Which sign of hypokalemia would the nurse monitor for in a client who is taking furosemide

Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in elderly patients. As with any effective diuretic, electrolyte depletion may occur during LASIX therapy, especially in patients receiving higher doses and a restricted salt intake. Hypokalemia may develop with LASIX, especially with brisk diuresis, inadequate oral electrolyte intake, when cirrhosis is present, or during concomitant use of corticosteroids, ACTH, licorice in large amounts, or prolonged use of laxatives. Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially myocardial effects.

All patients receiving LASIX therapy should be observed for these signs or symptoms of fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia or hypocalcemia): dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, or gastrointestinal disturbances such as nausea and vomiting. Increases in blood glucose and alterations in glucose tolerance tests (with abnormalities of the fasting and 2-hour postprandial sugar) have been observed, and rarely, precipitation of diabetes mellitus has been reported.

In patients with severe symptoms of urinary retention (because of bladder emptying disorders, prostatic hyperplasia, urethral narrowing), the administration of furosemide can cause acute urinary retention related to increased production and retention of urine. Thus, these patients require careful monitoring, especially during the initial stages of treatment.

In patients at high risk for radiocontrast nephropathy LASIX can lead to a higher incidence of deterioration in renal function after receiving radiocontrast compared to high-risk patients who received only intravenous hydration prior to receiving radiocontrast.

In patients with hypoproteinemia (e.g., associated with nephrotic syndrome) the effect of LASIX may be weakened and its ototoxicity potentiated.

Asymptomatic hyperuricemia can occur and gout may rarely be precipitated.

Patients allergic to sulfonamides may also be allergic to LASIX. The possibility exists of exacerbation or activation of systemic lupus erythematosus.

As with many other drugs, patients should be observed regularly for the possible occurrence of blood dyscrasias, liver or kidney damage, or other idiosyncratic reactions.

Laboratory Tests

Serum electrolytes (particularly potassium), CO2, creatinine and BUN should be determined frequently during the first few months of LASIX therapy and periodically thereafter. Serum and urine electrolyte determinations are particularly important when the patient is vomiting profusely or receiving parenteral fluids. Abnormalities should be corrected or the drug temporarily withdrawn. Other medications may also influence serum electrolytes.

Reversible elevations of BUN may occur and are associated with dehydration, which should be avoided, particularly in patients with renal insufficiency.

Urine and blood glucose should be checked periodically in diabetics receiving LASIX, even in those suspected of latent diabetes.

LASIX may lower serum levels of calcium (rarely cases of tetany have been reported) and magnesium. Accordingly, serum levels of these electrolytes should be determined periodically.

In premature infants LASIX may precipitate nephrocalcinosis/nephrolithiasis, therefore renal function must be monitored and renal ultrasonography performed. (See PRECAUTIONS: Pediatric Use)

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Furosemide was tested for carcinogenicity by oral administration in one strain of mice and one strain of rats. A small but significantly increased incidence of mammary gland carcinomas occurred in female mice at a dose 17.5 times the maximum human dose of 600 mg. There were marginal increases in uncommon tumors in male rats at a dose of 15 mg/kg (slightly greater than the maximum human dose) but not at 30 mg/kg.

Furosemide was devoid of mutagenic activity in various strains of Salmonella typhimurium when tested in the presence or absence of an in vitro metabolic activation system, and questionably positive for gene mutation in mouse lymphoma cells in the presence of rat liver S9 at the highest dose tested. Furosemide did not induce sister chromatid exchange in human cells in vitro, but other studies on chromosomal aberrations in human cells in vitro gave conflicting results. In Chinese hamster cells it induced chromosomal damage but was questionably positive for sister chromatid exchange. Studies on the induction by furosemide of chromosomal aberrations in mice were inconclusive. The urine of rats treated with this drug did not induce gene conversion in Saccharomyces cerevisiae.

LASIX (furosemide) produced no impairment of fertility in male or female rats, at 100 mg/kg/day (the maximum effective diuretic dose in the rat and 8 times the maximal human dose of 600 mg/day).

Pregnancy

Pregnancy Category C -Furosemide has been shown to cause unexplained maternal deaths and abortions in rabbits at 2, 4 and 8 times the maximal recommended human dose. There are no adequate and well-controlled studies in pregnant women. LASIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Treatment during pregnancy requires monitoring of fetal growth because of the potential for higher birth weights.

The effects of furosemide on embryonic and fetal development and on pregnant dams were studied in mice, rats and rabbits.

Furosemide caused unexplained maternal deaths and abortions in the rabbit at the lowest dose of 25 mg/kg (2 times the maximal recommended human dose of 600 mg/day). In another study, a dose of 50 mg/kg (4 times the maximal recommended human dose of 600 mg/day) also caused maternal deaths and abortions when administered to rabbits between Days 12 and 17 of gestation. In a third study, none of the pregnant rabbits survived a dose of 100 mg/kg. Data from the above studies indicate fetal lethality that can precede maternal deaths.

The results of the mouse study and one of the three rabbit studies also showed an increased incidence and severity of hydronephrosis (distention of the renal pelvis and, in some cases, of the ureters) in fetuses derived from the treated dams as compared with the incidence in fetuses from the control group.

Nursing Mothers

Because it appears in breast milk, caution should be exercised when LASIX is administered to a nursing mother.

LASIX may inhibit lactation.

Pediatric Use

In premature infants LASIX may precipitate nephrocalcinosis/nephrolithiasis. Nephrocalcinosis/nephrolithiasis has also been observed in children under 4 years of age with no history of prematurity who have been treated chronically with LASIX. Monitor renal function, and renal ultrasonography should be considered, in pediatric patients receiving LASIX.

If LASIX is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus

Geriatric Use

Controlled clinical studies of LASIX did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function. (See PRECAUTIONS: General and DOSAGE AND ADMINISTRATION.)

All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance, e.g., hypomagnesemia, hyponatremia, hypochloremic alkalosis, and hyperkalemia.

Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Hyperkalemia may occur in patients with impaired renal function or excessive potassium intake and can cause cardiac irregularities, which may be fatal. Consequently, no potassium supplement should ordinarily be given with ALDACTONE.

If hyperkalemia is suspected (warning signs include paresthesia, muscle weakness, fatigue, flaccid paralysis of the extremities, bradycardia, and shock), an electrocardiogram (ECG) should be obtained. However, it is important to monitor serum potassium levels because mild hyperkalemia may not be associated with ECG changes.

If hyperkalemia is present, ALDACTONE should be discontinued immediately. With severe hyperkalemia, the clinical situation dictates the procedures to be employed. These may include the intravenous administration of calcium chloride solution, sodium bicarbonate solution and/or the oral or parenteral administration of glucose with a rapid-acting insulin preparation. These are temporary measures to be repeated as required. Cationic exchange resins such as sodium polystyrene sulfonate may be orally or rectally administered. Persistent hyperkalemia may require dialysis.

Reversible hyperchloremic metabolic acidosis, usually in association with hyperkalemia, has been reported to occur in some patients with decompensated hepatic cirrhosis, even in the presence of normal renal function.

Dilutional hyponatremia, manifested by dryness of the mouth, thirst, lethargy, and drowsiness, and confirmed by a low serum sodium level, may be caused or aggravated, especially when ALDACTONE is administered in combination with other diuretics, and dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than administration of sodium, except in rare instances when the hyponatremia is life-threatening.

ALDACTONE therapy may cause a transient elevation of BUN, especially in patients with pre-existing renal impairment. ALDACTONE may cause mild acidosis.

Gynecomastia may develop in association with the use of ALDACTONE; physicians should be alert to its possible onset. The development of gynecomastia appears to be related to both dosage level and duration of therapy and is normally reversible when ALDACTONE is discontinued. In rare instances, some breast enlargement may persist when ALDACTONE is discontinued.

Somnolence and dizziness have been reported to occur in some patients. Caution is advised when driving or operating machinery until the response to initial treatment has been determined.

Laboratory Tests

Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be done at appropriate intervals, particularly in the elderly and those with significant renal or hepatic impairments.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Orally administered ALDACTONE has been shown to be a tumorigen in dietary administration studies performed in rats, with its proliferative effects manifested on endocrine organs and the liver. In an 18- month study using doses of about 50, 150, and 500 mg/kg/day, there were statistically significant increases in benign adenomas of the thyroid and testes and, in male rats, a dose-related increase in proliferative changes in the liver (including hepatocytomegaly and hyperplastic nodules). In a 24-month study in which the same strain of rat was administered doses of about 10, 30, 100, and 150 mg ALDACTONE/kg/day, the range of proliferative effects included significant increases in hepatocellular adenomas and testicular interstitial cell tumors in males, and significant increases in thyroid follicular cell adenomas and carcinomas in both sexes. There was also a statistically significant, but not dose-related, increase in benign uterine endometrial stromal polyps in females.

A dose-related (above 20 mg/kg/day) incidence of myelocytic leukemia was observed in rats fed daily doses of potassium canrenoate (a compound chemically similar to ALDACTONE and whose primary metabolite, canrenone, is also a major product of ALDACTONE in man) for a period of one year. In two-year studies in the rat, oral administration of potassium canrenoate was associated with myelocytic leukemia and hepatic, thyroid, testicular, and mammary tumors.

Neither ALDACTONE nor potassium canrenoate produced mutagenic effects in tests using bacteria or yeast. In the absence of metabolic activation, neither ALDACTONE nor potassium canrenoate has been shown to be mutagenic in mammalian tests in vitro. In the presence of metabolic activation, ALDACTONE has been reported to be negative in some mammalian mutagenicity tests in vitro and inconclusive (but slightly positive) for mutagenicity in other mammalian tests in vitro. In the presence of metabolic activation, potassium canrenoate has been reported to test positive for mutagenicity in some mammalian tests in vitro, inconclusive in others, and negative in still others.

In a three-litter reproduction study in which female rats received dietary doses of 15 and 50 mg ALDACTONE/kg/day, there were no effects on mating and fertility, but there was a small increase in incidence of stillborn pups at 50 mg/kg/day. When injected into female rats (100 mg/kg/day for 7 days, i.p.), ALDACTONE was found to increase the length of the estrous cycle by prolonging diestrus during treatment and inducing constant diestrus during a two-week post-treatment observation period. These effects were associated with retarded ovarian follicle development and a reduction in circulating estrogen levels, which would be expected to impair mating, fertility, and fecundity. ALDACTONE (100 mg/kg/day), administered i.p. to female mice during a two-week cohabitation period with untreated males, decreased the number of mated mice that conceived (effect shown to be caused by an inhibition of ovulation) and decreased the number of implanted embryos in those that became pregnant (effect shown to be caused by an inhibition of implantation), and at 200 mg/kg, also increased the latency period to mating.

Pregnancy

Teratogenic Effects

Teratology studies with ALDACTONE have been carried out in mice and rabbits at doses of up to 20 mg/kg/day. On a body surface area basis, this dose in the mouse is substantially below the maximum recommended human dose and, in the rabbit, approximates the maximum recommended human dose. No teratogenic or other embryotoxic effects were observed in mice, but the 20 mg/kg dose caused an increased rate of resorption and a lower number of live fetuses in rabbits. Because of its antiandrogenic activity and the requirement of testosterone for male morphogenesis, ALDACTONE may have the potential for adversely affecting sex differentiation of the male during embryogenesis. When administered to rats at 200 mg/kg/day between gestation days 13 and 21 (late embryogenesis and fetal development), feminization of male fetuses was observed. Offspring exposed during late pregnancy to 50 and 100 mg/kg/day doses of ALDACTONE exhibited changes in the reproductive tract including dose-dependent decreases in weights of the ventral prostate and seminal vesicle in males, ovaries and uteri that were enlarged in females, and other indications of endocrine dysfunction, that persisted into adulthood. There are no adequate and well-controlled studies with ALDACTONE in pregnant women. ALDACTONE has known endocrine effects in animals including progestational and antiandrogenic effects. The antiandrogenic effects can result in apparent estrogenic side effects in humans, such as gynecomastia. Therefore, the use of ALDACTONE in pregnant women requires that the anticipated benefit be weighed against the possible hazards to the fetus.

Nursing Mothers

Canrenone, a major (and active) metabolite of ALDACTONE, appears in human breast milk. Because ALDACTONE has been found to be tumorigenic in rats, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother. If use of the drug is deemed essential, an alternative method of infant feeding should be instituted.