Antiepileptic Drugs (AEDs) - Exam-Oriented Review

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_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import BaseDocTemplate, Frame, PageTemplate

# ── Color palette ──────────────────────────────────────────────────
DARK_BLUE    = colors.HexColor("#1A237E")
MID_BLUE     = colors.HexColor("#1565C0")
LIGHT_BLUE   = colors.HexColor("#BBDEFB")
ACCENT_TEAL  = colors.HexColor("#00838F")
LIGHT_TEAL   = colors.HexColor("#E0F7FA")
ORANGE       = colors.HexColor("#E65100")
LIGHT_ORANGE = colors.HexColor("#FFF3E0")
GREEN        = colors.HexColor("#1B5E20")
LIGHT_GREEN  = colors.HexColor("#E8F5E9")
RED          = colors.HexColor("#B71C1C")
LIGHT_RED    = colors.HexColor("#FFEBEE")
YELLOW_BG    = colors.HexColor("#FFFDE7")
GRAY_DARK    = colors.HexColor("#37474F")
GRAY_LIGHT   = colors.HexColor("#ECEFF1")
WHITE        = colors.white

OUTPUT = "/home/daytona/workspace/aed_summary/Antiepileptic_Drugs_Summary.pdf"

# ── Document setup ─────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=15*mm, rightMargin=15*mm,
    topMargin=18*mm, bottomMargin=18*mm,
)

W = A4[0] - 30*mm   # usable width

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

def S(name, **kw):
    s = ParagraphStyle(name, **kw)
    return s

title_style  = S("Title2",  fontName="Helvetica-Bold",  fontSize=20, textColor=WHITE,       alignment=TA_CENTER, spaceAfter=2)
sub_style    = S("Sub",     fontName="Helvetica",        fontSize=10, textColor=LIGHT_BLUE,  alignment=TA_CENTER, spaceAfter=4)
h1_style     = S("H1",      fontName="Helvetica-Bold",  fontSize=13, textColor=WHITE,        spaceBefore=6, spaceAfter=3)
h2_style     = S("H2",      fontName="Helvetica-Bold",  fontSize=11, textColor=DARK_BLUE,    spaceBefore=8, spaceAfter=3)
body_style   = S("Body2",   fontName="Helvetica",        fontSize=8.5, textColor=GRAY_DARK,  leading=12, spaceAfter=2)
mnem_style   = S("Mnem",    fontName="Helvetica-BoldOblique", fontSize=8.5, textColor=ORANGE, leading=12, spaceAfter=2)
note_style   = S("Note",    fontName="Helvetica-Oblique", fontSize=8, textColor=ACCENT_TEAL, leading=11, spaceAfter=2)
th_style     = S("TH",      fontName="Helvetica-Bold",  fontSize=8,  textColor=WHITE,        alignment=TA_CENTER, leading=10)
td_style     = S("TD",      fontName="Helvetica",        fontSize=7.5, textColor=GRAY_DARK,  alignment=TA_CENTER, leading=10)
td_l_style   = S("TDL",     fontName="Helvetica",        fontSize=7.5, textColor=GRAY_DARK,  alignment=TA_LEFT,   leading=10)
bold_td      = S("BTD",     fontName="Helvetica-Bold",  fontSize=7.5, textColor=DARK_BLUE,   alignment=TA_LEFT,   leading=10)
warn_style   = S("Warn",    fontName="Helvetica-Bold",  fontSize=8,   textColor=RED,         alignment=TA_LEFT,   leading=11)

def P(text, style=body_style): return Paragraph(text, style)
def TH(t): return Paragraph(t, th_style)
def TD(t): return Paragraph(t, td_style)
def TDL(t): return Paragraph(t, td_l_style)
def BTD(t): return Paragraph(t, bold_td)

story = []

# ════════════════════════════════════════════════════════════════════
# COVER BANNER
# ════════════════════════════════════════════════════════════════════
banner_data = [[P("ANTIEPILEPTIC DRUGS", title_style)],
               [P("Mechanism of Action · Side Effects · Drug Comparison Tables", sub_style)],
               [P("Exam-Oriented Quick Revision Guide", sub_style)]]
banner_tbl = Table(banner_data, colWidths=[W])
banner_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE),
    ("TOPPADDING",  (0,0), (-1,-1), 10),
    ("BOTTOMPADDING",(0,0),(-1,-1), 8),
    ("LEFTPADDING", (0,0), (-1,-1), 10),
    ("ALIGN",       (0,0), (-1,-1), "CENTER"),
    ("VALIGN",      (0,0), (-1,-1), "MIDDLE"),
    ("ROUNDEDCORNERS", [6]),
]))
story.append(banner_tbl)
story.append(Spacer(1, 6*mm))

# ════════════════════════════════════════════════════════════════════
# SECTION HEADER HELPER
# ════════════════════════════════════════════════════════════════════
def section_header(text, color=MID_BLUE):
    t = Table([[P(text, h1_style)]], colWidths=[W])
    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), 8),
        ("ROUNDEDCORNERS",[4]),
    ]))
    return t

def info_box(text, bg=LIGHT_TEAL, tc=ACCENT_TEAL):
    st = S("IB", fontName="Helvetica-BoldOblique", fontSize=8.5, textColor=tc, leading=12, spaceAfter=0)
    t = Table([[P(text, st)]], colWidths=[W])
    t.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(-1,-1), bg),
        ("TOPPADDING",   (0,0),(-1,-1), 5),
        ("BOTTOMPADDING",(0,0),(-1,-1), 5),
        ("LEFTPADDING",  (0,0),(-1,-1), 8),
        ("ROUNDEDCORNERS",[4]),
    ]))
    return t

# ════════════════════════════════════════════════════════════════════
# 1. CLASSIFICATION BY MECHANISM
# ════════════════════════════════════════════════════════════════════
story.append(section_header("1.  Classification by Mechanism of Action"))
story.append(Spacer(1, 3*mm))

mech_data = [
    [TH("Mechanism"), TH("Primary Site"), TH("Drugs")],
    [TD("Na⁺ Channel Blockers"),
     TDL("Inactive state of VG-Na⁺ channel\n→ ↓ high-freq firing"),
     TDL("Phenytoin, Carbamazepine, Oxcarbazepine,\nLamotrigine, Lacosamide, Eslicarbazepine")],
    [TD("Ca²⁺ Channel Blockers\n(T-type)"),
     TDL("Thalamic T-type Ca²⁺ channels\n→ ↓ spike-wave discharge"),
     TDL("Ethosuximide, Valproate (partial)")],
    [TD("Ca²⁺ Channel Blockers\n(α₂δ subunit)"),
     TDL("VG-Ca²⁺ α₂δ subunit\n→ ↓ excitatory NT release"),
     TDL("Gabapentin, Pregabalin")],
    [TD("GABA Enhancement"),
     TDL("GABA-A receptor Cl⁻ channel\n(↑ duration = barbiturates;\n↑ frequency = BZDs)"),
     TDL("Phenobarbital, Primidone,\nBenzodiazepines, Vigabatrin, Tiagabine")],
    [TD("SV2A Ligand"),
     TDL("Synaptic vesicle protein SV2A\n→ modulates NT release"),
     TDL("Levetiracetam, Brivaracetam")],
    [TD("Multiple / Broad"),
     TDL("Na⁺ channels + T-Ca²⁺ +\nGABA + NMDA antagonism"),
     TDL("Valproate, Topiramate, Zonisamide,\nFelbamate")],
]

mech_tbl = Table(mech_data, colWidths=[W*0.22, W*0.33, W*0.45])
mech_tbl.setStyle(TableStyle([
    ("BACKGROUND",   (0,0), (-1,0),  MID_BLUE),
    ("TEXTCOLOR",    (0,0), (-1,0),  WHITE),
    ("BACKGROUND",   (0,1), (-1,1),  LIGHT_BLUE),
    ("BACKGROUND",   (0,2), (-1,2),  GRAY_LIGHT),
    ("BACKGROUND",   (0,3), (-1,3),  LIGHT_BLUE),
    ("BACKGROUND",   (0,4), (-1,4),  GRAY_LIGHT),
    ("BACKGROUND",   (0,5), (-1,5),  LIGHT_BLUE),
    ("BACKGROUND",   (0,6), (-1,6),  GRAY_LIGHT),
    ("GRID",         (0,0), (-1,-1), 0.4, colors.white),
    ("TOPPADDING",   (0,0), (-1,-1), 4),
    ("BOTTOMPADDING",(0,0), (-1,-1), 4),
    ("LEFTPADDING",  (0,0), (-1,-1), 5),
    ("RIGHTPADDING", (0,0), (-1,-1), 5),
    ("VALIGN",       (0,0), (-1,-1), "TOP"),
    ("ALIGN",        (0,0), (0,-1),  "CENTER"),
    ("ALIGN",        (0,0), (-1,0),  "CENTER"),
]))
story.append(mech_tbl)
story.append(Spacer(1, 4*mm))
story.append(info_box("⚡ Key Distinction: Barbiturates ↑ DURATION of Cl⁻ opening | Benzodiazepines ↑ FREQUENCY of Cl⁻ opening"))
story.append(Spacer(1, 5*mm))

# ════════════════════════════════════════════════════════════════════
# 2. MAIN DRUG COMPARISON TABLE
# ════════════════════════════════════════════════════════════════════
story.append(section_header("2.  Main Drug Comparison Table"))
story.append(Spacer(1, 3*mm))

drug_data = [
    [TH("Drug"), TH("Mechanism"), TH("Uses"), TH("Major Side Effects"), TH("Unique / Exam Tips")],

    [BTD("Phenytoin\n(Dilantin)"),
     TDL("VG-Na⁺ channel\nblocker (inactive\nstate)"),
     TDL("Focal, tonic-clonic,\nstatus epilepticus,\ntrigeminal neuralgia"),
     TDL("Nystagmus, ataxia, diplopia,\nGingival hyperplasia,\nHirsutism, Peripheral neuropathy,\nOsteoporosis, Folate def."),
     TDL("Nonlinear (zero-order) PK\nCYP enzyme inducer\nTeratogenic (fetal hydantoin)\nNEVER give IM")],

    [BTD("Carbamazepine\n(Tegretol)"),
     TDL("VG-Na⁺ channel\nblocker"),
     TDL("Focal, tonic-clonic,\ntrigeminal neuralgia,\nbipolar disorder"),
     TDL("Diplopia, ataxia, nausea,\nHyponatremia (SIADH),\nAplastic anemia,\nStevens-Johnson (HLA-B*1502)"),
     TDL("Autoinduces own metabolism\nCYP inducer\nContraindicated in ABSENCE\nTeratogenic")],

    [BTD("Valproate\n(Depakote)"),
     TDL("Broad: Na⁺, T-Ca²⁺,\nGABA ↑, NMDA ↓"),
     TDL("ALL seizure types,\nmigraine, bipolar,\nJME (drug of choice)"),
     TDL("Nausea, tremor, weight gain,\nAlopecia, Hepatotoxicity,\nPancreatitis, Thrombocytopenia"),
     TDL("CYP INHIBITOR (↑ lamotrigine)\nMOST teratogenic (neural tube\ndefects, spina bifida)\nDOC for JME + absence + GTC")],

    [BTD("Ethosuximide\n(Zarontin)"),
     TDL("T-type Ca²⁺ channel\nblocker (thalamic)"),
     TDL("ABSENCE SEIZURES\nONLY"),
     TDL("GI upset, anorexia,\nDrowsiness, headache\nSkin rash (rare SJS)"),
     TDL("NO effect on other seizure\ntypes. If absence + GTC\ncoexist → use Valproate")],

    [BTD("Phenobarbital\n(Luminal)"),
     TDL("GABA-A ↑ duration\nof Cl⁻ opening;\n↓ glutamate"),
     TDL("Tonic-clonic,\nstatus epilepticus (IV),\nneonatal seizures"),
     TDL("Sedation, cognitive slowing,\nTolerance & dependence,\nWithdrawal seizures"),
     TDL("CYP inducer\nTeratogenic (cleft palate)\nLong t½ (40-120h)")],

    [BTD("Lamotrigine\n(Lamictal)"),
     TDL("Na⁺ channel blocker;\n↓ glutamate release"),
     TDL("Focal, GTC, absence,\nmyoclonic, bipolar\ndepression"),
     TDL("Dizziness, diplopia,\nSerious rash / SJS\n(esp. with valproate)"),
     TDL("Valproate DOUBLES lamotrigine\nlevels (reduce dose!)\nTitrate dose SLOWLY to\navoid SJS rash")],

    [BTD("Levetiracetam\n(Keppra)"),
     TDL("SV2A synaptic\nvesicle protein\nbinding"),
     TDL("Focal, GTC,\nmyoclonic seizures"),
     TDL("'Keppra Rage': irritability,\naggression, depression,\nanxiety, dizziness"),
     TDL("Minimal drug interactions\nRenal excretion\nNo hepatic metabolism\nMost widely used new AED")],

    [BTD("Gabapentin &\nPregabalin"),
     TDL("α₂δ subunit of\nVG-Ca²⁺ channels\n→ ↓ NT release"),
     TDL("Adjunct focal Sz;\nneuropathic pain,\nfibromyalgia"),
     TDL("Sedation, dizziness, ataxia,\nWeight gain, peripheral edema\nPregabalin: euphoria/abuse"),
     TDL("Despite 'GABA' in name, do\nNOT act on GABA receptors!\nPregabalin: Schedule V\nDose adjust in renal failure")],

    [BTD("Topiramate\n(Topamax)"),
     TDL("Multiple: Na⁺ block,\nGABA ↑, AMPA/\nkainate antagonist,\nCA inhibitor"),
     TDL("Focal + generalized,\nLennox-Gastaut,\nmigraine prophylaxis"),
     TDL("Cognitive slowing ('Dopamax'),\nWord-finding difficulty,\nRenal stones (CA inhibition),\nMetabolic acidosis, Anorexia"),
     TDL("Weight LOSS (off-label obesity)\nContraceptive failure\nTeratogenic (cleft lip/palate)")],

    [BTD("Benzodiazepines\n(Diazepam,\nLorazepam,\nClonazepam)"),
     TDL("GABA-A ↑ frequency\nof Cl⁻ opening"),
     TDL("Status epilepticus\n(lorazepam = 1st line)\nAbsence, myoclonic\n(clonazepam)"),
     TDL("Sedation, respiratory depression,\nTolerance & dependence,\nAnterograde amnesia"),
     TDL("Tolerance limits long-term use\nDiazepam: rectal/intranasal\nfor prolonged seizures\nClobazam: Lennox-Gastaut")],
]

drug_tbl = Table(drug_data, colWidths=[W*0.12, W*0.16, W*0.17, W*0.28, W*0.27])
drug_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),  (-1,0),   DARK_BLUE),
    ("TEXTCOLOR",     (0,0),  (-1,0),   WHITE),
    # alternating rows
    ("BACKGROUND",    (0,1),  (-1,1),   LIGHT_BLUE),
    ("BACKGROUND",    (0,2),  (-1,2),   GRAY_LIGHT),
    ("BACKGROUND",    (0,3),  (-1,3),   LIGHT_BLUE),
    ("BACKGROUND",    (0,4),  (-1,4),   GRAY_LIGHT),
    ("BACKGROUND",    (0,5),  (-1,5),   LIGHT_BLUE),
    ("BACKGROUND",    (0,6),  (-1,6),   GRAY_LIGHT),
    ("BACKGROUND",    (0,7),  (-1,7),   LIGHT_BLUE),
    ("BACKGROUND",    (0,8),  (-1,8),   GRAY_LIGHT),
    ("BACKGROUND",    (0,9),  (-1,9),   LIGHT_BLUE),
    ("BACKGROUND",    (0,10), (-1,10),  GRAY_LIGHT),
    ("GRID",          (0,0),  (-1,-1),  0.4, colors.white),
    ("TOPPADDING",    (0,0),  (-1,-1),  4),
    ("BOTTOMPADDING", (0,0),  (-1,-1),  4),
    ("LEFTPADDING",   (0,0),  (-1,-1),  5),
    ("RIGHTPADDING",  (0,0),  (-1,-1),  5),
    ("VALIGN",        (0,0),  (-1,-1),  "TOP"),
    ("ALIGN",         (0,0),  (-1,0),   "CENTER"),
]))
story.append(drug_tbl)
story.append(PageBreak())

# ════════════════════════════════════════════════════════════════════
# 3. SEIZURE TYPE → DRUG OF CHOICE
# ════════════════════════════════════════════════════════════════════
story.append(section_header("3.  Seizure Type → Drug of Choice", color=ACCENT_TEAL))
story.append(Spacer(1, 3*mm))

sz_data = [
    [TH("Seizure Type"), TH("1st Choice (DOC)"), TH("Alternatives"), TH("Avoid")],
    [TD("Absence (Petit Mal)"),         TD("Ethosuximide"),             TD("Valproate, Lamotrigine"),              TD("Carbamazepine, Phenytoin,\nTiagabine, Vigabatrin")],
    [TD("Tonic-Clonic (Grand Mal)"),    TD("Valproate"),                TD("Phenytoin, Carbamazepine,\nLamotrigine, Levetiracetam"),  TD("—")],
    [TD("Focal (Partial)"),             TD("Carbamazepine"),            TD("Phenytoin, Lamotrigine,\nLevetiracetam, Oxcarbazepine"), TD("—")],
    [TD("Myoclonic"),                   TD("Valproate"),                TD("Levetiracetam, Clonazepam,\nTopiramate"),                TD("Carbamazepine, Phenytoin,\nGabapentin")],
    [TD("Juvenile Myoclonic\nEpilepsy (JME)"), TD("Valproate"),        TD("Levetiracetam, Topiramate,\nLamotrigine"),               TD("Carbamazepine")],
    [TD("Status Epilepticus"),          TD("Lorazepam IV (1st)\nor Diazepam IV"), TD("Phenytoin/Fosphenytoin (2nd)\nPhenobarbital IV (3rd)\nMidazolam, Propofol, Pentobarbital"), TD("—")],
    [TD("Lennox-Gastaut\nSyndrome"),    TD("Valproate"),                TD("Topiramate, Clobazam,\nRufinamide, Cannabidiol"),        TD("Carbamazepine\n(worsens atonic Sz)")],
    [TD("Trigeminal Neuralgia"),        TD("Carbamazepine"),            TD("Oxcarbazepine, Phenytoin,\nLamotrigine"),                TD("—")],
    [TD("Absence + GTC\n(coexisting)"), TD("Valproate"),               TD("Lamotrigine"),                         TD("Ethosuximide alone")],
    [TD("Neonatal Seizures"),           TD("Phenobarbital"),            TD("Phenytoin, Levetiracetam"),            TD("—")],
    [TD("Bipolar Disorder"),            TD("Valproate / Lithium"),      TD("Carbamazepine, Lamotrigine\n(bipolar depression)"),      TD("—")],
    [TD("Migraine Prophylaxis"),        TD("Valproate / Topiramate"),   TD("—"),                                   TD("—")],
]
sz_tbl = Table(sz_data, colWidths=[W*0.22, W*0.22, W*0.31, W*0.25])
sz_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),  (-1,0),  ACCENT_TEAL),
    ("TEXTCOLOR",     (0,0),  (-1,0),  WHITE),
    *[("BACKGROUND",  (0,i),  (-1,i),  LIGHT_TEAL if i%2==1 else GRAY_LIGHT) for i in range(1, len(sz_data))],
    ("GRID",          (0,0),  (-1,-1), 0.4, colors.white),
    ("TOPPADDING",    (0,0),  (-1,-1), 4),
    ("BOTTOMPADDING", (0,0),  (-1,-1), 4),
    ("LEFTPADDING",   (0,0),  (-1,-1), 5),
    ("RIGHTPADDING",  (0,0),  (-1,-1), 5),
    ("VALIGN",        (0,0),  (-1,-1), "TOP"),
    ("ALIGN",         (0,0),  (-1,0),  "CENTER"),
]))
story.append(sz_tbl)
story.append(Spacer(1, 5*mm))

# ════════════════════════════════════════════════════════════════════
# 4. SIDE EFFECT COMPARISON TABLE
# ════════════════════════════════════════════════════════════════════
story.append(section_header("4.  Distinctive Side Effects — Quick Comparison", color=colors.HexColor("#4A148C")))
story.append(Spacer(1, 3*mm))

PURPLE_DARK  = colors.HexColor("#4A148C")
PURPLE_LIGHT = colors.HexColor("#EDE7F6")
PURPLE_MID   = colors.HexColor("#D1C4E9")

se_data = [
    [TH("Side Effect / Toxicity"), TH("Drug(s) Responsible")],
    [TDL("Gingival Hyperplasia (gum overgrowth)"),    TDL("Phenytoin")],
    [TDL("Hirsutism + Coarsening of facial features"),TDL("Phenytoin")],
    [TDL("Nonlinear (zero-order) pharmacokinetics"),  TDL("Phenytoin")],
    [TDL("Hyponatremia / SIADH-like"),                TDL("Carbamazepine, Oxcarbazepine")],
    [TDL("Aplastic anemia / Agranulocytosis"),         TDL("Carbamazepine, Felbamate")],
    [TDL("Stevens-Johnson Syndrome (SJS)"),            TDL("Carbamazepine (HLA-B*1502), Lamotrigine,\nPhenytoin, Phenobarbital")],
    [TDL("Autoinduction of own metabolism"),           TDL("Carbamazepine")],
    [TDL("Hepatotoxicity (esp. children <2 on\npolytherapy)"),TDL("Valproate (most serious!)")],
    [TDL("Pancreatitis"),                              TDL("Valproate")],
    [TDL("Alopecia (hair loss)"),                      TDL("Valproate")],
    [TDL("Weight GAIN"),                               TDL("Valproate, Gabapentin, Pregabalin")],
    [TDL("Weight LOSS"),                               TDL("Topiramate, Felbamate, Zonisamide")],
    [TDL("Neural tube defects (teratogenicity)"),       TDL("Valproate (highest risk!), Carbamazepine")],
    [TDL("Cognitive slowing / 'Dopamax' effect"),       TDL("Topiramate")],
    [TDL("Renal stones (nephrolithiasis)"),             TDL("Topiramate, Zonisamide, Acetazolamide")],
    [TDL("Behavioral disturbance ('Keppra rage')"),     TDL("Levetiracetam")],
    [TDL("Tolerance & Dependence"),                     TDL("Benzodiazepines, Barbiturates")],
    [TDL("Sedation / Cognitive slowing in children"),   TDL("Phenobarbital (major limitation)")],
    [TDL("Peripheral edema + euphoria/abuse potential"),TDL("Pregabalin")],
    [TDL("Rash — severely worsened by Valproate"),      TDL("Lamotrigine (dose escalate slowly!)")],
    [TDL("Osteoporosis / Osteomalacia"),                TDL("Phenytoin, Phenobarbital, Carbamazepine\n(enzyme inducers → ↓ Vit D)")],
    [TDL("Folic acid deficiency / Megaloblastic anemia"),TDL("Phenytoin, Phenobarbital")],
    [TDL("Tissue necrosis if given IM"),                TDL("Phenytoin (use Fosphenytoin instead!)")],
]
se_tbl = Table(se_data, colWidths=[W*0.52, W*0.48])
se_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),  (-1,0),  PURPLE_DARK),
    ("TEXTCOLOR",     (0,0),  (-1,0),  WHITE),
    *[("BACKGROUND",  (0,i),  (-1,i),  PURPLE_LIGHT if i%2==1 else GRAY_LIGHT) for i in range(1, len(se_data))],
    ("GRID",          (0,0),  (-1,-1), 0.4, colors.white),
    ("TOPPADDING",    (0,0),  (-1,-1), 4),
    ("BOTTOMPADDING", (0,0),  (-1,-1), 4),
    ("LEFTPADDING",   (0,0),  (-1,-1), 6),
    ("RIGHTPADDING",  (0,0),  (-1,-1), 6),
    ("VALIGN",        (0,0),  (-1,-1), "TOP"),
    ("ALIGN",         (0,0),  (-1,0),  "CENTER"),
]))
story.append(se_tbl)
story.append(PageBreak())

# ════════════════════════════════════════════════════════════════════
# 5. ENZYME INTERACTIONS TABLE
# ════════════════════════════════════════════════════════════════════
story.append(section_header("5.  Drug Interactions — Enzyme Inducers vs Inhibitors", color=ORANGE))
story.append(Spacer(1, 3*mm))

int_data = [
    [TH("Drug"), TH("Enzyme Effect"), TH("Drugs Affected (levels ↓ unless noted)"), TH("Exam Tip")],
    [BTD("Phenytoin"),       TD("CYP INDUCER\n(2C9, 2C19, 3A4)"), TDL("OCP, warfarin, steroids,\ncyclosporine, digoxin,\ncarbamazepine"), TDL("Can lower its OWN level\n+ raises phenobarb level")],
    [BTD("Carbamazepine"),   TD("CYP INDUCER\n(1A2, 2C, 3A4, UGT)"),TDL("OCP, warfarin, valproate,\nlamotrigine, phenytoin,\nclonazepam"), TDL("AUTOINDUCES itself\n→ t½ falls over weeks")],
    [BTD("Phenobarbital"),   TD("CYP INDUCER\n(broad)"),           TDL("OCP, steroids, warfarin,\nmost AEDs"),                          TDL("Valproate INHIBITS\nphenobarb metabolism\n→ ↑ sedation")],
    [BTD("Valproate"),       TD("CYP INHIBITOR\n(2C9, UGT)"),      TDL("Lamotrigine LEVEL ↑ 2×\nPhenobarb level ↑\nEthosuximide level ↑"),TDL("Most important interaction:\n↑ lamotrigine → SJS risk!")],
    [BTD("Levetiracetam"),   TD("MINIMAL interactions"),           TDL("Virtually none"),                                               TDL("Safest for polypharmacy\nPolycystic epilepsy patients")],
    [BTD("Gabapentin /\nPregabalin"), TD("NONE"),                  TDL("No CYP interactions"),                                          TDL("Renally excreted,\nadjust in renal failure")],
    [BTD("Lamotrigine"),     TD("NONE (substrate only)"),          TDL("—"),                                                            TDL("Its OWN level:\n↑ by valproate (inhibit)\n↓ by CBZ, PHT, PHB (induce)")],
]
int_tbl = Table(int_data, colWidths=[W*0.14, W*0.18, W*0.37, W*0.31])
int_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),  (-1,0),  ORANGE),
    ("TEXTCOLOR",     (0,0),  (-1,0),  WHITE),
    *[("BACKGROUND",  (0,i),  (-1,i),  LIGHT_ORANGE if i%2==1 else GRAY_LIGHT) for i in range(1, len(int_data))],
    ("GRID",          (0,0),  (-1,-1), 0.4, colors.white),
    ("TOPPADDING",    (0,0),  (-1,-1), 4),
    ("BOTTOMPADDING", (0,0),  (-1,-1), 4),
    ("LEFTPADDING",   (0,0),  (-1,-1), 5),
    ("RIGHTPADDING",  (0,0),  (-1,-1), 5),
    ("VALIGN",        (0,0),  (-1,-1), "TOP"),
    ("ALIGN",         (0,0),  (-1,0),  "CENTER"),
]))
story.append(int_tbl)
story.append(Spacer(1, 5*mm))

# ════════════════════════════════════════════════════════════════════
# 6. TERATOGENICITY TABLE
# ════════════════════════════════════════════════════════════════════
story.append(section_header("6.  Teratogenicity — AEDs in Pregnancy", color=RED))
story.append(Spacer(1, 3*mm))

tera_data = [
    [TH("Drug"), TH("Risk"), TH("Main Defect(s)"), TH("Notes")],
    [BTD("Valproate"),      TD("HIGHEST ⚠⚠⚠"),  TDL("Neural tube defects (spina bifida),\ncognitive impairment in child,\nAutism spectrum disorder"), TDL("Use supplemental folic acid;\nconsider alternatives if possible")],
    [BTD("Carbamazepine"),  TD("HIGH ⚠⚠"),       TDL("Neural tube defects (lower risk than\nvalproate), facial anomalies"),  TDL("HLA-B*1502 screening before use\nin Asian patients")],
    [BTD("Phenytoin"),      TD("HIGH ⚠⚠"),       TDL("Fetal hydantoin syndrome:\nhypertelorism, digital hypoplasia,\ncleft lip/palate"),             TDL("CYP inducer → ↓ folic acid\nUse folic acid supplementation")],
    [BTD("Phenobarbital"),  TD("MODERATE ⚠"),    TDL("Cleft lip/palate, cardiac defects"),   TDL("Neonatal withdrawal + bleeding\nGive vit K to mother + neonate")],
    [BTD("Topiramate"),     TD("MODERATE ⚠"),    TDL("Cleft lip/palate, low birth weight"),  TDL("FDA Category D")],
    [BTD("Lamotrigine"),    TD("LOW-MODERATE"),  TDL("Cleft palate (dose-dependent risk)"),   TDL("Relatively safer option;\nmonitor levels in pregnancy")],
    [BTD("Levetiracetam"),  TD("LOW"),           TDL("Limited data; no major teratogen\nidentified so far"),                TDL("Often preferred in pregnancy\nwhen AED needed")],
]
tera_tbl = Table(tera_data, colWidths=[W*0.14, W*0.14, W*0.38, W*0.34])
tera_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),  (-1,0),  RED),
    ("TEXTCOLOR",     (0,0),  (-1,0),  WHITE),
    *[("BACKGROUND",  (0,i),  (-1,i),  LIGHT_RED if i%2==1 else GRAY_LIGHT) for i in range(1, len(tera_data))],
    ("GRID",          (0,0),  (-1,-1), 0.4, colors.white),
    ("TOPPADDING",    (0,0),  (-1,-1), 4),
    ("BOTTOMPADDING", (0,0),  (-1,-1), 4),
    ("LEFTPADDING",   (0,0),  (-1,-1), 5),
    ("RIGHTPADDING",  (0,0),  (-1,-1), 5),
    ("VALIGN",        (0,0),  (-1,-1), "TOP"),
    ("ALIGN",         (0,0),  (-1,0),  "CENTER"),
    ("ALIGN",         (0,1),  (0,-1),  "CENTER"),
]))
story.append(tera_tbl)
story.append(Spacer(1, 5*mm))

# ════════════════════════════════════════════════════════════════════
# 7. PHARMACOKINETICS TABLE
# ════════════════════════════════════════════════════════════════════
story.append(section_header("7.  Key Pharmacokinetics at a Glance", color=GREEN))
story.append(Spacer(1, 3*mm))

pk_data = [
    [TH("Drug"), TH("t½ (hours)"), TH("Therapeutic Level (µg/mL)"), TH("Protein Binding"), TH("Metabolism / Excretion"), TH("Special PK Notes")],
    [BTD("Phenytoin"),      TD("12–36"),  TD("10–20"),   TD("~90%"),  TDL("CYP2C9, 2C19\nLiver"),          TDL("NONLINEAR kinetics\n(zero-order at high doses)")],
    [BTD("Carbamazepine"),  TD("8–20\n(adult, after\nautoinduction)"), TD("4–12"), TD("75%"),TDL("CYP3A4 → active\nepoxide metabolite"),TDL("Autoinduction ↓ t½\nover first weeks")],
    [BTD("Valproate"),      TD("5–16"),   TD("50–100"),  TD("~90%"),  TDL("Liver (mitochondrial\n+ glucuronidation)"), TDL("Inhibits own + other\ndrug metabolism")],
    [BTD("Ethosuximide"),   TD("30–60"),  TD("40–100"),  TD("Minimal"),TDL("CYP3A4, liver"),               TDL("DOC for pure absence;\nlong t½ → once daily OK")],
    [BTD("Phenobarbital"),  TD("40–120"), TD("15–40"),   TD("~50%"),  TDL("CYP2C9, glucuronide,\nliver"),   TDL("Very long t½\n→ once daily dosing")],
    [BTD("Lamotrigine"),    TD("8–35\n(varies with\nco-meds)"),TD("2–7"), TD("55%"),  TDL("Glucuronidation (UGT);\nno active metabolites"), TDL("t½ ↑ with valproate;\nt½ ↓ with CBZ, PHT")],
    [BTD("Levetiracetam"),  TD("6–11"),   TD("12–46"),   TD("<10%"),  TDL("Minimal; 66% excreted\nunchanged in urine"),TDL("Dose reduce in CKD;\nno hepatic interactions")],
    [BTD("Gabapentin"),     TD("5–9"),    TD("Variable"), TD("<5%"),   TDL("Not metabolized;\nexcreted unchanged in urine"), TDL("Dose reduce in CKD;\nzero CYP interactions")],
    [BTD("Pregabalin"),     TD("6–7"),    TD("Variable"), TD("<5%"),   TDL("Not metabolized;\nexcreted unchanged in urine"), TDL("Dose reduce in CKD;\nschedule V (abuse risk)")],
    [BTD("Topiramate"),     TD("21"),     TD("Variable"), TD("~15%"),  TDL("~50% excreted\nunchanged in urine"),           TDL("Mild renal excretion;\nsome hepatic")],
]
pk_tbl = Table(pk_data, colWidths=[W*0.13, W*0.10, W*0.16, W*0.12, W*0.24, W*0.25])
pk_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),  (-1,0),  GREEN),
    ("TEXTCOLOR",     (0,0),  (-1,0),  WHITE),
    *[("BACKGROUND",  (0,i),  (-1,i),  LIGHT_GREEN if i%2==1 else GRAY_LIGHT) for i in range(1, len(pk_data))],
    ("GRID",          (0,0),  (-1,-1), 0.4, colors.white),
    ("TOPPADDING",    (0,0),  (-1,-1), 3),
    ("BOTTOMPADDING", (0,0),  (-1,-1), 3),
    ("LEFTPADDING",   (0,0),  (-1,-1), 4),
    ("RIGHTPADDING",  (0,0),  (-1,-1), 4),
    ("VALIGN",        (0,0),  (-1,-1), "TOP"),
    ("ALIGN",         (0,0),  (-1,0),  "CENTER"),
    ("ALIGN",         (0,1),  (1,-1),  "CENTER"),
    ("ALIGN",         (0,2),  (2,-1),  "CENTER"),
    ("ALIGN",         (0,3),  (3,-1),  "CENTER"),
]))
story.append(pk_tbl)
story.append(PageBreak())

# ════════════════════════════════════════════════════════════════════
# 8. HIGH-YIELD MNEMONICS & EXAM TIPS
# ════════════════════════════════════════════════════════════════════
story.append(section_header("8.  High-Yield Mnemonics & Exam Tips", color=colors.HexColor("#4A148C")))
story.append(Spacer(1, 3*mm))

mnemonic_data = [
    [TH("Drug / Topic"), TH("Mnemonic / Key Point")],
    [BTD("Phenytoin\nSide Effects"),
     TDL('"HAGG-SNOD"\nH = Hirsutism\nA = Ataxia / nystagmus\nG = Gingival hyperplasia\nG = Gait disturbance (ataxia)\nS = Stevens-Johnson\nN = Neuropathy (peripheral)\nO = Osteoporosis\nD = Diplopia / Drug interactions (CYP inducer)')],
    [BTD("Valproate\nSide Effects"),
     TDL('"PANTHER"\nP = Pancreatitis\nA = Alopecia\nN = Neural tube defects (teratogen #1)\nT = Tremor, Thrombocytopenia\nH = Hepatotoxicity\nE = Enzyme Inhibitor\nR = Rampant weight gain')],
    [BTD("Carbamazepine\nSide Effects"),
     TDL('"HAS" + SJS\nH = Hyponatremia\nA = Aplastic anemia\nS = Stevens-Johnson (check HLA-B*1502 in Asians!)\nAlso: autoinduces, teratogenic, worsens ABSENCE')],
    [BTD("GABA-A receptor:\nBZD vs Barbiturate"),
     TDL('BZD = B-F: increases FREQUENCY of Cl⁻ channel opening\nBarbiturate = B-D: increases DURATION of Cl⁻ channel opening\n(Remember: "BZD = F-requency; Barbiturate = D-uration")')],
    [BTD("AEDs that WORSEN\nAbsence Seizures"),
     TDL('"Can These Villains Go?" → CBZ, Tiagabine, Vigabatrin, GABApentin (and Phenytoin)\nAll Na⁺ channel blockers except Valproate + Lamotrigine can worsen absence')],
    [BTD("Enzyme INDUCERS\n(forget your OCP!)"),
     TDL('"PPCRBR" (Pile Pheno, Carba, Rifampin, Barb, Rifabutin)\nPhenytoin, Phenobarbital, Carbamazepine, Primidone = classic enzyme inducers\n→ Reduce OCP efficacy! Warn women of childbearing age')],
    [BTD("Status Epilepticus\nManagement Steps"),
     TDL('Step 1 (0–5 min): ABCs, IV access, glucose\nStep 2 (5–20 min): Lorazepam IV 0.1 mg/kg OR Diazepam IV\nStep 3 (20–40 min): Fosphenytoin IV OR Valproate IV OR Levetiracetam IV\nStep 4 (>40 min): Intubation + Midazolam / Propofol / Phenobarbital\nStep 5 (refractory): Pentobarbital coma, Ketamine, Isoflurane')],
    [BTD("Ethosuximide\nvs Valproate for Absence"),
     TDL('Pure absence only → Ethosuximide (T-Ca²⁺ channel only)\nAbsence + Tonic-clonic → Valproate (broad spectrum)\nIf valproate fails absence → add/switch to Lamotrigine')],
    [BTD("Phenytoin\nspecial facts"),
     TDL('• Fosphenytoin = prodrug → preferred for IV/IM use\n• Phenytoin SODIUM: NEVER IM → causes tissue necrosis\n• Nonlinear PK: small dose change → huge plasma level change\n• Zero-order kinetics at therapeutic doses')],
    [BTD("Levetiracetam\n'Keppra Rage'"),
     TDL('Behavioral effects: irritability, depression, psychosis\nAdd B6 (pyridoxine) supplementation may help\nMinimal drug interactions → useful in polypharmacy\nRenal dosing required in CKD')],
]

mn_tbl = Table(mnemonic_data, colWidths=[W*0.20, W*0.80])
mn_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),  (-1,0),  colors.HexColor("#4A148C")),
    ("TEXTCOLOR",     (0,0),  (-1,0),  WHITE),
    *[("BACKGROUND",  (0,i),  (-1,i),  YELLOW_BG if i%2==1 else GRAY_LIGHT) for i in range(1, len(mnemonic_data))],
    ("GRID",          (0,0),  (-1,-1), 0.4, colors.white),
    ("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), "TOP"),
    ("ALIGN",         (0,0),  (-1,0),  "CENTER"),
]))
story.append(mn_tbl)
story.append(Spacer(1, 5*mm))

# ════════════════════════════════════════════════════════════════════
# FOOTER
# ════════════════════════════════════════════════════════════════════
footer_data = [[P("Sources: Katzung's Basic & Clinical Pharmacology 16e | Lippincott Illustrated Reviews: Pharmacology | Adams & Victor's Principles of Neurology 12e | Barash Clinical Anesthesia 9e", note_style)]]
footer_tbl = Table(footer_data, colWidths=[W])
footer_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,-1), LIGHT_TEAL),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 8),
    ("ROUNDEDCORNERS",[4]),
]))
story.append(footer_tbl)

# ── Build PDF ──────────────────────────────────────────────────────
doc.build(story)
print(f"PDF created: {OUTPUT}")