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PH2.6-8 | Autacoids and Pain Pharmacology — PBL Case

CLINICAL SETTING

Mrs. Kavitha Moorthy, a 44-year-old schoolteacher from a semi-urban town near Coimbatore, visits the medicine OPD of a district hospital. She has been suffering from intermittent joint pain for the past year and recently developed new symptoms that are worrying her. She works long hours and often self-medicates with whatever is available at the local pharmacy. Her husband accompanies her and seems concerned about the medicines she has been taking.

Trigger 1: The Initial Presentation

Mrs. Kavitha presents with: (1) Painful swollen right knee for 5 days — she reports this has happened twice before in the past 8 months, each time in different joints. This time it is the knee; previously it was the left ankle and right wrist. (2) New-onset dry cough and mild wheezing for 3 days. She has no fever. Her husband reveals that she has been regularly taking 'three red tablets twice a day' (he produces a blister pack of diclofenac 50 mg) for the past 10 days for joint pain. She also has a 5-year history of hypertension treated with enalapril 5 mg OD and a diuretic (hydrochlorothiazide 25 mg OD). Vitals: BP 148/92 mmHg, RR 18/min, no fever. Examination: right knee warm, swollen, and tender; bilateral end-expiratory wheeze on auscultation.

DISCUSSION POINTS

  • What are the possible diagnoses for the acute joint swelling with a history of migrating joint involvement?
  • What is the likely cause of her new wheezing and cough? How does her current medication profile explain this symptom?
  • What immediate investigations would you order at this stage?
  • Identify any potentially dangerous drug combination in her current medication list.
Click to reveal Trigger 2: Investigations and Diagnosis (discuss previous trigger first!)

Trigger 2: Investigations and Diagnosis

Results return: Serum uric acid: 10.4 mg/dL. Joint fluid aspirate: weakly negatively birefringent needle-shaped crystals under polarised light. Serum creatinine: 1.4 mg/dL (eGFR estimated 48 mL/min — CKD stage 3). FBC: normal. CRP: mildly elevated. Peak expiratory flow rate: 68% predicted. Spirometry: reversible obstructive pattern. She admits to also occasionally using aspirin 650 mg (purchased OTC) for headaches. She mentions headaches occur 2–3 times per month — severe, unilateral, throbbing, with nausea.

DISCUSSION POINTS

  • Confirm the diagnosis. What is the triad of aspirin-exacerbated respiratory disease (AERD), and does this patient fit?
  • Given her CKD (eGFR 48) and new bronchospasm, which drugs are now contraindicated for her gout attack? What are your remaining options?
  • Explain the mechanism by which NSAIDs and aspirin trigger bronchospasm in susceptible individuals (link COX-1 and leukotriene pathways).
  • The uric acid is 10.4 mg/dL. Should allopurinol be started today? If not, when should it be started and at what dose?
Click to reveal Trigger 3: Management and Counselling (discuss previous trigger first!)

Trigger 3: Management and Counselling

You have diagnosed: (1) acute gouty arthritis — right knee; (2) AERD (aspirin/NSAID-exacerbated respiratory disease + asthma); (3) CKD stage 3 (eGFR 48); (4) probable migraine (2–3 attacks/month, unilateral throbbing with nausea). Her husband asks: 'Doctor, can she take any antihistamines? She also gets sneezing and itchy eyes every morning.' She asks: 'The pharmacy gave me some tablets for the wheezing — is it safe to take them? Can I take aspirin for my headaches?' You must now write a complete management plan including safe drug choices, patient counselling, and a follow-up plan.

DISCUSSION POINTS

  • Draft a complete drug management plan for today: (a) acute gout treatment given AERD + CKD; (b) asthma/AERD management; (c) antihistamine for rhinitis considering her comorbidities; (d) safe analgesic for migraine without triggering AERD.
  • What specific counselling will you give Mrs. Kavitha about avoiding OTC NSAIDs and aspirin? How does AERD change her permissible analgesic list permanently?
  • Is sumatriptan safe for her migraines? What drug can safely treat her acute migraine attacks given AERD and CKD?
  • Design a 4-week follow-up plan — what will you monitor and when will you initiate allopurinol?

Group Task Assignments

Group 1: NSAID mechanism and adverse effects

  • Diagram the arachidonic acid pathway showing COX-1, COX-2, lipoxygenase, and their products
  • Explain how NSAID-induced COX-1 inhibition shunts arachidonic acid into the lipoxygenase pathway, producing leukotrienes that trigger bronchospasm in AERD
  • List all the pharmacological effects of PGE2 and PGI2 and how their suppression causes renal, GI, and pulmonary adverse effects

Competencies: PH2.7

Group 2: Gout pharmacology — acute and chronic management

  • Compare NSAIDs, colchicine, and corticosteroids for acute gout — mechanisms, doses, contraindications table
  • Explain why allopurinol worsens or prolongs an acute attack if started during the episode
  • Calculate appropriate colchicine dose reduction for a patient with eGFR 48 mL/min

Competencies: PH2.8

Group 3: Antihistamine pharmacology and AERD

  • Create a comparison table: first-generation vs second-generation antihistamines (receptor selectivity, BBB penetration, side effects, dosing in renal impairment)
  • Explain why AERD specifically affects aspirin/NSAID sensitivity but NOT antihistamine use
  • Identify which antihistamine is safest for Mrs. Kavitha, justifying each choice criterion

Competencies: PH2.6

Group 4: Migraine pharmacology in a complex patient

  • List abortive and prophylactic migraine drugs with mechanisms
  • Explain why triptans are contraindicated in Mrs. Kavitha (or if they are — justify)
  • Identify the safest abortive analgesic for Mrs. Kavitha's migraines given AERD and CKD, with dose and mechanism

Competencies: PH2.8

Group 5: Drug interactions and patient safety in polypharmacy

  • Identify the triple whammy combination present in her medication history and explain each component's contribution to renal injury
  • Draft a medication safety counselling script in plain Tamil/English for Mrs. Kavitha explaining which OTC medications she must avoid permanently
  • Propose a long-term monitoring plan: parameters, intervals, and thresholds for review

Competencies: PH2.7, PH2.8

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [PH2.6] How do H1 antihistamines differ between generations in terms of CNS penetration, receptor selectivity, and side-effect profiles? How should cetirizine dose be adjusted in CKD stage 3?
  2. [PH2.7] What is the mechanism by which NSAIDs and aspirin exacerbate asthma in susceptible individuals? How does COX-1 inhibition lead to increased leukotriene synthesis? What are the safe analgesic options for a patient with AERD?
  3. [PH2.8] What is the management algorithm for acute gouty arthritis when the patient has AERD and CKD stage 3? When and how should urate-lowering therapy (allopurinol) be initiated? What is the role of triptans in migraine management, and what are their cardiovascular contraindications?