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PH10.1-17 | Applied Pharmacology and Prescribing Skills — PBL Case

CLINICAL SETTING

Mr Balakrishnan, a 72-year-old retired school headmaster from a small town in Tamil Nadu, arrives at the medicine outpatient department of a district hospital accompanied by his daughter. He carries a battered plastic bag containing 14 different medication strips. His daughter says: 'Father has been getting weaker and more confused over the last three weeks. He was completely fine before — sharp as a pin, never missed his medicines.' She places the medication bag on the desk. 'He sees three doctors. The government hospital doctor, the private cardiologist in the city, and the orthopaedic surgeon who operated on his hip last year. Each one gave him tablets, and I think they are all fighting each other in his body.' Vital signs: BP 88/58 mmHg (lying), 76/50 mmHg (standing), Pulse 48/min (irregular), RR 16/min, SpO2 94% on room air, Temperature 36.4°C, Weight 58 kg. Serum creatinine 2.8 mg/dL (baseline 1.1 mg/dL 6 months ago). Serum potassium 6.2 mEq/L. Serum digoxin level (random, drawn 1 hour after morning dose): 3.8 ng/mL.

Trigger 1: The Medication Bag

You review the 14 medications: 1. Digoxin 0.25 mg OD (cardiologist, for atrial fibrillation) 2. Metoprolol 25 mg BD (cardiologist, for rate control) 3. Spironolactone 50 mg OD (cardiologist, for heart failure) 4. Furosemide 40 mg OD (cardiologist) 5. Aspirin 75 mg OD (cardiologist) 6. Atorvastatin 40 mg OD (cardiologist) 7. Amlodipine 10 mg OD (government hospital doctor, for hypertension) 8. Ramipril 10 mg OD (government hospital doctor, for hypertension/diabetes) 9. Metformin 1000 mg BD (government hospital doctor, for type 2 diabetes) 10. Glibenclamide 5 mg BD (government hospital doctor) 11. Tramadol 100 mg TDS (orthopaedic surgeon, for hip pain) 12. Diclofenac 50 mg BD (orthopaedic surgeon, for hip pain) 13. Alprazolam 0.5 mg nocte (orthopaedic surgeon, prescribed 8 months ago 'for pain-related insomnia') 14. Pantoprazole 40 mg OD (orthopaedic surgeon, to protect stomach from diclofenac) The daughter adds: 'The orthopaedic doctor in the city said we should stop seeing the government hospital doctor because he gave 'wrong medicines' — but father likes the government doctor and kept seeing both. Can you please sort this out?'

DISCUSSION POINTS

Identify all potentially harmful drug-drug interactions in this medication list. Which ones are most likely responsible for Mr Balakrishnan's current clinical deterioration?
The digoxin level is 3.8 ng/mL drawn 1 hour post-dose. Is this result interpretable? What is the correct TDM sampling window for digoxin, and what does this level tell you?
Mr Balakrishnan has acute-on-chronic kidney injury (creatinine 2.8 from baseline 1.1). Which drugs on this list are directly nephrotoxic or contraindicated in renal impairment, and why?
Calculate his Cockcroft-Gault creatinine clearance using his current creatinine. What does this tell you about his current drug dosing safety?

Click to reveal Trigger 2: Untangling the Crisis (discuss previous trigger first!)

Trigger 2: Untangling the Crisis

You repeat the digoxin level 8 hours after his last dose: 2.6 ng/mL. You calculate his Cockcroft-Gault CrCl: [(140-72) × 58 × 1] / [72 × 2.8] = 19.4 mL/min (assuming male). ECG shows atrial fibrillation with ventricular rate 48/min and two premature ventricular complexes. There are no ST changes. Chest X-ray: cardiomegaly, no pulmonary oedema. Your senior colleague remarks: 'The orthopaedic surgeon has essentially poisoned him with three different problems simultaneously.' The daughter overhears this and becomes distressed: 'Are you saying the doctor poisoned my father? I am going to file a complaint.' You need to address the daughter's concern, resolve the immediate medical emergency, and then reconstruct a rational medication list for Mr Balakrishnan.

DISCUSSION POINTS

Based on the corrected digoxin level (drawn 8 hours post-dose) and CrCl of 19.4 mL/min, what is your revised assessment of digoxin toxicity risk? What is the mechanism by which renal impairment raises digoxin levels?
Construct your differential diagnosis for the acute deterioration: which drugs are most responsible and through which mechanisms? (Consider: digoxin toxicity, NSAID nephrotoxicity, tramadol accumulation in renal impairment, alprazolam sedation, potassium imbalance from spironolactone/ramipril combination)
Which drugs would you stop immediately, which would you dose-adjust, and which would you continue unchanged? Justify each decision using patient-specific renal function, electrolytes, and clinical status.
How would you communicate with Mr Balakrishnan's daughter — explaining the situation accurately, compassionately, and without inappropriately assigning blame to any of his three doctors? What does the counselling framework tell you about managing this conversation?

Click to reveal Trigger 3: Reconstructing a Rational Regimen (discuss previous trigger first!)

Trigger 3: Reconstructing a Rational Regimen

Mr Balakrishnan stabilises over 48 hours with IV fluids and withdrawal of nephrotoxic drugs. Creatinine improves to 1.6 mg/dL. Digoxin level is now 1.1 ng/mL (8 hours post-dose). Heart rate is 64/min in controlled AF. Blood glucose 186 mg/dL (fasting). His daughter asks: 'How do I make sure this never happens again? He is seeing three doctors — who is responsible for the whole picture?' She also mentions: 'He was taking the alprazolam every night for 8 months. I tried to give him only half a tablet last night because I was worried — and he had a very bad night, shaking and couldn't sleep. Should I have done that?' You now write a reconstructed medication list, prepare a shared medication record for all three of his treating doctors, and counsel Mr Balakrishnan and his daughter on the new regimen and how to manage multiple prescribers safely.

DISCUSSION POINTS

Write a reconstructed medication list for Mr Balakrishnan on discharge. For each drug retained: confirm it is appropriate at his new baseline renal function (CrCl estimated ~40 mL/min on improving creatinine). For each drug stopped: confirm why and document the reason.
Mr Balakrishnan has been on alprazolam 0.5 mg nightly for 8 months. His daughter's experience of abrupt half-dose reduction causing severe symptoms demonstrates benzodiazepine dependence. How would you manage this safely? Why is abrupt discontinuation dangerous?
Design a shared medication reconciliation record for Mr Balakrishnan that he can carry and present to each of his three doctors. What essential information must it contain?
What systemic/health-system interventions could have prevented this polypharmacy crisis? How does the multi-prescriber Indian healthcare model create specific risks that single-prescriber systems do not?

Group Task Assignments

Group 1: Drug-drug interaction analysis and acute management

Systematically identify all clinically significant drug-drug interactions in the medication list
Prioritise by severity: rank which interactions are responsible for the acute crisis
Propose immediate management: which drugs to stop, withhold, or dose-reduce first

Competencies: PH10.6

Group 2: Renal dose adjustment and TDM interpretation

Calculate Cockcroft-Gault CrCl at presentation (creatinine 2.8 mg/dL) and on recovery (creatinine 1.6 mg/dL)
For each drug on the list, determine the appropriate dose at each CrCl value using standard references
Interpret the two digoxin levels (1h post-dose and 8h post-dose) and explain the difference

Competencies: PH10.9, PH10.10

Group 3: Alprazolam dependence management and rational prescribing of dependence-risk drugs

Diagnose alprazolam dependence from the clinical history
Design a safe tapering protocol for alprazolam discontinuation over 8-12 weeks
Review all other dependence-risk drugs on the list (tramadol Schedule H1) and propose management

Competencies: PH10.16

Group 4: Patient and family counselling and adherence planning

Write a structured counselling script for the daughter explaining the polypharmacy crisis without assigning blame
Design an adherence plan for Mr Balakrishnan's simplified post-discharge regimen
Identify which adherence barrier categories apply to Mr Balakrishnan and propose solutions

Competencies: PH10.14, PH10.15

Group 5: Systems-level polypharmacy prevention and medication reconciliation

Design a patient-held shared medication record for Mr Balakrishnan to use across three prescribers
Identify the systems-level failures that led to this crisis in the Indian multi-prescriber context
Propose three practice-level interventions a district hospital could implement to reduce polypharmacy harm

Competencies: PH10.4, PH10.6

Learning Issues

Research these questions and bring your findings to the discussion.

[PH10.4] What are all the mandatory elements of a legally valid prescription in India, and what are the special documentation requirements for Schedule H1 drugs like tramadol?
[PH10.6] How do you systematically appraise a polypharmacy prescription for drug-drug interactions, contraindications, and dose appropriateness? Describe a structured framework.
[PH10.9] How is the Cockcroft-Gault equation used to estimate creatinine clearance, and how does eGFR/CrCl guide dose adjustment for renally-cleared drugs? What are the limitations of Cockcroft-Gault in elderly, cachectic patients?
[PH10.10] When should therapeutic drug monitoring be used for digoxin, and what are the correct sampling times, therapeutic ranges (for AF rate control vs heart failure), and how do renal impairment and electrolyte abnormalities affect digoxin toxicity risk?
[PH10.15] What are the five WHO-recognised dimensions of non-adherence, and what evidence-based strategies are recommended for each dimension? How does polypharmacy itself contribute to non-adherence?
[PH10.16] What is benzodiazepine physical dependence, how does it develop, what are the risks of abrupt discontinuation (including the risk of fatal seizures), and how should benzodiazepine tapering be conducted in a patient who has been on regular alprazolam for 8 months?