize: 13, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.2 });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 15 – EQUIANALGESIC DOSES
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = midSlide(pres);
  slideTitle(s, "Equianalgesic Dose Table", "Morphine as the reference standard (10 mg IV)");
  const eqData = [
    [{ text: "Opioid", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "IV/IM (mg)", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Oral (mg)", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Notes", options: { bold: true, fill: ACCENT, color: DARK_BG } }],
    [{ text: "Morphine" }, { text: "10" }, { text: "30" }, { text: "Reference standard" }],
    [{ text: "Hydromorphone" }, { text: "1.5" }, { text: "7.5" }, { text: "~7× more potent IV" }],
    [{ text: "Oxycodone" }, { text: "—" }, { text: "20–30" }, { text: "No parenteral form in most countries" }],
    [{ text: "Codeine" }, { text: "130" }, { text: "200" }, { text: "Prodrug; CYP2D6 dependent" }],
    [{ text: "Fentanyl" }, { text: "0.1 (100 mcg)" }, { text: "—" }, { text: "~100× more potent than morphine" }],
    [{ text: "Methadone" }, { text: "Variable" }, { text: "Variable" }, { text: "Complex equianalgesic; specialist input required" }],
    [{ text: "Meperidine" }, { text: "75–100" }, { text: "300" }, { text: "Not recommended for chronic use (normeperidine)" }],
    [{ text: "Tramadol" }, { text: "—" }, { text: "150" }, { text: "Partial opioid; CYP2D6 dependent" }],
    [{ text: "Oxymorphone" }, { text: "1" }, { text: "10" }, { text: "~10× more potent than oral morphine" }],
  ];
  s.addTable(eqData, { x: 0.3, y: 1.08, w: 9.5, h: 4.4, border: { pt: 0.5, color: "2A4A6A" }, fill: DARK_BG, color: WHITE, fontSize: 13, fontFace: BODY_FONT, rowH: 0.43, align: "center", valign: "middle" });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 16 – SPECIAL POPULATIONS
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Dosing in Special Populations", "Barash Clinical Anesthesia 9e  •  Miller's Anesthesia 10e");
  const pops = [
    { label: "ELDERLY", color: ACCENT, items: [
      "↑ Sensitivity to opioids; ↑ duration of action",
      "Start with 25–50% of usual adult dose",
      "↑ Risk of respiratory depression, confusion, falls",
      "Age correlates with increased duration of analgesia",
    ]},
    { label: "RENAL IMPAIRMENT", color: RED, items: [
      "M6G accumulates → prolonged analgesia + respiratory depression",
      "M3G accumulation → CNS excitation (myoclonus, seizures, delirium)",
      "Reduce dose and increase dosing intervals",
      "Monitor closely; consider fentanyl or hydromorphone instead",
    ]},
    { label: "HEPATIC IMPAIRMENT", color: ACCENT, items: [
      "Morphine metabolism dependent on liver; ↓ conjugation in cirrhosis",
      "Bioavailability ↑ (↓ first-pass effect)",
      "Use with caution; reduce dose by ~50% and titrate",
    ]},
    { label: "PEDIATRIC", color: ACCENT2, items: [
      "Neonates (esp. premature): ↓ clearance; dose q4–6h; 0.01–0.05 mg/kg/dose IV",
      "Infants/children: 0.05–0.1 mg/kg IV q2–4h; 0.2–0.5 mg/kg PO q4–6h",
      "M6G sensitivity increases with maturation",
      "Apnea risk in neonates – monitor SpO₂",
    ]},
    { label: "PREGNANCY", color: SUBTEXT, items: [
      "Crosses placenta; can cause neonatal respiratory depression",
      "Use lowest effective dose for shortest duration",
      "Chronic use: neonatal opioid withdrawal syndrome (NOWS)",
      "Labor analgesia: small IV doses (1–2 mg) acceptable",
    ]},
    { label: "OBESITY", color: GREEN, items: [
      "Use ideal body weight (IBW) for initial dosing calculations",
      "Loading dose: 0.1–0.15 mg/kg IBW IV",
      "Monitor for ↑ respiratory risk (OSA, positioning)",
    ]},
  ];
  pops.forEach((pop, i) => {
    const col = i < 3 ? 0 : 1;
    const row = i < 3 ? i : i - 3;
    const x = col === 0 ? 0.3 : 5.2;
    const y = 1.05 + row * 1.5;
    s.addShape(pres.ShapeType.rect, { x, y, w: 4.6, h: 0.3, fill: { color: pop.color }, line: { color: pop.color } });
    s.addText(pop.label, { x, y, w: 4.6, h: 0.3, fontSize: 11, bold: true, color: DARK_BG, fontFace: HEADING_FONT, align: "center", valign: "middle", margin: 0 });
    const items = pop.items.map(t => ({ text: t, options: { bullet: { code: "2022" }, breakLine: true } }));
    s.addText(items, { x: x + 0.05, y: y + 0.3, w: 4.55, h: 1.15, fontSize: 11, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.1, valign: "top" });
  });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 17 – ADVERSE EFFECTS
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = midSlide(pres);
  slideTitle(s, "Adverse Effects");
  const adrData = [
    [{ text: "System", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Effect", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Management", options: { bold: true, fill: ACCENT, color: DARK_BG } }],
    [{ text: "RESPIRATORY" }, { text: "Respiratory depression (most dangerous; dose-dependent)" }, { text: "Naloxone 0.4 mg IV (titrate); O₂; mechanical ventilation if needed" }],
    [{ text: "CNS" }, { text: "Sedation, euphoria, dysphoria, confusion, myoclonus (M3G), seizures" }, { text: "Reduce dose; consider opioid rotation" }],
    [{ text: "CARDIOVASCULAR" }, { text: "Hypotension, bradycardia, vasodilation (histamine release)" }, { text: "IV fluids, positioning; diphenhydramine for histamine" }],
    [{ text: "GI" }, { text: "Constipation (NO tolerance), nausea/vomiting, delayed gastric emptying" }, { text: "Stimulant laxative (senna/bisacodyl) routinely; antiemetics (ondansetron)" }],
    [{ text: "GU" }, { text: "Urinary retention, bladder spasm" }, { text: "Catheterisation if needed; dose reduction" }],
    [{ text: "ENDOCRINE" }, { text: "Hypogonadism, ↓ libido (chronic use), ↑ ADH" }, { text: "Hormone replacement if symptomatic" }],
    [{ text: "SKIN" }, { text: "Pruritus (particularly neuraxial), sweating, flushing" }, { text: "Ondansetron, nalbuphine, low-dose naloxone" }],
    [{ text: "IMMUNE" }, { text: "Histamine release (IV bolus) → bronchoconstriction, urticaria" }, { text: "Slow IV infusion; antihistamines" }],
  ];
  s.addTable(adrData, { x: 0.3, y: 1.06, w: 9.5, h: 4.4, border: { pt: 0.5, color: "2A4A6A" }, fill: DARK_BG, color: WHITE, fontSize: 11.5, fontFace: BODY_FONT, rowH: 0.46, align: "center", valign: "middle" });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 18 – CONTRAINDICATIONS & PRECAUTIONS
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Contraindications & Precautions");
  s.addText("ABSOLUTE CONTRAINDICATIONS", { x: 0.4, y: 1.06, w: 4.5, h: 0.35, fontSize: 14, bold: true, color: RED, fontFace: HEADING_FONT, margin: 0 });
  s.addText([
    bullet("Severe respiratory depression / respiratory arrest"),
    bullet("Acute asthma or severe bronchospasm (relative – use with extreme caution)"),
    bullet("Paralytic ileus"),
    bullet("Hypersensitivity to morphine (true allergy, rare)"),
    bullet("Concomitant use of MAO inhibitors (within 14 days) – serotonin syndrome risk"),
    bullet("Head injury + raised intracranial pressure (relative – CO₂ retention worsens ICP)"),
  ], { x: 0.4, y: 1.44, w: 4.6, h: 2.5, fontSize: 13, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.2 });

  s.addText("PRECAUTIONS / USE WITH CARE", { x: 5.2, y: 1.06, w: 4.5, h: 0.35, fontSize: 14, bold: true, color: ACCENT, fontFace: HEADING_FONT, margin: 0 });
  s.addText([
    bullet("Elderly: reduce dose by 25–50%"),
    bullet("Renal impairment: reduce dose / extend interval; monitor for M6G toxicity"),
    bullet("Hepatic failure: ↑ bioavailability; reduce dose"),
    bullet("Hypothyroidism: ↑ CNS/respiratory depression"),
    bullet("Adrenal insufficiency: additive hypotension"),
    bullet("Hypovolemia / shock: ↑ risk of severe hypotension"),
    bullet("Seizure disorders: M3G may lower threshold"),
    bullet("Pregnancy: neonatal depression; NOWS with chronic use"),
    bullet("Neonates/premature infants: ↓ clearance; monitor closely"),
    bullet("Concurrent CNS depressants: ↑ sedation + respiratory depression"),
  ], { x: 5.2, y: 1.44, w: 4.5, h: 3.9, fontSize: 12.5, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.15 });

  s.addShape(pres.ShapeType.rect, { x: 0.3, y: 3.95, w: 4.6, h: 1.45, fill: { color: "1A1A2E" }, line: { color: RED, width: 1.5 } });
  s.addText("⚠ BLACK BOX WARNING (FDA)\nConcomitant use with benzodiazepines or CNS depressants increases risk of profound sedation, respiratory depression, coma, and death", {
    x: 0.4, y: 4.0, w: 4.5, h: 1.3, fontSize: 11.5, color: WHITE, fontFace: BODY_FONT, align: "center", valign: "middle"
  });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 19 – DRUG INTERACTIONS
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = midSlide(pres);
  slideTitle(s, "Drug Interactions");
  const diData = [
    [{ text: "Drug / Class", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Interaction", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Significance", options: { bold: true, fill: ACCENT, color: DARK_BG } }],
    [{ text: "Benzodiazepines / CNS depressants" }, { text: "↑ Respiratory depression, sedation, coma" }, { text: "MAJOR / Black Box" }],
    [{ text: "MAO Inhibitors (phenelzine, tranylcypromine)" }, { text: "Serotonin syndrome, hyperpyrexia, death" }, { text: "CONTRAINDICATED" }],
    [{ text: "Alcohol" }, { text: "↑ CNS/respiratory depression" }, { text: "MAJOR – avoid" }],
    [{ text: "Tricyclic antidepressants" }, { text: "↑ Sedation, ↑ respiratory depression" }, { text: "MODERATE" }],
    [{ text: "Phenothiazines (e.g. chlorpromazine)" }, { text: "↑ Sedation, hypotension; potentiation" }, { text: "MODERATE" }],
    [{ text: "Anticholinergic drugs" }, { text: "↑ Constipation, urinary retention, ileus" }, { text: "MODERATE" }],
    [{ text: "Muscle relaxants (e.g. baclofen)" }, { text: "↑ CNS depression, ↓ respiratory drive" }, { text: "MODERATE" }],
    [{ text: "Cimetidine" }, { text: "Inhibits morphine metabolism → ↑ plasma levels" }, { text: "MODERATE" }],
    [{ text: "Rifampicin" }, { text: "↑ Morphine metabolism → ↓ efficacy" }, { text: "MODERATE" }],
    [{ text: "Naloxone / Naltrexone" }, { text: "Competitive antagonism; precipitates withdrawal" }, { text: "Therapeutic / Caution" }],
  ];
  s.addTable(diData, { x: 0.3, y: 1.06, w: 9.5, h: 4.45, border: { pt: 0.5, color: "2A4A6A" }, fill: DARK_BG, color: WHITE, fontSize: 12, fontFace: BODY_FONT, rowH: 0.39, align: "center", valign: "middle" });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 20 – OVERDOSE & REVERSAL
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Overdose & Reversal (Naloxone)");
  s.addText("OPIOID OVERDOSE TRIAD", { x: 0.4, y: 1.06, w: 9.2, h: 0.35, fontSize: 15, bold: true, color: RED, fontFace: HEADING_FONT, margin: 0 });
  // triad boxes
  const triad = [
    ["Miosis\n(pinpoint pupils)", "1"],
    ["Respiratory\nDepression", "2"],
    ["Decreased\nConsciousness", "3"],
  ];
  triad.forEach((item, i) => {
    s.addShape(pres.ShapeType.rect, { x: 0.4 + i * 3.1, y: 1.44, w: 2.8, h: 0.95, fill: { color: RED }, line: { color: RED } });
    s.addText(item[0], { x: 0.4 + i * 3.1, y: 1.44, w: 2.8, h: 0.95, fontSize: 15, bold: true, color: WHITE, fontFace: HEADING_FONT, align: "center", valign: "middle", margin: 0 });
  });
  s.addText("Additional: cyanosis, bradycardia, hypotension, pulmonary edema, cardiac arrest", {
    x: 0.4, y: 2.42, w: 9.3, h: 0.35, fontSize: 12, color: SUBTEXT, fontFace: BODY_FONT, margin: 0, italic: true
  });

  s.addText("NALOXONE (Narcan) – Opioid Antagonist", { x: 0.4, y: 2.82, w: 9.2, h: 0.35, fontSize: 15, bold: true, color: ACCENT2, fontFace: HEADING_FONT, margin: 0 });
  const nxData = [
    [{ text: "Route", options: { bold: true, fill: ACCENT2, color: DARK_BG } },
     { text: "Dose (Adults)", options: { bold: true, fill: ACCENT2, color: DARK_BG } },
     { text: "Dose (Pediatric)", options: { bold: true, fill: ACCENT2, color: DARK_BG } },
     { text: "Notes", options: { bold: true, fill: ACCENT2, color: DARK_BG } }],
    [{ text: "IV" }, { text: "0.4–2 mg; repeat q2–3 min (max 10 mg)" }, { text: "0.01 mg/kg IV; repeat prn" }, { text: "Titrate; avoid precipitating acute withdrawal in dependent patients" }],
    [{ text: "IM/SC" }, { text: "0.4–2 mg" }, { text: "0.01 mg/kg" }, { text: "Slower onset than IV" }],
    [{ text: "Intranasal (IN)" }, { text: "4 mg IN; repeat in 2–3 min" }, { text: "0.1 mg/kg IN" }, { text: "Community setting (Narcan nasal spray)" }],
    [{ text: "Duration" }, { text: "30–90 min (shorter than morphine!)" }, { text: "Repeat dosing required" }, { text: "Monitor for re-narcotization after initial reversal" }],
  ];
  s.addTable(nxData, { x: 0.3, y: 3.2, w: 9.5, h: 2.2, border: { pt: 0.5, color: "2A4A6A" }, fill: MID_BG, color: WHITE, fontSize: 11.5, fontFace: BODY_FONT, rowH: 0.4, align: "center", valign: "middle" });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 21 – TOLERANCE, DEPENDENCE & WITHDRAWAL
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = midSlide(pres);
  slideTitle(s, "Tolerance, Dependence & Withdrawal");
  // Tolerance
  s.addText("TOLERANCE", { x: 0.4, y: 1.06, w: 3.0, h: 0.35, fontSize: 14, bold: true, color: ACCENT, fontFace: HEADING_FONT, margin: 0 });
  s.addText([
    bullet("Decreased drug effect with repeated dosing"),
    bullet("Develops to: analgesia, euphoria, sedation, respiratory depression, nausea"),
    bullet("Does NOT develop to: constipation, miosis"),
    bullet("Mechanisms: receptor desensitization, phosphorylation, internalization, G-protein uncoupling, downregulation"),
    bullet("Cross-tolerance within opioid class (rotation may be useful)"),
  ], { x: 0.4, y: 1.44, w: 4.5, h: 2.1, fontSize: 12.5, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.2 });

  // Dependence
  s.addText("PHYSICAL DEPENDENCE", { x: 0.4, y: 3.58, w: 4.5, h: 0.35, fontSize: 14, bold: true, color: RED, fontFace: HEADING_FONT, margin: 0 });
  s.addText([
    bullet("Physiologic adaptation – withdrawal on abrupt cessation or antagonist use"),
    bullet("NOT synonymous with addiction"),
    bullet("Withdrawal onset: 6–12 h after last dose (short-acting opioids)"),
    bullet("Taper dose by ≤10–20% per day to avoid severe withdrawal"),
  ], { x: 0.4, y: 3.95, w: 4.5, h: 1.5, fontSize: 12.5, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.2 });

  // Withdrawal symptoms box
  s.addShape(pres.ShapeType.rect, { x: 5.2, y: 1.06, w: 4.5, h: 4.45, fill: { color: "0A1520" }, line: { color: RED, width: 1.5 } });
  s.addText("WITHDRAWAL SIGNS & SYMPTOMS", { x: 5.2, y: 1.06, w: 4.5, h: 0.4, fontSize: 12, bold: true, color: RED, fontFace: HEADING_FONT, align: "center", margin: 0 });
  s.addText([
    bullet("Agitation, anxiety, dysphoria"),
    bullet("Hyperalgesia, myalgia, arthralgia"),
    bullet("Piloerection (gooseflesh), diaphoresis"),
    bullet("Mydriasis (dilated pupils)"),
    bullet("Lacrimation, rhinorrhea, yawning"),
    bullet("Nausea, vomiting, diarrhea, cramping"),
    bullet("Hypertension, tachycardia, hyperthermia"),
    bullet("Release of virtually all pituitary / adrenomedullary hormones"),
    bullet("Treatment: methadone/buprenorphine taper; clonidine (α₂-agonist) for autonomic symptoms; supportive care"),
  ], { x: 5.3, y: 1.5, w: 4.3, h: 4.0, fontSize: 12, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.15 });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 22 – OPIOID USE DISORDER
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Opioid Use Disorder (OUD) & Safe Prescribing");
  s.addText([
    bullet("OUD: compulsive drug-seeking despite physical, emotional, or societal harm – NOT simply tolerance/dependence"),
    bullet("From 1999–2019: nearly 500,000 opioid overdose deaths in the US (prescription + illicit opioids)"),
    bullet("Cancer patients on long-term morphine develop tolerance and dependence but NOT necessarily OUD"),
    bullet("Risk factors: prior substance use disorder, mental health comorbidity, young age, high-dose/long-duration prescribing"),
  ], { x: 0.4, y: 1.05, w: 9.3, h: 2.0, fontSize: 13.5, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.25 });
  s.addText("SAFE PRESCRIBING PRINCIPLES", { x: 0.4, y: 3.05, w: 9.2, h: 0.38, fontSize: 15, bold: true, color: ACCENT, fontFace: HEADING_FONT, margin: 0 });
  s.addText([
    bullet("Use lowest effective dose for shortest duration"),
    bullet("Reassess pain regularly; taper and discontinue when appropriate"),
    bullet("Use multimodal analgesia (NSAIDs, acetaminophen, regional blocks) to reduce morphine requirements"),
    bullet("Prescription drug monitoring programs (PDMPs) and urine drug testing for chronic use"),
    bullet("Co-prescribe naloxone (Narcan) for patients on high-dose opioids or at overdose risk"),
    bullet("Avoid concurrent benzodiazepines when possible"),
    bullet("Use equianalgesic tables when rotating opioids; reduce dose by 25–50% due to incomplete cross-tolerance"),
  ], { x: 0.4, y: 3.46, w: 9.3, h: 2.0, fontSize: 13, color: WHITE, fontFace: BODY_FONT, lineSpacingMultiple: 1.15 });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 23 – SUMMARY CARD
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  slideTitle(s, "Quick Reference Summary – Morphine");
  const summaryData = [
    [{ text: "Category", options: { bold: true, fill: ACCENT, color: DARK_BG } },
     { text: "Key Information", options: { bold: true, fill: ACCENT, color: DARK_BG } }],
    [{ text: "Class / Receptor" }, { text: "Opioid analgesic; μ > κ, δ agonist; GPCR (Gi/Go)" }],
    [{ text: "Bioavailability" }, { text: "Oral 20–30% | IM/SC ~100% | Neuraxial: direct spinal action" }],
    [{ text: "Half-life" }, { text: "2–3 h (parent); M6G ~9 h; ↑ in renal failure" }],
    [{ text: "Adult IV dose (acute pain)" }, { text: "0.1–0.15 mg/kg IV loading; then q5–15 min titration" }],
    [{ text: "Adult PO dose (cancer pain)" }, { text: "5–15 mg q4h IR; 15 mg q12h ER (opioid-naive)" }],
    [{ text: "Epidural / IT dose" }, { text: "Epidural 2–5 mg; Intrathecal 0.1–0.3 mg (preservative-free)" }],
    [{ text: "Pediatric IV" }, { text: "0.05–0.1 mg/kg q2–4h; neonates 0.01–0.02 mg/kg q4–6h" }],
    [{ text: "Main ADRs" }, { text: "Respiratory depression, constipation, nausea, pruritus, urinary retention" }],
    [{ text: "Key contraindications" }, { text: "MAO inhibitors, severe respiratory depression, paralytic ileus" }],
    [{ text: "Reversal" }, { text: "Naloxone 0.4–2 mg IV (repeat q2–3 min); IN 4 mg" }],
    [{ text: "Equianalgesic" }, { text: "10 mg IV = 30 mg PO = 100 mcg fentanyl IV = 1.5 mg hydromorphone IV" }],
  ];
  s.addTable(summaryData, { x: 0.3, y: 1.06, w: 9.5, h: 4.4, border: { pt: 0.5, color: "2A4A6A" }, fill: MID_BG, color: WHITE, fontSize: 12, fontFace: BODY_FONT, rowH: 0.37, align: "left", valign: "middle" });
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 24 – CLOSING / REFERENCES
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = darkSlide(pres);
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 0.18, h: 5.625, fill: { color: ACCENT } });
  s.addText("REFERENCES", {
    x: 0.5, y: 0.4, w: 9, h: 0.5, fontSize: 28, bold: true, color: WHITE, fontFace: HEADING_FONT, margin: 0
  });
  s.addShape(pres.ShapeType.rect, { x: 0.5, y: 0.88, w: 5, h: 0.05, fill: { color: ACCENT } });
  const refs = [
    "Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th Edition – Chapter 23: Opioid Analgesics",
    "Miller's Anesthesia, 10th Edition – Chapter 22: Opioids; Chapter 16: Neuraxial Analgesia",
    "Barash, Cullen & Stoelting's Clinical Anesthesia, 9th Edition – Chapter 14: Pediatric Anesthesia",
    "Rosen's Emergency Medicine: Concepts and Clinical Practice, 9th Edition – Chapter 6: Analgesics",
    "Swanson's Family Medicine Review – Cancer Pain Management",
    "Harriet Lane Handbook, 23rd Edition – Opioid Tapering",
    "WHO Essential Medicines List – Morphine Sulfate",
  ];
  refs.forEach((ref, i) => {
    s.addText(`${i + 1}. ${ref}`, {
      x: 0.5, y: 1.05 + i * 0.6, w: 9.2, h: 0.52,
      fontSize: 12, color: i % 2 === 0 ? WHITE : LIGHT,
      fontFace: BODY_FONT, margin: 0
    });
  });
  s.addText("Prepared by Orris Medical AI • June 2026", {
    x: 0.5, y: 5.22, w: 9, h: 0.3, fontSize: 10, color: SUBTEXT, fontFace: BODY_FONT, margin: 0, italic: true
  });
}

// ─── WRITE FILE ─────────────────────────────────────────────────────────────
pres.writeFile({ fileName: "/home/daytona/workspace/morphine-pptx/Morphine_Pharmacology.pptx" })
  .then(() => console.log("Done: Morphine_Pharmacology.pptx"))
  .catch(e => { console.error(e); process.exit(1); });

from reportlab.lib.pagesizes import A4, landscape
from reportlab.lib import colors
from reportlab.lib.units import mm, cm
from reportlab.platypus import (
    SimpleDocTemplate, Table, TableStyle, Paragraph, Spacer,
    HRFlowable, KeepTogether
)
from reportlab.lib.styles import ParagraphStyle, getSampleStyleSheet
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_RIGHT
from reportlab.platypus.flowables import BalancedColumns
from reportlab.pdfgen import canvas
from reportlab.lib.colors import HexColor
import io

# ── PALETTE ──────────────────────────────────────────────────────────────────
NAVY        = HexColor("#0D1B2A")
NAVY2       = HexColor("#1B2A3B")
AMBER       = HexColor("#E8A020")
AMBER_LIGHT = HexColor("#FDF0D5")
SKY         = HexColor("#3DA5D9")
SKY_LIGHT   = HexColor("#D6EEF8")
RED         = HexColor("#C0392B")
RED_LIGHT   = HexColor("#FDECEA")
GREEN       = HexColor("#1E7A3C")
GREEN_LIGHT = HexColor("#D6F0E0")
GREY_DARK   = HexColor("#4A4A5A")
GREY_MID    = HexColor("#7A8899")
GREY_LIGHT  = HexColor("#EEF2F6")
WHITE       = colors.white
BLACK       = colors.black

PAGE   = landscape(A4)
W, H   = PAGE   # 297 x 210 mm

# ── CANVAS-BASED DRAWING APPROACH ────────────────────────────────────────────
# We draw everything directly onto the canvas for pixel-perfect layout.

OUTPUT = "/home/daytona/workspace/morphine-pptx/Morphine_Dosing_CheatSheet.pdf"

c = canvas.Canvas(OUTPUT, pagesize=PAGE)
c.setTitle("Morphine Dosing Cheat Sheet")
c.setAuthor("Orris Medical")

# ── HELPERS ───────────────────────────────────────────────────────────────────
def rgb(h): return HexColor(h)

def rect_filled(c, x, y, w, h, fill, radius=0):
    c.setFillColor(fill)
    if radius:
        c.roundRect(x, y, w, h, radius, fill=1, stroke=0)
    else:
        c.rect(x, y, w, h, fill=1, stroke=0)

def rect_outline(c, x, y, w, h, stroke_col, lw=0.5, radius=0):
    c.setStrokeColor(stroke_col)
    c.setLineWidth(lw)
    if radius:
        c.roundRect(x, y, w, h, radius, fill=0, stroke=1)
    else:
        c.rect(x, y, w, h, fill=0, stroke=1)

def text(c, txt, x, y, font="Helvetica-Bold", size=8, color=BLACK, align="left"):
    c.setFont(font, size)
    c.setFillColor(color)
    if align == "center":
        c.drawCentredString(x, y, txt)
    elif align == "right":
        c.drawRightString(x, y, txt)
    else:
        c.drawString(x, y, txt)

def wrap_text(c, txt, x, y, max_w, font="Helvetica", size=7.5, color=BLACK, leading=10):
    """Very simple word-wrap for short strings."""
    from reportlab.pdfbase.pdfmetrics import stringWidth
    c.setFont(font, size)
    c.setFillColor(color)
    words = txt.split()
    line = ""
    cy = y
    for word in words:
        test = (line + " " + word).strip()
        if stringWidth(test, font, size) <= max_w:
            line = test
        else:
            c.drawString(x, cy, line)
            cy -= leading
            line = word
    if line:
        c.drawString(x, cy, line)
    return cy - leading  # return bottom y

def section_header(c, x, y, w, h, title, bg=NAVY, fg=WHITE, fsize=7.5):
    rect_filled(c, x, y, w, h, bg)
    text(c, title, x + w/2, y + h/2 - fsize*0.35, "Helvetica-Bold", fsize, fg, "center")

def cell(c, txt, x, y, w, h, bg=WHITE, fg=BLACK, font="Helvetica", fsize=7, bold=False,
         align="center", pad=1.5*mm):
    rect_filled(c, x, y, w, h, bg)
    fn = "Helvetica-Bold" if bold else font
    c.setFont(fn, fsize)
    c.setFillColor(fg)
    cx = x + w/2 if align == "center" else x + pad
    cy_base = y + h/2 - fsize * 0.35
    if align == "center":
        c.drawCentredString(cx, cy_base, txt)
    else:
        c.drawString(cx, cy_base, txt)

def grid_outline(c, x, y, w, h, col=GREY_MID, lw=0.3):
    rect_outline(c, x, y, w, h, col, lw)

# ── LAYOUT CONSTANTS ─────────────────────────────────────────────────────────
MAR   = 6*mm        # margin
CW    = W - 2*MAR   # content width
CH    = H - 2*MAR   # content height
X0    = MAR
Y_TOP = H - MAR

# ─── PAGE BACKGROUND ─────────────────────────────────────────────────────────
rect_filled(c, 0, 0, W, H, NAVY)
# white content area
rect_filled(c, X0-1*mm, MAR-1*mm, CW+2*mm, CH+2*mm, WHITE)

# ── HEADER BAR ────────────────────────────────────────────────────────────────
hdr_h = 11*mm
rect_filled(c, X0-1*mm, Y_TOP - hdr_h + 1*mm, CW+2*mm, hdr_h, NAVY)
# accent line
rect_filled(c, X0-1*mm, Y_TOP - hdr_h + 1*mm, 3*mm, hdr_h, AMBER)

text(c, "MORPHINE", X0 + 5*mm, Y_TOP - 6.5*mm, "Helvetica-Bold", 16, WHITE)
text(c, "Dosing & Clinical Quick Reference", X0 + 46*mm, Y_TOP - 5.5*mm, "Helvetica", 8, AMBER_LIGHT)
text(c, "Goodman & Gilman 14e  ·  Miller's Anesthesia 10e  ·  Rosen's Emergency Medicine 9e  ·  Barash 9e",
     X0 + 5*mm, Y_TOP - 10*mm, "Helvetica-Oblique", 6, GREY_MID)
text(c, "Orris Medical · June 2026", W - MAR - 1*mm, Y_TOP - 7*mm, "Helvetica", 6.5, GREY_MID, "right")

# Starting y below header
Y = Y_TOP - hdr_h - 1.5*mm

# ═══════════════════════════════════════════════════════════════════════════════
# COLUMN LAYOUT  (3 columns)
# Left (col1): ~100mm  Mid (col2): ~93mm  Right (col3): ~90mm
# ═══════════════════════════════════════════════════════════════════════════════
GAP   = 2.5*mm
COL1W = 101*mm
COL2W = 94*mm
COL3W = CW - COL1W - COL2W - 2*GAP
X1    = X0
X2    = X1 + COL1W + GAP
X3    = X2 + COL2W + GAP

# ═══════════════════════════════════════════════════════════════════════════════
# ── COL 1 ─ LEFT ──────────────────────────────────────────────────────────────
# ═══════════════════════════════════════════════════════════════════════════════
cy1 = Y

# ─── PHARMACOKINETIC SNAPSHOT ───────────────────────────────────────────────
pk_rows = [
    ("Bioavailability",  "PO 20–30%  |  IM/SC ~100%  |  Neuraxial: direct"),
    ("Protein binding",  "20–40% (albumin)"),
    ("Lipid solubility", "LOW (pKa 8.0; only 10–20% un-ionized at pH 7.4)"),
    ("Vd",               "3–5 L/kg"),
    ("t½ parent",        "2–3 hours"),
    ("t½ M6G",           "~9 h (↑ in renal failure)"),
    ("Onset IV",         "5 min (peak 15–20 min)"),
    ("Onset IM/SC",      "10–15 min"),
    ("Onset PO",         "30–45 min"),
    ("Duration IR",      "3–6 hours"),
    ("Duration ER",      "8–24 hours"),
    ("Metabolism",       "Hepatic glucuronidation (UGT2B7)"),
    ("M3G (~60%)",       "Inactive/excitatory – NO analgesia; CNS excitation"),
    ("M6G (~10%)",       "More potent μ-agonist; major active metabolite oral"),
    ("Excretion",        "Renal (>90% as glucuronides within 24 h)"),
]
pk_lbl_w  = 26*mm
pk_val_w  = COL1W - pk_lbl_w
pk_row_h  = 4.2*mm
pk_total  = len(pk_rows) * pk_row_h + 5*mm   # header + rows

section_header(c, X1, cy1 - pk_total, COL1W, 5*mm, "PHARMACOKINETICS", NAVY, WHITE, 7.5)
for i, (lbl, val) in enumerate(pk_rows):
    ry = cy1 - pk_total + (len(pk_rows) - 1 - i) * pk_row_h
    bg = GREY_LIGHT if i % 2 == 0 else WHITE
    cell(c, lbl, X1, ry, pk_lbl_w, pk_row_h, bg=NAVY2, fg=AMBER_LIGHT, font="Helvetica-Bold", fsize=6.5, align="left")
    cell(c, val, X1 + pk_lbl_w, ry, pk_val_w, pk_row_h, bg=bg, fg=GREY_DARK, font="Helvetica", fsize=6.5, align="left")
    grid_outline(c, X1, ry, COL1W, pk_row_h)
grid_outline(c, X1, cy1 - pk_total, COL1W, pk_total, NAVY, 0.8)
cy1 -= (pk_total + 2.5*mm)

# ─── MECHANISM OF ACTION ────────────────────────────────────────────────────
moa_lines = [
    "μ (mu) > κ, δ opioid receptor agonist  ·  Gi/Go GPCR",
    "↓ cAMP  ·  Opens K⁺ channels (hyperpolarisation)",
    "Closes Ca²⁺ channels → ↓ neurotransmitter release",
    "Sites: PAG (supraspinal), dorsal horn (spinal), periphery",
    "Miosis: Edinger-Westphal nucleus (CN III) – no tolerance",
]
moa_h = 5*mm + len(moa_lines)*4*mm
section_header(c, X1, cy1 - moa_h, COL1W, 5*mm, "MECHANISM OF ACTION", SKY, WHITE, 7.5)
for i, ln in enumerate(moa_lines):
    ry = cy1 - moa_h + (len(moa_lines) - 1 - i)*4*mm
    bg = SKY_LIGHT if i % 2 == 0 else WHITE
    cell(c, "• " + ln, X1, ry, COL1W, 4*mm, bg=bg, fg=GREY_DARK, font="Helvetica", fsize=6.5, align="left")
    grid_outline(c, X1, ry, COL1W, 4*mm)
grid_outline(c, X1, cy1 - moa_h, COL1W, moa_h, SKY, 0.8)
cy1 -= (moa_h + 2.5*mm)

# ─── KEY ADVERSE EFFECTS ────────────────────────────────────────────────────
adr_rows = [
    ("Respiratory depression",  "MOST DANGEROUS · dose-dependent · ↓ CO₂ sensitivity",  RED),
    ("Constipation",            "NO tolerance develops · give stimulant laxative routinely", RED),
    ("Nausea / Vomiting",       "CTZ stimulation · worse on ambulation · antiemetics",    AMBER),
    ("Sedation",                "Potentiated by CNS depressants / benzodiazepines",       AMBER),
    ("Hypotension",             "Histamine release + venodilation · caution hypovolaemia",AMBER),
    ("Urinary retention",       "↑ bladder sphincter tone · catheterise if needed",       AMBER),
    ("Pruritus (neuraxial)",    "Ondansetron or low-dose naloxone for treatment",         SKY),
    ("Miosis",                  "Diagnostic marker – no tolerance",                       SKY),
    ("M3G toxicity (renal)",    "Myoclonus, seizures, delirium · reduce dose or rotate",  RED),
]
adr_lbl_w = 31*mm
adr_val_w = COL1W - adr_lbl_w
adr_row_h = 4*mm
adr_total = 5*mm + len(adr_rows)*adr_row_h
section_header(c, X1, cy1 - adr_total, COL1W, 5*mm, "KEY ADVERSE EFFECTS", RED, WHITE, 7.5)
for i, (eff, mgmt, col) in enumerate(adr_rows):
    ry = cy1 - adr_total + (len(adr_rows) - 1 - i)*adr_row_h
    rect_filled(c, X1, ry, adr_lbl_w, adr_row_h, col)
    rect_outline(c, X1, ry, adr_lbl_w, adr_row_h, WHITE, 0.2)
    c.setFont("Helvetica-Bold", 6.3)
    c.setFillColor(WHITE)
    c.drawString(X1 + 1.5*mm, ry + adr_row_h/2 - 2.2, eff)
    bg = GREY_LIGHT if i % 2 == 0 else WHITE
    cell(c, mgmt, X1 + adr_lbl_w, ry, adr_val_w, adr_row_h, bg=bg, fg=GREY_DARK, font="Helvetica", fsize=6.2, align="left")
    grid_outline(c, X1, ry, COL1W, adr_row_h)
grid_outline(c, X1, cy1 - adr_total, COL1W, adr_total, RED, 0.8)
cy1 -= (adr_total + 2.5*mm)

# ═══════════════════════════════════════════════════════════════════════════════
# ── COL 2 ─ MIDDLE ────────────────────────────────────────────────────────────
# ═══════════════════════════════════════════════════════════════════════════════
cy2 = Y

# ─── ORAL DOSING ────────────────────────────────────────────────────────────
def dose_table(c, x, start_y, col_w, header, col_headers, rows, row_h=4.5*mm, hdr_col=NAVY, accent=AMBER):
    n_cols  = len(col_headers)
    col_ws  = [col_w * f for f in ([0.26, 0.22, 0.22, 0.30] if n_cols == 4 else
                                    [0.28, 0.26, 0.46] if n_cols == 3 else
                                    [0.25, 0.35, 0.40])]
    total_h = 5*mm + 5*mm + len(rows)*row_h   # section hdr + col hdr + rows
    section_header(c, x, start_y - total_h, col_w, 5*mm, header, hdr_col, WHITE, 7.5)
    # column headers
    cx = x
    for j, (ch, cw) in enumerate(zip(col_headers, col_ws)):
        cell(c, ch, cx, start_y - total_h + 5*mm, cw, 5*mm, bg=accent, fg=NAVY, font="Helvetica-Bold", fsize=6.5)
        grid_outline(c, cx, start_y - total_h + 5*mm, cw, 5*mm)
        cx += cw
    # data rows
    for i, row in enumerate(rows):
        ry = start_y - total_h + 5*mm + 5*mm + i*row_h
        cx = x
        for j, (val, cw) in enumerate(zip(row, col_ws)):
            bg = GREY_LIGHT if i % 2 == 0 else WHITE
            is_lbl = (j == 0)
            cell(c, val, cx, ry, cw, row_h, bg=NAVY2 if is_lbl else bg,
                 fg=AMBER_LIGHT if is_lbl else GREY_DARK,
                 font="Helvetica-Bold" if is_lbl else "Helvetica", fsize=6.5, align="left")
            grid_outline(c, cx, ry, cw, row_h)
            cx += cw
    grid_outline(c, x, start_y - total_h, col_w, total_h, hdr_col, 0.8)
    return start_y - total_h - 2.5*mm

# ORAL IR
cy2 = dose_table(c, X2, cy2, COL2W,
    "ORAL – IMMEDIATE RELEASE (q4h)",
    ["Population", "Dose", "Frequency", "Notes"],
    [
        ("Adult (opioid-naive)",  "5–15 mg",    "q4h",   "30–60 mg/day starting dose"),
        ("Adult (severe pain)",   "10–30 mg",   "q4h",   "Titrate; monitor RR"),
        ("Elderly (≥65 yr)",      "2.5–5 mg",   "q4–6h", "Start low; ↑ ADR risk"),
        ("Child (>6 mo)",         "0.2–0.5 mg/kg","q4–6h","Max 15–20 mg/dose"),
    ], row_h=4.3*mm, hdr_col=NAVY, accent=AMBER)

# ORAL ER
cy2 = dose_table(c, X2, cy2, COL2W,
    "ORAL – EXTENDED RELEASE (MS Contin) – Do NOT crush",
    ["Population", "Starting Dose", "Notes"],
    [
        ("Opioid-naive adult",   "15 mg q12h",    "Do not crush/chew; add IR breakthrough"),
        ("Cancer pain (convert)","24-hr IR ÷ 2",  "Give as q12h ER; IR for breakthrough"),
        ("Cancer (Swanson)",     "30–60 mg/day",  "Titrate IR × 1 wk → switch to ER"),
    ], row_h=4.3*mm, hdr_col=NAVY, accent=AMBER)

# IV TABLE
cy2 = dose_table(c, X2, cy2, COL2W,
    "INTRAVENOUS (IV) – Onset 5 min; Peak 15–20 min",
    ["Indication", "Dose", "Notes"],
    [
        ("Acute pain (adults)",  "0.1–0.15 mg/kg load; ½ dose q5–15 min", "Titrate to effect; onset 5 min"),
        ("Post-op PRN",          "2–5 mg q2–4h",       "PCA preferred for sustained need"),
        ("ICU infusion",         "2–10 mg/h",           "Titrate to CPOT ≤2 / NRS ≤3"),
        ("Pediatric (>6 mo)",    "0.05–0.1 mg/kg",      "q2–4h; dilute; SpO₂ monitor"),
        ("Neonate (premature)",  "0.01–0.02 mg/kg",     "q4–6h; ↓ clearance → accumulation risk"),
    ], row_h=4.3*mm, hdr_col=SKY, accent=SKY)

# IM/SC TABLE
cy2 = dose_table(c, X2, cy2, COL2W,
    "IM / SUBCUTANEOUS (SC)",
    ["Route", "Adult", "Pediatric"],
    [
        ("IM",  "5–20 mg q4h",  "0.1–0.2 mg/kg q4h  (unpredictable absorption)"),
        ("SC",  "5–15 mg q4h",  "0.1–0.15 mg/kg q4h  (palliative SC infusion)"),
    ], row_h=4.3*mm, hdr_col=GREY_DARK, accent=GREY_MID)

# PCA TABLE
cy2 = dose_table(c, X2, cy2, COL2W,
    "PCA – IV MORPHINE",
    ["Setting", "Typical", "Range"],
    [
        ("Demand (bolus)",   "1 mg",        "0.5–2.5 mg"),
        ("Lockout interval", "6 min",       "5–10 min"),
        ("Basal rate",       "0 mg/h",      "0–2 mg/h (opioid-tolerant)"),
        ("1-hour limit",     "10 mg",       "Per protocol"),
    ], row_h=4.3*mm, hdr_col=GREEN, accent=GREEN)

# ═══════════════════════════════════════════════════════════════════════════════
# ── COL 3 ─ RIGHT ─────────────────────────────────────────────────────────────
# ═══════════════════════════════════════════════════════════════════════════════
cy3 = Y

# NEURAXIAL
neuraxial_rows = [
    ("Epidural post-op",         "2–5 mg",           "q12–24h"),
    ("Epidural – labour",        "2–3 mg",           "Single dose"),
    ("Epidural – C/S",           "3–5 mg",           "Single dose"),
    ("DepoDur (Epidural ER)",     "10–20 mg",         "Single dose"),
    ("Intrathecal post-op",      "0.1–0.3 mg",       "Single dose"),
    ("Intrathecal – C/S",        "0.1–0.2 mg",       "Single dose"),
]
nr_h = 4.3*mm
nr_col_ws = [COL3W*0.38, COL3W*0.32, COL3W*0.30]
nr_total  = 5*mm + 5*mm + len(neuraxial_rows)*nr_h
section_header(c, X3, cy3 - nr_total, COL3W, 5*mm,
               "NEURAXIAL – Preservative-Free ONLY", NAVY, WHITE, 7.5)
# col headers
cx = X3
for j, (ch, cw) in enumerate(zip(["Indication","Dose","Frequency"], nr_col_ws)):
    cell(c, ch, cx, cy3 - nr_total + 5*mm, cw, 5*mm, bg=AMBER, fg=NAVY, font="Helvetica-Bold", fsize=6.5)
    grid_outline(c, cx, cy3 - nr_total + 5*mm, cw, 5*mm)
    cx += cw
for i, (ind, dose, freq) in enumerate(neuraxial_rows):
    ry = cy3 - nr_total + 5*mm + 5*mm + i*nr_h
    cx = X3
    for j, (val, cw) in enumerate(zip([ind, dose, freq], nr_col_ws)):
        bg = GREY_LIGHT if i % 2 == 0 else WHITE
        is_lbl = (j == 0)
        cell(c, val, cx, ry, cw, nr_h, bg=NAVY2 if is_lbl else bg,
             fg=AMBER_LIGHT if is_lbl else GREY_DARK,
             font="Helvetica-Bold" if is_lbl else "Helvetica", fsize=6.5, align="left")
        grid_outline(c, cx, ry, cw, nr_h)
        cx += cw
# warning bar
warn_y = cy3 - nr_total + 5*mm + 5*mm + len(neuraxial_rows)*nr_h
# It's at the top of the table actually (rows drawn bottom-up)
# Let's add warning at the very bottom
warn_y = cy3 - nr_total
rect_filled(c, X3, warn_y - 4.5*mm, COL3W, 4.5*mm, RED)
text(c, "⚠ Monitor respiratory depression for 12–24 h post neuraxial morphine",
     X3 + COL3W/2, warn_y - 3.2*mm, "Helvetica-Bold", 6.3, WHITE, "center")
grid_outline(c, X3, cy3 - nr_total, COL3W, nr_total, NAVY, 0.8)
cy3 -= (nr_total + 4.5*mm + 3*mm)

# EQUIANALGESIC TABLE
eq_rows = [
    ("MORPHINE",          "10 mg",    "30 mg",   "Reference standard"),
    ("Hydromorphone",     "1.5 mg",   "7.5 mg",  "~7× more potent IV"),
    ("Oxycodone",         "—",        "20–30 mg","No parenteral (most)"),
    ("Fentanyl",          "100 mcg",  "—",       "~100× more potent"),
    ("Codeine",           "130 mg",   "200 mg",  "CYP2D6 prodrug"),
    ("Meperidine",        "75–100 mg","300 mg",  "Not for chronic use"),
    ("Tramadol",          "—",        "150 mg",  "Partial opioid"),
    ("Oxymorphone",       "1 mg",     "10 mg",   "~10× PO morphine"),
]
eq_col_ws = [COL3W*0.27, COL3W*0.19, COL3W*0.18, COL3W*0.36]
eq_h      = 4.3*mm
eq_total  = 5*mm + 5*mm + len(eq_rows)*eq_h
section_header(c, X3, cy3 - eq_total, COL3W, 5*mm,
               "EQUIANALGESIC TABLE (equiv. to Morphine 10 mg IV)", RED, WHITE, 7.5)
cx = X3
for j, (ch, cw) in enumerate(zip(["Opioid","IV/IM","PO","Notes"], eq_col_ws)):
    cell(c, ch, cx, cy3 - eq_total + 5*mm, cw, 5*mm, bg=RED, fg=WHITE, font="Helvetica-Bold", fsize=6.5)
    grid_outline(c, cx, cy3 - eq_total + 5*mm, cw, 5*mm)
    cx += cw
for i, row in enumerate(eq_rows):
    ry = cy3 - eq_total + 5*mm + 5*mm + i*eq_h
    cx = X3
    for j, (val, cw) in enumerate(zip(row, eq_col_ws)):
        bg_is_morphine = (i == 0)
        if j == 0:
            bg2 = AMBER if bg_is_morphine else NAVY2
            fg2 = NAVY if bg_is_morphine else AMBER_LIGHT
        else:
            bg2 = AMBER_LIGHT if bg_is_morphine else (GREY_LIGHT if i % 2 == 0 else WHITE)
            fg2 = NAVY if bg_is_morphine else GREY_DARK
        cell(c, val, cx, ry, cw, eq_h, bg=bg2, fg=fg2,
             font="Helvetica-Bold" if j == 0 else "Helvetica", fsize=6.5, align="left")
        grid_outline(c, cx, ry, cw, eq_h)
        cx += cw
grid_outline(c, X3, cy3 - eq_total, COL3W, eq_total, RED, 0.8)
cy3 -= (eq_total + 2.5*mm)

# SPECIAL POPULATIONS
sp_rows = [
    ("Elderly ≥65 yr",     "Start at 25–50% usual adult dose; ↑ duration of action; ↑ ADR risk"),
    ("Renal impairment",   "Reduce dose + extend interval; M6G accumulates → prolong resp depression"),
    ("Hepatic failure",    "↑ Bioavailability; reduce dose ~50%; titrate slowly"),
    ("Neonate (prem)",     "0.01–0.02 mg/kg IV q4–6h; direct correlate with gestational age"),
    ("Infant/child",       "0.05–0.1 mg/kg IV q2–4h  |  0.2–0.5 mg/kg PO q4–6h"),
    ("Pregnancy",          "Crosses placenta; NOWS with chronic use; lowest dose + duration"),
    ("Obesity",            "Use ideal body weight (IBW) for initial dosing calculations"),
]
sp_h       = 4.3*mm
sp_lbl_w   = COL3W * 0.33
sp_val_w   = COL3W - sp_lbl_w
sp_total   = 5*mm + len(sp_rows)*sp_h
section_header(c, X3, cy3 - sp_total, COL3W, 5*mm,
               "SPECIAL POPULATIONS", GREEN, WHITE, 7.5)
for i, (pop, note) in enumerate(sp_rows):
    ry = cy3 - sp_total + (len(sp_rows) - 1 - i)*sp_h
    cell(c, pop, X3, ry, sp_lbl_w, sp_h, bg=GREEN, fg=WHITE, font="Helvetica-Bold", fsize=6.5, align="left")
    bg = GREEN_LIGHT if i % 2 == 0 else WHITE
    cell(c, note, X3 + sp_lbl_w, ry, sp_val_w, sp_h, bg=bg, fg=GREY_DARK, font="Helvetica", fsize=6.2, align="left")
    grid_outline(c, X3, ry, COL3W, sp_h)
grid_outline(c, X3, cy3 - sp_total, COL3W, sp_total, GREEN, 0.8)
cy3 -= (sp_total + 2.5*mm)

# OVERDOSE + REVERSAL
od_rows = [
    ("Triad",           "Miosis  ·  Respiratory depression  ·  ↓ Consciousness + cyanosis, bradycardia"),
    ("Naloxone IV",     "0.4–2 mg IV; repeat q2–3 min (max 10 mg); Peds: 0.01 mg/kg IV"),
    ("Naloxone IN",     "4 mg intranasal; repeat 2–3 min; Peds: 0.1 mg/kg  (Narcan nasal)"),
    ("Naloxone IM/SC",  "0.4–2 mg; slower onset than IV"),
    ("Duration warning","Naloxone t½ < morphine → re-narcotisation; repeat dosing / infusion may be needed"),
    ("Contraindications","MAO inhibitors (14 days) · Severe respiratory depression · Paralytic ileus"),
]
od_lbl_w = COL3W * 0.28
od_val_w = COL3W - od_lbl_w
od_h     = 4.3*mm
od_total = 5*mm + len(od_rows)*od_h
section_header(c, X3, cy3 - od_total, COL3W, 5*mm,
               "OVERDOSE TRIAD & REVERSAL (NALOXONE)", RED, WHITE, 7.5)
for i, (lbl, val) in enumerate(od_rows):
    ry = cy3 - od_total + (len(od_rows) - 1 - i)*od_h
    col = RED if (lbl == "Triad" or "Contraind" in lbl) else (AMBER if "Naloxone" in lbl else GREY_DARK)
    cell(c, lbl, X3, ry, od_lbl_w, od_h, bg=col, fg=WHITE, font="Helvetica-Bold", fsize=6.5, align="left")
    bg = RED_LIGHT if (lbl == "Triad" or "Contraind" in lbl) else (AMBER_LIGHT if "Naloxone" in lbl else (GREY_LIGHT if i % 2 == 0 else WHITE))
    cell(c, val, X3 + od_lbl_w, ry, od_val_w, od_h, bg=bg, fg=GREY_DARK, font="Helvetica", fsize=6.2, align="left")
    grid_outline(c, X3, ry, COL3W, od_h)
grid_outline(c, X3, cy3 - od_total, COL3W, od_total, RED, 0.8)
cy3 -= (od_total + 2.5*mm)

# ─── FOOTER ──────────────────────────────────────────────────────────────────
foot_y = MAR - 1*mm
rect_filled(c, X0-1*mm, foot_y, CW+2*mm, 5.5*mm, NAVY)
text(c, "FOR CLINICAL REFERENCE ONLY – Verify all doses against current institutional guidelines and patient-specific factors. Not a substitute for clinical judgment.",
     W/2, foot_y + 1.8*mm, "Helvetica-Oblique", 6, GREY_MID, "center")

c.save()
print("PDF created:", OUTPUT)