# NSAIDs, Paracetamol, Gout and Migraine Drugs for NEET PG Pharmacology: COX-2, Overdose Antidotes, Allopurinol, Triptans, Methotrexate Source: https://tracknation.in/story/nsaids-paracetamol-gout-and-migraine-drugs-for-neet-pg-pharmacology-cox-2-overdose-antidotes-allopurinol-triptans-methotrexate (TrackNation — free UPSC notes with PYQs) > NEET PG Pharmacology: how NSAIDs differ (aspirin's irreversible COX block, coxibs), their gut, kidney and heart risks, paracetamol and aspirin poisoning with N-acetylcysteine and alkaline diuresis, gout flare and urate-lowering drugs, triptans and migraine prophylaxis as in India's ICMR headache workflow, methotrexate and hydroxychloroquine in RA, and antihistamines — from official labels, MSD and ICMR, with a diagram, hooks, vignette MCQs and cards. ## Start Here 🎯 **Exam priority: High.** *Expect vignettes: a teenager after a paracetamol overdose, an older adult with confusion and tachypnoea (aspirin), a gout patient on azathioprine starting allopurinol, a migraine patient with angina asking for a triptan.* CBME mapping: **PH 2.4–2.8** (autacoids, NSAIDs, gout, rheumatoid arthritis, migraine) and **PH 9** (poisoning). ## NSAIDs and Paracetamol NSAIDs block **cyclooxygenase (COX)** and so reduce prostaglandin production. Neither NSAIDs nor paracetamol cause physical dependence or tolerance. | **Drug or group** | **Key fact (source)** | | Non-selective NSAIDs (ibuprofen, naproxen) | Block COX-1 and COX-2 reversibly | | Aspirin | Blocks COX-1 and COX-2 irreversibly | | Coxibs (celecoxib) | Mainly COX-2; lowest ulcer risk, but no GI advantage if taken with low-dose aspirin; not kidney-sparing; contraindicated in sulfonamide allergy and around CABG | | Ketorolac | Opioid-level acute pain; total use (injection + tablets) not more than 5 days | | Paracetamol | No anti-inflammatory or antiplatelet effect, no gastric irritation; liver toxicity above 4 g a day or with liver disease or alcohol | | All NSAIDs | Prothrombotic (MI, stroke): risk lower with ibuprofen, naproxen, celecoxib than with ketorolac, diclofenac; caution in kidney disease | **Gut protection:** misoprostol reduces the risk of NSAID-induced (including aspirin-induced) gastric ulcers in high-risk patients, but it can cause abortion, birth defects and uterine rupture, so it must not be given to pregnant women for this purpose. ## Paracetamol Poisoning *Paracetamol overdose: CYP450 makes NAPQI; glutathione detoxifies it until it runs out; N-acetylcysteine restores glutathione. Drawn by TrackNation from the MSD Manual and the Acetadote label.* - **Toxic dose**: ≥ 150 mg/kg within 24 hours (about 7.5–10 g in an adult). Symptoms are minor until ≥ 48 hours, so a well-looking patient is not safe. - **Decide with a level** taken ≥ 4 hours after a single acute ingestion, on the **Rumack-Matthew nomogram**. The nomogram may underestimate risk in chronic alcoholism, malnutrition or with CYP2E1 inducers such as isoniazid. - **N-acetylcysteine**: best within **8 hours**; still given after 24 hours; IV and oral are equally effective. The IV three-bag regimen is **150 mg/kg over 1 hour, 50 mg/kg over 4 hours, 100 mg/kg over 16 hours**. ## Aspirin (Salicylate) Poisoning - **Toxic dose**: ≥ 150 mg/kg. Oil of wintergreen (methyl salicylate) is the most concentrated form: less than 5 mL can kill a young child. - **Acid-base**: salicylates stimulate the respiratory centre (**primary respiratory alkalosis**) and, independently, cause **metabolic acidosis** by uncoupling oxidative phosphorylation. - **Early**: nausea, vomiting, **tinnitus**, hyperventilation. **Chronic** poisoning in older adults can look like sepsis (confusion, fever, hypoxia, non-cardiogenic pulmonary oedema). - **Treatment**: activated charcoal and **alkaline diuresis** (salicylate excretion rises as urine pH rises), or haemodialysis. ## Gout Hyperuricaemia (urate > 6.8 mg/dL) is almost always present, but the diagnosis needs **crystals in synovial fluid**. Thiazide and loop diuretics raise urate. Long-term target: urate usually **< 6 mg/dL**. | **Drug** | **Role** | **Must know (source)** | | NSAIDs, colchicine, glucocorticoids | Treat the acute flare | Colchicine: reduce or avoid in renal failure and with CYP3A4/P-gp inhibitors (e.g. macrolides) | | Allopurinol | Preferred first urate-lowering drug (xanthine oxidase inhibitor) | HLA-B*5801 → hypersensitivity; raises azathioprine and 6-mercaptopurine levels; not for asymptomatic hyperuricaemia | | Febuxostat | Xanthine oxidase inhibitor when allopurinol unsuitable | Boxed warning: higher cardiovascular death than allopurinol in gout with CV disease | | Probenecid | Uricosuric | Loses effect when GFR < 50 | | Pegloticase | Recombinant uricase (urate → allantoin) | Refractory or tophaceous gout | ## Migraine - **Triptans** (sumatriptan): 5-HT1B/1D agonists for the **acute attack** only — not for prophylaxis or cluster headache. **Contraindicated** in ischaemic heart disease, coronary vasospasm (Prinzmetal angina) and WPW syndrome. - **Prevention** (MSD): beta-blockers, amitriptyline, topiramate, divalproex, monoclonal antibodies. The migraine attack involves trigeminovascular release of neuropeptides such as **CGRP**. - **India's ICMR headache workflow (PHC level)**: acute attack — paracetamol 650 mg or indomethacin 50 mg, with prochlorperazine 10 mg for nausea; start **prophylaxis if more than 2 attacks a month** — **propranolol 40 mg** or **flunarizine 10 mg** once daily, tried for 2 months. Chronic tension-type headache: amitriptyline 10 mg at night. ## Rheumatoid Arthritis Drugs and Antihistamines - **Methotrexate** (a dihydrofolate reductase inhibitor) is the usual starting DMARD: **10–15 mg once a week** with **folic acid 1 mg daily**. Contraindicated in pregnancy for non-cancer use. Triple therapy = methotrexate + hydroxychloroquine + sulfasalazine. - **Hydroxychloroquine**: retinopathy rises with daily doses above **5 mg/kg** of actual body weight. - **Diphenhydramine** (first-generation H1 antihistamine): sedating and anticholinergic (drying); in anaphylaxis it is only an adjunct after adrenaline. ## Traps the Examiner Sets - Aspirin's COX block is irreversible; other NSAIDs are reversible. - Coxibs spare the stomach but not the kidney or the heart. - Paracetamol level before 4 hours cannot be plotted; treat with NAC if the time is unknown or the level is delayed. - Aspirin poisoning: alkalinise the urine. - Allopurinol + azathioprine = marrow suppression; reduce the azathioprine dose. - Febuxostat carries a CV-death boxed warning; allopurinol is preferred. - Triptans: acute attack only, never with angina; propranolol or flunarizine prevent. - Methotrexate for RA is weekly, not daily. ## Memory Hooks & Shortcuts *Shortcuts to lock in this article's numbers and lists. Each one only re-packages facts proven above.* - 🧠 **Aspirin Arrests for good** — aspirin is the irreversible COX blocker - 🧠 **4 hours to plot, 8 hours to save** — paracetamol level at ≥ 4 h; NAC best within 8 h - 🧠 **150 for both poisons** — paracetamol and aspirin toxicity both start around 150 mg/kg - 🧠 **Salicylate: Alkalose then Acid, Alkalinise the urine** — respiratory alkalosis + metabolic acidosis; alkaline diuresis - 🧠 **Allo + Aza = Agranulocytosis risk** — allopurinol raises azathioprine and 6-MP exposure - 🧠 **Triptan stops the attack, Propranolol prevents the next** — triptans acute only; propranolol or flunarizine prophylaxis - 🧠 **Methotrexate on Mondays only** — weekly dosing in RA, with folic acid ## Rapid-Revision Cards - Irreversible COX-1 + COX-2 block. - Least ulcers; no GI edge with low-dose aspirin; not renal-sparing. - Sulfonamide allergy, NSAID asthma, CABG. - Lower with ibuprofen, naproxen, celecoxib; higher with ketorolac, diclofenac. - ≤ 5 days total. - No anti-inflammatory or antiplatelet effect; no gastric irritation. - Hepatotoxicity risk above 4 g/day. - ≥ 150 mg/kg (7.5–10 g adult). - Toxic CYP450 metabolite; detoxified by glutathione. - Level ≥ 4 h after single acute ingestion; ≤ 150 mcg/mL = very unlikely toxicity. - Best within 8 h; still give after 24 h. - 150/1 h → 50/4 h → 100/16 h (mg/kg). - Respiratory alkalosis + metabolic acidosis. - Charcoal, alkaline diuresis, haemodialysis. - < 5 mL can kill a child. - Prevents NSAID ulcers; abortifacient — avoid in pregnancy. - Crystals in synovial fluid; urate may be normal. - Usually < 6 mg/dL. - First-line XOI; HLA-B*5801; ↑ azathioprine. - Boxed warning: CV death. - Flares + prophylaxis + FMF; toxic with CYP3A4/P-gp inhibitors. - Uricosuric; fails if GFR < 50. - IHD, Prinzmetal, WPW. - > 2/month: propranolol 40 mg or flunarizine 10 mg. - 10–15 mg weekly + folic acid; not in pregnancy. - Retinopathy > 5 mg/kg/day. ## Sources *Facts in this article were checked against these documents.* - MSD Manual Professional Edition: Treatment of Pain; Acetaminophen Poisoning; Aspirin and Other Salicylate Poisoning; Gout; Migraine; Rheumatoid Arthritis — Merck & Co. (MSD Manuals), 2025–2026 (link) - Standard Treatment Workflow: Management of Headache — Indian Council of Medical Research / Department of Health Research, MoHFW, 2019 (link) - Prescribing labels: Celebrex, ketorolac, indomethacin, Acetadote, allopurinol, Uloric, Colcrys, probenecid, Imitrex, methotrexate, Plaquenil, Cytotec, diphenhydramine injection — DailyMed, US National Library of Medicine, current labels, accessed November 2026 (link) - Competency Based Undergraduate Curriculum, Pharmacology (PH 2.4–2.8, PH 9) — National Medical Commission, 2024 ## Test Yourself: Practice Questions Twenty-five questions in NEET PG style, most of them clinical vignettes. ## Practice Questions (NEET PG pattern) *Original questions written in the style of the exam: +4 for a correct answer, −1 for a wrong one. Every answer was checked against the sources listed above. NEET PG papers are not published by NBEMS, so these are not past-paper questions.* **Q1.** A 19-year-old took 40 paracetamol tablets of 500 mg (20 g) 3 hours ago and feels well. The best next step is to - (a) reassure and discharge, as she has no symptoms - (b) measure a paracetamol level at 4 hours after ingestion and plot it on the nomogram, starting N-acetylcysteine as indicated - (c) give activated charcoal and discharge - (d) start haemodialysis **Answer: (b)** — Symptoms are minor until ≥ 48 hours; the level is taken ≥ 4 hours after ingestion and plotted on the Rumack-Matthew nomogram. **Q2.** N-acetylcysteine protects the liver in paracetamol overdose mainly by - (a) blocking cytochrome P-450 - (b) reversing established necrosis - (c) increasing renal excretion of paracetamol - (d) restoring glutathione, which detoxifies NAPQI **Answer: (d)** — It is a glutathione precursor; it does not reverse damage already done. **Q3.** N-acetylcysteine is most effective if started within - (a) 48 hours - (b) 8 hours of ingestion - (c) 24 hours - (d) 72 hours **Answer: (b)** — Most effective within 8 hours; benefit after 24 hours is questionable but it is still given. **Q4.** The IV three-bag N-acetylcysteine regimen gives, in order, - (a) 140 mg/kg once orally - (b) 70 mg/kg every 4 h for 17 doses IV - (c) 150 mg/kg over 1 h, 50 mg/kg over 4 h, 100 mg/kg over 16 h - (d) 50, 100, 150 mg/kg each over 8 h **Answer: (c)** — Acetadote label: 150 mg/kg over 1 hour, then 50 over 4 hours, then 100 over 16 hours. **Q5.** In which patient may the paracetamol nomogram underestimate liver risk? - (a) A patient on paracetamol 1 g a day - (b) A child after an accidental single small dose - (c) A healthy young woman - (d) A man with chronic alcoholism on isoniazid **Answer: (d)** — Chronic alcoholism, malnutrition and CYP2E1 inducers such as isoniazid. **Q6.** A 70-year-old on long-term aspirin for arthritis is confused, febrile and tachypnoeic with tinnitus; sepsis is suspected. Arterial gas shows mixed respiratory alkalosis and metabolic acidosis. Treatment should include - (a) acidifying the urine - (b) activated charcoal and alkaline diuresis (or haemodialysis) - (c) naloxone - (d) N-acetylcysteine **Answer: (b)** — Chronic salicylate poisoning mimics sepsis; excretion rises as urine pH rises; severe cases need haemodialysis. **Q7.** The acid-base picture in early salicylate poisoning is - (a) primary respiratory alkalosis with an independent metabolic acidosis - (b) normal acid-base status - (c) pure metabolic alkalosis - (d) respiratory acidosis only **Answer: (a)** — Salicylates stimulate the medullary respiratory centre and independently cause metabolic acidosis. **Q8.** Which NSAID inhibits cyclooxygenase irreversibly? - (a) Celecoxib - (b) Ibuprofen - (c) Naproxen - (d) Aspirin **Answer: (d)** — Aspirin irreversibly inhibits both COX-1 and COX-2; others are typically reversible. **Q9.** A patient with a sulfonamide allergy needs an NSAID. Which is contraindicated? - (a) Indomethacin - (b) Naproxen - (c) Ibuprofen - (d) Celecoxib **Answer: (d)** — Celebrex is contraindicated with allergic-type reactions to sulfonamides, in aspirin/NSAID asthma, and around CABG. **Q10.** A man takes low-dose aspirin for coronary disease and needs long-term NSAID therapy. Adding celecoxib instead of ibuprofen - (a) abolishes all GI risk - (b) is renal-sparing - (c) removes all cardiovascular risk - (d) may give no GI advantage, because coxib benefit is lost with low-dose aspirin **Answer: (d)** — When a coxib is used with low-dose aspirin it may have no GI benefit over other NSAIDs; coxibs are not renal-sparing. **Q11.** Ketorolac (injection plus tablets) may be used for a total of at most - (a) 2 days - (b) 30 days - (c) 14 days - (d) 5 days **Answer: (d)** — The combined duration should not exceed 5 days. **Q12.** Misoprostol, given to prevent NSAID ulcers, is contraindicated in pregnancy because it - (a) can cause abortion, birth defects and uterine rupture - (b) raises blood pressure - (c) is hepatotoxic - (d) causes neural tube defects only **Answer: (a)** — Cytotec's boxed warning. **Q13.** A man with a red, hot first MTP joint has serum urate 5.9 mg/dL. Gout is - (a) confirmed by the urate level - (b) still possible; definite diagnosis needs urate crystals in synovial fluid - (c) excluded because urate is normal - (d) ruled out without X-ray changes **Answer: (b)** — Hyperuricaemia is almost always present, but diagnosis requires crystals in synovial fluid. **Q14.** A renal-transplant patient on azathioprine develops gout. If allopurinol is started, the azathioprine dose must be reduced because - (a) azathioprine blocks allopurinol - (b) allopurinol raises azathioprine exposure, risking myelosuppression - (c) both cause hyperuricaemia - (d) allopurinol induces azathioprine metabolism **Answer: (b)** — Allopurinol increases exposure to azathioprine and mercaptopurine. **Q15.** Severe hypersensitivity to allopurinol is more likely in carriers of - (a) HLA-DR4 - (b) HLA-B*1502 - (c) HLA-B27 - (d) HLA-B*5801 **Answer: (d)** — HLA-B*5801 carriers are at higher risk of allopurinol hypersensitivity syndrome. **Q16.** Febuxostat carries a boxed warning for - (a) Stevens-Johnson syndrome in HLA-B*5801 carriers - (b) agranulocytosis - (c) higher cardiovascular death than allopurinol in gout patients with CV disease - (d) hepatic failure in children **Answer: (c)** — Uloric boxed warning: cardiovascular death. **Q17.** A gout patient on colchicine prophylaxis is prescribed clarithromycin. The concern is - (a) reduced colchicine effect - (b) colchicine toxicity from CYP3A4/P-gp inhibition - (c) QT shortening - (d) hyperuricaemia **Answer: (b)** — CYP3A4/P-gp inhibitors increase colchicine toxicity; reduce dose or avoid. **Q18.** Probenecid becomes ineffective when - (a) GFR falls below about 50 mL/min/1.73 m² - (b) colchicine is co-prescribed - (c) serum urate exceeds 9 mg/dL - (d) the patient is over 60 **Answer: (a)** — Uricosurics lose efficacy with declining renal function. **Q19.** Pegloticase lowers urate by - (a) increasing renal excretion - (b) binding urate in the gut - (c) blocking xanthine oxidase - (d) converting urate to allantoin as a recombinant uricase **Answer: (d)** — Uricase, absent in humans, converts urate to more soluble allantoin. **Q20.** A 45-year-old with migraine has had angina for a year. For acute attacks, sumatriptan is - (a) safe if taken with aspirin - (b) safe in a lower dose - (c) contraindicated because of ischaemic heart disease - (d) first choice **Answer: (c)** — Triptans are contraindicated in ischaemic CAD, coronary vasospasm (Prinzmetal) and WPW syndrome. **Q21.** Under India's ICMR headache workflow, migraine prophylaxis is started when attacks exceed - (a) 1 a year - (b) never; only acute treatment is used - (c) 2 a month, with propranolol 40 mg or flunarizine 10 mg daily - (d) 10 a month only **Answer: (c)** — Frequency > 2/month: trial of propranolol 40 mg OD or flunarizine 10 mg OD for 2 months. **Q22.** Sumatriptan is indicated for - (a) tension-type headache prophylaxis - (b) prophylaxis of migraine - (c) cluster headache prevention - (d) the acute treatment of migraine **Answer: (d)** — Imitrex: acute treatment only; not for prophylaxis or cluster headache. **Q23.** A woman with rheumatoid arthritis is starting methotrexate. The correct schedule is - (a) 15 mg twice daily - (b) 10 mg daily - (c) monthly injection only - (d) 10–15 mg once a week with daily folic acid **Answer: (d)** — MSD: methotrexate 10–15 mg once a week with folic acid 1 mg daily; weekly, not daily. **Q24.** The risk of retinopathy with hydroxychloroquine rises above a daily dose of - (a) 400 mg regardless of weight - (b) 1 mg/kg - (c) 5 mg/kg of actual body weight - (d) 20 mg/kg **Answer: (c)** — Plaquenil: daily doses exceeding 5 mg/kg actual weight increase the incidence of retinopathy. **Q25.** In anaphylaxis, diphenhydramine is - (a) contraindicated - (b) an adjunct after adrenaline - (c) the first-line drug - (d) a replacement for adrenaline in children **Answer: (b)** — The label: in anaphylaxis as an adjunct to epinephrine and other standard measures. ### Active Recall From memory: compare aspirin, non-selective NSAIDs, coxibs and paracetamol; explain paracetamol toxicity, the nomogram and the N-acetylcysteine regimen; describe salicylate poisoning and its treatment; list the drugs for gout flares and urate lowering with their key cautions; and give the acute and preventive treatment of migraine and the methotrexate schedule in RA.