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Diuretics |
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Loop Diuretics |
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Depletions |
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Calcium |
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Mechanism |
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Short-term treatment with furosemide (4 to 7 days) increased urinary calcium
excretion and reduced serum ionized calcium levels in normal subjects (Fujita et
al. 1985). However, along with marked calciuresis, furosemide (40 mg) elevated
serum calcium levels in another study with five healthy male volunteers (Ogawa
et al. 1984). Chronic treatment (25 days) with furosemide (40 mg/day) altered
calcium levels in rats (Warshaw et al. 1980). The effects on calcium may be less
pronounced with bumetanide; urinary calcium loss was initially elevated but was
followed by retention at 24 hours in 16 healthy volunteers treated with the drug
(0.25 to 1 mg po) (Davies et al. 1974). More studies are needed to clarify the
clinical effects of loop diuretics on calcium metabolism and
homeostasis. |
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Significance of
Depletion |
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Osteoporosis is the primary disease associated with chronic calcium
deficiency; it can result in pathologic fractures associated with bone pain,
spinal deformity, and premature morbidity and mortality (Cashman and Flynn 1999;
Covington 1999). Other signs and symptoms of depleted serum calcium levels
include arrhythmias, neuromuscular irritability, and mental status changes such
as depression and psychosis (Potts 1998). |
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Replacement Therapy |
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Calcium supplementation in the form of citrate, malate, gluconate, or
carbonate salts may range from 1000 mg to 1500 mg or more daily (Adler and Rosen
1999; Covington 1999). Doses as high as 3000 mg/day with 10 to 50 mcg/day of
25-OH-D3 may be appropriate if plasma calcium and phosphate levels are stable
and within normal range (Drüeke 1999). In cases where calcium deficits are
associated with vitamin D deficiency, up to 6000 mg/day of calcium (acetate or
carbonate) may be warranted. These values should be adjusted on an individual
basis depending upon the patient's age, gender, clinical presentation, serum
calcium levels, dietary habits, and medication regimen. Calcium replacement
should be part of a comprehensive approach to the evaluation and treatment of
osteoporosis. |
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Magnesium |
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Mechanism |
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Loop diuretics inhibit passive magnesium absorption and promote urinary loss
of this electrolyte that could lead to a deficiency (Abrams 1981; Davies et al.
1974; Leary et al. 1990; Quamme 1997; Ryan 1986). |
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Significance of
Depletion |
|
Magnesium deficiency can be a serious side effect of loop diuretic therapy;
it is implicated in the development of cardiac arrhythmias and sudden death in
certain patient populations, including those with congestive heart failure
(Iseri et al. 1975; Schwinger and Erdmann 1992). Severely depleted levels of
magnesium affect calcium and vitamin D metabolism and are associated with
hypocalcemia (Cashman and Flynn 1999). Clinically, neuromuscular
hyperexcitability may be the first symptom manifested in patients with
hypomagnesemia (reflected in a serum concentration of 17 mg/L or less). Recent
evidence supports a possible connection between chronically low magnesium levels
and various illnesses such as cardiovascular disease, hypertension, diabetes,
and osteoporosis. |
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Replacement Therapy |
|
The current recommended dietary allowance (RDA) for magnesium ranges from 30
to 420 mg/day, depending upon age and gender (Cashman and Flynn 1999). For
replacement therapy, doses should be tailored to the patient's clinical
condition, taking into account serum magnesium levels, dietary habits, and
medication regimen. |
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Phosphorus |
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Mechanism |
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The rate of phosphorus elimination doubled in healthy volunteers treated with
bumetanide (2 mg/day) compared to furosemide or placebo (Carriere and Dandavino
1976). This effect was observed under conditions of normal diet and fluid intake
as well as over-hydration. In contrast, furosemide produced no phosphaturic
effect under the conditions studied. |
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Significance of
Depletion |
|
Although rare, suboptimal intake of phosphorus can lead to hypophosphatemia,
which is associated with general debility characterized by muscle weakness, bone
pain, paraesthesia, ataxia, acute respiratory failure, mental confusion,
seizures, anorexia, anemia, increased susceptibility to infection, and even
death (Cashman and Flynn 1999; Covington 1999). In chronic situations, patients
with severely depleted phosphate levels below approximately 0.3 mmol/L may
exhibit signs of rickets (children) or osteomalacia (adults) (Cashman and Flynn
1999). |
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Replacement Therapy |
|
The recommended dietary allowance (RDA) for phosphorus ranges from 100 to
1250 mg/day depending on age (Cashman and Flynn 1999; Covington 1999). Doses for
replacement therapy should be adjusted to reflect individual circumstances,
including the patient's age, gender, clinical presentation, serum phosphate
levels, dietary habits, and medication regimen. |
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Potassium |
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Mechanism |
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Loop diuretics increase potassium excretion (Rastogi et al. 1985). This may
occur as a result of inhibition of renal reabsorption of cations at the proximal
and distal tubules as well as at the Loop of Henle (Hines Burnham et al. 2000).
Increased potassium excretion could lead to hypokalemia, which could be of
particular concern in patients with hepatic cirrhosis, congestive heart failure,
and ventricular arrhythmias. |
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Significance of
Depletion |
|
Potassium depletion as a consequence of prolonged drug therapy is usually
associated with chloride deficiency and manifests as hypokalemic, hypochloremic
metabolic acidosis (Covington 1999). Signs and symptoms of deficiency include
anorexia, apprehension, drowsiness, listlessness, fatigue, nausea, muscle cramps
and weakness, tetany, excessive thirst, altered mental status, and irrational
behavior. Severe hypokalemia could also result in clinical manifestations of
cardiac arrythmia, including primarily palpitations, cardiac arrest, and death.
A loss from total body stores of approximately 100 to 200 mEq of potassium is
usually required to cause a decrease in serum potassium levels of 1 mEq/L.
|
|
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Replacement Therapy |
|
The usual range of treatment is 20 to 100 mEq/day of potassium (PDR 2000).
The appropriate doses for replacement therapy should be determined on an
individual basis, considering the patient's age, gender, clinical presentation,
serum potassium levels, dietary habits, and medication regimen. The chloride
salt is appropriate treatment for cases of alkalosis (Covington 1999). In cases
of acidosis, other potassium salts such as bicarbonate, citrate, acetate, or
gluconate are preferred. |
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Vitamin
B1
(Thiamine) |
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Mechanism |
|
Low doses of furosemide (1, 3, and 10 mg IV over 6 hours) caused significant
urinary losses of thiamine in healthy volunteers (Rieck et al. 1999). Long-term
furosemide therapy can cause thiamine deficiency and impair cardiac performance
in patients with CHF; poor dietary intake of thiamine increases this risk (Brady
et al. 1995; Seligmann et al. 1991). |
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Significance of
Depletion |
|
Early nonspecific manifestations of depleted thiamine levels include
weakness, fatigue, anorexia, constipation, nystagmus, and mental status changes
such as memory loss, confusion, and depression (Covington 1999). Beriberi is the
classic condition associated with thiamine deficiency. Symptoms include
polyneuritis, cardiac disturbances (bradycardia, heart failure, hypertrophy),
and possibly edema. Thiamine deficiency rarely occurs alone; it is usually
accompanied by deficiencies in other B vitamins. |
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Replacement Therapy |
|
Although the recommended dietary allowance (RDA) for this nutrient ranges
from 1.1 to 1.5 mg for adults depending on gender, treatment of beriberi
requires oral doses as high as 5 to 10 mg/day for one month to achieve tissue
saturation and replenish body stores of thiamine (Covington 1999). Treatment of
deficiency secondary to alcoholism may require up to 40 mg/day of thiamine
orally; cardiovascular disease may warrant a total daily intake of 90 mg (Marcus
and Coulston 1996). Replacement therapy should be tailored to the patient's
needs depending on age, gender, clinical presentation, serum vitamin B1 levels,
dietary habits, and medication regimen. |
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Vitamin
B6
(Pyridoxine);
Vitamin C (Ascorbic
Acid) |
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Mechanism |
|
Furosemide (20 mg IV) increased urinary excretion of vitamins B6 and C in
patients with chronic renal failure; these patients should be monitored for
deficiency of these vitamins if they are on chronic treatment with this drug
(Mydlik et al. 1998). |
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Significance of
Depletion |
|
Vitamin B6: Usually, vitamin B6 deficiency is accompanied by
depletions of other B vitamins (National Research Council 1989). Signs and
symptoms of low levels of this vitamin include epileptiform convulsions with
abnormal EEG findings, dermatitis, anemia, weakness, mental confusion,
irritability, nervousness, insomnia, and abnormal tryptophan metabolism
(Covington 1999; National Research Council 1989; Wilson 1998). Depleted levels
may increase the risk of colon and prostate cancers, heart disease, brain
dysfunction, and birth defects (Ames 2000).
Vitamin C: Patients with depleted levels of vitamin C may present with
anemia, icterus, edema, lethargy, fatigue, fever, ecchymoses, hypotension,
convulsions, gum disorders, tooth loss, emotional changes, and perifollicular
hyperkeratotic papules (Carr and Frei 1999; Covington 1999; National Research
Council 1989; Wilson 1998). In addition, they may exhibit signs of poor wound
healing, increased susceptibility to infection, and markedly defective collagen
synthesis. Severe deficiency results in scurvy, which is potentially fatal (Carr
and Frei 1999; National Research Council 1989; Wilson 1998). Scurvy involves
degenerative changes in capillaries, bone, and connective tissue, resulting in
clinical symptoms that include weakness, joint tenderness and swelling, and
spontaneous hemorrhages (Carr and Frei 1999; Covington 1999; National Research
Council 1989; Wilson 1998). Patients with vitamin C deficiency may also be at
increased risk of developing cataracts and heart disease (Ames
2000). |
|
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Replacement Therapy |
|
Vitamin B6: Neuropathology resulting from vitamin B6 deficiency
should be treated with doses of 50 to 200 mg/day (Covington 1999). Dietary
deficiency usually responds to doses of 10 to 20 mg/day. Doses should be
tailored to account for the patient's age, gender, clinical presentation, serum
vitamin B6 levels, dietary habits, and medication regimen.
Vitamin C: Treatment of scurvy requires doses between 300 and 1000
mg/day for adults (Covington 1999). Other recommendations range from the
recommended dietary allowance (RDA) of 60 mg to 2000 mg/day for adults (Carr and
Frei 1999; Wilson 1998). One study proposes that no adult receive more than 1000
mg/day because higher doses could cause nausea and diarrhea (Ausman 1999). To
minimize the possibility of gastric upset, buffered and sustained-release
vitamin C preparations are recommended. Specific doses account for the patient's
age, gender, overall health status, dietary habits, and medication regimen.
Smokers must consume 2 to 3 times more vitamin C than non-smokers (Ames
2000). |
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Editorial Note |
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This information is intended to serve as a concise reference for healthcare
professionals to identify substances that may be depleted by many commonly
prescribed medications. Depletion of these substances depends upon a number of
factors including medical history, lifestyle, dietary habits, and duration of
treatment with a particular medication. The signs and symptoms associated with
deficiency may be nonspecific and could be indicative of clinical conditions
other than deficiency. The material presented in these monographs should not in
any event be construed as specific instructions for individual
patients. |
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References |
|
Abrams J. Intramuscular bumetanide and furosemide in congestive heart
failure. J Clin Pharmacol. 1981;21:673-679.
Adler RA, Rosen CJ. Glucocorticoids and osteoporosis. Endocrinol Metab
Clin North Am. 1999;23:641-654.
Ames BN. Micronutrient deficiencies: A major cause of DNA damage. Ann NY
Acad Sci. 2000;889:87-106.
Ausman LM. Criteria and recommendations for vitamin C intake. Nutr
Review. 1999;57(7):222-229.
Brady JA, Rock CL, Horneffer MR. Thiamin status, diuretic medications, and
the management of congestive heart failure. J Am Diet Assoc.
1995;95(5):541-544.
Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C
based on antioxidant and health effects in humans. Am J Clin Nutr
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Carriere S, Dandavino R. Bumetanide, a new loop diuretic. Clin Pharm
Ther. 1976;20:424-438.
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Covington T, ed. Nonprescription Drug Therapy Guiding Patient
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Drüeke T. Medical management of secondary hyperparathyroidism in uremia.
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Fujita T, Delea CS, Bartter FC. The effects of oral furosemide on the
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Leary WP, Reyes AJ, Wynne RD, van der Byl K. Renal excretory actions of
furosemide, of hydrocholorothiazide and of the vasodilator flosequinan in
healthy subjects. J Int Med Res. 1990;18:120-141.
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calcium balance – a comparative study of furosemide and
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|
Copyright © 2000 Integrative Medicine
Communications This publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
responsibility for the accuracy of the information or the consequences arising
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including any injury and/or damage to any person or property as a matter of
product liability, negligence, or otherwise. No warranty, expressed or implied,
is made in regard to the contents of this material. No claims or endorsements
are made for any drugs or compounds currently marketed or in investigative use.
The reader is advised to check product information (including package inserts)
for changes and new information regarding dosage, precautions, warnings,
interactions, and contraindications before administering any drug, herb, or
supplement discussed herein. | |