#!/usr/bin/env python3
"""FACEM Notes: Paracetamol Toxicity - PDF Generator"""

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import mm, cm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether, PageBreak
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.platypus import ListFlowable, ListItem
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

# ── Colour palette ──────────────────────────────────────────────────────────
C_NAVY   = colors.HexColor("#1B2A4A")
C_BLUE   = colors.HexColor("#2E5FA3")
C_TEAL   = colors.HexColor("#1A7B8C")
C_AMBER  = colors.HexColor("#E8A020")
C_RED    = colors.HexColor("#C0392B")
C_GREEN  = colors.HexColor("#1E8449")
C_LGRAY  = colors.HexColor("#F4F6FA")
C_MGRAY  = colors.HexColor("#D5DCE8")
C_WHITE  = colors.white

PAGE_W, PAGE_H = A4
MARGIN = 20 * mm

# ── Document ─────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    "/home/daytona/workspace/facem-notes/Paracetamol_Toxicity_FACEM.pdf",
    pagesize=A4,
    leftMargin=MARGIN, rightMargin=MARGIN,
    topMargin=22 * mm, bottomMargin=18 * mm,
    title="Paracetamol Toxicity - FACEM Notes",
    author="Orris Medical Notes"
)

# ── Styles ───────────────────────────────────────────────────────────────────
base = getSampleStyleSheet()

def S(name, parent="Normal", **kw):
    return ParagraphStyle(name, parent=base[parent], **kw)

TITLE   = S("TITLE",   "Normal", fontSize=22, textColor=C_WHITE,
             fontName="Helvetica-Bold", alignment=TA_CENTER, leading=28)
SUBTITLE= S("SUBTITLE","Normal", fontSize=11, textColor=C_MGRAY,
             fontName="Helvetica", alignment=TA_CENTER, leading=16)
H1      = S("H1",      "Normal", fontSize=13, textColor=C_WHITE,
             fontName="Helvetica-Bold", leading=18, spaceAfter=2)
H2      = S("H2",      "Normal", fontSize=10.5, textColor=C_NAVY,
             fontName="Helvetica-Bold", leading=15, spaceBefore=6, spaceAfter=2)
H3      = S("H3",      "Normal", fontSize=9.5, textColor=C_TEAL,
             fontName="Helvetica-Bold", leading=13, spaceBefore=4, spaceAfter=1)
BODY    = S("BODY",    "Normal", fontSize=9, leading=13, spaceAfter=3,
             textColor=colors.HexColor("#1C1C1C"))
BODYSM  = S("BODYSM",  "Normal", fontSize=8.5, leading=12, spaceAfter=2,
             textColor=colors.HexColor("#1C1C1C"))
BULLET  = S("BULLET",  "Normal", fontSize=9, leading=13, leftIndent=10,
             bulletIndent=0, spaceAfter=2, textColor=colors.HexColor("#1C1C1C"))
WARN    = S("WARN",    "Normal", fontSize=8.5, textColor=C_RED,
             fontName="Helvetica-Bold", leading=12)
NOTE    = S("NOTE",    "Normal", fontSize=8.5, textColor=C_TEAL,
             fontName="Helvetica-Oblique", leading=12)
FOOTER  = S("FOOTER",  "Normal", fontSize=7.5, textColor=colors.HexColor("#888888"),
             alignment=TA_CENTER)
CELL_HD = S("CELL_HD", "Normal", fontSize=8.5, textColor=C_WHITE,
             fontName="Helvetica-Bold", alignment=TA_CENTER, leading=11)
CELL    = S("CELL",    "Normal", fontSize=8.5, leading=11, alignment=TA_CENTER)
CELL_L  = S("CELL_L",  "Normal", fontSize=8.5, leading=11, alignment=TA_LEFT)

# ── Helpers ───────────────────────────────────────────────────────────────────
def section_header(text, color=C_BLUE):
    t = Table([[Paragraph(text, H1)]], colWidths=[PAGE_W - 2*MARGIN])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), color),
        ("TOPPADDING",   (0,0), (-1,-1), 6),
        ("BOTTOMPADDING",(0,0), (-1,-1), 6),
        ("LEFTPADDING",  (0,0), (-1,-1), 10),
        ("RIGHTPADDING", (0,0), (-1,-1), 10),
        ("ROUNDEDCORNERS", [4]),
    ]))
    return t

def box(content_rows, bg=C_LGRAY, border=C_MGRAY, padding=8):
    """Wrap a list of flowables in a coloured box table."""
    inner = [[c] for c in content_rows]
    # Flatten to single-cell table with a paragraph list
    combined = Table([[r] for r in content_rows], colWidths=[PAGE_W - 2*MARGIN - 2*padding])
    combined.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("TOPPADDING",   (0,0), (-1,-1), 4),
        ("BOTTOMPADDING",(0,0), (-1,-1), 4),
        ("LEFTPADDING",  (0,0), (-1,-1), 0),
        ("RIGHTPADDING", (0,0), (-1,-1), 0),
        ("GRID", (0,0), (-1,-1), 0, bg),
    ]))
    outer = Table([[combined]], colWidths=[PAGE_W - 2*MARGIN])
    outer.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("BOX", (0,0), (-1,-1), 1, border),
        ("TOPPADDING",   (0,0), (-1,-1), padding),
        ("BOTTOMPADDING",(0,0), (-1,-1), padding),
        ("LEFTPADDING",  (0,0), (-1,-1), padding),
        ("RIGHTPADDING", (0,0), (-1,-1), padding),
        ("ROUNDEDCORNERS", [4]),
    ]))
    return outer

def alert_box(title, items, color=C_AMBER):
    rows = [[Paragraph(f"<b>{title}</b>", S("ah","Normal",fontSize=9,
                        textColor=C_WHITE, fontName="Helvetica-Bold", leading=12))]]
    for item in items:
        rows.append([Paragraph(f"• {item}", S("ai","Normal",fontSize=8.5,
                                textColor=C_WHITE, leading=12))])
    t = Table(rows, colWidths=[PAGE_W - 2*MARGIN])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), color),
        ("TOPPADDING",   (0,0), (-1,-1), 5),
        ("BOTTOMPADDING",(0,0), (-1,-1), 5),
        ("LEFTPADDING",  (0,0), (-1,-1), 10),
        ("RIGHTPADDING", (0,0), (-1,-1), 10),
        ("ROUNDEDCORNERS", [4]),
    ]))
    return t

def two_col_table(headers, rows, col_widths=None, header_color=C_NAVY):
    W = PAGE_W - 2*MARGIN
    if col_widths is None:
        col_widths = [W/len(headers)] * len(headers)
    table_data = [[Paragraph(h, CELL_HD) for h in headers]]
    for row in rows:
        styles = [CELL_L if i == 0 else CELL for i in range(len(row))]
        table_data.append([Paragraph(str(c), styles[i]) for i, c in enumerate(row)])
    t = Table(table_data, colWidths=col_widths)
    t.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),  (-1,0),  header_color),
        ("BACKGROUND",   (0,1),  (-1,-1), C_LGRAY),
        ("ROWBACKGROUNDS",(0,1), (-1,-1), [C_WHITE, C_LGRAY]),
        ("GRID",         (0,0),  (-1,-1), 0.5, C_MGRAY),
        ("TOPPADDING",   (0,0),  (-1,-1), 5),
        ("BOTTOMPADDING",(0,0),  (-1,-1), 5),
        ("LEFTPADDING",  (0,0),  (-1,-1), 6),
        ("RIGHTPADDING", (0,0),  (-1,-1), 6),
        ("VALIGN",       (0,0),  (-1,-1), "MIDDLE"),
    ]))
    return t

def bp(text):
    return Paragraph(f"• {text}", BULLET)

def sp(n=4):
    return Spacer(1, n)

def hr(color=C_MGRAY):
    return HRFlowable(width="100%", thickness=0.5, color=color, spaceAfter=4, spaceBefore=4)

# ═══════════════════════════════════════════════════════════════════════════════
# BUILD CONTENT
# ═══════════════════════════════════════════════════════════════════════════════
story = []

# ── COVER / TITLE ─────────────────────────────────────────────────────────────
cover = Table(
    [[Paragraph("PARACETAMOL TOXICITY", TITLE)],
     [Spacer(1, 4)],
     [Paragraph("FACEM Examination Notes", SUBTITLE)],
     [Paragraph("Emergency Medicine  |  Toxicology", SUBTITLE)],
     [Spacer(1, 6)],
     [Paragraph("Sources: Tintinalli's EM, Rosen's EM, Bailey &amp; Love's Surgery • Aus/NZ Guidelines 2019 (Chiew et al.) • NSW ECI 2024", FOOTER)]],
    colWidths=[PAGE_W - 2*MARGIN]
)
cover.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), C_NAVY),
    ("TOPPADDING",    (0,0), (-1,-1), 18),
    ("BOTTOMPADDING", (0,0), (-1,-1), 18),
    ("LEFTPADDING",   (0,0), (-1,-1), 16),
    ("RIGHTPADDING",  (0,0), (-1,-1), 16),
    ("ROUNDEDCORNERS", [6]),
]))
story.append(cover)
story.append(sp(10))

# ── 1. BACKGROUND & PHARMACOKINETICS ─────────────────────────────────────────
story.append(section_header("1.  BACKGROUND & PHARMACOKINETICS", C_NAVY))
story.append(sp(6))

story.append(Paragraph("Overview", H2))
story.append(bp("Paracetamol (acetaminophen/APAP) is the <b>most common drug overdose</b> presenting to Australian EDs"))
story.append(bp("Leading cause of <b>acute liver failure</b> in Australia, UK and USA"))
story.append(bp("Two main patterns: <b>acute single ingestion</b> vs <b>repeated supratherapeutic ingestion (RSTI)</b>"))
story.append(sp(4))

story.append(Paragraph("Therapeutic vs Toxic Doses", H2))
W = PAGE_W - 2*MARGIN
dose_table = two_col_table(
    ["Parameter", "Value"],
    [
        ["Adult therapeutic dose", "500 mg – 1 g every 4–6 h; max 4 g/day"],
        ["Toxic threshold (single ingestion)", ">10 g or >200 mg/kg (whichever is less)"],
        ["Toxic threshold (>24 h period)", ">10 g or >200 mg/kg over 24 h"],
        ["RSTI threshold", ">6 g or >150 mg/kg/day for ≥2 consecutive days"],
        ["Children <6 yrs (single/8 h)", ">200 mg/kg"],
        ["Massive overdose", ">500 mg/kg; paracetamol level >750 mcg/mL"],
    ],
    col_widths=[W*0.45, W*0.55]
)
story.append(dose_table)
story.append(sp(6))

story.append(Paragraph("Mechanism of Toxicity", H2))
story.append(Paragraph(
    "At <b>therapeutic doses</b>: ~90% conjugated via glucuronidation/sulfation → non-toxic metabolites; "
    "~5–10% oxidised by CYP2E1/CYP3A4 → <b>NAPQI</b> (N-acetyl-p-benzoquinoneimine), immediately "
    "detoxified by hepatic <b>glutathione</b>.",
    BODY))
story.append(sp(2))
story.append(Paragraph(
    "At <b>overdose</b>: Glucuronidation and sulfation pathways become saturated. "
    "NAPQI production overwhelms glutathione stores (when &lt;30% normal). "
    "Free NAPQI binds hepatic macromolecules → <b>centrilobular hepatic necrosis</b>. "
    "Hepatocyte lysis occurs ~Day 2, releasing transaminases + NAPQI-protein adducts.",
    BODY))
story.append(sp(4))

story.append(alert_box("High-Risk Populations for Enhanced Toxicity",
    ["Chronic alcohol use (CYP2E1 induction + depleted glutathione)",
     "Hepatic enzyme inducers: rifampicin, phenytoin, carbamazepine",
     "Malnutrition / anorexia nervosa / prolonged fasting (depleted glutathione)",
     "HIV/AIDS on antiretroviral therapy",
     "Chronic liver disease (pre-existing reduced synthetic function)"],
    color=C_RED))
story.append(sp(8))

# ── 2. CLINICAL FEATURES: FOUR STAGES ──────────────────────────────────────
story.append(section_header("2.  CLINICAL FEATURES: FOUR STAGES OF TOXICITY", C_TEAL))
story.append(sp(6))

W = PAGE_W - 2*MARGIN
stages = two_col_table(
    ["Stage", "Timing", "Clinical Features", "Investigations"],
    [
        ["Stage 1\n(Early)", "0–24 h", "Nausea, vomiting, anorexia, malaise\nMay be ASYMPTOMATIC\n(No signs of hepatotoxicity)", "Paracetamol level\nPlot on Rumack-Matthew nomogram"],
        ["Stage 2\n(Latent)", "Days 2–3", "GI symptoms improve\nRUQ pain & tenderness\nSubclinical hepatotoxicity begins", "↑ ALT/AST\n↑ INR\n↑ Bilirubin (mild)"],
        ["Stage 3\n(Hepatic)", "Days 3–4", "Fulminant hepatic failure:\n- Metabolic acidosis\n- Coagulopathy (↑INR)\n- Renal failure\n- Encephalopathy\n- Recurrent GI symptoms\n- Jaundice", "Peak ALT/AST (may be >10,000)\nINR >6.5 → transplant criteria\nCreatinine ↑\nArterial lactate ↑"],
        ["Stage 4\n(Recovery)", "Day 5–2 wks", "Survivors begin hepatic recovery\nComplete resolution 1–3 months", "Gradual normalisation of LFTs"],
    ],
    col_widths=[W*0.10, W*0.12, W*0.42, W*0.36]
)
story.append(stages)
story.append(sp(5))

story.append(alert_box("Massive Overdose (>500 mg/kg or level >750 mcg/mL)",
    ["Early-onset HIGH ANION GAP metabolic acidosis even WITHOUT liver failure",
     "Raised lactate (5-oxoproline accumulation from glutathione depletion)",
     "Altered sensorium independent of hepatic encephalopathy",
     "Mechanism: inhibition of mitochondrial respiration by NAPQI metabolites"],
    color=C_RED))
story.append(sp(5))

story.append(Paragraph("Extrahepatic Toxicity (rare)", H2))
story.append(bp("<b>Renal failure</b>: direct tubular toxicity via CYP450 enzymes in proximal tubule; can occur without hepatotoxicity"))
story.append(bp("<b>Pancreatitis</b>: rare, mechanism unclear"))
story.append(bp("<b>Cardiac toxicity</b>: rare"))
story.append(sp(8))

# ── 3. DIAGNOSIS & INVESTIGATIONS ───────────────────────────────────────────
story.append(section_header("3.  DIAGNOSIS & INVESTIGATIONS", C_BLUE))
story.append(sp(6))

story.append(Paragraph("Check paracetamol level in ALL intentional overdoses", H2))
story.append(bp("Routinely measure paracetamol level in <b>all intentional overdose patients</b> — even if paracetamol not mentioned (often co-ingested and denied)"))
story.append(bp("Level is only interpretable on the Rumack-Matthew nomogram if drawn <b>4–24 h post-ingestion</b> from a single acute oral exposure"))
story.append(bp("Level drawn <b>&lt;4 h</b> cannot be plotted (absorption may not be complete)"))
story.append(sp(5))

story.append(Paragraph("Rumack-Matthew Nomogram", H2))
story.append(Paragraph(
    "Derived from retrospective analysis of outcomes. Plots serum paracetamol concentration (4–24 h "
    "post-ingestion) against time to predict risk of hepatotoxicity.",
    BODY))
story.append(sp(2))
nomogram_table = two_col_table(
    ["Nomogram Line", "4-hour Concentration", "Clinical Significance"],
    [
        ["Possible toxicity line (original)", "200 mcg/mL (1300 µmol/L)", "60% risk of hepatotoxicity without treatment"],
        ["Treatment line (modified - USE THIS)", "150 mcg/mL (1000 µmol/L)", "Treatment with NAC indicated if above this line"],
        ["Double-dose NAC line", "≥2x nomogram line (i.e. ~300 mcg/mL at 4h)", "Double-dose NAC second bag (see treatment)"],
        ["Triple-line / massive", "≥3x nomogram line", "Discuss with clinical toxicologist"],
    ],
    col_widths=[W*0.28, W*0.28, W*0.44]
)
story.append(nomogram_table)
story.append(sp(3))
story.append(Paragraph(
    "<b>Nomogram limitations</b>: Cannot be used for (1) levels drawn &lt;4 h or &gt;24 h; "
    "(2) modified-release/extended-release formulations; (3) repeated/chronic ingestions; "
    "(4) unknown time of ingestion.",
    NOTE))
story.append(sp(6))

story.append(Paragraph("Recommended Investigations", H2))
inv_table = two_col_table(
    ["Investigation", "Rationale / Key Points"],
    [
        ["Serum paracetamol level", "At 4 h post-ingestion (minimum); plot on nomogram"],
        ["ALT / AST", "Elevated from Day 2; peak Day 3–4; AST >1000 IU/L = hepatotoxicity"],
        ["INR / PT", "↑ INR is sensitive marker of hepatic synthetic dysfunction; INR >6.5 = transplant threshold"],
        ["Serum creatinine", "Renal failure in Stage 3; creatinine >301 µmol/L = transplant threshold"],
        ["Arterial blood gas", "Metabolic acidosis (pH <7.3 = transplant threshold); arterial lactate"],
        ["Serum bilirubin", "Rises in Stage 3"],
        ["Blood glucose", "Hypoglycaemia in fulminant hepatic failure"],
        ["Serum phosphate", "Hyperphosphataemia = poor prognostic marker for transplant-free survival"],
        ["FBC", "Baseline; thrombocytopaenia in ALF"],
        ["Paracetamol-hepatic adducts (APAP-CYS)", "Research marker; not routine clinical use"],
        ["Pregnancy test (females)", "Standard in reproductive-age women with OD"],
        ["Alcohol level + UDS", "Co-ingestion screen"],
    ],
    col_widths=[W*0.32, W*0.68]
)
story.append(inv_table)
story.append(sp(8))

# ── 4. RISK STRATIFICATION ────────────────────────────────────────────────────
story.append(section_header("4.  RISK STRATIFICATION", C_NAVY))
story.append(sp(6))

story.append(Paragraph("Acute Immediate-Release Ingestion (Single)", H2))
story.append(bp("Time of ingestion KNOWN → draw level at <b>4 h post-ingestion</b>, plot on Rumack-Matthew nomogram"))
story.append(bp("Level <b>above the treatment line</b> → start NAC"))
story.append(bp("Level below treatment line AND <b>ALT normal</b> → NAC not required"))
story.append(bp("If paracetamol level <b>not available within 8 h</b> of ingestion AND dose exceeds toxicity threshold → <b>start NAC empirically</b>"))
story.append(sp(4))

story.append(Paragraph("Modified-Release (MR/XR) Paracetamol Ingestion", H2))
story.append(bp("<b>All ingestions ≥10 g or ≥200 mg/kg</b> → full course of NAC"))
story.append(bp("Nomogram cannot be reliably used — delayed and prolonged absorption kinetics"))
story.append(bp("If first level &lt;2 h from last dose → repeat level at 2 h to confirm no ongoing absorption"))
story.append(bp("Level AND ALT 4 h after last known dose; if either above nomogram line → start or continue NAC"))
story.append(sp(4))

story.append(Paragraph("Repeated Supratherapeutic Ingestion (RSTI)", H2))
story.append(bp("Nomogram CANNOT be used"))
story.append(bp("Risk assessment based on: total dose, duration, ALT, paracetamol level"))
story.append(bp("Measure serum paracetamol AND ALT in any patient with criteria for RSTI"))
story.append(bp("Elevated ALT regardless of paracetamol level → start NAC"))
story.append(sp(5))

story.append(alert_box("Start NAC Empirically (Do Not Wait for Level) If:",
    ["More than 8 hours since ingestion (or level won't be available within 8 h) AND dose exceeds threshold",
     "Clinical signs of toxicity: nausea, vomiting, RUQ pain/tenderness",
     "Modified-release ingestion ≥10 g or ≥200 mg/kg",
     "Elevated ALT on presentation",
     "Patient with pre-existing liver disease",
     "Unknown time of ingestion with any concerning history"],
    color=C_TEAL))
story.append(sp(8))

# ── 5. MANAGEMENT ─────────────────────────────────────────────────────────────
story.append(section_header("5.  MANAGEMENT", C_GREEN))
story.append(sp(6))

story.append(Paragraph("A. Initial Resuscitation & Decontamination", H2))
story.append(bp("<b>DRSABCD</b> — ABCs first; manage haemodynamic instability"))
story.append(bp("<b>Activated charcoal (AC)</b>: consider if presentation ≤1–2 h post-ingestion AND patient alert/airway intact; most benefit in massive ingestions (≥40 g)"))
story.append(bp("AC is <b>NOT routinely recommended</b> for paracetamol OD given availability of NAC — use only if may prevent need for NAC (e.g. paediatric accidental ingestions)"))
story.append(bp("<b>Gastric lavage</b>: generally not recommended"))
story.append(bp("Contact <b>Poisons Information Centre: 13 11 26</b> (Australia) for all significant ingestions"))
story.append(sp(6))

story.append(Paragraph("B. N-Acetylcysteine (NAC) — Primary Antidote", H2))
story.append(Paragraph(
    "NAC replenishes glutathione stores and scavenges NAPQI directly. "
    "Most effective within 8 h of ingestion — risk of hepatotoxicity &lt;1% and mortality approaches zero "
    "when started within 8 h.",
    BODY))
story.append(sp(4))

story.append(Paragraph("Australian/NZ Guidelines 2019 — Two-Bag IV Regimen (Standard)", H3))
nac_table = two_col_table(
    ["Bag", "Dose", "Diluent", "Duration"],
    [
        ["Bag 1", "200 mg/kg (max 22 g)\nAdult ceiling weight: 110 kg", "500 mL glucose 5% or NaCl 0.9%\n(Paeds: 7 mL/kg up to 500 mL)", "4 hours"],
        ["Bag 2", "100 mg/kg (max 11 g)", "1000 mL glucose 5% or NaCl 0.9%\n(Paeds: 14 mL/kg up to 1000 mL)", "16 hours"],
    ],
    col_widths=[W*0.10, W*0.28, W*0.38, W*0.24]
)
story.append(nac_table)
story.append(sp(3))
story.append(Paragraph(
    "<b>Total duration: 20 hours</b> | Always prescribe BOTH bags together",
    NOTE))
story.append(sp(4))

story.append(Paragraph("Double-Dose NAC Regimen", H3))
story.append(bp("Indicated when paracetamol level is <b>≥2× above the nomogram line</b> (massive overdose >30 g)"))
story.append(bp("Bag 1: 200 mg/kg over 4 h (same as standard)"))
story.append(bp("<b>Bag 2: 200 mg/kg</b> (double dose) over 16 h"))
story.append(bp("Level ≥3× nomogram line → discuss with clinical toxicologist (may require higher doses)"))
story.append(sp(4))

story.append(Paragraph("Duration of NAC / When to Stop / When to Continue", H3))
nac_stop = two_col_table(
    ["Situation", "Action"],
    [
        ["Completed 20 h course, ALT normal, paracetamol level clearing", "Cease NAC — can be discharged if psychiatrically safe"],
        ["Completed 20 h course but ALT rising or remains elevated", "Continue NAC at 100 mg/kg per 16 h infusion until ALT trending down AND INR <2"],
        ["Hepatic failure (acidosis, coagulopathy, encephalopathy)", "Continue IV NAC INDEFINITELY — reduces mortality even with undetectable paracetamol"],
        ["AST >1000 IU/L at end of course (even if paracetamol undetectable)", "Continue NAC"],
        ["Patient vomiting, cannot tolerate oral NAC", "Use IV NAC exclusively"],
    ],
    col_widths=[W*0.50, W*0.50]
)
story.append(nac_stop)
story.append(sp(5))

story.append(Paragraph("C. NAC Adverse Reactions", H2))
story.append(bp("<b>Anaphylactoid reaction</b>: most common (~20% with 3-bag, ~8% with 2-bag regimen); usually occurs during Bag 1 loading dose"))
story.append(bp("Features: flushing, urticaria, pruritus, nausea, vomiting, bronchospasm (rare: hypotension)"))
story.append(bp("<b>Management</b>: pause infusion, administer antihistamine (e.g. promethazine 25 mg IV) ± salbutamol if bronchospasm; "
                "restart at slower rate once symptoms resolve"))
story.append(bp("True anaphylaxis (with hypotension/airway compromise) is very rare — treat with adrenaline"))
story.append(bp("Two-bag regimen significantly reduces adverse reactions vs. three-bag — key reason for guideline change"))
story.append(sp(5))

story.append(Paragraph("D. Oral NAC (if IV unavailable)", H2))
story.append(bp("Oral NAC regimen: 140 mg/kg loading dose, then 70 mg/kg every 4 h for 17 doses (total 72 h)"))
story.append(bp("Equally efficacious if started within 8 h, but IV preferred due to compliance and vomiting issues"))
story.append(bp("Avoid oral NAC in altered conscious state or severe vomiting"))
story.append(sp(5))

story.append(Paragraph("E. Haemodialysis — Indications (EXTRIP Guidelines)", H2))
story.append(bp("Not routinely indicated given highly effective antidote"))
story.append(alert_box("Indications for Emergent Haemodialysis (EXTRIP Consensus)",
    ["Paracetamol level >1000 mcg/mL AND NAC NOT administered",
     "Altered mental status + metabolic acidosis + lactate elevated + level >700 mcg/mL AND NAC NOT given",
     "Altered mental status + metabolic acidosis + lactate elevated + level >900 mcg/mL EVEN IF NAC given",
     "Note: Continue NAC DURING haemodialysis"],
    color=C_NAVY))
story.append(sp(8))

# ── 6. FULMINANT HEPATIC FAILURE ──────────────────────────────────────────────
story.append(section_header("6.  ACUTE LIVER FAILURE & TRANSPLANT CRITERIA", C_RED))
story.append(sp(6))

story.append(Paragraph("Recognition of Acute Liver Failure (ALF)", H2))
story.append(bp("ALF = <b>coagulopathy (INR >1.5) + hepatic encephalopathy</b> in absence of pre-existing liver disease"))
story.append(bp("Paracetamol-induced ALF typically develops within 72–96 h of ingestion"))
story.append(bp("Poor prognostic signs: metabolic acidosis (pH &lt;7.3), rising creatinine, encephalopathy, hyperlactataemia, hyperphosphataemia"))
story.append(sp(5))

story.append(Paragraph("King's College Criteria — Paracetamol-Induced ALF", H2))
story.append(Paragraph(
    "Criteria met for liver transplant listing if:", BODY))
kcc_table = two_col_table(
    ["Criterion", "Threshold"],
    [
        ["Arterial pH (after adequate resuscitation)", "<7.30 (alone is sufficient OR in combination below)"],
        ["INR", ">6.5 (PT >100 s)"],
        ["Serum creatinine", ">301 µmol/L (3.4 mg/dL)"],
        ["Hepatic encephalopathy grade", "Grade III or IV"],
        ["Additional poor prognostic markers", "Hyperlactataemia OR hyperphosphataemia"],
    ],
    col_widths=[W*0.42, W*0.58]
)
story.append(kcc_table)
story.append(sp(3))
story.append(Paragraph(
    "<b>Criteria met if</b>: Arterial pH &lt;7.30 (alone) OR <b>ALL THREE of</b>: "
    "INR &gt;6.5 AND creatinine &gt;301 µmol/L AND grade III/IV encephalopathy. "
    "Addition of lactate/phosphate improves sensitivity.",
    NOTE))
story.append(sp(5))

story.append(Paragraph("Hepatic Encephalopathy Grading", H2))
enc_table = two_col_table(
    ["Grade", "Clinical Features"],
    [
        ["Grade I", "Inverted sleep pattern, agitation, forgetfulness, irritability, apraxia"],
        ["Grade II", "Lethargy, time/place disorientation, personality change, ataxia"],
        ["Grade III", "Somnolence to semistupor (responds to verbal stimuli), asterixis, hyperreflexia"],
        ["Grade IV", "Coma (no response to verbal stimuli)"],
    ],
    col_widths=[W*0.12, W*0.88]
)
story.append(enc_table)
story.append(sp(5))

story.append(Paragraph("Management of ALF", H2))
story.append(bp("<b>ICU admission</b> + consideration for liver transplant listing"))
story.append(bp("<b>Continue IV NAC</b> — reduces mortality even in established ALF; decreases cerebral oedema, hypotension, and multiorgan failure"))
story.append(bp("<b>Hypoglycaemia</b>: IV dextrose; regular monitoring"))
story.append(bp("<b>Coagulopathy</b>: FFP only for active bleeding or invasive procedures (NOT routine); INR used as prognostic marker"))
story.append(bp("<b>Cerebral oedema</b>: elevate HOB 30°; avoid hypotension; consider mannitol/hypertonic saline for raised ICP"))
story.append(bp("<b>Infection surveillance</b>: immunocompromised state; early broad-spectrum antibiotics if sepsis"))
story.append(bp("<b>Renal replacement therapy</b>: CVVHDF preferred in haemodynamic instability"))
story.append(bp("<b>Early referral to transplant centre</b> if King's College Criteria approaching or met"))
story.append(sp(8))

# ── 7. SPECIAL SCENARIOS ──────────────────────────────────────────────────────
story.append(section_header("7.  SPECIAL SCENARIOS", C_TEAL))
story.append(sp(6))

story.append(Paragraph("Pregnancy", H2))
story.append(bp("NAC crosses placenta — <b>use standard dosing</b>; NAC is safe in pregnancy"))
story.append(bp("Paracetamol toxicity in pregnancy associated with fetal loss, especially if maternal hepatotoxicity develops"))
story.append(bp("Low threshold for NAC treatment; consult obstetrics"))
story.append(bp("Fetal monitoring if >20 weeks gestation"))
story.append(sp(4))

story.append(Paragraph("Paediatric Considerations", H2))
story.append(bp("Children &lt;6 yrs: level if >200 mg/kg ingested; take level ≥2 h after ingestion"))
story.append(bp("If 2–4 h level &lt;150 mg/L (1000 µmol/L) → NAC not required"))
story.append(bp("Children more resistant to hepatotoxicity than adults (higher sulfation capacity)"))
story.append(bp("NAC dosing: same mg/kg dosing; use weight-based diluent volumes"))
story.append(sp(4))

story.append(Paragraph("Intravenous Paracetamol Toxicity", H2))
story.append(bp("Higher peak levels than oral — nomogram thresholds may not apply directly"))
story.append(bp("Treat with low threshold for NAC"))
story.append(sp(4))

story.append(Paragraph("Co-ingestions to Consider", H2))
story.append(bp("Opioids, benzodiazepines, alcohol — may mask symptoms and alter mental status"))
story.append(bp("Antimuscarinics (e.g. diphenhydramine): delayed gastric emptying → delayed paracetamol absorption → recheck level at 8 h if 4 h level below treatment line"))
story.append(bp("Always screen with paracetamol level regardless of history in intentional OD"))
story.append(sp(8))

# ── 8. INDICATIONS FOR TOXICOLOGY CONSULTATION ───────────────────────────────
story.append(section_header("8.  WHEN TO CONSULT TOXICOLOGY / ESCALATE", C_AMBER))
story.append(sp(6))

consult_items = [
    "Hepatotoxicity present at time of presentation",
    "Pre-existing liver disease (cirrhosis, chronic hepatitis)",
    "Level cannot be obtained within 8 h of ingestion",
    "Supratherapeutic ingestion (RSTI) — complex risk assessment",
    "Modified-release paracetamol ingestion",
    "Massive ingestion / level ≥2–3× nomogram line",
    "Patient develops ALF — contact transplant centre",
    "Uncertain ingestion time",
    "NAC anaphylactoid reaction not responding to standard management",
    "Renal failure complicating overdose — consider haemodialysis",
    "Paediatric overdose with concerns about dosing",
    "All suspected paracetamol poisoning: call Poisons Info 13 11 26 (Aus)",
]
for item in consult_items:
    story.append(bp(item))
story.append(sp(8))

# ── 9. DISPOSITION ─────────────────────────────────────────────────────────────
story.append(section_header("9.  DISPOSITION", C_BLUE))
story.append(sp(6))

disp_table = two_col_table(
    ["Scenario", "Disposition"],
    [
        ["Level below treatment line, ALT normal, asymptomatic", "Medical clearance possible; psychiatric assessment if intentional OD"],
        ["NAC commenced — completing 20-h course", "Admit to ED or short stay unit"],
        ["ALT elevated at end of 20-h course", "Admit; continue NAC; hepatology/toxicology review"],
        ["Evidence of hepatotoxicity / rising INR", "Admit to HDU/ICU; consider transplant centre referral"],
        ["King's College Criteria met", "Urgent transfer to liver transplant centre"],
        ["Modified-release or RSTI — complex risk", "Admit for monitoring; early toxicology input"],
        ["Any intentional overdose", "Mandatory psychiatric assessment before discharge"],
    ],
    col_widths=[W*0.48, W*0.52]
)
story.append(disp_table)
story.append(sp(8))

# ── 10. HIGH-YIELD FACEM SUMMARY ──────────────────────────────────────────────
story.append(section_header("10.  HIGH-YIELD FACEM SUMMARY", C_NAVY))
story.append(sp(6))

story.append(Paragraph("Key Numbers to Know", H2))
numbers_table = two_col_table(
    ["Parameter", "Key Number / Threshold"],
    [
        ["NAC Bag 1", "200 mg/kg in 500 mL over 4 h"],
        ["NAC Bag 2", "100 mg/kg in 1000 mL over 16 h"],
        ["Double NAC bag 2 threshold", "Paracetamol level ≥2× nomogram line"],
        ["Nomogram treatment line (4 h)", "150 mcg/mL (1000 µmol/L)"],
        ["KCC pH", "<7.30 alone = sufficient for transplant listing"],
        ["KCC INR", ">6.5"],
        ["KCC creatinine", ">301 µmol/L"],
        ["KCC encephalopathy", "Grade III or IV"],
        ["Haemodialysis threshold (no NAC)", ">1000 mcg/mL"],
        ["Haemodialysis threshold (NAC given)", ">900 mcg/mL + AMS + acidosis + ↑lactate"],
        ["Toxic single dose", ">10 g or >200 mg/kg (whichever less)"],
        ["Time window for best NAC outcome", "<8 h from ingestion (hepatotoxicity <1%)"],
        ["4-hour level for nomogram", "Earliest valid time to plot"],
        ["NAC risk of hepatotox when started <8h", "<1%; mortality ≈ 0"],
    ],
    col_widths=[W*0.50, W*0.50]
)
story.append(numbers_table)
story.append(sp(5))

story.append(Paragraph("FACEM Exam Traps", H2))
story.append(alert_box("Common Exam Traps",
    ["Modified-release paracetamol: nomogram does NOT apply — all ≥10g or ≥200mg/kg get NAC regardless",
     "Level <4h post-ingestion CANNOT be plotted — do not use to rule out toxicity",
     "Asymptomatic in Stage 1 does NOT mean safe — this is a classic false reassurance trap",
     "RSTI: total daily dose matters, not a single spike — threshold is 6g/day for ≥2 days",
     "NAC adverse reaction: PAUSE then RESTART at slower rate — do NOT abandon NAC",
     "Continue NAC even if paracetamol level undetectable if ALT >1000 or ALF present",
     "KCC acidosis criterion: pH <7.30 AFTER adequate fluid resuscitation",
     "Hyperphosphataemia adds to KCC sensitivity — do not forget phosphate in ALF workup",
     "Two-bag regimen (AUS/NZ 2019): NOT three-bag — know the current guideline change"],
    color=C_RED))
story.append(sp(6))

story.append(Paragraph("References", H2))
story.append(Paragraph(
    "1. Chiew AL et al. Updated guidelines for the management of paracetamol poisoning in Australia and NZ. "
    "<i>Med J Aust</i> 2020;212(4):175–183. "
    "2. Tintinalli JE et al. <i>Tintinalli's Emergency Medicine</i>, 9th ed. Chapter 190. "
    "3. Walls R et al. <i>Rosen's Emergency Medicine</i>, 10th ed. Chapter 138. "
    "4. Bailey &amp; Love's <i>Short Practice of Surgery</i>, 28th ed. Chapter 69. "
    "5. Nakatsu L et al. Two-bag vs three-bag acetylcysteine: systematic review and meta-analysis. "
    "<i>Clin Toxicol</i> 2025 Mar. PMID: 40013897. "
    "6. NSW ECI Paracetamol Overdose Management Tool, 2024.",
    BODYSM))
story.append(sp(4))
story.append(hr(C_MGRAY))
story.append(Paragraph(
    "Orris Medical Notes | FACEM Exam Preparation | Paracetamol Toxicity | June 2026 | "
    "Always verify against current local guidelines and Poisons Information Centre (13 11 26)",
    FOOTER))

# ── BUILD PDF ─────────────────────────────────────────────────────────────────
doc.build(story)
print("PDF generated successfully!")