#!/usr/bin/env python3
"""
ANS & Autacoids - Comprehensive Notes PDF Generator
Module 4.1: ANS AND AUTACOIDS (HomUG-Mod.Phar)
Topics: Cholinergic/Anticholinergic, Adrenergic/Antiadrenergic, 
        Serotonin/Autacoids, Histamine/Antihistaminic, Migraine
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.colors import (
    HexColor, white, black, red, blue, green, orange, purple,
    lightblue, lightyellow, lightgreen, Color
)
from reportlab.lib.units import cm, mm
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether, PageBreak
)
from reportlab.platypus.flowables import Flowable
from reportlab.graphics.shapes import (
    Drawing, Rect, String, Line, Polygon, Arrow, Circle, Ellipse,
    Group, Path
)
from reportlab.graphics import renderPDF
from reportlab.graphics.charts.barcharts import VerticalBarChart
import os

# ── Color Palette ──────────────────────────────────────────────────────────────
C_NAVY      = HexColor("#1A237E")
C_BLUE      = HexColor("#1565C0")
C_LIGHTBLUE = HexColor("#E3F2FD")
C_TEAL      = HexColor("#00695C")
C_TEAL_LT   = HexColor("#E0F2F1")
C_RED       = HexColor("#B71C1C")
C_RED_LT    = HexColor("#FFEBEE")
C_ORANGE    = HexColor("#E65100")
C_ORANGE_LT = HexColor("#FFF3E0")
C_PURPLE    = HexColor("#4A148C")
C_PURPLE_LT = HexColor("#F3E5F5")
C_GREEN     = HexColor("#1B5E20")
C_GREEN_LT  = HexColor("#E8F5E9")
C_YELLOW    = HexColor("#F57F17")
C_YELLOW_LT = HexColor("#FFFDE7")
C_GREY      = HexColor("#424242")
C_GREY_LT   = HexColor("#F5F5F5")
C_WHITE     = white

W, H = A4  # 595 x 842

# ── Styles ─────────────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

def make_style(name, parent="Normal", **kw):
    s = ParagraphStyle(name, parent=styles[parent], **kw)
    return s

TITLE_STYLE = make_style("TitlePage", fontSize=28, textColor=C_WHITE,
                         alignment=TA_CENTER, spaceAfter=8, fontName="Helvetica-Bold")
SUBTITLE_STYLE = make_style("SubtitlePage", fontSize=14, textColor=C_LIGHTBLUE,
                            alignment=TA_CENTER, spaceAfter=4, fontName="Helvetica")
H1 = make_style("H1", fontSize=17, textColor=C_WHITE, fontName="Helvetica-Bold",
                spaceAfter=6, spaceBefore=2, alignment=TA_CENTER)
H2 = make_style("H2", fontSize=13, textColor=C_NAVY, fontName="Helvetica-Bold",
                spaceAfter=4, spaceBefore=8)
H3 = make_style("H3", fontSize=11, textColor=C_BLUE, fontName="Helvetica-Bold",
                spaceAfter=3, spaceBefore=5)
BODY = make_style("Body", fontSize=9.5, textColor=C_GREY, spaceAfter=3,
                  leading=14, fontName="Helvetica")
BODY_BOLD = make_style("BodyBold", fontSize=9.5, textColor=black, fontName="Helvetica-Bold",
                       spaceAfter=2, leading=13)
SMALL = make_style("Small", fontSize=8.5, textColor=C_GREY, spaceAfter=2, leading=12)
EXAM_TIP = make_style("ExamTip", fontSize=9, textColor=C_RED, fontName="Helvetica-Bold",
                      spaceAfter=2, leading=13, leftIndent=6)
KEY_POINT = make_style("KeyPoint", fontSize=9.5, textColor=C_TEAL, fontName="Helvetica-BoldOblique",
                       spaceAfter=2, leading=13)
BULLET = make_style("Bullet", fontSize=9.5, textColor=C_GREY, spaceAfter=2, leading=13,
                    leftIndent=12, bulletIndent=4, fontName="Helvetica")
TABLE_HDR = make_style("TableHdr", fontSize=9, textColor=C_WHITE, fontName="Helvetica-Bold",
                       alignment=TA_CENTER)
TABLE_CELL = make_style("TableCell", fontSize=8.5, textColor=C_GREY, fontName="Helvetica",
                        alignment=TA_LEFT)
TABLE_CELL_C = make_style("TableCellC", fontSize=8.5, textColor=C_GREY, fontName="Helvetica",
                           alignment=TA_CENTER)
CENTER = make_style("Center", fontSize=9.5, textColor=C_GREY, alignment=TA_CENTER)

# ── Helper flowables ───────────────────────────────────────────────────────────
def sp(h=6): return Spacer(1, h)
def hr(color=C_BLUE, thickness=1): return HRFlowable(width="100%", thickness=thickness, color=color)

class ColorBox(Flowable):
    """Colored background rectangle with centered text."""
    def __init__(self, text, bg_color, text_color=C_WHITE, width=None, height=28, font="Helvetica-Bold", font_size=13):
        super().__init__()
        self.text = text
        self.bg_color = bg_color
        self.text_color = text_color
        self._width = width
        self._height = height
        self.font = font
        self.font_size = font_size

    def wrap(self, aw, ah):
        self.width = self._width or aw
        self.height = self._height
        return self.width, self.height

    def draw(self):
        c = self.canv
        c.setFillColor(self.bg_color)
        c.roundRect(0, 0, self.width, self.height, 6, fill=1, stroke=0)
        c.setFillColor(self.text_color)
        c.setFont(self.font, self.font_size)
        c.drawCentredString(self.width / 2, self.height / 2 - self.font_size / 3, self.text)

class SectionHeader(Flowable):
    """Gradient-like section header bar."""
    def __init__(self, text, bg=C_NAVY, sub="", icon=""):
        super().__init__()
        self.text = text
        self.bg = bg
        self.sub = sub
        self.icon = icon

    def wrap(self, aw, ah):
        self.width = aw
        self.height = 36 if not self.sub else 52
        return self.width, self.height

    def draw(self):
        c = self.canv
        c.setFillColor(self.bg)
        c.roundRect(0, 0, self.width, self.height, 8, fill=1, stroke=0)
        # Accent stripe
        c.setFillColor(HexColor("#FFFFFF30"))
        c.roundRect(self.width - 80, 4, 76, self.height - 8, 4, fill=1, stroke=0)
        c.setFillColor(C_WHITE)
        c.setFont("Helvetica-Bold", 14)
        y = self.height / 2 + (8 if self.sub else 0) - 5
        label = (self.icon + " " if self.icon else "") + self.text
        c.drawString(14, y, label)
        if self.sub:
            c.setFont("Helvetica", 9)
            c.setFillColor(HexColor("#BBDEFB"))
            c.drawString(14, y - 16, self.sub)


class DiagramFlowchart(Flowable):
    """Renders a vertical flowchart from a list of (text, color) tuples."""
    def __init__(self, steps, width=480, arrow=True):
        super().__init__()
        self.steps = steps
        self._w = width
        self.arrow = arrow
        self.box_h = 34
        self.gap = 18
        total = len(steps) * (self.box_h + self.gap) - self.gap
        self._h = total + 10

    def wrap(self, aw, ah):
        self.width = min(self._w, aw)
        return self.width, self._h

    def draw(self):
        c = self.canv
        bh = self.box_h
        gap = self.gap
        bw = self.width - 30
        x0 = 15
        y = self._h - bh - 5

        for i, (text, color) in enumerate(self.steps):
            # Box
            c.setFillColor(color)
            c.roundRect(x0, y, bw, bh, 7, fill=1, stroke=0)
            # Text
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 9)
            # Wrap long text
            lines = []
            words = text.split()
            line = ""
            for w in words:
                test = (line + " " + w).strip()
                if c.stringWidth(test, "Helvetica-Bold", 9) < bw - 16:
                    line = test
                else:
                    lines.append(line)
                    line = w
            if line:
                lines.append(line)
            total_text_h = len(lines) * 12
            ty = y + bh / 2 + total_text_h / 2 - 10
            for ln in lines:
                c.drawCentredString(x0 + bw / 2, ty, ln)
                ty -= 12
            # Arrow
            if self.arrow and i < len(self.steps) - 1:
                ax = x0 + bw / 2
                ay_top = y - 2
                ay_bot = y - gap + 2
                c.setStrokeColor(C_GREY)
                c.setFillColor(C_GREY)
                c.setLineWidth(1.5)
                c.line(ax, ay_top, ax, ay_bot + 6)
                # Arrowhead
                c.setLineWidth(0)
                p = c.beginPath()
                p.moveTo(ax, ay_bot)
                p.lineTo(ax - 5, ay_bot + 8)
                p.lineTo(ax + 5, ay_bot + 8)
                p.close()
                c.drawPath(p, fill=1, stroke=0)
            y -= bh + gap


class ANSNervesDiagram(Flowable):
    """Custom ANS division diagram."""
    def __init__(self, width=500):
        super().__init__()
        self._w = width
        self._h = 200

    def wrap(self, aw, ah):
        self.width = min(self._w, aw)
        self.height = self._h
        return self.width, self.height

    def draw(self):
        c = self.canv
        w = self.width
        h = self.height

        # CNS box
        c.setFillColor(C_NAVY)
        c.roundRect(w/2 - 70, h - 45, 140, 38, 6, fill=1, stroke=0)
        c.setFillColor(C_WHITE)
        c.setFont("Helvetica-Bold", 10)
        c.drawCentredString(w/2, h - 22, "CNS (Brain & Spinal Cord)")

        # Left branch: Parasympathetic
        c.setFillColor(C_TEAL)
        c.roundRect(20, h/2 - 15, 130, 32, 6, fill=1, stroke=0)
        c.setFillColor(C_WHITE)
        c.setFont("Helvetica-Bold", 9)
        c.drawCentredString(85, h/2 + 2, "PARASYMPATHETIC")
        c.setFont("Helvetica", 7.5)
        c.drawCentredString(85, h/2 - 9, "(Craniosacral)")

        # Right branch: Sympathetic
        c.setFillColor(C_RED)
        c.roundRect(w - 150, h/2 - 15, 130, 32, 6, fill=1, stroke=0)
        c.setFillColor(C_WHITE)
        c.setFont("Helvetica-Bold", 9)
        c.drawCentredString(w - 85, h/2 + 2, "SYMPATHETIC")
        c.setFont("Helvetica", 7.5)
        c.drawCentredString(w - 85, h/2 - 9, "(Thoracolumbar)")

        # Lines from CNS
        c.setStrokeColor(C_TEAL)
        c.setLineWidth(2)
        c.line(w/2 - 50, h - 45, 150, h/2 + 17)
        c.setStrokeColor(C_RED)
        c.line(w/2 + 50, h - 45, w - 150, h/2 + 17)

        # NT labels: Para -> ACh
        c.setFillColor(C_TEAL_LT)
        c.roundRect(15, 30, 140, 52, 5, fill=1, stroke=0)
        c.setFillColor(C_TEAL)
        c.setFont("Helvetica-Bold", 8.5)
        c.drawCentredString(85, 65, "Neurotransmitter:")
        c.setFont("Helvetica", 8.5)
        c.drawCentredString(85, 53, "Acetylcholine (ACh)")
        c.setFont("Helvetica-Bold", 8)
        c.setFillColor(C_TEAL)
        c.drawCentredString(85, 40, "Receptors: M1-M5 / N")

        # NT labels: Sym -> NE/Epi
        c.setFillColor(C_RED_LT)
        c.roundRect(w - 155, 30, 140, 52, 5, fill=1, stroke=0)
        c.setFillColor(C_RED)
        c.setFont("Helvetica-Bold", 8.5)
        c.drawCentredString(w - 85, 65, "Neurotransmitter:")
        c.setFont("Helvetica", 8.5)
        c.drawCentredString(w - 85, 53, "NE / Epinephrine")
        c.setFont("Helvetica-Bold", 8)
        c.drawCentredString(w - 85, 40, "Receptors: α1,α2 / β1,β2,β3")

        # Lines to NT boxes
        c.setStrokeColor(C_TEAL)
        c.setLineWidth(1.5)
        c.line(85, h/2 - 15, 85, 82)
        c.setStrokeColor(C_RED)
        c.line(w - 85, h/2 - 15, w - 85, 82)

        # "REST & DIGEST" vs "FIGHT OR FLIGHT"
        c.setFont("Helvetica-BoldOblique", 8)
        c.setFillColor(C_TEAL)
        c.drawCentredString(85, 20, '"Rest & Digest"')
        c.setFillColor(C_RED)
        c.drawCentredString(w - 85, 20, '"Fight or Flight"')


class ReceptorDiagram(Flowable):
    """Adrenergic receptors summary diagram."""
    def __init__(self, width=500):
        super().__init__()
        self._w = width
        self._h = 190

    def wrap(self, aw, ah):
        self.width = min(self._w, aw)
        self.height = self._h
        return self.width, self.height

    def draw(self):
        c = self.canv
        w = self.width

        # Title
        c.setFillColor(C_NAVY)
        c.roundRect(0, 165, w, 22, 4, fill=1, stroke=0)
        c.setFillColor(C_WHITE)
        c.setFont("Helvetica-Bold", 10)
        c.drawCentredString(w/2, 171, "ADRENERGIC RECEPTORS - Overview")

        # Alpha receptors
        items = [
            ("α1", "Vasoconstriction\nMydriasis\nUrinary retention", C_RED, 5),
            ("α2", "Presynaptic inhibition\nDecreased NE release", HexColor("#C62828"), 130),
            ("β1", "↑HR, ↑Contractility\nRenin release\n(Heart & Kidney)", C_BLUE, 255),
            ("β2", "Bronchodilation\nVasodilation\nUterine relaxation", HexColor("#1565C0"), 380),
        ]
        for label, desc, col, xpos in items:
            bw = 110
            c.setFillColor(col)
            c.roundRect(xpos, 95, bw, 32, 5, fill=1, stroke=0)
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 13)
            c.drawCentredString(xpos + bw/2, 110, label)

            c.setFillColor(HexColor("#F5F5F5"))
            c.roundRect(xpos, 5, bw, 86, 4, fill=1, stroke=0)
            c.setFillColor(C_GREY)
            c.setFont("Helvetica", 7.5)
            lines = desc.split("\n")
            ty = 75
            for ln in lines:
                c.drawCentredString(xpos + bw/2, ty, ln)
                ty -= 13

            # connect line
            c.setStrokeColor(col)
            c.setLineWidth(1.5)
            c.line(xpos + bw/2, 95, xpos + bw/2, 91)


class SerotoninPathway(Flowable):
    """Serotonin synthesis and action diagram."""
    def __init__(self, width=500):
        super().__init__()
        self._w = width
        self._h = 160

    def wrap(self, aw, ah):
        self.width = min(self._w, aw)
        self.height = self._h
        return self.width, self.height

    def draw(self):
        c = self.canv
        w = self.width

        steps = [
            ("Tryptophan\n(Diet)", w*0.1, 100),
            ("5-HTP", w*0.3, 100),
            ("Serotonin (5-HT)", w*0.55, 100),
            ("Releases into\nSynapse", w*0.8, 100),
        ]
        colors = [C_GREEN, C_TEAL, C_PURPLE, C_BLUE]
        for i, ((label, x, y), col) in enumerate(zip(steps, colors)):
            bw, bh = 95, 38
            c.setFillColor(col)
            c.roundRect(x - bw/2, y - bh/2, bw, bh, 6, fill=1, stroke=0)
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 8)
            lns = label.split("\n")
            ty = y + (len(lns)-1)*6
            for ln in lns:
                c.drawCentredString(x, ty, ln)
                ty -= 12
            # arrow
            if i < len(steps) - 1:
                nx = steps[i+1][1]
                ax1 = x + bw/2 + 2
                ax2 = nx - bw/2 - 2
                mid_y = y
                c.setStrokeColor(C_GREY)
                c.setFillColor(C_GREY)
                c.setLineWidth(1.5)
                c.line(ax1, mid_y, ax2, mid_y)
                p = c.beginPath()
                p.moveTo(ax2, mid_y)
                p.lineTo(ax2 - 7, mid_y + 4)
                p.lineTo(ax2 - 7, mid_y - 4)
                p.close()
                c.drawPath(p, fill=1, stroke=0)
            # enzyme label
            if i == 0:
                c.setFillColor(C_ORANGE)
                c.setFont("Helvetica-Oblique", 7.5)
                mid = (x + steps[1][1])/2
                c.drawCentredString(mid + 5, y + 26, "Tryptophan")
                c.drawCentredString(mid + 5, y + 16, "Hydroxylase")
            elif i == 1:
                c.setFillColor(C_ORANGE)
                c.setFont("Helvetica-Oblique", 7.5)
                mid = (x + steps[2][1])/2
                c.drawCentredString(mid, y + 26, "AADC")
                c.drawCentredString(mid, y + 16, "(Decarboxylase)")

        # Reuptake transporter
        c.setFillColor(C_RED_LT)
        c.roundRect(w*0.55 - 55, 20, 110, 50, 5, fill=1, stroke=0)
        c.setFillColor(C_RED)
        c.setFont("Helvetica-Bold", 8)
        c.drawCentredString(w*0.55, 55, "SERT (Reuptake)")
        c.setFont("Helvetica", 7.5)
        c.drawCentredString(w*0.55, 43, "Blocked by SSRIs/SNRIs")
        c.drawCentredString(w*0.55, 31, "→ ↑ synaptic 5-HT")

        # Arrow from synapse down to SERT
        c.setStrokeColor(C_RED)
        c.setLineWidth(1.2)
        c.line(w*0.55, 70, w*0.55, 79)


class MigrainePathway(Flowable):
    """Migraine pathophysiology flowchart."""
    def __init__(self, width=480):
        super().__init__()
        self._w = width
        self._h = 200

    def wrap(self, aw, ah):
        self.width = min(self._w, aw)
        self.height = self._h
        return self.width, self.height

    def draw(self):
        c = self.canv
        w = self.width

        boxes = [
            ("Trigger\n(Stress/Hormones/Food)", C_ORANGE, w/2, 183),
            ("Cortical Spreading\nDepression (CSD)", C_RED, w/2, 143),
            ("Trigeminal Nerve\nActivation", C_PURPLE, w/2, 103),
            ("CGRP + Substance P\nRelease", C_BLUE, w/2, 63),
            ("Neurogenic\nInflammation + PAIN", C_RED, w/2, 23),
        ]
        bw, bh = 180, 30
        for i, (label, col, x, y) in enumerate(boxes):
            c.setFillColor(col)
            c.roundRect(x - bw/2, y, bw, bh, 6, fill=1, stroke=0)
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 8)
            lns = label.split("\n")
            ty = y + bh/2 + (len(lns)-1)*5
            for ln in lns:
                c.drawCentredString(x, ty, ln)
                ty -= 11
            if i < len(boxes) - 1:
                ny = boxes[i+1][3] + bh
                c.setStrokeColor(C_GREY)
                c.setFillColor(C_GREY)
                c.setLineWidth(1.5)
                c.line(x, y, x, ny + 2)
                p = c.beginPath()
                p.moveTo(x, ny + 2)
                p.lineTo(x - 5, ny + 10)
                p.lineTo(x + 5, ny + 10)
                p.close()
                c.drawPath(p, fill=1, stroke=0)

        # Treatment annotation on right
        c.setFillColor(C_GREEN_LT)
        c.roundRect(w*0.62, 55, 130, 40, 5, fill=1, stroke=0)
        c.setFillColor(C_GREEN)
        c.setFont("Helvetica-Bold", 8)
        c.drawCentredString(w*0.62 + 65, 84, "CGRP Antagonists:")
        c.setFont("Helvetica", 7.5)
        c.drawCentredString(w*0.62 + 65, 73, "Erenumab, Rimegepant")
        c.drawCentredString(w*0.62 + 65, 62, "Triptans (5-HT1 agonists)")
        c.setStrokeColor(C_GREEN)
        c.setLineWidth(1)
        c.line(w/2 + bw/2, 78, w*0.62, 78)


# ── Build Document ─────────────────────────────────────────────────────────────
def build_pdf(output_path):
    doc = SimpleDocTemplate(
        output_path,
        pagesize=A4,
        rightMargin=1.8*cm, leftMargin=1.8*cm,
        topMargin=1.8*cm, bottomMargin=1.8*cm,
        title="ANS & Autacoids - Module 4.1 Notes",
        author="PharmNotes",
    )

    story = []

    # ══════════════════════════════════════════════════════════════
    # COVER PAGE
    # ══════════════════════════════════════════════════════════════
    class CoverPage(Flowable):
        def wrap(self, aw, ah):
            self.width = aw
            self.height = ah
            return aw, ah

        def draw(self):
            c = self.canv
            w, h = W - 3.6*cm, H - 3.6*cm
            # Background gradient bands
            bands = [
                (C_NAVY, h),
                (HexColor("#1A3A6E"), h*0.7),
                (HexColor("#1B4F8A"), h*0.4),
            ]
            c.setFillColor(C_NAVY)
            c.rect(0, 0, w, h, fill=1, stroke=0)
            # Top accent
            c.setFillColor(C_BLUE)
            c.roundRect(0, h - 10, w, 10, 0, fill=1, stroke=0)
            c.setFillColor(C_ORANGE)
            c.roundRect(0, h - 18, w, 8, 0, fill=1, stroke=0)

            # Module badge
            c.setFillColor(C_ORANGE)
            c.roundRect(w/2 - 90, h*0.78, 180, 34, 8, fill=1, stroke=0)
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 11)
            c.drawCentredString(w/2, h*0.78 + 20, "MODULE 4.1 | HomUG-Mod.Phar")
            c.setFont("Helvetica", 9)
            c.drawCentredString(w/2, h*0.78 + 8, "Pharmacology Notes")

            # Main title
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 30)
            c.drawCentredString(w/2, h*0.62, "ANS & AUTACOIDS")
            c.setFillColor(HexColor("#BBDEFB"))
            c.setFont("Helvetica", 14)
            c.drawCentredString(w/2, h*0.54, "Autonomic Nervous System Drugs")

            # Divider
            c.setStrokeColor(C_ORANGE)
            c.setLineWidth(2)
            c.line(w/2 - 120, h*0.51, w/2 + 120, h*0.51)

            # Topic chips
            topics = [
                ("Cholinergic", C_TEAL, 50, h*0.44),
                ("Anticholinergic", HexColor("#00897B"), 160, h*0.44),
                ("Adrenergic", C_RED, 285, h*0.44),
                ("Antiadrenergic", HexColor("#C62828"), 405, h*0.44),
                ("Serotonin", C_PURPLE, 90, h*0.36),
                ("Histamine", C_ORANGE, 210, h*0.36),
                ("Migraine", HexColor("#880E4F"), 330, h*0.36),
                ("Autacoids", HexColor("#1A237E"), 450, h*0.36),
            ]
            for label, col, x, y in topics:
                tw = c.stringWidth(label, "Helvetica-Bold", 8.5) + 14
                c.setFillColor(col)
                c.roundRect(x, y, tw, 18, 5, fill=1, stroke=0)
                c.setFillColor(C_WHITE)
                c.setFont("Helvetica-Bold", 8.5)
                c.drawCentredString(x + tw/2, y + 5, label)

            # Bottom info
            c.setFillColor(HexColor("#1565C0"))
            c.roundRect(0, 0, w, 60, 0, fill=1, stroke=0)
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 10)
            c.drawCentredString(w/2, 42, "Exam-Oriented Study Notes")
            c.setFont("Helvetica", 8.5)
            c.setFillColor(HexColor("#BBDEFB"))
            c.drawCentredString(w/2, 28, "Topics: 4.1.1 | 4.1.2 | 4.1.3 | 4.1.4")
            c.drawCentredString(w/2, 16, "Includes Diagrams | Flowcharts | Key Points | MCQ Tips")

    story.append(CoverPage())
    story.append(PageBreak())

    # ══════════════════════════════════════════════════════════════
    # TABLE OF CONTENTS
    # ══════════════════════════════════════════════════════════════
    story.append(SectionHeader("TABLE OF CONTENTS", C_NAVY, "Module 4.1 - ANS & Autacoids"))
    story.append(sp(10))
    toc_data = [
        [Paragraph("<b>Section</b>", TABLE_HDR), Paragraph("<b>Topic</b>", TABLE_HDR), Paragraph("<b>Page</b>", TABLE_HDR)],
        [Paragraph("4.1.1", TABLE_CELL_C), Paragraph("Cholinergic & Anticholinergic Drugs", TABLE_CELL), Paragraph("3", TABLE_CELL_C)],
        [Paragraph("4.1.2", TABLE_CELL_C), Paragraph("Adrenergic & Antiadrenergic Drugs", TABLE_CELL), Paragraph("5", TABLE_CELL_C)],
        [Paragraph("4.1.3", TABLE_CELL_C), Paragraph("Serotonin & Serotonergic Drugs (SSRIs, SNRIs, Triptans)", TABLE_CELL), Paragraph("8", TABLE_CELL_C)],
        [Paragraph("4.1.4", TABLE_CELL_C), Paragraph("Histamine & Antihistaminics", TABLE_CELL), Paragraph("10", TABLE_CELL_C)],
        [Paragraph("4.1.4", TABLE_CELL_C), Paragraph("Migraine - Pathophysiology & Treatment", TABLE_CELL), Paragraph("11", TABLE_CELL_C)],
        [Paragraph("—", TABLE_CELL_C), Paragraph("Exam Quick Reference & MCQ Tips", TABLE_CELL), Paragraph("13", TABLE_CELL_C)],
    ]
    toc_table = Table(toc_data, colWidths=[2*cm, 12*cm, 2*cm])
    toc_table.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_NAVY),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_LIGHTBLUE]),
        ("GRID", (0,0), (-1,-1), 0.5, HexColor("#BBDEFB")),
        ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"),
        ("FONTNAME", (0,1), (-1,-1), "Helvetica"),
        ("FONTSIZE", (0,0), (-1,-1), 9.5),
        ("ROWHEIGHT", (0,0), (-1,-1), 18),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROUNDEDCORNERS", [4,4,4,4]),
    ]))
    story.append(toc_table)
    story.append(PageBreak())

    # ══════════════════════════════════════════════════════════════
    # SECTION 1: ANS OVERVIEW
    # ══════════════════════════════════════════════════════════════
    story.append(SectionHeader("ANS OVERVIEW", C_NAVY, "Autonomic Nervous System - Foundation"))
    story.append(sp(8))
    story.append(Paragraph("The <b>Autonomic Nervous System (ANS)</b> is the involuntary division of the peripheral nervous system that regulates visceral functions. It is divided into two main divisions that often oppose each other.", BODY))
    story.append(sp(6))
    story.append(ANSNervesDiagram(width=W - 3.6*cm - 0))
    story.append(sp(8))

    ans_overview = [
        [Paragraph("<b>Feature</b>", TABLE_HDR), Paragraph("<b>Parasympathetic (PNS)</b>", TABLE_HDR), Paragraph("<b>Sympathetic (SNS)</b>", TABLE_HDR)],
        [Paragraph("Origin", BODY_BOLD), Paragraph("Craniosacral (CN III, VII, IX, X + S2-S4)", BODY), Paragraph("Thoracolumbar (T1-L2)", BODY)],
        [Paragraph("Neurotransmitter", BODY_BOLD), Paragraph("Acetylcholine (ACh) - all synapses", BODY), Paragraph("NE (postganglionic), ACh (ganglionic)", BODY)],
        [Paragraph("Receptors", BODY_BOLD), Paragraph("Muscarinic (M1-M5) + Nicotinic (Nm, Nn)", BODY), Paragraph("α1, α2, β1, β2, β3 adrenoceptors", BODY)],
        [Paragraph("Overall Effect", BODY_BOLD), Paragraph("Rest & Digest: ↓HR, ↑GI, constrict pupil", BODY), Paragraph("Fight or Flight: ↑HR, bronchodilate, ↑BP", BODY)],
        [Paragraph("Ganglia", BODY_BOLD), Paragraph("Terminal ganglia (near target organ)", BODY), Paragraph("Paravertebral ganglia (far from target)", BODY)],
    ]
    ans_table = Table(ans_overview, colWidths=[3.5*cm, 7.5*cm, 7.5*cm])
    ans_table.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_NAVY),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_GREY_LT]),
        ("GRID", (0,0), (-1,-1), 0.5, HexColor("#BBDEFB")),
        ("FONTSIZE", (0,0), (-1,-1), 8.5),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 16),
    ]))
    story.append(ans_table)
    story.append(PageBreak())

    # ══════════════════════════════════════════════════════════════
    # SECTION 2: CHOLINERGIC DRUGS (4.1.1)
    # ══════════════════════════════════════════════════════════════
    story.append(SectionHeader("4.1.1 - CHOLINERGIC DRUGS", C_TEAL, "Parasympathomimetics - Agonists & Indirect"))
    story.append(sp(6))

    story.append(Paragraph("Cholinergic drugs <b>mimic ACh</b> or enhance its activity. They activate muscarinic and/or nicotinic receptors.", BODY))
    story.append(sp(4))

    # Classification flowchart
    story.append(Paragraph("<b>Classification of Cholinergic Drugs</b>", H3))
    chol_steps = [
        ("CHOLINERGIC DRUGS (Parasympathomimetics)", C_TEAL),
        ("Direct-Acting: Bind directly to cholinergic receptors", HexColor("#00897B")),
        ("Muscarinic Agonists: Pilocarpine, Bethanechol, Carbachol, Muscarine", HexColor("#2E7D32")),
        ("Nicotinic Agonists: Nicotine, Succinylcholine (at NMJ)", HexColor("#388E3C")),
        ("Indirect-Acting: Inhibit AChE → ↑ ACh at synapse", HexColor("#1B5E20")),
        ("Reversible AChE Inhibitors: Neostigmine, Physostigmine, Pyridostigmine, Edrophonium", HexColor("#00695C")),
        ("Irreversible AChE Inhibitors (Organophosphates): Echothiophate, Malathion, Sarin", C_RED),
    ]
    story.append(DiagramFlowchart(chol_steps, width=W - 3.6*cm))
    story.append(sp(8))

    # Muscarinic Effects Table (SLUDGE)
    story.append(Paragraph("<b>Muscarinic Effects - SLUDGE Mnemonic</b>", H3))
    sludge_data = [
        [Paragraph("<b>Letter</b>", TABLE_HDR), Paragraph("<b>Effect</b>", TABLE_HDR), Paragraph("<b>System</b>", TABLE_HDR), Paragraph("<b>Clinical Use</b>", TABLE_HDR)],
        [Paragraph("S - Salivation", BODY_BOLD), Paragraph("↑ saliva secretion", BODY), Paragraph("Salivary glands", BODY), Paragraph("Dry mouth reversal", BODY)],
        [Paragraph("L - Lacrimation", BODY_BOLD), Paragraph("↑ tear production", BODY), Paragraph("Lacrimal glands", BODY), Paragraph("Dry eye conditions", BODY)],
        [Paragraph("U - Urination", BODY_BOLD), Paragraph("↑ bladder contraction", BODY), Paragraph("Urinary bladder", BODY), Paragraph("Urinary retention (Bethanechol)", BODY)],
        [Paragraph("D - Defecation", BODY_BOLD), Paragraph("↑ GI motility", BODY), Paragraph("GI tract", BODY), Paragraph("Paralytic ileus", BODY)],
        [Paragraph("G - GI cramps", BODY_BOLD), Paragraph("↑ peristalsis", BODY), Paragraph("Intestines", BODY), Paragraph("Constipation", BODY)],
        [Paragraph("E - Emesis", BODY_BOLD), Paragraph("↑ vomiting reflex", BODY), Paragraph("GI/CNS", BODY), Paragraph("Nausea side effect", BODY)],
    ]
    sludge_table = Table(sludge_data, colWidths=[3.5*cm, 4*cm, 4*cm, 5*cm])
    sludge_table.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_TEAL),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_TEAL_LT, C_WHITE]),
        ("GRID", (0,0), (-1,-1), 0.5, C_TEAL),
        ("FONTSIZE", (0,0), (-1,-1), 8.5),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 15),
    ]))
    story.append(sludge_table)
    story.append(sp(8))

    # Key drugs table
    story.append(Paragraph("<b>Key Cholinergic Drugs & Clinical Uses</b>", H3))
    chol_drugs = [
        [Paragraph("<b>Drug</b>", TABLE_HDR), Paragraph("<b>Class</b>", TABLE_HDR), Paragraph("<b>Mechanism</b>", TABLE_HDR), Paragraph("<b>Clinical Uses</b>", TABLE_HDR), Paragraph("<b>Key Side Effects</b>", TABLE_HDR)],
        [Paragraph("Pilocarpine", BODY_BOLD), Paragraph("Direct M-agonist", BODY), Paragraph("M3 agonist → miosis + ↑aqueous outflow", BODY), Paragraph("Glaucoma, Sjogren's", BODY), Paragraph("Sweating, bradycardia", BODY)],
        [Paragraph("Bethanechol", BODY_BOLD), Paragraph("Direct M-agonist", BODY), Paragraph("M3 agonist → bladder contraction", BODY), Paragraph("Urinary retention, Ileus", BODY), Paragraph("Diarrhea, cramps", BODY)],
        [Paragraph("Neostigmine", BODY_BOLD), Paragraph("Reversible AChEI", BODY), Paragraph("Inhibits AChE reversibly", BODY), Paragraph("Myasthenia gravis, NMJ reversal", BODY), Paragraph("SLUDGE effects", BODY)],
        [Paragraph("Pyridostigmine", BODY_BOLD), Paragraph("Reversible AChEI", BODY), Paragraph("Long-acting AChE inhibitor", BODY), Paragraph("Myasthenia gravis (preferred)", BODY), Paragraph("GI upset, bradycardia", BODY)],
        [Paragraph("Physostigmine", BODY_BOLD), Paragraph("Reversible AChEI", BODY), Paragraph("CNS-penetrating AChEI", BODY), Paragraph("Atropine OD, Glaucoma", BODY), Paragraph("Seizures in overdose", BODY)],
        [Paragraph("Donepezil", BODY_BOLD), Paragraph("Reversible AChEI", BODY), Paragraph("CNS-selective AChEI", BODY), Paragraph("Alzheimer's dementia", BODY), Paragraph("Nausea, insomnia", BODY)],
    ]
    ct = Table(chol_drugs, colWidths=[3*cm, 3*cm, 4.5*cm, 3.5*cm, 3*cm])
    ct.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_TEAL),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_TEAL_LT]),
        ("GRID", (0,0), (-1,-1), 0.4, C_TEAL),
        ("FONTSIZE", (0,0), (-1,-1), 8),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 18),
    ]))
    story.append(ct)
    story.append(sp(6))
    story.append(Paragraph("<b>★ EXAM TIP:</b> SLUDGE = Salivation, Lacrimation, Urination, Defecation, GI cramps, Emesis - all cholinergic toxicity signs!", EXAM_TIP))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Neostigmine cannot cross BBB; Physostigmine CAN cross BBB → used for CNS atropine toxicity.", EXAM_TIP))
    story.append(PageBreak())

    # ── ANTICHOLINERGIC DRUGS ──
    story.append(SectionHeader("4.1.1b - ANTICHOLINERGIC DRUGS", C_ORANGE, "Parasympatholytics - Muscarinic Antagonists"))
    story.append(sp(6))
    story.append(Paragraph("Anticholinergic drugs <b>block muscarinic receptors</b> (M1-M5), opposing parasympathetic effects. They produce the 'anti-SLUDGE' picture.", BODY))
    story.append(sp(4))

    # Anti-SLUDGE Mnemonic - visual
    story.append(Paragraph("<b>Anticholinergic Effects - 'Dry as a Bone' Mnemonic</b>", H3))
    mnemonic_data = [
        [Paragraph("<b>Mnemonic</b>", TABLE_HDR), Paragraph("<b>Effect</b>", TABLE_HDR), Paragraph("<b>Clinical Relevance</b>", TABLE_HDR)],
        [Paragraph("Dry as a Bone", BODY_BOLD), Paragraph("↓ secretions (dry mouth, dry skin, no sweating)", BODY), Paragraph("Heat intolerance, xerostomia", BODY)],
        [Paragraph("Red as a Beet", BODY_BOLD), Paragraph("Flushing (cutaneous vasodilation)", BODY), Paragraph("Atropine overdose sign", BODY)],
        [Paragraph("Hot as a Hare", BODY_BOLD), Paragraph("Hyperthermia (↓ sweating)", BODY), Paragraph("Dangerous in hot weather", BODY)],
        [Paragraph("Blind as a Bat", BODY_BOLD), Paragraph("Mydriasis + cycloplegia (blurred near vision)", BODY), Paragraph("Pre-op mydriasis, caution in glaucoma", BODY)],
        [Paragraph("Mad as a Hatter", BODY_BOLD), Paragraph("CNS excitation/confusion (esp. in elderly)", BODY), Paragraph("Delirium in geriatric patients", BODY)],
        [Paragraph("Full as a Flask", BODY_BOLD), Paragraph("Urinary retention", BODY), Paragraph("Caution in BPH patients", BODY)],
    ]
    mt = Table(mnemonic_data, colWidths=[4*cm, 6.5*cm, 6*cm])
    mt.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_ORANGE),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_ORANGE_LT, C_WHITE]),
        ("GRID", (0,0), (-1,-1), 0.4, C_ORANGE),
        ("FONTSIZE", (0,0), (-1,-1), 8.5),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 18),
    ]))
    story.append(mt)
    story.append(sp(8))

    story.append(Paragraph("<b>Key Anticholinergic Drugs</b>", H3))
    anti_drugs = [
        [Paragraph("<b>Drug</b>", TABLE_HDR), Paragraph("<b>Selectivity</b>", TABLE_HDR), Paragraph("<b>Clinical Uses</b>", TABLE_HDR), Paragraph("<b>Notes</b>", TABLE_HDR)],
        [Paragraph("Atropine", BODY_BOLD), Paragraph("Non-selective M-blocker", BODY), Paragraph("Bradycardia, Organophosphate poisoning, Pre-op", BODY), Paragraph("DOC for OP poisoning; crosses BBB", BODY)],
        [Paragraph("Scopolamine", BODY_BOLD), Paragraph("M1 preference", BODY), Paragraph("Motion sickness, post-op nausea", BODY), Paragraph("Transdermal patch; CNS depressant", BODY)],
        [Paragraph("Ipratropium", BODY_BOLD), Paragraph("M3 in airways", BODY), Paragraph("COPD, Asthma (bronchodilator)", BODY), Paragraph("Inhaled; minimal systemic effects", BODY)],
        [Paragraph("Tiotropium", BODY_BOLD), Paragraph("M1/M3 blocker", BODY), Paragraph("COPD (long-acting)", BODY), Paragraph("Once daily dosing; preferred in COPD", BODY)],
        [Paragraph("Benztropine", BODY_BOLD), Paragraph("M1 in CNS", BODY), Paragraph("Parkinson's disease", BODY), Paragraph("Reduces tremor; CNS penetrating", BODY)],
        [Paragraph("Oxybutynin", BODY_BOLD), Paragraph("M3 in bladder", BODY), Paragraph("Overactive bladder, urge incontinence", BODY), Paragraph("Dry mouth most common SE", BODY)],
    ]
    adt = Table(anti_drugs, colWidths=[3*cm, 3.5*cm, 5.5*cm, 5.5*cm])
    adt.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_ORANGE),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_ORANGE_LT]),
        ("GRID", (0,0), (-1,-1), 0.4, C_ORANGE),
        ("FONTSIZE", (0,0), (-1,-1), 8.5),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 18),
    ]))
    story.append(adt)
    story.append(sp(6))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Anticholinergic = anti-SLUDGE. Key differences: Ipratropium (inhaled for COPD) vs. Atropine (systemic). Scopolamine = motion sickness patch.", EXAM_TIP))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Contraindications: Angle-closure glaucoma, BPH, paralytic ileus, tachycardia.", EXAM_TIP))
    story.append(PageBreak())

    # ══════════════════════════════════════════════════════════════
    # SECTION 3: ADRENERGIC DRUGS (4.1.2)
    # ══════════════════════════════════════════════════════════════
    story.append(SectionHeader("4.1.2 - ADRENERGIC DRUGS", C_RED, "Sympathomimetics - Agonists & Mechanisms"))
    story.append(sp(6))
    story.append(Paragraph("Adrenergic drugs act on <b>adrenoceptors (α and β)</b>, mimicking or blocking SNS activity. They are classified by receptor selectivity.", BODY))
    story.append(sp(6))
    story.append(ReceptorDiagram(width=W - 3.6*cm))
    story.append(sp(8))

    story.append(Paragraph("<b>Classification of Adrenergic Agonists</b>", H3))
    adr_steps = [
        ("ADRENERGIC AGONISTS (Sympathomimetics)", C_RED),
        ("Direct-Acting: Bind directly to adrenoceptors", HexColor("#C62828")),
        ("Non-selective: Epinephrine (α+β), Norepinephrine (α1+α2+β1), Isoproterenol (β1+β2)", HexColor("#AD1457")),
        ("Alpha-selective: Phenylephrine (α1), Clonidine (α2)", HexColor("#6A1B9A")),
        ("Beta-selective: Salbutamol/Albuterol (β2), Dobutamine (β1), Metaproterenol (β2)", C_BLUE),
        ("Indirect-Acting: Stimulate NE release or block reuptake", HexColor("#37474F")),
        ("Amphetamine (NE release), Cocaine (reuptake blocker), Tyramine (NE release)", HexColor("#546E7A")),
        ("Mixed-Acting: Both direct & indirect", C_TEAL),
        ("Ephedrine, Pseudoephedrine (direct + NE release)", HexColor("#00695C")),
    ]
    story.append(DiagramFlowchart(adr_steps, width=W - 3.6*cm))
    story.append(sp(8))

    story.append(Paragraph("<b>Key Adrenergic Agonists - Clinical Uses</b>", H3))
    adr_drugs = [
        [Paragraph("<b>Drug</b>", TABLE_HDR), Paragraph("<b>Receptors</b>", TABLE_HDR), Paragraph("<b>Effects</b>", TABLE_HDR), Paragraph("<b>Clinical Uses</b>", TABLE_HDR)],
        [Paragraph("Epinephrine", BODY_BOLD), Paragraph("α1, α2, β1, β2", BODY), Paragraph("↑HR, bronchodilation, vasoconstriction", BODY), Paragraph("Anaphylaxis (DOC), Cardiac arrest, Asthma", BODY)],
        [Paragraph("Norepinephrine", BODY_BOLD), Paragraph("α1, α2, β1 (weak β2)", BODY), Paragraph("↑BP, reflex bradycardia, vasoconstriction", BODY), Paragraph("Septic shock, vasopressor", BODY)],
        [Paragraph("Dopamine", BODY_BOLD), Paragraph("D1, β1 (low dose), α1 (high dose)", BODY), Paragraph("Dose-dependent effects", BODY), Paragraph("Cardiogenic shock, acute HF, renal dose", BODY)],
        [Paragraph("Dobutamine", BODY_BOLD), Paragraph("β1 selective", BODY), Paragraph("↑Contractility (inotrope), ↑HR", BODY), Paragraph("Acute heart failure, cardiogenic shock", BODY)],
        [Paragraph("Salbutamol", BODY_BOLD), Paragraph("β2 selective", BODY), Paragraph("Bronchodilation, uterine relaxation", BODY), Paragraph("Asthma (DOC), COPD, Tocolysis", BODY)],
        [Paragraph("Phenylephrine", BODY_BOLD), Paragraph("α1 selective", BODY), Paragraph("Vasoconstriction, ↑BP, mydriasis", BODY), Paragraph("Nasal decongestant, hypotension, mydriasis", BODY)],
        [Paragraph("Clonidine", BODY_BOLD), Paragraph("α2 (CNS)", BODY), Paragraph("↓Sympathetic outflow, ↓BP, ↓HR", BODY), Paragraph("Hypertension, ADHD, opioid withdrawal", BODY)],
    ]
    adrt = Table(adr_drugs, colWidths=[3*cm, 3.5*cm, 5*cm, 5*cm])
    adrt.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_RED),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_RED_LT]),
        ("GRID", (0,0), (-1,-1), 0.4, HexColor("#EF9A9A")),
        ("FONTSIZE", (0,0), (-1,-1), 8),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 18),
    ]))
    story.append(adrt)
    story.append(sp(6))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Epinephrine = DOC for anaphylaxis. Dobutamine = inotrope (β1). Salbutamol = bronchodilator (β2). Phenylephrine = pure α1 agonist.", EXAM_TIP))
    story.append(Paragraph("<b>★ Dopamine Dose Rule:</b> Low dose (renal/D1), Medium dose (cardiac/β1), High dose (vasopressor/α1).", EXAM_TIP))
    story.append(PageBreak())

    # ── ANTIADRENERGIC DRUGS ──
    story.append(SectionHeader("4.1.2b - ANTIADRENERGIC DRUGS", HexColor("#880E4F"), "Alpha & Beta Blockers"))
    story.append(sp(6))
    story.append(Paragraph("Antiadrenergic drugs <b>block adrenoceptors</b> or reduce SNS outflow. They oppose sympathetic effects - reducing HR, BP, and cardiac output.", BODY))
    story.append(sp(4))

    story.append(Paragraph("<b>Alpha Blockers (α-antagonists)</b>", H3))
    alpha_data = [
        [Paragraph("<b>Drug</b>", TABLE_HDR), Paragraph("<b>Selectivity</b>", TABLE_HDR), Paragraph("<b>Uses</b>", TABLE_HDR), Paragraph("<b>Side Effects</b>", TABLE_HDR)],
        [Paragraph("Prazosin", BODY_BOLD), Paragraph("Selective α1", BODY), Paragraph("Hypertension, BPH", BODY), Paragraph("First-dose hypotension, dizziness", BODY)],
        [Paragraph("Tamsulosin", BODY_BOLD), Paragraph("Selective α1A (prostate)", BODY), Paragraph("BPH (preferred)", BODY), Paragraph("Retrograde ejaculation", BODY)],
        [Paragraph("Doxazosin", BODY_BOLD), Paragraph("Selective α1", BODY), Paragraph("Hypertension, BPH", BODY), Paragraph("Postural hypotension", BODY)],
        [Paragraph("Phentolamine", BODY_BOLD), Paragraph("Non-selective α1+α2", BODY), Paragraph("Pheochromocytoma (pre-op), HA crisis", BODY), Paragraph("Reflex tachycardia, nasal stuffiness", BODY)],
        [Paragraph("Phenoxybenzamine", BODY_BOLD), Paragraph("Irreversible α1+α2", BODY), Paragraph("Pheochromocytoma (long-term)", BODY), Paragraph("Prolonged hypotension", BODY)],
    ]
    at = Table(alpha_data, colWidths=[3.5*cm, 3.5*cm, 5.5*cm, 5*cm])
    at.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), HexColor("#880E4F")),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_PURPLE_LT]),
        ("GRID", (0,0), (-1,-1), 0.4, HexColor("#CE93D8")),
        ("FONTSIZE", (0,0), (-1,-1), 8.5),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 18),
    ]))
    story.append(at)
    story.append(sp(8))

    story.append(Paragraph("<b>Beta Blockers (β-antagonists) - Classified by Selectivity</b>", H3))
    beta_steps = [
        ("BETA BLOCKERS (Sympatholytics)", HexColor("#1A237E")),
        ("NON-SELECTIVE (β1 + β2): Propranolol, Timolol, Nadolol, Carvedilol (also α1)", HexColor("#283593")),
        ("SELECTIVE β1 (Cardioselective): Atenolol, Metoprolol, Bisoprolol, Esmolol, Nebivolol", C_BLUE),
        ("Mechanism: Compete with catecholamines at β receptors → ↓HR, ↓contractility, ↓BP", HexColor("#0277BD")),
        ("Clinical Uses: HTN, Angina, Post-MI, CHF, Arrhythmias, Thyrotoxicosis, Glaucoma (Timolol)", C_TEAL),
        ("Adverse Effects: Bradycardia, Hypotension, Fatigue, Bronchoconstriction (non-selective)", C_RED),
        ("CONTRAINDICATED in: Asthma, AV block, Acute decompensated heart failure, Prinzmetal angina", HexColor("#B71C1C")),
    ]
    story.append(DiagramFlowchart(beta_steps, width=W - 3.6*cm))
    story.append(sp(6))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Selective β1 blockers (Metoprolol, Atenolol) are safer in asthma patients. Carvedilol = α1+β - used in heart failure. Propranolol = prototype non-selective β blocker.", EXAM_TIP))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Non-selective β blockers are CONTRAINDICATED in asthma (block β2 → bronchoconstriction).", EXAM_TIP))
    story.append(PageBreak())

    # ══════════════════════════════════════════════════════════════
    # SECTION 4: SEROTONIN & SEROTONERGIC DRUGS (4.1.3)
    # ══════════════════════════════════════════════════════════════
    story.append(SectionHeader("4.1.3 - SEROTONIN & SEROTONERGIC DRUGS", C_PURPLE, "SSRIs, SNRIs, Triptans & Modulators"))
    story.append(sp(6))
    story.append(Paragraph("Serotonin (5-Hydroxytryptamine, <b>5-HT</b>) is a monoamine neurotransmitter synthesized from tryptophan. It acts in both CNS (mood, sleep, appetite) and periphery (GI motility, platelet aggregation).", BODY))
    story.append(sp(4))
    story.append(Paragraph("<b>Serotonin Synthesis & Reuptake Pathway</b>", H3))
    story.append(SerotoninPathway(width=W - 3.6*cm))
    story.append(sp(8))

    story.append(Paragraph("<b>Classification of Serotonergic Drugs</b>", H3))
    sero_class = [
        [Paragraph("<b>Class</b>", TABLE_HDR), Paragraph("<b>Drugs</b>", TABLE_HDR), Paragraph("<b>Mechanism</b>", TABLE_HDR), Paragraph("<b>Clinical Use</b>", TABLE_HDR)],
        [Paragraph("SSRIs", BODY_BOLD), Paragraph("Fluoxetine, Sertraline, Paroxetine, Escitalopram, Citalopram", BODY), Paragraph("Block SERT → ↑ synaptic 5-HT", BODY), Paragraph("Depression, OCD, Panic disorder, PTSD, Social anxiety", BODY)],
        [Paragraph("SNRIs", BODY_BOLD), Paragraph("Venlafaxine, Duloxetine, Desvenlafaxine", BODY), Paragraph("Block SERT + NET → ↑5-HT + ↑NE", BODY), Paragraph("Depression, GAD, Neuropathic pain, Fibromyalgia", BODY)],
        [Paragraph("5-HT1 Agonists (Triptans)", BODY_BOLD), Paragraph("Sumatriptan, Rizatriptan, Zolmitriptan, Almotriptan", BODY), Paragraph("5-HT1B/1D agonism → vasoconstriction + inhibit CGRP release", BODY), Paragraph("Acute migraine, Cluster headache", BODY)],
        [Paragraph("5-HT3 Antagonists", BODY_BOLD), Paragraph("Ondansetron, Granisetron, Palonosetron", BODY), Paragraph("Block 5-HT3 in CTZ and vagal afferents", BODY), Paragraph("Chemotherapy-induced N&V, post-op nausea", BODY)],
        [Paragraph("5-HT4 Agonists", BODY_BOLD), Paragraph("Metoclopramide (partial), Mosapride, Tegaserod", BODY), Paragraph("5-HT4 agonism → ↑GI motility/peristalsis", BODY), Paragraph("GERD, IBS-C, gastroparesis", BODY)],
        [Paragraph("Serotonin Modulators", BODY_BOLD), Paragraph("Buspirone, Mirtazapine, Trazodone, Vilazodone", BODY), Paragraph("Mixed 5-HT agonist/antagonist + reuptake block", BODY), Paragraph("Anxiety, Depression (with sleep disturbance)", BODY)],
    ]
    st = Table(sero_class, colWidths=[3*cm, 4*cm, 5*cm, 4.5*cm])
    st.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_PURPLE),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_PURPLE_LT]),
        ("GRID", (0,0), (-1,-1), 0.4, HexColor("#CE93D8")),
        ("FONTSIZE", (0,0), (-1,-1), 8),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 22),
    ]))
    story.append(st)
    story.append(sp(6))
    story.append(Paragraph("<b>★ EXAM TIP:</b> SSRIs are FIRST-LINE for depression, OCD, anxiety disorders. Take 2-6 weeks for full effect. Risk: Serotonin syndrome (hyperthermia, hypertension, myoclonus, confusion).", EXAM_TIP))
    story.append(Paragraph("<b>★ Serotonin Syndrome Triad:</b> (1) Altered mental status, (2) Autonomic instability, (3) Neuromuscular abnormalities. Treat with Cyproheptadine (5-HT antagonist).", EXAM_TIP))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Triptans contraindicated in: Ischemic heart disease, uncontrolled HTN, basilar/hemiplegic migraine, pregnancy (relative).", EXAM_TIP))
    story.append(PageBreak())

    # ══════════════════════════════════════════════════════════════
    # SECTION 5: HISTAMINE & ANTIHISTAMINICS (4.1.4)
    # ══════════════════════════════════════════════════════════════
    story.append(SectionHeader("4.1.4 - HISTAMINE & ANTIHISTAMINICS", C_YELLOW, "H1, H2 Receptors & Drug Classification"))
    story.append(sp(6))
    story.append(Paragraph("Histamine is an autacoid stored in mast cells and basophils. It plays roles in allergic reactions, gastric acid secretion, neurotransmission, and immune responses.", BODY))
    story.append(sp(4))

    hist_class = [
        [Paragraph("<b>Receptor</b>", TABLE_HDR), Paragraph("<b>Location</b>", TABLE_HDR), Paragraph("<b>Effects when activated</b>", TABLE_HDR), Paragraph("<b>Blocked by</b>", TABLE_HDR)],
        [Paragraph("H1", BODY_BOLD), Paragraph("Smooth muscle, endothelium, CNS", BODY), Paragraph("Bronchoconstriction, vasodilation, itch, pain, allergy symptoms", BODY), Paragraph("H1 antihistamines (1st & 2nd gen)", BODY)],
        [Paragraph("H2", BODY_BOLD), Paragraph("Gastric parietal cells, heart", BODY), Paragraph("↑ Gastric acid secretion, ↑ HR", BODY), Paragraph("H2 blockers (Ranitidine, Famotidine)", BODY)],
        [Paragraph("H3", BODY_BOLD), Paragraph("Presynaptic CNS neurons", BODY), Paragraph("Inhibit histamine release (autoreceptor), modulate CNS NT", BODY), Paragraph("Pitolisant (narcolepsy)", BODY)],
        [Paragraph("H4", BODY_BOLD), Paragraph("Immune cells, GI tract", BODY), Paragraph("Immune modulation, eosinophil chemotaxis", BODY), Paragraph("Research / investigational agents", BODY)],
    ]
    ht = Table(hist_class, colWidths=[2*cm, 4*cm, 5.5*cm, 5*cm])
    ht.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_YELLOW),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_YELLOW_LT, C_WHITE]),
        ("GRID", (0,0), (-1,-1), 0.4, C_YELLOW),
        ("FONTSIZE", (0,0), (-1,-1), 8.5),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 20),
    ]))
    story.append(ht)
    story.append(sp(8))

    story.append(Paragraph("<b>Antihistaminic Drugs - Classification</b>", H3))
    anti_hist = [
        [Paragraph("<b>Generation</b>", TABLE_HDR), Paragraph("<b>Drugs</b>", TABLE_HDR), Paragraph("<b>Properties</b>", TABLE_HDR), Paragraph("<b>Clinical Uses</b>", TABLE_HDR)],
        [Paragraph("1st Generation\n(Sedating)", BODY_BOLD), Paragraph("Diphenhydramine\nChlorpheniramine\nPromethazine\nCyproheptadine\nHydroxyzine", BODY), Paragraph("- Cross BBB → sedation\n- Anticholinergic effects\n- Short duration (4-6h)", BODY), Paragraph("Allergic rhinitis, Urticaria, Anaphylaxis (adjunct), Motion sickness, Sleep aid, Cold/flu", BODY)],
        [Paragraph("2nd Generation\n(Non-sedating)", BODY_BOLD), Paragraph("Cetirizine\nFexofenadine\nLoratadine\nBilastine\nAzelastine", BODY), Paragraph("- Poor BBB penetration\n- No anticholinergic effects\n- Long duration (12-24h)\n- Preferred clinically", BODY), Paragraph("Allergic rhinitis (preferred), Urticaria (chronic), Hay fever, Allergic conjunctivitis", BODY)],
        [Paragraph("H2 Blockers\n(Gastric)", BODY_BOLD), Paragraph("Ranitidine\nFamotidine\nCimetidine\nNizatidine", BODY), Paragraph("- Block H2 → ↓gastric acid\n- No H1 activity\n- Cimetidine: multiple DDI", BODY), Paragraph("Peptic ulcer, GERD, Zollinger-Ellison, Upper GI bleeding", BODY)],
    ]
    aht = Table(anti_hist, colWidths=[3*cm, 3.5*cm, 5*cm, 5*cm])
    aht.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_YELLOW),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_YELLOW_LT]),
        ("GRID", (0,0), (-1,-1), 0.4, C_YELLOW),
        ("FONTSIZE", (0,0), (-1,-1), 8),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 60),
    ]))
    story.append(aht)
    story.append(sp(6))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Diphenhydramine = 1st gen, sedating, anticholinergic. Fexofenadine = 2nd gen, non-sedating, preferred. Cyproheptadine = also used in Serotonin syndrome + appetite stimulant.", EXAM_TIP))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Cimetidine inhibits CYP450 → multiple drug interactions. Famotidine has fewest drug interactions among H2 blockers.", EXAM_TIP))
    story.append(PageBreak())

    # ══════════════════════════════════════════════════════════════
    # SECTION 6: MIGRAINE (4.1.4)
    # ══════════════════════════════════════════════════════════════
    story.append(SectionHeader("MIGRAINE - Pathophysiology & Treatment", HexColor("#880E4F"), "Acute & Preventive Therapies | CGRP | Triptans"))
    story.append(sp(6))
    story.append(Paragraph("<b>Pathophysiology of Migraine</b>", H3))
    story.append(Paragraph("Migraine is a <b>neurovascular disorder</b> involving abnormal activation of the trigeminovascular system, cortical spreading depression, and release of neuropeptides (CGRP, Substance P).", BODY))
    story.append(sp(6))

    # Two-column layout: Flowchart + Types
    class TwoColumnFlowable(Flowable):
        def __init__(self, left_items, right_items, col_width, height, left_title, right_title):
            super().__init__()
            self._cw = col_width
            self._h = height
            self.left_items = left_items
            self.right_items = right_items
            self.lt = left_title
            self.rt = right_title

        def wrap(self, aw, ah):
            self.width = aw
            self.height = self._h
            return aw, self._h

        def draw(self):
            c = self.canv
            w = self.width
            mid = w / 2 - 5

            # Left panel
            c.setFillColor(HexColor("#FCE4EC"))
            c.roundRect(0, 0, mid, self._h, 6, fill=1, stroke=0)
            c.setFillColor(HexColor("#880E4F"))
            c.roundRect(0, self._h - 24, mid, 24, 6, fill=1, stroke=0)
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 9)
            c.drawCentredString(mid/2, self._h - 10, self.lt)

            for i, (label, detail) in enumerate(self.left_items):
                y = self._h - 40 - i * 28
                c.setFillColor(HexColor("#880E4F"))
                c.roundRect(8, y, mid - 16, 22, 3, fill=1, stroke=0)
                c.setFillColor(C_WHITE)
                c.setFont("Helvetica-Bold", 8)
                c.drawString(16, y + 12, label)
                c.setFont("Helvetica", 7.5)
                c.drawString(16, y + 3, detail)

            # Right panel
            c.setFillColor(HexColor("#E8F5E9"))
            c.roundRect(mid + 10, 0, w - mid - 10, self._h, 6, fill=1, stroke=0)
            c.setFillColor(C_GREEN)
            c.roundRect(mid + 10, self._h - 24, w - mid - 10, 24, 6, fill=1, stroke=0)
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 9)
            c.drawCentredString(mid + 10 + (w - mid - 10)/2, self._h - 10, self.rt)

            for i, (label, detail) in enumerate(self.right_items):
                y = self._h - 40 - i * 28
                c.setFillColor(C_GREEN)
                c.roundRect(mid + 18, y, w - mid - 26, 22, 3, fill=1, stroke=0)
                c.setFillColor(C_WHITE)
                c.setFont("Helvetica-Bold", 8)
                c.drawString(mid + 26, y + 12, label)
                c.setFont("Helvetica", 7.5)
                c.drawString(mid + 26, y + 3, detail)

    migraine_types = [
        ("Migraine with Aura", "Visual/sensory/motor symptoms 20-60 min before headache"),
        ("Migraine without Aura", "No prodromal neurological symptoms; most common type"),
        ("Chronic Migraine", "≥15 headache days/month for >3 months"),
        ("Basilar Migraine", "Brainstem aura; diplopia, vertigo, dysarthria"),
        ("Hemiplegic Migraine", "Motor weakness; CACNA1A/ATP1A2 gene mutations"),
    ]
    migraine_triggers = [
        ("Hormonal", "Estrogen fluctuations, menstruation, OCPs"),
        ("Dietary", "Tyramine, alcohol, caffeine withdrawal, MSG"),
        ("Environmental", "Bright lights, strong odors, weather changes"),
        ("Stress", "Emotional stress, sleep deprivation, fatigue"),
        ("Pharmacological", "Analgesic overuse (MOH), nitrates, vasodilators"),
    ]
    story.append(TwoColumnFlowable(migraine_types, migraine_triggers, 
                                    W/2, 180, "MIGRAINE TYPES", "COMMON TRIGGERS"))
    story.append(sp(8))

    story.append(Paragraph("<b>Migraine Pathophysiology Flowchart</b>", H3))
    story.append(MigrainePathway(width=W - 3.6*cm))
    story.append(sp(8))

    story.append(Paragraph("<b>Treatment of Migraine - Acute vs. Preventive</b>", H3))
    migraine_tx = [
        [Paragraph("<b>Category</b>", TABLE_HDR), Paragraph("<b>Drug Class</b>", TABLE_HDR), Paragraph("<b>Drugs</b>", TABLE_HDR), Paragraph("<b>Mechanism</b>", TABLE_HDR)],
        [Paragraph("ACUTE\nTreatment", BODY_BOLD), Paragraph("Triptans (DOC for moderate-severe)", BODY), Paragraph("Sumatriptan, Rizatriptan, Zolmitriptan, Eletriptan", BODY), Paragraph("5-HT1B/1D agonist → vasoconstriction, ↓CGRP", BODY)],
        [Paragraph("ACUTE", BODY_BOLD), Paragraph("NSAIDs (mild-moderate)", BODY), Paragraph("Ibuprofen, Naproxen, Aspirin, Diclofenac", BODY), Paragraph("COX inhibition → ↓prostaglandins", BODY)],
        [Paragraph("ACUTE", BODY_BOLD), Paragraph("Ergot Alkaloids", BODY), Paragraph("Ergotamine, Dihydroergotamine (DHE)", BODY), Paragraph("Vasoconstriction via α+5-HT agonism", BODY)],
        [Paragraph("ACUTE", BODY_BOLD), Paragraph("Anti-emetics", BODY), Paragraph("Metoclopramide, Prochlorperazine, Ondansetron", BODY), Paragraph("Reduce nausea; improve absorption of analgesics", BODY)],
        [Paragraph("ACUTE", BODY_BOLD), Paragraph("Gepants (new)", BODY), Paragraph("Rimegepant, Ubrogepant, Atogepant", BODY), Paragraph("CGRP receptor antagonists - safe in CVD", BODY)],
        [Paragraph("PREVENTIVE\n(Prophylaxis)", BODY_BOLD), Paragraph("Beta Blockers (DOC)", BODY), Paragraph("Propranolol, Metoprolol, Timolol", BODY), Paragraph("Stabilize neuronal membranes", BODY)],
        [Paragraph("PREVENTIVE", BODY_BOLD), Paragraph("Anticonvulsants", BODY), Paragraph("Topiramate (preferred), Valproate, Gabapentin", BODY), Paragraph("↓cortical excitability", BODY)],
        [Paragraph("PREVENTIVE", BODY_BOLD), Paragraph("TCAs", BODY), Paragraph("Amitriptyline (most used)", BODY), Paragraph("Inhibit 5-HT/NE reuptake; also anticholinergic", BODY)],
        [Paragraph("PREVENTIVE", BODY_BOLD), Paragraph("Ca²⁺ Channel Blockers", BODY), Paragraph("Flunarizine, Verapamil (cluster HA)", BODY), Paragraph("Block CSD, vasodilation", BODY)],
        [Paragraph("PREVENTIVE", BODY_BOLD), Paragraph("Anti-CGRP MAbs", BODY), Paragraph("Erenumab, Fremanezumab, Galcanezumab", BODY), Paragraph("Monthly SC injection; bind CGRP ligand/receptor", BODY)],
        [Paragraph("PREVENTIVE", BODY_BOLD), Paragraph("Botulinum Toxin A", BODY), Paragraph("OnabotulinumtoxinA (Botox)", BODY), Paragraph("Chronic migraine only; every 12 weeks", BODY)],
    ]
    mtt = Table(migraine_tx, colWidths=[2.5*cm, 4*cm, 4.5*cm, 5.5*cm])
    mtt.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), HexColor("#880E4F")),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, HexColor("#FCE4EC")]),
        ("GRID", (0,0), (-1,-1), 0.4, HexColor("#F48FB1")),
        ("FONTSIZE", (0,0), (-1,-1), 8),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 22),
        ("SPAN", (0,1), (0,5)),  # Acute spans
    ]))
    story.append(mtt)
    story.append(sp(6))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Propranolol = DOC for migraine prevention. Sumatriptan = DOC for acute moderate-severe migraine. Topiramate = preferred anticonvulsant for prevention (weight loss as SE).", EXAM_TIP))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Ergotamine is CONTRAINDICATED in: pregnancy, vascular disease, liver/kidney disease, sepsis. It causes ergotism.", EXAM_TIP))
    story.append(Paragraph("<b>★ EXAM TIP:</b> Anti-CGRP monoclonal antibodies (erenumab) are new class - first to target migraine pathophysiology directly.", EXAM_TIP))
    story.append(PageBreak())

    # ══════════════════════════════════════════════════════════════
    # SECTION 7: QUICK REFERENCE & EXAM TIPS
    # ══════════════════════════════════════════════════════════════
    story.append(SectionHeader("EXAM QUICK REFERENCE", C_NAVY, "High-Yield MCQ Facts | Key Comparisons"))
    story.append(sp(6))

    story.append(Paragraph("<b>DOC (Drug of Choice) Summary</b>", H3))
    doc_data = [
        [Paragraph("<b>Condition</b>", TABLE_HDR), Paragraph("<b>Drug of Choice</b>", TABLE_HDR), Paragraph("<b>Drug Class</b>", TABLE_HDR)],
        [Paragraph("Anaphylaxis", BODY_BOLD), Paragraph("Epinephrine (IM)", BODY), Paragraph("Non-selective adrenergic agonist", BODY)],
        [Paragraph("Myasthenia Gravis", BODY_BOLD), Paragraph("Pyridostigmine", BODY), Paragraph("Reversible AChE inhibitor", BODY)],
        [Paragraph("Glaucoma (acute)", BODY_BOLD), Paragraph("Pilocarpine", BODY), Paragraph("Muscarinic agonist (M3)", BODY)],
        [Paragraph("Organophosphate poisoning", BODY_BOLD), Paragraph("Atropine + Pralidoxime", BODY), Paragraph("Muscarinic antagonist + AChE reactivator", BODY)],
        [Paragraph("Acute migraine (mod-severe)", BODY_BOLD), Paragraph("Sumatriptan", BODY), Paragraph("5-HT1B/1D agonist (Triptan)", BODY)],
        [Paragraph("Migraine prevention", BODY_BOLD), Paragraph("Propranolol", BODY), Paragraph("Non-selective β blocker", BODY)],
        [Paragraph("Allergic rhinitis (preferred)", BODY_BOLD), Paragraph("Cetirizine / Fexofenadine", BODY), Paragraph("2nd generation H1 antihistamine", BODY)],
        [Paragraph("Motion sickness", BODY_BOLD), Paragraph("Scopolamine (patch)", BODY), Paragraph("Anticholinergic (M1 blocker)", BODY)],
        [Paragraph("Bronchospasm in COPD", BODY_BOLD), Paragraph("Ipratropium / Tiotropium", BODY), Paragraph("Anticholinergic (M3 blocker, inhaled)", BODY)],
        [Paragraph("Asthma (acute)", BODY_BOLD), Paragraph("Salbutamol (Albuterol)", BODY), Paragraph("Selective β2 agonist", BODY)],
        [Paragraph("Septic shock", BODY_BOLD), Paragraph("Norepinephrine", BODY), Paragraph("α1, α2, β1 adrenergic agonist", BODY)],
        [Paragraph("Depression (1st line)", BODY_BOLD), Paragraph("SSRIs (e.g. Fluoxetine)", BODY), Paragraph("Serotonin reuptake inhibitor", BODY)],
        [Paragraph("Chemotherapy-induced nausea", BODY_BOLD), Paragraph("Ondansetron", BODY), Paragraph("5-HT3 antagonist", BODY)],
        [Paragraph("BPH (enlarged prostate)", BODY_BOLD), Paragraph("Tamsulosin", BODY), Paragraph("Selective α1A blocker", BODY)],
    ]
    doct = Table(doc_data, colWidths=[5*cm, 5*cm, 6.5*cm])
    doct.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_NAVY),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_LIGHTBLUE]),
        ("GRID", (0,0), (-1,-1), 0.4, HexColor("#BBDEFB")),
        ("FONTSIZE", (0,0), (-1,-1), 8.5),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 16),
    ]))
    story.append(doct)
    story.append(sp(8))

    story.append(Paragraph("<b>Critical Comparisons (High-Yield for MCQs)</b>", H3))
    compare = [
        [Paragraph("<b>Topic</b>", TABLE_HDR), Paragraph("<b>Drug A</b>", TABLE_HDR), Paragraph("<b>Drug B</b>", TABLE_HDR), Paragraph("<b>Key Difference</b>", TABLE_HDR)],
        [Paragraph("AChE Inhibitors", BODY_BOLD), Paragraph("Neostigmine", BODY), Paragraph("Physostigmine", BODY), Paragraph("Neostigmine: No BBB penetration. Physostigmine: Crosses BBB (CNS use)", BODY)],
        [Paragraph("Beta Blockers", BODY_BOLD), Paragraph("Propranolol", BODY), Paragraph("Atenolol/Metoprolol", BODY), Paragraph("Propranolol: non-selective (avoid in asthma). Atenolol: β1 selective, safer in asthma", BODY)],
        [Paragraph("Antihistamines", BODY_BOLD), Paragraph("Diphenhydramine (1st)", BODY), Paragraph("Fexofenadine (2nd)", BODY), Paragraph("1st gen: sedating, anticholinergic; 2nd gen: non-sedating, preferred in daytime", BODY)],
        [Paragraph("Triptans vs Ergots", BODY_BOLD), Paragraph("Sumatriptan", BODY), Paragraph("Ergotamine", BODY), Paragraph("Triptans: selective 5-HT1B/1D, fewer SE. Ergots: non-selective, more SE, more contraindications", BODY)],
        [Paragraph("Cholinomimetics", BODY_BOLD), Paragraph("Direct (Pilocarpine)", BODY), Paragraph("Indirect (Neostigmine)", BODY), Paragraph("Direct: bind receptor. Indirect: inhibit AChE to increase ACh availability", BODY)],
        [Paragraph("SSRIs vs SNRIs", BODY_BOLD), Paragraph("Fluoxetine (SSRI)", BODY), Paragraph("Venlafaxine (SNRI)", BODY), Paragraph("SSRIs: only 5-HT reuptake. SNRIs: 5-HT + NE reuptake; better for pain syndromes", BODY)],
        [Paragraph("α1 vs α2", BODY_BOLD), Paragraph("Phenylephrine (α1)", BODY), Paragraph("Clonidine (α2)", BODY), Paragraph("α1 agonist: vasoconstriction, ↑BP. α2 agonist: ↓NE release, ↓BP (central action)", BODY)],
    ]
    ct2 = Table(compare, colWidths=[3*cm, 3*cm, 3.5*cm, 7*cm])
    ct2.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_NAVY),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_LIGHTBLUE]),
        ("GRID", (0,0), (-1,-1), 0.4, HexColor("#BBDEFB")),
        ("FONTSIZE", (0,0), (-1,-1), 8),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 22),
    ]))
    story.append(ct2)
    story.append(PageBreak())

    # ── CONTRAINDICATIONS TABLE ──
    story.append(SectionHeader("CONTRAINDICATIONS & ADVERSE EFFECTS", C_RED, "High-Risk Combinations | Must-Know Safety Profiles"))
    story.append(sp(6))
    ci_data = [
        [Paragraph("<b>Drug/Class</b>", TABLE_HDR), Paragraph("<b>Contraindications</b>", TABLE_HDR), Paragraph("<b>Notable Adverse Effects</b>", TABLE_HDR)],
        [Paragraph("Non-selective β blockers\n(Propranolol)", BODY_BOLD), Paragraph("Asthma/COPD, AV block, Decompensated HF, Prinzmetal angina, IDDM", BODY), Paragraph("Bradycardia, Hypotension, Fatigue, Bronchoconstriction, Masks hypoglycemia", BODY)],
        [Paragraph("Anticholinergics\n(Atropine, etc.)", BODY_BOLD), Paragraph("Angle-closure glaucoma, BPH, Paralytic ileus, Tachycardia, Pyloric stenosis", BODY), Paragraph("Dry mouth, Urinary retention, Constipation, Confusion (elderly), Hyperthermia", BODY)],
        [Paragraph("SSRIs", BODY_BOLD), Paragraph("MAOIs (within 14 days), Linezolid (serotonin syndrome risk)", BODY), Paragraph("GI upset, Sexual dysfunction, Serotonin syndrome, SIADH, Bleeding risk (↓platelet)", BODY)],
        [Paragraph("Triptans", BODY_BOLD), Paragraph("IHD, Uncontrolled HTN, Hemiplegic/basilar migraine, Pregnancy (caution)", BODY), Paragraph("Flushing, Chest tightness, Coronary vasospasm, Serotonin syndrome (with SSRIs)", BODY)],
        [Paragraph("Ergot Alkaloids", BODY_BOLD), Paragraph("Pregnancy, Peripheral vascular disease, Hypertension, Liver/kidney disease, Sepsis", BODY), Paragraph("Ergotism (gangrene), Vasospasm, Nausea/vomiting", BODY)],
        [Paragraph("1st Gen Antihistamines", BODY_BOLD), Paragraph("Glaucoma (narrow angle), BPH, Elderly patients (Beers list), MAOIs", BODY), Paragraph("Sedation, Anticholinergic effects, Paradoxical excitation in children", BODY)],
        [Paragraph("Organophosphates\n(Cholinergic excess)", BODY_BOLD), Paragraph("Treatment: Atropine + Pralidoxime. Avoid succinylcholine!", BODY), Paragraph("SLUDGE BBB crisis: Bradycardia, Miosis, Salivation, Diarrhea, Bronchospasm", BODY)],
    ]
    cit = Table(ci_data, colWidths=[3.5*cm, 7*cm, 6*cm])
    cit.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_RED),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_WHITE, C_RED_LT]),
        ("GRID", (0,0), (-1,-1), 0.4, HexColor("#EF9A9A")),
        ("FONTSIZE", (0,0), (-1,-1), 8),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 28),
    ]))
    story.append(cit)
    story.append(sp(8))

    # ── MNEMONICS BOX ──
    story.append(Paragraph("<b>Key Mnemonics for Exam</b>", H3))
    mnemonics = [
        [Paragraph("<b>Mnemonic</b>", TABLE_HDR), Paragraph("<b>Stands for</b>", TABLE_HDR), Paragraph("<b>Relevance</b>", TABLE_HDR)],
        [Paragraph("SLUDGE", BODY_BOLD), Paragraph("Salivation, Lacrimation, Urination, Defecation, GI cramps, Emesis", BODY), Paragraph("Cholinergic toxicity signs (OP poisoning, excess AChE inhibition)", BODY)],
        [Paragraph("DUMBELS", BODY_BOLD), Paragraph("Defecation, Urination, Miosis, Bradycardia, Emesis, Lacrimation, Salivation", BODY), Paragraph("Another mnemonic for organophosphate/cholinergic crisis", BODY)],
        [Paragraph("Dry as Bone\n(6 signs)", BODY_BOLD), Paragraph("Dry, Red, Hot, Blind, Mad, Full (as Flask)", BODY), Paragraph("Anticholinergic toxidrome signs", BODY)],
        [Paragraph("MAST cells", BODY_BOLD), Paragraph("Main site for histamine storage", BODY), Paragraph("Released in allergy, trauma, complement activation", BODY)],
        [Paragraph("Triple-S for SSRIs", BODY_BOLD), Paragraph("Safety, Selectivity, Second-line→1st line", BODY), Paragraph("SSRIs replaced TCAs as 1st-line antidepressants", BODY)],
    ]
    mnt = Table(mnemonics, colWidths=[3.5*cm, 7*cm, 6*cm])
    mnt.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), C_TEAL),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [C_TEAL_LT, C_WHITE]),
        ("GRID", (0,0), (-1,-1), 0.4, C_TEAL),
        ("FONTSIZE", (0,0), (-1,-1), 8.5),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWHEIGHT", (0,0), (-1,-1), 22),
    ]))
    story.append(mnt)
    story.append(sp(8))

    # FINAL SUMMARY FLOWCHART
    story.append(Paragraph("<b>Module Summary - Drug Classification Overview</b>", H3))
    summary_steps = [
        ("ANS DRUGS - MODULE 4.1 CLASSIFICATION OVERVIEW", C_NAVY),
        ("CHOLINERGIC (4.1.1): Pilocarpine, Neostigmine, Physostigmine | Glaucoma, Myasthenia Gravis, OP poisoning", C_TEAL),
        ("ANTICHOLINERGIC (4.1.1): Atropine, Scopolamine, Ipratropium | Bradycardia, Motion sickness, COPD", C_ORANGE),
        ("ADRENERGIC (4.1.2): Epinephrine, Salbutamol, Dopamine | Anaphylaxis, Shock, Asthma", C_RED),
        ("ANTIADRENERGIC (4.1.2): Propranolol, Metoprolol, Prazosin | HTN, Angina, HF, Arrhythmias", HexColor("#AD1457")),
        ("SEROTONERGIC (4.1.3): Fluoxetine (SSRI), Sumatriptan (triptan), Ondansetron | Depression, Migraine, N&V", C_PURPLE),
        ("HISTAMINE/ANTIHISTAMINIC (4.1.4): Diphenhydramine, Cetirizine, Ranitidine | Allergy, GERD, Urticaria", C_YELLOW),
        ("MIGRAINE: Acute = Triptans + NSAIDs | Prevention = Propranolol + Topiramate + Anti-CGRP", HexColor("#880E4F")),
    ]
    story.append(DiagramFlowchart(summary_steps, width=W - 3.6*cm, arrow=False))

    # ── Build the PDF ──
    doc.build(story)
    print(f"PDF generated: {output_path}")


if __name__ == "__main__":
    out = "/home/daytona/workspace/ans-autacoids-notes/ANS_Autacoids_Notes.pdf"
    build_pdf(out)