chapter
Diuretics
Pages 12

Not thought to be clinically significant unless a poor CYP2C19 metabolizer. No specific recommendations. Different proton pump inhibitors may interaction differently – monitor if changing therapy or doses

DIGOXIN SUCRALFATE Plasma concentrations of digoxin may be ↓ by sucralfate

Uncertain; possibly sucralfate binds with digoxin and ↓ its absorption

Watch for poor response to digoxin

DIURETICS

CARBONIC ANHYDRASE INHIBITORS – ACETAZOLAMIDE CARBONIC ANHYDRASE INHIBITORS

ANTIARRHYTHMICS

CARBONIC ANHYDRASE INHIBITORS

AMIODARONE, DISOPYRAMIDE, FLECAINIDE

Risk of ≠ myocardial depression Cardiac toxicity directly related to hypokalaemia

Monitor potassium levels closely

CARBONIC ANHYDRASE INHIBITORS

MEXILETINE Effect of mexiletine ↓ by hypokalaemia

Uncertain Normalize potassium levels before starting mexiletine

CARBONIC ANHYDRASE INHIBITORS

ANTIBIOTICS – METHENAMINE

↓ efficacy of methenamine Methenamine is only effective at a low pH; raising the urinary pH ↓ its effect

Avoid co-administration

CARBONIC ANHYDRASE INHIBITORS

ANTIDEMENTIA DRUGS – MEMANTINE

Possibly ≠ memantine levels ↓ renal excretion Watch for early features of memantine toxicity

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Mechanism Precautions

therapeutic effect

≠ renal elimination of lithium Monitor clinically and by measuring blood lithium levels to ensure adequate therapeutic efficacy

CARBONIC ANHYDRASE INHIBITORS

ANTIEPILEPTICS – BARBITURATES, PHENYTOIN

Risk of osteomalacia Barbiturates and phenytoin have a small risk of causing osteomalacia; this may be ≠ by acetazolamide-induced urinary excretion of calcium

Be aware

CARBONIC ANHYDRASE INHIBITORS

ANTIPLATELET AGENTS – ASPIRIN

≠ risk of salicylate toxicity with high-dose aspirin

Uncertain at present Use low-dose aspirin

CARBONIC ANHYDRASE INHIBITORS

BETA-BLOCKERS – SOTALOL

≠ risk of ventricular arrhythmias, particularly torsades de pointes, caused by sotalol

Hypokalaemia, a side-effect of these diuretics, predisposes to arrhythmias during sotalol therapy

Normalize potassium levels before starting sotalol in patients already taking these diuretics. When starting these diuretics in patients already taking sotalol, monitor potassium levels every 4-6 weeks until stable

CARBONIC ANHYDRASE INHIBITORS

BRONCHODILATORS – BETA-2 AGONISTS, THEOPHYLLINE

Risk of hypokalaemia Additive effects Monitor blood potassium levels prior to concomitant administration and during therapy. Administer potassium supplements to prevent hypokalaemia

CARBONIC ANHYDRASE INHIBITORS

CARDIAC GLYCOSIDES Risk of digoxin toxicity ≠ by acetazolamide due to hypokalaemia

Uncertain Monitor potassium levels closely. Watch for digoxin toxicity and check levels

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CARDIOVASCULAR DRUGS DIURETICS Loop diuretics

LOOP DIURETICS 1. ANTICANCER AND IMMUNOMODULATING DRUGS – IL-2 2. ANTIHYPERTENSIVES AND HEART FAILURE DRUGS 3. BETA-BLOCKERS 4. CALCIUM CHANNEL BLOCKERS 5. MUSCLE RELAXANTS – baclofen and tizanidine 6. NITRATES 7. PERIPHERAL VASODILATORS – moxisylyte (thymoxamine) 8. POTASSIUM CHANNEL ACTIVATORS

≠ hypotensive effect. Risk of first-dose ↓ BP greater when ACE inhibitors or angiotensin II receptor antagonists are added to high-dose diuretics. Also, ≠ risk of first-dose ↓ BP with alfuzosin, prazosin and terazosin

Additive hypotensive effect; may be used therapeutically

Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Patients with congestive cardiac failure on diuretics should be started on a low dose of alpha-blocker

LOOP DIURETICS ALISKIREN ↓ plasma levels of furosemide Uncertain Watch for poor response to furosemide

LOOP DIURETICS ANAESTHETICS – GENERAL ≠ hypotensive effect Additive hypotensive effect Monitor BP closely, especially during induction of anaesthesia

LOOP DIURETICS ANTIARRHYTHMICS

LOOP DIURETICS AMIODARONE, DISOPYRAMIDE, FLECAINIDE

Risk of arrhythmias Cardiac toxicity directly related to hypokalaemia

Monitor potassium levels every 4-6 weeks until stable, then at least annually

LOOP DIURETICS MEXILETINE Effect of mexiletine ↓ by hypokalaemia

Uncertain Normalize potassium levels before starting mexiletine

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deafness as a result of concomitant use of furosemide and gentamicin

Both furosemide and gentamicin are associated with ototoxicity; this risk is ≠ if they are used together

If used concurrently patients should be monitored for any hearing impairment

LOOP DIURETICS COLISTIN ≠ risk of ototoxicity and possible deafness as a result of concomitant use of furosemide and colistin

Additive effect If used concurrently, patients should be monitored for any hearing impairment

LOOP DIURETICS TETRACYCLINES Possible risk of renal toxicity Additive effect Some recommend avoiding co-administration; others advise monitoring renal function closely. Doxycycline is likely to be less of a problem

LOOP DIURETICS VANCOMYCIN Risk of renal toxicity Additive effect Monitor renal function closely

LOOP DIURETICS ANTICANCER AND IMMUNOMODULATING DRUGS

LOOP DIURETICS CISPLATIN ≠ risk of auditory toxic effects with cisplatin

Loop diuretics cause tinnitus and deafness as side-effects. Additive toxic effects on auditory system likely

Monitor hearing – test auditory function regularly, particularly if patients report symptoms such as tinnitus or impaired hearing

LOOP DIURETICS PORFIMER ≠ risk of photosensitivity reactions when porfimer is co-administered with bumetanide or furosemide

Attributed to additive effects Avoid exposure of skin and eyes to direct sunlight for 30 days after porfimer therapy

LOOP DIURETICS CICLOSPORIN Risk of nephrotoxicity Additive effect Monitor renal function weekly

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CARDIOVASCULAR DRUGS DIURETICS Loop diuretics

↓ renal excretion of lithium Monitor clinically and by measuring blood lithium levels for lithium toxicity. Loop diuretics are safer than thiazides

LOOP DIURETICS ANTIEPILEPTICS – PHENYTOIN

↓ efficacy of furosemide Uncertain Be aware; watch for poor response to furosemide

LOOP DIURETICS ANTIFUNGALS – AMPHOTERICIN

Risk of hypokalaemia Additive effect Monitor potassium closely

LOOP DIURETICS ANTIPARKINSON’S DRUGS – LEVODOPA

≠ hypotensive effect Additive effect Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)

LOOP DIURETICS ANTIPSYCHOTICS – ATYPICALS, PHENOTHIAZINES, PIMOZIDE

Risk of arrhythmias Cardiac toxicity directly related to hypokalaemia

Monitor potassium levels every 4-6 weeks until stable, then at least annually

LOOP DIURETICS BETA-BLOCKERS – SOTALOL

≠ risk of ventricular arrhythmias, particularly torsades de pointes

Hypokalaemia, a side-effect of these diuretics, predisposes to arrhythmias during sotalol therapy

Normalize potassium levels before starting sotalol in patients already taking these diuretics. When starting these diuretics in patients already taking sotalol, monitor potassium levels every 4-6 weeks until stable

LOOP DIURETICS BRONCHODILATORS – BETA-2 AGONISTS, THEOPHYLLINE

Risk of hypokalaemia Additive effects Monitor blood potassium levels prior to concomitant administration and during therapy. Administer potassium supplements to prevent hypokalaemia

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Uncertain Monitor potassium levels closely.