Lithium diuretics

Bachofen M, Bock H, Beglinger C, Fischer JA, Thiel G. Calcitonin, ein proximal tubular wirkendes Diuretikum Lithium-Clearance-Messungen am Menschen. [Calcitonin, a proximal-tubular-acting diuretic lithium clearance measurements in humans.] Schweiz Med Wochenschr 1997 127(18) 747-52. 

POTASSIUM-SPARING DIURETICS LITHIUM T plasma concentrations of lithium, with risk of toxic effects 1 renal excretion of lithium Monitor clinically and by measuring blood lithium levels for lithium toxicity... 

Chronic renal failure Acute renal failure—diuretic phase Post-renal transplantation Chlorothiazide diuretics Lithium therapy Milk-aUcali syndrome Hyperalimentation regimens Immobilization Increased serum proteins Hemoconcentration... 

Use adjunct to K -wasting diuretics, lithium-induced nephrogenic diabetes insipidus (amiloride)... 

In nephrogenic diabetes insipidus the kidney s ability to respond to AVP is impaired by different causes, such as drugs (e.g. lithium), chronic disorders (e.g. sickle cell disease, kidney failure) or inherited genetic disorders (X-linked or autosomal NDI). This type of diabetes insipidus can not be treated by exogenous administration of AVP or AVP analogues. Instead, diuretics (hydrochlorothiazide combined or not with amiloride) and NSAI (indomethacin) are administrated to ameliorate polyuria. 

The NSAIDs prolong bleeding time and increase the effects of anticoagulants, lithium, cyclosporine, and the hydantoins. These dru may decrease the effects of diuretics or antihypertensive drug >. Long-term use of the NSAIDs with acetaminophen may increase the risk of renal impairment. 

No significant interactions have been reported when tiie expectorants are used as directed. The exception is iodine products. Lithium and other antithyroid drug may potentiate the hypotliyroid effects of these drug if used concurrently with iodine products. When potassium-containing medications and potassium-sparing diuretics are administered with iodine products, the patient may experience hypokalemia, cardiac arrhythmias, or cardiac arrest. Thyroid function tests may also be altered by iodine... 

Thiazide diuretics, calcium-containing antacids, vitamin D, and lithium... 

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

The answer is c. (Katzung, p 493.) Lithium treatment frequently causes polyuria and polydipsia. The collecting tubule of the kidney loses the capacity to conserve water via anti diuretic hormone. This results in significant free-water clearance, which is referred to as nephrogenic diabetes insipidus. 

The most potentially serious drug interactions include the concomitant use of NSAIDs with lithium, warfarin, oral hypoglycemics, high-dose methotrexate, antihypertensives, angiotensin-converting enzyme inhibitors, fi-blockers, and diuretics. 

Lithium reduces the kidney s ability to concentrate urine and may cause a nephrogenic diabetes insipidus with low urine specific gravity and low osmolality polyuria (urine volume greater than 3 L/day). This may be treated with loop diuretics, thiazide diuretics, or triamterene. If a thiazide diuretic is used, lithium doses should be decreased by 50% and lithium and potassium levels monitored. 

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. 

Lithium toxicity can occur as a result of intentional overdose therefore, care must be taken when administering lithium to potentially suicidal patients with BPAD. Inadvertent lithium toxicity may also occur. For example, diuretics and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin) slow the excretion of lithium and can lead to accidental toxicity. Consequently, the patient should be advised not to take such commonly available medications while treated with lithium. In addition, dehydration resulting from varied causes such as diarrhea, vomiting, and profuse sweating can lead to accidental lithium toxicity. One should advise the patient who takes lithium to be careful to remain well hydrated at all times and to contact his/her physician if any medical condition arises that may cause rapid fluid losses (e.g., stomach virus, high fevers). 

Most of the lithium is eliminated in the urine, the first phase of the elimination being 6-8 hours after administration, followed by a slower phase which may last for 2 weeks. Sodium-depleting diuretics such as frusemide, ethacrynic acid and the thiazides increase lithium retention and therefore toxicity, while osmotic diuretics as exemplified by mannitol and urea enhance lithium excretion. The principal side effects of lithium are summarized in Table 8.1. 

Lithium is a drug with a narrow therapeutic index and therefore plasma concentrations are regularly monitored. Lithium is used in the prophylaxis and treatment of mania. Concurrent administration of lithium and diuretics, particularly the thiazides, is contraindicated as lithium excretion is reduced, resulting in increased plasma-lithium concentration and hence toxicity. 

Drugs that may affect ACEIs may include antacids, capsaicin, indomethacin, phenothiazines, probenecid, and rifampin. Drugs that may be affected by ACEIs include allopurinol, digoxin, lithium, potassium preparations/potassium-sparing diuretics, and tetracycline. 

Unlabeled uses Amiloride (10 to 20 mg/day) may be useful in reducing lithium-induced polyuria without increasing lithium levels as is seen with thiazide diuretics. 

Drugs that may be affected by NSAIDs include the following Aminoglycosides, anticoagulants, ACE inhibitors, beta blockers, cyclosporine, dextromethorphan, digoxin, dipyridamole, hydantoins, lithium, loop diuretics, methotrexate, penicillamine, potassium-sparing diuretics, sympathomimetics, theophylline, thiazide diuretics. 

High-risk patients The risk of lithium toxicity is very high in patients with significant renal or cardiovascular disease, severe debilitation, dehydration, or sodium depletion, or in patients receiving diuretics. Undertake treatment with extreme caution. 

Drugs that may affect lithium include acetazolamide, carbamazepine, fluoxetine, haloperidol, loop diuretics, methyidopa, NSAIDs, osmotic diuretics, theophyllines. 

Forced diuresis is occasionally useful. It may cause volume overload or electrolyte disturbances. Forced diuresis is useful for phenobarbital, bromides, lithium, salicylate, or amphetamines overdoses. Do not use for tricyclic antidepressants, sedative-hypnotics, or highly protein-bound medications. The most common agents employed are furosemide and osmotic diuretics with mannitol. 

Diuretics, interaction with lithium, 36 65-66 Divalent cations hydration shell, 34 211 structure, 34 210-212... 

Lithium intoxication can be precipitated by the use of diuretics, particularly thiazides and metola-zone, and ACE inhibitors. NSAIDs can also precipitate lithium toxicity, mainly due to NSAID inhibition of prostaglandin-dependent renal excretion mechanisms. NSAIDs also impair renal function and cause sodium and water retention, effects which can predispose to interactions. Many case reports describe the antagonistic effects of NSAIDs on diuretics and antihypertensive drugs. The combination of triamterene and indomethacin appears particularly hazardous as it may result in acute renal failure. NSAIDs may also interfere with the beneficial effects of diuretics and ACE inhibitors in heart failure. It is not unusual to see patients whose heart failure has deteriorated in spite of increased doses of frusemide who are also concurrently taking an NSAID. 

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. 

Geriatric Considerations - Summary Volume of distribution (Vd), clearance, and half-life are significantly altered in older adults. Lithium toxicity may occur within the usual adult therapeutic range. Older adults are likely to exhibit toxic effects at lower serum concentrations. Significantly lower doses are often efficacious for affective disorders than are used in younger adults. Monitor serum concentrations closely, increased riskof lithium toxicity when a diuretic, NSAID, or ACE Inhibitor is started in a patient already taking lithium. 

Lithium with diuretics Altered excretion Increased risks of toxicity... 

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