Drug Classifications and Their Mechanisms of Action

ls /home/daytona/workspace/ 2>/dev/null && echo "---" && python3 -c "import repo…

mkdir -p /home/daytona/workspace/drug-reference

~/drug-reference/build_pdf.py

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, PageBreak, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT
from reportlab.platypus import BaseDocTemplate, Frame, PageTemplate

OUTPUT = "/home/daytona/workspace/drug-reference/Drug_Classes_Quick_Reference.pdf"

# ─── Colour palette ───────────────────────────────────────────────────────────
NAVY    = colors.HexColor("#1B3A5C")
TEAL    = colors.HexColor("#1A7A8A")
LBLUE   = colors.HexColor("#D6EAF8")
MINT    = colors.HexColor("#D1F2EB")
LEMON   = colors.HexColor("#FEF9E7")
LAVEN   = colors.HexColor("#EBE6F5")
SALMON  = colors.HexColor("#FDECEA")
PEACH   = colors.HexColor("#FEF3E7")
WHITE   = colors.white
LGRAY   = colors.HexColor("#F2F3F4")
DGRAY   = colors.HexColor("#5D6D7E")
BLACK   = colors.black

# ─── System colour map ────────────────────────────────────────────────────────
SYS_COLORS = {
    "Cardiovascular":    (colors.HexColor("#154360"), colors.HexColor("#D6EAF8")),
    "Nervous System":    (colors.HexColor("#1B5E20"), colors.HexColor("#D5F5E3")),
    "Antimicrobials":    (colors.HexColor("#6E2F0A"), colors.HexColor("#FDEBD0")),
    "Endocrine":         (colors.HexColor("#4A235A"), colors.HexColor("#F5EEF8")),
    "Respiratory":       (colors.HexColor("#1A5276"), colors.HexColor("#D6EAF8")),
    "Anticancer":        (colors.HexColor("#7B241C"), colors.HexColor("#FDEDEC")),
    "GI":                (colors.HexColor("#0E6655"), colors.HexColor("#D0ECE7")),
    "Anticoag/Platelet": (colors.HexColor("#784212"), colors.HexColor("#FDEBD0")),
    "Immunosuppressants":(colors.HexColor("#283747"), colors.HexColor("#D6DBDF")),
}

# ─── Styles ───────────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

def make_style(name, parent="Normal", **kwargs):
    return ParagraphStyle(name, parent=styles[parent], **kwargs)

cover_title = make_style("CoverTitle", fontSize=32, textColor=WHITE,
                         alignment=TA_CENTER, fontName="Helvetica-Bold", leading=38)
cover_sub   = make_style("CoverSub",   fontSize=14, textColor=colors.HexColor("#A9CCE3"),
                         alignment=TA_CENTER, fontName="Helvetica", leading=20)
cover_date  = make_style("CoverDate",  fontSize=10, textColor=colors.HexColor("#85C1E9"),
                         alignment=TA_CENTER, fontName="Helvetica")

sys_heading = make_style("SysHeading", fontSize=13, textColor=WHITE,
                         fontName="Helvetica-Bold", leading=16, spaceAfter=0, spaceBefore=0)
cls_name    = make_style("ClsName",    fontSize=9,  textColor=NAVY,
                         fontName="Helvetica-Bold", leading=12)
moa_text    = make_style("MoaText",    fontSize=8,  textColor=colors.HexColor("#2C3E50"),
                         fontName="Helvetica", leading=11)
eg_text     = make_style("EgText",     fontSize=7.5,textColor=DGRAY,
                         fontName="Helvetica-Oblique", leading=10)
note_text   = make_style("NoteText",   fontSize=7,  textColor=colors.HexColor("#7F8C8D"),
                         fontName="Helvetica", leading=9)
toc_style   = make_style("TocStyle",   fontSize=10, textColor=NAVY,
                         fontName="Helvetica", leading=16)
toc_heading = make_style("TocHeading", fontSize=14, textColor=NAVY,
                         fontName="Helvetica-Bold", leading=20, spaceAfter=6)
footer_sty  = make_style("Footer",     fontSize=7,  textColor=DGRAY,
                         fontName="Helvetica", alignment=TA_CENTER)

# ─── Drug data ────────────────────────────────────────────────────────────────
DRUG_DATA = {
    "Cardiovascular": [
        ("ACE Inhibitors",
         "Inhibit angiotensin-converting enzyme → ↓ angiotensin II → vasodilation + ↓ aldosterone",
         "Lisinopril, Enalapril, Ramipril, Perindopril"),
        ("ARBs (Angiotensin Receptor Blockers)",
         "Block AT1 receptor → vasodilation (angiotensin II still formed but cannot act)",
         "Losartan, Valsartan, Irbesartan, Candesartan"),
        ("Beta-Blockers (β-blockers)",
         "Competitive antagonism at β1 (± β2) adrenoceptors → ↓ HR, ↓ CO, ↓ renin release",
         "Metoprolol, Atenolol, Bisoprolol, Carvedilol, Propranolol"),
        ("Calcium Channel Blockers (CCBs)",
         "Block L-type voltage-gated Ca²⁺ channels → vasodilation (dihydropyridines) / ↓ nodal conduction (non-DHP)",
         "Amlodipine, Nifedipine (DHP); Verapamil, Diltiazem (non-DHP)"),
        ("Thiazide Diuretics",
         "Inhibit Na⁺/Cl⁻ cotransporter (NCC) in distal convoluted tubule → ↑ NaCl excretion",
         "Hydrochlorothiazide, Chlorthalidone, Indapamide"),
        ("Loop Diuretics",
         "Inhibit Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2) in thick ascending loop of Henle",
         "Furosemide, Bumetanide, Torsemide"),
        ("Aldosterone Antagonists",
         "Block mineralocorticoid receptor → ↓ Na⁺ reabsorption, K⁺-sparing",
         "Spironolactone, Eplerenone, Finerenone"),
        ("Statins (HMG-CoA Reductase Inhibitors)",
         "Inhibit HMG-CoA reductase → ↓ cholesterol synthesis → upregulate hepatic LDL receptors",
         "Atorvastatin, Rosuvastatin, Simvastatin, Pravastatin"),
        ("PCSK9 Inhibitors",
         "Monoclonal antibodies blocking PCSK9 → prevent LDL receptor degradation → ↓↓ LDL",
         "Evolocumab, Alirocumab"),
        ("Antiarrhythmics – Class I (Na⁺ blockers)",
         "Ia: ↓ conduction + prolong APD (quinidine). Ib: shorten APD (lidocaine). Ic: ↓↓ conduction (flecainide)",
         "Ia: Quinidine, Procainamide; Ib: Lidocaine, Mexiletine; Ic: Flecainide, Propafenone"),
        ("Antiarrhythmics – Class III (K⁺ blockers)",
         "Block K⁺ channels → prolong repolarisation and QT interval",
         "Amiodarone, Sotalol, Dofetilide, Ibutilide"),
        ("Digoxin",
         "Inhibits Na⁺/K⁺-ATPase → ↑ intracellular Ca²⁺ → ↑ contractility; vagal tone ↑ → ↓ AV conduction",
         "Digoxin"),
        ("Nitrates",
         "Metabolised to NO → activate guanylyl cyclase → ↑ cGMP → vascular smooth muscle relaxation",
         "GTN (nitroglycerin), Isosorbide mononitrate/dinitrate"),
        ("SGLT2 Inhibitors (cardiac/renal)",
         "Block SGLT2 in proximal tubule → glucosuria; reduce preload/afterload, cardioprotective",
         "Empagliflozin, Dapagliflozin, Canagliflozin"),
    ],
    "Nervous System": [
        ("Opioid Analgesics",
         "Agonists at μ (mu), κ (kappa), δ (delta) opioid receptors (Gi-coupled) → ↓ cAMP, ↓ Ca²⁺ influx, ↑ K⁺ efflux → analgesia",
         "Morphine, Fentanyl, Oxycodone, Codeine, Tramadol, Buprenorphine"),
        ("NSAIDs",
         "Non-selective inhibition of COX-1 and COX-2 → ↓ prostaglandin synthesis → analgesia, antipyresis, anti-inflammation",
         "Ibuprofen, Naproxen, Diclofenac, Ketorolac"),
        ("Selective COX-2 Inhibitors",
         "Selectively inhibit inducible COX-2 → ↓ prostaglandins with fewer GI effects (COX-1 spared)",
         "Celecoxib, Etoricoxib"),
        ("SSRIs (Antidepressants)",
         "Selectively inhibit serotonin reuptake transporter (SERT) → ↑ synaptic serotonin",
         "Fluoxetine, Sertraline, Escitalopram, Paroxetine, Citalopram"),
        ("SNRIs (Antidepressants)",
         "Inhibit both SERT and norepinephrine transporter (NET) → ↑ synaptic 5-HT and NE",
         "Venlafaxine, Duloxetine, Desvenlafaxine"),
        ("TCAs (Tricyclic Antidepressants)",
         "Inhibit NET and SERT; also block H1, muscarinic M1, α1 receptors → multiple side effects",
         "Amitriptyline, Imipramine, Nortriptyline, Clomipramine"),
        ("MAO Inhibitors",
         "Irreversibly inhibit monoamine oxidase A/B → ↑ NE, 5-HT, dopamine at synapse",
         "Phenelzine, Tranylcypromine; Moclobemide (reversible MAO-A)"),
        ("Typical Antipsychotics",
         "Primarily D2 dopamine receptor antagonists → block mesolimbic pathway (antipsychotic) + nigrostriatal (EPS)",
         "Haloperidol, Chlorpromazine, Fluphenazine, Trifluoperazine"),
        ("Atypical Antipsychotics",
         "D2 antagonism + 5-HT2A antagonism (and other receptors) → antipsychotic with lower EPS risk",
         "Olanzapine, Quetiapine, Risperidone, Aripiprazole, Clozapine"),
        ("Benzodiazepines",
         "Positive allosteric modulators of GABAA receptors → ↑ frequency of Cl⁻ channel opening → CNS depression",
         "Diazepam, Lorazepam, Clonazepam, Alprazolam, Midazolam"),
        ("Antiepileptics – Na⁺ Channel Blockers",
         "Stabilise inactivated state of voltage-gated Na⁺ channels → prevent repetitive firing",
         "Phenytoin, Carbamazepine, Lamotrigine, Oxcarbazepine, Valproate"),
        ("Antiepileptics – SV2A Modulators",
         "Bind synaptic vesicle glycoprotein 2A → modulate neurotransmitter release",
         "Levetiracetam, Brivaracetam"),
        ("Levodopa / Dopamine Agonists",
         "Levodopa: precursor converted to dopamine in CNS. DA agonists: directly stimulate D2/D3 receptors",
         "Levodopa + Carbidopa; Pramipexole, Ropinirole, Rotigotine"),
        ("Acetylcholinesterase Inhibitors",
         "Inhibit AChE → ↑ acetylcholine at cholinergic synapses (central and peripheral)",
         "Donepezil, Rivastigmine, Galantamine (dementia); Neostigmine (NMJ)"),
    ],
    "Antimicrobials": [
        ("Beta-Lactams (Penicillins / Cephalosporins / Carbapenems)",
         "Inhibit transpeptidases (PBPs) → prevent peptidoglycan cross-linking → cell wall synthesis failure → bactericidal",
         "Amoxicillin, Flucloxacillin; Cefazolin, Ceftriaxone; Meropenem, Ertapenem"),
        ("Glycopeptides",
         "Bind D-Ala-D-Ala terminus of peptidoglycan precursors → block transglycosylation and transpeptidation",
         "Vancomycin, Teicoplanin"),
        ("Aminoglycosides",
         "Irreversibly bind 30S ribosomal subunit (16S rRNA) → misreading of mRNA → premature termination → bactericidal",
         "Gentamicin, Amikacin, Tobramycin, Streptomycin"),
        ("Tetracyclines",
         "Reversibly bind 30S ribosome → block aminoacyl-tRNA entry at A site → bacteriostatic",
         "Doxycycline, Minocycline, Tetracycline, Tigecycline"),
        ("Macrolides",
         "Bind 50S ribosome (23S rRNA) at peptidyl transferase site → block translocation → bacteriostatic",
         "Azithromycin, Clarithromycin, Erythromycin"),
        ("Fluoroquinolones",
         "Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV → prevent DNA replication and repair → bactericidal",
         "Ciprofloxacin, Levofloxacin, Moxifloxacin, Norfloxacin"),
        ("Sulfonamides + Trimethoprim",
         "Sulfonamides: inhibit dihydropteroate synthase. TMP: inhibits DHFR. Both block folate synthesis at sequential steps",
         "Sulfamethoxazole-Trimethoprim (Co-trimoxazole / TMP-SMX)"),
        ("Metronidazole",
         "Reduced to cytotoxic nitroso free-radical intermediates inside anaerobic/microaerophilic organisms → DNA strand breaks",
         "Metronidazole, Tinidazole"),
        ("Oxazolidinones",
         "Bind 50S+30S junction → prevent 70S initiation complex formation → inhibit protein synthesis",
         "Linezolid, Tedizolid"),
        ("NRTIs (Antiretrovirals)",
         "Nucleoside/nucleotide analogues incorporated into viral DNA → chain termination (lack 3'-OH group)",
         "Zidovudine (AZT), Tenofovir (TDF/TAF), Emtricitabine, Lamivudine, Abacavir"),
        ("NNRTIs (Antiretrovirals)",
         "Bind allosteric pocket on HIV reverse transcriptase (non-competitive) → conformational change → enzyme inactivation",
         "Efavirenz, Nevirapine, Rilpivirine, Doravirine"),
        ("HIV Protease Inhibitors",
         "Block HIV aspartyl protease → prevent polyprotein cleavage → immature, non-infectious virions",
         "Ritonavir, Darunavir, Lopinavir, Atazanavir"),
        ("HIV Integrase Inhibitors",
         "Block HIV integrase strand transfer → prevent integration of viral DNA into host genome",
         "Raltegravir, Dolutegravir, Bictegravir, Cabotegravir"),
        ("Antifungals – Azoles",
         "Inhibit fungal CYP51 (lanosterol 14α-demethylase) → ↓ ergosterol synthesis → membrane disruption",
         "Fluconazole, Itraconazole, Voriconazole, Posaconazole"),
        ("Antifungals – Polyenes",
         "Bind directly to ergosterol in fungal membrane → pore formation → ion leakage → fungicidal",
         "Amphotericin B, Nystatin"),
        ("Antifungals – Echinocandins",
         "Inhibit β-1,3-glucan synthase → disrupt fungal cell wall synthesis → fungicidal for Candida",
         "Caspofungin, Micafungin, Anidulafungin"),
        ("Neuraminidase Inhibitors (Influenza)",
         "Block influenza neuraminidase → prevent cleavage of sialic acid → inhibit viral release from cells",
         "Oseltamivir (Tamiflu), Zanamivir, Baloxavir (different MOA: cap-dependent endonuclease inhibitor)"),
    ],
    "Endocrine": [
        ("Insulin",
         "Binds insulin receptor (receptor tyrosine kinase) → GLUT4 translocation → glucose uptake; anabolic effects on fat, protein",
         "Rapid: Lispro, Aspart, Glulisine; Short: Regular; Inter: NPH; Long: Glargine, Detemir, Degludec"),
        ("Metformin (Biguanide)",
         "Activates AMPK; inhibits mitochondrial Complex I → ↓ hepatic gluconeogenesis; does not cause hypoglycaemia",
         "Metformin"),
        ("Sulfonylureas",
         "Block ATP-sensitive K⁺ channels (KATP) on β-cells → membrane depolarisation → Ca²⁺ influx → insulin secretion",
         "Glibenclamide, Glipizide, Gliclazide, Glimepiride"),
        ("GLP-1 Receptor Agonists",
         "Bind GLP-1R (Gs-coupled) → ↑ glucose-dependent insulin secretion, ↓ glucagon, slow gastric emptying, ↓ appetite",
         "Semaglutide, Liraglutide, Dulaglutide, Exenatide, Tirzepatide (dual GLP-1/GIP)"),
        ("DPP-4 Inhibitors (Gliptins)",
         "Block dipeptidyl peptidase-4 enzyme → prevent degradation of endogenous GLP-1 and GIP → modest incretin enhancement",
         "Sitagliptin, Saxagliptin, Linagliptin, Alogliptin"),
        ("SGLT2 Inhibitors (metabolic)",
         "Block Na⁺-glucose cotransporter 2 in proximal tubule → glucosuria → ↓ plasma glucose; weight loss, BP reduction",
         "Empagliflozin, Dapagliflozin, Canagliflozin, Ertugliflozin"),
        ("Thiazolidinediones (TZDs)",
         "Activate PPARγ nuclear receptor → regulate adipokine and glucose transporter gene expression → ↑ insulin sensitivity",
         "Pioglitazone, Rosiglitazone"),
        ("Levothyroxine",
         "Replaces/supplements T4 → converted peripherally to T3 → binds nuclear thyroid hormone receptors → regulate metabolism",
         "Levothyroxine (T4); Liothyronine (T3)"),
        ("Thionamides (Antithyroid)",
         "Inhibit thyroid peroxidase → block T3/T4 synthesis. PTU also blocks T4→T3 peripheral conversion",
         "Methimazole, Carbimazole, Propylthiouracil (PTU)"),
        ("Glucocorticoids",
         "Bind intracellular GR → translocate to nucleus → suppress NF-κB, AP-1 → broad anti-inflammatory and immunosuppressive",
         "Prednisolone, Dexamethasone, Hydrocortisone, Methylprednisolone, Budesonide"),
    ],
    "Respiratory": [
        ("Short-Acting β2-Agonists (SABA)",
         "Activate β2-adrenoceptors → Gs → ↑ cAMP → PKA activation → smooth muscle relaxation → bronchodilation (rapid onset)",
         "Albuterol (Salbutamol), Terbutaline, Levalbuterol"),
        ("Long-Acting β2-Agonists (LABA)",
         "Same mechanism as SABA; lipophilic tail anchors in membrane → prolonged receptor engagement (12–24 h duration)",
         "Salmeterol, Formoterol, Indacaterol, Vilanterol"),
        ("Short-Acting Muscarinic Antagonists (SAMA)",
         "Block M3 muscarinic receptors on bronchial smooth muscle → prevent ACh-induced bronchoconstriction",
         "Ipratropium bromide"),
        ("Long-Acting Muscarinic Antagonists (LAMA)",
         "Same mechanism as SAMA; selectively dissociate from M3 slowly (kinetically selective) → 24 h bronchodilation",
         "Tiotropium, Umeclidinium, Glycopyrronium, Aclidinium"),
        ("Inhaled Corticosteroids (ICS)",
         "Bind GR → suppress inflammatory gene transcription → ↓ cytokines, ↓ eosinophil infiltration → reduce airway inflammation",
         "Budesonide, Fluticasone, Beclomethasone, Ciclesonide, Mometasone"),
        ("Leukotriene Receptor Antagonists (LTRA)",
         "Block CysLT1 receptors → prevent leukotriene-mediated bronchoconstriction, mucus secretion, eosinophil recruitment",
         "Montelukast, Zafirlukast"),
        ("PDE4 Inhibitors",
         "Inhibit phosphodiesterase-4 → ↑ cAMP in inflammatory cells → anti-inflammatory; used in COPD",
         "Roflumilast"),
        ("Anti-IgE Biologic",
         "Binds free IgE → prevents IgE binding to mast cell FcεRI receptors → inhibit mast cell degranulation",
         "Omalizumab"),
        ("Anti-IL-5 / IL-4/13 Biologics",
         "IL-5 blockade: ↓ eosinophil survival/recruitment. IL-4/13 blockade: ↓ Th2 inflammation, ↓ IgE, ↓ mucus",
         "Mepolizumab, Benralizumab (anti-IL-5); Dupilumab (anti-IL-4Rα/IL-13)"),
    ],
    "Anticancer": [
        ("Alkylating Agents",
         "Form covalent bonds with DNA → intra/inter-strand cross-links → prevent replication and transcription → apoptosis",
         "Cyclophosphamide, Ifosfamide, Cisplatin, Carboplatin, Oxaliplatin, Dacarbazine"),
        ("Antimetabolites – Folate Antagonists",
         "Inhibit dihydrofolate reductase (DHFR) → ↓ THF → impair thymidylate and purine synthesis",
         "Methotrexate, Pemetrexed"),
        ("Antimetabolites – Pyrimidine Analogues",
         "5-FU: inhibit thymidylate synthase + incorporated into RNA. Cytarabine: incorporated into DNA → chain termination",
         "5-Fluorouracil (5-FU), Capecitabine (prodrug of 5-FU), Cytarabine, Gemcitabine"),
        ("Topoisomerase Inhibitors",
         "Topo I inhibitors (camptothecins): stabilise Topo I-DNA complex → single-strand breaks. Topo II inhibitors: stabilise cleavable complex → double-strand breaks",
         "Irinotecan, Topotecan (Topo I); Doxorubicin, Etoposide, Epirubicin (Topo II)"),
        ("Vinca Alkaloids",
         "Bind β-tubulin → inhibit tubulin polymerisation → prevent spindle formation → metaphase arrest → apoptosis",
         "Vincristine, Vinblastine, Vinorelbine"),
        ("Taxanes",
         "Bind and stabilise polymerised microtubules → prevent depolymerisation → disrupt spindle dynamics → cell death",
         "Paclitaxel, Docetaxel, Nab-paclitaxel, Cabazitaxel"),
        ("Tyrosine Kinase Inhibitors (TKIs)",
         "Competitively inhibit ATP binding site of tyrosine kinases → block downstream proliferation/survival signalling",
         "Imatinib (BCR-ABL), Erlotinib/Gefitinib (EGFR), Trastuzumab+Lapatinib (HER2), Ibrutinib (BTK)"),
        ("VEGF Pathway Inhibitors",
         "Bevacizumab: anti-VEGF antibody → prevents VEGF binding to receptor → inhibit tumour angiogenesis",
         "Bevacizumab, Ramucirumab; Sunitinib, Sorafenib (multi-target TKIs incl. VEGFR)"),
        ("Immune Checkpoint Inhibitors",
         "Block PD-1/PD-L1 or CTLA-4 co-inhibitory pathways → restore T-cell anti-tumour immune response",
         "Pembrolizumab, Nivolumab (anti-PD-1); Atezolizumab (anti-PD-L1); Ipilimumab (anti-CTLA-4)"),
        ("Hormone Therapy",
         "SERMs/aromatase inhibitors: block estrogen signalling in ER+ breast cancer. Anti-androgens: block AR in prostate cancer",
         "Tamoxifen (SERM), Letrozole/Anastrozole (aromatase inhibitors); Enzalutamide, Abiraterone (prostate)"),
    ],
    "GI": [
        ("Proton Pump Inhibitors (PPIs)",
         "Irreversibly inhibit H⁺/K⁺-ATPase (proton pump) on gastric parietal cells → profound ↓ acid secretion",
         "Omeprazole, Pantoprazole, Lansoprazole, Esomeprazole, Rabeprazole"),
        ("H2 Receptor Antagonists",
         "Competitively block H2 receptors on parietal cells → reduce histamine-stimulated acid secretion",
         "Ranitidine, Famotidine, Cimetidine"),
        ("5-HT3 Antagonists (Antiemetics)",
         "Block 5-HT3 receptors on vagal afferents and in chemoreceptor trigger zone → suppress nausea/vomiting",
         "Ondansetron, Granisetron, Palonosetron"),
        ("NK1 Receptor Antagonists (Antiemetics)",
         "Block substance P at NK1 receptors in nucleus tractus solitarius → prevent chemotherapy-induced delayed emesis",
         "Aprepitant, Fosaprepitant, Netupitant"),
        ("Prokinetics",
         "Metoclopramide/Domperidone: D2 antagonism → ↑ GI motility + antiemetic. Metoclopramide also 5-HT4 agonist",
         "Metoclopramide, Domperidone, Prucalopride (5-HT4 agonist)"),
        ("Laxatives",
         "Osmotic: draw water into lumen (lactulose, macrogol). Stimulant: activate myenteric plexus (senna, bisacodyl). Bulk: increase stool bulk (psyllium)",
         "Lactulose, Macrogol; Senna, Bisacodyl; Psyllium, Methylcellulose"),
        ("Antidiarrhoeals",
         "Loperamide: agonist at enteric μ-opioid receptors → ↓ peristalsis, ↑ anal sphincter tone, ↓ secretion (does not cross BBB)",
         "Loperamide; Codeine phosphate; Bismuth subsalicylate"),
        ("IBD Biologics",
         "Anti-TNF: block TNF-α-mediated inflammation. Anti-integrins: block gut-homing lymphocyte trafficking",
         "Infliximab, Adalimumab (anti-TNF); Vedolizumab (anti-α4β7 integrin); Ustekinumab (anti-IL-12/23)"),
    ],
    "Anticoag/Platelet": [
        ("Unfractionated Heparin (UFH)",
         "Activates antithrombin III → accelerates inhibition of thrombin (IIa), Factor Xa and others; effect monitored by aPTT",
         "Unfractionated Heparin (IV/SC)"),
        ("Low Molecular Weight Heparins (LMWH)",
         "Activate antithrombin III with preference for Factor Xa inhibition over thrombin; more predictable PK, no routine monitoring",
         "Enoxaparin, Dalteparin, Tinzaparin"),
        ("Vitamin K Antagonists",
         "Inhibit VKORC1 (Vitamin K epoxide reductase) → deplete Factors II, VII, IX, X + Protein C/S; effect monitored by INR/PT",
         "Warfarin, Acenocoumarol, Phenprocoumon"),
        ("Direct Thrombin Inhibitors (DTIs)",
         "Directly inhibit thrombin (Factor IIa) independent of antithrombin; dabigatran is oral, bivalirudin is parenteral",
         "Dabigatran (oral DOAC); Bivalirudin, Argatroban (parenteral)"),
        ("Direct Factor Xa Inhibitors",
         "Directly inhibit Factor Xa at active site → block prothrombinase complex; predictable PK, no routine monitoring",
         "Rivaroxaban, Apixaban, Edoxaban, Betrixaban"),
        ("Aspirin (Antiplatelet)",
         "Irreversibly acetylates serine residue on COX-1 → prevents TXA2 synthesis → ↓ platelet aggregation for platelet lifespan",
         "Aspirin 75–100 mg (antiplatelet dose)"),
        ("P2Y12 Receptor Antagonists",
         "Block ADP-activated P2Y12 purinergic receptor on platelets → prevent Gi-mediated ↓ cAMP → ↓ platelet activation",
         "Clopidogrel, Prasugrel (irreversible); Ticagrelor, Cangrelor (reversible)"),
        ("GP IIb/IIIa Inhibitors",
         "Block fibrinogen/vWF binding site on glycoprotein IIb/IIIa (αIIbβ3 integrin) → prevent platelet cross-linking/aggregation",
         "Abciximab (mAb), Eptifibatide, Tirofiban (small molecules)"),
    ],
    "Immunosuppressants": [
        ("Calcineurin Inhibitors",
         "Inhibit calcineurin phosphatase → prevent NFAT dephosphorylation → block IL-2 gene transcription → ↓ T-cell activation",
         "Cyclosporine (CsA), Tacrolimus (FK506)"),
        ("mTOR Inhibitors",
         "Inhibit mTOR kinase (FKBP12 complex) → block IL-2 receptor signalling → prevent T- and B-cell proliferation",
         "Sirolimus (Rapamycin), Everolimus"),
        ("Antimetabolites (Immunosuppressant)",
         "Azathioprine: prodrug → 6-MP → inhibit de novo purine synthesis → ↓ lymphocyte proliferation. MMF: inhibit IMPDH",
         "Azathioprine, Mycophenolate mofetil (MMF)"),
        ("Anti-TNF Biologics",
         "Block TNF-α (soluble or membrane-bound) → ↓ downstream NF-κB activation → reduce systemic inflammation",
         "Infliximab, Adalimumab, Etanercept, Certolizumab, Golimumab"),
        ("JAK Inhibitors",
         "Inhibit Janus kinases (JAK1, JAK2, JAK3, TYK2) → block cytokine receptor signalling (JAK-STAT pathway)",
         "Tofacitinib (JAK1/3), Baricitinib (JAK1/2), Upadacitinib (JAK1), Ruxolitinib (JAK1/2)"),
        ("IL-6 Receptor Antagonists",
         "Block IL-6 receptor → prevent IL-6-mediated pro-inflammatory signalling (STAT3 activation)",
         "Tocilizumab, Sarilumab"),
        ("Anti-CD20 (B-cell depletion)",
         "Bind CD20 on B-cell surface → antibody-dependent cellular cytotoxicity (ADCC), CDC, and apoptosis → B-cell depletion",
         "Rituximab, Obinutuzumab, Ocrelizumab"),
    ],
}

# ─── Page decorators ──────────────────────────────────────────────────────────
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    canvas.setFillColor(TEAL)
    canvas.rect(0, A4[1]*0.38, A4[0], 4, fill=1, stroke=0)
    canvas.setFillColor(colors.HexColor("#2E86C1"))
    canvas.rect(0, A4[1]*0.38-6, A4[0], 3, fill=1, stroke=0)
    canvas.restoreState()

def inner_page(canvas, doc):
    canvas.saveState()
    # Subtle top bar
    canvas.setFillColor(NAVY)
    canvas.rect(0, A4[1]-18*mm, A4[0], 18*mm, fill=1, stroke=0)
    # Footer
    canvas.setFillColor(LGRAY)
    canvas.rect(0, 0, A4[0], 12*mm, fill=1, stroke=0)
    canvas.setFont("Helvetica", 7)
    canvas.setFillColor(DGRAY)
    canvas.drawCentredString(A4[0]/2, 4*mm,
        f"Drug Classes Quick Reference  |  Page {doc.page}  |  For educational use only")
    # Header text
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica-Bold", 9)
    canvas.drawString(1.5*cm, A4[1]-12*mm, "DRUG CLASSES QUICK REFERENCE")
    canvas.setFont("Helvetica", 9)
    canvas.drawRightString(A4[0]-1.5*cm, A4[1]-12*mm, "Pharmacology by Body System")
    canvas.restoreState()

# ─── Build flowables ──────────────────────────────────────────────────────────
def build_system_table(system, entries, hdr_color, bg_color):
    """Return a KeepTogether block for one drug system section."""
    flowables = []

    # Section header bar
    hdr_data = [[Paragraph(f"  {system.upper()}", sys_heading)]]
    hdr_tbl = Table(hdr_data, colWidths=[17.5*cm])
    hdr_tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), hdr_color),
        ("TOPPADDING",    (0,0), (-1,-1), 6),
        ("BOTTOMPADDING", (0,0), (-1,-1), 6),
        ("LEFTPADDING",   (0,0), (-1,-1), 8),
        ("ROUNDEDCORNERS", [4]),
    ]))
    flowables.append(hdr_tbl)
    flowables.append(Spacer(1, 3))

    # Build table rows
    rows = []
    rows.append([
        Paragraph("<b>Drug Class</b>", make_style("TH", fontSize=8, textColor=WHITE, fontName="Helvetica-Bold")),
        Paragraph("<b>Mechanism of Action</b>", make_style("TH2", fontSize=8, textColor=WHITE, fontName="Helvetica-Bold")),
        Paragraph("<b>Key Examples</b>", make_style("TH3", fontSize=8, textColor=WHITE, fontName="Helvetica-Bold")),
    ])
    for cls, moa, examples in entries:
        rows.append([
            Paragraph(cls, cls_name),
            Paragraph(moa, moa_text),
            Paragraph(examples, eg_text),
        ])

    col_w = [4.2*cm, 8.8*cm, 4.5*cm]
    tbl = Table(rows, colWidths=col_w, repeatRows=1)

    row_bg = []
    for i in range(1, len(rows)):
        c = bg_color if i % 2 == 1 else WHITE
        row_bg.append(("BACKGROUND", (0, i), (-1, i), c))

    tbl.setStyle(TableStyle([
        # Header row
        ("BACKGROUND",    (0,0), (-1,0), hdr_color),
        ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
        ("FONTNAME",      (0,0), (-1,0), "Helvetica-Bold"),
        ("FONTSIZE",      (0,0), (-1,0), 8),
        ("TOPPADDING",    (0,0), (-1,0), 5),
        ("BOTTOMPADDING", (0,0), (-1,0), 5),
        # Body
        ("FONTSIZE",      (0,1), (-1,-1), 8),
        ("TOPPADDING",    (0,1), (-1,-1), 4),
        ("BOTTOMPADDING", (0,1), (-1,-1), 4),
        ("LEFTPADDING",   (0,0), (-1,-1), 5),
        ("RIGHTPADDING",  (0,0), (-1,-1), 5),
        ("VALIGN",        (0,0), (-1,-1), "TOP"),
        # Borders
        ("GRID",          (0,0), (-1,-1), 0.3, colors.HexColor("#BDC3C7")),
        ("LINEBELOW",     (0,0), (-1,0), 1, hdr_color),
        *row_bg,
    ]))

    flowables.append(tbl)
    flowables.append(Spacer(1, 8))
    return flowables

# ─── Main ─────────────────────────────────────────────────────────────────────
def main():
    doc = SimpleDocTemplate(
        OUTPUT,
        pagesize=A4,
        leftMargin=1.5*cm,
        rightMargin=1.5*cm,
        topMargin=2.2*cm,
        bottomMargin=1.8*cm,
    )

    story = []

    # ── COVER PAGE ─────────────────────────────────────────────────────────────
    story.append(Spacer(1, 5*cm))
    story.append(Paragraph("DRUG CLASSES", cover_title))
    story.append(Spacer(1, 0.4*cm))
    story.append(Paragraph("Quick Reference Guide", cover_sub))
    story.append(Spacer(1, 0.3*cm))
    story.append(Paragraph("Mechanisms of Action · Key Examples · Body System Organisation",
                            cover_sub))
    story.append(Spacer(1, 2*cm))

    # Decorative divider on cover
    cover_div_data = [[""]]
    cover_div = Table(cover_div_data, colWidths=[12*cm])
    cover_div.setStyle(TableStyle([
        ("BACKGROUND",    (0,0), (-1,-1), TEAL),
        ("TOPPADDING",    (0,0), (-1,-1), 2),
        ("BOTTOMPADDING", (0,0), (-1,-1), 2),
    ]))
    story.append(cover_div)
    story.append(Spacer(1, 2*cm))

    story.append(Paragraph("Based on Goodman &amp; Gilman's, Katzung's, and Lippincott's Pharmacology",
                            cover_date))
    story.append(Spacer(1, 0.3*cm))
    story.append(Paragraph("For educational use only  |  2026", cover_date))
    story.append(PageBreak())

    # ── TABLE OF CONTENTS ──────────────────────────────────────────────────────
    story.append(Spacer(1, 0.5*cm))
    story.append(Paragraph("Contents", toc_heading))
    story.append(HRFlowable(width="100%", thickness=2, color=TEAL, spaceAfter=10))

    systems_list = list(DRUG_DATA.keys())
    for i, sys_name in enumerate(systems_list, 1):
        n_drugs = len(DRUG_DATA[sys_name])
        story.append(Paragraph(
            f"<b>{i}.</b>  {sys_name}  <font color='#7F8C8D' size='9'>({n_drugs} drug classes)</font>",
            toc_style))

    story.append(Spacer(1, 1*cm))
    story.append(Paragraph(
        "<font color='#7F8C8D'>Each section covers: Drug Class Name · Mechanism of Action · Prototypical Examples</font>",
        note_text))
    story.append(PageBreak())

    # ── DRUG SECTIONS ──────────────────────────────────────────────────────────
    for sys_name, entries in DRUG_DATA.items():
        hdr_color, bg_color = SYS_COLORS[sys_name]
        section_flowables = build_system_table(sys_name, entries, hdr_color, bg_color)
        story.extend(section_flowables)

    # ── LEGEND PAGE ────────────────────────────────────────────────────────────
    story.append(PageBreak())
    story.append(Spacer(1, 0.5*cm))
    story.append(Paragraph("Abbreviations & Legend", toc_heading))
    story.append(HRFlowable(width="100%", thickness=2, color=TEAL, spaceAfter=10))

    abbrevs = [
        ["↑ / ↓", "Increase / Decrease"],
        ["MOA", "Mechanism of Action"],
        ["GPCR", "G-protein coupled receptor"],
        ["cAMP", "Cyclic adenosine monophosphate"],
        ["cGMP", "Cyclic guanosine monophosphate"],
        ["PKA / PKC", "Protein kinase A / C"],
        ["NF-κB", "Nuclear factor kappa B"],
        ["STAT", "Signal transducer and activator of transcription"],
        ["PBP", "Penicillin-binding protein"],
        ["DHFR", "Dihydrofolate reductase"],
        ["SERT / NET / DAT", "Serotonin / Norepinephrine / Dopamine transporter"],
        ["DOAC", "Direct oral anticoagulant"],
        ["APD", "Action potential duration"],
        ["EPS", "Extrapyramidal symptoms"],
        ["AUC", "Area under the curve"],
        ["PK", "Pharmacokinetics"],
        ["aPTT / INR / PT", "Activated partial thromboplastin time / International normalised ratio / Prothrombin time"],
        ["BBB", "Blood-brain barrier"],
        ["VEGF", "Vascular endothelial growth factor"],
        ["TNF-α", "Tumour necrosis factor alpha"],
    ]

    abbrev_rows = [[Paragraph("<b>Term</b>", cls_name), Paragraph("<b>Meaning</b>", cls_name)]]
    for term, meaning in abbrevs:
        abbrev_rows.append([Paragraph(term, moa_text), Paragraph(meaning, moa_text)])

    abbrev_tbl = Table(abbrev_rows, colWidths=[5*cm, 12*cm])
    abbrev_tbl.setStyle(TableStyle([
        ("BACKGROUND",    (0,0), (-1,0), NAVY),
        ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
        ("FONTNAME",      (0,0), (-1,0), "Helvetica-Bold"),
        ("GRID",          (0,0), (-1,-1), 0.3, colors.HexColor("#BDC3C7")),
        ("ROWBACKGROUNDS",(0,1), (-1,-1), [LGRAY, WHITE]),
        ("TOPPADDING",    (0,0), (-1,-1), 4),
        ("BOTTOMPADDING", (0,0), (-1,-1), 4),
        ("LEFTPADDING",   (0,0), (-1,-1), 6),
    ]))
    story.append(abbrev_tbl)

    # ── BUILD ──────────────────────────────────────────────────────────────────
    def page_template(canvas, doc):
        if doc.page == 1:
            cover_bg(canvas, doc)
        else:
            inner_page(canvas, doc)

    doc.build(story, onFirstPage=page_template, onLaterPages=page_template)
    print(f"PDF saved: {OUTPUT}")

if __name__ == "__main__":
    main()

cd /home/daytona/workspace/drug-reference && python3 build_pdf.py 2>&1

ls -lh /home/daytona/workspace/drug-reference/Drug_Classes_Quick_Reference.pdf