Pharmacology Study Notes

ls /home/daytona/workspace/ && node --version && ls /home/daytona/skills/docx/

mkdir -p /home/daytona/workspace/pharmacology-guide && ls /home/daytona/skills/d…

cd /home/daytona/workspace/pharmacology-guide && npm install docx 2>&1 | tail -5

node -e "require('docx'); console.log('docx available')" 2>/dev/null || ls /usr/…

~/pharmacology-guide/generate.js

'use strict';

const {
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  HeadingLevel, AlignmentType, BorderStyle, WidthType, ShadingType,
  VerticalAlign, PageBreak, TabStopType, TabStopPosition,
  Header, Footer, PageNumber, NumberFormat, UnderlineType,
  LevelFormat, convertInchesToTwip, TableOfContents
} = require('docx');
const fs = require('fs');

// ── Colour palette ──────────────────────────────────────────
const BLUE_DARK  = '1F3864';   // navy headings
const BLUE_MID   = '2E75B6';   // section heading fill
const BLUE_LIGHT = 'D6E4F0';   // table header rows
const TEAL       = '00B0A0';   // flowchart boxes
const TEAL_LIGHT = 'E0F5F3';   // flowchart light
const AMBER      = 'F5A623';   // highlight / callout
const AMBER_LIGHT= 'FEF3DB';   // callout background
const GRAY_LIGHT = 'F2F2F2';   // alternating table rows
const WHITE      = 'FFFFFF';

// ── Border helper ────────────────────────────────────────────
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// ── Text helpers ─────────────────────────────────────────────
const bold   = (t, sz = 22, color = '000000') => new TextRun({ text: t, bold: true,  size: sz, color });
const normal = (t, sz = 20, color = '000000') => new TextRun({ text: t, bold: false, size: sz, color });
const italic = (t, sz = 20, color = '555555') => new TextRun({ text: t, italics: true, size: sz, color });
const colorBold = (t, color, sz = 20)         => new TextRun({ text: t, bold: true,  size: sz, color });

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const spacer = (before = 100, after = 100) =>
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// ── Heading helpers ──────────────────────────────────────────
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// ── Bullet helper ────────────────────────────────────────────
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// ── Callout box (amber) ──────────────────────────────────────
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}

// ── Flowchart box builder ─────────────────────────────────────
// We simulate a flowchart as a borderless table with styled cells + arrows
function flowBox(text, fill = TEAL, textColor = WHITE, sz = 20) {
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function flowRow(cells) {
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// Vertical flowchart (single column, boxes stacked with arrows)
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}

// ════════════════════════════════════════════════════════════════
//  DOCUMENT CONTENT
// ════════════════════════════════════════════════════════════════

const children = [];

// ── COVER ────────────────────────────────────────────────────
children.push(
  spacer(400, 200),
  new Paragraph({
    children: [new TextRun({ text: 'PHARMACOLOGY', bold: true, size: 72, color: BLUE_DARK })],
    alignment: AlignmentType.CENTER,
    spacing: { before: 200, after: 60 }
  }),
  new Paragraph({
    children: [new TextRun({ text: 'Study Guide with Drug Classification Flowcharts', size: 36, color: BLUE_MID, italics: true })],
    alignment: AlignmentType.CENTER,
    spacing: { before: 0, after: 80 }
  }),
  new Paragraph({
    children: [new TextRun({ text: '─────────────────────────────────────', size: 24, color: BLUE_MID })],
    alignment: AlignmentType.CENTER,
    spacing: { before: 40, after: 80 }
  }),
  new Paragraph({
    children: [new TextRun({ text: 'Topics Covered:', bold: true, size: 24, color: BLUE_DARK })],
    alignment: AlignmentType.CENTER,
    spacing: { before: 40, after: 40 }
  }),
  new Paragraph({
    children: [new TextRun({ text: '1. Introduction to Pharmacology', size: 22, color: '333333' })],
    alignment: AlignmentType.CENTER, spacing: { before: 20, after: 20 }
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  new Paragraph({
    children: [new TextRun({ text: '2. Definition and Scope of Pharmacology', size: 22, color: '333333' })],
    alignment: AlignmentType.CENTER, spacing: { before: 20, after: 20 }
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  new Paragraph({
    children: [new TextRun({ text: '3. Drug Nomenclature and Classification Systems', size: 22, color: '333333' })],
    alignment: AlignmentType.CENTER, spacing: { before: 20, after: 20 }
  }),
  spacer(200, 80),
  new Paragraph({
    children: [new TextRun({ text: 'Source: Katzung\'s Basic and Clinical Pharmacology, 16th Edition', size: 18, color: '777777', italics: true })],
    alignment: AlignmentType.CENTER
  }),
  new Paragraph({ children: [new PageBreak()], spacing: { before: 0, after: 0 } })
);

// ── SECTION 1: INTRODUCTION ──────────────────────────────────
children.push(
  h1('SECTION 1: Introduction to Pharmacology'),
  spacer(120, 60),
  h2('1.1  What is Pharmacology?'),
  spacer(60, 40),

  para([normal('Pharmacology is defined as the ', 20), bold('study of substances that interact with living systems', 20, BLUE_DARK), normal(' through chemical processes. These interactions occur by binding of the substance to regulatory molecules, activating or inhibiting normal body processes.', 20)]),
  spacer(80, 60),

  ...callout([
    'Key Definition',
    'Medical Pharmacology = the science of substances used to PREVENT, DIAGNOSE, and TREAT disease.',
    'Toxicology = the branch of pharmacology dealing with UNDESIRABLE effects of chemicals.'
  ]),
  spacer(80, 60),

  h3('Historical Milestones'),
  bullet('~1500 AD: Rational methods began replacing theoretical speculation in medicine'),
  bullet('18th-19th c: Magendie & Bernard developed experimental pharmacology'),
  bullet('1940s-50s: Rapid expansion - discovery of drug receptors and molecular mechanisms'),
  bullet('Today: Pharmacogenomics, biologics, and targeted therapies dominate research'),

  spacer(100, 60),
  h2('1.2  Flowchart: Scope of Pharmacology'),
  spacer(60, 40)
);

// Flowchart 1: Scope of Pharmacology
children.push(
  branchFlowchart('PHARMACOLOGY', [
    { label: 'Pharmacokinetics', sub: 'What body does to drug', fill: '1F3864' },
    { label: 'Pharmacodynamics', sub: 'What drug does to body', fill: '2E75B6' },
    { label: 'Toxicology', sub: 'Harmful effects', fill: 'C0392B' },
    { label: 'Pharmacogenomics', sub: 'Genetics & drug response', fill: '27AE60' }
  ]),
  spacer(120, 80),
  h2('1.3  Key Pharmacodynamic Terms'),
  spacer(60, 40)
);

// Table: Pharmacodynamic terms
children.push(
  dataTable(
    ['Term', 'Definition', 'Example'],
    [
      ['Agonist', 'Binds to receptor AND activates it; mimics endogenous ligand', 'Salbutamol at β2 receptors'],
      ['Full Agonist', 'Produces maximum possible response (100% efficacy)', 'Morphine at μ-opioid receptors'],
      ['Partial Agonist', 'Produces sub-maximal response even at full receptor occupancy; acts as mixed agonist-antagonist', 'Buprenorphine at μ-opioid receptors'],
      ['Inverse Agonist', 'Binds receptor but reduces activity below baseline', 'Some antihistamines at H1 receptors'],
      ['Competitive Antagonist', 'Blocks agonist by competing for same binding site; effect reversible by increasing agonist', 'Propranolol blocks adrenaline at β receptors'],
      ['Non-competitive Antagonist', 'Binds irreversibly or at allosteric site; reduces maximal response', 'Phenoxybenzamine at α receptors'],
      ['Positive Allosteric Modulator', 'Binds different site; enhances receptor activity', 'Benzodiazepines potentiate GABA-A'],
      ['Potency', 'Amount of drug needed for a given effect (EC50)', 'High potency = less drug needed'],
      ['Efficacy', 'Maximum pharmacological effect achievable regardless of dose', 'Ceiling effect of partial agonists']
    ],
    [25, 45, 30]
  ),
  spacer(120, 80)
);

// Flowchart 2: Agonist-Antagonist Spectrum
children.push(
  h2('1.4  Flowchart: Agonist-Antagonist Drug Spectrum'),
  spacer(60, 40),
  horizontalFlowchart([
    { label: 'Full Agonist\n(100% response)', fill: '27AE60' },
    { label: 'Partial Agonist\n(<100% response)', fill: '2E75B6' },
    { label: 'Antagonist\n(0% / blocks)', fill: BLUE_DARK },
    { label: 'Inverse Agonist\n(< Baseline)', fill: 'C0392B' }
  ], '→'),
  spacer(60, 40),
  ...callout([
    'Clinical Pearl: Partial Agonists',
    'Buprenorphine (partial agonist) is safer than fentanyl (full agonist) in opioid therapy because it suppresses breathing less strongly. However, it can antagonize other opioids in combined use.'
  ]),
  spacer(120, 80)
);

// Therapeutic Index
children.push(
  h2('1.5  Therapeutic Index'),
  spacer(60, 40),
  para([bold('Therapeutic Index (TI) = TD50 ÷ ED50', 22, BLUE_DARK)], { alignment: AlignmentType.CENTER, spacing: { before: 80, after: 80 } }),
  spacer(40, 40),
  dataTable(
    ['Term', 'Meaning'],
    [
      ['ED50', 'Dose effective in 50% of the population'],
      ['TD50', 'Dose toxic in 50% of the population'],
      ['LD50', 'Lethal dose in 50% of animals (preclinical)'],
      ['Narrow TI', 'Small margin; requires therapeutic drug monitoring (e.g., digoxin, warfarin, lithium, aminoglycosides)'],
      ['Wide TI', 'Large safety margin; less monitoring needed (e.g., penicillins, most statins)']
    ],
    [30, 70]
  ),
  spacer(120, 80)
);

// Pharmacokinetics
children.push(
  h2('1.6  Pharmacokinetics (PK) - ADME'),
  spacer(60, 40),
  para([normal('Pharmacokinetics describes ', 20), bold('what the body does to the drug', 20, BLUE_MID), normal(' - encompassing Absorption, Distribution, Metabolism, and Excretion.', 20)]),
  spacer(80, 60)
);

// Flowchart 3: ADME
children.push(
  h3('Flowchart: The ADME Process'),
  spacer(60, 40),
  verticalFlowchart([
    { label: 'ADMINISTRATION\n(Oral / IV / IM / SC / Inhaled)', fill: BLUE_DARK },
    { label: 'A - ABSORPTION\nDrug enters bloodstream from site of administration\nInfluenced by: solubility, formulation, first-pass metabolism', fill: '2980B9' },
    { label: 'D - DISTRIBUTION\nDrug moves from blood into tissues\nInfluenced by: plasma protein binding, lipid solubility, Vd', fill: '2E75B6' },
    { label: 'M - METABOLISM\nPrimarily hepatic (CYP450 enzymes)\nPhase I: oxidation/reduction | Phase II: conjugation', fill: '1A5276' },
    { label: 'E - EXCRETION\nPrimarily renal; also biliary, pulmonary\nDepends on glomerular filtration, tubular secretion', fill: '154360' },
    { label: 'ELIMINATION\nDrug cleared from body\nHalf-life determines dosing frequency', fill: BLUE_DARK }
  ]),
  spacer(80, 60),
  dataTable(
    ['PK Parameter', 'Definition', 'Clinical Relevance'],
    [
      ['Half-life (t½)', 'Time for plasma concentration to fall by 50%', 'Determines dosing interval; ~5 × t½ to reach steady state'],
      ['Volume of Distribution (Vd)', 'Apparent volume in which drug distributes', 'High Vd = extensive tissue binding; low Vd = stays in plasma'],
      ['Clearance (CL)', 'Rate of elimination per unit plasma concentration', 'Determines maintenance dose'],
      ['Bioavailability (F)', 'Fraction of oral dose reaching systemic circulation', 'IV = 100%; oral varies due to first-pass effect'],
      ['AUC', 'Area under plasma concentration-time curve', 'Reflects total drug exposure; used to determine bioequivalence']
    ],
    [25, 38, 37]
  ),
  spacer(120, 80)
);

// Concentration-time curve (text-based)
children.push(
  h2('1.7  Drug Concentration-Time Curve'),
  spacer(60, 40),
  para([normal('The plasma concentration-time curve shows how drug concentration changes over time after a single dose.', 20)]),
  spacer(60, 40),
  dataTable(
    ['Feature', 'Definition'],
    [
      ['Cmax', 'Peak plasma concentration reached'],
      ['Tmax', 'Time at which Cmax is reached'],
      ['MEC (Min. Effective Concentration)', 'Minimum plasma level needed for therapeutic effect'],
      ['MTC (Min. Toxic Concentration)', 'Plasma level above which toxicity occurs'],
      ['Therapeutic Window', 'Range between MEC and MTC — target for dosing'],
      ['AUC', 'Total drug exposure (area under the curve)'],
      ['Rising phase', 'Absorption phase — drug entering blood faster than elimination'],
      ['Falling phase', 'Elimination phase — slope reflects half-life']
    ],
    [40, 60]
  ),
  spacer(80, 60),
  ...callout([
    'Key Concept: Therapeutic Window',
    'Target: maintain plasma concentration ABOVE MEC (effective) and BELOW MTC (toxic).',
    'Narrow therapeutic window drugs (digoxin, phenytoin, lithium) require regular plasma level monitoring.'
  ]),
  spacer(120, 80),
  new Paragraph({ children: [new PageBreak()], spacing: { before: 0, after: 0 } })
);

// ── SECTION 2: DEFINITION AND SCOPE ──────────────────────────
children.push(
  h1('SECTION 2: Definition and Scope of Pharmacology'),
  spacer(120, 60),
  h2('2.1  Primary Components'),
  spacer(60, 40),
  dataTable(
    ['Component', 'Description'],
    [
      ['Drug Actions', 'How a drug interacts with its molecular target (receptor, enzyme, ion channel, transporter)'],
      ['Mechanisms of Action', 'Precise molecular/cellular events triggered by drug-receptor binding'],
      ['Therapeutic Uses', 'Clinical application to prevent, diagnose, or treat disease — determined by PK + PD profile']
    ],
    [30, 70]
  ),
  spacer(100, 60),
  h2('2.2  Subdivisions of Pharmacology'),
  spacer(60, 40)
);

// Flowchart 4: Subdivisions
children.push(
  branchFlowchart('SUBDIVISIONS OF PHARMACOLOGY', [
    { label: 'Clinical\nPharmacology', sub: 'Drug use in patients', fill: '2E75B6' },
    { label: 'Neuropharmacology', sub: 'CNS/PNS drugs', fill: '8E44AD' },
    { label: 'Chemotherapy', sub: 'Anti-infective / anticancer', fill: 'C0392B' },
    { label: 'Immunopharmacology', sub: 'Immune system drugs', fill: '27AE60' },
    { label: 'Toxicology', sub: 'Adverse chemical effects', fill: 'E67E22' }
  ]),
  spacer(120, 80),
  h2('2.3  Adverse Drug Reactions (ADRs)'),
  spacer(60, 40),
  dataTable(
    ['Type', 'Characteristics', 'Example'],
    [
      ['Type A (Augmented)', 'Predictable, dose-dependent; extension of pharmacological action; most common (~80%)', 'Hypoglycemia from excess insulin'],
      ['Type B (Bizarre)', 'Unpredictable, dose-independent; idiosyncratic or immunological; less common but serious', 'Anaphylaxis to penicillin'],
      ['Type C (Chronic)', 'Effects of long-term use', 'HPA axis suppression with prolonged corticosteroids'],
      ['Type D (Delayed)', 'Appear after drug discontinuation', 'Tardive dyskinesia after stopping antipsychotics'],
      ['Type E (End of use)', 'Withdrawal reactions on stopping drug', 'Beta-blocker rebound hypertension']
    ],
    [20, 50, 30]
  ),
  spacer(100, 60),
  h2('2.4  Drug Interactions'),
  spacer(60, 40)
);

// Flowchart 5: Drug Interactions
children.push(
  branchFlowchart('DRUG INTERACTIONS', [
    { label: 'Pharmacokinetic', sub: 'Affects ADME of other drug', fill: '2E75B6' },
    { label: 'Pharmacodynamic', sub: 'Affects receptor/pathway', fill: TEAL }
  ]),
  spacer(60, 40),
  dataTable(
    ['Interaction Type', 'Mechanism', 'Clinical Example'],
    [
      ['CYP450 Induction (PK)', 'Drug A induces liver enzymes → faster metabolism of Drug B → reduced Drug B levels', 'Rifampicin reduces efficacy of oral contraceptives'],
      ['CYP450 Inhibition (PK)', 'Drug A inhibits liver enzymes → slower metabolism of Drug B → Drug B toxicity', 'Clarithromycin + statins → statin toxicity'],
      ['Synergism (PD)', 'Two drugs act on same pathway, producing enhanced combined effect', 'Aspirin + warfarin → increased bleeding risk'],
      ['Antagonism (PD)', 'One drug reduces the effect of another', 'Naloxone reverses opioid effects'],
      ['Protein binding displacement (PK)', 'Drug A displaces Drug B from plasma proteins → increased free Drug B', 'Sulfonamides displace warfarin']
    ],
    [28, 42, 30]
  ),
  spacer(120, 80),
  new Paragraph({ children: [new PageBreak()], spacing: { before: 0, after: 0 } })
);

// ── SECTION 3: DRUG NOMENCLATURE ─────────────────────────────
children.push(
  h1('SECTION 3: Drug Nomenclature and Classification Systems'),
  spacer(120, 60),
  h2('3.1  Three Names of Every Drug'),
  spacer(60, 40),
  dataTable(
    ['Name Type', 'Description', 'Example (Painkiller)'],
    [
      ['Chemical Name', 'Full IUPAC systematic name based on molecular structure; used in chemistry', 'N-(4-hydroxyphenyl)acetamide'],
      ['Generic Name (INN)', 'International Nonproprietary Name — official, non-commercial, globally recognised', 'Paracetamol / Acetaminophen'],
      ['Brand (Proprietary) Name', 'Manufacturer\'s trade name; capitalized; may vary by country', 'Tylenol® / Panadol®']
    ],
    [25, 45, 30]
  ),
  spacer(100, 60),
  h2('3.2  INN Stem System — How to Read Drug Names'),
  spacer(60, 40),
  para([normal('The ', 20), bold('International Nonproprietary Name (INN)', 20, BLUE_DARK), normal(' system uses standardised stems embedded in drug names to indicate the pharmacological class. Learning stems lets you identify a drug\'s class at a glance.', 20)]),
  spacer(80, 60)
);

// Flowchart 6: INN Stems Map
children.push(
  h3('Flowchart: Major INN Suffix Stems'),
  spacer(60, 40),
  branchFlowchart('INN SUFFIX STEMS → Drug Class Identification', [
    { label: '-olol\nBeta-blockers', sub: 'propranolol, atenolol', fill: '1F3864' },
    { label: '-pril\nACE Inhibitors', sub: 'lisinopril, enalapril', fill: '2E75B6' },
    { label: '-sartan\nARBs', sub: 'losartan, valsartan', fill: '2980B9' },
    { label: '-dipine\nCa²⁺ Blockers', sub: 'amlodipine', fill: '1A5276' }
  ]),
  spacer(60, 40),
  branchFlowchart('MORE INN SUFFIX STEMS', [
    { label: '-statin\nHMG-CoA Inhibitors', sub: 'atorvastatin, rosuvastatin', fill: '27AE60' },
    { label: '-cillin\nPenicillins', sub: 'ampicillin, amoxicillin', fill: '1E8449' },
    { label: '-mycin/-micin\nAntibiotics', sub: 'erythromycin, gentamicin', fill: '145A32' },
    { label: '-cycline\nTetracyclines', sub: 'doxycycline', fill: '0E6655' }
  ]),
  spacer(60, 40),
  branchFlowchart('SPECIALTY & BIOLOGIC STEMS', [
    { label: '-mab\nMonoclonal Antibodies', sub: 'trastuzumab, rituximab', fill: '8E44AD' },
    { label: '-nib\nKinase Inhibitors', sub: 'imatinib, gefitinib', fill: '7D3C98' },
    { label: '-vir\nAntivirals', sub: 'aciclovir, oseltamivir', fill: 'E67E22' },
    { label: '-azole\nAntifungals/PPIs', sub: 'fluconazole, omeprazole', fill: 'D35400' }
  ]),
  spacer(100, 80)
);

// Full stems table
children.push(
  h3('Complete INN Stem Reference Table'),
  spacer(60, 40),
  dataTable(
    ['Stem', 'Class', 'Mechanism', 'Key Examples'],
    [
      ['-olol', 'Beta-blockers', 'Block β-adrenergic receptors → ↓ heart rate, BP, cardiac output', 'Propranolol (non-selective), Atenolol (β1-selective), Metoprolol (β1-selective), Bisoprolol'],
      ['-pril', 'ACE Inhibitors', 'Inhibit ACE → ↓ Angiotensin II, ↑ Bradykinin → vasodilation', 'Lisinopril, Enalapril, Ramipril, Captopril, Perindopril'],
      ['-sartan', 'ARBs (AT1 blockers)', 'Block angiotensin II AT1 receptor → vasodilation', 'Losartan, Valsartan, Irbesartan, Candesartan, Olmesartan'],
      ['-dipine', 'Dihydropyridine CCBs', 'Block L-type Ca²⁺ channels in vascular smooth muscle → vasodilation', 'Amlodipine, Nifedipine, Felodipine, Lercanidipine'],
      ['-statin', 'HMG-CoA reductase inhibitors', 'Inhibit rate-limiting step in cholesterol synthesis in liver', 'Atorvastatin, Rosuvastatin, Simvastatin, Pravastatin'],
      ['-cillin', 'Penicillin antibiotics', 'Inhibit bacterial cell wall synthesis by blocking PBPs (β-lactam ring)', 'Ampicillin, Amoxicillin, Flucloxacillin, Piperacillin'],
      ['-mycin/-micin', 'Macrolides / Aminoglycosides', 'Inhibit bacterial protein synthesis (30S or 50S ribosome)', 'Erythromycin, Azithromycin, Gentamicin, Tobramycin'],
      ['-cycline', 'Tetracycline antibiotics', 'Inhibit bacterial protein synthesis at 30S ribosomal subunit', 'Doxycycline, Tetracycline, Minocycline'],
      ['-mab', 'Monoclonal antibodies', 'Target-specific protein (receptor, cytokine, cell surface antigen)', 'Trastuzumab (HER2), Rituximab (CD20), Adalimumab (TNF-α)'],
      ['-nib', 'Tyrosine kinase inhibitors', 'Block intracellular kinase signalling → anti-proliferative', 'Imatinib (BCR-ABL), Gefitinib (EGFR), Erlotinib (EGFR)'],
      ['-vir', 'Antivirals', 'Various: nucleoside analogues, protease/neuraminidase inhibitors', 'Aciclovir, Oseltamivir, Ritonavir, Tenofovir'],
      ['-azole', 'Antifungals / PPIs', 'Azole antifungals: inhibit ergosterol synthesis; PPIs: inhibit H⁺/K⁺-ATPase', 'Fluconazole, Itraconazole, Omeprazole, Esomeprazole']
    ],
    [15, 20, 35, 30]
  ),
  spacer(100, 80)
);

// Prefixes
children.push(
  h2('3.3  INN Prefix Stems'),
  spacer(60, 40),
  dataTable(
    ['Prefix', 'Meaning', 'Clinical Significance', 'Examples'],
    [
      ['Es-', 'S-enantiomer of a racemic parent drug', 'Often has improved efficacy/selectivity vs. the racemate; launched as isomer switch', 'Esomeprazole (S-omeprazole), Escitalopram (S-citalopram)'],
      ['Levo- / L-', 'Levorotatory isomer (rotates polarized light to left)', 'Biologically active stereoisomer in many cases', 'Levothyroxine (L-T4 - active), Levofloxacin, Levothyroxine, Levodopa'],
      ['Dex- / Dextro-', 'Dextrorotatory isomer (right-rotating)', 'May be more potent or have different activity vs. L-form', 'Dextromethorphan, Dexamfetamine, Dexamethasone'],
      ['Nor-', 'Parent compound without N-methyl group (de-methylated)', 'Often less potent but longer-acting; some active metabolites', 'Norepinephrine (from epinephrine), Norfloxacin, Nortriptyline'],
      ['Iso-', 'Isomeric or isopropylamino form', 'Different receptor selectivity vs. parent', 'Isoproterenol (β1+β2 agonist), Isoflurane']
    ],
    [18, 22, 32, 28]
  ),
  spacer(80, 60),
  ...callout([
    'Isomer Switch Drugs - Exam Tip',
    'Es- and Levo- prefix drugs are "isomer switch" products — purified enantiomers of older racemic drugs.',
    'Esomeprazole = S-enantiomer of omeprazole → better acid suppression',
    'Levothyroxine = L-isomer of thyroxine → biologically active form for thyroid replacement'
  ]),
  spacer(120, 80)
);

// ── SECTION 4: CLASSIFICATION SYSTEMS ────────────────────────
children.push(
  h1('SECTION 4: Drug Classification Flowcharts'),
  spacer(120, 60),
  h2('4.1  Overview Flowchart: How Drugs are Classified'),
  spacer(60, 40)
);

children.push(
  branchFlowchart('DRUG CLASSIFICATION SYSTEMS', [
    { label: 'By Mechanism\n(Pharmacological)', sub: 'Most important clinically', fill: BLUE_DARK },
    { label: 'By Therapeutic\nUse', sub: 'e.g., antihypertensive', fill: '2E75B6' },
    { label: 'By Chemical\nStructure', sub: 'e.g., beta-lactams', fill: TEAL },
    { label: 'By Receptor\nTarget', sub: 'e.g., adrenergic', fill: '27AE60' },
    { label: 'ATC System\n(WHO)', sub: '5-level hierarchy', fill: '8E44AD' }
  ]),
  spacer(100, 80)
);

// Cardiovascular
children.push(
  h2('4.2  Cardiovascular Drug Classification Flowchart'),
  spacer(60, 40),
  branchFlowchart('CARDIOVASCULAR DRUGS', [
    { label: 'Antihypertensives', sub: 'Lower blood pressure', fill: '1F3864' },
    { label: 'Antiarrhythmics', sub: 'Restore rhythm', fill: '2E75B6' },
    { label: 'Antithrombotics', sub: 'Prevent clots', fill: 'C0392B' },
    { label: 'Heart Failure', sub: 'Inotropes / diuretics', fill: '27AE60' }
  ]),
  spacer(60, 40),
  h3('Antihypertensives by Mechanism'),
  spacer(40, 40),
  dataTable(
    ['Class (INN Stem)', 'Mechanism', 'Examples', 'Key Notes'],
    [
      ['Beta-blockers (-olol)', 'Block β1 receptors → ↓ HR and cardiac output', 'Atenolol, Metoprolol, Bisoprolol', 'Avoid in asthma; first-line in post-MI, heart failure'],
      ['ACE Inhibitors (-pril)', 'Block ACE → ↓ Ang II, ↑ bradykinin → vasodilation', 'Lisinopril, Ramipril, Enalapril', 'Cough (bradykinin); contraindicated in pregnancy; protect kidneys in diabetics'],
      ['ARBs (-sartan)', 'Block AT1 receptor → vasodilation', 'Losartan, Valsartan', 'No cough; preferred if ACEi cough; also renoprotective'],
      ['Dihydropyridine CCBs (-dipine)', 'Block L-type Ca²⁺ channels in vessels → vasodilation', 'Amlodipine, Nifedipine', 'Ankle oedema; reflex tachycardia with short-acting forms'],
      ['Thiazide diuretics (-ide)', 'Inhibit Na⁺/Cl⁻ cotransporter in DCT → natriuresis', 'Hydrochlorothiazide, Indapamide', 'First-line in elderly, Afro-Caribbean; watch K⁺'],
      ['Aldosterone antagonists', 'Block mineralocorticoid receptors → Na⁺ excretion', 'Spironolactone, Eplerenone', 'K⁺-sparing; useful in heart failure, Conn\'s syndrome']
    ],
    [22, 28, 25, 25]
  ),
  spacer(100, 80)
);

// Antibiotics
children.push(
  h2('4.3  Antibiotic Classification Flowchart'),
  spacer(60, 40),
  branchFlowchart('ANTIBIOTICS', [
    { label: 'Cell Wall\nSynthesis Inhibitors', sub: 'β-lactams, glycopeptides', fill: '1E8449' },
    { label: 'Protein Synthesis\nInhibitors', sub: '30S and 50S blockers', fill: '27AE60' },
    { label: 'DNA/RNA\nSynthesis Inhibitors', sub: 'Fluoroquinolones, rifampicin', fill: '145A32' },
    { label: 'Cell Membrane\nDisruptors', sub: 'Polymyxins, daptomycin', fill: '0B5345' }
  ]),
  spacer(60, 40),
  dataTable(
    ['Class (INN Stem)', 'Mechanism', 'Examples', 'Spectrum'],
    [
      ['Penicillins (-cillin)', 'Inhibit PBPs → block peptidoglycan crosslinking → cell lysis', 'Amoxicillin, Ampicillin, Piperacillin, Flucloxacillin', 'Variable; flucloxacillin for Staph; piperacillin for Pseudomonas'],
      ['Cephalosporins (-cef/-ceph)', 'Same as penicillins (β-lactam ring); broader spectrum across generations', 'Cefalexin (1st), Cefuroxime (2nd), Ceftriaxone (3rd), Cefepime (4th)', 'Progressively broader gram-negative; 3rd-gen cross BBB'],
      ['Carbapenems', 'Broadest β-lactam; resist most β-lactamases', 'Meropenem, Imipenem, Ertapenem', 'Gram+, Gram−, anaerobes; last resort for ESBL organisms'],
      ['Macrolides (-mycin)', 'Bind 50S ribosome → inhibit translocation', 'Azithromycin, Erythromycin, Clarithromycin', 'Atypicals (Legionella, Mycoplasma); good tissue penetration'],
      ['Aminoglycosides (-micin/-mycin)', 'Bind 30S ribosome → misreading of mRNA', 'Gentamicin, Tobramycin, Amikacin', 'Gram-negative bactericidal; nephrotoxic, ototoxic'],
      ['Tetracyclines (-cycline)', 'Bind 30S ribosome → block aminoacyl-tRNA binding', 'Doxycycline, Minocycline', 'Broad spectrum; atypicals, Chlamydia, Rickettsia'],
      ['Fluoroquinolones (-floxacin)', 'Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV', 'Ciprofloxacin, Levofloxacin, Moxifloxacin', 'Gram− and Gram+; UTI, RTI, anthrax'],
      ['Glycopeptides', 'Bind D-Ala-D-Ala on peptidoglycan → block cell wall synthesis', 'Vancomycin, Teicoplanin', 'MRSA, C. difficile (oral vancomycin); IV for serious Gram+']
    ],
    [20, 30, 25, 25]
  ),
  spacer(100, 80)
);

// Lipid-lowering
children.push(
  h2('4.4  Lipid-Lowering Drug Classification Flowchart'),
  spacer(60, 40),
  branchFlowchart('LIPID-LOWERING DRUGS', [
    { label: 'Statins (-statin)', sub: 'HMG-CoA reductase inhibitors', fill: '2C3E50' },
    { label: 'Fibrates (-fibrate)', sub: 'PPAR-α agonists', fill: '2E4057' },
    { label: 'Ezetimibe', sub: 'Cholesterol absorption inhibitor', fill: '27AE60' },
    { label: 'PCSK9 Inhibitors (-mab)', sub: 'Monoclonal antibodies', fill: '8E44AD' }
  ]),
  spacer(60, 40),
  dataTable(
    ['Class', 'Mechanism', 'Primary Effect', 'Examples'],
    [
      ['Statins (-statin)', 'Inhibit HMG-CoA reductase → ↓ hepatic cholesterol synthesis → upregulate LDL receptors → ↓ LDL', '↓ LDL-C (30-50%)', 'Atorvastatin, Rosuvastatin, Simvastatin, Pravastatin'],
      ['Fibrates (-fibrate)', 'Activate PPAR-α → ↑ lipoprotein lipase → ↑ TG clearance', '↓ Triglycerides (↑ HDL)', 'Fenofibrate, Gemfibrozil'],
      ['Ezetimibe', 'Blocks NPC1L1 transporter in intestinal brush border → ↓ cholesterol absorption', '↓ LDL-C (15-20%)', 'Ezetimibe (Ezetrol)'],
      ['PCSK9 Inhibitors (-mab)', 'Bind PCSK9 → prevent LDL receptor degradation → ↑↑ LDL receptor recycling', '↓ LDL-C (50-60%); for familial hypercholesterolemia', 'Evolocumab (Repatha), Alirocumab (Praluent)']
    ],
    [20, 35, 25, 20]
  ),
  spacer(120, 80)
);

// Quick Reference
children.push(
  h1('QUICK REFERENCE: INN Stems Cheat Sheet'),
  spacer(100, 60),
  dataTable(
    ['Stem', 'Class', 'Prototype Drug'],
    [
      ['-olol', 'Beta-blockers', 'Propranolol'],
      ['-pril', 'ACE Inhibitors', 'Lisinopril'],
      ['-sartan', 'ARBs', 'Losartan'],
      ['-dipine', 'Dihydropyridine CCBs', 'Amlodipine'],
      ['-statin', 'HMG-CoA reductase inhibitors', 'Atorvastatin'],
      ['-cillin', 'Penicillin antibiotics', 'Ampicillin'],
      ['-cycline', 'Tetracycline antibiotics', 'Doxycycline'],
      ['-mycin / -micin', 'Macrolides / Aminoglycosides', 'Azithromycin / Gentamicin'],
      ['-floxacin', 'Fluoroquinolones', 'Ciprofloxacin'],
      ['-mab', 'Monoclonal antibodies', 'Trastuzumab'],
      ['-nib', 'Tyrosine kinase inhibitors', 'Imatinib'],
      ['-vir', 'Antivirals', 'Aciclovir'],
      ['-azole', 'Antifungals / PPIs', 'Omeprazole'],
      ['Es-', 'S-enantiomer (isomer switch)', 'Esomeprazole'],
      ['Levo-', 'Levorotatory isomer', 'Levothyroxine'],
      ['Nor-', 'De-methylated derivative', 'Norepinephrine'],
      ['Dex-', 'Dextrorotatory isomer', 'Dexamethasone']
    ],
    [25, 45, 30]
  ),
  spacer(100, 80),
  ...callout([
    'Study Tip: Using Stems in Clinical Practice',
    '1. See a new drug name → identify the stem → know the class instantly',
    '2. Know the class → predict mechanism, side effects, contraindications, and monitoring',
    '3. Example: "empagliflozin" → contains "-flozin" stem → SGLT2 inhibitor → glucose excretion in urine'
  ]),
  spacer(120, 80),
  new Paragraph({
    children: [new TextRun({ text: 'Source: Katzung\'s Basic and Clinical Pharmacology, 16th Edition', size: 18, color: '777777', italics: true })],
    alignment: AlignmentType.CENTER,
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  })
);

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node /home/daytona/workspace/pharmacology-guide/generate.js 2>&1

python3 /home/daytona/skills/docx/scripts/office/validate.py /home/daytona/works…

ls -lh /home/daytona/workspace/pharmacology-guide/ && python3 -c " import zipfil…