NSAIDs, Paracetamol, Gout and Migraine Drugs for NEET PG Pharmacology: COX-2, Overdose Antidotes, Allopurinol, Triptans, Methotrexate

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🎯 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.

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.

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

• Aspirin and COX

  Irreversible COX-1 + COX-2 block.

• Coxibs

  Least ulcers; no GI edge with low-dose aspirin; not renal-sparing.

• Celecoxib contraindications

  Sulfonamide allergy, NSAID asthma, CABG.

• NSAID CV risk

  Lower with ibuprofen, naproxen, celecoxib; higher with ketorolac, diclofenac.

• Ketorolac limit

  ≤ 5 days total.

• Paracetamol vs NSAIDs

  No anti-inflammatory or antiplatelet effect; no gastric irritation.

• Paracetamol daily limit

  Hepatotoxicity risk above 4 g/day.

• Toxic paracetamol dose

  ≥ 150 mg/kg (7.5–10 g adult).

• NAPQI

  Toxic CYP450 metabolite; detoxified by glutathione.

• Nomogram

  Level ≥ 4 h after single acute ingestion; ≤ 150 mcg/mL = very unlikely toxicity.

• NAC timing

  Best within 8 h; still give after 24 h.

• NAC IV regimen

  150/1 h → 50/4 h → 100/16 h (mg/kg).

• Salicylate acid-base

  Respiratory alkalosis + metabolic acidosis.

• Salicylate treatment

  Charcoal, alkaline diuresis, haemodialysis.

• Oil of wintergreen

  < 5 mL can kill a child.

• Misoprostol

  Prevents NSAID ulcers; abortifacient — avoid in pregnancy.

• Gout diagnosis

  Crystals in synovial fluid; urate may be normal.

• Urate target

  Usually < 6 mg/dL.

• Allopurinol

  First-line XOI; HLA-B*5801; ↑ azathioprine.

• Febuxostat

  Boxed warning: CV death.

• Colchicine

  Flares + prophylaxis + FMF; toxic with CYP3A4/P-gp inhibitors.

• Probenecid

  Uricosuric; fails if GFR < 50.

• Triptan contraindications

  IHD, Prinzmetal, WPW.

• ICMR migraine prophylaxis

  > 2/month: propranolol 40 mg or flunarizine 10 mg.

• Methotrexate in RA

  10–15 mg weekly + folic acid; not in pregnancy.

• Hydroxychloroquine

  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

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

Q3. N-acetylcysteine is most effective if started within

• (a) 48 hours

• (b) 8 hours of ingestion

• (c) 24 hours

• (d) 72 hours

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

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

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

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

Q8. Which NSAID inhibits cyclooxygenase irreversibly?

• (a) Celecoxib

• (b) Ibuprofen

• (c) Naproxen

• (d) Aspirin

Q9. A patient with a sulfonamide allergy needs an NSAID. Which is contraindicated?

• (a) Indomethacin

• (b) Naproxen

• (c) Ibuprofen

• (d) Celecoxib

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

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

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

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

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

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

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

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

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

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

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

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

Q22. Sumatriptan is indicated for

• (a) tension-type headache prophylaxis

• (b) prophylaxis of migraine

• (c) cluster headache prevention

• (d) the acute treatment of migraine

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

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

Q25. In anaphylaxis, diphenhydramine is

• (a) contraindicated

• (b) an adjunct after adrenaline

• (c) the first-line drug

• (d) a replacement for adrenaline in children

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.