Common Names: Magnesium aspartate, Magnesium citrate, Magnesium
fumarate, Magnesium malate, Magnesium succinate
Clinical Name: Magnesium
Summary
Magnesium
chemical name:
Mg
forms: Magnesium aspartate, Magnesium citrate, Magnesium
fumarate, Magnesium malate, Magnesium succinate.
overview of
interactions:
nutrient affected by drug: Amiloride
nutrient affected by drug: Aminoglycosides
nutrient affecting drug performance: Calcium
Channel Blockers
nutrient affected by drug: Captopril
Magnesium-based (or Aluminum-based) Antacids affecting drug
performance: Ciprofloxacin
nutrient affected by drug: Cisplatin
nutrient affected by drug: Colchicine
nutrient affected by drug: Corticosteroids,
including Prednisone
nutrient affected
by drug and affecting drug toxicity: Cyclosporine
nutrient affected by drug: Digoxin
nutrient affected by drug: Loop
Diuretics and Thiazide
Diuretics
nutrient affected by drug: Gentamicin
nutrient affected by drug: Lithium
nutrient affected by drug: Neomycin
nutrient affecting drug performance: Ranitidine
(Zantacฎ)
nutrient affecting drug
toxicity: Sulfonylureas
nutrient affecting drug performance: Tetracyclines
nutrient affecting drug performance: Warfarin
metabolism:
The rate of magnesium absorption varies from as
low as 24% to as high as 85%. Many factors regulate magnesium absorption. As the
level of calcium intake goes down, the level of magnesium absorption goes up. A
significant amount goes to the stomach for HCL production.
Magnesium is
very involved with ATP production via the Kreb's cycle.
Glycolysis, adenyl
cyclase and other reactions involving nerve impulse transmission also require
high quantities of magnesium.
High intakes of calcium, protein, vitamin D
and alcohol all function to increase the magnesium requirement.
function:
Magnesium regulates the absorption of calcium and
is involved in the structural integrity of bones and teeth. If it is deficient
in the bones, the bones may be dense but have poor trabecular integrity and thus
be brittle. In both Finland and the Netherlands, there is a high ratio of
calcium to magnesium intake (4 to 1) and the rate of osteoporosis is the highest
in the world.
Magnesium regulates the contractility of the heart muscle.
It is concentrated 18x greater in the heart muscle than in the bloodstream. A
decreased magnesium level in the heart muscle may predispose a person to
coronary spasms. In areas where there is harder water (mainly due to magnesium),
there is a much lower rate of heart disease.
Magnesium has a relaxing
effect on smooth muscle. It may be helpful in relaxing the smooth muscle of the
bronchioles (improving asthma) and the arterioles (lowering blood pressure).
It may relax uterine tissue (decreasing the cramping of dysmenorrhea), and
also be useful in the treatment of angina and myocardial infarction.
Magnesium decreases coagulation and acts as a calcium channel blocker. Thus, it
helps the heart to pump more effectively.
It is also one of the cofactors
for delta 6 desaturase which is involved in the production of PGE1.
Magnesium is necessary for the actions of PTH and 1,25 DHCC in bone calcium
mobilization.
Cofactor in many enzyme reactions (especially ATP reactions)
Protein synthesis
Role in neuromuscular transmitters
Activates
vitamin B-complex
dietary sources:
High (200-400 mg/100 g
food): nuts (almonds, cashews, Brazil), soybeans, brewer's yeast, buckwheat,
wheat bran
Good: Corn, peas, carrots, barley, oats, rye, wheat, rice bran,
pecans, filberts, pistachios, black walnuts, green leafy vegetables (kale,
endive, chard beet tops), celery, alfalfa, figs, apples, lemons, peaches,
almonds, whole grains (millet, cornmeal, wheatgerm, barley, buckwheat, oats),
tahini, sunflower seeds, brown rice, sesame seeds, black-eyed peas, lima beans,
tofu, lentils, potato, sweet potato, peas, Brussel sprouts, broccoli,
cauliflower, corn, avocado, dates, banana, blueberries, grape juice, cantaloupe,
orange juice, milk
The average intake of magnesium by so-called healthy
adults in the U.S. and Western Europe ranges between 143-266 mg/day.
High
intakes of calcium, vitamin D, and protein increase the requirement for
magnesium.
Vitamin D, lactose and HCl all act to enhance absorption.
deficiency:
Magnesium deficiency is very common in the West
since magnesium is found predominantly in whole unprocessed foods.
Deficiency symptoms include fatigue, irritability, weakness, muscle tightness or
spasms, dysmenorrhea, high blood pressure, cardiomyopathy, nerve conduction
problems, anorexia, insomnia, sugar cravings, poor nail growth, anxiety.
Magnesium deficiency may be caused by any condition which increases loss or
shifts the electrolyte balance, (such as renal disease) or diuretic therapy
(such as antihypertensive medications).
Malabsorption, hyperthyroidism,
pancreatitis, kwashiorkor, diabetes, parathyroid gland disorders, poor intake,
and diarrhea may also cause a deficiency.
Serum magnesium is a very poor
indicator of how much magnesium is actually in the tissues. For example,
magnesium concentrates in the heart muscle at a 18x higher level than in the
serum.
Measuring white blood cell magnesium is a more sensitive indicator
of tissue levels. An anionic magnesium measurement, recently pioneered by Drs.
Burton and Bella Altura at Down-State University of New York in Brooklyn,
appears to be a considerably more accurate indicator of tissue levels of
magnesium than either WBC or RBC measurements.
known or potential
therapeutic uses: Acute myocardial infarction, alcohol
withdrawal, angina, anxiety, asthma, autism, cardiac arrhythmias,
cardiomyopathy, cardiovascular disease, celiac disease, chronic fatigue syndrome
(CFS), chronic obstructive pulmonary disease (COPD), congestive heart failure,
constipation, diabetes mellitus, dysmenorrhea, eclampsia,
eosinophilia-myalgia syndrome, fatigue, fibromyalgia, (acute) gastro-intestinal
spasms or cramping, glaucoma, hearing loss, high blood pressure, high
cholesterol, hyperactivity, hypoglycemia, intermittent claudication, kidney
stones, lead toxicity, low HDL-cholesterol levels, migraine, mitral valve
prolapse, muscle cramping, especially nocturnal, multiple sclerosis,
osteoporosis, premenstrual syndrome, Raynauds disease, retinopathy, stroke,
torticollis, toxemia of pregnancy.
maintenance dose: 500 mg per
day.
RDA:
Infants: 50-70 mg
Children: 150-300 mg
Adults:
females: 280 mg per day; males: 350 mg per day
Pregnancy and lactation 350
mg per day
therapeutic dose: 500-1500 mg per day. Also used
intravenously for many conditions.
side effects/toxicity:
Hypermagnesia is rare but may result with decreased excretion, greatly increased
absorption, or rarely with IM injection; toxicity results in depression of the
central nervous system and possibly death
Diarrhea is the most common
adverse effect from magnesium. Excessive magnesium can actually lead to a
magnesium deficiency if it causes chronic diarrhea. Magnesium also completes
with calcium and can induce a calcium deficiency if calcium intake levels are
already low. About 800 mg of elemental magnesium will generally cause loose
stools but some people may be able to tolerate much higher doses. Different
forms of magnesium, such as magnesium glycinate, may be tolerated differently as
well. There is a slow release magnesium, Slo-mag, that may be helpful in
elevating the intracellular levels of magnesium. Individuals with kidney failure
must be cautious about magnesium supplementation since they may experience
toxicity symptoms.
Intravenous magnesium, because of its effect on smooth
muscles, may cause hypotension along with dizziness and fainting. It may also
cause respiratory depression or depletion of potassium.
Intramuscular
injections can often be painful and may cause a persistent lump if injection
does not go deep enough to reach the muscle tissue. After the magnesium is
loaded into the syringe a small amount of 2% lidocaine can be drawn into the tip
of the syringe to ease the reaction. (Marz, 1997.)
contraindications: See interactions, most notably tetracyclines
where magnesium interferes with drug metabolism.
Interactions
nutrient affected by drug: Amiloride
mechanism: According to preliminary studies involving rats amiloride
has a magnesium-sparing effect in addition to its potassium-sparing effect.
Consequently there is the possibility that individuals who take a magnesium
supplement while also taking amiloride could build up excessively high levels of
magnesium. The concurrent use of hydrochlorothiazide and amiloride would make
this accumulation unlikely given the magnesium-depleting action of
hydrochlorothiazide.
(Devane J, Ryan MP. Br J Pharmacol. 1983
Aug;79(4):891-896; Devane J, Ryan MP. Br J Pharmacol. 1981
Feb;72(2):285-289.)
nutritional concern: Individuals taking amiloride
should refrain from taking supplemental magnesium without first consulting their
prescribing physician, pharmacist, or a healthcare professional experienced in
nutritional therapies.
nutrient affected by drug: Aminoglycosides
reports: Animal studies and case reports indicate that renal tubular
damage due to aminoglycosides, such as gentamicin, can lead to hypomagnesemia
combined with hypocalcemia, hypokalemia and alkalosis.
(Mazze RI, Cousins
MJ. Br J Anaesth. 1973 Apr;45(4):394-398; Valdivieso A, et al. Rev Med
Chil. 1992 Aug;120(8):914-919; Kes P, et al. Magnes Trace Elem.
1990;9(1):54-60. Parsons PP, et al. Br J Pharmacol 1997
Oct;122(3):570-576.)
research: Akbar et al have noted that
hypomagnesemia may be especially common among children with cystic fibrosis who
have a history of repeated use of aminoglycosides.
(Akbar A, et al. Acta
Paediatr. 1999 Jul;88(7):783-785.)
nutritional support:
Individuals using aminoglycosides, especially on a repeated or chronic basis,
should consult with their prescribing physician and/or a nutritionally oriented
healthcare professional about nutritional support to restore normal levels of
magnesium and these other important minerals. Patients undergoing extended
treatment with aminoglycosides may need to have their doctor regularly monitor
their kidney function along with magnesium and potassium status. Serum
creatinine, BUN and creatinine clearance should be measured prior to initiating
therapy and should be monitored throughout treatment. In this regard, many
nutritionally-oriented practitioners find that testing magnesium levels in red
blood cells is far more reliable than testing serum magnesium. Only after such
assessment should supplementation with magnesium or potassium be undertaken and
then only under close supervision by the prescribing physician.
Supplementation of magnesium in the dosage range of 300-500 mg per day
is usually appropriate but should be done in consultation with the prescribing
doctor or a nutritionally-oriented physician. Magnesium supplementation can be
risky in patients with kidney damage and is usually contraindicated in such
cases. It is also important to note that magnesium is needed to maintain
intracellular potassium.
nutrient affecting drug performance: Calcium
Channel Blockers
research: Patients with variant angina often
suffer from magnesium deficiency.
(Goto K, et al. Am J Cardiol. 1990
Mar 15;65(11):709-712.)
nutritional synergy: Individuals taking
calcium channel blockers, especially for variant angina, should consult with
their prescribing physician and/or a healthcare provider trained in nutritional
therapies about the potential benefits of supplementing with magnesium. Typical
therapeutic dosages of magnesium are in the range of 250-350 mg per day for
adults.
nutrient affected by drug: Captopril
mechanism: Captopril increases lymphocyte magnesium levels,
though possibly only in patients with pre-existing low levels.
(Lavin F, et
al. Cardiology 1993;82(6):405-408; O'Keeffe S, et al. Cardiology
1992;80(2):100-105.)
Magnesium-based (or Aluminum-based) Antacids
affecting drug performance: Ciprofloxacin
mechanism: The absorption of ciprofloxacin is reduced by 50 to
90% in the presence of antacids containing magnesium and/or aluminum.
(Hoffken G, et al. Eur J Clin Microbiol. 1985 Jun;4(3):345; Gugler R,
Allgayer H. Clin Pharmacokinet 1990 Mar;18(3):210-219; Polk RE. Am J
Med 1989 Nov 30;87(5A):76S-81S; Teixeira MH, et al. J Chemother 1995
Apr;7(2):126-132; Mizuki Y, et al. J Antimicrob Chemother 1996 May;37
Suppl A:41-55.)
nutritional concerns: Individuals taking
ciprofloxacin should avoid using aluminium- or magnesium-based antacids without
consulting the prescribing physician and/or a pharmacist.
nutrient
affected by drug: Cisplatin
mechanism: Cisplatin induces hypomagnesemia through its renal
toxicity possibly by a direct injury to mechanisms of magnesium reabsorption in
the ascending limb of the loop of Henle as well as the distal tubule.
Consequently, cisplatin increases the urinary loss of magnesium. This
drug-induced impairment of the renal tubules' ability to conserve magnesium may
persist for months, or possibly years, after discontinuing use of the drug.
(Toffaletti J. Analyt Chem 1991 63(12):192R-194R; Lajer H, et al.
Cancer Treat Rev. 1999 Feb;25(1):47-58; Koch Nogueira PC, et al. Pediatr
Nephrol 1998 Sep;12(7):572-575.)
nutritional support: One
British study found higher serum magnesium concentration levels that children
given intravenous magnesium before and after administration of cisplatin than in
those give magnesium only after the cisplatin. The researchers concluded that
magnesium supplements should be given to patients receiving cisplatin during the
precisplatin hydration period to prevent hypomagnesemia.
(Kibirige MS, et
al. Pediatr Hematol Oncol 1988;5(1):1-6.)
nutrient affected
by drug: Colchicine
mechanism: Colchicine has been linked to impaired absorption of
Magnesium.
(Roe DA. 1985, 159-160.)
nutritional support:
Individuals taking colchicine would most likely benefit from taking a
high-potency multivitamin/mineral supplement to compensate for these
interactions.
nutrient affected by drug: Corticosteroids,
including Prednisone
mechanism:
Corticosteroids can contribute to depletion of magnesium.
(Holt GA. 1998,
83; Pronsky, Z. 1991, 60.)
nutritional support: Individuals using
corticosteroids for periods longer than two weeks should consult with their
prescribing physician and/or a nutritionally trained healthcare professional
about the potential need to supplement with magnesium to counter the depleting
effects of the drug(s). A typical dose in such situations would be in the range
of 300-400 mg of magnesium per day.
nutrient affected by drug and
affecting drug toxicity: Cyclosporine
mechanism: Cyclosporine has been linked to reduced serum levels of
magnesium.
adverse drug effects: This systemic depletion of magnesium
produces a high risk of seizures due to cyclosporine-induced toxicity to the
nervous system.
testing: Individuals undergoing cyclosporine therapy
should have their magnesium levels tested regularly. Nutritionally-oriented
physicians generally find that monitoring red blood cell magnesium levels,
rather than serum magnesium, is the most accurate method for diagnosing a
deficiency.
nutritional support: Magnesium supplementation
prevents magnesium deficiency and subsequent neurotoxicity. In the event of
cyclosporine-induced depletion, the prescribing physician should be consulted
before starting any form of magnesium supplementation.
(Toffaletti J.
Analyt Chem 1994 63(12):192R-194R; Pere AK, et al. Nephrol Dial
Transplant 1998 Apr;13(4):904-910; Rob PM. Fortschr Med 1996 Apr
10;114(10):125-126; Thompson CB, et al. Lancet 1984;ii:1116.)
nutrients affected by drug: Digoxin
mechanism: Digoxin decreases intracellular magnesium, thereby causing
increased urinary magnesium loss. Magnesium deficiencies induced by concommitant
diuretic use are very common in individuals using digoxin. Hypomagnesemia may
predispose to digitalis toxicity.
(Toffaletti J. Analyt Chem 1991
63(12):192R-194R; al-Ghamdi SM, et al. Am J Kidney Dis 1994
Nov;24(5):737-752.)
clinical implications: Hypomagnesemia is known to
produce a wide variety of clinical presentations, including neuromuscular
irritability, cardiac arrhythmias, and increased sensitivity to digoxin.
Magnesium deficiency also inhibits the therapeutic efficacy of digoxin in
controlling atrial fibrillation. Refractory hypokalemia and hypocalcemia can be
caused by concomitant hypomagnesemia and can be corrected with magnesium
therapy.
(Toffaletti J. Analyt Chem 1991 63(12):192R-194R; Young IS,
et al. Br J Clin Pharmacol. 1991 Dec;32(6):717-721; Lewis R, et al. Br
J Clin Pharmacol. 1991 Feb;31(2):200-203.)
testing: Many
physicians are aware of the need to monitor and prescribe for potassium
depletion but do not consider the issue of magnesium deficiency unless serum
levels fall below acceptable levels. Furthermore, many physicians experienced in
nutritional assessment consider serum magnesium to be a very poor indicator of
how much magnesium is actually in the tissues. Serum magnesium concentration is
maintained within a narrow range by the kidney and small intestine since under
conditions of magnesium deprivation both organs increase their fractional
absorption of magnesium. If magnesium depletion continues, the bone store
contributes by exchanging part of its content with extracellular fluid (ECF).
The serum Mg can be normal in the presence of intracellular Mg depletion, and
the occurrence of a low level usually indicates significant magnesium
deficiency. Hypomagnesemia is frequently encountered in hospitalized patients
and is seen most often in patients admitted to intensive care units. The
detection of magnesium deficiency can be increased by measuring magnesium
concentration in the urine or using the parenteral magnesium load test.
(al-Ghamdi SM, et al. Am J Kidney Dis 1994 Nov;24(5):737-752; Marz R.
1997.)
nutritional support: Individuals taking digoxin will almost
always benefit from supplementation of magnesium. Studies and clinical
experience indicate that 300-500 mg of magnesium per day would be an appropriate
dosage level for supplementing such patients. Anyone taking digoxin should
consult the prescribing physician and/or a nutritionally-oriented healthcare
professional regarding the issue of magnesium supplementation.
(Kinlay S,
Buckley NA. J Toxicol Clin Toxicol 1995;33(1):55-59; Sueta CA, et al.
Magnes Res 1995 Dec;8(4):389-401.)
nutrient affected by
drug: Loop
Diuretics and Thiazide
Diuretics
mechanism: By definition potassium-depleting
diuretics increase potassium excretion and, in practice, they also usually
deplete blood levels of magnesium. In turn, the drug-induced magnesium
deficiency can contribute to further potassium depletion. Ultimately the
relationship between these two patterns of depletion can be difficult to
determine.
(Kroenke K, et al. Arch Intern Med 1987;147:1553-1556;
Martin BJ, et al. Arch Intern Med 1987 Oct;147(10):1768-1771.)
adverse drug effects: A lack of magnesium interferes with healthy cardiac muscle
function. This is especially important for patients on both diuretics and
digitalis as they are more likely to develop arrythmias if not adequately
supplemented with magnesium.
testing: Serum levels of magnesium are
not adequately sensitive to mild to moderate levels of depletion and thus are
poor indicators of nutritional status.
nutritional support: In
practice, it is generally advisable for individuals taking any
potassium-depleting diuretic, other than those with kidney failure, to
supplement with both potassium and magnesium.
Supplementation of
magnesium in the dosage range of 300-500 mg per day is usually appropriate but
should be done in consultation with the prescribing doctor or a
nutritionally-oriented physician. Magnesium supplementation can be risky in
patients with kidney failure and usually contraindicated in such cases.
(Whang R, et al. Arch Intern Med 1992;152:40-45.)
nutrient
affected by drug: Gentamicin
mechanism: Research indicates that gentamicin can cause increased
urinary magnesium loss.
reports: Animal studies and case reports
indicate that renal tubular damage due to aminoglycosides, such as gentamicin,
can lead to hypokalemia combined with hypocalcemia, hypomagnesemia and
alkalosis.
(Mazze RI, Cousins MJ. Br J Anaesth. 1973
Apr;45(4):394-398; Valdivieso A, et al. Rev Med Chil. 1992
Aug;120(8):914-919; Kes P, et al. Magnes Trace Elem. 1990;9(1):54-60.
Parsons PP, et al. Br J Pharmacol 1997 Oct;122(3):570-576.)
nutritional support: Even though there is no conclusive evidence showing the
need for therapeutic supplementation, 300 mg per day would be a safe, protective
dose of magnesium.
nutrient affected by drug: Lithium
mechanism: Magnesium and lithium are chemically related. The
consumption of lithium carbonate may cause high blood levels of magnesium.
(Herzberg L, Herzeberg B. J Nerv Ment Dis. 1977 Dec;165(6):423-426;
Nielsen J. Acta Psychiatr Scand 1964 40:190-196; Nielsen J. Acta
Psychiatr Scand 1964;40:197-202.)
nutritional concerns:
Individuals taking lithium should inform their prescribing physican if they are
also supplementing with magnesium. Likewise, the prescribing physician, a
pharmacist, and/or a healthcare professional trained in nutrition should be
consulted before starting any supplementation with magnesium, separately or as
part of a multivitamin-mineral formulation.
nutrient affected by
drug: Neomycin
mechanism: Neomycin impairs magnesium absorption as a result of
maldigestion when taken orally.
(Roe DA. 1985, 157-158.)
nutritional support: Individuals taking neomycin internally for more than 2-3
days may benefit from taking supplemental magnesium at doses of 250-400 mg per
day.
nutrient affecting drug performance: Ranitidine
(Zantacฎ)
research: The concern
regarding potential interaction between ranitidine and magnesium does not
primarily originate with a drug-nutrient interaction per se. Instead, research
on the interaction between magnesium hydroxide and ranitidine has found that
some antacids reduce the bioavailability of the H2-receptor antagonists. This is
particularly true when ranitidine is used at the same time as high doses of the
relevant antacids. Bachmann et al found that among healthy subjects, i.e., ones
who would not normally use the drug, a magnesium hydroxide/aluminum hydroxide
antacid decreased ranitidine absorption by 20%-25% when the two substances were
taken at the same time.
(Bachmann KA. et al. Scand J Gastroenterol
Suppl 1994;206:14-19; Propst A, et al. Arzneimittelforschung 1996
Jun;46(6):621-624.)
nutritional support: In relation to antacid use,
the potential for interaction can be reduced by taking the ranitidine at least
two hours before or after any antacid containing aluminum or magnesium. There is
concern that a multivitamin/mineral supplement containing magnesium could have
the same effect, especially if the magnesium is in the form of magnesium
hydroxide. In such cases, caution would advise taking the ranitidine at least
two hours before or after the magnesium-containing supplement.
nutrient affecting drug toxicity: Sulfonylureas
mechanism: Magnesium hydroxide administration may increase the risk of
hypoglycemia from sulfonylureas.
(Drug Evaluations Subscription. Vol.
II, Section 10, Chapter 3, Winter, 1994; Schwanstecher M, et al. Naunyn
Schmiedebergs Arch Pharmacol 1991 Jan;343(1):83-89.)
nutrient
affecting drug performance: Tetracyclines
mechanism: Magnesium interferes with tetracycline absorption and
reduces its effectiveness by chelating the drug. This interaction occurs not
only with supplemental magnesium but also with many antacids, such as
Pepto-Bismol, which contain aluminum magnesium hydroxide. Furthermore, in vitro
studies indicate that chelates of magnesium and tetracycline may play a role in
the toxicity of tetracycline.
(Machado FC, et al. J Inorg Biochem
1995 Nov 15;60(3):163-173; Drug Evaluation Subscription. Winter 1993.)
nutritional concerns: Magnesium in the form of supplements should be
avoided while using tetracycline. Tetracycline is best taken on an empty
stomach, with a full glass of water, one hour before or two hours after
ingestion of any supplements, food, or other drugs. Nevertheless, tetracycline
and antacids are often used together in combination therapies for
Helicobacter pylori. Individuals taking tetracyline should only use
magnesium supplements after consultation with the prescribing physician.
nutrient affecting drug performance: Warfarin
mechanism: Mineral such as iron, magnesium, and zinc may bind with
warfarin, thereby reducing their absorption and activity.
(Holt GA. 1998,
284.)
nutritional concerns: While the chemistry of common mineral
nutrients binding warfarin is well founded the clinical significance and
frequency of occurrence of this interaction are uncertain. Individuals using
warfarin should be aware of the possible risk of reduced effectiveness of
treatment when taking supplements containing iron, magnesium and/or zinc.
Usually taking these minerals at least two hours apart from the warfarin
provides adequate protection from unwanted interference.
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References
[No author given.] Drug Evaluations
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Akbar A, Rees JH, Nyamugunduru G, English MW,
Spencer DA, Weller PH. Aminoglycoside-associated hypomagnesaemia in children
with cystic fibrosis. Acta Paediatr. 1999 Jul;88(7):783-785.
Abstract: Hypomagnesaemia in children with cystic fibrosis (CF) is
under-recognized. We report a child with CF who developed significant
hypomagnesaemia following intravenous (i.v.) treatment with aminoglycosides for
exacerbations of Pseudomonas aeruginosa infection. Three additional cases have
also been observed. Investigations in two patients have revealed excessive renal
loss of magnesium. It is postulated that renal tubular damage secondary to the
cumulative effects of repeated courses of aminoglycosides resulted in
hypomagnesaemia, and we suggest screening for this problem by monitoring serum
magnesium regularly in all patients with CF receiving multiple courses of
aminoglycosides.
al-Ghamdi SM, Cameron EC, Sutton RA. Magnesium
deficiency: pathophysiologic and clinical overview. Am J Kidney Dis 1994
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Ariceta G, Rodriguez-Soriano J, Vallo A,
Navajas A. Acute and chronic effects of cisplatin therapy on renal magnesium
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Abstract:
Although the acute renal toxicity of cisplatin has been well documented,
long-term follow-up studies in cisplatin-treated children are scanty. We have
evaluated the incidence and characteristics of both acute and chronic
nephrotoxicity in 22 children (median age 8 years) treated with cisplatin as
part of different chemotherapeutic protocols. All patients exhibited a
significant and progressive decrease in plasma magnesium (Mg) values soon after
cisplatin administration. Magnesiuria also increased immediately after therapy.
Hypomagnesemia (plasma Mg < 1.4 mg/dl) occurred in 10 patients and it was
dose-dependent. Minimal and mean cumulated doses inducing hypomagnesemia were
300 and 500 mg/m2, respectively. In 18 children we followed renal function
prospectively for a mean time of 2.3 years after arrest of cisplatin therapy.
Chronic hypomagnesemia and moderate elevation of plasma creatinine were observed
in 6 children, hypocalciuria in 5 children, and hypokalemia in 1 child. Presence
of hypomagnesemia was unrelated to the total dose received or the time elapsed
since cisplatin therapy. Renal function studies, performed in the 6 children
with chronic hypomagnesemia, revealed different degrees of impairment in Mg
reabsorption. The functional characteristics of chronic cisplatin nephrotoxicity
found in the present series-contrary to prior reports-are not comparable to
those present in the inherited Gitelman's syndrome.
Bachmann KA,
Sullivan TJ, Jauregui L, Reese J, Miller K, Levine LDrug interactions of
H2-receptor antagonists. Scand J Gastroenterol Suppl 1994;206:14-19.
Abstract: Three drug interactions of nizatidine and of other antisecretory
agents were studied comparatively. First, the effects of nizatidine, cimetidine
and ranitidine on the dispositional kinetics of theophylline were evaluated in
chronic obstructive pulmonary disease (COPD) patients. Second, the effect of
magnesium/aluminium hydroxide on the relative bioavailability of nizatidine,
famotidine, cimetidine and ranitidine was evaluated in healthy volunteers.
Finally, the effects of nizatidine and omeprazole on the dispositional kinetics
of phenytoin were evaluated in healthy volunteers. Only cimetidine altered the
steady-state kinetics of oral theophylline, slowing theophylline clearance by
25%. Each of the H2-receptor antagonists exhibited a modest decline in relative
bioavailability when ingested with antacid. Antacid ingestion decreased the
bioavailability of famotidine, ranitidine and cimetidine by 20-25%, and the
bioavailability of nizatidine by 12%. Each of these effects was statistically
significant. Finally, it was found that neither omeprazole nor nizatidine
affected the single dose kinetics of phenytoin.
Barros LF, Chagas AC, da
Luz PL, Pileggi F. Magnesium treatment of acute myocardial infarction: effects
on necrosis in an occlusion/reperfusion dog model. Intl J Cardiol. 1995
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Bianchetti MG, Kanaka C, Ridolfi-Luthy A, Wagner HP,
Hirt A, Paunier L, Peheim E, Oetliker OH. Chronic renal magnesium loss,
hypocalciuria and mild hypokalaemic metabolic alkalosis after cisplatin.
Pediatr Nephrol 1990 May;4(3):219-222.
Abstract: Renotubular handling
of sodium, potassium (K) calcium (Ca), phosphate, hydrogen ions and glucose, and
urinary concentrating ability were studied in three children (aged 8, 8.5, 11
years) with renal magnesium (Mg) loss, persisting for more than 2 years after
discontinuation of cisplatin treatment for neuroblastoma. A group of healthy
children served as controls. Besides renal Mg wasting, a clear-cut tendency
towards reduced calciuria associated with normal or slightly elevated plasma Ca
was observed. Plasma K tended to be low (3.4-3.7 mmol/l), and plasma chloride
was normal. Plasma bicarbonate (HCO3) ranged from 24.9 to 27.8 mmol/l, and
urinary pH was always less than 6.0, indicating a renal HCO3 threshold exceeding
24 mmol/l. Plasma creatinine levels, glucosuria and phosphaturia, and urinary
concentrating capacity were adequate. Comparable features were found in three
children (aged 4.5, 9, 13 years) with primary renotubular
hypomagnesaemia-hypokalaemia and hypocalciuria. This study complements the
picture of chronic cisplatin tubulopathy in childhood demonstrating that, apart
from Mg wasting, a reduced Ca excretion, and a tendency to hypokalaemia and
metabolic alkalosis exist. Thus cisplatin may induce renal functional damage
identical to that found in primary renotubular hypomagnesaemia--hypokalaemia
with hypocalciuria.
Buckley JE, Clark VL, Meyer TJ, Pearlman NW.
Hypomagnesemia after cisplatin combination chemotherapy. Arch Intern Med
1984 Dec;144(12):2347-2348.
Abstract: Sixty-six patients receiving a
five-drug combination chemotherapy regimen containing low-dose cisplatin were
studied for the presence of hypomagnesemia. Thirty-eight (76%) of 50 patients
receiving treatment every four weeks became hypomagnesemic during treatment. The
incidence increased with the cumulative cisplatin dose, ranging from 41% after a
single course to 100% of patients receiving six cycles of therapy. The incidence
seemed lower in patients receiving the combination with a greater interval
(eight weeks v four weeks) between cycles. We report the incidence and severity
of hypomagnesemia to be dose dependent. The cause of the higher incidence of
hypomagnesemia observed in this series compared with others is unknown but may
be related to an interaction of cisplatin with another drug contained in this
regimen.
Cohen L, Kitzes R. Magnesium sulfate and digitalis-toxic
arrhythmias. JAMA 1983 May 27;249(20):2808-2810.
Abstract: Seven
patients with congestive heart failure receiving long-term diuretic treatment
(more than three years) experienced idionodal tachycardia in the presence of
apparently normal serum digoxin levels. Intravenous bolus administration of
magnesium (Mg) sulfate, followed by intramuscular Mg repletion, abolished the
digitalis-toxic arrhythmia. The finding of decreased lymphocyte Mg and potassium
contents proved the existence of cellular Mg depletion associated with normal
serum Mg levels in five patients and with hypomagnesemia in the other two.
Decreased cellular Mg content with normal serum Mg level predisposes to
digitalis-toxic arrhythmias.
Cohen L. Potassium replacement associated
with the development of tetany in a patient with hypomagnesaemia. Magnes Res
1993 Mar;6(1):43-45.
Abstract: A case of hypomagnesaemia secondary to
cisplatin therapy and diarrhoea had concomitant hypokalaemia. Increasing the
serum potassium level from 2.8 to 3.4 mmol/litre by potassium supplementation
induced tetany. Hypokalaemia in the face of hypomagnesaemia may have a
membrane-stabilizing effect and preserve excitability.
Cox IM, Campbell
MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome.
Lancet 1991 Mar 30;337(8744):757-760.
Abstract: The hypotheses that
patients with chronic fatigue syndrome (CFS) have low red blood cell magnesium
and that magnesium treatment would improve the wellbeing of such patients were
tested in a case-control study and a randomised, double-blind,
placebo-controlled trial, respectively. In the case-control study, 20 patients
with CFS had lower red cell magnesium concentrations than did 20 healthy control
subjects matched for age, sex, and social class (difference 0.1 mmol/l, 95%
confidence interval [CI] 0.05 to 0.15). In the clinical trial, 32 patients with
CFS were randomly allocated either to intramuscular magnesium sulphate every
week for 6 weeks (15 patients) or to placebo (17). Patients treated with
magnesium claimed to have improved energy levels, better emotional state, and
less pain, as judged by changes in the Nottingham health profile. 12 of the 15
treated patients said that they had benefited from treatment, and in 7 patients
energy score improved from the maximum to the minimum. By contrast, 3 of the 17
patients on placebo said that they felt better (difference 62%, 95% CI 35 to
90), and 1 patient had a better energy score. Red cell magnesium returned to
normal in all patients on magnesium but in only 1 patient on placebo. The
findings show that magnesium may have a role in CFS.
Deppermann KM, Lode
H, Hoffken G, Tschink G, Kalz C, Koeppe P. Influence of ranitidine, pirenzepine,
and aluminum magnesium hydroxide on the bioavailability of various antibiotics,
including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid.
Antimicrob Agents Chemother 1989 Nov;33(11):1901-1907.
Devane J,
Ryan MP. Evidence for a magnesium-sparing action by amiloride during renal
clearance studies in rats. Br J Pharmacol. 1983 Aug;79(4):891-896.
Abstract: The potassium-sparing diuretic, amiloride, reduced the fractional
excretion of magnesium in anaesthetized rats. Alterations in glomerular
filtration rate (GFR), the filtered load of magnesium, arterial blood pressure,
the status of the extracellular fluid volume, plasma aldosterone concentration
and acid-base balance were not involved. It was concluded that amiloride exerted
a magnesium-sparing effect by a direct renal action.
Devane J, Ryan MP.
The effects of amiloride and triamterene on urinary magnesium excretion in
conscious saline-loaded rats. Br J Pharmacol. 1981 Feb;72(2):285-289.
Abstract: 1 The potassium-sparing diuretics, triamterene and amiloride,
reduced urinary magnesium excretion in conscious saline-loaded rats. 2 Urinary
magnesium-conservation was also detected when amiloride was used in combination
with the potent 'loop-blocking' diuretic, frusemide.
Devane J, Ryan MP.
Urinary magnesium excretion during amiloride administration in saline-loaded
rats. Br J Pharmacol. 1979 Nov;67(3):493P.
Elisaf M, Milionis H,
Siamopoulos KC. Hypomagnesemic hypokalemia and hypocalcemia: clinical and
laboratory characteristics. Miner Electrolyte Metab 1997;23(2):105-112
Elliott WC, Patchin DS. Effects and interactions of gentamicin,
polyaspartic acid and diuretics on urine calcium concentration. J Pharmacol
Exp Ther 1995 Apr;273(1):280-284.
Abstract: Gentamicin causes isolated,
reversible calciuria in rats by an unknown mechanism. We hypothesized that
gentamicin calciuria is related to nonantibacterial properties that may
interfere with transtubular calcium transport (calcium channel blockade,
Na,K-ATPase inhibition or competition with calcium for binding to the
brush-border membrane). The calciuric effect of gentamicin was compared to the
calcium channel blockers lanthanum and cobalt, the Na,K-ATPase inhibitor ouabain
and the polycation aprotinin (which competes with gentamicin for brush-border
membrane binding). Although gentamicin 0.02 mmol/kg caused a 6-8-fold increase
in urine calcium concentration, none of the other agents was calciuric. We also
found that the calciuric effects of gentamicin and furosemide were additive,
whereas the noncalciuric diuretic chlorothiazide had no effect on gentamicin
calciuria. We also determined the effect of poly-L-aspartic acid (PAA), which
binds gentamicin and prevents nephrotoxicity. PAA caused isolated calciuria
similar in magnitude and character to gentamicin. However, PAA pretreatment
decreased the magnitude of gentamicin calciuria to insignificance. PAA
pretreatment did not prevent furosemide calciuresis. These results indicate
that: 1) gentamicin and furosemide calciuria are caused by different mechanisms;
2) gentamicin calciuria is probably not mediated by calcium channel blockade,
Na,K-ATPase inhibition or displacement of brush-border membrane-bound calcium;
3) gentamicin and PAA calciuria may reflect interference with intracellular
events related to transtubular calcium transport.
Friemann EFJ, Lasch
H-G, Friemann S, Golf S, Enzinger D, Temme H, Graef V, Katz N, Roka L, Tross H,
Morr H. [Effect of magnesium treatment on chronic obstructive lung diseases.]
Medizinische Welt. 1991; Vol 42(4) (pp 311-315. [Article in German]
Galloe AM, Rasmussen HS, Jorgensen LN, Aurup P, Balslov S, Cintin C,
Graudal N, McNair P. Influence of oral magnesium supplementation on cardiac
events among survivors of an acute myocardial infarction. BMJ. 1993 Sep
4;307(6904):585-587.
Galloe AM, Graudal NA. [Magnesium treatment of
patients with acute myocardial infarction. A meta-analysis]. Ugeskrift for
Laeger. 1995 Jan 23; 157(4):437-40. [Article in Danish]
Gantz NM.
Magnesium and chronic fatigue. Lancet 1991;338:66. (Letter)
Garland HO, Phipps DJ, Harpur ES. Gentamicin-induced hypercalciuria in
the rat: assessment of nephron site involved. J Pharmacol Exp Ther. 1992
Oct;263(1):293-297.
Abstract: Two independent techniques were used in
anesthetized rats in an attempt to locate the nephron site of the reduced
tubular calcium reabsorption accompanying acute gentamicin infusion. The first
technique was that of lithium clearance used to assess proximal sodium (and
secondarily calcium) handling. Observations that lithium clearance was
comparable in control and gentamicin-treated animals (1.83 +/- 0.39 vs. 1.46 +/-
0.14 ml.min-1 for first experimental period) suggests a lack of proximal effect
of the drug. The second technique was that of tracer microinjection whereby
superficial nephrons were injected with 45Ca and tubule calcium transport was
assessed from the recovery of radioactivity in the final urine. 45Ca recovery
values from distal microinjections were comparable in control and
gentamicin-treated groups (81.1 +/- 2.0 vs. 77.7 +/- 4.6%). However, 45Ca
recovery values from proximal microinjections were significantly higher in the
gentamicin group (9.4 +/- 1.0 vs. 3.5 +/- 0.8%; P < .001). These data suggest
that the effects of gentamicin on renal calcium handling are mediated at a
nephron site proximal to the distal tubule (i.e., loop of Henle or proximal
tubule itself). Closer examination of individual proximal micropuncture data may
point to an effect occurring predominantly in the pars recta of the proximal
tubule or loop of Henle. Taken together, the results of both parts of the
present study suggest that the early physiological effects of gentamicin on the
kidney occur in a different nephron segment from any subsequent nephrotoxicity.
Gaspar AZ, Gasser P, Flammer J. The influence of magnesium on visual
field and peripheral vasospasm in glaucoma. Ophthalmologica
1995;209:11-13.
Goto K, Yasue H, Okumura K, Matsuyama K, Kugiyama K,
Miyagi H, Higashi T. Magnesium deficiency detected by intravenous loading test
in variant angina pectoris. Am J Cardiol. 1990 Mar 15;65(11):709-712.
Abstract: To study whether magnesium (Mg) deficiency is present in patients
with variant angina, 24-hour Mg retention of low dose Mg (0.2 mEq/kg lean body
weight) administered intravenously over 4 hours in 20 patients with variant
angina was examined. No patient had received calcium antagonists before or
during the study. All had attacks of chest pain associated with ST elevation on
electrocardiograms. Twenty-one subjects without ischemic heart disease were
studied as control subjects. Ten patients with variant angina were restudied 10
to 529 days (mean 235 +/- 30) after the treatment with calcium antagonists
(diltiazem 120 to 240 or nifedipine 40 to 80 mg/day), which resulted in complete
suppression of anginal attacks. The mean serum Mg concentrations in the patients
with variant angina and the control subjects were 2.1 +/- 0.05 and 2.1 +/- 0.03
mg/dl, respectively (difference not significant). However, 24-hour Mg retention
in the patients with variant angina was 60 +/- 5%, while that in the control
subjects was 36 +/- 3% (p less than 0.001), suggesting that Mg deficiency is
present in at least some patients with variant angina. The mean serum Mg
concentrations before and after calcium antagonist treatment in 10 patients with
variant angina were 2.1 +/- 0.09 and 2.1 +/- 0.07 mg/dl, respectively
(difference not significant). However, 24-hour Mg retention decreased
significantly (p less than 0.01) from 60 +/- 6 to 34 +/- 7% after the treatment.
There is Mg deficiency in many patients with variant angina and it is corrected
after treatment with calcium antagonists.
Gugler R, Allgayer H. Effects
of antacids on the clinical pharmacokinetics of drugs. An update. Clin
Pharmacokinet 1990 Mar;18(3):210-219.
Abstract: Since a previous review
by Hurwitz was published in 1977 a large number of reports on drug interactions
with antacids have appeared, few of which are of clinical relevance.
Tetracyclines form insoluble complex molecules by metal ion chelation with
various antacids; tetracycline absorption may be decreased by more than 90% by
this interaction. Of the new class of quinolone antibiotics, the absorption of
ciprofloxacin and ofloxacin is reduced by 50 to 90% in the presence of
aluminium- and magnesium hydroxide-containing antacids. In contrast to early
work showing inhibition of the absorption of beta-adrenergic blocking drugs by
antacids, subsequent studies did not confirm a reduction in the bioavailability
of either atenolol or propranolol during antacid treatment; indeed, they showed
an increase in the plasma concentrations of metoprolol when the drug was
coadministered with an antacid. The bioavailability of captopril was
significantly reduced in the presence of an antacid, and lower plasma
concentrations of this angiotensin-converting enzyme inhibitor were accompanied
by a reduction of its effect on the systolic blood pressure of the patients. The
absorption of the cardiac glycosides digoxin and digitoxin is not inhibited by
antacids to a significant degree, although earlier studies had shown a positive
effect when the dissolution of the glycoside preparations was relatively poor.
Antacids reduce the bioavailability of the H2-receptor antagonists cimetidine
and ranitidine only when high antacid doses are used and when the drugs are
administered simultaneously. The bioavailability of famotidine was not
significantly altered by a potent antacid preparation, although a trend towards
reduced absorption was observed. Iron absorption is significantly decreased in
the presence of sodium bicarbonate and calcium carbonate, but is nearly complete
when coadministered with aluminium-magnesium hydroxide. Nonsteroidal
anti-inflammatory drugs such as naproxen, tenoxicam, ketoprofen, ibuprofen and
piroxicam are not affected in their absorption by antacid treatment.
Theophylline bioavailability is unchanged when the drug is given together with
antacids, although its rate of absorption may be altered, leading to a reduction
or an increase in the time of the occurrence of peak plasma drug concentrations.
Healy DP, Dansereau RJ, Dunn AB, Clendening CE, Mounts AW, Deepe GS Jr.
Reduced tetracycline bioavailability caused by magnesium aluminum silicate in
liquid formulations of bismuth subsalicylate. Ann Pharmacother 1997
Dec;31(12):1460-1464.
Herzberg L, Herzeberg B. Mood change and
magnesium. A possible interaction between magnesium and lithium? J Nerv Ment
Dis. 1977 Dec;165(6):423-426.
Abstract: Magnesium and lithium are
chemically related. Magnesium is an essential ion in many enzyme systems and
lithium is of value in the treatment of manic-depressive disease. A significant
sex difference in mean plasma magnesium levels is reported in 44 depressed
patients. It is suggested that further studies of magnesium metabolism are
indicated and that they may provide a better understanding of manic-depressive
disease and the mode of action of lithium.
Hinds G, Bell NP, McMaster D,
McCluskey DR. Normal red cell magnesium concentrations and magnesium loading
tests in patients with chronic fatigue syndrome. Ann Clin Biochem. 1994 Sep;31 (
Pt 5):459-461.
Abstract: Red blood cell magnesium concentrations were
measured in samples from 89 patients who fulfilled the diagnostic criteria for
chronic fatigue syndrome and the results compared to those found in an age and
sex matched group selected from the normal population. No significant difference
was found. Six patients were further investigated using a magnesium loading test
to determine if there was any evidence of magnesium deficiency associated with
this disorder. None was found. There is therefore no indication for the use of
magnesium therapy in the management of this condition.
Hoffken G, Borner
K, Glatzel PD, Koeppe P, Lode H. Reduced enteral absorption of ciprofloxacin in
the presence of antacids. Eur J Clin Microbiol. 1985 Jun;4(3):345.
(Letter)
Holt GA. Food and Drug Interactions. Chicago: Precept
Press, 1998.
Howard JM, Davies S, Hunnisett A. Magnesium and chronic
fatigue syndrome. Lancet 1992 Aug 15;340(8816):426.
Kawano Y,
Matsuoka H, Takishita S, Omae T. Effects of magnesium supplementation in
hypertensive patients. Hypertension 1998 Aug;32(2):260-265.
Abstract:
An increase in magnesium intake has been suggested to lower blood pressure (BP).
However, the results of clinical studies are inconsistent. We studied the
effects of magnesium supplementation on office, home, and ambulatory BPs in
patients with essential hypertension. Sixty untreated or treated patients (34
men and 26 women, aged 33 to 74 years) with office BP >140/90 mm Hg were
assigned to an 8-week magnesium supplementation period or an 8-week control
period in a randomized crossover design. The subjects were given 20 mmol/d
magnesium in the form of magnesium oxide during the intervention period. In the
control period, office, home, and average 24-hour BPs (mean+/-SE) were
148.6+/-1.6/90.0+/-0.9, 136.4+/-1.3/86.8+/-0.9, and 133.7+/-1.3/81.0+/-0.8 mmHg,
respectively. All of these BPs were significantly lower in the magnesium
supplementation period than in the control period, although the differences were
small (office, 3.7+/-1.3/1.7+/-0.7 mmHg; home, 2.0+/-0.8/1.4+/-0.6 mmHg;
24-hour, 2.5+/-1.0/1.4+/-0.6 mm Hg). Serum concentration and urinary excretion
of magnesium increased significantly with magnesium supplementation. Changes in
24-hour systolic and diastolic BPs were correlated negatively with baseline BP
or changes in serum magnesium concentration. These results indicate that
magnesium supplementation lowers BP in hypertensive subjects and this effect is
greater in subjects with higher BP. Our study supports the usefulness of
increasing magnesium intake as a lifestyle modification in the management of
hypertension, although its antihypertensive effect may be small.
Kelly
RA, Smith TW. Recognition and management of digitalis toxicity. Am J
Cardiol. 1992 Jun 4;69(18):108G-118G; disc. 118G-119G. (Review)
Kes
P, Reiner Z. Symptomatic hypomagnesemia associated with gentamicin therapy.
Magnes Trace Elem. 1990;9(1):54-60.
Abstract: Seven patients (3
females, 4 males) developed symptomatic hypomagnesemia, hypocalcemia, and
hypokalemia following gentamicin therapy. The excessive and inappropriate
urinary excretion of magnesium and potassium in the presence of subnormal serum
concentrations was noted. A significant correlation was found between the total
cumulative dose of gentamicin and serum Mg concentration (r = 0.76, p less than
0.05), as well as between the renal wasting of Mg and the total cumulative dose
of gentamicin administered (r = 0.89, p less than 0.01). The gentamicin-induced
Mg depletion is a very rare but important complication which is most likely to
occur when the drug is given to older patients in large doses over extended
periods of time.
Kibirige MS, Morris-Jones PH, Addison GM. Prevention of
cisplatin-induced hypomagnesemia. Pediatr Hematol Oncol 1988;5(1):1-6.
Abstract: Twenty-eight children were treated for various cancers with
protocols that included dichlorodiamine platinum (cisplatin). Sixteen children
were given intravenous magnesium after the administration of cisplatin, and 12
were given intravenous magnesium before and after administration of cisplatin.
Serum magnesium concentration levels were monitored before, during, and after
the full course of treatment and found to be lower in the first group of
patients than in the second group. We recommend that magnesium supplements be
given to patients receiving cisplatin during the precisplatin hydration period
to prevent hypomagnesemia.
Kinlay S, Buckley NA. Magnesium sulfate in
the treatment of ventricular arrhythmias due to digoxin toxicity. J Toxicol
Clin Toxicol 1995;33(1):55-59.
Abstract: Although digoxin antibodies are
the definitive treatment of cardiac arrhythmias due to digoxin toxicity,
magnesium can also be effective especially with low serum magnesium levels. The
case report describes a patient with digoxin toxicity, ventricular tachycardia
and a slightly elevated serum magnesium. Two 10 mmol doses of intravenous
magnesium sulfate were associated with a more stable junctional rhythm with
bigeminy. Magnesium is known to suppress early after depolarizations, and in
supraphysiological doses, may act as an indirect antagonist of digoxin at the
sarcolemma Na(+)-K(+)-ATPase pump. Intravenous magnesium may be used to treat
cardiac arrhythmias due to digoxin poisoning where there is likely to be a delay
in the availability of digoxin antibodies, even in the presence of elevated
serum magnesium.
Koch Nogueira PC, Hadj-Aissa A, Schell M, Dubourg L,
Brunat-Mentigny M, Cochat P. Long-term nephrotoxicity of cisplatin, ifosfamide,
and methotrexate in osteosarcoma. Pediatr Nephrol 1998 Sep;12(7):572-575.
Abstract: The acute renal effects of chemotherapy are known, but long-term
nephrotoxicity has rarely been investigated. The aim of the present study was to
assess long-term renal function in children and adolescents who received at-risk
chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an
osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and
renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg),
phosphorus (P), and uric acid] were prospectively performed 5.4+/-2.2 (+/-SD)
years after chemotherapy (total cumulative dose: methotrexate 41+/-31 g/m2,
ifosfamide 39+/-14 g/m2, cisplatin 674+/-188 mg/m2) in 18 children and
adolescents. The results were compared with 13 normal volunteers matched for age
and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in
all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05)
and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients.
Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal
excretion of P, Mg, and uric acid was higher in patients than in controls.
Glomerular function was not significantly altered and only mild tubular
dysfunction was present. Since renal excretion of P and Mg were increased in
patients compared with normal volunteers and hypercalciuria was occasionally
seen, divalent ion disorders are the most-likely potential complications.
Kosek JC, Mazze RI, Cousins MJ. Nephrotoxicity of gentamicin. Lab
Invest. 1974 Jan;30(1):48-57.
Kotsaki-Kovatsi VP,
Koehler-Samouilidis G, Kovatsis A, Rozos G. Fluctuation of zinc, copper,
magnesium and calcium concentrations in guinea pig tissues after administration
of captopril (SQ 14225). J Trace Elem Med Biol 1997 Apr;11(1):32-36.
Abstract: The effect of the administration of captopril on Zn (zinc), Cu
(copper), Ca (calcium) and Mg (magnesium) concentrations in guinea pig tissues
was studied. For nine weeks 2 mg captopril per kg b.w. were administered daily
to adult male guinea pigs intraperitoneally. The concentrations of the studied
metals were determined in several tissues. Captopril significantly decreased Zn
concentration in liver, Cu concentration in liver, adrenals, jejunum, urine and
hair and Mg concentrations in blood and urine. A significant increase was
observed in testicular and epididymal Zn, in heart, epididymal and fecal Cu, in
Mg concentration of lung, kidney, adrenals, jejunum, epididymis and hair and in
Ca concentrations in brain, heart, lung, kidney, spleen and stomach. No
significant changes were observed in the colon and the thigh bone concentrations
of the various elements tested. In conclusion Captopril treatment can produce
translocation and/or elimination of Zn, Cu, Mg and Ca ions in various tissues of
guinea pigs.
Kroenke K, Wood DR, Hanley JF. The value of serum magnesium
determination in hypertensive patients receiving diuretics. Arch Intern
Med 1987;147:1553-1556.
Kupfer S, Kosovsky JD. Effects of cardiac
Glycosides on renal tubular transport of calcium, magnesium inorganic phosphate
and glucose in the dog. J Clin Invest 1965 44:1132-1143.
Lajer H,
Daugaard G. Cisplatin and hypomagnesemia. Cancer Treat Rev. 1999
Feb;25(1):47-58. (Review)
Abstract: Hypomagnesemia is a well known
side-effect in patients receiving cisplatin-containing chemotherapy. Cisplatin
induces hypomagnesemia through its renal toxicity possibly by a direct injury to
mechanisms of magnesium reabsorption in the ascending limb of the loop of Henle
as well as the distal tubule. Since the magnesium reabsorption process still
remains to be fully characterized, the effect by cisplatin on this process
remains uncertain. Hypomagnesemia is a frequent complication to chemotherapy
with cisplatin affecting up to 90% of patients if no corrective measures are
initiated. The clinical importance of this hypomagnesemia remains uncertain.
Possible symptoms of hypomagnesemia can be impossible to distinguish from
symptoms related to the underlying disease or the treatment with chemotherapy.
Existing studies on how to supplement magnesium during treatment with cisplatin
have focused mainly on the effect on serum magnesium values and erythrocyte
magnesium concentrations but both parameters are poor indicators of body
magnesium stores. As long as the relationship between hypomagnesemia and
possible complications thereof remains poorly elucidated, it seems reasonable to
try to avoid hypomagnesemia. The best results seem to be provided by adding
magnesium to the pre- and posthydration fluids.
Landauer JA. Magnesium
deficiency and digitalis toxicity. JAMA 1984 Feb 10;251(6):730. (Letter,
Review)
Lavin F, O'Keeffe S, Grimes H, Finn J, Mannion A, Daly K. Effect
of prolonged nifedipine or captopril therapy on lymphocyte magnesium and
potassium levels in hypertension. Cardiology 1993;82(6):405-408.
Abstract: The effect of prolonged treatment with calcium channel blockers on
potassium and magnesium stores is uncertain. We measured lymphocyte and serum
magnesium and potassium in 28 patients treated for hypertension for 6 months
with nifedipine or captopril. There was no difference in serum or lymphocyte
concentrations in the two groups compared to 45 healthy, normotensive controls.
These results suggest that intracellular cation levels are maintained with
prolonged therapy with calcium channel blockers.
Lewis R, Durnin C,
McLay J, McEwen J, McDevitt DG. Magnesium deficiency may be an important
determinant of ventricular ectopy in digitalised patients with chronic atrial
fibrillation. Br J Clin Pharmacol. 1991 Feb;31(2):200-203
Abstract:
Digitalised patients with chronic atrial fibrillation (AF) have a high
prevalence of ventricular premature beats (VPB); magnesium deficiency may be a
contributory factor. We have used a magnesium loading-test to examine the
relationship between ventricular ectopy and magnesium status in 14 digitalised
patients with chronic AF. Among seven patients with infrequent VPB (less than
250 24 h-1; mean 107 24 h-1) mean magnesium retention was 10.1% and four
subjects retained no significant quantities of magnesium, indicating magnesium
repletion. Among the remaining seven patients, mean magnesium retention was
significantly higher (33.1%, P less than 0.02) and all patients retained 20% or
more of the load given. There was an overall relationship between Mg retention
and numbers of VPB (rs = 0.54; P less than 0.05). Magnesium deficiency may be
determinant of ventricular ectopy in digitalised patients with chronic AF.
Machado FC, Demicheli C, Garnier-Suillerot A, Beraldo H. Metal complexes
of anhydrotetracycline. 2. Absorption and circular dichroism study of Mg(II),
Al(III), and Fe(III) complexes. Possible influence of the Mg(II) complex on the
toxic side effects of tetracycline. J Inorg Biochem 1995 Nov
15;60(3):163-173.
Martin BJ, Milligan K. Diuretic-associated
hypomagnesemia in the elderly. Arch Intern Med 1987
Oct;147(10):1768-1771.
Abstract: Serum magnesium concentration was measured
in 320 consecutive elderly patients (mean age, 81 years) receiving diuretic
therapy at the time of hospital admission. When compared with serum
concentrations of 250 elderly patients who were not taking diuretics at the time
of hospital admission, only the group taking thiazide diuretics had a
significantly reduced mean serum level. The 24-hour urine sampling from
representative subgroups demonstrated impaired magnesium-conserving ability in
hypomagnesemic subjects receiving loop and thiazide diuretic therapy. Patients
taking therapy that included a potassium-sparing diuretic had no significant
evidence of reduced magnesium-conserving ability. Dietary assessments of the
study population revealed suboptimal magnesium intake in the diet.
Marz
R. Medical Nutrition From Marz. Second Edition. Portland, OR. 1997.
McLean, R. Magnesium and its therapeutic uses: A review. Am J Med
1994 Jan;96(1):63-76. (Review)
Mizuki Y, Fujiwara I, Yamaguchi T.
Pharmacokinetic interactions related to the chemical structures of
fluoroquinolones. J Antimicrob Chemother 1996 May;37 Suppl A:41-55.
Abstract: Fluoroquinolone derivatives interact with methylxanthines
(theophylline, caffeine) and metallic ion-containing drugs to different degrees.
The rat appears to be a suitable model for predicting such interactions in man.
It has been possible to determine the relationship between the chemical
structure of the fluoroquinolone and the magnitude of the interaction.
Fluoroquinolones with a bulky substituent at the position 8, such as
sparfloxacin, lomefloxacin and fieroxacin, are less prone to interact with
theophylline than those without an 8-substituent, such as enoxacin. This
substituent determines the planarity of the whole fluoroquinolone molecule and
the interaction tends to be more significant for planar fluoroquinolones.
Furthermore, a 4'-nitrogen atom in the 7-piperazinyl group is essential for the
interaction to occur. The nitrogen atom is possibly the site that binds
cytochrome P-450, which catalyses theophylline metabolism. The reduction in
bioavailability of fluoroquinolones by concurrent administration of aluminium
hydroxide is more striking for derivatives with fewer substituents on the
essential structure and on the piperazinyl group, such as norfloxacin,
ciprofloxacin and enoxacin. Substitution at the 5-position diminishes the
interaction, which suggests that the 5-substituent may affect the formation
and/or stability of unabsorbable chelate complex which is the probable cause of
the interaction. These findings are potentially useful in designing
fluoroquinolones less prone to drug interactions.
Morten and Rasmussen,
et al. Magnesium in the treatment of MI. Drugs 46:347-59, 1993.
Abstract: Magnesium needs to be given IV immediately during an MI to work
effectively. In 76 patients with MI there was a decrease mortality rate of 55%
of the patients treated with magnesium IV.
Nielsen J. Magnesium-lithium
studies. 1. Serum and erythrocyte magnesium in patients with manic states during
lithium treatment. Acta Psychiatr Scand 1964 40:190-196.
Nielsen
J. Magnesium-lithium studies. 2. The effect of lithium on serum magnesium in
rabbits. Acta Psychiatr Scand 1964;40:197-202.
O'Keeffe S, Grimes
H, Finn J, McMurrough P, Daly K. Effect of captopril therapy on lymphocyte
potassium and magnesium concentrations in patients with congestive heart
failure. Cardiology 1992;80(2):100-105.
Abstract: Lymphocyte
potassium and magnesium were measured before and 3 months after the introduction
of captopril in 18 patients taking diuretics for congestive heart failure.
Compared to 32 healthy controls, 9 patients who had been on potassium
supplements plus frusemide had decreased baseline lymphocyte magnesium and
potassium concentrations (p less than 0.01), in spite of similar plasma
electrolyte levels. There was a significant (p less than 0.01) increase in both
lymphocyte potassium and magnesium levels after 3 months' treatment with
captopril and frusemide in these patients. Nine patients who had been taking a
potassium-sparing combination diuretic also had an increase in lymphocyte
magnesium (p less than 0.05) following the introduction of captopril. Increased
intracellular potassium and magnesium may be one mechanism whereby
angiotensin-converting enzyme inhibitors reduced arrhythmias and improve
survival in patients with congestive heart failure.
OKeefe JH Jr,
Harris WS, Nelson J, Windsor SL. Effects of pravastatin with niacin or magnesium
on lipid levels and postprandial lipemia. Am J Cardiol 1995;76:480-484.
Oto A. Magnesium treatment in acute myocardial infarction: an unresolved
consensus. Eur Heart J. 1999 Jan;20(2):86-88. (Review)
Palmieri
GM, Thompson JS, Eliel LP. Modifications of plasma magnesium by thyrocalcitonin,
parathyroid extract and cortisone. Endocrinology 1969
Jun;84(6):1509-1511.
Parsons PP, Garland HO, Harpur ES, Old S. Acute
gentamicin-induced hypercalciuria and hypermagnesiuria in the rat: dose-response
relationship and role of renal tubular injury. Br J Pharmacol 1997
Oct;122(3):570-576.
Abstract: 1. Standard renal clearance techniques were
used to assess the dose-response relationship between acute gentamicin infusion
and the magnitude of hypercalciuria and hypermagnesiuria in the anaesthetized
Sprague-Dawley rat. Also investigated were whether these effects occurred
independently of renal tubular cell injury. 2. Acute gentamicin infusion was
associated with a significant hypercalciuria and hypermagnesiuria evident within
30 min of drug infusion. The magnitude of these responses was related to the
dose of drug infused (0.14-1.12 mg kg(-1) min[-1]). Increased urinary
electrolyte losses resulted from a decreased tubular reabsorption of calcium and
magnesium. 3. A rapid dose-related increase in urinary
N-acetyl-beta-D-glucosaminidase (NAG) excretion was also observed in response to
gentamicin infusion. However, there was no evidence of renal tubular cell injury
and no myeloid bodies were observed within the lysosomes of the proximal tubular
cells. Gentamicin may thus interfere with the mechanisms for cellular uptake and
intracellular processing of NAG causing increased NAG release into the tubular
lumen. 4. The absence of changes in renal cellular morphology indicates that the
excessive renal losses of calcium and magnesium were an effect of gentamicin per
se and not the result of underlying renal tubular injury. The renal effects
described in this paper were apparent after administration of relatively low
total drug doses, and with plasma concentrations calculated to be within the
clinical range. These findings suggest that disturbances of plasma electrolyte
homeostasis could occur in the absence of overt renal injury in patients
receiving aminoglycoside antibiotics.
Pere AK, Krogerus L, Mervaala EM,
Laakso J, Karppanen H, Inkinen K, Pere P, Ahonen J, Vapaatalo H, Lindgren L.
Detrimental effect of dietary sodium and beneficial effect of dietary magnesium
on glomerular changes in cyclosporin-A-treated spontaneously hypertensive rats.
Nephrol Dial Transplant 1998 Apr;13(4):904-910.
Perticone F,
Borelli D, Ceravolo R, Mattioli PL. Antiarrhythmic short-term protective
magnesium treatment in ischemic dilated cardiomyopathy. J Am Coll Nutr.
1990;9(5);492-499.
Polk RE. Drug-drug interactions with ciprofloxacin
and other fluoroquinolones. Am J Med 1989 Nov 30;87(5A):76S-81S.
Abstract: Early investigational trials with new quinolone antibiotics
revealed two important drug-drug interactions: decreased fluoroquinolone
absorption when co-administered with magnesium-aluminum antacids and inhibition
of theophylline metabolism. Subsequent studies have investigated the mechanisms
of these interactions. With respect to the effect of antacids, the absorption of
all quinolones appears to be significantly reduced by antacids containing
magnesium and/or aluminum, and concomitant administration must be avoided. Other
cations, such as calcium, iron, and probably zinc, appear to interact in a
similar manner. Chelation between the quinolone and cation is the most likely
mechanism. With respect to the effect on theophylline metabolism, quinolones
inhibit specific cytochrome P-450 isozymes responsible for metabolism of
methylxanthines, although there are major differences between the quinolones.
Enoxacin is the most potent inhibitor, followed by ciprofloxacin, pefloxacin,
norfloxacin, and ofloxacin. Caffeine metabolism is also inhibited, although the
clinical significance is uncertain. Case reports describe renal failure
associated with concomitant administration of cyclosporine and ciprofloxacin,
although controlled trials have not demonstrated an interaction. Enoxacin has
little effect on warfarin metabolism, suggesting that other quinolones may not
affect warfarin disposition. Case reports of central nervous system toxicity
from administration of nonsteroidal anti-inflammatory agents and quinolones need
confirmation. Patients should be monitored closely when potential interacting
agents are used; it is probable that not all interactions have been identified.
Polk RE, Healy DP, Sahai J, Drwal L, Racht E. Effect of ferrous sulfate
and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers.
Antimicrob Agents Chemother 1989 Nov;33(11):1841-1844.
Abstract:
Cations such as magnesium and aluminum significantly impair the absorption of
ciprofloxacin. Twelve healthy adult male volunteers participated in this
four-way crossover study to investigate the effects of ferrous sulfate and
multivitamins with zinc on the absorption of ciprofloxacin. Doses of
ciprofloxacin (500 mg) were given 7 days apart and after an overnight fast. Dose
1 was administered alone (regimen A). The subjects then received either a
ferrous sulfate tablet (325 mg three times a day; regimen B) or a once-daily
multivitamin with zinc (regimen C) for 7 days; dose 2 of ciprofloxacin was then
given with the last dose of regimen B or C. Subjects were crossed over to the
alternate regimen for 7 days, and dose 3 of ciprofloxacin was again administered
with the last dose of regimen B or C. After a 7-day washout, dose 4 of
ciprofloxacin was given (regimen D). Ciprofloxacin concentrations were
determined by high-pressure liquid chromatography. The areas under the
concentration-time curve (AUCs) of ciprofloxacin for regimens A and D were not
significantly different (14.5 +/- 2.3 versus 15.7 +/- 2.8 micrograms.h/ml, mean
+/- standard deviation). The AUCs for regimen B (5.4 +/- 1.7 micrograms.h/ml)
and regimen C (11.3 +/- 2.4 micrograms.h/ml) were significantly different from
the AUCs for regimens A and D. Peak concentrations of ciprofloxacin with regimen
B were below the MIC for 90% of strains of many organisms normally considered
susceptible. Ferrous sulfate and multivitamins with zinc significantly impaired
the absorption of ciprofloxacin. The effect of ferrous sulfate is likely to be
clinically significant; the responsible component of multivitamins with zinc
requires additional study.
Propst A, Propst T, Judmaier G. Comparison of
the effects of ranitidine effervescent tablets and magnesium hydroxide-aluminium
oxide on intragastric acidity. A single-centre, randomised, open cross-over
study. Arzneimittelforschung 1996 Jun;46(6):621-624.
Abstract: In
previous studies measuring intragastric pH in healthy volunteers it was shown
that there was a faster onset of action with ranitidine (CAS 66357-35-5) 300 mg
effervescent tablets (Zantac) compared to standard tablets. In a single-centre,
randomised, open cross-over study the pH-values obtained over 6 h following the
administration of one ranitidine 150 mg effervescent tablet were compared with
those after aluminium oxide-magnesium hydroxide (algeldrate, CAS 1330-44-5,
Al-Mg-hydroxide) 10 ml and placebo in healthy volunteers. 24 healthy male
subjects between 19 and 32 years of age entered the study, 19 subjects were
available for all three measurements. After an overnight fast, intragastric pH
was monitored for 7 h using a glass electrode and a digital data recorder. The
time in % during which the pH was > or = 3.5 and the area under the curve of
the obtained pH-curves were compared. There was a highly statistically
significant difference between ranitidine effervescent tablets versus
Al-Mg-hydroxide and placebo whereas there was no such difference between
Al-Mg-hydroxide and placebo. The onset of action of ranitidine effervescent
tablets was almost immediate. It is concluded that there was a clear superiority
of ranitidine effervescent tablets in healthy volunteers and it is suggested
that pH-metry in patients with acidity-related diseases should be investigated
for a better understanding of the function of effervescent tablets.
Pronsky Z. Powers and Moore's Food-Medications Interactions.
Ninth Edition. Food-Medication Interactions. Pottstown, PA, 1991.
Rasmussen HS. Clinical intervention studies on magnesium in myocardial
infarction. Magnesium. 1989;8(5-6):316-325. (Review)
Rasmussen
HS, Gronbaek M, Cintin C, Balslov S, Norregard P, McNair P. One-year death rate
in 270 patients with suspected acute myocardial infarction, initially treated
with intravenous magnesium or placebo. Clin Cardiol. 1988
Jun;11(6):377-381.
Abstract: In a double-blind, placebo-controlled study,
273 patients with suspected acute myocardial infarction (AMI) were randomized to
receive either 48-h magnesium (Mg) or placebo therapy intravenously, initiated
immediately on admission to hospital. We describe the results from a 1-year
survey in 270 of the patients, who were available for follow-up. Patients were
equally divided: 135 received Mg and 135 received placebo. Mg treatment was
associated with a marked reduction in 1-year death rate from 32% in the placebo
group to 20% in the Mg group (p = 0.018). If only death from ischemic heart
disease is considered, the figures were 28% in the placebo group as opposed to
15% in the Mg group (p = 0.006). This reduction was mainly due to a reduction in
mortality during the initial 30 days after inclusion in the study (17% vs. 7%),
after which the difference in mortality between the two groups did not reach
statistical significance (18% vs. 15%, p = 0.56). The beneficial effect of Mg on
mortality was partly linked to a reduced incidence of arrhythmias (27% vs. 16%),
and partly to a reduced incidence of infarction (63% vs. 48%) during the initial
hospitalization. However, factors unknown to us were also involved, as revealed
by a remaining statistically significant partial regression coefficient, when
sex, age, cardiovascular history, development of AMI, and development of
arrhythmias were considered. It is concluded that intravenous Mg treatment is
beneficial to patients with acute ischemic heart disease and should be adopted
as part of the routine treatment of these patients.
Rob PM. [Magnesium
deficiency after kidney transplantation and cyclosporine therapy]. Fortschr
Med 1996 Apr 10;114(10):125-126. [Article in German]
Robinson C,
Weigly E. Basic Nutrition and Diet Therapy. New York: MacMillan, 1984.
Roe DA. Diet and Drug Interactions. New York: Van Nostrand
Reinhold, 1989.
Roe DA. Drug-induced Nutritional Deficiencies.
2nd ed. Westport, CT: Avi Publishing, 1985.
Roe DA. Risk factors in
drug-induced nutritional deficiencies. In: Roe DA, Campbell T, eds. Drugs and
Nutrients: The Interactive Effects. New York: Marcel Decker, 1984: 505-523.
Ryan MP. Interrelationships of magnesium and potassium homeostasis.
Miner Electrolyte Metab 1993;19(4-5):290-295.
Abstract: The
interrelationships of magnesium (Mg) and potassium (K) homeostasis are reviewed.
Evidence from clinical and experimental studies including whole animal and cell
culture experiments indicate that (1) homeostasis of Mg and K are closely
related in the whole organism, (2) deficiencies of Mg and K frequently co-exist
with gastrointestinal and especially renal losses from diuretic and nephrotoxic
drug treatment being mainly responsible, and (3) Mg is required for maintenance
of normal cellular K. Evidence from many laboratories indicate that Mg has
direct effects at a cellular level on K transport. These include effects on
Na-K-ATPase, Na-K-Cl cotransport, K channels, charge screening and permeability
effects on membranes. New data on positive correlations between Mg and K in
cardiac tissue, skeletal muscle and lymphocytes from patients undergoing
cardiopulmonary bypass are presented. Interrelationships in Mg and K in cardiac
tissue have probably the greatest clinical significance in terms of arrhythmias,
digoxin toxicity, and myocardial infarction. Future studies will be aimed at
elucidating mechanisms of Mg-K interrelationships at a cellular level using new
techniques with the ability to detect concentrations and modulations of free
intracellular Mg.
Sadowski DC. Drug interactions with antacids.
Mechanisms and clinical significance. Drug Saf 1994 Dec;11(6):395-407.
Schwanstecher M, Loser S, Rietze I, Panten U. Phosphate and
thiophosphate group donating adenine and guanine nucleotides inhibit
glibenclamide binding to membranes from pancreatic islets. Naunyn
Schmiedebergs Arch Pharmacol 1991 Jan;343(1):83-89.
Abstract: In
microsomes obtained from mouse pancreatic islets, the Mg complex of adenosine
5'-triphosphate (MgATP) increased the dissociation constant (KD) for binding of
[3H]glibenclamide by sixfold. In the presence of Mg2+, not only ATP but also
adenosine 5'-0-(3-thiotriphosphate) (ATP gamma S), adenosine 5'-diphosphate
(ADP), guanosine 5'-triphosphate (GTP), guanosine 5'-diphosphate (GDP),
guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S) and guanosine
5'-0-(2-thiodiphosphate) (GDP beta S) inhibited binding of [3H]glibenclamide.
These effects were not observed in the absence of Mg2+. Half maximally effective
concentrations of the Mg complexes of ATP, ADP, ATP gamma S and GDP were 11.6,
19.0, 62.3 and 90.1 mumol/l, respectively. The non-hydrolyzable analogues
adenosine 5'-(beta,gamma-imidotriphosphate) (AMP-PNP) and guanosine
5'-(beta,gamma-imidotriphosphate) (GMP-PNP) did not alter [3H]glibenclamide
binding in the presence of Mg2+, MgADP acted much more slowly than MgATP and
both MgADP and MgGDP did not inhibit [3H]glibenclamide binding when the
concentrations of MgATP and MgGTP were kept low by the hexokinase reaction.
Development of MgATP-induced inhibition of [3H]glibenclamide binding and
dissociation of [3H]glibenclamide binding occurred at similar rates. However,
the reversal of MgATP-induced inhibition of [3H]glibenclamide binding was slower
than the association of [3H]glibenclamide with its binding site. Exogenous
alkaline phosphatase accelerated the reversal of MgATP-induced inhibition of
[3H]glibenclamide binding. MgATP enhanced displacement of [3H]glibenclamide
binding by diazoxide. The data suggest that sulfonylureas and diazoxide exert
their effects by interaction with the same binding site at the sulfonylurea
receptor and that protein phosphorylation modulates the affinity of the
receptor.
Schultes G.[High doses of magnesium in the treatment of angina
pectoris.] Fortschritte der Medizin. 1991; 109(35); 81. [Article in
German]
Shaheen BE, Cornish LA. Magnesium in the treatment of acute
myocardial infarction.Clinical Pharmacy. 1993 Aug;12(8):588-596. (Review)
Shechter M, Merz CN, Paul-Labrador M, Meisel SR, Rude RK, Molloy MD,
Dwyer JH, Shah PK, Kaul S. Oral magnesium supplementation inhibits
platelet-dependent thrombosis in patients with coronary artery disease. Am J
Cardiol. 1999 Jul 15;84(2):152-156.
Abstract: The use of magnesium in
the treatment of acute myocardial infarction remains controversial despite
preliminary experimental evidence that magnesium plays a beneficial role as a
regulator of thrombosis. This study examines whether oral magnesium treatment
inhibits platelet-dependent thrombosis (PDT) in patients with coronary artery
disease (CAD). In a randomized prospective, double-blind, crossover, and
placebo-controlled study, 42 patients with CAD (37 men, 5 women, mean age 68 +/-
9 years) on aspirin received either magnesium oxide tablets (800 to 1,200
mg/day) or placebo for 3 months (phase 1) followed by a 4-week wash-out period,
and the crossover treatment for 3 months (phase 2). PDT, platelet aggregation,
platelet P-selectin flow cytometry, monocyte tissue factor procoagulant activity
(TF-PCA), and adhesion molecule density were assessed before and after each
phase. PDT was evaluated by an ex vivo perfusion model using the Badimon
chamber. Median PDT was significantly reduced by 35% in patients who received
magnesium versus placebo (delta change from baseline -24 vs 26 mm2/mm; p = 0.02,
respectively). There was no significant effect of magnesium treatment on
platelet aggregation, P-selectin expression, monocyte TF-PCA, or adhesion
molecules. Oral magnesium treatment inhibited PDT in patients with stable CAD.
This effect appears to be independent of platelet aggregation or P-selectin
expression, and is evident despite aspirin therapy. These findings suggest a
potential mechanism whereby magnesium may beneficially alter outcomes in
patients with CAD.
Starobrat-Hermelin B, Kozielec T. The effects of
magnesium physiological supplementation on hyperactivity in children with
attention deficit hyperactivity disorder (ADHD): Positive response to magnesium
oral loading test. Magnesium Res 1997 Jun;10(2):149-156.
Abstract:
Children with ADHD are 'a group at risk' as far as their further emotional and
social development and educational possibilities are concerned, and the
consequences of the lack of an appropriate therapy appears to be serious. Some
of these children do not respond to prevailing therapy methods. It is reported
that dietetic factors can play a significant role in the etiology of ADHD
syndrome, and magnesium deficiency can help in revealing hyperactivity in
children. The aim of our work was to assess the influence of magnesium
supplementation on hyperactivity in patients with ADHD. The examination
comprised 50 hyperactive children, aged 7-12 years, who fulfilled DSM IV
criteria for ADHD syndrome, with recognized deficiency of magnesium in the blood
(blood serum and red blood cells) and in hair using atomic absorption
spectroscopy. In the period of 6 months those examined regularly took magnesium
preparations in a dose of about 200 mg/day. 30 of those examined with ADHD
showed coexisting disorders specific to developmental age, and 20 of them showed
disruptive behaviour. The control group consisted of 25 children with ADHD and
magnesium deficiency, who were treated in a standard way, without magnesium
preparations. 15 members of this group showed coexisting disorders specific for
developmental age, and 10 members showed disruptive behaviour. Hyperactivity was
assessed with the aid of psychometric scales: the Conners Rating Scale for
Parents and Teachers, Wender's Scale of Behavior and the Quotient of Development
to Freedom from Distractibility. In the group of children given 6 months of
magnesium supplementation, independently of other mental disorders coexisting
with hyperactivity, an increase in magnesium contents in hair and a significant
decrease of hyperactivity of those examined has been achieved, compared to their
clinical state before supplementation and compared to the control group which
had not been treated with magnesium.
Sueta CA, Patterson JH, Adams KF
Jr. Antiarrhythmic action of pharmacological administration of magnesium in
heart failure: a critical review of new data. Magnes Res 1995
Dec;8(4):389-401.
Abstract: Congestive heart failure is characterized by
contractile dysfunction and frequent complex ventricular ectopy. Despite
advances in therapy, mortality from heart failure is substantial, estimated at
10-80 percent per year, and sudden death is common. Magnesium is the second most
common intracellular cation, strongly influences cardiac cell membrane function,
and is an important catalyst of many enzymatic reactions in the myocyte.
Epidemiological studies have implicated magnesium deficit in the genesis of
sudden death. Patients with congestive heart failure are predisposed to
magnesium deficit for many reasons, including neurohormonal activation, poor
gastrointestinal absorption, and drug therapy. Hypomagnesaemia is common in
these patients and has been linked to an increased frequency of complex
ventricular ectopy. Several early, uncontrolled studies have suggested a
beneficial effect of magnesium administration on ventricular arrhythmias in
patients with congestive heart failure. Two recent randomized, double blind,
placebo-controlled trials have shown that both intravenous and oral
administration of magnesium chloride results in a significant reduction in the
frequency and complexity of ventricular arrhythmias in patients with congestive
heart failure. Magnesium administration is well tolerated and serious adverse
effects are rare. The potential mechanisms of the antiarrhythmic action of
magnesium and limitations of the available data are discussed. The evidence
reviewed suggests that serum magnesium concentrations should be monitored and
corrected in patients with congestive heart failure. Ventricular arrhythmias may
respond to acute intravenous magnesium administration, which should be
considered as early therapy. Further study is needed to define magnesium dose
and the effect of concomitant potassium administration. A prospective clinical
trial is warranted to determine the chronic effects of magnesium administration
in patients with heart failure.
Suzuki T, Koizumi J, Moroji T, Shiraishi
H, Hori T, Baba A, Kawai N, Tada K. Effects of long-term anticonvulsant therapy
on copper, zinc, and magnesium in hair and serum of epileptics. Biol
Psychiatry 1992 Mar 15;31(6):571-581.
Taubert K, Keil G. [Pilot
study on the use of magnesium in the treatment of migraine and stress headache.]
Zeitschrift fur Arztliche Fortbildung. 1991; 85(1-2);67-68.
Teixeira MH, Vilas-Boas LF, Gil VM, Teixeira F. Complexes of
ciprofloxacin with metal ions contained in antacid drugs. J Chemother
1995 Apr;7(2):126-132.
Abstract: Simultaneous administration of antacids
containing magnesium or aluminium and ciprofloxacin or other quinolones
decreases the gastrointestinal absorption of those antibacterial agents. Current
speculation about the mechanism of this interaction has focused on drug-cation
chelation. The present study was designed to detect the protonation in solutions
and the formation of the complex species at the pH levels typical of the
gastrointestinal tract. It involves the study of ciprofloxacin in aqueous
solutions containing Al3+ and (or) Mg2+ by combining the results of
potentiometric and spectroscopic (1H nuclear magnetic resonance) techniques.
Calculations were only performed for data in the range 4.5 < pH < 5.5 (pH
levels typical of gastrointestinal tract) and the results of both methods are
made self-consistent, assuming an equilibrium model including complex species
MHL, MLOH (where H2L denotes ciprofloxacin and M is Al3+ or Mg2+); their
formation constants are given.
Teixeira F, Geraldes CF, Gil VM, Helena
M, Teixeira SF. In vitro complexation of aluminum and magnesium by cimetidine
and ranitidine. A nuclear magnetic resonance study. Gastroenterol Clin Biol
1984 Nov;8(11):879-80. (Letter)
Thompson CB, et al. Association
between cyclosporine neurotoxicity and hypomagnesemia. Lancet
1984;ii:1116.
Toffaletti J. Electrolytes, divalent cations, and blood
gases (magnesium). Analyt Chem 1991 63(12):192R-194R.
Trovato A,
Nuhlicek DN, Midtling JE. Drug-nutrient interactions. Am Fam Physician
1991 Nov;44(5):1651-1658.(Review)
USDA. Composition of Foods. USDA
Handbook #8. Washington DC, ARS, USDA, 1976-1986.
Valdivieso A,
Mardones JM, Loyola MS, Cubillos AM. [Hypomagnesemia associated with
hypokalemia, hyponatremia and metabolic alkalosis. Possible complication of
gentamycin therapy]. Rev Med Chil. 1992 Aug;120(8):914-919. [Article in
Spanish]
Abstract: Hypomagnesemia is a serious abnormality with different
causes and usually associated to other disorders of electrolyte metabolism. We
report a female patient developing hypomagnesemia after administration of
gentamycin. This was associated to severe hypokalemia, hyponatremia and
metabolic alkalosis. Possible pathogenetic mechanisms and therapeutic measures
are discussed.
Watkins DW, Khalafi R, Cassidy MM, Vahouny GV.
Alterations in calcium, magnesium, iron, and zinc metabolism by dietary
cholestyramine. Dig Dis Sci 1985 May;30(5):477-482.
Abstract:
Cholestyramine is an effective drug for the reduction of plasma cholesterol
because of its ability to sequester intestinal bile acids. Since metabolic
alterations, including diminished intestinal absorption of vitamin D and
osteomalacia have been reported with long-term use of this resin, the influence
of cholestyramine on dietary balance of four mineral elements has been
investigated. Wistar-strain rats were fed either a 2% cholestyramine or control
diet for one month. Dietary intakes and fecal and urinary excretions of calcium,
magnesium, iron, and zinc were determined using atomic absorption
spectrophotometry during three, 3-day balance periods. Cholestyramine-fed rats
had a net negative balance for calcium and a lower net positive balance for
magnesium, iron, and zinc than the controls. Other effects of cholestyramine
were an increased urinary excretion of calcium and magnesium, a decreased
urinary zinc, and an alkalinization of urine. Blood and tissue cation content
was unchanged except for a reduction in serum magnesium with resin feeding.
Alterations in calcium, magnesium, and zinc metabolism might be explained by
inadequate vitamin D absorption from the intestine followed by an increased
secretion of parathyroid hormone. A diminished iron absorption due to resin
binding could account for the reported disturbance in iron balance.
Weisinger JR, Bellorin-font, E. Magnesium and phosphorus. Lancet
1998 Aug 1;352(9125):391-396. (Review)
Werbach MR. Foundations of
Nutritional Medicine. Tarzana, CA: Third Line Press, 1997. (Review).
Whang R, Oei TO, Watanabe A. Frequency of hypomagnesemia in hospitalized
patients receiving digitalis. Arch Intern Med 1985 Apr;145(4):655-656.
Abstract: We examined the frequency of hypokalemia and hypomagnesemia in
patients receiving digitalis. Serum sodium, magnesium, and potassium levels were
determined in 136 serum samples sent to the laboratory for digoxin assay.
Hyponatremia (less than or equal to 130 mEq/L) occurred most frequently (21%),
followed by hypomagnesemia (less than or equal to 1.25 mEq/L) in 19%,
hypokalemia (less than or equal to 3.5 mEq/L) in 9%, and hypermagnesemia
(greater than or equal to 2.25 mEq/L) in 7%. The twofold frequency of
hypomagnesemia (19%) contrasted with hypokalemia (9%) indicates that clinicians
are more attuned to avoiding hypokalemia than hypomagnesemia in patients
receiving digitalis. Because hypokalemia and/or hypomagnesemia may contribute to
the toxic effects of digitalis, ourobservation suggests that hypomagnesemia may
be a more frequent contributor than hypokalemia to induction of toxic reactions
to digitalis. Routine serum magnesium determination in patients receiving
digitalis, who often are also receiving potent diuretics, may assist in
identifying additional patients at risk for the toxic effects of digitalis.
Whang R, Whang DD, Ryan MP. Refractory potassium repletion-a consequence
of magnesium deficiency. Arch Intern Med 1992;152:40-45.
Abstract:
Experimental and clinical observations support the view that uncorrected
magnesium (Mg) deficiency impairs repletion of cellular potassium (K). This is
consistent with the observed close association between K and Mg depletion.
Concomitant Mg deficiency in K-depleted patients ranges from 38% to 42%.
Refractory K repletion due to unrecognized concurrent Mg deficiency can be
clinically perplexing. Refractory K repletion as a consequence of Mg deficiency
may be operative in patients with congestive failure, digitalis toxicity,
cisplatin therapy, and in patients receiving potent loop diuretics. Therefore,
we recommend that: (1) serum Mg be routinely assessed in any patients in whom
serum electrolytes are necessary for clinical management and (2) until serum Mg
is routinely performed consideration should be given to treating hypokalemic
patients with both Mg as well as K to avoid the problem of refractory K
repletion due to coexisting Mg deficiency.
Young IS, Goh EM, McKillop
UH, Stanford CF, Nicholls DP, Trimble ER. Magnesium status and digoxin
toxicity. Br J Clin Pharmacol. 1991 Dec;32(6):717-721.
Abstract: 1.
Eighty-one hospital patients receiving digoxin were separated into groups with
and without digoxin toxicity using clinical criteria. Serum digoxin, sodium,
potassium, calcium, creatinine, magnesium and monocyte magnesium concentrations
were compared. 2. Subjects with digoxin toxicity had impaired colour vision (P
less than 0.0001, Farnsworth-Munsell 100 hue test) and increased digoxin levels
(1.89 (1.56-2.21) vs 1.34 (1.20-1.47) nmol l-1, P less than 0.01) (mean (95%
confidence limits], though there was considerable overlap between two groups. 3.
Subjects with digoxin toxicity had lower levels of serum magnesium (0.80
(0.76-0.84) vs 0.88 (0.85-0.91) mmol l-1, P less than 0.01) and monocyte
magnesium (6.40 (5.65-7.16) vs 8.76 (7.81-9.71) mg g-1 DNA, P less than 0.01),
but there were no significant differences in other biochemical parameters. A
greater proportion of toxic subjects were receiving concomitant diuretic therapy
(20/21 vs 37/60, P less than 0.05). 4. Magnesium deficiency was the most
frequently identified significant electrolyte disturbance in relation to digoxin
toxicity. In the presence of magnesium deficiency digoxin toxicity developed at
relatively low serum digoxin concentrations.
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