ADR: A harmful/unpleasant reaction from use of a medicinal product at normal dose → predicts risk from future use → warrants prevention, specific treatment, altered dose regimen, or withdrawal of drug ^[1]

ADRs trigger increased hospitalisation, prolonged hospital stay, additional clinical investigations, and prescription cascades ^[1].

From Budnitz et al., NEJM 2011 ^[1]:

Four medication classes implicated alone or in combination in 67% of hospitalisations:

• Warfarin (33.3%)
• Insulins (13.9%)
• Oral antiplatelet agents (13.3%)
• Oral hypoglycaemic agents (10.7%)

From Hong Kong data (Chan et al., Drug Safety 1992) ^[1]:

4.4% of admissions attributed to ADRs. 84% from sulphonylureas, NSAIDs, insulin, diuretics, aspirin. Most frequent ADRs: hypoglycaemia (43%), GI haemorrhage (29.7%), dehydration/hypoNa/hypoK (5.4%). Old age & impaired renal function = important risk factors.

Antihistamines have anticholinergic properties → decrease detrusor tone & impair bladder sensation. Sympathomimetic (decongestant) properties → increase smooth muscle tone in neck of bladder. Combined effect in a patient with underlying BPH → acute urinary retention ^[1]

Learning point: Pay attention to drug–disease interaction when initiating drug treatment in a patient with underlying medical conditions ^[1]

The most frequent pharmacokinetic drug–drug interactions involve CYP450 isoenzymes and drug transporters such as P-glycoprotein ^[1]

CYP450 Inducers and Inhibitors (Directly from Lecture)

Mechanism of enzyme induction:

Enzyme inducers + substrate drugs → Increased clearance → Reduced effects of substrate drugs ^[1]

Substrates affected: antidepressants, calcium antagonists, corticosteroids, cyclosporin, theophylline, thyroxine, warfarin, nirmatrelvir ^[1]

Mechanism of enzyme inhibition:

Enzyme inhibitors + substrate drugs → Decreased clearance → Enhanced effects of substrate drugs ^[1]

Same substrates are affected but in the opposite direction.

Paxlovid = nirmatrelvir (SARS-CoV-2 main protease inhibitor) + ritonavir (inhibits metabolism of nirmatrelvir → increases its plasma concentration). Ritonavir itself is NOT active against SARS-CoV-2 ^[1]

Ritonavir is a STRONG CYP3A4 inhibitor AND a P-glycoprotein inhibitor → concomitant use of Paxlovid and certain drugs may result in significant drug interactions ^[1]

Paxlovid Drug Interaction Table (HIGH YIELD — Directly from Lecture)

Management strategies for Paxlovid drug interactions ^[1]:

1. Increasing monitoring for potential adverse reactions
2. Adjusting dose of concomitant medication
3. Temporarily withholding the concomitant medication
4. Using an alternative to the concomitant medication
5. Using alternative COVID-19 therapies

Elderly have reduced homeostatic mechanisms → particularly sensitive to combined effects of two drugs. Even additive (not synergistic) effects may be sufficient to cause adverse effects ^[1]

Dangerous Pharmacodynamic Combinations (Directly from Lecture)

Five steps ^[1]:

1. Review all drugs for appropriate indications
2. Discontinue the drug causing the interaction, or the drug affected
3. Substitute with another drug of similar efficacy but lower interaction potential
4. Decrease the dose
5. Change the time of administration

Polypharmacy = use of multiple medications by a patient. The minimum number is variable (generally 5–10). Must also consider OTC drugs and herbal/supplements ^[1]

The lecture illustrates this with two dramatic cases:

• A patient discharged on 23 drugs ^[1]
• Madam Yip, F/72 with 19 diagnoses, 11 specialist clinics, and 33 medications spanning 8 specialty prescribers ^[1]

Increased risk of: ADRs, drug-drug interactions, drug-disease interactions, non-compliance, inappropriate drug use, medication errors + Adverse clinical outcomes: disability, cognitive impairment, falls and fractures, malnutrition, hospitalisation, institutionalisation, mortality, rising healthcare costs ^[1]

Deprescribing = the process of supervised withdrawal of inappropriate medications, for which potential harms outweigh benefits ^[1]

Through medication review → withdraw medications no longer appropriate or taper to minimum effective dosage → balance benefits & risks according to patient's current health status. Particularly relevant to patients with burden of polypharmacy or changing clinical conditions ^[1]

Evidence is growing: systematic reviews show carefully planned medication withdrawal had no detrimental effects. Benefits include reduced fall risk & improved cognition & psychomotor function. Deprescribing is feasible and safe ^[1]

Common cause of polypharmacy. An adverse effect of one drug is misinterpreted as a new medical condition → prescription of another drug → additional unnecessary medications → increased medication burden ^[1]

Prescribing Cascade Examples (Directly from Lecture)

Example 1: BPSD → Antipsychotic → Extrapyramidal side effects → Levodopa ^[1]

• The antipsychotic blocks dopamine receptors → drug-induced Parkinsonism → treated with levodopa, creating a contradictory drug regimen

Example 2: Dihydropyridine CCB → Peripheral oedema → Diuretic → HypoNa/K → Na/K supplements ^[1]

• The ankle oedema from amlodipine is NOT fluid overload — it's peripheral vasodilation and capillary leak. Adding a diuretic doesn't address the cause and creates electrolyte disturbances.

As a general principle: Prescription of drugs solely for the purpose of treating drug side effects should be avoided in elderly patients ^[1]

Defaulted ALL medications for 3 weeks → admitted with SOB/CHF secondary to medication non-compliance ^[1]

Take thorough history: medical Hx including cognitive Hx, social Hx, medication Hx (hospital records, private doctors, OTC medicines, traditional Chinese medicines) ^[1]

Prescribe only if necessary. Always look for non-drug alternatives. Avoid over- or under-use. Use the lowest possible effective dose ^[1]

The right drug → The right dose → The right route → Check allergy → Check RFT → Aware of side effects → START LOW & GO SLOW ^[1]

Monitor patient for efficacy → Monitor side-effects → Check compliance → Discontinue unnecessary medications ^[1]

The STOPP (Screening Tool of Older Persons' Prescriptions) identifies potentially inappropriate medications (PIMs) that should be stopped, while START (Screening Tool to Alert to Right Treatment) identifies potential prescribing omissions (PPOs) ^[4][5].

Key STOPP criteria relevant to this lecture ^[4]:

Key updates relevant to this lecture ^[6][7]:

Aspirin for primary prevention of CVD: AVOID initiating in older adults. Consider deprescribing in those already taking it. Risk of major bleeding increases markedly with age. Note: Aspirin IS generally indicated for secondary prevention ^[6]

Avoid all sulfonylureas as first- or second-line therapy (not just long-acting ones). If a sulfonylurea is used, shorter-acting ones (e.g. gliclazide) pose less risk than glibenclamide/chlorpropamide ^[7]

Diphenhydramine (oral): avoid in older adults. Consider total anticholinergic burden during regular medication reviews ^[6]

Avoid baclofen when eGFR < 60 (risk of encephalopathy in older adults) ^[7]

• Reinforces the systematic approach to checking indications, contraindications, dose adjustment, allergy, and interactions before every prescription
• Emphasises the role of clinical pharmacists in medication reconciliation

• Iatrogenesis (including drug-related harm) is one of the "geriatric giants" alongside immobility, instability, incontinence, and intellectual impairment
• ADRs are a leading cause of hospital admission in the elderly

• Frail patients have even less physiologic reserve → lower thresholds for ADRs
• Deprescribing is a key component of frailty management

• Drug-induced Parkinsonism (from antipsychotics, metoclopramide) is a key differential for Parkinsonism in the elderly
• Falls in the elderly are often multifactorial, with drugs being a modifiable risk factor

1. Which of the following is NOT a risk factor for MALA? → Options testing knowledge that dehydration, sepsis, CHF, advanced age, and renal impairment are all risk factors; the distractor might be "well-controlled diabetes" or "obesity."

2. A 78-year-old man on warfarin is prescribed Paxlovid for COVID-19. What is the most appropriate management? → Temporarily withhold warfarin or use alternative COVID therapy; monitor INR closely; ritonavir inhibits CYP3A4 → increased warfarin effect → bleeding risk.

3. An 80-year-old with Parkinson's disease develops nausea. Which antiemetic should be AVOIDED? → Metoclopramide (D2 blocker worsens Parkinsonism). Use domperidone instead.

4. Which ADR type is characterised by being uncommon, unpredictable, and having high mortality? → Type B (Bizarre).

5. A 75-year-old woman on amlodipine develops ankle swelling. Her doctor adds frusemide. She then develops hypokalaemia and a potassium supplement is added. Identify the prescribing error and explain the concept. → This is a prescribing cascade. The ankle oedema from amlodipine is a pharmacological side effect (vasodilation), not fluid overload. Adding a diuretic is inappropriate and leads to electrolyte disturbance. The correct approach: reassess need for amlodipine, consider switching to a non-DHP CCB or alternative antihypertensive.

6. List four approaches to optimise medication management in older adults. → Avoid ADRs, reduce polypharmacy (overuse), avoid PIMs (misuse), enhance adherence, avoid drug interactions ^[1].

7. An 85-year-old with CKD (eGFR 25) is due for denosumab. Her calcium supplement was inadvertently stopped during a recent admission. What risks and actions would you take? → Risk of severe hypocalcaemia (denosumab inhibits osteoclastic resorption → ↓ calcium mobilisation; risk factors: CKD + no calcium/vitamin D supplementation). Action: check serum calcium and vitamin D, resume Calcichew D3 before giving denosumab, recheck calcium 2 weeks after injection.