General prescribing guidelines for lactation

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general prescribing guidelines drugs during lactation breastfeeding 2024

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https://www.aafp.org/afp/2022/1200/medication-safety-breastf…

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General Prescribing Guidelines for Lactation

Core Principle

The number of drugs truly contraindicated during breastfeeding is small. Most women and many clinicians over-estimate this risk. The goal is to weigh the well-documented benefits of breastfeeding against the risk of a specific medication to the specific infant, and to make an evidence-based rather than a reflexive decision. Arbitrary interference with breastfeeding "until more information is found" is rarely justified.

Creasy & Resnik's Maternal-Fetal Medicine, p. 253

1. General Approach to Prescribing

Principle	Details
Avoid drug therapy when possible	Non-pharmacologic options first
Benefit-risk assessment	Benefits of breastfeeding are substantial; contraindications are few
Safe in infants = generally safe	If a drug is safely used directly in infants, it is generally safe during breastfeeding
Pregnancy safety ≠ lactation safety	These are pharmacologically distinct scenarios
Use topical therapy where possible	Minimises systemic absorption and milk transfer; avoid applying to nipples
Use the lowest effective dose	For the shortest necessary duration
Use well-studied agents	Prefer medications with established safety data in nursing mothers

AAFP - Medication Safety in Breastfeeding (2022)

2. Pharmacokinetic Factors: What Determines Drug Transfer into Breast Milk?

The mammary alveolar epithelium acts as a lipid barrier with water-filled pores. Key drug properties that influence milk transfer include:

Property	Effect on Milk Transfer
High lipid solubility	Increases transfer into milk
Low molecular weight (<200 Da)	Passes through water-filled membrane pores
Low protein binding	More free drug available to enter milk
Non-ionised form	Enters mammary cells more readily via diffusion
Long half-life	Prolonged infant exposure
High oral bioavailability	Drug absorbed from milk by infant
Basic (high pKa) drugs	"Ion trapping" in milk (pH 7.0 vs. plasma pH 7.4) - concentrate in milk

Most drugs have a milk-to-plasma (M:P) ratio of less than 1. Drug amounts in milk usually do not exceed 1% of the maternal ingested dose.

Creasy & Resnik's Maternal-Fetal Medicine, p. 253, Box 11.4

When selecting drugs, prefer:

Lowest lipid solubility
Poorest oral absorption (infant cannot absorb from gut)
Shortest half-life
Highest protein-binding ability

3. Milk-to-Plasma (M:P) Ratio and Relative Infant Dose (RID)

M:P ratio: The level of drug in breast milk relative to maternal plasma at a given time. Most drugs have M:P <1. A ratio near or equal to 1 does not automatically mean the drug is harmful - the absolute level in milk may still be very low.
Relative Infant Dose (RID): The infant's weight-adjusted dose as a percentage of the maternal dose. An RID <10% is generally considered acceptable and is the threshold used by the American Academy of Pediatrics (AAP) to classify most drugs as compatible with breastfeeding.
Bradley and Daroff's Neurology in Clinical Practice, Chapter 30

4. Hale's Lactation Risk Categories

Thomas Hale's Medications and Mothers' Milk (regularly updated) classifies drugs into 5 categories widely used in clinical practice:

Category	Meaning
L1 - Safest	Extensive data; no adverse effects observed
L2 - Safer	Limited data; no increased risk
L3 - Moderately Safe	No controlled studies; risk possible but benefit may outweigh risk
L4 - Possibly Hazardous	Positive evidence of risk; use only when benefit justifies risk
L5 - Contraindicated	Risk to infant clearly outweighs any benefit

Creasy & Resnik's Maternal-Fetal Medicine, p. 252

5. AAP Classification of Drugs in Breast Milk

The AAP classifies drugs into 7 categories:

Cytotoxic drugs that may interfere with infant cellular metabolism (e.g. antineoplastic agents)
Drugs of abuse with reported adverse effects in breastfed infants (e.g. cocaine, heroin)
Radioactive compounds requiring temporary cessation of breastfeeding (e.g. I-131)
Drugs with unknown effect but possible concern (e.g. bromocriptine, ergotamine, lithium)
Drugs with significant effects on some nursing infants - use with caution (e.g. chloramphenicol, aspirin in high doses)
Drugs usually compatible with breastfeeding (the vast majority)
Food and environmental agents with potential effects

Creasy & Resnik's Maternal-Fetal Medicine, p. 252

6. Key Prescribing Strategies

Timing of Doses

Administer single daily-dose medications just before the infant's longest sleep interval (usually after the bedtime feeding). This allows peak drug levels to fall before the next feed.
Avoid breastfeeding at the time of peak milk drug concentration.

"Pump and Dump" / Temporary Cessation

For short-term medications (e.g. anesthesia, contrast agents, single-dose drugs), the mother can pump and discard milk for the period required for drug clearance, then resume.
For most contrast agents: <1% of the maternal dose enters milk, and <1% of that is absorbed by the infant's GI tract - interruption is usually not needed.
Tc-99m renal/cardiac imaging: interruption generally not required (or brief 4-12 hour window only).
Creasy & Resnik's Maternal-Fetal Medicine, p. 254, Box 11.5

Infant Factors to Consider

Age and maturity: Premature or newborn infants have less mature liver and kidney function - more caution needed.
Extent of breastfeeding: An 18-month-old nursing 4 times/day for comfort has far less drug exposure than a neonate exclusively breastfed.
Oral bioavailability: Drugs with poor GI absorption (e.g. aminoglycosides, heparin, omeprazole) are unlikely to cause harm even if present in milk.

7. Reliable Reference Resources

Resource	Details
LactMed (NIH)	Free, continuously updated government database; generally considered the least restrictive and most up-to-date
Hale's Medications and Mothers' Milk	Widely used handbook; updated regularly
InfantRisk Center (infantrisk.com)	Expert consultations; phone helpline
MotherToBaby.org	Teratogen information service
Academy of Breastfeeding Medicine (ABM) Protocols	Evidence-based clinical protocols
AAP Committee on Drugs statements	Periodically updated drug lists

Package inserts tend to be the most restrictive and are not a reliable guide - they often state "avoid in breastfeeding" due to liability rather than evidence. LactMed is typically more accurate.

8. Drugs Absolutely Contraindicated During Breastfeeding

A short but important list:

Cytotoxic/chemotherapy agents (e.g. methotrexate, cyclophosphamide)
Radioactive iodine (I-131)
Drugs of abuse (cocaine, heroin, amphetamines in high doses)
Ergotamine (in high doses - may cause ergotism)
Bromocriptine (suppresses lactation)
Amiodarone (high iodine content; long half-life)
Lithium (monitor if used; generally discouraged)
Certain antiretrovirals in specific settings
Clofazimine (concentrated in breast milk - dermatology use)

9. Drug-Class Specific Guidance (Highlights)

Condition	Preferred Agents	Comments
Pain	Acetaminophen, ibuprofen	Naproxen discouraged (long half-life, bleeding risk)
Depression/Anxiety	Sertraline, paroxetine (SSRIs)	Best studied, lowest RID; fluoxetine less preferred (long half-life)
Hypertension	Labetalol, nifedipine, methyldopa	Generally compatible
Diabetes	Insulin, metformin, 2nd-gen sulfonylureas	Newer agents (SGLT-2i, GLP-1) lack lactation data
Asthma/Allergic rhinitis	Inhaled steroids, intranasal treatments	Minimal systemic absorption; preferred
Antiepileptics	Valproate, carbamazepine, phenytoin, phenobarbital	All compatible with breastfeeding (despite pregnancy teratogenicity)
Antibiotics	Most penicillins, cephalosporins, azithromycin	Generally safe; metronidazole compatible at standard doses
Contraception	Progestin-only (mini-pill), barrier methods	Combined estrogen-progestin may reduce milk supply
Antipsychotics	Quetiapine, olanzapine (with monitoring)	Clozapine - caution; agranulocytosis risk to infant

AAFP AFP 2022; Creasy & Resnik's Maternal-Fetal Medicine

10. Contraindications to Breastfeeding (Maternal Conditions)

Maternal HIV infection (in resource-adequate settings)
Human T-cell lymphotropic virus (HTLV-I/II)
Active herpetic lesions on the breast
Active untreated tuberculosis
Infant with classic galactosemia
Textbook of Family Medicine, 9e, p. 539

Summary Decision Framework

Is drug therapy necessary? Consider non-pharmacologic alternatives first.
Check reliable resources (LactMed, Hale's) - not the package insert.
Choose the safest drug in the class - lowest lipid solubility, shortest half-life, lowest RID.
Use the lowest effective dose for the shortest duration.
Time the dose to just before the infant's longest sleep interval.
Consider infant age and maturity - premature/newborn needs more caution.
Monitor the infant for unexpected effects: sedation, poor feeding, irritability, poor weight gain.
For short-term medications, pump-and-discard during drug clearance if needed.
Do not stop breastfeeding reflexively - the benefits of breastfeeding are substantial and real contraindications are few.

Create a ppt presentation for migraine therapy for pharmacology subject

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mkdir -p /tmp/workspace/migraine-ppt && ls /tmp/workspace/migraine-ppt/

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~/migraine-ppt/build_migraine_ppt.py

from pptx import Presentation
from pptx.util import Inches, Pt, Emu
from pptx.dml.color import RGBColor
from pptx.enum.text import PP_ALIGN, MSO_ANCHOR
from pptx.enum.shapes import MSO_SHAPE
from io import BytesIO

# ── Colour palette ─────────────────────────────────────────────────────────
DARK_PURPLE   = RGBColor(0x3B, 0x10, 0x5E)   # deep purple (header / bg)
MID_PURPLE    = RGBColor(0x6A, 0x2C, 0x9A)   # medium purple accent
LIGHT_PURPLE  = RGBColor(0xD9, 0xCB, 0xF5)   # very light lavender (body bg)
ACCENT_TEAL   = RGBColor(0x00, 0xB0, 0xC0)   # teal highlight
ACCENT_ORANGE = RGBColor(0xF7, 0x83, 0x1F)   # warm orange accent
WHITE         = RGBColor(0xFF, 0xFF, 0xFF)
DARK_GRAY     = RGBColor(0x22, 0x22, 0x22)
MID_GRAY      = RGBColor(0x55, 0x55, 0x55)
LIGHT_GRAY    = RGBColor(0xF0, 0xEC, 0xF8)

W = Inches(13.333)
H = Inches(7.5)

prs = Presentation()
prs.slide_width  = W
prs.slide_height = H
blank = prs.slide_layouts[6]   # fully blank

# ── Helper: solid-fill background rect ─────────────────────────────────────
def bg_rect(slide, color, left=0, top=0, width=None, height=None):
    width  = width  or W
    height = height or H
    shp = slide.shapes.add_shape(MSO_SHAPE.RECTANGLE, left, top, width, height)
    shp.fill.solid(); shp.fill.fore_color.rgb = color
    shp.line.fill.background()
    return shp

# ── Helper: add a textbox ───────────────────────────────────────────────────
def txt(slide, text, left, top, width, height,
        size=18, bold=False, color=WHITE, align=PP_ALIGN.LEFT,
        wrap=True, italic=False, v_anchor=MSO_ANCHOR.TOP):
    tb = slide.shapes.add_textbox(left, top, width, height)
    tf = tb.text_frame
    tf.word_wrap = wrap
    tf.vertical_anchor = v_anchor
    tf.margin_left = tf.margin_right = tf.margin_top = tf.margin_bottom = 0
    p  = tf.paragraphs[0]
    p.alignment = align
    run = p.add_run()
    run.text = text
    run.font.size  = Pt(size)
    run.font.bold  = bold
    run.font.color.rgb = color
    run.font.italic = italic
    return tb

# ── Helper: add a bullet textbox (multiple items) ──────────────────────────
def bullets(slide, items, left, top, width, height,
            size=16, color=DARK_GRAY, bold_first=False,
            sub_items=None):
    """items: list of str.  sub_items: dict {idx: [sub1,sub2,...]}"""
    sub_items = sub_items or {}
    tb = slide.shapes.add_textbox(left, top, width, height)
    tf = tb.text_frame
    tf.word_wrap = True
    tf.margin_left = Inches(0.05)
    tf.margin_top  = Pt(4)
    for i, item in enumerate(items):
        p = tf.paragraphs[0] if i == 0 else tf.add_paragraph()
        p.space_before = Pt(3)
        p.space_after  = Pt(3)
        run = p.add_run()
        run.text = "\u2022  " + item
        run.font.size = Pt(size)
        run.font.color.rgb = color
        run.font.bold = bold and (i == 0) if bold_first else False
        if i in sub_items:
            for sub in sub_items[i]:
                sp = tf.add_paragraph()
                sp.space_before = Pt(1)
                sr = sp.add_run()
                sr.text = "      \u2013  " + sub
                sr.font.size  = Pt(size - 2)
                sr.font.color.rgb = color
    return tb

# ── Helper: section header bar ─────────────────────────────────────────────
def header_bar(slide, title, subtitle=None):
    bg_rect(slide, DARK_PURPLE, 0, 0, W, Inches(1.35))
    # accent stripe
    shp = slide.shapes.add_shape(MSO_SHAPE.RECTANGLE,
                                  0, Inches(1.35), W, Pt(5))
    shp.fill.solid(); shp.fill.fore_color.rgb = ACCENT_TEAL
    shp.line.fill.background()

    txt(slide, title, Inches(0.5), Inches(0.1), Inches(10), Inches(0.85),
        size=32, bold=True, color=WHITE)
    if subtitle:
        txt(slide, subtitle, Inches(0.5), Inches(0.9), Inches(10), Inches(0.45),
            size=16, color=LIGHT_PURPLE)

# ── Helper: coloured card ───────────────────────────────────────────────────
def card(slide, left, top, width, height, fill_color, text,
         text_size=15, text_color=WHITE, bold=False):
    shp = slide.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                                  left, top, width, height)
    shp.fill.solid(); shp.fill.fore_color.rgb = fill_color
    shp.line.fill.background()
    tf = shp.text_frame
    tf.word_wrap = True
    tf.vertical_anchor = MSO_ANCHOR.MIDDLE
    tf.margin_left = Inches(0.12)
    tf.margin_right = Inches(0.08)
    tf.margin_top = tf.margin_bottom = Pt(6)
    p = tf.paragraphs[0]
    p.alignment = PP_ALIGN.LEFT
    run = p.add_run()
    run.text = text
    run.font.size = Pt(text_size)
    run.font.color.rgb = text_color
    run.font.bold = bold

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 1 – Title
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, DARK_PURPLE)
# decorative gradient-like overlay (two overlapping shapes)
shp = s.shapes.add_shape(MSO_SHAPE.OVAL, Inches(9), Inches(-1), Inches(6), Inches(6))
shp.fill.solid(); shp.fill.fore_color.rgb = MID_PURPLE
shp.line.fill.background()
shp2 = s.shapes.add_shape(MSO_SHAPE.OVAL, Inches(10), Inches(3.5), Inches(5), Inches(5))
shp2.fill.solid(); shp2.fill.fore_color.rgb = RGBColor(0x55, 0x1F, 0x8A)
shp2.line.fill.background()

# accent bar left
bar = s.shapes.add_shape(MSO_SHAPE.RECTANGLE, 0, 0, Pt(10), H)
bar.fill.solid(); bar.fill.fore_color.rgb = ACCENT_TEAL
bar.line.fill.background()

txt(s, "MIGRAINE THERAPY", Inches(0.7), Inches(1.6), Inches(9), Inches(1.4),
    size=52, bold=True, color=WHITE)
txt(s, "Pharmacology  |  Mechanisms, Acute Treatment & Prophylaxis",
    Inches(0.7), Inches(3.1), Inches(9), Inches(0.7),
    size=22, color=LIGHT_PURPLE)
txt(s, "Department of Pharmacology", Inches(0.7), Inches(4.1),
    Inches(8), Inches(0.5), size=17, color=ACCENT_TEAL)
# bottom line
ln = s.shapes.add_shape(MSO_SHAPE.RECTANGLE, Inches(0.7), Inches(4.75),
                         Inches(7), Pt(3))
ln.fill.solid(); ln.fill.fore_color.rgb = ACCENT_ORANGE
ln.line.fill.background()

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 2 – Overview / Table of Contents
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, WHITE)
bg_rect(s, LIGHT_GRAY, 0, 0, Inches(4.0), H)
header_bar(s, "Overview", "What we will cover today")

topics = [
    ("1", "Migraine: Definition & Epidemiology"),
    ("2", "Pathophysiology"),
    ("3", "Classification of Migraine"),
    ("4", "Non-Specific (Symptomatic) Therapy"),
    ("5", "Triptans – 5-HT\u2081B/\u2081D Agonists"),
    ("6", "Ergot Alkaloids"),
    ("7", "Ditans & Gepants (Newer Agents)"),
    ("8", "Migraine Prophylaxis"),
    ("9", "CGRP Monoclonal Antibodies"),
    ("10", "Drug Selection Guide"),
]
colors = [MID_PURPLE, ACCENT_TEAL, DARK_PURPLE, MID_PURPLE, ACCENT_TEAL,
          DARK_PURPLE, MID_PURPLE, ACCENT_TEAL, DARK_PURPLE, MID_PURPLE]

for i, (num, topic) in enumerate(topics):
    col = 0 if i < 5 else 1
    row = i % 5
    left = Inches(0.25 + col * 6.6)
    top  = Inches(1.6 + row * 1.1)
    card(s, left, top, Inches(6.3), Inches(0.95), colors[i],
         f"  {num}.  {topic}", text_size=16, bold=False)

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 3 – Definition & Epidemiology
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, WHITE)
header_bar(s, "Migraine – Definition & Epidemiology")

# Left column
bg_rect(s, LIGHT_GRAY, 0, Inches(1.45), Inches(6.4), Inches(6.1))
txt(s, "Definition", Inches(0.3), Inches(1.6), Inches(6), Inches(0.5),
    size=20, bold=True, color=DARK_PURPLE)
bullets(s, [
    "Primary episodic headache disorder",
    "Unilateral, pulsating, moderate-to-severe pain lasting 2–72 hours",
    "Associated: nausea, vomiting, photophobia, phonophobia",
    "Worsened by routine physical activity",
    "May be preceded by neurologic aura (visual, sensory, motor, speech)",
], Inches(0.3), Inches(2.1), Inches(5.9), Inches(3.0), size=15, color=DARK_GRAY)

txt(s, "Two Main Types", Inches(0.3), Inches(5.1), Inches(6), Inches(0.5),
    size=18, bold=True, color=MID_PURPLE)
card(s, Inches(0.3), Inches(5.6), Inches(2.8), Inches(0.75), MID_PURPLE,
     "Migraine WITHOUT Aura\n(~85% of patients)", text_size=13)
card(s, Inches(3.35), Inches(5.6), Inches(2.8), Inches(0.75), ACCENT_TEAL,
     "Migraine WITH Aura\n(~15% of patients)", text_size=13)

# Right column
txt(s, "Epidemiology", Inches(6.8), Inches(1.6), Inches(6.2), Inches(0.5),
    size=20, bold=True, color=DARK_PURPLE)
epi_items = [
    "~12–15% of the general population affected",
    "Women 3× more likely than men (hormonal influence)",
    "Peak prevalence: ages 25–55 years",
    "3rd most prevalent disorder worldwide (WHO)",
    "Leading cause of disability in under-50 age group",
    "Strong genetic component (family history in 70%)",
]
bullets(s, epi_items, Inches(6.8), Inches(2.1), Inches(6.1), Inches(3.5),
        size=15, color=DARK_GRAY)

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 4 – Pathophysiology
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, WHITE)
header_bar(s, "Pathophysiology of Migraine")

# 4 pathway boxes
phases = [
    (DARK_PURPLE,    "1. Cortical Spreading\nDepression (CSD)",
     "Slow wave of depolarisation spreading across cortex\nat ~3 mm/min. Produces hypoperfusion (aura)."),
    (MID_PURPLE,     "2. Trigeminal Activation",
     "CSD activates trigeminal nerve fibres innervating\npial and dural blood vessels."),
    (ACCENT_TEAL,    "3. Neurogenic Inflammation",
     "Release of CGRP, substance P, neurokinin A → vasodilation\nand plasma protein extravasation around meningeal vessels."),
    (ACCENT_ORANGE,  "4. Central Sensitisation",
     "Peripheral sensitisation → central sensitisation in trigeminal\nnucleus → allodynia and prolonged headache."),
]
for i, (col, title, body) in enumerate(phases):
    left = Inches(0.3 + i * 3.2)
    shp = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                              left, Inches(1.55), Inches(3.0), Inches(2.5))
    shp.fill.solid(); shp.fill.fore_color.rgb = col
    shp.line.fill.background()
    tf = shp.text_frame; tf.word_wrap = True
    tf.vertical_anchor = MSO_ANCHOR.TOP
    tf.margin_left = tf.margin_right = Inches(0.1)
    tf.margin_top = Inches(0.1)
    p = tf.paragraphs[0]; p.alignment = PP_ALIGN.LEFT
    r = p.add_run(); r.text = title
    r.font.size = Pt(15); r.font.bold = True; r.font.color.rgb = WHITE
    p2 = tf.add_paragraph(); p2.space_before = Pt(6)
    r2 = p2.add_run(); r2.text = body
    r2.font.size = Pt(13); r2.font.color.rgb = WHITE
    # arrow (except last)
    if i < 3:
        arr = s.shapes.add_shape(MSO_SHAPE.RIGHT_ARROW,
                                  left + Inches(3.0), Inches(2.2),
                                  Inches(0.2), Inches(0.7))
        arr.fill.solid(); arr.fill.fore_color.rgb = MID_GRAY
        arr.line.fill.background()

# Key molecules box
txt(s, "Key Mediators in Migraine", Inches(0.3), Inches(4.3),
    Inches(12.7), Inches(0.45), size=18, bold=True, color=DARK_PURPLE)
mols = [
    ("CGRP", DARK_PURPLE,
     "Potent vasodilator released from trigeminal fibres.\nElevated during acute migraine. PRIMARY drug target."),
    ("Serotonin (5-HT)", MID_PURPLE,
     "5-HT\u2081B/\u2081D: vasoconstriction + inhibits neuropeptide release.\n5-HT\u2081F: neuronal inhibition (ditan target)."),
    ("Substance P &\nNeurokinin A", ACCENT_TEAL,
     "Promote neurogenic inflammation and\nplasma protein extravasation."),
    ("Dopamine", ACCENT_ORANGE,
     "Involved in prodrome symptoms\n(yawning, nausea, osmophobia)."),
]
for i, (mol, col, desc) in enumerate(mols):
    left = Inches(0.3 + i * 3.2)
    shp = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                              left, Inches(4.85), Inches(3.0), Inches(2.3))
    shp.fill.solid(); shp.fill.fore_color.rgb = col
    shp.line.fill.background()
    tf = shp.text_frame; tf.word_wrap = True
    tf.margin_left = tf.margin_right = Inches(0.1); tf.margin_top = Inches(0.08)
    p = tf.paragraphs[0]
    r = p.add_run(); r.text = mol
    r.font.size = Pt(14); r.font.bold = True; r.font.color.rgb = WHITE
    p2 = tf.add_paragraph(); p2.space_before = Pt(4)
    r2 = p2.add_run(); r2.text = desc
    r2.font.size = Pt(12); r2.font.color.rgb = WHITE

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 5 – Acute Therapy: Non-Specific
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, WHITE)
header_bar(s, "Acute Therapy – Non-Specific (Symptomatic)")

txt(s, "Step-care strategy: Start with non-specific analgesics for mild-to-moderate attacks",
    Inches(0.4), Inches(1.5), Inches(12.5), Inches(0.5),
    size=15, color=MID_GRAY, italic=True)

# 3 cards
categories = [
    (DARK_PURPLE, "NSAIDs & Analgesics",
     ["Aspirin 900 mg, Ibuprofen 400–800 mg, Naproxen 500–1000 mg",
      "Ketorolac (IV/IM) – useful in ED settings",
      "Acetaminophen 1000 mg – safe, effective for mild attacks",
      "Mechanism: COX inhibition → ↓ prostaglandin-mediated sensitisation",
      "ADRs: GI irritation, dyspepsia; avoid in peptic ulcer disease"]),
    (MID_PURPLE, "Antiemetics (Adjuncts)",
     ["Metoclopramide 10 mg IV/oral – prokinetic + antiemetic",
      "Prochlorperazine 10 mg IV/oral – D2 receptor blocker",
      "Domperidone 20 mg oral",
      "Dual benefit: control nausea AND enhance analgesic absorption",
      "Metoclopramide alone has mild acute antimigraine effect"]),
    (ACCENT_TEAL, "Combination Analgesics",
     ["Aspirin + acetaminophen + caffeine (e.g., Excedrin)",
      "Caffeine enhances vasoconstriction and analgesic efficacy",
      "Butalbital combinations – limited use (dependence risk)",
      "Opioids: generally AVOIDED – cause MOH and central sensitisation",
      "Corticosteroids (dexamethasone) – reduce headache recurrence"]),
]
for i, (col, title, pts) in enumerate(categories):
    left = Inches(0.25 + i * 4.35)
    shp = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                              left, Inches(2.1), Inches(4.1), Inches(0.6))
    shp.fill.solid(); shp.fill.fore_color.rgb = col
    shp.line.fill.background()
    tf = shp.text_frame; tf.vertical_anchor = MSO_ANCHOR.MIDDLE
    tf.margin_left = Inches(0.1)
    p = tf.paragraphs[0]
    r = p.add_run(); r.text = title
    r.font.size = Pt(16); r.font.bold = True; r.font.color.rgb = WHITE

    tb = s.shapes.add_textbox(left, Inches(2.75), Inches(4.1), Inches(4.5))
    tf2 = tb.text_frame; tf2.word_wrap = True; tf2.margin_left = Inches(0.1)
    for j, pt in enumerate(pts):
        p2 = tf2.paragraphs[0] if j == 0 else tf2.add_paragraph()
        p2.space_before = Pt(4)
        r2 = p2.add_run(); r2.text = "\u2022  " + pt
        r2.font.size = Pt(13); r2.font.color.rgb = DARK_GRAY

# Medication overuse warning
warn = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                           Inches(0.3), Inches(6.55), Inches(12.7), Inches(0.75))
warn.fill.solid(); warn.fill.fore_color.rgb = ACCENT_ORANGE
warn.line.fill.background()
tf = warn.text_frame; tf.vertical_anchor = MSO_ANCHOR.MIDDLE
tf.margin_left = Inches(0.2)
p = tf.paragraphs[0]
r = p.add_run()
r.text = "\u26a0  Medication Overuse Headache (MOH): Using acute analgesics >10–15 days/month leads to rebound headache. Limit acute medication use!"
r.font.size = Pt(13); r.font.bold = True; r.font.color.rgb = WHITE

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 6 – Triptans
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, WHITE)
header_bar(s, "Triptans – Selective 5-HT₁B/₁D Receptor Agonists",
           "First-line migraine-specific therapy")

# Mechanism box
mbox = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                           Inches(0.3), Inches(1.55), Inches(4.6), Inches(2.7))
mbox.fill.solid(); mbox.fill.fore_color.rgb = DARK_PURPLE
mbox.line.fill.background()
tf = mbox.text_frame; tf.word_wrap = True
tf.margin_left = tf.margin_right = Inches(0.15); tf.margin_top = Inches(0.1)
p = tf.paragraphs[0]; r = p.add_run()
r.text = "Mechanism of Action"; r.font.size = Pt(17); r.font.bold = True; r.font.color.rgb = WHITE
items2 = [
    "Agonists at 5-HT\u2081B receptors \u2192 cerebral vasoconstriction",
    "Agonists at 5-HT\u2081D receptors \u2192 inhibit trigeminal neuropeptide release (CGRP, substance P)",
    "Peripheral: reduce neurogenic inflammation",
    "Central: modulate trigeminal nucleus activity",
]
for it in items2:
    pp = tf.add_paragraph(); pp.space_before = Pt(5)
    rr = pp.add_run(); rr.text = "\u2022  " + it
    rr.font.size = Pt(12.5); rr.font.color.rgb = WHITE

# Adverse effects box
abox = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                           Inches(0.3), Inches(4.35), Inches(4.6), Inches(2.85))
abox.fill.solid(); abox.fill.fore_color.rgb = MID_PURPLE
abox.line.fill.background()
tf = abox.text_frame; tf.word_wrap = True
tf.margin_left = tf.margin_right = Inches(0.15); tf.margin_top = Inches(0.1)
p = tf.paragraphs[0]; r = p.add_run()
r.text = "Adverse Effects & Contraindications"; r.font.size = Pt(15); r.font.bold = True; r.font.color.rgb = WHITE
aes = [
    "Triptan sensations: chest tightness, tingling",
    "Nausea, dizziness, somnolence",
    "CONTRAINDICATED: ischaemic heart disease, uncontrolled HTN, stroke",
    "Do NOT use within 24 h of ergotamine (risk of coronary ischaemia)",
    "Serotonin syndrome risk with concomitant serotonergic drugs",
]
for it in aes:
    pp = tf.add_paragraph(); pp.space_before = Pt(4)
    rr = pp.add_run(); rr.text = "\u2022  " + it
    rr.font.size = Pt(12); rr.font.color.rgb = WHITE

# Triptans table
txt(s, "Available Triptans", Inches(5.2), Inches(1.55), Inches(7.8), Inches(0.45),
    size=18, bold=True, color=DARK_PURPLE)

table_data = [
    ["Drug", "Route(s)", "T½ (h)", "Notes"],
    ["Sumatriptan", "PO, SC, IN, PR", "~2", "Prototype; most formulations; first-choice"],
    ["Rizatriptan", "PO, ODT", "~2–3", "Fastest onset; highest efficacy on population basis"],
    ["Eletriptan", "PO", "~4", "High efficacy; less headache recurrence"],
    ["Zolmitriptan", "PO, nasal", "~2.5–3", "Nasal: useful with early nausea/vomiting"],
    ["Naratriptan", "PO", "~5–6", "Slowest onset; fewest side effects; ↓ recurrence"],
    ["Frovatriptan", "PO", "~26", "Longest T½; useful for menstrual migraine prevention"],
    ["Almotriptan", "PO", "~3.5", "Good tolerability; fewer ADRs than sumatriptan"],
]
col_widths = [Inches(2.0), Inches(2.1), Inches(0.9), Inches(2.75)]
row_height = Inches(0.56)
table_left = Inches(5.2)
table_top  = Inches(2.1)
header_color = DARK_PURPLE
row_colors   = [LIGHT_GRAY, WHITE]

for r_idx, row in enumerate(table_data):
    for c_idx, cell_text in enumerate(row):
        left = table_left + sum(col_widths[:c_idx])
        top  = table_top + r_idx * row_height
        fill = header_color if r_idx == 0 else row_colors[r_idx % 2]
        shp  = s.shapes.add_shape(MSO_SHAPE.RECTANGLE, left, top,
                                   col_widths[c_idx], row_height)
        shp.fill.solid(); shp.fill.fore_color.rgb = fill
        shp.line.color.rgb = RGBColor(0xCC, 0xCC, 0xCC)
        shp.line.width = Pt(0.5)
        tf = shp.text_frame; tf.vertical_anchor = MSO_ANCHOR.MIDDLE
        tf.margin_left = Inches(0.08); tf.margin_right = Inches(0.04)
        p2 = tf.paragraphs[0]; p2.alignment = PP_ALIGN.LEFT
        rr = p2.add_run(); rr.text = cell_text
        rr.font.size = Pt(12.5 if r_idx > 0 else 13)
        rr.font.bold = (r_idx == 0)
        rr.font.color.rgb = WHITE if r_idx == 0 else DARK_GRAY

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 7 – Ergot Alkaloids
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, WHITE)
header_bar(s, "Ergot Alkaloids", "Non-selective receptor agonists – historical & second-line")

left_items = [
    ("Ergotamine", DARK_PURPLE,
     ["Binds 5-HT\u2081, \u03b1-adrenergic & dopamine receptors",
      "Causes VASOCONSTRICTION of cranial blood vessels",
      "Available: sublingual, oral (with caffeine), suppository",
      "Most effective when used EARLY in migraine attack",
      "Strict daily & weekly dose limits due to rebound headache risk",
      "Dependence and medication overuse headache common"]),
    ("Dihydroergotamine\n(DHE)", MID_PURPLE,
     ["Semisynthetic derivative; better tolerability than ergotamine",
      "Routes: IV, IM, intranasal spray (2 mg)",
      "Efficacy similar to sumatriptan SC",
      "Reserved for SEVERE / refractory migraine",
      "Nausea is common ADR (pre-treat with antiemetic)",
      "DHE 45 protocol: IV DHE + metoclopramide, q8h × 3 doses"]),
]
for i, (drug, col, pts) in enumerate(left_items):
    left_x = Inches(0.3 + i * 6.4)
    shp = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                              left_x, Inches(1.55), Inches(6.1), Inches(0.6))
    shp.fill.solid(); shp.fill.fore_color.rgb = col
    shp.line.fill.background()
    tf = shp.text_frame; tf.vertical_anchor = MSO_ANCHOR.MIDDLE
    tf.margin_left = Inches(0.12)
    p = tf.paragraphs[0]; r = p.add_run()
    r.text = drug; r.font.size = Pt(17); r.font.bold = True; r.font.color.rgb = WHITE
    # bullet list below
    tb = s.shapes.add_textbox(left_x, Inches(2.22), Inches(6.1), Inches(3.3))
    tf2 = tb.text_frame; tf2.word_wrap = True; tf2.margin_left = Inches(0.1)
    for j, pt in enumerate(pts):
        p2 = tf2.paragraphs[0] if j == 0 else tf2.add_paragraph()
        p2.space_before = Pt(4)
        r2 = p2.add_run(); r2.text = "\u2022  " + pt
        r2.font.size = Pt(14); r2.font.color.rgb = DARK_GRAY

# Contraindications box
cibox = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                            Inches(0.3), Inches(5.55), Inches(12.7), Inches(1.65))
cibox.fill.solid(); cibox.fill.fore_color.rgb = RGBColor(0xFF, 0xEE, 0xE0)
cibox.line.color.rgb = ACCENT_ORANGE; cibox.line.width = Pt(2)
tf = cibox.text_frame; tf.word_wrap = True
tf.margin_left = Inches(0.2); tf.margin_top = Inches(0.1)
p = tf.paragraphs[0]; r = p.add_run()
r.text = "\u26a0  Contraindications to Ergot Alkaloids"
r.font.size = Pt(15); r.font.bold = True; r.font.color.rgb = ACCENT_ORANGE
ci_list = "  Ischaemic heart disease  |  Peripheral vascular disease  |  Uncontrolled hypertension  |  Hepatic/renal impairment  |  Pregnancy  |  Sepsis  |  Within 24 h of triptan use  |  Co-administration with potent CYP3A4 inhibitors (risk of peripheral ischaemia)"
p2 = tf.add_paragraph(); p2.space_before = Pt(4)
r2 = p2.add_run(); r2.text = ci_list
r2.font.size = Pt(13); r2.font.color.rgb = DARK_GRAY

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 8 – Newer Agents: Ditans & Gepants
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, WHITE)
header_bar(s, "Newer Acute Agents – Ditans & Gepants",
           "Options for patients with cardiovascular contraindications to triptans")

# Lasmiditan (Ditan) – left half
bg_rect(s, LIGHT_GRAY, 0, Inches(1.45), Inches(6.4), Inches(5.85))
txt(s, "DITANS  –  5-HT\u2081F Agonists", Inches(0.3), Inches(1.6),
    Inches(6.0), Inches(0.55), size=18, bold=True, color=DARK_PURPLE)
card(s, Inches(0.3), Inches(2.2), Inches(5.9), Inches(0.55), DARK_PURPLE,
     "Lasmiditan (REYVOW)", text_size=16, bold=True)
ditan_pts = [
    "Selective 5-HT\u2081F receptor agonist (neuronal, NOT vascular)",
    "Does NOT cause vasoconstriction \u2192 cardiovascular-safe",
    "Mechanism: inhibition of trigeminal pain pathways",
    "Dose: 50 mg, 100 mg, or 200 mg orally",
    "Indicated for acute migraine WITH or WITHOUT aura",
    "Classified as CONTROLLED SUBSTANCE (Schedule V in US)",
    "Major ADR: dizziness, somnolence, paresthesia",
    "Patients must NOT drive or operate machinery for \u22658 hours after dose",
    "No contraindication in ischaemic heart disease",
]
bullets(s, ditan_pts, Inches(0.3), Inches(2.85), Inches(5.9), Inches(3.8),
        size=13.5, color=DARK_GRAY)

# Gepants – right half
txt(s, "GEPANTS  –  CGRP Receptor Antagonists", Inches(6.6), Inches(1.6),
    Inches(6.4), Inches(0.55), size=18, bold=True, color=MID_PURPLE)

gepant_data = [
    (ACCENT_TEAL, "Rimegepant (NURTEC ODT)", [
        "75 mg orally disintegrating tablet",
        "Acute treatment AND episodic prevention of migraine",
        "T½ ~11 h \u2192 fewer rebound headaches",
        "Can be used every other day for prevention",
    ]),
    (MID_PURPLE, "Ubrogepant (UBRELVY)", [
        "50 mg or 100 mg oral tablet",
        "Acute treatment only",
        "Contraindicated with strong CYP3A4 inhibitors",
        "No significant cardiovascular effects",
    ]),
    (DARK_PURPLE, "Zavegepant (ZAVZPRET)", [
        "10 mg intranasal spray",
        "Useful when nausea/vomiting prevents oral dosing",
        "Fastest onset among gepants",
        "ADR: nasal discomfort, dysgeusia",
    ]),
    (ACCENT_ORANGE, "Atogepant (QULIPTA)", [
        "10–60 mg oral \u2013 PREVENTION use only",
        "Once daily for episodic and chronic migraine",
        "Not indicated for acute treatment",
        "ADR: nausea, constipation, fatigue",
    ]),
]
for i, (col, name, pts) in enumerate(gepant_data):
    top = Inches(2.2 + i * 1.3)
    card(s, Inches(6.6), top, Inches(6.4), Inches(0.5), col, name,
         text_size=14, bold=True)
    tb = s.shapes.add_textbox(Inches(6.65), top + Inches(0.52),
                               Inches(6.3), Inches(0.75))
    tf = tb.text_frame; tf.word_wrap = True; tf.margin_left = Inches(0.1)
    for j, pt in enumerate(pts):
        p2 = tf.paragraphs[0] if j == 0 else tf.add_paragraph()
        r2 = p2.add_run(); r2.text = "\u2022  " + pt
        r2.font.size = Pt(12.5); r2.font.color.rgb = DARK_GRAY; p2.space_before = Pt(1)

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 9 – Prophylaxis
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, WHITE)
header_bar(s, "Migraine Prophylaxis (Preventive Therapy)")

# Indications strip
ind = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                          Inches(0.3), Inches(1.55), Inches(12.7), Inches(0.65))
ind.fill.solid(); ind.fill.fore_color.rgb = ACCENT_TEAL
ind.line.fill.background()
tf = ind.text_frame; tf.vertical_anchor = MSO_ANCHOR.MIDDLE
tf.margin_left = Inches(0.2)
p = tf.paragraphs[0]; r = p.add_run()
r.text = "INDICATIONS:  \u2265 4 migraine days/month  |  Severe/disabling attacks  |  Failure of acute therapy  |  Medication overuse headache  |  Specific migraine subtypes (hemiplegic, brainstem aura)"
r.font.size = Pt(13.5); r.font.bold = True; r.font.color.rgb = WHITE

# Drug class table
proph_data = [
    ("Drug Class", "Agents", "Dose", "Key Notes"),
    ("\u03b2-Blockers\n(1st line)", "Propranolol\nMetoprolol\nTimolol", "80–240 mg/day\n25–200 mg/day\n10–30 mg/day", "Most widely used. Avoid in asthma,\nbradycardia, depression. FDA-approved."),
    ("Anticonvulsants\n(1st line)", "Topiramate\nValproate (VPA)", "50–200 mg/day\n500–1500 mg/day", "Topiramate: weight loss, cognitive slowing, renal stones.\nVPA: teratogenic – AVOID in women of childbearing age."),
    ("TCAs", "Amitriptyline\nNortriptyline", "10–75 mg/night\n10–75 mg/night", "Useful when comorbid depression/insomnia.\nSedation, anticholinergic effects. Not FDA-approved."),
    ("CCBs", "Verapamil\nFlunarizine*", "80–320 mg/day\n5–10 mg/night", "Verapamil: 2nd line. Constipation, bradycardia.\nFlunarizine: not available in USA; weight gain."),
    ("ARBs / ACEi", "Candesartan\nLisinopril", "16 mg/day\n10–40 mg/day", "Well-tolerated alternatives.\nUseful in hypertensive migraineurs."),
    ("OnabotulinumtoxinA\n(BOTOX\u00ae)", "Botulinum toxin A", "155–195 U q12wk\nIM injection", "FDA-approved for CHRONIC migraine (\u226515 days/month).\nNOT for episodic migraine."),
]

col_w2 = [Inches(2.2), Inches(2.2), Inches(2.2), Inches(5.7)]
rh2 = Inches(0.79)
t_top = Inches(2.35)
for r_idx, row in enumerate(proph_data):
    for c_idx, cell in enumerate(row):
        lft = Inches(0.3) + sum(col_w2[:c_idx])
        top = t_top + r_idx * rh2
        fill = DARK_PURPLE if r_idx == 0 else (LIGHT_GRAY if r_idx % 2 == 0 else WHITE)
        shp = s.shapes.add_shape(MSO_SHAPE.RECTANGLE, lft, top, col_w2[c_idx], rh2)
        shp.fill.solid(); shp.fill.fore_color.rgb = fill
        shp.line.color.rgb = RGBColor(0xCC, 0xCC, 0xCC); shp.line.width = Pt(0.5)
        tf = shp.text_frame; tf.word_wrap = True; tf.vertical_anchor = MSO_ANCHOR.MIDDLE
        tf.margin_left = Inches(0.07); tf.margin_right = Inches(0.05)
        p2 = tf.paragraphs[0]
        rr = p2.add_run(); rr.text = cell
        rr.font.size = Pt(12 if r_idx > 0 else 13); rr.font.bold = (r_idx == 0)
        rr.font.color.rgb = WHITE if r_idx == 0 else DARK_GRAY

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 10 – CGRP Monoclonal Antibodies
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, WHITE)
header_bar(s, "CGRP-Targeted Monoclonal Antibodies",
           "Novel preventive therapy – FDA-approved for episodic & chronic migraine")

txt(s, "Mechanism: Block CGRP ligand or its receptor \u2192 prevent trigeminovascular activation. Monthly or quarterly SC injection.",
    Inches(0.4), Inches(1.55), Inches(12.5), Inches(0.5),
    size=14.5, color=MID_GRAY, italic=True)

mab_data = [
    (DARK_PURPLE,  "Erenumab\n(AIMOVIG)",
     ["Anti-CGRP receptor mAb", "70 mg or 140 mg SC monthly",
      "First CGRP mAb approved (2018)", "AEs: injection site reactions, constipation"]),
    (MID_PURPLE,   "Fremanezumab\n(AJOVY)",
     ["Anti-CGRP ligand mAb", "225 mg SC monthly\nOR 675 mg SC quarterly",
      "Flexible dosing schedule", "AEs: injection site reactions"]),
    (ACCENT_TEAL,  "Galcanezumab\n(EMGALITY)",
     ["Anti-CGRP ligand mAb", "Loading: 240 mg SC, then 120 mg/month",
      "Also approved for cluster headache", "AEs: injection site pain"]),
    (ACCENT_ORANGE,"Eptinezumab\n(VYEPTI)",
     ["Anti-CGRP ligand mAb", "100 mg or 300 mg IV every 3 months",
      "Only IV formulation; rapid onset (day 1)", "AEs: nasopharyngitis, hypersensitivity"]),
]
for i, (col, name, pts) in enumerate(mab_data):
    left_x = Inches(0.3 + i * 3.25)
    # header card
    shp = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                              left_x, Inches(2.15), Inches(3.05), Inches(0.75))
    shp.fill.solid(); shp.fill.fore_color.rgb = col; shp.line.fill.background()
    tf = shp.text_frame; tf.vertical_anchor = MSO_ANCHOR.MIDDLE; tf.margin_left = Inches(0.1)
    p = tf.paragraphs[0]; r = p.add_run()
    r.text = name; r.font.size = Pt(15); r.font.bold = True; r.font.color.rgb = WHITE
    # body
    tb = s.shapes.add_textbox(left_x, Inches(2.98), Inches(3.05), Inches(2.8))
    tf2 = tb.text_frame; tf2.word_wrap = True; tf2.margin_left = Inches(0.08)
    for j, pt in enumerate(pts):
        p2 = tf2.paragraphs[0] if j == 0 else tf2.add_paragraph()
        p2.space_before = Pt(5)
        r2 = p2.add_run(); r2.text = "\u2022  " + pt
        r2.font.size = Pt(13); r2.font.color.rgb = DARK_GRAY

# Advantages box
advbox = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE,
                             Inches(0.3), Inches(5.8), Inches(12.7), Inches(1.5))
advbox.fill.solid(); advbox.fill.fore_color.rgb = LIGHT_GRAY; advbox.line.fill.background()
tf = advbox.text_frame; tf.word_wrap = True
tf.margin_left = Inches(0.2); tf.margin_top = Inches(0.1)
p = tf.paragraphs[0]; r = p.add_run()
r.text = "Advantages of CGRP mAbs over conventional prophylaxis:"
r.font.size = Pt(15); r.font.bold = True; r.font.color.rgb = DARK_PURPLE
adv_txt = "  \u2022  Onset within 1 month (vs. 2–12 weeks for oral drugs)    \u2022  Excellent tolerability profile    \u2022  Monthly or quarterly dosing improves adherence    \u2022  Effective in patients who failed multiple oral preventive drugs    \u2022  Also useful in medication overuse headache"
p2 = tf.add_paragraph(); p2.space_before = Pt(5)
r2 = p2.add_run(); r2.text = adv_txt
r2.font.size = Pt(13); r2.font.color.rgb = DARK_GRAY

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 11 – Drug Selection Guide
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, WHITE)
header_bar(s, "Drug Selection Guide for Migraine")

scenarios = [
    (DARK_PURPLE,  "Mild-to-Moderate Attack",
     "NSAIDs (ibuprofen 400–800 mg) or\nAcetaminophen 1000 mg\n± Antiemetic (metoclopramide)"),
    (MID_PURPLE,   "Moderate-to-Severe / NSAID Failure",
     "Triptan (sumatriptan 50–100 mg PO\nor rizatriptan 10 mg)\n± Antiemetic"),
    (ACCENT_TEAL,  "Nausea / Vomiting Present",
     "Zolmitriptan 5 mg nasal spray\nZavegepant 10 mg nasal spray\nSumatriptan 6 mg SC"),
    (ACCENT_ORANGE,"CV Contraindication to Triptans",
     "Lasmiditan (ditan) 50–200 mg PO\nRimegepant 75 mg ODT\nUbrogepant 50–100 mg PO"),
    (DARK_PURPLE,  "Very Severe / Refractory",
     "DHE 1 mg IM or intranasal 2 mg\nIV DHE protocol + metoclopramide\nIV valproate, IV ketorolac"),
    (MID_PURPLE,   "Menstrual Migraine",
     "Frovatriptan 2.5 mg PO (long T½)\nRimegepant 75 mg q2 days (perimenstrual)\nEstrogen patches (short-term prevention)"),
    (ACCENT_TEAL,  "Episodic Prevention (\u22654 days/month)",
     "Propranolol 40–240 mg/day (1st line)\nTopiramate 50–200 mg/day\nAmitriptyline 10–75 mg/night"),
    (ACCENT_ORANGE,"Chronic Migraine Prevention",
     "OnabotulinumtoxinA (BOTOX\u00ae) 155–195 U\nCGRP mAbs (erenumab, fremanezumab)\nTopiramate + CGRP mAb combination"),
]

for i, (col, scenario, advice) in enumerate(scenarios):
    col_idx = i % 4
    row_idx = i // 4
    lft = Inches(0.25 + col_idx * 3.27)
    top = Inches(1.6 + row_idx * 2.75)
    shp = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE, lft, top,
                              Inches(3.05), Inches(0.55))
    shp.fill.solid(); shp.fill.fore_color.rgb = col; shp.line.fill.background()
    tf = shp.text_frame; tf.vertical_anchor = MSO_ANCHOR.MIDDLE; tf.margin_left = Inches(0.1)
    p = tf.paragraphs[0]; r = p.add_run()
    r.text = scenario; r.font.size = Pt(13.5); r.font.bold = True; r.font.color.rgb = WHITE
    # body text
    tb = s.shapes.add_textbox(lft, top + Inches(0.58), Inches(3.05), Inches(2.1))
    tf2 = tb.text_frame; tf2.word_wrap = True; tf2.margin_left = Inches(0.1)
    p2 = tf2.paragraphs[0]; r2 = p2.add_run()
    r2.text = advice; r2.font.size = Pt(13); r2.font.color.rgb = DARK_GRAY

# ══════════════════════════════════════════════════════════════════════════
# SLIDE 12 – Summary & Key Points
# ══════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
bg_rect(s, DARK_PURPLE)
# decorative
for ox, oy, sz, alpha_col in [
    (Inches(11), Inches(-1), Inches(5), RGBColor(0x55, 0x1F, 0x8A)),
    (Inches(-1), Inches(5), Inches(4), RGBColor(0x4A, 0x17, 0x7A)),
]:
    shp = s.shapes.add_shape(MSO_SHAPE.OVAL, ox, oy, sz, sz)
    shp.fill.solid(); shp.fill.fore_color.rgb = alpha_col; shp.line.fill.background()
bar = s.shapes.add_shape(MSO_SHAPE.RECTANGLE, 0, 0, Pt(10), H)
bar.fill.solid(); bar.fill.fore_color.rgb = ACCENT_TEAL; bar.line.fill.background()

txt(s, "Summary & Key Take-Aways", Inches(0.7), Inches(0.3),
    Inches(11), Inches(0.8), size=32, bold=True, color=WHITE)

key_points = [
    "Migraine pathophysiology involves cortical spreading depression, trigeminal activation, CGRP release and neurogenic inflammation.",
    "Non-specific treatment (NSAIDs, antiemetics) is appropriate for mild attacks; limit use to <10–15 days/month to avoid MOH.",
    "Triptans (5-HT\u2081B/\u2081D agonists) are first-line migraine-specific acute therapy; rizatriptan and eletriptan are among the most efficacious.",
    "Ergot alkaloids (ergotamine, DHE) are nonselective; reserved for refractory cases; contraindicated in CV disease.",
    "Lasmiditan (ditan) is cardiovascular-safe but is a controlled substance with driving impairment risk.",
    "Gepants (rimegepant, ubrogepant, zavegepant) block CGRP receptors; safe in CV disease; rimegepant also approved for prevention.",
    "Prophylaxis is indicated when attacks occur \u22654 days/month; \u03b2-blockers (propranolol) and topiramate are 1st-line oral options.",
    "CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) represent a major advance in prevention with rapid onset and excellent tolerability.",
    "OnabotulinumtoxinA is FDA-approved specifically for CHRONIC migraine (\u226515 days/month) – not for episodic.",
    "Always assess for medication overuse headache (MOH) in any patient with frequent headaches.",
]
tb = s.shapes.add_textbox(Inches(0.7), Inches(1.2), Inches(12.3), Inches(6.0))
tf = tb.text_frame; tf.word_wrap = True; tf.margin_left = Inches(0.05)
for i, pt in enumerate(key_points):
    p = tf.paragraphs[0] if i == 0 else tf.add_paragraph()
    p.space_before = Pt(5)
    r = p.add_run(); r.text = f"{i+1}.  " + pt
    r.font.size = Pt(14.5); r.font.color.rgb = WHITE if i % 2 == 0 else LIGHT_PURPLE

# ══════════════════════════════════════════════════════════════════════════
# SAVE
# ══════════════════════════════════════════════════════════════════════════
out = "/tmp/workspace/migraine-ppt/Migraine_Therapy_Pharmacology.pptx"
buf = BytesIO()
prs.save(buf)
with open(out, "wb") as f:
    f.write(buf.getvalue())
print(f"Saved: {out}  ({len(buf.getvalue())//1024} KB)")

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