General Pharmacology - MBBS Professional Exam Answers

ls -la /tmp/workspace/ 2>/dev/null || mkdir -p /tmp/workspace && echo "workspace ready"

mkdir -p /tmp/workspace/pharmacology-cheatsheet && cat > /tmp/workspace/pharmacology-cheatsheet/gen_pdf.py << 'PYEOF' from reportlab.lib.pagesizes import A4 from reportlab.lib import colors from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle from reportlab.lib.units import cm, mm from reportlab.platypus import (SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable, KeepTogether, PageBreak) from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY from reportlab.graphics.shapes import Drawing, Rect, String, Line, Polygon from reportlab.graphics import renderPDF from reportlab.platypus.flowables import Flowable import io # ─── COLOUR PALETTE ─────────────────────────────────────────────────────────── DARK_BLUE = colors.HexColor("#1A3A5C") MID_BLUE = colors.HexColor("#2E6DA4") LIGHT_BLUE = colors.HexColor("#D6E8F7") ACCENT_TEAL = colors.HexColor("#00897B") ACCENT_GREEN= colors.HexColor("#E8F5E9") WARN_RED = colors.HexColor("#C62828") WARN_YELLOW = colors.HexColor("#FFF9C4") WARN_BORDER = colors.HexColor("#F9A825") GRAY_BG = colors.HexColor("#F5F5F5") DARK_TEXT = colors.HexColor("#212121") TABLE_HEAD = colors.HexColor("#1A3A5C") TABLE_ALT = colors.HexColor("#EBF3FB") BOX_BG = colors.HexColor("#E3F2FD") BOX_BORDER = colors.HexColor("#1565C0") ORANGE_BG = colors.HexColor("#FFF3E0") ORANGE_BDR = colors.HexColor("#E65100") W, H = A4 # 595.27 x 841.89 pts # ─── STYLES ─────────────────────────────────────────────────────────────────── styles = getSampleStyleSheet() def sty(name, **kw): s = ParagraphStyle(name, **kw) return s TITLE = sty("TITLE", fontName="Helvetica-Bold", fontSize=20, textColor=colors.white, spaceAfter=4, alignment=TA_CENTER) SUBTITLE = sty("SUBTITLE", fontName="Helvetica", fontSize=11, textColor=colors.HexColor("#B0C4DE"), alignment=TA_CENTER, spaceAfter=2) H1 = sty("H1", fontName="Helvetica-Bold", fontSize=13, textColor=colors.white, spaceBefore=2, spaceAfter=4) H2 = sty("H2", fontName="Helvetica-Bold", fontSize=10, textColor=DARK_BLUE, spaceBefore=6, spaceAfter=3) H3 = sty("H3", fontName="Helvetica-BoldOblique", fontSize=9, textColor=ACCENT_TEAL, spaceBefore=4, spaceAfter=2) BODY = sty("BODY", fontName="Helvetica", fontSize=8.5, textColor=DARK_TEXT, leading=13, spaceAfter=3, alignment=TA_JUSTIFY) BULLET = sty("BULLET", fontName="Helvetica", fontSize=8.5, textColor=DARK_TEXT, leading=13, leftIndent=14, firstLineIndent=-8, spaceAfter=2) SMALL = sty("SMALL", fontName="Helvetica", fontSize=7.5, textColor=colors.HexColor("#555555"), leading=11, spaceAfter=2) MONO = sty("MONO", fontName="Courier", fontSize=7.5, textColor=DARK_TEXT, leading=11, backColor=GRAY_BG, leftIndent=8, spaceAfter=2) WARN = sty("WARN", fontName="Helvetica-Bold", fontSize=8.5, textColor=WARN_RED, spaceBefore=2, spaceAfter=2) KEY = sty("KEY", fontName="Helvetica-Bold", fontSize=8.5, textColor=DARK_BLUE, spaceBefore=2, spaceAfter=2) TABLE_HEAD_S = sty("TH", fontName="Helvetica-Bold", fontSize=8, textColor=colors.white, alignment=TA_CENTER) TABLE_CELL = sty("TC", fontName="Helvetica", fontSize=8, textColor=DARK_TEXT, leading=11, alignment=TA_LEFT) TABLE_CELLC = sty("TCC", fontName="Helvetica", fontSize=8, textColor=DARK_TEXT, leading=11, alignment=TA_CENTER) def bullet(txt, indent=14): return Paragraph(f"<bullet>\u2022</bullet> {txt}", BULLET) def bold(txt): return f"<b>{txt}</b>" def it(txt): return f"<i>{txt}</i>" def col(txt, c): return f'<font color="{c}">{txt}</font>' def hdr(p, text): """Section header with coloured background.""" d = Drawing(W - 3*cm, 20) d.add(Rect(0, 0, W - 3*cm, 18, fillColor=DARK_BLUE, strokeColor=None)) d.add(String(8, 5, text, fontName="Helvetica-Bold", fontSize=11, fillColor=colors.white)) p.append(d) p.append(Spacer(1, 4)) def subhdr(text): d = Drawing(W - 3*cm, 16) d.add(Rect(0, 0, W - 3*cm, 15, fillColor=MID_BLUE, strokeColor=None)) d.add(String(6, 4, text, fontName="Helvetica-Bold", fontSize=9.5, fillColor=colors.white)) return d def box(content_list, bg=BOX_BG, border=BOX_BORDER): """Wrap a list of flowables in a coloured box via Table.""" inner = [Spacer(1,4)] + content_list + [Spacer(1,4)] t = Table([[inner]], colWidths=[W - 3.2*cm]) t.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,-1), bg), ("BOX", (0,0), (-1,-1), 1, border), ("LEFTPADDING", (0,0), (-1,-1), 8), ("RIGHTPADDING", (0,0), (-1,-1), 8), ("TOPPADDING", (0,0), (-1,-1), 2), ("BOTTOMPADDING", (0,0), (-1,-1), 4), ])) return t def std_table(headers, rows, col_widths=None): data = [[Paragraph(h, TABLE_HEAD_S) for h in headers]] for row in rows: data.append([Paragraph(str(c), TABLE_CELL) for c in row]) if not col_widths: n = len(headers) col_widths = [(W - 3.2*cm)/n] * n t = Table(data, colWidths=col_widths, repeatRows=1) style = [ ("BACKGROUND", (0,0), (-1,0), TABLE_HEAD), ("TEXTCOLOR", (0,0), (-1,0), colors.white), ("ROWBACKGROUNDS", (0,1), (-1,-1), [colors.white, TABLE_ALT]), ("GRID", (0,0), (-1,-1), 0.4, colors.HexColor("#BBBBBB")), ("LEFTPADDING", (0,0), (-1,-1), 5), ("RIGHTPADDING", (0,0), (-1,-1), 5), ("TOPPADDING", (0,0), (-1,-1), 3), ("BOTTOMPADDING", (0,0), (-1,-1), 3), ("VALIGN", (0,0), (-1,-1), "TOP"), ] t.setStyle(TableStyle(style)) return t def two_col(left_items, right_items): """Two-column layout.""" cw = (W - 3.4*cm) / 2 - 4 left_t = Table([[f] for f in left_items], colWidths=[cw]) right_t = Table([[f] for f in right_items], colWidths=[cw]) left_t.setStyle(TableStyle([("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0),("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0)])) right_t.setStyle(TableStyle([("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0),("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0)])) outer = Table([[left_t, right_t]], colWidths=[cw+4, cw+4]) outer.setStyle(TableStyle([ ("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0), ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0), ("VALIGN",(0,0),(-1,-1),"TOP"), ])) return outer # ─── ASCII DIAGRAM HELPER ────────────────────────────────────────────────────── def ascii_box(lines, bg=GRAY_BG): content = [Paragraph(line, MONO) for line in lines] return box(content, bg=bg, border=colors.HexColor("#90A4AE")) # ══════════════════════════════════════════════════════════════════════════════ # BUILD DOCUMENT # ══════════════════════════════════════════════════════════════════════════════ out_path = "/tmp/workspace/pharmacology-cheatsheet/General_Pharmacology_Cheatsheet.pdf" doc = SimpleDocTemplate(out_path, pagesize=A4, leftMargin=1.5*cm, rightMargin=1.5*cm, topMargin=1.5*cm, bottomMargin=1.5*cm) story = [] # ───────────────────────────────────────────────────────────────────────────── # COVER HEADER # ───────────────────────────────────────────────────────────────────────────── cover_table = Table( [[Paragraph("GENERAL PHARMACOLOGY", TITLE)], [Paragraph("MBBS Professional Exam Cheat Sheet | All 16 Topics", SUBTITLE)]], colWidths=[W - 3*cm] ) cover_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE), ("TOPPADDING", (0,0), (-1,-1), 10), ("BOTTOMPADDING", (0,0), (-1,-1), 10), ("LEFTPADDING", (0,0), (-1,-1), 12), ])) story.append(cover_table) story.append(Spacer(1, 8)) # INDEX index_data = [ ["1. Routes of Administration", "2. Generic & Chemical Names", "3. Special Drug Delivery / TDDS"], ["4. Anaphylactic Shock", "5. Teratogenic Drugs", "6. Drug Antagonism"], ["7. Plasma Protein Binding", "8. First Pass Metabolism", "9. Bioavailability"], ["10. Omeprazole – Empty Stomach", "11. Zero & First Order Kinetics", "12. Plasma Half-Life"], ["13. Therapeutic Drug Monitoring", "14. Fixed Dose Combination", "15. Clinical Trials"], ["16. Adverse Drug Reactions", "", ""], ] idx_t = Table(index_data, colWidths=[(W-3*cm)/3]*3) idx_t.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,-1), LIGHT_BLUE), ("TEXTCOLOR", (0,0), (-1,-1), DARK_BLUE), ("FONTNAME", (0,0), (-1,-1), "Helvetica"), ("FONTSIZE", (0,0), (-1,-1), 8), ("GRID", (0,0), (-1,-1), 0.3, MID_BLUE), ("LEFTPADDING", (0,0), (-1,-1), 6), ("TOPPADDING", (0,0), (-1,-1), 4), ("BOTTOMPADDING", (0,0), (-1,-1), 4), ])) story.append(idx_t) story.append(Spacer(1, 10)) # ════════════════════════════════════════════════════════════════════════ # TOPIC 1 – Routes of Administration # ════════════════════════════════════════════════════════════════════════ hdr(story, "1. ROUTES OF DRUG ADMINISTRATION") routes = [ ["Route", "Onset", "Bioavail.", "Advantages", "Disadvantages", "Examples"], ["IV", "Seconds", "100%", "Immediate, accurate titration, large vol.", "Irreversible, infection risk, skilled staff", "Morphine, Lignocaine"], ["IM", "10–30 min", "75–100%", "Faster than oral, depot possible", "Painful, nerve injury risk", "Penicillin, Vaccines"], ["SC", "15–30 min", "75–100%", "Sustained release, self-admin", "Small vol only (<2 mL), necrosis risk", "Insulin, Heparin"], ["Oral", "30–90 min", "Variable", "Safe, cheap, convenient", "First-pass, food interactions, slow", "Metformin, Aspirin"], ["Sublingual", "1–2 min", "High", "Bypasses first pass, rapid", "Small doses only, taste", "GTN, Buprenorphine"], ["Rectal", "5–30 min", "~50%", "Useful if vomiting/unconscious", "Irregular absorption, inconvenient", "Diazepam, Paracetamol"], ["Transdermal", "Hours", "Moderate", "Bypass first pass, sustained, non-invasive", "Slow onset, skin irritation", "GTN patch, Nicotine patch"], ["Inhalation", "Minutes", "High (local)", "Direct lung delivery, low systemic SE", "Difficult technique", "Salbutamol, Beclometasone"], ] story.append(std_table(routes[0], routes[1:], col_widths=[1.8*cm, 1.4*cm, 1.4*cm, 3.8*cm, 3.8*cm, 3.3*cm])) story.append(Spacer(1, 6)) # ════════════════════════════════════════════════════════════════════════ # TOPIC 2 – Generic & Chemical Names # ════════════════════════════════════════════════════════════════════════ hdr(story, "2. GENERIC AND CHEMICAL NAMES OF DRUGS") story.append(two_col( [ Paragraph(bold("Definitions"), H2), bullet("<b>Chemical name:</b> Full IUPAC structure name"), bullet("<b>Generic (INN) name:</b> Official non-proprietary name – used in prescriptions"), bullet("<b>Brand name:</b> Manufacturer's trade name (capital letter)"), Spacer(1,4), Paragraph(bold("Rule:") + " Prescriptions should always use <b>generic (INN)</b> names – reduces cost, prevents confusion", BODY), ], [ Paragraph(bold("Examples"), H2), std_table( ["Chemical Name", "Generic Name", "Brand"], [ ["2-Acetoxybenzoic acid", "Aspirin", "Ecosprin"], ["N-(4-hydroxyphenyl)acetamide", "Paracetamol", "Crocin"], ["7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one", "Diazepam", "Valium"], ["(S)-Omeprazole", "Esomeprazole", "Nexium"], ], col_widths=[5.5*cm, 2.5*cm, 1.8*cm] ), ] )) story.append(Spacer(1, 8)) # ════════════════════════════════════════════════════════════════════════ # TOPIC 3 – Special Drug Delivery / TDDS # ════════════════════════════════════════════════════════════════════════ hdr(story, "3. SPECIAL DRUG DELIVERY SYSTEMS | TRANSDERMAL (TDDS)") story.append(two_col( [ Paragraph(bold("Types of Special Delivery Systems"), H2), bullet("<b>SR/ER tablets:</b> Sustained release over 8–12 h (Nifedipine SR, Metformin XR)"), bullet("<b>Enteric-coated:</b> Resists gastric acid; dissolves at alkaline intestinal pH (Aspirin EC, Omeprazole)"), bullet("<b>OROS (osmotic pump):</b> Laser-drilled tablet, constant release (Nifedipine GITS)"), bullet("<b>Liposomes:</b> Phospholipid vesicles – targeted delivery (Liposomal Amphotericin B)"), bullet("<b>Nanoparticles:</b> <500 nm carriers – cancer targeting"), bullet("<b>Implants:</b> Long-term SC; Norplant (levonorgestrel 5 yr)"), Spacer(1,4), Paragraph(bold("TDDS Drug Requirements"), H2), bullet("High <b>lipid solubility</b>"), bullet("Low MW (<500 Da)"), bullet("Low effective dose (potent)"), bullet("Non-irritating to skin"), Spacer(1,4), Paragraph(bold("TDDS Examples"), H2), std_table(["Drug","Indication"],[ ["GTN","Angina"],["Scopolamine","Motion sickness"], ["Nicotine","Smoking cessation"],["Fentanyl","Chronic pain"], ["Clonidine","Hypertension"],["Estradiol","HRT"], ], col_widths=[4.5*cm, 4.0*cm]), ], [ Paragraph(bold("TDDS Patch Structure"), H2), ascii_box([ "┌─────────────────────────────────┐", "│ BACKING LAYER (occlusive film) │", "├─────────────────────────────────┤", "│ DRUG RESERVOIR (gel/matrix) │", "├─────────────────────────────────┤", "│ RATE-CONTROLLING MEMBRANE │", "├─────────────────────────────────┤", "│ CONTACT ADHESIVE LAYER │", "├─────────────────────────────────┤", "│ RELEASE LINER (peel before use) │", "└─────────────────────────────────┘", " ↓↓ Drug permeates skin ↓↓", " Stratum corneum → Dermis", " → Capillaries", ]), Spacer(1,6), Paragraph(bold("Advantages vs Disadvantages"), H2), std_table(["Advantage","Disadvantage"],[ ["Avoid first-pass metabolism","Slow onset of action"], ["Sustained drug levels","Skin irritation/allergy"], ["Non-invasive","Only lipophilic drugs qualify"], ["Easy removal (stops drug delivery)","Expensive"], ["Good patient compliance","Cannot use for high-dose drugs"], ], col_widths=[4.5*cm,4.5*cm]), ] )) story.append(PageBreak()) # ════════════════════════════════════════════════════════════════════════ # TOPIC 4 – Anaphylactic Shock # ════════════════════════════════════════════════════════════════════════ hdr(story, "4. MANAGEMENT OF ANAPHYLACTIC SHOCK") story.append(box([ Paragraph(bold("Definition:") + " Life-threatening Type I (IgE-mediated) hypersensitivity reaction with systemic mast cell/basophil degranulation.", BODY), Paragraph(bold("Features:") + " Urticaria, angioedema, bronchospasm, hypotension, tachycardia, loss of consciousness.", BODY), ], bg=WARN_YELLOW, border=WARN_BORDER)) story.append(Spacer(1,4)) story.append(two_col( [ Paragraph(bold("IMMEDIATE MANAGEMENT"), H2), bullet("1. <b>STOP</b> the offending agent"), bullet("2. Lay patient flat, legs elevated (Trendelenburg)"), bullet("3. <b>ADRENALINE (Epinephrine) 0.5 mg IM</b> (1:1000) into anterolateral thigh — <b>DRUG OF CHOICE</b>"), bullet(" Repeat every 5 min if no improvement"), bullet("4. <b>Oxygen</b> 10–15 L/min via face mask"), bullet("5. <b>IV access</b> + 0.9% NaCl rapid bolus (fluid resuscitation)"), bullet("6. <b>Chlorphenamine 10 mg IV</b> (H1 antihistamine — adjunct)"), bullet("7. <b>Hydrocortisone 200 mg IV</b> (prevents late-phase — adjunct)"), bullet("8. <b>Salbutamol nebulizer</b> if bronchospasm persists"), bullet("9. Refractory: IV adrenaline infusion; <b>Glucagon</b> if on β-blockers"), ], [ Paragraph(bold("Mechanism of Adrenaline"), H2), std_table(["Receptor","Effect","Benefit"],[ ["α1","Vasoconstriction","Reverses hypotension"], ["β1","↑ HR, ↑ contractility","Treats shock"], ["β2","Bronchodilation","Relieves bronchospasm"], ["β2","↓ Mast cell degranulation","Limits mediator release"], ], col_widths=[1.8*cm,3.8*cm,3.8*cm]), Spacer(1,6), Paragraph(bold("Key Points"), H2), bullet("Adrenaline is the ONLY life-saving drug"), bullet("Antihistamines and steroids are ADJUNCTS only"), bullet("IM route preferred over IV in non-arrested patients"), bullet("Adrenaline dose in children: 0.01 mg/kg IM (max 0.5 mg)"), Spacer(1,4), box([Paragraph(bold("MNEMONIC: STOAE") + " — Stop, Trendelenburg, Oxygen, Adrenaline, Extras (fluids/steroids/antihistamine)", BODY)], bg=ACCENT_GREEN, border=ACCENT_TEAL), ] )) story.append(Spacer(1, 8)) # ════════════════════════════════════════════════════════════════════════ # TOPIC 5 – Teratogenic Drugs # ════════════════════════════════════════════════════════════════════════ hdr(story, "5. TERATOGENIC DRUGS") story.append(two_col( [ Paragraph(bold("Definition:") + " Agent causing structural/functional defect in embryo/fetus", BODY), Paragraph(bold("Most vulnerable period:") + " <b>Organogenesis (Wk 3–8)</b> — differentiation of organs", BODY), Spacer(1,4), Paragraph(bold("FDA Pregnancy Categories"), H2), std_table(["Category","Safety","Example"],[ ["A","Safe in humans","Folic acid, Thyroxine"], ["B","Safe in animals; no human data","Metformin, Amoxicillin"], ["C","Animal risk; inadequate human data","Aspirin (low dose), Furosemide"], ["D","Human fetal risk; benefit > risk","Phenytoin, Valproate, Carbamazepine"], ["X","CONTRAINDICATED in pregnancy","Thalidomide, Isotretinoin, Warfarin, MTX"], ], col_widths=[1.5*cm, 4.5*cm, 3.5*cm]), ], [ Paragraph(bold("Key Teratogenic Drugs"), H2), std_table(["Drug","Effect"],[ ["Thalidomide","Phocomelia (limb reduction)"], ["Valproic acid","Neural tube defects (spina bifida)"], ["Phenytoin","Fetal hydantoin syndrome"], ["Warfarin (T1)","Warfarin embryopathy, nasal hypoplasia"], ["Tetracyclines","Yellow teeth, bone growth inhibition"], ["Isotretinoin (Vit A)","CNS, cardiac, craniofacial defects"], ["ACE inhibitors (T2/T3)","Renal tubular dysplasia, oligohydramnios"], ["Methotrexate","Neural tube defects, limb anomalies"], ["Diethylstilbestrol","Vaginal clear cell carcinoma (daughters)"], ["Lithium","Ebstein's cardiac anomaly"], ["Aminoglycosides","Ototoxicity (CN VIII damage)"], ["Carbamazepine","Neural tube defects"], ["Misoprostol","Möbius syndrome"], ], col_widths=[4.0*cm, 5.5*cm]), ] )) story.append(PageBreak()) # ════════════════════════════════════════════════════════════════════════ # TOPIC 6 – Drug Antagonism # ════════════════════════════════════════════════════════════════════════ hdr(story, "6. DRUG ANTAGONISM") story.append(two_col( [ Paragraph(bold("Types of Antagonism"), H2), std_table(["Type","Mechanism","Key Feature","Example"],[ ["Competitive (reversible)","Competes at same receptor","Parallel right shift; Emax UNCHANGED","Naloxone vs Morphine; Atropine vs ACh"], ["Non-competitive (irreversible)","Binds same/allosteric site permanently","Emax REDUCED; right shift","Phenoxybenzamine vs Adrenaline"], ["Partial agonist","Lower intrinsic activity at receptor","Competes with full agonist","Buprenorphine vs Morphine"], ["Physiological","Opposite effects via different receptors","Different receptors, same endpoint","Adrenaline vs Histamine (bronchi)"], ["Chemical","Direct chemical neutralization","No receptor involved","Protamine vs Heparin; EDTA chelation"], ["Pharmacokinetic","Alters PK of other drug","Changes absorption/metabolism","Rifampicin (inducer) vs OCP"], ], col_widths=[2.2*cm, 3.2*cm, 2.8*cm, 3.0*cm]), ], [ Paragraph(bold("Dose-Response Curve Diagram"), H2), ascii_box([ "Effect", " |", " |───────────────────────────── Agonist alone (Emax)", " | /", " | / ───────────── Competitive antagonist", " | / (parallel right shift; same Emax)", " | /", " | / ─ ─ ─ ─ ─ ─ Non-competitive antagonist", " | / (right shift + REDUCED Emax)", " | /", " └─────────────────────────────▶ Log [Dose]", ]), Spacer(1,4), box([ Paragraph(bold("Exam Key Points:"), H2), bullet("Competitive: Right shift, SAME Emax, overcome by ↑dose"), bullet("Non-competitive: Reduced Emax, CANNOT be overcome"), bullet("Chemical antagonism has NO receptor involvement"), ], bg=ACCENT_GREEN, border=ACCENT_TEAL), ] )) story.append(Spacer(1, 8)) # ════════════════════════════════════════════════════════════════════════ # TOPIC 7 – Plasma Protein Binding # ════════════════════════════════════════════════════════════════════════ hdr(story, "7. PLASMA PROTEIN BINDING") story.append(two_col( [ Paragraph(bold("Key Concept"), H2), Paragraph("Drugs circulate as <b>bound</b> (inactive reservoir) + <b>free/unbound</b> (pharmacologically ACTIVE) fractions.", BODY), Spacer(1,4), std_table(["Protein","Binds","Examples"],[ ["Albumin","Acidic drugs","Warfarin (99%), Phenytoin (90%), Furosemide (99%), Aspirin"], ["α1-acid glycoprotein","Basic drugs","Lignocaine, Propranolol, Quinidine"], ["Globulins","Hormones, vitamins","Cortisol, Vit D, Testosterone"], ], col_widths=[3.0*cm, 3.0*cm, 3.5*cm]), Spacer(1,4), Paragraph(bold("Only FREE drug:"), H2), bullet("Crosses blood-brain barrier"), bullet("Filtered at glomerulus (renally eliminated)"), bullet("Metabolized by liver"), bullet("Exerts pharmacological effect"), bullet("Determines volume of distribution"), ], [ Paragraph(bold("Clinical Significance"), H2), std_table(["Situation","Effect"],[ ["Hypoalbuminaemia (liver disease, nephrotic syndrome)","↑ Free drug → toxicity at normal doses"], ["Drug displacement from binding sites","Transient ↑ free drug (rapidly re-equilibrates)"], ["Neonates (low albumin)","↑ Free drug fraction — adjust dose"], ["Renal failure","Uremic acids displace acidic drugs"], ], col_widths=[4.5*cm, 4.9*cm]), Spacer(1,6), box([ Paragraph(bold("Important Note (Katzung):"), WARN), Paragraph("Protein binding displacement alone rarely causes clinically significant interactions because displaced drug is quickly redistributed and eliminated. Relevant only if the displacing drug <b>also inhibits clearance</b>.", BODY), ], bg=WARN_YELLOW, border=WARN_BORDER), ] )) story.append(PageBreak()) # ════════════════════════════════════════════════════════════════════════ # TOPIC 8 – First Pass Metabolism # ════════════════════════════════════════════════════════════════════════ hdr(story, "8. FIRST PASS METABOLISM") story.append(two_col( [ Paragraph(bold("Definition:") + " Metabolism of drug in <b>gut wall + liver</b> before reaching systemic circulation after oral administration", BODY), Spacer(1,4), ascii_box([ "ORAL DRUG", " ↓", "GI Lumen", " ↓ (CYP3A4 in gut wall)", "Portal Vein", " ↓", "LIVER (CYP450 enzymes)", " ↓", "SYSTEMIC CIRCULATION", "(reduced amount — ↓ bioavailability)", ]), Spacer(1,4), Paragraph(bold("Drugs with High First Pass Effect"), H2), std_table(["Drug","Oral Bioavailability"],[ ["GTN (Glyceryl trinitrate)","< 1%"], ["Lidocaine","~ 3%"], ["Propranolol","~ 25%"], ["Morphine","~ 25%"], ["Testosterone","Very low"], ["Aspirin","~70% (partly)"], ], col_widths=[5.5*cm, 4.0*cm]), ], [ Paragraph(bold("Ways to Bypass First Pass"), H2), std_table(["Route","Example"],[ ["Sublingual","GTN tablet"], ["Transdermal","GTN patch, Estradiol patch"], ["Rectal (50% bypass)","Diazepam, Paracetamol suppository"], ["IV / IM / SC","Morphine injection"], ["Inhalation","Salbutamol MDI"], ], col_widths=[4.5*cm, 5.0*cm]), Spacer(1,6), Paragraph(bold("Factors Affecting First Pass"), H2), bullet("<b>Hepatic blood flow</b> — reduced in liver disease → ↑ bioavailability"), bullet("<b>Enzyme induction</b> (Rifampicin, Phenobarbitone) → ↓ bioavailability"), bullet("<b>Enzyme inhibition</b> (Cimetidine, Grapefruit) → ↑ bioavailability"), bullet("<b>CYP3A4</b> in gut wall — major site for pre-systemic metabolism"), bullet("<b>Cardiac output</b> — high extraction drugs are flow-dependent"), ] )) story.append(Spacer(1, 8)) # ════════════════════════════════════════════════════════════════════════ # TOPIC 9 – Bioavailability # ════════════════════════════════════════════════════════════════════════ hdr(story, "9. BIOAVAILABILITY") story.append(two_col( [ Paragraph(bold("Definition:") + " Fraction of administered dose reaching systemic circulation in pharmacologically active form", BODY), Spacer(1,4), ascii_box([ "F = (AUC_oral / AUC_IV) × 100%", "", "AUC = Area Under Plasma Conc.–Time Curve", ]), Spacer(1,4), ascii_box([ "PLASMA CONC–TIME CURVE", "Cp | ╭─────────╮", " | / \\ ← IV (100%)", " | / ╭────╮", " | / / \\ ← Oral (<100%)", " | / / \\", " └───────────────────▶ Time", " ↑ Tmax", ]), Spacer(1,4), Paragraph(bold("Absolute vs Relative Bioavailability"), H2), bullet("<b>Absolute:</b> Compared to IV (reference = 100%)"), bullet("<b>Relative:</b> Compared to another oral formulation"), ], [ Paragraph(bold("Bioavailability by Route"), H2), std_table(["Route","F (approx.)"],[ ["IV","100%"], ["IM","75–100%"], ["SC","75–100%"], ["Sublingual","50–75%"], ["Rectal","~50%"], ["Oral","5–100% (variable)"], ["Transdermal","Variable"], ], col_widths=[5*cm, 4.5*cm]), Spacer(1,6), Paragraph(bold("Factors Affecting Bioavailability"), H2), bullet("First pass metabolism (main factor for oral drugs)"), bullet("Drug solubility and dissolution rate"), bullet("Gut motility (↑ motility → ↓ absorption time)"), bullet("Food effect (can increase or decrease)"), bullet("Drug formulation (particle size, excipients)"), bullet("Drug–drug interactions (e.g., antacids + fluoroquinolones)"), bullet("Hepatic/gut wall CYP enzyme activity"), ] )) story.append(PageBreak()) # ════════════════════════════════════════════════════════════════════════ # TOPIC 10 – Omeprazole Empty Stomach # ════════════════════════════════════════════════════════════════════════ hdr(story, "10. WHY IS OMEPRAZOLE GIVEN ON EMPTY STOMACH IN THE MORNING?") story.append(two_col( [ Paragraph(bold("Mechanism of Omeprazole (PPI)"), H2), bullet("Prodrug — activated in <b>acidic canalicular pH</b> of parietal cells"), bullet("Active sulphenamide form <b>irreversibly inhibits H⁺/K⁺ ATPase</b> (proton pump)"), bullet("Proton pump must be <b>ACTIVE (secreting acid)</b> to be inhibited"), bullet("Given as <b>enteric-coated</b> capsule (unstable in gastric acid)"), Spacer(1,6), Paragraph(bold("Why Empty Stomach?"), H2), bullet("After overnight fast → maximum proton pumps recruited to canalicular membrane → ready to be inhibited"), bullet("Food intake after dosing stimulates acid secretion → activates pumps → omeprazole now present to bind them"), bullet("Timing: <b>30–60 minutes BEFORE breakfast</b> = optimal"), Spacer(1,4), box([Paragraph(bold("Note:") + " Evening dosing is LESS effective. Twice-daily dosing for nocturnal GERD.", BODY)], bg=ORANGE_BG, border=ORANGE_BDR), ], [ Paragraph(bold("Sequence for Maximum Effect"), H2), ascii_box([ "OVERNIGHT FAST", " ↓", "Proton pumps recruited to", "canalicular membrane (most active)", " ↓", "Take Omeprazole 30–60 min BEFORE", "breakfast (enteric coat dissolves", "in small intestine)", " ↓", "Absorbed → portal blood →", "parietal cell → converted to", "active SULPHENAMIDE", " ↓", "Eat breakfast → stimulates", "acid secretion → pumps ACTIVATE", " ↓", "Sulphenamide irreversibly binds", "active H⁺/K⁺ ATPase", " ↓", "MAXIMUM ACID SUPPRESSION", ]), ] )) story.append(Spacer(1, 8)) # ════════════════════════════════════════════════════════════════════════ # TOPIC 11 – Zero and First Order Kinetics # ════════════════════════════════════════════════════════════════════════ hdr(story, "11. ZERO ORDER AND FIRST ORDER KINETICS") story.append(two_col( [ Paragraph(bold("First Order Kinetics"), H2), std_table(["Feature","Detail"],[ ["Definition","Constant FRACTION (%) eliminated per unit time"], ["Graph (linear)","Exponential decline"], ["Graph (semi-log)","STRAIGHT LINE"], ["Half-life","CONSTANT"], ["When?","Most drugs at therapeutic doses"], ["Formula","dC/dt = –k × C"], ], col_widths=[3.5*cm, 6.0*cm]), Spacer(1,4), Paragraph(bold("Zero Order Kinetics"), H2), std_table(["Feature","Detail"],[ ["Definition","Constant AMOUNT eliminated per unit time"], ["Graph (linear)","STRAIGHT LINE (linear decline)"], ["Graph (semi-log)","Curved line"], ["Half-life","NOT constant (increases with dose)"], ["When?","Elimination SATURATED (capacity-limited)"], ["Danger","Small ↑ in dose → huge ↑ in plasma level"], ["Examples","Phenytoin, Ethanol, Aspirin (high dose)"], ], col_widths=[3.5*cm, 6.0*cm]), ], [ Paragraph(bold("Graphical Comparison"), H2), ascii_box([ "FIRST ORDER (semi-log plot):", "log Cp | ─────────────────────────", " │ ──────", " │ ──────", " └──────────────────────▶ Time", " (Straight line)", "", "ZERO ORDER (linear plot):", "Cp | ─────────────────────", " │ ─────", " └──────────────────────────▶ Time", " (Straight line on linear)", ]), Spacer(1,6), Paragraph(bold("Michaelis-Menten Equation"), H2), ascii_box([ "v = Vmax × C", " ─────────────", " Km + C", "", "When C << Km → FIRST ORDER", "When C >> Km → ZERO ORDER", ]), Spacer(1,4), box([ Paragraph(bold("Classic Exam Example – PHENYTOIN:"), WARN), Paragraph("Switches from first-order to zero-order at therapeutic doses. Small dose changes cause DISPROPORTIONATE plasma level changes → toxicity.", BODY), ], bg=WARN_YELLOW, border=WARN_BORDER), ] )) story.append(PageBreak()) # ════════════════════════════════════════════════════════════════════════ # TOPIC 12 – Plasma Half Life # ════════════════════════════════════════════════════════════════════════ hdr(story, "12. PLASMA HALF LIFE (t½)") story.append(two_col( [ Paragraph(bold("Definition:") + " Time for plasma concentration to fall to <b>50% of its initial value</b>", BODY), Spacer(1,4), ascii_box([ "t½ = 0.693 × Vd / CL", "", "Vd = Volume of distribution (L)", "CL = Clearance (L/h)", "0.693 = ln2", ]), Spacer(1,4), ascii_box([ "% REMAINING (half-life concept):", "After 1 t½ → 50% remains", "After 2 t½ → 25% remains", "After 3 t½ → 12.5% remains", "After 4 t½ → 6.25% remains", "After 5 t½ → ~3% remains (97% eliminated)", ]), Spacer(1,4), ascii_box([ "ACCUMULATION TO STEADY STATE:", "% SS | ─────────────── 100% (5 t½)", " | ─────── 94% (4 t½)", " | ─── 75% (3 t½)", " | 50% (2 t½)", " └─────────────────────▶ t½", ]), ], [ Paragraph(bold("Clinical Significance"), H2), std_table(["Parameter","Relationship to t½"],[ ["Steady state", "Reached after ~4–5 t½"], ["Drug elimination", "~97% eliminated after 5 t½"], ["Dosing interval", "Usually = one t½"], ["Loading dose needed", "If t½ is long (to reach SS quickly)"], ], col_widths=[3.5*cm, 5.5*cm]), Spacer(1,4), Paragraph(bold("Clinical Examples"), H2), std_table(["Drug","t½","Clinical Note"],[ ["Penicillin G","30 min","4–6 hourly dosing needed"], ["Digoxin","36 hours","Once daily; ~7 days to SS"], ["Warfarin","36–42 hours","INR 3–4 days to stabilize"], ["Phenobarbitone","4–5 days","Once daily"], ["Amiodarone","40–55 days","Very long; drug interactions linger"], ["Thiopentone","Short dist. t½","Short action; cumulation on repeat"], ], col_widths=[3.0*cm, 2.2*cm, 4.3*cm]), Spacer(1,4), box([Paragraph(bold("Vd ↑") + " → t½ ↑ (drug distributes widely, less available for elimination). " + bold("CL ↑") + " → t½ ↓ (eliminated faster).", BODY)], bg=BOX_BG, border=BOX_BORDER), ] )) story.append(Spacer(1, 8)) # ════════════════════════════════════════════════════════════════════════ # TOPIC 13 – Therapeutic Drug Monitoring # ════════════════════════════════════════════════════════════════════════ hdr(story, "13. THERAPEUTIC DRUG MONITORING (TDM)") story.append(two_col( [ Paragraph(bold("Definition:") + " Measurement of drug levels in plasma to maintain concentrations within the <b>Therapeutic Window</b>", BODY), Spacer(1,4), ascii_box([ "THERAPEUTIC WINDOW", "Cp |───────────────────── MTC (Minimum Toxic Conc.)", " | THERAPEUTIC RANGE", " |───────────────────── MEC (Min. Effective Conc.)", " | SUBTHERAPEUTIC", " └──────────────────────▶ Time", " Goal: Keep drug level BETWEEN MEC and MTC", ]), Spacer(1,4), Paragraph(bold("Indications for TDM"), H2), bullet("<b>Narrow Therapeutic Index (NTI)</b> drugs"), bullet("Non-linear pharmacokinetics (Phenytoin)"), bullet("High inter-individual variability"), bullet("Serious/irreversible toxicity risk (aminoglycosides)"), bullet("Suspected non-compliance"), bullet("Suspected toxicity"), bullet("Organ failure (renal/hepatic impairment)"), ], [ Paragraph(bold("Drugs Monitored (+ Therapeutic Ranges)"), H2), std_table(["Drug","Therapeutic Range","Main Concern"],[ ["Digoxin","0.8–2 ng/mL","Narrow TI; toxicity common"], ["Phenytoin","10–20 μg/mL","Zero-order kinetics, toxicity"], ["Lithium","0.6–1.2 mEq/L","Narrow TI; serious neurotoxicity"], ["Aminoglycosides","Peak 5–10; Trough <2 μg/mL","Nephro/ototoxicity"], ["Vancomycin","Trough 10–20 μg/mL","Nephrotoxicity"], ["Carbamazepine","4–12 μg/mL","NTI"], ["Valproate","50–100 μg/mL","NTI"], ["Theophylline","10–20 μg/mL","Narrow TI, cardiac arrhythmias"], ["Cyclosporin","100–400 ng/mL","Nephrotoxicity, rejection"], ["Methotrexate","<1 μmol/L @ 48h","High-dose toxicity"], ], col_widths=[2.8*cm, 2.8*cm, 3.9*cm]), Spacer(1,4), box([Paragraph(bold("Sampling:") + " At steady state (after 4–5 t½). Trough level (just before next dose) for most drugs. Peak and trough for aminoglycosides.", BODY)], bg=ACCENT_GREEN, border=ACCENT_TEAL), ] )) story.append(PageBreak()) # ════════════════════════════════════════════════════════════════════════ # TOPIC 14 – Fixed Dose Combination # ════════════════════════════════════════════════════════════════════════ hdr(story, "14. FIXED DOSE COMBINATION (FDC)") story.append(two_col( [ Paragraph(bold("Definition:") + " Two or more APIs combined in a <b>fixed ratio</b> in a single dosage form", BODY), Spacer(1,4), Paragraph(bold("Advantages"), H2), bullet("Synergistic effect → enhanced efficacy at lower individual doses"), bullet("Reduced adverse effects (lower doses used)"), bullet("Improved patient compliance (fewer tablets)"), bullet("Delays development of drug resistance (anti-TB, HIV)"), bullet("Convenient and cost-effective"), Spacer(1,4), Paragraph(bold("Disadvantages"), H2), bullet("Cannot adjust dose of individual component"), bullet("Cannot identify which drug caused ADR"), bullet("Pharmacokinetic incompatibility possible"), bullet("Regulatory challenges"), ], [ Paragraph(bold("Important FDC Examples"), H2), std_table(["FDC Name","Components","Use"],[ ["Augmentin","Amoxicillin + Clavulanate","Beta-lactamase producing organisms"], ["Co-trimoxazole","Trimethoprim + Sulfamethoxazole","UTI, PCP prophylaxis"], ["Sinemet","Levodopa + Carbidopa","Parkinson's disease"], ["Kaletra","Lopinavir + Ritonavir","HIV (ritonavir boosts lopinavir levels)"], ["Combivir","Zidovudine + Lamivudine","HIV"], ["Atripla","TDF + FTC + Efavirenz","HIV (once daily)"], ["Anti-TB (RHEZ)","Rifampicin + INH + Ethambutol + PZA","Tuberculosis"], ["Lodoz","Bisoprolol + HCTZ","Hypertension"], ["Glucovance","Metformin + Glibenclamide","Type 2 Diabetes"], ], col_widths=[2.4*cm, 4.0*cm, 3.1*cm]), ] )) story.append(Spacer(1, 8)) # ════════════════════════════════════════════════════════════════════════ # TOPIC 15 – Clinical Trials # ════════════════════════════════════════════════════════════════════════ hdr(story, "15. CLINICAL TRIALS") story.append(two_col( [ Paragraph(bold("Definition:") + " Prospective study in human participants evaluating a new drug/device intervention", BODY), Spacer(1,4), Paragraph(bold("Phases of Clinical Trials"), H2), std_table(["Phase","Subjects","Focus","Design"],[ ["0 (Microdosing)","<10 healthy volunteers","Sub-therapeutic PK; target binding","Observational"], ["I","20–100 healthy volunteers","SAFETY, tolerance, PK, dose range","Open label"], ["II","100–300 patients","EFFICACY + safety; dose optimization","Double-blind, placebo-controlled"], ["III (Pivotal)","300–3000+ patients","Confirm efficacy vs standard treatment","Multicenter RCT"], ["IV (Post-marketing)","General population","Rare ADRs; long-term safety","Pharmacovigilance"], ], col_widths=[1.8*cm, 3.0*cm, 3.2*cm, 3.0*cm]), Spacer(1,4), box([Paragraph(bold("Phase III is basis for regulatory approval") + " (FDA/CDSCO). Phase IV is where rare/delayed ADRs emerge — drug may be WITHDRAWN (e.g., Rofecoxib/Vioxx).", BODY)], bg=WARN_YELLOW, border=WARN_BORDER), ], [ Paragraph(bold("Key Study Design Terms"), H2), std_table(["Term","Definition"],[ ["Randomization","Random assignment to groups — eliminates selection bias"], ["Single-blind","Patient unaware of treatment allocation"], ["Double-blind","Both patient AND investigator unaware"], ["Triple-blind","Patient + investigator + statistician unaware"], ["Placebo","Inert substance identical in appearance to test drug"], ["Crossover design","Each patient receives both treatments sequentially"], ["Informed consent","Mandatory ethical requirement before enrolment"], ["ITT analysis","Intention-to-treat — all randomized patients analyzed"], ], col_widths=[3.5*cm, 5.5*cm]), Spacer(1,4), Paragraph(bold("Ethical Requirements (Declaration of Helsinki)"), H2), bullet("Informed written consent from all participants"), bullet("Independent Ethics Committee (IEC) approval"), bullet("Right to withdraw at any time without penalty"), bullet("Scientific integrity + pre-registration of trial"), ] )) story.append(PageBreak()) # ════════════════════════════════════════════════════════════════════════ # TOPIC 16 – Adverse Drug Reactions # ════════════════════════════════════════════════════════════════════════ hdr(story, "16. ADVERSE DRUG REACTIONS (ADR)") story.append(Paragraph(bold("WHO Definition:") + " Any noxious, unintended, and undesired effect of a drug occurring at doses used for prophylaxis, diagnosis, or therapy", BODY)) story.append(Spacer(1,4)) story.append(two_col( [ Paragraph(bold("Rawlins & Thompson Classification"), H2), std_table(["Type","Name","Features","Examples"],[ ["A","Augmented","Predictable; dose-dependent; ~80% of ADRs; extension of pharmacology","Bleeding (Warfarin), Hypoglycemia (Insulin), Bradycardia (Propranolol)"], ["B","Bizarre","Unpredictable; dose-independent; immunological or idiosyncratic","Anaphylaxis (Penicillin), Aplastic anemia (Chloramphenicol), Malignant hyperthermia (Succinylcholine)"], ["C","Chronic","Occur with prolonged use","Adrenal suppression (long-term steroids), Tardive dyskinesia (antipsychotics)"], ["D","Delayed","Appear long after drug exposure","Carcinogenesis (DES), Teratogenicity"], ["E","End of use","Withdrawal reactions on stopping drug","Opioid withdrawal, Rebound hypertension (Clonidine)"], ["F","Failure","Unexpected failure of therapy","Drug resistance, Subtherapeutic levels"], ], col_widths=[0.8*cm, 2.0*cm, 3.5*cm, 3.2*cm]), ], [ Paragraph(bold("ADR Severity Grading"), H2), std_table(["Grade","Features","Examples"],[ ["Mild","No therapy needed, not disabling","Mild nausea, dizziness"], ["Moderate","Requires change in therapy","Rash, vomiting"], ["Severe","Life-threatening, hospitalization required","SJS, Anaphylaxis, Agranulocytosis"], ], col_widths=[1.6*cm, 3.5*cm, 4.4*cm]), Spacer(1,6), Paragraph(bold("Important ADR Examples"), H2), std_table(["Drug","ADR"],[ ["ACE inhibitors","Dry cough (↑ bradykinin)"], ["Aminoglycosides","Nephrotoxicity, Ototoxicity"], ["Chloramphenicol","Aplastic anemia, Grey baby syndrome"], ["Metformin","Lactic acidosis"], ["Statins","Myopathy, Rhabdomyolysis"], ["Quinolones","Tendon rupture, QT prolongation"], ["Clozapine","Agranulocytosis"], ["Halothane","Hepatitis"], ["Sulfonamides","Stevens-Johnson syndrome"], ], col_widths=[3.5*cm, 6.0*cm]), ] )) story.append(Spacer(1,4)) story.append(two_col( [ Paragraph(bold("Pharmacovigilance"), H2), bullet("Science of monitoring drug safety post-marketing"), bullet("<b>Yellow Card</b> (UK), <b>MedWatch</b> (USA), <b>PVPI</b> (India)"), bullet("<b>Naranjo Algorithm</b>: assesses causality — Definite / Probable / Possible / Doubtful"), ], [ Paragraph(bold("Factors Predisposing to ADRs"), H2), bullet("Age extremes (neonates, elderly — altered PK/PD)"), bullet("Renal/hepatic impairment"), bullet("Polypharmacy (drug interactions)"), bullet("Genetic polymorphisms (G6PD deficiency, slow/fast acetylators)"), bullet("Previous history of drug allergy"), ] )) # ── FOOTER ──────────────────────────────────────────────────────────────────── story.append(Spacer(1, 12)) story.append(HRFlowable(width="100%", thickness=1, color=DARK_BLUE)) story.append(Spacer(1, 4)) story.append(Paragraph( "<i>References: Katzung's Basic & Clinical Pharmacology 16e | Goodman & Gilman's Pharmacological Basis of Therapeutics | KD Tripathi's Essentials of Medical Pharmacology</i>", SMALL )) # ─── BUILD PDF ──────────────────────────────────────────────────────────────── doc.build(story) print(f"PDF generated: {out_path}") PYEOF echo "Script written"

cd /tmp/workspace/pharmacology-cheatsheet && python gen_pdf.py 2>&1

ls -lh /tmp/workspace/pharmacology-cheatsheet/General_Pharmacology_Cheatsheet.pdf