Furosemide

Mechanism

Additive hypotension and fall risk in older patients. No direct pharmacokinetic interaction.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

In older patients, check standing and sitting blood pressure 1–2 weeks after starting alprazolam. Alternative anxiolytic: hydroxyzine or a short lorazepam course.

Mechanism

Additive orthostatic hypotension. Amitriptyline blocks α1-adrenoceptors and reduces the compensatory vascular response to hypovolaemia (from the diuretic).

Symptoms

Postural dizziness, syncope, fatigue. Older patients: fall and fracture risk.

Management

In older patients, check standing and sitting blood pressure 1–2 weeks after starting amitriptyline. Advise slow rising. For neuropathic pain, alternative: gabapentin or pregabalin (no α1-blockade).

Mechanism

Standard combination in heart failure and hypertension. Additive hypotensive effect; furosemide causes hypokalaemia, amplifying arrhythmia risk with concomitant QT-prolonging drugs.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk. With additional antihypertensives: bradycardia (pulse below 60/min).

Management

Standard combination. Check potassium and magnesium every 1–3 months. If potassium drops below 4.0 mmol/L, add a potassium-sparing diuretic (spironolactone) or potassium supplement. Check blood pressure and pulse 1–2 weeks after start.

Mechanism

Furosemide is a loop diuretic that increases urinary loss of potassium and magnesium. Low serum potassium (hypokalaemia) and low magnesium increase digoxin binding to the cardiac sodium-potassium ATPase and intensify its toxicity even when digoxin plasma levels are within range. Furosemide does not change digoxin concentration directly – the danger is the electrolyte shift.

Symptoms

Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias ranging from premature beats to ventricular tachycardia. Confusion in older adults. Symptoms emerge once potassium falls below 3.5 mmol/L.

Management

Check serum potassium before starting the combination, again at 1–2 weeks, and every 1–3 months thereafter. Monitor magnesium in parallel. If potassium drops below 4 mmol/L in a digoxin patient, add a potassium-sparing diuretic (spironolactone, eplerenone) or oral potassium. Replete magnesium when levels are below 0.7 mmol/L.

Mechanism

Additive antihypertensive effect; in hypovolaemic patients it can trigger acute kidney injury. The triad of ACE inhibitor + diuretic + NSAID is especially dangerous (the "triple whammy").

Symptoms

Decreased urine output, rising creatinine, oedema, nausea, fatigue. Higher risk in older patients and in dehydration.

Management

On starting the combination, begin enalapril at the lowest dose (2.5 mg). Check creatinine and potassium at 1–2 weeks, then every 3 months. In older patients with acute illness and dehydration, both drugs are temporarily stopped until volume is restored.

Mechanism

Sequential nephron blockade: furosemide acts at the loop of Henle, the thiazide at the distal tubule. Additive diuresis in fluid retention resistant to a single diuretic.

Symptoms

Weakness, dizziness, thirst, reduced urine output, rising creatinine. In older patients, fall risk from orthostatic hypotension. Weakness, muscle cramps, fatigue, palpitations, arrhythmia (particularly dangerous with digoxin). Symptoms appear at potassium below 3.5 mmol/L.

Management

Use only as short courses (3–7 days) with daily weight and creatinine every 1–2 days. Potassium, sodium, magnesium every 2–3 days. When weight loss reaches 1–1.5 kg/day, reduce diuresis pace — return to a single diuretic. For sustained need, consider an SGLT-2 inhibitor or tolvaptan.

Mechanism

Both cause hypokalaemia: glucocorticoids via mineralocorticoid effect and muscle catabolism; furosemide via direct urinary potassium loss. Additive risk, especially on long-term prednisolone.

Symptoms

Weakness, muscle cramps, fatigue, palpitations, arrhythmia (particularly dangerous with digoxin). Symptoms appear at potassium below 3.5 mmol/L.

Management

For short prednisolone courses (3–7 days), no specific adjustment needed. For long-term therapy, check potassium at 1, 2, and 4 weeks, then monthly. If it falls below 3.5 mmol/L, add potassium supplements (10–20 mmol/day) or a potassium-sparing diuretic. On digoxin, hypokalaemia is dangerous — arrhythmia risk.

Mechanism

Both can cause hyponatraemia: furosemide via natriuresis, sertraline via SIADH-like mechanism. Additive risk, especially in older women with low body weight.

Symptoms

Headache, nausea, confusion, drowsiness; severe cases: seizures. Develops slowly over 1–2 weeks and is often missed in older patients.

Management

Check sodium 2 weeks after sertraline start, then every 6 months. If sodium falls below 130 mmol/L, switch sertraline to mirtazapine or agomelatine (do not cause hyponatraemia). In older patients with moderate hyponatraemia, fluid restriction to 1.5 L/day.

Mechanism

Opposing effects on potassium: furosemide depletes it via the loop of Henle, spironolactone retains it by blocking aldosterone in collecting ducts. Target combination in heart failure, resistant hypertension, and ascites.

Symptoms

With a balanced combination, no specific symptoms. In chronic kidney disease, hyperkalaemia may occur: Weakness, fatigue, paraesthesias, arrhythmia. Symptoms develop at potassium above 5.5 mmol/L; life-threatening above 6.5 mmol/L.

Management

Check potassium and creatinine at 1 and 4 weeks after starting, then every 3 months. With creatinine clearance below 30 mL/min, do not prescribe spironolactone, or cap at 25 mg every other day. In dehydration, temporarily stop both until volume is restored.