mkdir -p /home/daytona/workspace/thiopentone-pdf && cat > /home/daytona/workspace/thiopentone-pdf/build.py << 'PYEOF' from reportlab.lib.pagesizes import A4 from reportlab.lib import colors from reportlab.lib.units import mm, cm from reportlab.lib.styles import ParagraphStyle from reportlab.platypus import ( SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable, KeepTogether, PageBreak ) from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY from reportlab.platypus.flowables import Flowable from reportlab.pdfbase import pdfmetrics from reportlab.pdfbase.ttfonts import TTFont import os # ── Register Liberation Sans ────────────────────────────────────────────────── font_paths = [ "/usr/share/fonts/truetype/liberation", "/usr/share/fonts/liberation", "/usr/share/fonts", ] def find_font(name): for d in font_paths: p = os.path.join(d, name) if os.path.exists(p): return p return None reg = find_font("LiberationSans-Regular.ttf") bold = find_font("LiberationSans-Bold.ttf") ital = find_font("LiberationSans-Italic.ttf") boit = find_font("LiberationSans-BoldItalic.ttf") if reg: pdfmetrics.registerFont(TTFont("LibSans", reg)) if bold: pdfmetrics.registerFont(TTFont("LibSans-Bold", bold)) if ital: pdfmetrics.registerFont(TTFont("LibSans-Italic", ital)) if boit: pdfmetrics.registerFont(TTFont("LibSans-BoldItalic", boit)) FONT = "LibSans" if reg else "Helvetica" FONT_BOLD = "LibSans-Bold" if bold else "Helvetica-Bold" FONT_ITAL = "LibSans-Italic" if ital else "Helvetica-Oblique" FONT_BI = "LibSans-BoldItalic" if boit else "Helvetica-BoldOblique" # ── Colour Palette (Teal/Olive/Amber theme) ─────────────────────────────────── C_H1_BG = colors.HexColor("#1B4F5E") # deep teal -- heading bg C_H1_FG = colors.white C_H2_FG = colors.HexColor("#1B4F5E") # deep teal text C_H2_BG = colors.HexColor("#D6EEF5") # very light blue highlight C_H3_FG = colors.HexColor("#5C4B00") # dark amber C_ACCENT = colors.HexColor("#C47D00") # amber accent C_DOSE_BG = colors.HexColor("#FFF3CC") # soft amber highlight for doses C_CAUTION_BG = colors.HexColor("#FDECEA") # soft red highlight for cautions C_PEARL_BG = colors.HexColor("#E8F5E9") # soft green for pearls C_DARK_TEXT = colors.HexColor("#000000") # 100% black C_TABLE_HDR = colors.HexColor("#1B4F5E") C_TABLE_ALT = colors.HexColor("#EAF5F9") C_TABLE_ALT2 = colors.HexColor("#F7FCFE") C_RULE = colors.HexColor("#1B4F5E") FS = 10.5 # base font size LS = 15.5 # body leading CLS = 13 # cell leading PW, PH = A4 ML, MR, MT, MB = 20*mm, 20*mm, 22*mm, 22*mm # ── Style helpers ──────────────────────────────────────────────────────────── def s_body(): return ParagraphStyle("body", fontName=FONT, fontSize=FS, leading=LS, textColor=C_DARK_TEXT, spaceAfter=4, alignment=TA_JUSTIFY) def s_cell(): return ParagraphStyle("cell", fontName=FONT, fontSize=FS, leading=CLS, textColor=C_DARK_TEXT, wordWrap='CJK') def s_cell_bold(): return ParagraphStyle("cell_bold", fontName=FONT_BOLD, fontSize=FS, leading=CLS, textColor=C_DARK_TEXT, wordWrap='CJK') def s_cell_hdr(): return ParagraphStyle("cell_hdr", fontName=FONT_BOLD, fontSize=FS, leading=CLS, textColor=colors.white, wordWrap='CJK') def s_bullet(): return ParagraphStyle("bullet", fontName=FONT, fontSize=FS, leading=LS, leftIndent=14, firstLineIndent=0, textColor=C_DARK_TEXT, bulletIndent=4, spaceAfter=2) def s_sub_bullet(): return ParagraphStyle("sub_bullet", fontName=FONT, fontSize=FS, leading=LS, leftIndent=28, firstLineIndent=0, textColor=C_DARK_TEXT, bulletIndent=18, spaceAfter=2) # ── Heading flowables ───────────────────────────────────────────────────────── class H1(Flowable): def __init__(self, text): Flowable.__init__(self) self.text = text self.width = PW - ML - MR self.height = 22 def draw(self): c = self.canv c.setFillColor(C_H1_BG) c.roundRect(0, 0, self.width, self.height, 4, stroke=0, fill=1) c.setFillColor(C_H1_FG) c.setFont(FONT_BOLD, 12.5) c.drawString(10, 6, self.text) def wrap(self, aw, ah): return (self.width, self.height) class H2(Flowable): def __init__(self, text): Flowable.__init__(self) self.text = text self.width = PW - ML - MR self.height = 19 def draw(self): c = self.canv c.setFillColor(C_H2_BG) c.rect(0, 0, self.width, self.height, stroke=0, fill=1) c.setFillColor(C_H2_FG) c.setFont(FONT_BOLD, 11) c.drawString(8, 5, self.text) def wrap(self, aw, ah): return (self.width, self.height) def h3(text): return Paragraph(f'<font color="#5C4B00"><b>{text}</b></font>', ParagraphStyle("h3", fontName=FONT_BOLD, fontSize=10.5, leading=14, textColor=C_H3_FG, spaceAfter=3, spaceBefore=5)) def body(text): return Paragraph(text, s_body()) def bullet(text, level=1): st = s_bullet() if level == 1 else s_sub_bullet() marker = "- " if level == 1 else " * " return Paragraph(marker + text, st) def sp(h=4): return Spacer(1, h*mm) def rule(): return HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3*mm, spaceBefore=1*mm) def dose_box(text): return Paragraph( f'<font color="#6B4200"><b>DOSE: </b></font>{text}', ParagraphStyle("dose", fontName=FONT, fontSize=FS, leading=LS, backColor=C_DOSE_BG, textColor=C_DARK_TEXT, leftIndent=8, rightIndent=8, borderPad=5, spaceAfter=4, borderColor=C_ACCENT, borderWidth=0.8)) def caution_box(text): return Paragraph( f'<font color="#8B1A1A"><b>CAUTION: </b></font>{text}', ParagraphStyle("caut", fontName=FONT, fontSize=FS, leading=LS, backColor=C_CAUTION_BG, textColor=C_DARK_TEXT, leftIndent=8, rightIndent=8, borderPad=5, spaceAfter=4, borderColor=colors.HexColor("#E57373"), borderWidth=0.8)) def pearl_box(text): return Paragraph( f'<font color="#2E6B3A"><b>PEARL: </b></font>{text}', ParagraphStyle("pearl", fontName=FONT, fontSize=FS, leading=LS, backColor=C_PEARL_BG, textColor=C_DARK_TEXT, leftIndent=8, rightIndent=8, borderPad=5, spaceAfter=4, borderColor=colors.HexColor("#66BB6A"), borderWidth=0.8)) def make_table(data, col_widths, hdr_rows=1): """data = list of lists of Paragraph objects""" t = Table(data, colWidths=col_widths, repeatRows=hdr_rows) n = len(data) style = [ # Header ('BACKGROUND', (0,0), (-1, hdr_rows-1), C_TABLE_HDR), ('TEXTCOLOR', (0,0), (-1, hdr_rows-1), colors.white), ('ALIGN', (0,0), (-1,-1), 'LEFT'), ('VALIGN', (0,0), (-1,-1), 'TOP'), ('GRID', (0,0), (-1,-1), 0.4, colors.HexColor("#B0D0DC")), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING',(0,0),(-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 6), ('RIGHTPADDING',(0,0), (-1,-1), 6), ] for i in range(hdr_rows, n): bg = C_TABLE_ALT if i % 2 == 0 else C_TABLE_ALT2 style.append(('BACKGROUND', (0,i), (-1,i), bg)) t.setStyle(TableStyle(style)) return t # ── Helper: cell paragraph ───────────────────────────────────────────────────── def cp(text, bold=False): st = s_cell_bold() if bold else s_cell() return Paragraph(text, st) def ch(text): return Paragraph(text, s_cell_hdr()) # ═══════════════════════════════════════════════════════════════════════════════ # CONTENT BUILD # ═══════════════════════════════════════════════════════════════════════════════ story = [] # ── TITLE PAGE ──────────────────────────────────────────────────────────────── story.append(sp(10)) title_style = ParagraphStyle("title", fontName=FONT_BOLD, fontSize=20, leading=26, textColor=C_H1_BG, alignment=TA_CENTER, spaceAfter=6) sub_style = ParagraphStyle("sub", fontName=FONT, fontSize=12, leading=16, textColor=C_H3_FG, alignment=TA_CENTER) story.append(Paragraph("THIOPENTONE SODIUM", title_style)) story.append(Paragraph("A Comprehensive Pharmacological Reference", sub_style)) story.append(sp(4)) story.append(HRFlowable(width="80%", thickness=2, color=C_ACCENT, spaceAfter=3*mm, hAlign='CENTER')) story.append(Paragraph( "Intravenous Barbiturate Anaesthetic Agent", ParagraphStyle("tag", fontName=FONT_ITAL, fontSize=11, leading=14, textColor=colors.HexColor("#888800"), alignment=TA_CENTER))) story.append(sp(8)) # ── TOC-style overview box ───────────────────────────────────────────────────── toc_data = [ [ch("Section"), ch("Topic")], [cp("1"), cp("Drug Group & Classification")], [cp("2"), cp("Chemical Structure")], [cp("3"), cp("Formulation & Dilution")], [cp("4"), cp("Available Market Forms")], [cp("5"), cp("Routes of Administration")], [cp("6"), cp("Dosage")], [cp("7"), cp("Mechanism of Action")], [cp("8"), cp("Pharmacokinetics")], [cp("9"), cp("Pharmacodynamics")], [cp("10"), cp("Indications")], [cp("11"), cp("Contraindications")], [cp("12"), cp("Adverse Effects")], [cp("13"), cp("Special Points & Pearls")], ] story.append(make_table(toc_data, [30*mm, 120*mm])) story.append(PageBreak()) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 1 – DRUG GROUP & CLASSIFICATION # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("1. DRUG GROUP AND CLASSIFICATION")) story.append(sp(2)) story.append(body( "Thiopentone sodium (also known as thiopental sodium) is an ultra-short-acting " "intravenous barbiturate anaesthetic. It belongs to the thiobarbiturate subclass " "of barbiturates - compounds derived from barbituric acid (2,4,6-trioxohexahydropyrimidine) " "with a sulfur atom substituted at position 2 of the pyrimidine ring." )) story.append(sp(2)) class_data = [ [ch("Classification Level"), ch("Description")], [cp("Drug Class"), cp("Barbiturate")], [cp("Sub-class"), cp("Thiobarbiturate (sulfur at C-2 of pyrimidine ring)")], [cp("Pharmacological Category"), cp("Intravenous general anaesthetic / CNS depressant")], [cp("WHO Classification"), cp("General anaesthetic - intravenous agent")], [cp("Controlled Status"), cp("Schedule II or equivalent controlled substance in most countries")], [cp("DEA Schedule (USA)"), cp("Schedule III controlled substance")], [cp("Onset"), cp("Ultra-short-acting (onset 30-60 seconds IV)")], [cp("Duration"), cp("Short (awakening in 5-10 min from single dose due to redistribution)")], ] story.append(make_table(class_data, [60*mm, 110*mm])) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 2 – CHEMICAL STRUCTURE # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("2. CHEMICAL STRUCTURE")) story.append(sp(2)) story.append(body( "Thiopentone sodium is formed from barbituric acid (pyrimidine-2,4,6(1H,3H,5H)-trione) " "by two substitutions that confer anaesthetic activity:" )) story.append(sp(1)) story.append(bullet("Position 2: Sulfur replaces oxygen (=S instead of =O) - thiobarbiturate; " "increases lipid solubility and speeds CNS penetration.")) story.append(bullet("Position 5: Substitution with an ethyl group and a 1-methylbutyl group " "confers hypnotic potency.")) story.append(bullet("N-1 atom: Unsubstituted (no methyl group) - distinguishes from methohexital.")) story.append(sp(2)) chem_data = [ [ch("Property"), ch("Value")], [cp("IUPAC Name"), cp("5-Ethyl-5-(1-methylbutyl)-2-thioxo-1,3-diazinane-4,6-dione, sodium salt")], [cp("Molecular Formula"), cp("C11H17N2NaO2S")], [cp("Molecular Weight"), cp("264.32 g/mol (free acid 242.34 g/mol)")], [cp("CAS Number"), cp("71-73-8 (sodium salt)")], [cp("Physical State"), cp("Yellow-white hygroscopic powder or granules")], [cp("Odour"), cp("Slightly unpleasant (sulfur-containing compound)")], [cp("Solubility"), cp("Freely soluble in water; practically insoluble in ether, petroleum spirit")], [cp("pH of 2.5% solution"), cp("10.5 - 11.0 (highly alkaline)")], [cp("pKa"), cp("7.45 (clinically important - near physiologic pH)")], [cp("Protein Binding"), cp("80-86% bound to plasma albumin")], [cp("Ionisation"), cp("Highly ionised at pH 7.4 (ionised form less active, non-ionised crosses BBB)")], [cp("Key Structural Features"), cp("Sulfur at C-2 makes it lipophilic, rapidly crosses blood-brain barrier")], ] story.append(make_table(chem_data, [65*mm, 105*mm])) story.append(sp(2)) story.append(pearl_box( "The pKa of 7.45 is nearly identical to physiologic pH. At normal blood pH, " "approximately 50% is non-ionised (active, lipid-soluble form) - allowing rapid CNS penetration. " "Acidosis increases non-ionised fraction and potentiates the drug effect." )) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 3 – FORMULATION & DILUTION # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("3. FORMULATION AND DILUTION")) story.append(sp(2)) story.append(H2("3.1 Formulation")) story.append(sp(1)) story.append(body( "Thiopentone is formulated as the sodium salt mixed with 6% w/w anhydrous sodium carbonate " "(Na2CO3) as a preservative and to maintain alkalinity. The powder is supplied in amber vials " "for protection from light. The alkaline pH (>10) is essential for solubility - if pH drops, " "the drug precipitates as the free acid." )) story.append(sp(2)) story.append(H2("3.2 Reconstitution and Dilution")) story.append(sp(1)) dil_data = [ [ch("Preparation"), ch("Diluent"), ch("Final Concentration"), ch("Standard Vial"), ch("Notes")], [cp("Standard solution"), cp("Water for injection or Normal Saline (0.9% NaCl)"), cp("2.5% (25 mg/mL)"), cp("500 mg in 20 mL"), cp("Most common clinical use")], [cp("Dilute solution"), cp("Water for injection or Normal Saline"), cp("1.25% (12.5 mg/mL)"), cp("500 mg in 40 mL"), cp("Preferred in elderly / haemodynamically unstable")], [cp("Concentrated solution"), cp("Not recommended for routine use"), cp("5% (50 mg/mL)"), cp("1 g in 20 mL"), cp("Reserved for ICP reduction protocols only")], ] story.append(make_table(dil_data, [38*mm, 44*mm, 38*mm, 28*mm, 22*mm])) story.append(sp(2)) story.append(caution_box( "Do NOT reconstitute with Lactated Ringer (Hartmann) solution or any acidic solution - " "precipitation occurs. Do NOT mix with: succinylcholine, atracurium, vecuronium, rocuronium, " "pancuronium, alfentanil, sufentanil, morphine, dopamine, dobutamine, or midazolam." )) story.append(sp(1)) story.append(dose_box( "Standard clinical preparation: Add 20 mL water for injection to 500 mg vial -> 2.5% solution. " "Each mL = 25 mg thiopentone. Always prepare fresh on the day of use." )) story.append(sp(1)) story.append(body( "Stability after reconstitution: Thiobarbiturates are stable for 7 days when refrigerated " "(2-8 degrees C) after reconstitution. Once removed from refrigerator, use within 24 hours. " "Discard if solution becomes cloudy or precipitate is visible." )) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 4 – AVAILABLE MARKET FORMS # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("4. AVAILABLE FORMS IN THE MARKET")) story.append(sp(2)) story.append(body( "Thiopentone sodium is available as a dry powder for reconstitution (lyophilised powder) " "in sealed glass vials. Liquid pre-mixed solutions are not commercially available due to " "instability of the reconstituted solution over time." )) story.append(sp(2)) market_data = [ [ch("Brand Name"), ch("Manufacturer / Region"), ch("Pack Sizes"), ch("Concentration after Reconstitution")], [cp("Pentothal"), cp("Pfizer / Abbott (USA, Europe, India)"), cp("500 mg, 1 g, 5 g vials"), cp("2.5% standard; 5% for high-dose")], [cp("Intraval Sodium"), cp("Archimedes Pharma (UK)"), cp("500 mg vials"), cp("2.5%")], [cp("Thiopental Sodium"), cp("Various generic manufacturers (India, EU)"), cp("500 mg, 1 g vials"), cp("2.5%")], [cp("Tiopental"), cp("Laboratorio Almirall (Spain)"), cp("500 mg vials"), cp("2.5%")], [cp("Nesdonal"), cp("Sanofi-Aventis (France)"), cp("500 mg, 1 g vials"), cp("2.5%")], [cp("Ravonal"), cp("Hameln Pharma (Germany)"), cp("500 mg vials"), cp("2.5%")], ] story.append(make_table(market_data, [38*mm, 52*mm, 38*mm, 42*mm])) story.append(sp(2)) story.append(pearl_box( "Pentothal by Abbott was the original brand, used globally for decades. " "Abbott discontinued manufacture of Pentothal in the USA in 2011 due to concerns about its use " "in lethal injections. Many countries now rely on generic formulations." )) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 5 – ROUTES OF ADMINISTRATION # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("5. ROUTES OF ADMINISTRATION")) story.append(sp(2)) route_data = [ [ch("Route"), ch("Concentration"), ch("Clinical Use"), ch("Notes")], [cp("Intravenous (IV)"), cp("2.5% (25 mg/mL)"), cp("Induction of general anaesthesia; status epilepticus"), cp("PRIMARY route. Rapid onset 30-60 sec. Use slow injection rate.")], [cp("Rectal"), cp("5-10% suppository / solution"), cp("Premedication / sedation in children"), cp("Onset 10-15 min. Poorly titratable. Rarely used now.")], [cp("Intraosseous (IO)"), cp("2.5%"), cp("Emergency when IV unavailable"), cp("Can be used in emergencies; onset slightly slower")], [cp("Intramuscular (IM)"), cp("Not recommended"), cp("Not used clinically"), cp("Painful; causes tissue necrosis. CONTRAINDICATED")], [cp("Intraarterial"), cp("NOT PERMITTED"), cp("NEVER use"), cp("Causes intense arterial spasm, ischaemia, gangrene - CATASTROPHIC")], ] story.append(make_table(route_data, [32*mm, 32*mm, 52*mm, 54*mm])) story.append(sp(2)) story.append(caution_box( "Intraarterial injection is a serious EMERGENCY. Causes intense vasospasm, " "crystal precipitation in arterioles, ischaemia, and gangrene. " "Management: stop injection, leave needle in situ, inject heparin + papaverine intra-arterially, " "sympathetic block, urgent vascular surgery consult." )) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 6 – DOSAGE # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("6. DOSAGE")) story.append(sp(2)) story.append(H2("6.1 Induction of Anaesthesia")) story.append(sp(1)) dose_data = [ [ch("Patient Group"), ch("Dose (mg/kg IV)"), ch("Typical Adult Dose"), ch("Key Notes")], [cp("Healthy adult (unpremedicated)"), cp("3 - 5 mg/kg"), cp("250-350 mg (10-14 mL of 2.5%)"), cp("Titrate: give 100 mg over 10-15 sec, pause, then increments")], [cp("Premedicated adult"), cp("1.5 - 3 mg/kg"), cp("100-200 mg"), cp("Opioid or benzodiazepine premedication reduces requirement")], [cp("Elderly (>65 years)"), cp("1 - 2 mg/kg"), cp("50-150 mg"), cp("Use lowest dose; slower injection; increased sensitivity")], [cp("Obese patient"), cp("Dose on LBW"), cp("Based on lean body weight"), cp("Do NOT use total body weight - risk of overdose")], [cp("Children (2-12 years)"), cp("5 - 7 mg/kg"), cp("Per body weight"), cp("Higher dose per kg; faster redistribution in children")], [cp("Infants (3 months - 2 years)"), cp("7 - 8 mg/kg"), cp("Per body weight"), cp("Very careful titration required")], [cp("Neonates"), cp("3 - 4 mg/kg"), cp("Per body weight"), cp("Use with extreme caution; respiratory depression risk")], [cp("Debilitated / shocked patient"), cp("0.5 - 2 mg/kg"), cp("Minimal effective dose"), cp("Haemodynamic compromise markedly increases sensitivity")], ] story.append(make_table(dose_data, [44*mm, 30*mm, 40*mm, 56*mm])) story.append(sp(2)) story.append(H2("6.2 Other Clinical Uses")) story.append(sp(1)) otherdose_data = [ [ch("Indication"), ch("Dose"), ch("Notes")], [cp("Maintenance of anaesthesia"), cp("Intermittent 25-50 mg boluses"), cp("Not preferred; long context-sensitive half-time; accumulates")], [cp("Status epilepticus (refractory)"), cp("3-5 mg/kg bolus, then infusion 1-5 mg/kg/hr"), cp("ICU setting only; requires intubation and ventilation")], [cp("Raised ICP / cerebral protection"), cp("High-dose: 3-10 mg/kg bolus or 3-10 mg/kg/hr infusion"), cp("Burst suppression EEG endpoint; requires ICU monitoring")], [cp("Procedural sedation"), cp("50-75 mg increments IV"), cp("Rarely used now; propofol preferred")], [cp("Electroconvulsive therapy (ECT)"), cp("2-3 mg/kg IV"), cp("Standard induction agent for ECT; prevents tonic-clonic phase")], [cp("Rectal (children - premedication)"), cp("25-44 mg/kg rectally (5% solution)"), cp("Onset 10-15 min; max 1 g; rarely used currently")], ] story.append(make_table(otherdose_data, [50*mm, 60*mm, 60*mm])) story.append(sp(2)) story.append(dose_box( "Standard induction adult technique: Inject 100-150 mg over 10-15 seconds. " "Observe for loss of eyelash reflex and apnoea. Give additional 25-50 mg increments if needed. " "Total dose rarely exceeds 500 mg." )) story.append(sp(2)) story.append(caution_box( "Injection rate: Maximum 50 mg per 15 seconds for routine induction. " "Rapid injection (>50 mg/sec) markedly increases risk of apnoea, cardiovascular depression, " "and fall in blood pressure." )) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 7 – MECHANISM OF ACTION # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("7. MECHANISM OF ACTION")) story.append(sp(2)) story.append(H2("7.1 Primary Mechanism - GABA-A Receptor Potentiation")) story.append(sp(1)) story.append(body( "Thiopentone exerts its CNS depressant effects primarily through positive allosteric modulation " "of the GABA-A (gamma-aminobutyric acid type A) receptor-chloride ionophore complex. " "GABA-A receptors are ligand-gated chloride ion channels that mediate inhibitory " "neurotransmission throughout the CNS." )) story.append(sp(1)) story.append(bullet("At low/anaesthetic concentrations: Thiopentone binds to distinct sites on the " "GABA-A receptor (beta subunit) and prolongs the duration of chloride channel " "opening in response to GABA, enhancing inhibitory neurotransmission.")) story.append(bullet("At high concentrations: Thiopentone can directly activate the GABA-A receptor " "and open chloride channels even in the ABSENCE of GABA - this \"GABA-mimetic\" " "effect is responsible for full anaesthetic state.")) story.append(bullet("Result: Increased chloride ion influx -> hyperpolarisation of neuronal membrane " "-> reduced neuronal excitability -> CNS depression.")) story.append(sp(2)) story.append(H2("7.2 Secondary Mechanisms")) story.append(sp(1)) story.append(bullet("Inhibition of excitatory neurotransmitters: Blocks synaptic transmission via " "AMPA-type glutamate receptors and nicotinic acetylcholine receptors.")) story.append(bullet("Sodium channel blockade: At high concentrations, reduces neuronal sodium " "conductance (contributing to anticonvulsant properties).")) story.append(bullet("Potassium channel activation: Increases potassium conductance, contributing " "to membrane hyperpolarisation.")) story.append(bullet("Reduction in brain metabolic rate (CMRO2): Dose-dependent reduction in " "cerebral metabolic rate for oxygen, reducing cerebral blood flow and ICP.")) story.append(sp(2)) # Mechanism flowchart as table story.append(h3("Mechanism Flowchart")) story.append(sp(1)) fc_data = [ [ch("Step"), ch("Event")], [cp("1. Drug entry"), cp("IV injection -> rapid redistribution from blood to brain (highly lipophilic)")], [cp("2. Receptor binding"), cp("Binds GABA-A receptor beta-1 subunit (allosteric site)")], [cp("3. Channel modulation"), cp("Prolongs duration of Cl- channel opening per GABA activation")], [cp("4. Ion flux"), cp("Increased Cl- influx into neuron -> hyperpolarisation")], [cp("5. CNS effect"), cp("Suppressed neuronal firing -> unconsciousness (RAS depression)")], [cp("6. High dose effect"), cp("Direct GABA-mimetic activation -> burst suppression -> isoelectric EEG")], [cp("7. Redistribution"), cp("Drug moves from brain to muscle/fat -> consciousness returns (5-10 min)")], ] story.append(make_table(fc_data, [42*mm, 128*mm])) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 8 – PHARMACOKINETICS # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("8. PHARMACOKINETICS")) story.append(sp(2)) story.append(H2("8.1 Compartmental Model")) story.append(sp(1)) story.append(body( "Thiopentone follows a three-compartment pharmacokinetic model after IV administration. " "The rapid initial distribution (brain uptake) is followed by redistribution to lean tissues " "(muscle) and ultimately to fat, explaining the short clinical duration despite a long " "elimination half-life." )) story.append(sp(1)) pk_data = [ [ch("Parameter"), ch("Value"), ch("Clinical Significance")], [cp("Onset of action (IV)"), cp("30 - 60 seconds"), cp("Due to high lipid solubility and brain blood flow")], [cp("Peak brain concentration"), cp("~1 minute"), cp("Rapid equilibration with effect site")], [cp("Duration of action (single dose)"), cp("5 - 10 minutes"), cp("Due to redistribution, NOT metabolism")], [cp("Bioavailability (IV)"), cp("100%"), cp("Complete by definition")], [cp("Volume of distribution (Vd)"), cp("2.5 L/kg"), cp("Highly lipophilic; distributes to fat extensively")], [cp("Protein binding"), cp("80 - 86%"), cp("Mainly albumin; reduced in hypoalbuminaemia")], [cp("Ionisation at pH 7.4"), cp("~60% ionised"), cp("Non-ionised form penetrates CNS; pKa 7.45")], [cp("Distribution half-life (t1/2 alpha)"), cp("2 - 4 minutes"), cp("Accounts for rapid awakening after single dose")], [cp("Elimination half-life (t1/2 beta)"), cp("10 - 12 hours"), cp("Long! Explains hangover and accumulation with repeat doses")], [cp("Context-sensitive half-time"), cp("Very long (hours with infusion)"), cp("NOT suitable for infusion maintenance in short cases")], [cp("Hepatic clearance"), cp("3.4 mL/kg/min"), cp("Mainly hepatic; low extraction ratio")], [cp("Metabolism"), cp("Hepatic (CYP2C19, CYP3A4)"), cp("Oxidation at C-5 position; ring desulfuration to pentobarbital")], [cp("Metabolites"), cp("Inactive hydroxylated metabolites + pentobarbitone (minor active metabolite)"), cp("Pentobarbitone has longer t1/2")], [cp("Excretion"), cp("Renal (metabolites); <1% unchanged"), cp("No significant renal adjustment needed")], ] story.append(make_table(pk_data, [58*mm, 44*mm, 68*mm])) story.append(sp(2)) story.append(H2("8.2 Distribution Phases")) story.append(sp(1)) dist_data = [ [ch("Phase"), ch("Compartment"), ch("Time"), ch("Effect")], [cp("Alpha - Rapid distribution"), cp("Blood -> Brain, Heart, Kidneys (VRG)"), cp("Minutes 1-5"), cp("Peak CNS effect, unconsciousness")], [cp("Beta - Redistribution"), cp("Brain -> Muscle (lean tissue)"), cp("Minutes 5-30"), cp("Awakening - plasma/brain levels fall rapidly")], [cp("Gamma - Elimination"), cp("Fat / slow tissues -> Liver"), cp("Hours"), cp("Slow release from fat; hangover effect")], ] story.append(make_table(dist_data, [46*mm, 50*mm, 28*mm, 46*mm])) story.append(sp(2)) story.append(pearl_box( "The brief clinical effect of a single induction dose is due to REDISTRIBUTION from the " "brain to muscle and fat - NOT to metabolism. This is why repeated doses or infusions lead " "to prolonged sedation as fat stores become saturated and cannot absorb more drug." )) story.append(sp(2)) story.append(H2("8.3 Factors Altering Pharmacokinetics")) story.append(sp(1)) factors_data = [ [ch("Factor"), ch("Effect on Thiopentone")], [cp("Elderly patients"), cp("Reduced Vd, reduced plasma protein binding, reduced clearance -> greater effect; use lower doses")], [cp("Obesity"), cp("Increased Vd (distributes to fat); prolonged t1/2; dose on lean body weight")], [cp("Hypoalbuminaemia"), cp("Increased free drug fraction -> greater/longer CNS effect at same dose")], [cp("Liver disease"), cp("Reduced protein binding and reduced metabolism -> prolonged action")], [cp("Renal disease"), cp("Minimal direct effect; hypoalbuminaemia increases free fraction")], [cp("Pregnancy"), cp("Reduced protein binding; crosses placenta easily; neonatal depression")], [cp("Cardiac failure / shock"), cp("Reduced Vd and cardiac output -> higher brain concentration per dose")], [cp("Hypothermia"), cp("Reduced metabolism; prolonged action")], [cp("Acidosis"), cp("Increased non-ionised fraction (pKa 7.45) -> enhanced CNS penetration")], [cp("Children"), cp("Higher Vd/kg and faster metabolism; require higher mg/kg doses")], ] story.append(make_table(factors_data, [60*mm, 110*mm])) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 9 – PHARMACODYNAMICS # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("9. PHARMACODYNAMICS")) story.append(sp(2)) story.append(H2("9.1 CNS Effects")) story.append(sp(1)) cns_data = [ [ch("Parameter"), ch("Effect"), ch("Clinical Notes")], [cp("Consciousness"), cp("Loss in 30-60 sec"), cp("Smooth rapid onset without excitement phase")], [cp("Analgesia"), cp("NONE"), cp("Thiopentone is NOT analgesic - anti-analgesic at sub-anaesthetic doses")], [cp("Cerebral blood flow (CBF)"), cp("Decreased 25-40%"), cp("Due to reduced CMRO2; used in raised ICP management")], [cp("CMRO2"), cp("Reduced up to 55%"), cp("Protective in cerebral ischaemia")], [cp("ICP"), cp("Reduced"), cp("Reduction in CBF and CMRO2 reduces ICP")], [cp("EEG"), cp("Burst suppression at high doses; isoelectric at maximum"), cp("Useful endpoint in neuroprotection")], [cp("Anticonvulsant"), cp("Yes - potent"), cp("Increases seizure threshold; used in status epilepticus")], [cp("Muscle relaxation"), cp("Minimal central"), cp("Does not relax skeletal muscle - NMBAs still needed")], [cp("Amnesia"), cp("Yes - anterograde"), cp("Impairs memory formation during anaesthesia")], ] story.append(make_table(cns_data, [46*mm, 38*mm, 86*mm])) story.append(sp(2)) story.append(H2("9.2 Cardiovascular Effects")) story.append(sp(1)) cvs_data = [ [ch("Parameter"), ch("Effect")], [cp("Arterial blood pressure"), cp("Decreased 10-25% (dose-dependent; reduced vasomotor tone + myocardial depression)")], [cp("Heart rate"), cp("Reflex tachycardia (baroreceptor compensation for fall in BP)")], [cp("Cardiac output"), cp("Reduced (decreased stroke volume and myocardial contractility)")], [cp("SVR"), cp("Reduced (venodilation, reduced central sympathetic tone)")], [cp("Coronary blood flow"), cp("Reduced but proportional to CMRO2 reduction")], [cp("Myocardial depression"), cp("Direct depression of myocardial contractility at higher doses")], [cp("Pre-existing CVS disease"), cp("Marked hypotension risk; use with extreme caution")], ] story.append(make_table(cvs_data, [60*mm, 110*mm])) story.append(sp(2)) story.append(H2("9.3 Respiratory Effects")) story.append(sp(1)) resp_data = [ [ch("Parameter"), ch("Effect")], [cp("Respiratory rate"), cp("Decreased / apnoea (dose-dependent central respiratory depression)")], [cp("Tidal volume"), cp("Decreased")], [cp("Ventilatory response to CO2"), cp("Severely blunted - hypercapnia and hypoxia do not stimulate breathing")], [cp("Apnoea"), cp("Common after induction dose - brief (30-90 sec); have airway equipment ready")], [cp("Bronchospasm"), cp("May occur - thiopentone is a HISTAMINE RELEASER; avoid in severe asthma")], [cp("Laryngospasm"), cp("Risk if airway stimulation at light plane of anaesthesia")], ] story.append(make_table(resp_data, [60*mm, 110*mm])) story.append(sp(2)) story.append(H2("9.4 Other System Effects")) story.append(sp(1)) other_data = [ [ch("System"), ch("Effect")], [cp("Renal"), cp("Reduced renal blood flow and GFR (secondary to reduced CO and BP)")], [cp("Hepatic"), cp("Reduced hepatic blood flow; induces hepatic microsomal enzymes (CYP450) with repeat doses")], [cp("Uterine"), cp("Crosses placenta rapidly - causes neonatal CNS depression; use minimised in obstetrics")], [cp("Intraocular P"), cp("Reduces IOP - useful in open eye injuries")], [cp("Antiemetic"), cp("Mild antiemetic property (less PONV than volatile agents)")], [cp("Pain on injection"), cp("LOW (unlike propofol) - thiopentone is not painful IV")], [cp("Shivering"), cp("May occur on emergence")], ] story.append(make_table(other_data, [40*mm, 130*mm])) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 10 – INDICATIONS # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("10. INDICATIONS")) story.append(sp(2)) ind_data = [ [ch("Indication"), ch("Details")], [cp("Induction of general anaesthesia"), cp("Primary historical use; smooth, rapid induction in 30-60 seconds; single bolus technique")], [cp("Rapid Sequence Induction (RSI)"), cp("Used with succinylcholine in full-stomach/aspiration risk patients; though now often replaced by propofol")], [cp("Status epilepticus - refractory"), cp("When benzodiazepines and phenytoin fail; thiopentone infusion achieves burst suppression")], [cp("Raised intracranial pressure (ICP)"), cp("Reduces ICP by lowering CMRO2 and CBF; thiopentone coma in severe TBI with refractory ICP")], [cp("Electroconvulsive therapy (ECT)"), cp("Standard induction agent for ECT procedures; prevents somatic seizure manifestation")], [cp("Neuroprotection (perioperative)"), cp("During neurosurgery - burst suppression to protect brain during expected ischaemia")], [cp("Premedication in children (rectal)"), cp("Rarely used currently; rectal administration for pre-op sedation in uncooperative children")], [cp("Anaesthesia for electroencephalography"), cp("Thiopentone-induced changes are well characterised for EEG interpretation")], [cp("Procedure sedation (historical)"), cp("Short procedures; now largely replaced by propofol and midazolam")], ] story.append(make_table(ind_data, [65*mm, 105*mm])) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 11 – CONTRAINDICATIONS # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("11. CONTRAINDICATIONS")) story.append(sp(2)) story.append(H2("11.1 Absolute Contraindications")) story.append(sp(1)) abs_data = [ [ch("Contraindication"), ch("Reason")], [cp("Hypersensitivity to barbiturates"), cp("Risk of severe anaphylaxis / anaphylactoid reaction; skin testing may identify risk")], [cp("Acute porphyria (all types)"), cp("MOST IMPORTANT ABSOLUTE CI. Barbiturates induce delta-aminolaevulinic acid (ALA) synthetase, precipitating a life-threatening porphyric crisis with severe abdominal pain, neuropathy, and autonomic instability")], [cp("Absence of suitable vein / IV access"), cp("Cannot give intramuscularly - tissue necrosis; cannot give IA - catastrophic")], [cp("Complete airway obstruction"), cp("Respiratory depression will worsen airway obstruction fatally")], [cp("Status asthmaticus"), cp("Risk of histamine release causing fatal bronchospasm")], ] story.append(make_table(abs_data, [58*mm, 112*mm])) story.append(sp(2)) story.append(caution_box( "PORPHYRIA - The single most important absolute contraindication. " "NEVER give thiopentone to a patient with known or suspected acute porphyria. " "All barbiturates are porphyrinogenic. Even small amounts can precipitate a potentially " "fatal porphyric crisis. Safe alternatives: propofol, ketamine, etomidate, regional anaesthesia." )) story.append(sp(2)) story.append(H2("11.2 Relative Contraindications")) story.append(sp(1)) rel_data = [ [ch("Condition"), ch("Reason / Action")], [cp("Severe cardiovascular disease / shock"), cp("Marked hypotension and cardiac depression; use reduced dose or alternative agent")], [cp("Severe liver disease"), cp("Impaired metabolism; prolonged effect; use reduced dose with monitoring")], [cp("Severe renal impairment"), cp("Hypoalbuminaemia increases free drug fraction; use reduced dose")], [cp("Myasthenia gravis"), cp("Increased sensitivity to CNS depressants")], [cp("Addison disease / adrenal insufficiency"), cp("Haemodynamic instability risk; consider etomidate")], [cp("Asthma (mild to moderate)"), cp("Histamine release risk; propofol or ketamine preferred but thiopentone can be used cautiously")], [cp("Raised ICP with poor compliance"), cp("Brief hypotension after induction can reduce CPP; careful titration required")], [cp("Pregnancy (term)"), cp("Crosses placenta; neonatal depression risk; minimise dose; have resuscitation ready")], [cp("Elderly and debilitated patients"), cp("Increased sensitivity; markedly reduced dose; slower injection rate")], [cp("Obstructive sleep apnoea (OSA)"), cp("Exaggerated respiratory depression; have airway management ready")], ] story.append(make_table(rel_data, [62*mm, 108*mm])) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 12 – ADVERSE EFFECTS # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("12. ADVERSE EFFECTS")) story.append(sp(2)) ae_data = [ [ch("System"), ch("Adverse Effect"), ch("Frequency"), ch("Management")], [cp("CVS"), cp("Hypotension"), cp("Common (>10%)"), cp("Fluid preload; reduce dose; pressors if needed")], [cp("CVS"), cp("Reflex tachycardia"), cp("Common"), cp("Usually transient; treat underlying hypotension")], [cp("CVS"), cp("Myocardial depression"), cp("Dose-dependent"), cp("Avoid in poor LV function")], [cp("Respiratory"), cp("Apnoea (transient 30-90 sec)"), cp("Common after induction dose"), cp("Have airway adjuncts; mask ventilate")], [cp("Respiratory"), cp("Bronchospasm"), cp("Uncommon; risk in asthma"), cp("Histamine release; avoid in asthma")], [cp("Respiratory"), cp("Laryngospasm"), cp("Risk if stimulated at light plane"), cp("Jaw thrust; succinylcholine if needed")], [cp("Neuro"), cp("Hangover / sedation"), cp("Common after large doses"), cp("Due to slow release from fat")], [cp("Neuro"), cp("Excitatory phenomena"), cp("Rare: tremor, hiccough, cough"), cp("Antianalgesic effect at sub-anaesthetic doses")], [cp("Neuro"), cp("Hyperalgesia"), cp("At sub-anaesthetic doses"), cp("Thiopentone is anti-analgesic")], [cp("Local"), cp("Venous thrombophlebitis"), cp("Uncommon with 2.5% solution"), cp("5% solution causes phlebitis; use 2.5% only")], [cp("Local"), cp("Tissue necrosis"), cp("With extravasation"), cp("Highly alkaline (pH 11); treat with hyaluronidase + saline")], [cp("Local"), cp("Arterial spasm / gangrene"), cp("With intra-arterial injection"), cp("EMERGENCY - see Section 5")], [cp("Allergic"), cp("Anaphylaxis / anaphylactoid reaction"), cp("Rare ~1:30,000"), cp("Adrenaline (epinephrine), fluids, steroids, antihistamines")], [cp("Haematologic"), cp("Porphyria crisis"), cp("Rare but fatal if susceptible"), cp("Absolute CI - never use in porphyria")], [cp("Metabolic"), cp("Hypothermia"), cp("With prolonged use / infusion"), cp("Active warming")], [cp("GI"), cp("Nausea / vomiting (PONV)"), cp("Less than volatile agents"), cp("Usually mild; antiemetics prophylactically")], [cp("Hepatic"), cp("Enzyme induction (CYP450)"), cp("With repeated dosing"), cp("Drug interactions (warfarin, anticonvulsants)")], ] story.append(make_table(ae_data, [24*mm, 46*mm, 34*mm, 66*mm])) story.append(sp(3)) # ═══════════════════════════════════════════════════════════════════════════════ # SECTION 13 – SPECIAL POINTS AND PEARLS # ═══════════════════════════════════════════════════════════════════════════════ story.append(H1("13. SPECIAL POINTS AND CLINICAL PEARLS")) story.append(sp(2)) story.append(H2("13.1 The 5-Year PEARL Rule for Duration")) story.append(sp(1)) story.append(pearl_box( "The brief clinical duration (5-10 min) is due to REDISTRIBUTION from brain to muscle/fat, " "NOT metabolism. With repeated doses or infusions, fat becomes saturated and duration " "progressively lengthens - this is the context-sensitive half-time problem. " "Thiopentone is unsuitable for TIVA." )) story.append(sp(2)) story.append(H2("13.2 Incompatibilities - Quick Reference")) story.append(sp(1)) incompat_data = [ [ch("Drug Class"), ch("Specific Agents"), ch("Consequence")], [cp("Neuromuscular blockers"), cp("Vecuronium, pancuronium, rocuronium, atracurium, succinylcholine"), cp("Precipitate forms; may occlude IV line during RSI")], [cp("Opioids"), cp("Alfentanil, sufentanil, morphine, fentanyl (in solution)"), cp("Precipitation in solution; give separately")], [cp("Antibiotics"), cp("Penicillins, cephalosporins (acidic solutions)"), cp("pH-mediated precipitation")], [cp("Acidic solutions"), cp("5% glucose (borderline), Ringer lactate"), cp("Precipitation; use only NS or Water for injection")], [cp("Vasopressors"), cp("Dopamine, dobutamine"), cp("Incompatible; give via separate IV")], [cp("Other anaesthetics"), cp("Midazolam, esketamine in same syringe"), cp("Incompatible; give sequentially")], ] story.append(make_table(incompat_data, [44*mm, 64*mm, 62*mm])) story.append(sp(2)) story.append(H2("13.3 Comparison with Propofol (Key Differences)")) story.append(sp(1)) comp_data = [ [ch("Feature"), ch("Thiopentone"), ch("Propofol")], [cp("Analgesic"), cp("NO (anti-analgesic)"), cp("NO")], [cp("Anticonvulsant"), cp("YES - potent"), cp("YES - but weaker")], [cp("Pain on injection"), cp("Minimal"), cp("Common (30-40% patients)")], [cp("PONV"), cp("Low"), cp("Very low (antiemetic)")], [cp("Cardiovascular"), cp("Moderate depression"), cp("Greater depression")], [cp("Suitable for infusion"), cp("NO (accumulates)"), cp("YES (TIVA)")], [cp("Porphyria safe"), cp("NO - CONTRAINDICATED"), cp("YES (safe)") ], [cp("Cerebral protection"), cp("Superior (burst suppression)"), cp("Moderate")], [cp("Cost"), cp("Cheaper"), cp("More expensive")], [cp("Current use"), cp("Declining / limited"), cp("First-line IV induction agent")], ] story.append(make_table(comp_data, [50*mm, 65*mm, 55*mm])) story.append(sp(2)) story.append(H2("13.4 Special Clinical Situations")) story.append(sp(1)) spec_data = [ [ch("Situation"), ch("Recommendation")], [cp("Head injury / raised ICP"), cp("PREFERRED agent - reduces ICP, CMRO2, CBF. Titrate carefully to avoid hypotension (reduces CPP). Target burst suppression on EEG for refractory ICP.")], [cp("Status epilepticus"), cp("Third-line agent after benzodiazepines and phenytoin. IV infusion at 1-5 mg/kg/hr with EEG monitoring in ICU. Intubation mandatory.")], [cp("Obstetrics"), cp("Historically used for CS induction (4-5 mg/kg). Crosses placenta rapidly. Neonatal depression possible. Propofol and ketamine now more common.")], [cp("Paediatric anaesthesia"), cp("Children require higher mg/kg doses due to larger Vd and faster metabolism. Rectal administration for premedication is an option.")], [cp("RSI - full stomach"), cp("Thiopentone 3-5 mg/kg + succinylcholine 1.5 mg/kg is the classic RSI regimen. Do NOT mix in same syringe.")], [cp("Cardiac disease"), cp("Use with caution or avoid. Reduce dose to 0.5-2 mg/kg. Etomidate is preferred for its cardiovascular stability.")], [cp("Porphyria screening"), cp("Always ask about family history of porphyria and dark urine after anaesthesia. If positive: use propofol + regional or ketamine.")], [cp("ECT"), cp("2-3 mg/kg IV. Produces smooth induction. Motor seizure prevented but EEG seizure proceeds normally. May shorten seizure duration vs. methohexital.")], ] story.append(make_table(spec_data, [50*mm, 120*mm])) story.append(sp(2)) story.append(H2("13.5 Storage and Handling")) story.append(sp(1)) store_data = [ [ch("Aspect"), ch("Details")], [cp("Storage (powder)"), cp("Controlled room temperature 15-30 degrees C. Protect from light. Keep sealed.")], [cp("Storage (reconstituted)"), cp("Refrigerate 2-8 degrees C if not used immediately. Stable 7 days refrigerated.")], [cp("pH of solution"), cp("10.5-11.0. Highly alkaline. Extravasation causes tissue necrosis.")], [cp("Colour"), cp("Clear pale yellow solution. Discard if cloudy, precipitate, or colour change.")], [cp("Compatibility check"), cp("Always inspect visually before use. Do NOT mix with other drugs in same syringe.")], [cp("Disposal"), cp("Controlled substance - follow institutional protocol for disposal of unused drug.")], ] story.append(make_table(store_data, [50*mm, 120*mm])) story.append(sp(2)) story.append(H2("13.6 Key Clinical Pearls Summary")) story.append(sp(1)) story.append(pearl_box( "PEARL 1: Thiopentone is anti-analgesic at sub-anaesthetic doses - it can increase pain perception. " "Always ensure adequate analgesia." )) story.append(sp(1)) story.append(pearl_box( "PEARL 2: The pKa of 7.45 means acidosis (e.g. shock) significantly increases the non-ionised " "(active) fraction - patients in acidosis are MUCH more sensitive to thiopentone." )) story.append(sp(1)) story.append(pearl_box( "PEARL 3: Intra-arterial injection is catastrophic. Crystals of free acid precipitate in " "arterioles causing spasm and gangrene. Always confirm venous placement. Light-brown crystals " "are visible in a syringe held to light if intra-arterial blood is aspirated." )) story.append(sp(1)) story.append(pearl_box( "PEARL 4: Na2CO3 (sodium carbonate) is added to thiopentone vials to maintain alkalinity " "and solubility. This also means thiopentone is chemically incompatible with acidic drugs." )) story.append(sp(1)) story.append(pearl_box( "PEARL 5: Thiopentone was abandoned in the USA as a lethal injection agent in 2011 when " "manufacturer Hospira (Abbott) discontinued supply. This triggered its global shortage and " "accelerated the shift to propofol as the primary induction agent." )) story.append(sp(1)) story.append(caution_box( "NEVER use thiopentone as the sole agent for intubation without checking for: (1) porphyria, " "(2) haemodynamic status, (3) airway equipment readiness, (4) IV line patency and site " "(avoid hand/wrist veins where IA injection risk is higher)." )) # ── FOOTER ────────────────────────────────────────────────────────────────────── story.append(sp(4)) story.append(HRFlowable(width="100%", thickness=1, color=C_RULE)) story.append(Paragraph( "References: Miller's Anesthesia 10th Ed.; Morgan and Mikhail's Clinical Anesthesiology 7th Ed.; " "Barash Clinical Anesthesia 9th Ed.; British National Formulary; Goodman and Gilman Pharmacology 14th Ed.", ParagraphStyle("ref", fontName=FONT_ITAL, fontSize=9, leading=12, textColor=colors.HexColor("#555555"), alignment=TA_CENTER))) # ═══════════════════════════════════════════════════════════════════════════════ # BUILD PDF # ═══════════════════════════════════════════════════════════════════════════════ outpath = "/home/daytona/workspace/thiopentone-pdf/Thiopentone_Sodium_Reference.pdf" doc = SimpleDocTemplate( outpath, pagesize=A4, leftMargin=ML, rightMargin=MR, topMargin=MT, bottomMargin=MB, title="Thiopentone Sodium - Comprehensive Pharmacological Reference", author="Orris Medical Reference", ) def add_page_number(canvas, doc): canvas.saveState() canvas.setFont(FONT if reg else "Helvetica", 8) canvas.setFillColor(colors.HexColor("#888888")) canvas.drawCentredString(PW/2, 12*mm, f"Thiopentone Sodium - Page {doc.page}") canvas.restoreState() doc.build(story, onFirstPage=add_page_number, onLaterPages=add_page_number) print(f"PDF saved to: {outpath}") PYEOF echo "Script written OK"

cd /home/daytona/workspace/thiopentone-pdf && python build.py 2>&1

ls -lh /home/daytona/workspace/thiopentone-pdf/Thiopentone_Sodium_Reference.pdf