#!/usr/bin/env python3
"""
Safe Drugs in Pregnancy - Comprehensive Flowchart Generator
Based on ACOG, AAFP, Katzung Pharmacology, and current guidelines (2024-2025)
"""

import matplotlib
matplotlib.use('Agg')
import matplotlib.pyplot as plt
import matplotlib.patches as mpatches
from matplotlib.patches import FancyBboxPatch, FancyArrowPatch
import numpy as np

fig = plt.figure(figsize=(28, 38), dacecolor='white')
fig.patch.set_facecolor('#FAFBFC')

# ── Colour palette ──────────────────────────────────────────────────────────
C_HEADER   = '#1A237E'   # deep navy
C_SAFE     = '#1B5E20'   # dark green
C_CAUTION  = '#E65100'   # deep orange
C_AVOID    = '#B71C1C'   # dark red
C_CAT_BG   = '#E8EAF6'   # light lavender for category headers
C_SAFE_BG  = '#E8F5E9'   # light green bg
C_CAUT_BG  = '#FFF3E0'   # light orange bg
C_AVOID_BG = '#FFEBEE'   # light red bg
C_NOTE_BG  = '#E3F2FD'   # light blue for notes
C_SUBHDR   = '#283593'   # medium navy
C_TEXT     = '#212121'
C_LINE     = '#546E7A'
C_TITLE_BG = '#1A237E'

ax = fig.add_axes([0, 0, 1, 1])
ax.set_xlim(0, 28)
ax.set_ylim(0, 38)
ax.axis('off')

# ── Helper functions ─────────────────────────────────────────────────────────
def rounded_box(x, y, w, h, fc, ec, lw=1.2, radius=0.3, zorder=2, alpha=1.0):
    box = FancyBboxPatch((x, y), w, h,
                         boxstyle=f"round,pad=0.05,rounding_size={radius}",
                         linewidth=lw, edgecolor=ec, facecolor=fc,
                         zorder=zorder, alpha=alpha)
    ax.add_patch(box)
    return box

def text(x, y, txt, fs=8, fc=C_TEXT, ha='center', va='center',
         bold=False, wrap=False, style='normal'):
    weight = 'bold' if bold else 'normal'
    ax.text(x, y, txt, fontsize=fs, color=fc, ha=ha, va=va,
            fontweight=weight, fontstyle=style,
            zorder=5, wrap=wrap,
            multialignment='left' if ha == 'left' else 'center')

def section_header(x, y, w, h, title, subtitle=''):
    rounded_box(x, y, w, h, C_CAT_BG, C_SUBHDR, lw=2, radius=0.25, zorder=3)
    ax.plot([x, x+w], [y+h-0.38, y+h-0.38], color=C_SUBHDR, lw=1.5, zorder=4)
    text(x+w/2, y+h-0.19, title, fs=9.5, fc=C_SUBHDR, bold=True)
    if subtitle:
        text(x+w/2, y+0.15, subtitle, fs=7.5, fc='#546E7A', style='italic')

def drug_row(x, y, w, drug, dose, status, note=''):
    """status: 'safe','caution','avoid'"""
    colors = {'safe':(C_SAFE_BG, C_SAFE), 'caution':(C_CAUT_BG, C_CAUTION),
              'avoid':(C_AVOID_BG, C_AVOID)}
    bg, ec = colors[status]
    h = 0.52 if not note else 0.68
    rounded_box(x, y, w, h, bg, ec, lw=1, radius=0.18, zorder=3)
    # coloured left bar
    bar = FancyBboxPatch((x, y), 0.12, h,
                         boxstyle="round,pad=0,rounding_size=0.05",
                         linewidth=0, facecolor=ec, zorder=4)
    ax.add_patch(bar)
    # drug name
    text(x+0.22, y+h-(0.26 if not note else 0.38), drug, fs=7.2, fc=ec,
         ha='left', va='center', bold=True)
    # dose
    text(x+0.22, y+(0.14 if not note else 0.22), dose, fs=6.8, fc=C_TEXT,
         ha='left', va='center')
    if note:
        text(x+0.22, y+0.08, note, fs=6.2, fc='#5D4037', ha='left',
             va='center', style='italic')
    return h

# ═══════════════════════════════════════════════════════════════════════════════
#  TITLE BANNER
# ═══════════════════════════════════════════════════════════════════════════════
rounded_box(0.3, 36.4, 27.4, 1.35, C_TITLE_BG, C_TITLE_BG, lw=0, radius=0.4, zorder=2)
text(14, 37.28, '⬥  SAFE DRUGS IN PREGNANCY  ⬥', fs=18, fc='white', bold=True)
text(14, 36.72, 'Comprehensive Guide with Doses — Based on ACOG / AAFP / RCOG / EULAR / Katzung Guidelines (Updated 2024–2025)',
     fs=8, fc='#B0BEC5')

# ── Legend ───────────────────────────────────────────────────────────────────
rounded_box(0.3, 35.35, 27.4, 0.82, '#ECEFF1', '#90A4AE', lw=1, radius=0.2, zorder=2)
for xpos, label, color in [(1.0, '■  Generally Safe (use as indicated)', C_SAFE),
                             (9.5, '■  Use with Caution (trimester-dependent)', C_CAUTION),
                             (19.0, '■  Avoid / Contraindicated', C_AVOID)]:
    text(xpos, 35.76, label, fs=8.2, fc=color, ha='left', bold=True)

# ── Trimester note ────────────────────────────────────────────────────────────
rounded_box(0.3, 34.52, 27.4, 0.6, '#E3F2FD', '#1565C0', lw=1.2, radius=0.2, zorder=2)
text(14, 34.82, '⚠  1st Trimester (0–12 wks): Organogenesis — highest teratogenic risk  |  '
               '2nd Trimester (13–26 wks): Generally safest window  |  '
               '3rd Trimester (27–40 wks): Neonatal effects / labour concerns',
     fs=7.8, fc='#0D47A1', bold=False)

# ═══════════════════════════════════════════════════════════════════════════════
#  COLUMN LAYOUT  — 4 columns
#  col1: x=0.3   col2: x=7.1   col3: x=13.9   col4: x=20.7
# ═══════════════════════════════════════════════════════════════════════════════
COL = [0.35, 7.15, 13.95, 20.75]
CW  = 6.55   # column width

# ══════════════════════════ COLUMN 1 ══════════════════════════════════════════
cy = 33.8

# 1A: ANALGESICS / ANTIPYRETICS
section_header(COL[0], cy-0.45, CW, 0.72, '💊 ANALGESICS / ANTIPYRETICS')
cy -= 0.5

drugs_analgesic = [
    ('Paracetamol (Acetaminophen)', '500–1000 mg q4-6h  Max 4 g/day', 'caution',
     'Preferred. Recent data: caution with prolonged use (neurodevelopmental concern, ACOG 2025)'),
    ('Codeine', '15–60 mg q4h (short-term)', 'caution',
     'Avoid near term; neonatal opioid withdrawal risk'),
    ('Low-dose Aspirin', '81–150 mg/day (preeclampsia prophylaxis)', 'safe',
     'ACOG recommends from 12–16 wks in high-risk. Avoid high doses.'),
    ('NSAIDs (Ibuprofen etc.)', 'Avoid after 20 wks gestation', 'avoid',
     'Premature ductus arteriosus closure; oligohydramnios (FDA 2020)'),
    ('Opioids (morphine, etc.)', 'Only if clearly needed; lowest dose', 'caution',
     'Neonatal abstinence syndrome risk; avoid near delivery'),
]
for drug, dose, st, note in drugs_analgesic:
    h = drug_row(COL[0], cy-0.72, CW, drug, dose, st, note)
    cy -= (h + 0.1)

cy -= 0.2
# 1B: ANTIEMETICS
section_header(COL[0], cy-0.45, CW, 0.72, '💊 ANTIEMETICS')
cy -= 0.5
drugs_antiemetic = [
    ('Pyridoxine (Vit B6)', '10–25 mg TID or 25 mg QID  (<100 mg/day)', 'safe',
     'First-line (ACOG). Alone or combined with doxylamine'),
    ('Doxylamine + Pyridoxine', '10/10 mg at bedtime (Diclegis/Bonjesta)', 'safe',
     'FDA-approved for NVP; safe throughout pregnancy'),
    ('Promethazine', '12.5–25 mg q4-6h PO/PR/IM', 'safe',
     '2nd-line; sedating; avoid IV due to gangrene risk'),
    ('Metoclopramide', '5–10 mg TID (before meals)', 'safe',
     'Generally safe; limit to <12 weeks continuous use'),
    ('Ondansetron', '4–8 mg TID PO/IV', 'caution',
     'Use in refractory NVP. Some data: small oral cleft risk 1st trim — limited to 2nd/3rd trim if possible'),
    ('Ginger', '250 mg QID or 1000–1500 mg/day', 'safe',
     'Evidence-based (multiple RCTs); safe for mild-moderate NVP'),
]
for drug, dose, st, note in drugs_antiemetic:
    h = drug_row(COL[0], cy-0.72, CW, drug, dose, st, note)
    cy -= (h + 0.1)

cy -= 0.2
# 1C: GI DRUGS
section_header(COL[0], cy-0.45, CW, 0.72, '💊 GASTROINTESTINAL')
cy -= 0.5
drugs_gi = [
    ('Calcium carbonate antacids', '500–1000 mg PO with meals / PRN', 'safe', ''),
    ('Magnesium hydroxide', 'Standard antacid doses PRN', 'safe',
     'Avoid near term in large doses (neonatal hypermagnesemia)'),
    ('Omeprazole / Pantoprazole', '20–40 mg OD (PPI)', 'safe',
     'Safe for GERD; omeprazole preferred; avoid 1st trim if possible'),
    ('Ranitidine / Famotidine', 'Famotidine 20 mg BD (H2RA)', 'safe',
     'Ranitidine withdrawn (NDMA); famotidine now preferred'),
    ('Lactulose', '15–30 mL BD-TID for constipation', 'safe', ''),
    ('Psyllium / Ispaghula', 'Standard doses; increase fluids', 'safe', 'First-line for constipation'),
    ('Bisacodyl', '5–10 mg PO PRN', 'caution', 'Occasional use acceptable; avoid chronic use'),
]
for drug, dose, st, note in drugs_gi:
    h = drug_row(COL[0], cy-0.72, CW, drug, dose, st, note)
    cy -= (h + 0.1)

# ══════════════════════════ COLUMN 2 ══════════════════════════════════════════
cy = 33.8

# 2A: ANTIBIOTICS
section_header(COL[1], cy-0.45, CW, 0.72, '💊 ANTIBIOTICS')
cy -= 0.5
drugs_abx = [
    ('Penicillins', 'Standard doses (Amoxicillin 500 mg TID)', 'safe',
     'Drug of choice across all trimesters (PMC 2025)'),
    ('Cephalosporins (all gen.)', 'Standard doses (Cephalexin 500 mg QID)', 'safe',
     'Generally safe. Ceftriaxone: caution at term — kernicterus risk'),
    ('Azithromycin', '500 mg Day 1, then 250 mg Days 2–5', 'safe',
     'Preferred macrolide; avoid erythromycin (hepatotoxicity in pregnancy)'),
    ('Clindamycin', '300–600 mg q6-8h', 'safe', 'Safe all trimesters'),
    ('Nitrofurantoin', '100 mg BD (modified release) × 5–7 days', 'safe',
     'Safe 1st–2nd trim (UTI). AVOID at term: neonatal haemolysis'),
    ('Fosfomycin', '3 g single dose (UTI)', 'safe',
     'Safe 1st trim; limited data 2nd/3rd; good for uncomplicated UTI'),
    ('Metronidazole (systemic)', '400–500 mg BD–TID', 'caution',
     'AVOID 1st trim systemically. Safe 2nd/3rd trim for BV, trichomoniasis'),
    ('Metronidazole (topical/vaginal)', 'Standard vaginal preparation', 'safe', 'Safe all trimesters'),
    ('Vancomycin', '15–20 mg/kg IV q8-12h', 'safe',
     'Use for serious Gram+ infections; TDM required'),
    ('Fluoroquinolones', 'Avoid if alternatives exist', 'avoid',
     'Cartilage damage, CNS toxicity; reserve for no-alternative situations'),
    ('Tetracyclines', 'Avoid in all trimesters', 'avoid',
     'Teeth discolouration, bone growth inhibition in fetus'),
    ('TMP-SMX', 'Avoid (use only if no alternative)', 'avoid',
     'Folate antagonist; neonatal jaundice; supplement with folic acid 4 mg/day if used'),
    ('Aminoglycosides', 'Avoid; short-term only if life-saving', 'avoid',
     'Congenital deafness (streptomycin). Others: short-term acceptable with monitoring'),
    ('Chloramphenicol', 'Avoid especially at term', 'avoid', '"Grey baby syndrome"'),
]
for drug, dose, st, note in drugs_abx:
    h = drug_row(COL[1], cy-0.72, CW, drug, dose, st, note)
    cy -= (h + 0.08)

# ══════════════════════════ COLUMN 3 ══════════════════════════════════════════
cy = 33.8

# 3A: ANTIHYPERTENSIVES
section_header(COL[2], cy-0.45, CW, 0.72, '💊 ANTIHYPERTENSIVES')
cy -= 0.5
drugs_htn = [
    ('Labetalol', '100–400 mg BD-TID PO\nIV: 20 mg bolus → 40–80 mg q10min (acute)', 'safe',
     'ACOG first-line oral agent for chronic HTN in pregnancy'),
    ('Nifedipine (extended-release)', '30–60 mg OD; acute: 10 mg immediate-release', 'safe',
     'First-line; preferred over short-acting (avoid sublingual)'),
    ('Methyldopa', '250 mg BD–TID; max 3 g/day', 'safe',
     'Longest safety record; first-line especially in 1st trim'),
    ('Hydralazine', 'IV: 5–10 mg q20min for acute crisis', 'safe',
     'Second-line for hypertensive emergency; PO also used'),
    ('Hydrochlorothiazide', '12.5–25 mg OD', 'caution',
     'Second-line; avoid if pre-eclampsia; possible neonatal electrolyte issues'),
    ('ACE Inhibitors', 'CONTRAINDICATED', 'avoid',
     'Fetal renal dysgenesis, oligohydramnios, skull hypoplasia — ALL trimesters'),
    ('ARBs (e.g. losartan)', 'CONTRAINDICATED', 'avoid',
     'Same fetal toxicity as ACEi; avoid all trimesters'),
    ('Magnesium Sulphate', 'Loading 4–6 g IV over 20 min, then 1–2 g/h infusion', 'safe',
     'DRUG OF CHOICE for eclampsia seizure prophylaxis/treatment (MAGPIE trial)'),
]
for drug, dose, st, note in drugs_htn:
    h = drug_row(COL[2], cy-0.72, CW, drug, dose, st, note)
    cy -= (h + 0.1)

cy -= 0.2
# 3B: ANTIDIABETIC AGENTS
section_header(COL[2], cy-0.45, CW, 0.72, '💊 ANTIDIABETIC AGENTS')
cy -= 0.5
drugs_dm = [
    ('Insulin (all types)', 'Individualised — target FBG <5.3 mmol/L\nPostprandial 1h <7.8 mmol/L', 'safe',
     'GOLD STANDARD. Drug of choice for all types of diabetes in pregnancy'),
    ('Metformin', '500 mg OD–BD; max 2500 mg/day', 'caution',
     'Used in GDM/T2DM; crosses placenta; long-term fetal effects unknown. ACOG & NICE allow it.'),
    ('Glibenclamide (Glyburide)', 'Starting 2.5 mg OD; max 20 mg/day', 'caution',
     'Used in GDM if insulin refused; neonatal hypoglycaemia risk; crosses placenta'),
    ('Other oral hypoglycaemics', 'Avoid', 'avoid',
     'Insufficient safety data in pregnancy; switch to insulin'),
    ('GLP-1 agonists / SGLT-2i', 'STOP before conception / immediately', 'avoid',
     'Potential fetal harm; no safety data'),
]
for drug, dose, st, note in drugs_dm:
    h = drug_row(COL[2], cy-0.72, CW, drug, dose, st, note)
    cy -= (h + 0.1)

cy -= 0.2
# 3C: ANTICOAGULANTS
section_header(COL[2], cy-0.45, CW, 0.72, '💊 ANTICOAGULANTS / ANTITHROMBOTICS')
cy -= 0.5
drugs_ac = [
    ('LMWH (enoxaparin)', 'Prophylaxis: 40 mg SC OD\nTreatment: 1 mg/kg SC BD', 'safe',
     'DRUG OF CHOICE for VTE in pregnancy. Does not cross placenta.'),
    ('UFH (Unfractionated Heparin)', '5000 units SC q8-12h (prophylaxis)\nTherapeutic: TDM-guided IV/SC', 'safe',
     'Does not cross placenta. Use if LMWH unavailable or near delivery'),
    ('Low-dose Aspirin', '81–150 mg/day', 'safe',
     'Preeclampsia prophylaxis (ACOG: start 12–16 wks in high-risk)'),
    ('Warfarin', 'AVOID (especially 1st trim)', 'avoid',
     'Warfarin embryopathy (6–12 wks); fetal haemorrhage; fetal CNS defects'),
    ('DOACs (apixaban, rivaroxaban)', 'CONTRAINDICATED', 'avoid',
     'Cross placenta; no safety data; fetal haemorrhage'),
]
for drug, dose, st, note in drugs_ac:
    h = drug_row(COL[2], cy-0.72, CW, drug, dose, st, note)
    cy -= (h + 0.1)

# ══════════════════════════ COLUMN 4 ══════════════════════════════════════════
cy = 33.8

# 4A: PSYCHIATRIC / NEUROLOGICAL
section_header(COL[3], cy-0.45, CW, 0.72, '💊 PSYCHIATRIC / NEUROLOGICAL')
cy -= 0.5
drugs_psych = [
    ('SSRIs (Sertraline preferred)', 'Sertraline: 50–200 mg/day\nFluoxetine: 20–60 mg/day', 'safe',
     'ACOG 2025: safe in pregnancy; do not discontinue for pregnancy alone. Paroxetine: avoid (cardiac defects).'),
    ('Sertraline', '50–200 mg/day', 'safe', 'Most-studied SSRI in pregnancy; preferred choice'),
    ('SNRIs (Venlafaxine)', '75–225 mg/day', 'caution',
     'Use if SSRIs insufficient; neonatal adaptation syndrome possible'),
    ('TCAs (Amitriptyline)', '10–75 mg nocte', 'caution',
     '3rd trim: neonatal withdrawal symptoms. Avoid clomipramine near term.'),
    ('Lithium', '300–600 mg BD-TID (TDM: 0.6–1.0 mEq/L)', 'caution',
     'Risk of Ebstein anomaly (weaker than historically thought); fetal cardiac USS. Perinatal toxicity.'),
    ('Valproate', 'AVOID in women of childbearing age', 'avoid',
     'Neural tube defects (1–2%), fetal valproate syndrome; IQ reduction. Banned/restricted (EMA).'),
    ('Carbamazepine', 'If essential: 400–1200 mg/day + folic acid 5 mg/day', 'caution',
     'Neural tube defects (~0.5–1%); supplemental folic acid mandatory'),
    ('Lamotrigine', '100–400 mg/day (doses may need increase in pregnancy)', 'caution',
     'Preferred AED in pregnancy; monitor levels (clearance increases markedly)'),
    ('Haloperidol', '0.5–5 mg OD–BD', 'caution',
     'If antipsychotic needed; avoid high doses near term (EPS in neonate)'),
    ('Quetiapine', '50–400 mg/day', 'caution',
     'Most data among atypicals; gestational diabetes risk; monitor blood glucose'),
    ('Benzodiazepines', 'Avoid prolonged use; lorazepam for acute seizure', 'caution',
     'Neonatal withdrawal, "floppy infant syndrome" with chronic use'),
    ('Phenobarbital', '60–180 mg/day if essential', 'caution',
     'Neonatal withdrawal; vitamin K for neonate at birth'),
]
for drug, dose, st, note in drugs_psych:
    h = drug_row(COL[3], cy-0.72, CW, drug, dose, st, note)
    cy -= (h + 0.08)

cy -= 0.2
# 4B: RESPIRATORY
section_header(COL[3], cy-0.45, CW, 0.72, '💊 RESPIRATORY')
cy -= 0.5
drugs_resp = [
    ('SABA (Salbutamol inhaled)', '100–200 mcg (1–2 puffs) PRN via inhaler', 'safe',
     'Preferred reliever. GINA: safe in pregnancy.'),
    ('ICS (Budesonide inhaled)', '200–400 mcg BD (preferred ICS)', 'safe',
     'Most data in pregnancy; preferred ICS for asthma control'),
    ('LABA + ICS (Budesonide/Formoterol)', 'Standard doses per severity', 'safe',
     'Formoterol safe in pregnancy; combination preferred over separate inhalers'),
    ('Oral prednisolone', '40 mg OD (acute exacerbation, reducing course)', 'caution',
     'Use for severe/uncontrolled asthma; slight cleft palate risk 1st trim at high doses'),
    ('Montelukast', '10 mg nocte', 'caution',
     'Limited human data; generally considered acceptable if asthma inadequately controlled'),
    ('Antihistamines (loratadine/cetirizine)', 'Loratadine 10 mg OD; Cetirizine 10 mg OD', 'safe',
     'Both safe; cetirizine & loratadine preferred (non-sedating). Diphenhydramine also safe.'),
    ('Pseudoephedrine', 'Avoid', 'avoid',
     'Placental vasoconstriction; gastroschisis risk; avoid 1st trim'),
]
for drug, dose, st, note in drugs_resp:
    h = drug_row(COL[3], cy-0.72, CW, drug, dose, st, note)
    cy -= (h + 0.1)

cy -= 0.2
# 4C: THYROID / ENDOCRINE
section_header(COL[3], cy-0.45, CW, 0.72, '💊 THYROID / SUPPLEMENTS')
cy -= 0.5
drugs_thy = [
    ('Levothyroxine', 'Adjusted doses — TSH target 1st trim: 0.1–2.5 mIU/L', 'safe',
     'Continue in hypothyroidism; dose often needs increase 25–50% in pregnancy'),
    ('Propylthiouracil (PTU)', '100–150 mg TID (1st trimester only)', 'caution',
     '1st trim preferred antithyroid; switch to carbimazole 2nd/3rd trim if possible'),
    ('Carbimazole / Methimazole', '10–40 mg OD (2nd/3rd trim preferred)', 'caution',
     'AVOID 1st trim: aplasia cutis, choanal/oesophageal atresia risk'),
    ('Folic Acid', '400 mcg/day (standard); 5 mg/day (high risk)', 'safe',
     'MANDATORY: start 3 months before conception, continue through 1st trim'),
    ('Iron (ferrous sulphate)', '200 mg BD-TID', 'safe', 'Treat iron-deficiency anaemia'),
    ('Calcium + Vit D', 'Ca 1000–1500 mg/day + Vit D 600–800 IU/day', 'safe',
     'WHO: 1.5–2g elemental Ca/day for preeclampsia prevention in low-Ca populations'),
    ('Vitamin K (neonatal)', 'Neonate: 1 mg IM at birth', 'safe',
     'MANDATORY for all neonates; prevents haemorrhagic disease of newborn'),
]
for drug, dose, st, note in drugs_thy:
    h = drug_row(COL[3], cy-0.72, CW, drug, dose, st, note)
    cy -= (h + 0.1)

# ── Footer ────────────────────────────────────────────────────────────────────
footer_y = 0.05
rounded_box(0.3, footer_y, 27.4, 0.7, '#ECEFF1', '#90A4AE', lw=1, radius=0.2, zorder=2)
text(14, footer_y + 0.35,
     'Sources: ACOG 2023-25 | AAFP AFP 2023 | RCOG | EULAR 2024 | Katzung Pharmacology 16e | '
     'Fishman Pulmonary Diseases | PMC Antibiotic Review 2025 | FDA PLLR  |  '
     'This chart is for clinical guidance only — always verify with current labelling and consult specialist.',
     fs=6.5, fc='#607D8B')

plt.tight_layout(pad=0)
plt.savefig('/home/daytona/workspace/drug-pregnancy-flowchart/safe_drugs_pregnancy.png',
            dpi=180, bbox_inches='tight', facecolor='#FAFBFC',
            format='png', transparent=False)
print("Saved successfully.")
plt.close()

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/drug-pregnancy-flowchart/generate_flowchart.py'