Spironolactone

Mechanism

Aspirin suppresses renal prostaglandin synthesis that maintains glomerular perfusion. Diuretic and natriuretic effects of spironolactone diminish and potassium accumulates.

Symptoms

Oedema, weight gain, rising blood pressure. Weakness, paraesthesia, and arrhythmias from hyperkalaemia. Reduced diuretic effect emerges within 1–2 weeks of starting aspirin.

Management

At low aspirin doses (75–100 mg for cardioprotection), the clinical effect is minimal; co-prescription is acceptable with potassium and creatinine monitoring. At full anti-inflammatory doses, the diuretic response drops markedly – titrate spironolactone clinically.

Mechanism

Captopril (ACE-I) reduces aldosterone synthesis, while spironolactone directly blocks aldosterone receptors. Both retain potassium. In chronic kidney disease and older patients, severe hyperkalaemia risk reaches 10–15% in the first weeks.

Symptoms

Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. ECG shows peaked T waves and widened QRS. Severe cases progress to cardiac arrest. Symptoms typically appear within 1–2 weeks of starting the combination.

Management

The combination is appropriate in heart failure. Check potassium and creatinine 1 week after start, then monthly. If potassium exceeds 5.5 mmol/L, reduce the spironolactone dose; above 6.0 mmol/L, stop one of the drugs.

Mechanism

Trimethoprim in co-trimoxazole blocks epithelial sodium channels in renal collecting ducts via the same mechanism as amiloride. Combined with spironolactone this produces dual potassium retention. In the elderly and in chronic kidney disease cohort studies show increased sudden death rates with the combination.

Symptoms

Hyperkalaemia within 1–2 weeks: weakness, paresthesia, arrhythmia. Detected on labs; symptoms appear late.

Management

Switch to an alternative antibiotic when possible (amoxicillin, cefalexin for urinary tract infection). If co-trimoxazole is required, check potassium and creatinine on days 3–5 and at end of course. Avoid the combination in patients over 65 with eGFR below 60 mL/min/1.73 m².

Mechanism

Enalapril (an angiotensin-converting enzyme inhibitor, ACE-I) reduces aldosterone synthesis, while spironolactone directly blocks aldosterone receptors. Both retain potassium; hyperkalaemia develops in renal impairment or diabetes.

Symptoms

Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. ECG shows peaked T waves and widened QRS. Severe cases progress to cardiac arrest. Symptoms typically appear within 1–2 weeks of starting the combination.

Management

The combination is appropriate in heart failure with reduced ejection fraction – a standard regimen. Check potassium and creatinine 1 week after start, then monthly. If potassium exceeds 5.5 mmol/L, stop spironolactone or cut its dose; above 6.0 mmol/L, review both agents.

Mechanism

Losartan (angiotensin II receptor blocker, ARB) suppresses the renin-angiotensin-aldosterone system and reduces aldosterone release. Spironolactone directly blocks aldosterone receptors. Both retain potassium.

Symptoms

Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. ECG shows peaked T waves and widened QRS. Severe cases progress to cardiac arrest. Symptoms typically appear within 1–2 weeks of starting the combination.

Management

The combination is appropriate in heart failure. Check potassium and creatinine 1 week after start, then monthly. If potassium exceeds 5.5 mmol/L, reduce the dose of one agent; above 6.0 mmol/L, stop one of them.

Mechanism

Spironolactone retains potassium via aldosterone receptor blockade. Tacrolimus reduces renal potassium secretion via a distal tubular inhibitory effect. Additive hyperkalaemia.

Symptoms

Muscle weakness, paraesthesia, slowed pulse, arrhythmias. ECG: peaked T waves, widened QRS. Severe cases progress to cardiac arrest.

Management

Avoid the combination in transplant patients. Alternative diuretics: furosemide (loop, removes potassium) or hydrochlorothiazide. If spironolactone is needed, check potassium and creatinine every 1–2 weeks.

Mechanism

Additive hyperkalaemia. Both drugs retain potassium: spironolactone directly blocks aldosterone receptors; telmisartan (ARB) reduces aldosterone synthesis.

Symptoms

Muscle weakness, paraesthesia, slowed pulse, arrhythmias. ECG: peaked T waves, widened QRS. Severe cases progress to cardiac arrest.

Management

The combination is appropriate in heart failure with reduced ejection fraction. Check potassium and creatinine 1 week after start, then monthly. If potassium exceeds 5.5 mmol/L, reduce the dose of one agent.

Mechanism

Valsartan (ARB) suppresses the RAAS, while spironolactone blocks aldosterone receptors. Dual aldosterone blockade raises hyperkalaemia risk.

Symptoms

Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. ECG shows peaked T waves and widened QRS. Severe cases progress to cardiac arrest. Symptoms typically appear within 1–2 weeks of starting the combination.

Management

The combination is appropriate in heart failure with reduced ejection fraction. Check potassium and creatinine 1 week after start, then monthly. If potassium exceeds 5.5 mmol/L, reduce the spironolactone dose.