from reportlab.lib.pagesizes import A4
from reportlab.platypus import SimpleDocTemplate, Paragraph, Spacer, PageBreak, Image, Table, TableStyle, KeepTogether
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib import colors
from reportlab.lib.units import cm
from reportlab.pdfbase.ttfonts import TTFont
from reportlab.pdfbase import pdfmetrics
from reportlab.lib.enums import TA_CENTER, TA_LEFT
from reportlab.pdfgen.canvas import Canvas
from reportlab.lib.utils import ImageReader
from PIL import Image as PILImage
import os

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# Six study pages per topic. These are academic notes, not patient-specific prescribing directions.
topics=[
('1. Newer approaches that increase pulmonary surfactant synthesis', [
('Scope and learning goals', ['Pulmonary surfactant is a phospholipid-protein complex made by type II pneumocytes. It lowers alveolar surface tension, stabilizes small alveoli and reduces the work of breathing.', 'The main clinical setting is prevention or treatment of neonatal respiratory distress syndrome (RDS), where surfactant deficiency is central.', 'Distinguish drugs that accelerate fetal surfactant maturation from exogenous surfactant replacement. “New generation” usually refers to modern preparations and supportive strategies, not a single uniform drug class.']),
('Drug groups and examples', ['Antenatal corticosteroids: betamethasone and dexamethasone accelerate fetal lung maturation and surfactant production before anticipated preterm birth.', 'Exogenous surfactants: poractant alfa, beractant and calfactant are animal-derived preparations; synthetic preparations have been developed with surfactant-protein analogues.', 'Supportive respiratory strategies, such as early CPAP, reduce alveolar collapse and complement surfactant treatment.']),
('Mechanism of action', ['Glucocorticoids enter cells, bind intracellular receptors and modify gene transcription. In fetal lung they promote type II pneumocyte maturation and expression of enzymes/proteins needed for surfactant synthesis.', 'Surfactant replacement does not stimulate synthesis immediately. It provides surface-active material directly in the alveoli, reducing surface tension and improving compliance.', 'Endogenous surfactant consists mainly of dipalmitoylphosphatidylcholine plus surfactant proteins. SP-B and SP-C are important for rapid adsorption and film stability.']),
('Clinical use and administration concepts', ['Antenatal corticosteroids are used when preterm birth is likely, according to obstetric protocols. Timing, maternal infection status and gestational age require clinician assessment.', 'For neonatal RDS, early rescue surfactant through an endotracheal tube or less-invasive delivery technique may be used with respiratory support.', 'Surfactant is also used in selected neonatal conditions with secondary surfactant inactivation, but evidence and local protocols differ.']),
('Adverse effects and precautions', ['Maternal corticosteroid courses can transiently affect glucose control. Repeated or inappropriate courses should not be used casually.', 'During intratracheal surfactant administration, transient bradycardia, oxygen desaturation, airway obstruction or reflux can occur. Continuous monitoring is required.', 'Surfactant is a hospital treatment. It is not a medicine for home administration.']),
('Exam summary', ['RDS is fundamentally a deficiency or dysfunction of surfactant. Antenatal corticosteroids promote maturation; exogenous surfactant replaces deficient material.', 'High-yield comparison: corticosteroid effect is genomic and develops over time; exogenous surfactant has a direct physical effect in alveoli.', 'Remember the key outcome: improved lung compliance and reduced alveolar collapse.'])]),
('2. Cardiotonic drugs in acute and chronic heart failure', [
('Core concept', ['Heart failure is a clinical syndrome in which cardiac output is insufficient for tissue needs or is maintained only at elevated filling pressures.', 'Treatment depends on phenotype, acuity, blood pressure, congestion, rhythm, renal function and cause. Acute decompensated heart failure and stable chronic HFrEF are managed differently.', 'Cardiotonic usually means a positive inotrope, but modern chronic heart-failure therapy emphasizes disease-modifying neurohormonal drugs rather than routine inotrope use.']),
('Drug classification', ['Acute low-output states: dobutamine, milrinone and, in selected settings, dopamine are IV inotropes. Norepinephrine may be needed if cardiogenic shock includes hypotension.', 'Cardiac glycoside: digoxin increases inotropy and slows AV nodal conduction; it is mainly used for selected HFrEF patients or atrial fibrillation rate control.', 'Chronic HFrEF foundation therapy: ARNI or ACE inhibitor/ARB, evidence-based beta-blocker, mineralocorticoid receptor antagonist and SGLT2 inhibitor. Diuretics relieve congestion.']),
('Mechanisms', ['Dobutamine stimulates beta-1 receptors, increasing contractility and heart rate. Milrinone inhibits phosphodiesterase-3, increasing cAMP and intracellular calcium while causing vasodilation.', 'Digoxin inhibits Na+/K+-ATPase. The resulting rise in intracellular sodium reduces Na+/Ca2+ exchange and raises intracellular calcium. It also increases vagal tone.', 'ARNI and RAAS blockers reduce maladaptive neurohormonal activation; beta-blockers reduce chronic sympathetic injury; SGLT2 inhibitors improve outcomes by mechanisms not limited to glucose lowering.']),
('Acute heart failure approach', ['Give oxygen only when hypoxemia is present and identify precipitants such as acute coronary syndrome, arrhythmia, infection, missed medicines or renal deterioration.', 'IV loop diuretics are central for fluid overload. Vasodilators may help hypertensive acute pulmonary edema if blood pressure is adequate.', 'Inotropes are reserved for hypoperfusion or cardiogenic shock because they can cause arrhythmias and may worsen long-term outcomes.']),
('Safety and monitoring', ['Digoxin has a narrow therapeutic range. Toxicity may cause nausea, confusion, visual disturbance, bradyarrhythmias or ventricular arrhythmias. Renal function, potassium and interacting drugs matter.', 'Dobutamine and milrinone can cause tachyarrhythmias; milrinone can cause hypotension and needs renal-dose consideration.', 'Monitor weight, symptoms, blood pressure, renal function and electrolytes when adjusting chronic therapy.']),
('Exam summary', ['Do not equate “cardiotonic” with standard long-term therapy. Chronic HFrEF outcome improvement is chiefly from neurohormonal and SGLT2-based therapies.', 'Digoxin improves symptoms or rate control in selected patients but does not replace guideline-directed therapy.', 'Acute inotropes are short-term, monitored therapies for low-output states.'])]),
('3. Medicines used in myocardial infarction', [
('Clinical context', ['Acute myocardial infarction (MI) is myocardial necrosis due to acute ischemia, commonly from coronary plaque rupture and thrombosis.', 'Initial management depends on STEMI versus NSTEMI, time since symptom onset, bleeding risk, hemodynamic state and planned reperfusion.', 'This page summarizes medicine classes. Emergency diagnosis and reperfusion decisions require urgent professional care.']),
('Major medicine groups', ['Antiplatelets: aspirin plus a P2Y12 inhibitor such as ticagrelor, prasugrel or clopidogrel form dual antiplatelet therapy in many acute coronary syndrome pathways.', 'Anticoagulants: unfractionated heparin, enoxaparin, bivalirudin or fondaparinux are selected according to presentation and invasive strategy.', 'Anti-ischemic and supportive drugs: nitrates, beta-blockers in appropriate patients, high-intensity statins, ACE inhibitor/ARB or ARNI where indicated, and mineralocorticoid antagonist in selected reduced-EF patients.']),
('Mechanisms and reperfusion', ['Aspirin irreversibly inhibits platelet COX-1 and thromboxane A2 formation. P2Y12 inhibitors suppress ADP-mediated platelet activation.', 'Heparins enhance antithrombin activity and reduce thrombin/Xa activity. Fibrinolytics such as tenecteplase promote plasmin generation and fibrin breakdown.', 'Primary percutaneous coronary intervention is preferred reperfusion for eligible STEMI when timely available. Fibrinolysis is an alternative in selected patients when PCI cannot be delivered promptly and no contraindication exists.']),
('Role of individual drugs', ['Nitrates reduce preload and may relieve ischemic pain, but they are avoided in hypotension, suspected right-ventricular infarction or recent phosphodiesterase-5 inhibitor use.', 'Beta-blockers reduce heart rate and myocardial oxygen demand. Early use is inappropriate in shock, acute pulmonary edema, severe bradycardia or heart block.', 'High-intensity statins are started early unless contraindicated and provide substantial secondary-prevention benefit.']),
('Adverse effects and cautions', ['Antithrombotic therapy can cause major bleeding. Assess prior hemorrhage, anemia, anticoagulant use, renal dysfunction and planned procedures.', 'Fibrinolytics can cause intracranial and other serious bleeding. Absolute contraindications must be checked carefully.', 'Nitrates can cause headache and hypotension; ACE inhibitors may cause hypotension, hyperkalemia and renal-function changes.']),
('Exam summary', ['The treatment pillars are rapid reperfusion when indicated, antiplatelet therapy, anticoagulation in appropriate pathways, symptom/hemodynamic management and long-term secondary prevention.', 'STEMI is a reperfusion emergency. NSTEMI treatment is risk-stratified and fibrinolysis is not routine.', 'Avoid harmful reflexes: do not give nitrates in marked hypotension or routine beta-blockade in cardiogenic shock.'])]),
('4. Medicines used in hypertensive crisis', [
('Definitions', ['Hypertensive emergency means severe blood-pressure elevation with acute target-organ damage, such as encephalopathy, aortic dissection, acute pulmonary edema, acute kidney injury, retinal injury, eclampsia or ischemic events.', 'Severe asymptomatic hypertension does not automatically require IV therapy. It is evaluated, oral therapy may be adjusted, and blood pressure is reduced gradually.', 'The aim in emergency is controlled reduction, not normalization within minutes. The target and agent depend on the organ emergency.']),
('Common IV agents', ['Nicardipine and clevidipine: titratable dihydropyridine calcium-channel blockers that reduce arteriolar resistance.', 'Labetalol: alpha-1 and beta blockade; useful in several neurologic and pregnancy-related settings when no contraindication exists.', 'Sodium nitroprusside: potent arterial and venous vasodilator, but toxicity and monitoring issues limit use. Nitroglycerin is useful especially with acute coronary ischemia or pulmonary edema.', 'Esmolol is important for aortic dissection, usually with an additional vasodilator after heart-rate control.']),
('Mechanisms and selection', ['Nicardipine and clevidipine block L-type calcium channels in vascular smooth muscle, causing arteriolar vasodilation.', 'Labetalol reduces heart rate and systemic vascular resistance. Avoid it in certain bradycardic, heart-block or bronchospastic states.', 'Hydralazine is sometimes used in pregnancy but its response can be less predictable. In eclampsia, magnesium sulfate treats seizures, not blood pressure itself.']),
('Condition-specific principles', ['Aortic dissection: rapidly reduce impulse on the aortic wall with IV beta blockade first, then lower systolic pressure with vasodilation under intensive monitoring.', 'Acute pulmonary edema: nitrates and loop diuretics may be used with ventilatory support as required.', 'Acute ischemic stroke: blood-pressure targets depend on whether thrombolysis or thrombectomy is planned; avoid indiscriminate reduction.']),
('Safety and monitoring', ['Use titratable IV drugs with frequent blood-pressure measurement, often in an emergency or critical-care setting.', 'Overly rapid reduction can lower perfusion to brain, heart and kidneys, especially in chronically hypertensive patients.', 'Nitroprusside can lead to cyanide/thiocyanate toxicity, particularly with prolonged infusion or organ dysfunction.']),
('Exam summary', ['Emergency = severe BP plus acute organ damage. Treat the emergency and choose an IV agent that fits the clinical situation.', 'Most emergencies need gradual reduction, often no more than about 20-25% of mean arterial pressure in the first hour unless a special condition dictates otherwise.', 'Aortic dissection is an exception requiring fast, carefully monitored anti-impulse therapy.'])]),
('5. Newer drugs affecting the renin-angiotensin system', [
('RAAS overview', ['Renin converts angiotensinogen to angiotensin I; ACE converts it to angiotensin II. Angiotensin II causes vasoconstriction, aldosterone release and adverse remodeling.', 'RAAS inhibition benefits hypertension, heart failure, chronic kidney disease and post-MI remodeling in appropriate patients.', 'Drug selection depends on indication, kidney function, potassium, pregnancy status and prior intolerance.']),
('Classes and examples', ['ACE inhibitors: enalapril, lisinopril and ramipril reduce formation of angiotensin II and increase bradykinin.', 'ARBs: losartan, valsartan and candesartan block the AT1 receptor without directly increasing bradykinin.', 'Direct renin inhibitor: aliskiren suppresses renin activity. Its clinical role is limited and it must not be combined inappropriately with ACE inhibitor/ARB therapy.', 'ARNI: sacubitril/valsartan combines neprilysin inhibition with AT1 receptor blockade.']),
('Mechanisms and clinical significance', ['ACE inhibitors and ARBs decrease intraglomerular pressure and reduce albuminuria, but can initially lower GFR. They are commonly used in albuminuric CKD unless contraindicated.', 'Sacubitril inhibits neprilysin, increasing natriuretic peptides. Valsartan blocks RAAS activation. In symptomatic HFrEF, ARNI is a major disease-modifying option.', 'Finerenone is a newer nonsteroidal mineralocorticoid receptor antagonist. It blocks downstream aldosterone signaling and is used in selected CKD associated with type 2 diabetes.']),
('Therapeutic uses', ['Hypertension: ACE inhibitor or ARB may be first-line, particularly with albuminuric CKD, diabetes or heart failure.', 'HFrEF: ARNI preferred when tolerated, or ACE inhibitor/ARB; use alongside beta-blocker, mineralocorticoid receptor antagonist and SGLT2 inhibitor.', 'Diabetic CKD: ACE inhibitor/ARB for albuminuria, with finerenone considered in suitable patients after potassium and eGFR assessment.']),
('Adverse effects and contraindications', ['ACE inhibitors may cause cough and angioedema due to bradykinin. ARBs have lower cough risk but may still rarely cause angioedema.', 'All RAAS inhibitors can cause hyperkalemia, hypotension and creatinine rise. Check renal function and potassium after initiation and dose changes.', 'ACE inhibitors, ARBs, aliskiren and ARNI are contraindicated in pregnancy. A 36-hour washout is required when changing from an ACE inhibitor to sacubitril/valsartan because of angioedema risk.']),
('Exam summary', ['ACE inhibitor: blocks ACE and raises bradykinin. ARB: blocks AT1 receptor. Aliskiren: blocks renin. ARNI: neprilysin inhibition plus ARB.', 'Do not combine ACE inhibitor, ARB and direct renin inhibitor routinely because renal injury, hyperkalemia and hypotension increase.', 'Monitor potassium and creatinine with every RAAS pathway drug.'])]),
('6. Modern gastroprotectors, liver-function medicines and hepatoprotectors', [
('Scope', ['Gastroprotection prevents or heals drug-related or acid-related mucosal injury. Liver-directed therapy depends on the specific diagnosis; “hepatoprotector” is a broad and sometimes imprecise term.', 'Avoid treating abnormal liver tests with supplements before identifying the cause, such as viral hepatitis, alcohol, metabolic disease, biliary obstruction, autoimmune disease or drug injury.', 'Management should include withdrawal of hepatotoxic exposure when appropriate and specialist assessment for significant jaundice, coagulopathy or encephalopathy.']),
('Gastroprotective drug groups', ['Proton-pump inhibitors: omeprazole, pantoprazole and esomeprazole irreversibly inhibit the gastric H+/K+-ATPase. They are the strongest acid suppressors.', 'H2-receptor blockers: famotidine reduces histamine-stimulated acid secretion.', 'Mucosal protectants: sucralfate forms a protective barrier; bismuth has local protective and antimicrobial actions; misoprostol is a prostaglandin analogue useful for NSAID-ulcer prevention but limited by diarrhea and pregnancy risk.']),
('Mechanisms and uses', ['PPIs are used for peptic ulcer disease, gastroesophageal reflux disease, upper GI bleeding protocols and prevention of NSAID-related ulcers in high-risk patients.', 'Misoprostol restores prostaglandin-mediated mucus, bicarbonate and mucosal blood flow. It is contraindicated in pregnancy unless used for a specific obstetric indication under care.', 'For H. pylori infection, acid suppression is combined with appropriate antibiotics according to local resistance guidance.']),
('Liver-directed medicines', ['N-acetylcysteine replenishes glutathione and is the antidote for acetaminophen overdose. It may also be considered in selected acute liver-failure contexts by specialists.', 'Ursodeoxycholic acid is used for specific cholestatic disorders, including primary biliary cholangitis, not as a universal liver tonic.', 'Disease-specific treatments include antivirals for viral hepatitis, immunosuppression for autoimmune hepatitis, and alcohol-cessation support for alcohol-associated liver disease.']),
('Safety', ['Long-term PPI use should have a clear indication and periodic review. Risks may include enteric infection and nutrient effects in some patients, though association does not always prove causation.', 'Sucralfate can impair absorption of other oral medicines. Separate administration times when required.', 'Herbal or “hepatoprotective” products can themselves cause liver injury and should be reported during medication review.']),
('Exam summary', ['PPIs reduce acid by irreversible proton-pump inhibition. Misoprostol replaces prostaglandin effects. Sucralfate protects locally.', 'There is no substitute for finding the cause of liver dysfunction. N-acetylcysteine is specific therapy for acetaminophen toxicity.', 'Use “hepatoprotector” carefully: evidence and indication differ widely among agents.'])]),
('7. Hepatoprotective agents in drug-induced hepatitis', [
('Definition and first action', ['Drug-induced liver injury (DILI) is liver damage caused by prescribed medicine, over-the-counter drugs, herbal products or supplements.', 'The first and most important action is to stop the suspected offending agent unless it is essential and continuation is directed by a specialist.', 'Assess severity urgently: jaundice, rising INR, encephalopathy, hypoglycemia, severe abdominal pain or marked systemic illness require immediate hospital evaluation.']),
('Assessment', ['Classify the biochemical pattern using ALT, alkaline phosphatase and bilirubin, and exclude viral, autoimmune, ischemic and obstructive causes.', 'Obtain a complete exposure history including supplements, traditional medicines, alcohol and recent dose changes.', 'Hy’s law pattern, hepatocellular injury with jaundice without another cause, signals increased risk of severe outcome.']),
('Specific therapies', ['N-acetylcysteine is indicated for acetaminophen toxicity and should be administered promptly according to established protocols. It can be beneficial even after delayed presentation.', 'L-carnitine is used in significant valproate toxicity, particularly with hyperammonemia, under toxicology or specialist direction.', 'Corticosteroids may be used for immune-mediated or autoimmune-like DILI in selected cases, but are not routine for all DILI.']),
('Supportive and specialist management', ['Most idiosyncratic DILI improves after drug withdrawal and supportive care. Monitor liver tests, bilirubin, INR, renal function and clinical status.', 'Cholestatic pruritus may be managed symptomatically. Ursodeoxycholic acid is sometimes used in cholestatic diseases but is not proven as a universal DILI antidote.', 'Acute liver failure requires referral to a liver-transplant center.']),
('What not to do', ['Do not rechallenge with a medicine strongly suspected of causing serious DILI unless benefits are exceptional and expert supervision is available.', 'Do not rely on unproven herbal “liver protectors”; they can delay diagnosis or worsen injury.', 'Do not assume a normal early bilirubin excludes serious evolving injury.']),
('Exam summary', ['DILI management: recognize, stop culprit, evaluate severity and exclude other causes. Use targeted antidotes where known.', 'Acetaminophen overdose: N-acetylcysteine. Valproate toxicity with hyperammonemia: consider L-carnitine in specialist care.', 'The most effective “hepatoprotection” is prevention, medication review and early withdrawal of the culprit.'])]),
('8. Comparative analysis of iron preparations (often termed iron-sparing/iron-containing drugs)', [
('Terminology and purpose', ['The syllabus phrase “iron-sparing drugs” is ambiguous. This section interprets it as comparative pharmacology of iron replacement preparations used to correct iron deficiency.', 'Confirm iron deficiency when possible using ferritin and transferrin saturation, interpreted in clinical context. Anemia has many causes and empiric iron is not always appropriate.', 'Treatment includes correcting the source of deficiency, such as blood loss, dietary insufficiency or malabsorption.']),
('Oral iron preparations', ['Ferrous sulfate, ferrous fumarate and ferrous gluconate are common oral salts. Their elemental-iron content differs, so compare doses by elemental iron rather than tablet weight.', 'Ferrous salts are inexpensive and effective when absorbed and tolerated. Modified-release products may improve tolerability but may release iron beyond the optimal absorption site.', 'Polysaccharide iron complex and ferric maltol are alternative formulations in selected settings, with different cost and tolerability profiles.']),
('Parenteral iron', ['IV iron is considered when oral iron fails, is not tolerated, cannot be absorbed, or when repletion is urgent. Examples include iron sucrose, ferric carboxymaltose, ferumoxytol and ferric derisomaltose, depending on availability.', 'IV complexes deliver iron to reticuloendothelial processing sites, then to transferrin for erythropoiesis.', 'Choice depends on total replacement dose, number of infusions, kidney disease status, local formularies and adverse-effect profile.']),
('Comparison table concepts', ['Oral iron: convenient and low cost but slower repletion and frequent GI adverse effects. Absorption is reduced by inflammation and may be affected by food, calcium and acid suppression.', 'IV iron: faster repletion and avoids absorption limits, but requires infusion resources and observation for reactions.', 'Do not give iron when iron overload is present. Inflammation can elevate ferritin, so interpretation needs care.']),
('Adverse effects and counseling', ['Oral iron can cause nausea, epigastric discomfort, constipation, diarrhea and dark stool. Accidental ingestion is dangerous for children.', 'IV iron can cause infusion reactions; true severe hypersensitivity is uncommon but facilities must be prepared. Ferric carboxymaltose can cause hypophosphatemia.', 'Response is assessed by symptoms, hemoglobin trend and iron indices, not by immediate symptom change alone.']),
('Exam summary', ['Ferrous salts are standard oral therapy. Compare elemental iron, tolerance and adherence.', 'IV iron is preferred for malabsorption, intolerance, failed oral therapy or selected urgent/high-need situations.', 'Investigate why iron deficiency developed rather than only replacing iron.'])]),
('9. Combined sulfonamide preparations: mechanism and applications', [
('Overview', ['Sulfonamides are synthetic antimicrobials that inhibit bacterial folate synthesis. The classic combined preparation is trimethoprim-sulfamethoxazole, abbreviated TMP-SMX or co-trimoxazole.', 'The combination produces sequential blockade of folate metabolism and is usually bactericidal against susceptible organisms, whereas either drug alone may be only bacteriostatic.', 'Local resistance patterns and patient factors determine whether it is appropriate.']),
('Components and mechanism', ['Sulfamethoxazole is a structural analogue of para-aminobenzoic acid (PABA) and inhibits dihydropteroate synthase.', 'Trimethoprim inhibits bacterial dihydrofolate reductase. The two steps together reduce tetrahydrofolate, impairing nucleotide synthesis.', 'Humans obtain folate from diet and have different enzyme sensitivity, giving selective toxicity, although adverse effects still occur.']),
('Clinical applications', ['TMP-SMX is used for susceptible urinary tract infections, some skin/soft-tissue infections including community-associated MRSA in appropriate settings, and selected gastrointestinal or respiratory infections.', 'It is a first-line treatment and prophylaxis option for Pneumocystis jirovecii pneumonia in many guidelines, with alternatives for intolerance.', 'It may be used for Nocardia and Stenotrophomonas infections when susceptibility and clinical context support it.']),
('Pharmacokinetics and interactions', ['Both components are absorbed orally and distributed widely. Dose adjustment is needed in renal impairment.', 'Trimethoprim can increase potassium and raise serum creatinine by reducing tubular secretion without always reducing actual GFR.', 'Important interactions include warfarin, certain antidiabetic drugs and other medicines that raise potassium or suppress bone marrow.']),
('Adverse effects and cautions', ['Rash, photosensitivity, nausea, bone-marrow suppression, hyperkalemia and renal effects can occur.', 'Severe cutaneous adverse reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis are rare but potentially fatal. Stop medicine and seek urgent care for blistering rash or mucosal involvement.', 'Avoid or use specialist advice in serious sulfonamide allergy, significant renal impairment, late pregnancy or very young infants, depending on indication.']),
('Exam summary', ['Co-trimoxazole = sulfamethoxazole plus trimethoprim. It blocks two sequential folate-synthesis steps.', 'Key adverse-effect clues: rash, marrow suppression, hyperkalemia and interactions with warfarin.', 'Pneumocystis prophylaxis/treatment is a classic high-yield indication.'])]),
('10. Medicines used in HIV/AIDS infection', [
('Principles of antiretroviral therapy', ['HIV treatment uses combination antiretroviral therapy (ART) to suppress viral replication, restore immune function and prevent transmission.', 'ART is recommended for all people living with HIV. Regimens are chosen based on prior exposure, resistance, pregnancy potential, hepatitis B status, kidney/liver function, drug interactions and availability.', 'Adherence, viral-load monitoring and nonjudgmental follow-up are central to success.']),
('Antiretroviral classes', ['NRTIs: tenofovir, lamivudine, emtricitabine, abacavir. They inhibit reverse transcriptase after intracellular activation.', 'INSTIs: dolutegravir, bictegravir, raltegravir and cabotegravir inhibit integration of viral DNA into the host genome.', 'Other classes: NNRTIs, protease inhibitors, entry/attachment inhibitors and capsid inhibitors have roles in selected regimens, resistance or long-acting strategies.']),
('Common regimen concepts', ['Many first-line regimens use two NRTIs plus an INSTI, for example tenofovir plus lamivudine/emtricitabine plus dolutegravir, subject to national guidelines.', 'Long-acting injectable cabotegravir/rilpivirine is an option for selected virally suppressed adults where available and after careful assessment.', 'Hepatitis B co-infection usually requires a regimen active against both HIV and HBV, often containing tenofovir plus lamivudine or emtricitabine.']),
('Opportunistic infections and prophylaxis', ['Advanced HIV may need prophylaxis or treatment for opportunistic infections based on CD4 count, geography and clinical findings.', 'TMP-SMX commonly prevents Pneumocystis pneumonia in eligible patients. Tuberculosis, cryptococcal disease and other infections require disease-specific therapy.', 'Timing of ART around opportunistic infection treatment can be complex due to immune reconstitution inflammatory syndrome and drug interactions.']),
('Adverse effects and monitoring', ['Tenofovir disoproxil fumarate can affect kidney function and bone density; formulation choice may differ by risk profile.', 'Dolutegravir is generally well tolerated but interacts with polyvalent cations and some enzyme inducers. Protease inhibitors have important CYP-mediated interactions.', 'Monitor viral load, CD4 count where indicated, renal/liver function, metabolic effects, adherence and interactions.']),
('Exam summary', ['ART is combination treatment. INSTI plus two NRTIs is a common modern framework.', 'The goal is sustained undetectable viral load. People with sustained viral suppression do not sexually transmit HIV, expressed as U=U.', 'Never use incomplete therapy or stop HBV-active agents in co-infection without a plan.'])]),
('11. Anthelmintics', [
('Overview', ['Anthelmintics treat infections caused by nematodes, cestodes and trematodes. Diagnosis depends on parasite, geography, symptoms, stool/serology/imaging and exposure history.', 'Drug choice is organism-specific. Empiric treatment may be reasonable only in defined public-health or clinical contexts.', 'Mass drug administration programs use selected agents at population level under public-health guidance.']),
('Major drugs and spectra', ['Albendazole and mebendazole are benzimidazoles used for many intestinal nematodes. Albendazole is also used in tissue helminth infections such as neurocysticercosis and hydatid disease under specialist care.', 'Ivermectin treats strongyloidiasis, onchocerciasis and scabies; it has important precautions in Loa loa endemic areas.', 'Praziquantel is active against many cestodes and trematodes, including schistosomiasis. Pyrantel is used for enterobiasis and other susceptible intestinal nematodes.']),
('Mechanisms', ['Benzimidazoles bind parasite beta-tubulin, disrupt microtubules and impair glucose uptake.', 'Ivermectin activates parasite glutamate-gated chloride channels, causing hyperpolarization and paralysis.', 'Praziquantel increases parasite membrane permeability to calcium, causing contraction and tegumental damage. Pyrantel produces depolarizing neuromuscular blockade.']),
('Condition-focused examples', ['Enterobiasis: pyrantel or albendazole/mebendazole with household hygiene and often repeat dosing to manage reinfection.', 'Strongyloidiasis: ivermectin is preferred. This matters before corticosteroids or other immunosuppression because hyperinfection can be life-threatening.', 'Neurocysticercosis: treatment requires imaging, seizure management and specialist assessment; antiparasitic therapy can provoke inflammatory reactions.']),
('Adverse effects and cautions', ['Benzimidazoles may cause abdominal symptoms and, with prolonged/high-dose therapy, liver-test abnormalities or marrow toxicity. Avoid in early pregnancy unless benefit clearly outweighs risk.', 'Ivermectin adverse effects can reflect inflammatory response to dying parasites. In high Loa loa microfilaremia, serious encephalopathy risk exists.', 'Praziquantel can cause dizziness and abdominal symptoms; caution is needed in ocular cysticercosis and with interacting enzyme inducers.']),
('Exam summary', ['Albendazole: broad benzimidazole. Ivermectin: Strongyloides/onchocerciasis. Praziquantel: cestodes and trematodes.', 'The mechanism often predicts the parasite effect: tubulin disruption, chloride-channel activation or calcium permeability.', 'Confirm the organism and consider pregnancy, CNS/ocular involvement and regional epidemiology.'])]),
('12. Antitumor agents: targeted therapy, monoclonal antibodies and protein kinase inhibitors', [
('Introduction', ['Cancer pharmacotherapy includes cytotoxic chemotherapy, endocrine therapy, immunotherapy, targeted small molecules and monoclonal antibodies. Choice is driven by tumor type, stage, molecular markers, patient fitness and treatment goal.', 'Targeted therapy acts on a defined molecular abnormality or pathway, but it is not automatically free of toxicity.', 'Molecular testing can identify actionable biomarkers such as HER2 amplification, EGFR mutations, BCR-ABL fusion, ALK rearrangement or PD-L1 expression.']),
('Monoclonal antibodies', ['Trastuzumab targets HER2 and is used in HER2-positive breast and gastric cancers. Cardiac function must be monitored.', 'Rituximab targets CD20 on B cells and is used in several B-cell malignancies. Infusion reactions and hepatitis B reactivation are important concerns.', 'Bevacizumab targets VEGF and impairs tumor angiogenesis. It can cause hypertension, thrombosis, bleeding, proteinuria and impaired wound healing.', 'Immune-checkpoint inhibitors such as pembrolizumab or nivolumab block PD-1/PD-L1 pathways and activate antitumor immunity.']),
('Protein kinase inhibitors', ['Imatinib inhibits BCR-ABL tyrosine kinase and transformed chronic myeloid leukemia therapy. It also targets KIT/PDGFRA in certain tumors.', 'EGFR inhibitors include osimertinib for selected EGFR-mutant non-small-cell lung cancer. Rash and diarrhea are common class effects; interstitial lung disease is uncommon but serious.', 'Other examples include BTK inhibitors, BRAF/MEK inhibitors, VEGFR inhibitors and CDK4/6 inhibitors. Each requires biomarker-based selection and specific monitoring.']),
('Mechanisms and resistance', ['Small-molecule kinase inhibitors usually enter cells and inhibit intracellular signaling enzymes. Monoclonal antibodies bind extracellular targets or immune ligands.', 'Cancer resistance can arise through secondary mutations, pathway bypass, impaired drug binding, tumor heterogeneity or pharmacokinetic factors.', 'Combination strategies may delay resistance but also increase toxicity and cost.']),
('Adverse effects and clinical safety', ['Targeted drugs can cause serious organ-specific toxicity: trastuzumab cardiomyopathy, VEGF-pathway hypertension/proteinuria, BCR-ABL inhibitor cytopenias, and EGFR inhibitor rash/diarrhea.', 'Checkpoint inhibitors can cause immune-related adverse events affecting skin, colon, liver, endocrine glands, lungs, kidneys and heart. Early recognition and multidisciplinary management are needed.', 'Anticancer medicines require oncology supervision, monitoring plans and attention to reproductive safety and drug interactions.']),
('Exam summary', ['Monoclonal antibodies often end in -mab; many small-molecule kinase inhibitors end in -nib, but naming alone does not prove indication.', 'Match treatment to biomarker: BCR-ABL to imatinib, HER2 to trastuzumab, EGFR mutation to EGFR-targeted therapy.', 'Targeted therapy is precise in target selection, not necessarily mild in adverse effects.'])])
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    canvas.setFont('Helvetica',8)
    canvas.setFillColor(colors.HexColor('#4D6378'))
    canvas.drawString(1.55*cm, .85*cm, 'Pharmacology Study Guide | Educational use only')
    canvas.drawRightString(A4[0]-1.55*cm, .85*cm, f'Page {doc.page}')
    canvas.restoreState()

def info_table(rows):
    data=[[Paragraph('<b>Key point</b>', styles['Small']), Paragraph('<b>Details</b>', styles['Small'])]]
    for a,b in rows: data.append([Paragraph(a,styles['Small']),Paragraph(b,styles['Small'])])
    t=Table(data, colWidths=[4.0*cm, 12.2*cm], repeatRows=1)
    t.setStyle(TableStyle([('BACKGROUND',(0,0),(-1,0),colors.HexColor('#DDEBF7')),('TEXTCOLOR',(0,0),(-1,0),colors.HexColor('#12355B')),('GRID',(0,0),(-1,-1),.35,colors.HexColor('#AFC7DA')),('VALIGN',(0,0),(-1,-1),'TOP'),('LEFTPADDING',(0,0),(-1,-1),6),('RIGHTPADDING',(0,0),(-1,-1),6),('TOPPADDING',(0,0),(-1,-1),5),('BOTTOMPADDING',(0,0),(-1,-1),5),('BACKGROUND',(0,1),(-1,-1),colors.white)]))
    return t

def make_doc():
    doc=SimpleDocTemplate(OUT,pagesize=A4,leftMargin=1.55*cm,rightMargin=1.55*cm,topMargin=1.35*cm,bottomMargin=1.7*cm,title='Pharmacology Study Guide: 12 Topics')
    story=[]
    story.append(Spacer(1,2.0*cm))
    story.append(Paragraph('PHARMACOLOGY STUDY GUIDE',styles['Cover']))
    story.append(Paragraph('Twelve illustrated topics from the supplied 5th-semester list',ParagraphStyle('sub',parent=styles['Body2'],alignment=TA_CENTER,fontSize=14,leading=19,textColor=colors.HexColor('#376D89'))))
    story.append(Spacer(1,.45*cm))
    story.append(Paragraph('Each topic is organized into six concise learning pages: scope, classification, mechanisms, clinical applications, safety, and examination revision.',ParagraphStyle('disc',parent=styles['Body2'],alignment=TA_CENTER,fontSize=11,leading=15)))
    story.append(Spacer(1,.8*cm))
    story.append(Paragraph('<b>Important:</b> This guide is for study. It is not a prescribing manual. Doses and patient-specific decisions are intentionally omitted. Follow local protocols and current specialist guidance.',styles['Callout']))
    story.append(PageBreak())
    for idx,(topic,pages) in enumerate(topics, start=1):
        imgpath=f'{ASSETS}/topic_{idx}.png'
        for pnum,(heading,bullets) in enumerate(pages, start=1):
            story.append(Paragraph(topic,styles['Topic']))
            story.append(Paragraph(f'Page {pnum} of 6: {heading}',styles['PageTitle']))
            if pnum==1 and os.path.exists(imgpath):
                im=PILImage.open(imgpath); w,h=im.size
                draw_w=13.2*cm; draw_h=draw_w*h/w
                story.append(Image(imgpath,width=draw_w,height=min(draw_h,7.0*cm)))
                story.append(Spacer(1,.18*cm))
            story.append(Paragraph(bullet_list(bullets),styles['Body2']))
            # study table reinforces each page with safe structured content
            rows=[('Focus', heading),('Core message', bullets[0]),('Study cue', bullets[-1])]
            story.append(info_table(rows))
            if pnum==6:
                story.append(Spacer(1,.35*cm))
                story.append(Paragraph('Revision prompt: Can you name the principal class, mechanism, key indication and major safety concern without looking at the notes?',styles['Callout']))
            story.append(PageBreak())
    doc.build(story,onFirstPage=header_footer,onLaterPages=header_footer)

if __name__=='__main__': make_doc()

from pathlib import Path
from pypdf import PdfReader, PdfWriter

src = Path('/tmp/workspace/pharmacology-72-page-pdf/output/Pharmacology_Study_Guide_12_Topics.pdf')
out = Path('/tmp/workspace/pharmacology-72-page-pdf/output/topic_pdfs')
out.mkdir(exist_ok=True)

reader = PdfReader(str(src))
topics = [
    (16, 'New_Generation_Drugs_Increasing_Surfactant_Synthesis'),
    (17, 'Cardiotonic_Drugs_in_Acute_and_Chronic_Heart_Failure'),
    (18, 'Medicines_Used_in_Myocardial_Infarction'),
    (19, 'Medicines_Used_in_Hypertensive_Crisis'),
    (20, 'New_Drugs_Affecting_the_Renin_Angiotensin_System'),
    (21, 'Modern_Gastroprotectors_and_Hepatoprotectors'),
    (22, 'Hepatoprotective_Agents_for_Drug_Induced_Hepatitis'),
    (23, 'Comparative_Analysis_of_Iron_Sparing_Drugs'),
    (24, 'Combined_Sulfonamide_Preparations'),
    (25, 'Medicines_Used_in_HIV_AIDS_Infection'),
    (26, 'Anthelmintics'),
    (27, 'Antitumor_Targeted_Drugs_Monoclonal_Antibodies_and_Kinase_Inhibitors'),
]

for i, (number, slug) in enumerate(topics):
    writer = PdfWriter()
    start = 1 + i * 6  # skip combined guide cover page
    for page_index in range(start, start + 6):
        writer.add_page(reader.pages[page_index])
    writer.add_metadata({
        '/Title': f'Topic {number}: {slug.replace("_", " ")}',
        '/Subject': 'Pharmacology study guide',
    })
    with open(out / f'{number}_{slug}.pdf', 'wb') as output_file:
        writer.write(output_file)

print(f'Created {len(topics)} topic PDFs in {out}')