Loop diuretics toxicity

Acetaminophen may alter blood glucose test results, causing falsely lower blood glucose values. Use with the barbiturates, hydantoins, isoniazid, and rifampin may increase the toxic effects and possibly decrease the therapeutic effects of acetaminophen. The effects of the loop diuretics may be decreased when administered with acetaminophen. Hepatotoxicity has occurred in chronic alcoholics who are taking moderate doses of acetaminophen. 

Fhtients taking a diuretic and a digitalis glycoside must be monitored closely. Thiazide and loop diuretics (see Chap. 46) may increase the risk and effects of toxicity. 

Lithium is commonly used for bipolar affective disorders. Lithium however has a narrow therapeutic index and high risk for toxicity (Groleau 1994). The use of loop diuretics or ACE-inhibitors significantly increases the risk of hospitalisation for lithium toxicity in the elderly (Juurlink et al. 2004). Treatment of elderly patients with lithium should be thoroughly monitored. 

Many interactions with lithium have been described. Thiazide and loop diuretics decrease lithium excretion predisposing to serious lithium toxicity. Also non-steroidal anti-inflammatory agents, especially indomethacin can increase the risks for lithium toxicity due to decreased renal excretion. 

Hypercalcemia is a common clinical condition that can accompany a variety of other medical conditions, such as sarcoidosis, vitamin D toxicity, hyperparathyroidism, and malignancy. When calcium levels are exceptionally high, adjunctive measures for the control of plasma calcium levels are necessary, as this is a medical emergency. Various modalities in combination are used to treat this condition intravenous hydration with normal saline and the use of loop diuretics (e.g., furosemide) to induce calcium diuresis are the most important supportive measures. 

Furosemide Loop diuretic Decreases NaCI and KCI reabsorption in thick ascending limb of the loop of Henle in the nephron (see Chapter 15) Increased excretion of salt and water reduces cardiac preload and afterload reduces pulmonary and peripheral edema Acute and chronic heart failure severe hypertension edematous conditions Oral and IV duration 2-4 h Toxicity Hypovolemia, hypokalemia, orthostatic hypotension, ototoxicity, sulfonamide allergy... 

Loop diuretics are useful in treating toxic ingestions of bromide, fluoride, and iodide, which are reabsorbed in the TAL. Saline solution must be administered to replace urinary losses of Na+ and to provide , so as to avoid extracellular fluid volume depletion. 

By inhibiting salt reabsorption in the TAL, loop diuretics increase delivery to the collecting duct. Increased delivery leads to increased secretion of K+ and H+ by the duct, causing hypokalemic metabolic alkalosis (Table 15-2). This toxicity is a function of the magnitude of the diuresis and can be reversed by K+ replacement and correction of hypovolemia. 

All loop diuretics, with the exception of ethacrynic acid, are sulfonamides. Therefore, skin rash, eosinophilia, and less often, interstitial nephritis are occasional adverse effects of these drugs. This toxicity usually resolves rapidly after drug withdrawal. Allergic reactions are much less common with ethacrynic acid. 

These toxicities are similar to those observed with loop diuretics (see previous text and Table 15-2). 

Therapy with hydrochlorothiazide, up to 50 mg twice daily, or chlorthalidone, 50-100 mg daily, is recommended. Loop diuretics such as furosemide and ethacrynic acid should not be used because they increase urinary calcium excretion. The major toxicity of thiazide diuretics, besides hypokalemia, hypomagnesemia, and hyperglycemia, is hypercalcemia. This is seldom more than a biochemical observation unless the patient has a disease such as hyperparathyroidism in which bone turnover is accelerated. Accordingly, one should screen patients for such disorders before starting thiazide therapy and monitor serum and urine calcium when therapy has begun. 

The risk of hospital admission related to lithium toxicity has been estimated in a case-control study of 10 615 elderly patients over 9 years (512). Lithium toxicity occurred at least once in 413 of the patients who were taking lithium. Factors that increase the likelihood of hospital admission included starting treatment with a loop diuretic or ACE inhibitors during the month before hospitalization. Although furosemide has been suggested as the diuretic of choice for patients taking lithium, the authors suggested that furosemide may cause lithium... 

AMIODARONE CARBONIC ANHYDRASE ANTAGONISTS, LOOP DIURETICS, THIAZIDES Risk of arrhythmias Cardiac toxicity directly related to hypokalaemia Monitor potassium levels eveiy 4-6 weeks until stable, then at least annually... 

DIGOXIN CARBONIC ANHYDRASE INHIBITORS, LOOP DIURETICS, THIAZIDES Risk of digoxin toxicity t due to hypokalaemia Uncertain Monitor potassium levels closely. Monitor digoxin levels watch for digoxin toxicity... 

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

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

LOOP DIURETICS CISPLATIN t 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 ANTIDEPRESSANTS-LITHIUM t plasma concentrations of lithium, with risk of toxic effects L renal excretion of lithium Monitor clinically and by measuring blood lithium levels for lithium toxicity. Loop diuretics are safer than thiazides... 

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