Magnezijum sulfat (Magnesii sulfas heptahydricum solutio)

Magnezijum sulfat (Magnesii sulfas heptahydricum solutio)

MINERALNI PREPARATI MAGNEZIJUMA – MAGNEZIJUM SULFAT:

RASTVORI MAGNEZIJUM SULFATA 10% – 40% (100 – 400 mg/ g),

MAGNEZIJUM SULFAT 100% monokomponentni prašak.

Magnesii sulfas solutio 10% – 40% (Magnesium sulfas heptahydricum),

Magnesii sulfas pulvis.

– namenjeni za prevenciju infarkta miokarda i hipomagnezijemije, kod hipomagneziemije (E83.4) različite etiologije, kao izvori elektrolita, laksativi. Preparat u kom je magnezijum (Mg2+potpuno jonizovan, sa konstantom stabilnosti 0.

MINERALNI PREPARATI MAGNEZIJUMA – MAGNEZIJUM SULFAT:

RASTVORI MAGNEZIJUM SULFATA 10% – 40% (100 – 400 mg/ g),

MAGNEZIJUM SULFAT 100% monokomponentni prašak.

Magnesii sulfas solutio 10% – 40% (Magnesium sulfas heptahydricum),

Magnesii sulfas pulvis.

 

ATC:

A06AD04 – droge za konstipaciju, osmotski aktivni laksativi, magnezijum sulfat,

A12CC02 – mineralni suplementi, magnezijum sulfat,

B05XA05 – rastvori elektrolita,

D11AX05 – dermatologici,

V04CC02 – dijagnostici, test prolaznosti žučnih kanala,

V60AB – monokomponentni homeopatik,

V60B – antropozofik.

 

 U skladu sa:

Eu. Ph. 8,  01.07.2015. monografijom:01/2008:0044 corrected 6.0: 0044 Magnesium sulfate heptahydrate (Magnesii sulfas heptahydricus)

Pharmacopée française 2002 ANSM: MAGNÉSIUM (SULFATE DE) HEPTAHYDRATÉ POUR PRÉPARATIONS HOMÉOPATHIQUES

MAGNESIA SULFURICA POUR PRÉPARATIONS HOMÉOPATHIQUES

Magnesii sulfas heptahydricus ad praeparationes homoeopathicas

HAB: Magnesium sulfuricum Urtinktur D1 Dilution Ph. Eur. Method 3.1.1 (HAB 5a) Class A or Class B,

USP 29: Magnesium sulfate

Mineralni preparati u tečnom obliku (nerazblaženi ili razblaženi) za oralnu i lokalnu (topikalnu) upotrebu.

 

a) Magnesii sulfas solutio 10%, 20%, 33%, 40% (Magnesium sulfate heptahydrate dilution 10%, 20%, 33%, 40%),

 

Sastav:

sadrži magnezijum sulfat p.a. (pro analysi – analitičke čistoće 99,9%)

Molecular formula: MgSO4 x 7H2O  Molecular weight ; 246.47456 (heptahydrate) H14MgO11S

a) Magnesii sulfas solutio 10% – 40% 100 – 400 mg magnezijum sulfata/ grama rastvora (100 – 400 g u 100g rastvora),

b) Magnesii sulfas pulvis 100% magnezijum sulfat.

Magnezijum sulfat ispoljava mnogobrojna istražena dejstva.

 

Sadržaj:

sadrži magnezijum sulfat p.a. (pro analysi – analitičke čistoće 99,9%)

Molecular formula: MgSO4 x 7H2O  Molecular weight 95.21 (anhydrous); 246.47456 (heptahydrate) H14MgO11S

 

a) Magnesii sulfas solutio 10% – 40% 100 – 400 mg magnezijum sulfata/ grama rastvora (xx mmol – xxx mmol 100g rastvora),

b) sterilna voda (aqua sterilisata).

 

Magnezijum se označava jedinicom miliekvivalent na litar (mEq/L) ili milimol po litru (mmol/L). 1 gram MgSO4 x7H2O sadrži 4 mola elementarnog Mg.

 

Normalne vrednosti su :

odrasli: 0.66 – 1.07 mmol/L (1.6 – 2.6 mg/dL)

0.7-1 mmol/L (1,5 – 2 mEq/ L ; 1.7 – 2.4 mg/ dL)

Kritična vrednost : < 1,0 ;  > 4,9 mg/ dL.

Magnezijum je jedan od glavnih intracelularnih katjona. Za normalnu neuromuskularnu aktivnost potrebna je normalna koncentracija ekstracelularnog kalcijuma i magnezijuma.

Intracelularni magnezijum je važan kofaktor za razne enzime, transportere i nukleinske kiseline koje su neophodne za normalnu celularnu funkciju, replikaciju i energetski metabolizam.

 

Niska vrednost magnezijuma (< 0,65 mmol/L) u krvi može biti izazvana:

– gubitkom magnezijuma zbog dijareje, znojenja, povraćanja ili

– zbog nedovoljnog unosa magnezijuma hranom,

– gubitka magnezijuma zbog teških opekotina ili odvodnjavanja rane

– bolestima kao što su cistična fibroza, ciroza jetre, akutni pankreatitis, hipo i hipertiroidizam, hipoparatiroidizam,

– upotrebom lekova kao što su diuretici ili antibiotici,

– dobijanjem tečnosti IV putem bez dovoljno magnezijuma,

– alkoholizmom, hiperaldosteronizmom, dijabetičkom acidozom.

– velikim fizičkim naporima (planinari, biciklisti, drvoseče, …),

– trudnoćom.

 

Visoka vrednosti magnezijuma u krvi može biti izazvana:

– insuficijencijom bubrega,

– traumama kao što su opekotine, udesi ili operacije,

– nekontrolisanim dijabetesom,

– hiperparatiroidizam.

Indikacije: Mineralni preparati su namenjeni poboljšanju opšteg stanja organizma kroz razna naučno dokazana dejstva.

Upotreba kod profilakse hipomagnezijemije i hipomagnezijemije, kod infarkta miokarda.

 

Indikacije za upotrebu su:

– neuromuskularna preosetljivost (tremor, trzanje mišića, tetanije, grčevi),

– kardiološki problemi (tahikardija, aritmija, fibrilacija komore, u EKG-u produženje KT),

– gastrointestinalni problemi (ulcerozni kolitis, morbus Chron, celijakija, sindrom kratkog creva),

– kontinuirana upotreba diuretika ili nefrotoksičnih lekova,

 – opstipacija (konstipacija).

 

Ima jako dejstvo kod: hipomagnezijemije.

 

Upotrebljava se kao: izvor elektrolita, kod infarkta miokarda, poremećaja u radu jetre, probavnih smetnji, konstipacije, inkontinencije urina, poremećaja  mokrenja, kod problema sa prostatom, menstrualnih bolova, krvarenja, obilne vaginalne sekrecije, nervnih tegoba, osmotski laksans, kod prevencije i tretmana eklampsije, …

 

Doziranje i način primene:

individualno u zavisnosti od godina starosti i stanja organizma

Magnesii sulfas solutio 10% – 40%:

(10% = 100 mg/ g; 20% = 200 mg/ g; 33,3% = 333 mg/ g; 40% = 400 mg/ g   Mg2+ u obliku magnezijum sulfata).

2 g (55 kapi) podeljeno u 2 do 4 doze.

Mineralni  preparati MAGNEZIJUM SULFAT HSS i TM:

pojedinačna doza: 0,5-1 g, preporučena dnevna doza (PDD): 2 g.

Oralna (sat vremena pre obroka) i lokalna primena.

Upotreba na koži: aplicirati na obolelo mesto u tankom sloju ili obliku impregniranog zavoja.

 

Napraviti pauzu posle 4 nedelje neprekidne upotrebe.

Po preporukama, preparat postiže najbolje efekte pri upotrebi od 8 do 12 nedelja, duža upotreba je bezbedna uz pauze.

Toksičnost: akutna toksičnost: kvantitativni podaci o toksičnosti nisu dostupni, toksični uticaji očekuju se samo kod velikih doza, nakon gutanja većih količina: mučnina, povraćanje, proliv.

Kontraindikacije: preosetljivost na aktivne supstance, preosetljivost na jedinjenja magnezijuma, bubrežna insuficijencija, anurija, dehidracija, poremećaj u srčanoj provodljivosti, intestinalna opstrukcija, inflamatorna bolest creva, abdominalni bol nepoznatog porekla, bubrežna insuficijencija, elektrolitička neravnoteža (poremećaj elektrolita) i hipermagnesemia.

U većim koncentracijama nadražuje GIT, izaziva proliv, slabost, hiporefleksiju, respiratornu depresiju i komu, smetnje u kardiovaskularnom sistemu (hipotenzija).

Interakcije: magnezijumove soli utiču na apsorpciju lekova (tetraciklina, Chinolone, …) i ne treba ih uzimati zajedno već u razmaku od 2 do 4 sata.

Čuvanje: na tamnom, suvom i hladnom mestu do 20˚C, van domašaja dece i izlaganja EM zračenju, u dobro zatvorenoj originalnoj ambalaži.

 Rok upotrebe: 1 godina, posle prvog otvaranja 6 meseci.

 Pakovanje: 50 g i 100 g, farmaceutske braon bočice standarno, 250 g, 500 g, 1000 g i 5000 g na zahtev.

 

Nutritivne informacije:

MAGNEZIJUM SULFAT HSS i TM:

energetska vrednost u 100 mL: 0 kJ/ 0 kcal,

u preporučenoj dnevnoj dozi (PDD) 2 g: 0kJ/ 0 kcal,

suve materije (DR) više od

Magnesii sulfas solutio 10% – 40%.

10,0% – 40,0% (Fr. Ph.).

 

Bez konzervanasa, proteina, masti i ugljenih hidrata.

 

MAGNEZIJUM SULFAT HSS i TM su rukom rađeni proizvodi. 

Analizu na teške metale broj 146-353/06-15 od juna 2015. godine i analizu broj 147/05/16 od 16. maja 2016. godine izvršila CH analitička laboratorija. ANALIZA MgSO4 p.a.

CENOVNIK

Cena zavisi od količine magnezijum sulfata; obrazac za izračunavanje: 2 + (MgCl2 g% x 0,04) x 100 RSD

40% RSD – 280,00/ 50 g, 360,00/ 100 g,  sadrži 40 grama MgSO4 x7H2O u 100 grama rastvora,

33% RSD – 280,00/ 60 g, 330,00/ 100 g, sadrži 33 grama MgSO4 x7H2O u 100 u grama rastvora,

20% RSD – 240,00/ 50 g, 280,00/ 100 g,sadrži 20 grama MgSO4 x7H2O u 100  grama rastvora,

10% RSD – 220,00/ 50 g, 240,00/ 100 g, sadrži 10 grama MgSO4 x7H2O u 100  grama rastvora,

100% 33 grama MgSO4 x7H2O – RSD 132,00 monokomponentni prah (kristal), p.a. (analitičke) čistoće,

100% 100 grama MgSO4 x7H2O – RSD 400,00 monokomponentni prah (kristal), p.a. (analitičke) čistoće.

Podaci ažurirani oktobra 2016.

http://www.biljni-preparati.com/preparati/magnezijum-sulfat-magnesii-sulfas-heptahydricum-solutio/#top 

X X X X X

Epsom Salts BP

Last Updated on eMC 03-Mar-2016   Thornton & Ross Ltd 

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  • 1. Name of the medicinal product
  • 2. Qualitative and quantitative composition
  • 3. Pharmaceutical form
  • 4. Clinical particulars
  • 4.1 Therapeutic indications
  • 4.2 Posology and method of administration
  • 4.3 Contraindications
  • 4.4 Special warnings and precautions for use
  • 4.5 Interaction with other medicinal products and other forms of interaction
  • 4.6 Pregnancy and lactation
  • 4.7 Effects on ability to drive and use machines
  • 4.8 Undesirable effects
  • 4.9 Overdose
  • 5. Pharmacological properties
  • 5.1 Pharmacodynamic properties
  • 5.2 Pharmacokinetic properties
  • 5.3 Preclinical safety data
  • 6. Pharmaceutical particulars
  • 6.1 List of excipients
  • 6.2 Incompatibilities
  • 6.3 Shelf life
  • 6.4 Special precautions for storage
  • 6.5 Nature and contents of container
  • 6.6 Special precautions for disposal and other handling
  • 7. Marketing authorisation holder
  • 8. Marketing authorisation number(s)
  • 9. Date of first authorisation/renewal of the authorisation
  • 10. Date of revision of the text

 

  1. Name of the medicinal product

Epsom Salts BP

  1. Qualitative and quantitative composition

Magnesium Sulfate Heptahydrate BP 100% W/W.

  1. Pharmaceutical form

Crystals or Crystalline Powder.

Brilliant colourless crystals or a white crystalline powder.

  1. Clinical particulars

4.1 Therapeutic indications

  1. For the relief of occasional constipation.
  2. For the relief of pain from sprains, bruises and boils.

4.2 Posology and method of administration

  1. Oral. As a dilute solution.
  2. Cutaneous. As a concentrated solution or paste.

Recommended doses and dosage schedules

Indication 1

Adults and children over 12 years: 5-15g (1 – 3 teaspoons) to be taken as required in 250 ml of water, which may be flavoured with citrus juices.
The elderly: To be used with caution, not exceeding the adult dose.

Indication 2

As a wet dressing suitable for all ages: Dissolve one tablespoonful in a small cupful of warm water and apply with lint or cotton wool as required.

4.3 Contraindications

Internal use is contraindicated in all cases of acute gastro-intestinal conditions (except constipation), renal impairment, and in children with intestinal parasitic diseases.

Do not give internally to children under 12 years old.

Hypersensitivity to magnesium sulfate.

4.4 Special warnings and precautions for use

Keep out of the sight and reach of children.

Avoid prolonged use.

If symptoms persist for longer than 7 days consult your doctor.

Laxatives should not be taken where there is severe abdominal pain.

Osmotic laxatives may produce dehydration so sufficient water should always be taken.

Use with caution in elderly or debilitated patients.

4.5 Interaction with other medicinal products and other forms of interaction

Oral magnesium salts have the properties of antacids therefore it is recommended that this product is not taken within two to four hours of any other medicinal products to minimise interactions.

There is a risk of metabolic alkalosis when oral magnesium salts are given with polystyrene sulphonate resins. Magnesium salts, taken internally, potentiate the effects of competitive neuromuscular blocking drugs such as tubocurarine.

Magnesium salts may interfere with the absorption of many drugs including (but not limited to) ACE inhibitors (captopril, enalapril, fosinopril); antibacterials and antifungals (azithromycin, cefaclor, cefpodoxime, isoniazid, itraconazole, ketoconazole, methenamine, tetracyclines, rifampicin and quinolone antibacterials); antivirals (atazanavir and tipranavir); antihistamines (fexofenadine); bisphosphonates; corticosteroids (deflazacort); dipyridamole; antiepileptics (gabapentin and phenytoin); ulcer healing drugs (lansoprazole); levothyroxine; mycophenolate; rosuvastatin; antipsychotics (sulpiride and phenothiazines); chloroquine and hydroxychloroquine; penicillamine, and digoxin if given concomitantly.

Alkaline urine may result, increasing excretion of aspirin. Magnesium salts possibly reduce absorption of bile acids and may reduce absorption of eltrombopag (give at least 4 hours apart). The plasma concentration of ulipristal may be reduced. Magnesium salts possibly reduce the plasma concentration of erlotinib (give at least 4 hours before or 2 hours after erlotinib).

4.6 Pregnancy and lactation

Do not use in pregnancy or while breastfeeding.

4.7 Effects on ability to drive and use machines

No or negligible influence.

4.8 Undesirable effects

Hypermagnesaemia may occur after prolonged usage of magnesium sulfate as a purgative. May cause colic. Ingestion of magnesium salts may cause gastrointestinal irritation and watery diarrhoea. Rarely paralytic ileus has been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Though magnesium is poorly absorbed following oral administration there may be sufficient accumulation to produce toxic effects if given to a patient with impaired renal function.

Symptoms of hypermagnesaemia may include extreme thirst, a feeling of heat, hypotension due to vasodilation, drowsiness, nausea, vomiting, gastrointestinal irritation and watery diarrhoea, flushing, confusion, slurred speech, double vision and muscle weakness, loss of tendon reflexes due to neuromuscular blockade, CNS and respiratory depression, cardiac arrhythmias (including bradycardia), coma and cardiac arrest.

Treatment of mild hypermagnesaemia is usually limited to restricting magnesium intake. In severe hypermagnesaemia, ventilatory and circulatory support may be required. Slow intravenous injection of calcium gluconate (10 to 20ml of 10% calcium gluconate) is recommended to reverse the effects on cardiovascular and respiratory systems. If renal function is normal, adequate fluids should be given to promote renal magnesium clearance. This may be increased by the use of furosemide. Haemodialysis using a magnesium-free dialysis solution effectively removes magnesium, and this may be necessary in patients with renal impairment, or for whom other methods prove ineffective.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

A06A D04 Osmotically acting laxatives

Magnesium sulfate is a saline purgative.

It can be employed locally in various inflammatory conditions, due to its osmotic action.

5.2 Pharmacokinetic properties

When a dilute solution of magnesium sulfate is taken by mouth, the absorption of water from the intestine is reduced, and the bulky fluid contents distend the bowel. Active peristalsis is excited and evacuation of the contents of the intestine results.

Magnesium salts cause the secretion of cholecystokinin from the duodenal mucosa, it has been suggested that cholecystokinin – mediated pancreatic secretion and increased secretion and motility of the small intestine and colon may contribute to the cathartic effect

Magnesium sulfate causes bowel evacuation normally within 2-4 hours.

5.3 Preclinical safety data

No data of relevance which is additional to that already included in other sections of the SPC.

  1. Pharmaceutical particulars

6.1 List of excipients

None.

6.2 Incompatibilities

Magnesium sulfate is incompatible with polymyxin B sulfate, with sodium and potassium tartrates, with soluble phosphates and arsenates and with alkali carbonates and bicarbonates in concentrated solution

6.3 Shelf life

36 months unopened

6.4 Special precautions for storage

Do not store above 25°C. Store in the original package.

6.5 Nature and contents of container

300gm: Polypropylene securitainer with LDPE/HDPE white cap

6.6 Special precautions for disposal and other handling

None.

  1. Marketing authorisation holder
  2. C. M. Ltd.

Linthwaite Laboratories

Huddersfield

HD7 5QH

  1. Marketing authorisation number(s)

PL: 12965/0023

  1. Date of first authorisation/renewal of the authorisation

20.08.93

  1. Date of revision of the text

22/02/2016

X X X X X

ANALIZA MAGNEZIJUM SULFAT p.a. 

MAGNESIUM

Dosage ADI=400-800 mg

(Davies, S., and Stewart, A. 1990. Nutritional Medicine. Avon Books, New York. 509pp.)

PTD=6,000 mg/day

RDA=40-400 mg/day

Total Plants: 538  Total Activities: 65

Activity: abecedno

antiaggregant 400 mg/day, antialcoholic, antianginal 400 mg/day, antianorectic, antianxiety 400 mg/day, antiarrhythmic 400 mg/day, antiarthritic, antiasthmatic, antiatherosclerotic 400 mg/day, anticephalagic, antiCFS, anticlimacteric 500-750 mg/day, anticonvulsant, anticoronary 400 mg/day, antidepressant, antidiabetic 400-800 mg/man/day, antidysmenorrheic 100 mg 4 x/day, antiendometriotic 500 mg/day, antienterotic, antiepileptic 450 mg/day, antifatigue, antifibromyalgic 200-300, mg, 3x/day, antigastrotic, antiglaucomic, antihyperkinetic, antihypertensive, antihypoglycemic, antiinflammatory 100 mg 4 x/day, antiinsomniac, antilithic, antiLyme 400-1,000 mg, antimastalgic, antimenopausal 500-750 mg/day, antimigraine 200 mg/day/man, antimitral-valve-prolapse, antiMS, antinephrolytic, antineurotic, antiosteoporotic 500-1,000 mg/day/wmn/orl, antiplaque 500-1,000 mg/day, AntiPMS 400-800 mg/day/wmn/orl, antiPMS 400-800 mg/day/wmn orl, antiRaynaud’s 280-350 mg/day, antiretinopathic 400 mg/day, antispasmodic, antispasmophilic 500 mg/day, antistress 500-750 mg/day, antistroke 400 mg/day, Antisyndrome-X 400 mg/man/day, anxiolytic 500-750 mg/day, Calcium-Antagonist, Cardioprotective, CNS-Depressant, diuretic, hypocholesterolemic 400 mg/day, hypotensive 260-500 mg/day, immunomodulator, insulinogenic 400 mg/day, laxative 300-500 mg/day, litholytic, myorelaxant 100 mg 4 x/day, neurotransmitter, tranquilizer 500-750 mg/day, uterorelaxant 100 mg 4 x/day, vasodilator

 

Reference:

Challem, J., Berkson, Burt, and Smith, Melissa Dianne. 2000. Syndrome X – The complete nutritional program to prevent and reservse insulin resistance. John Wiley & Sons, New York. 272 pp. $24.95

Davies, S., and Stewart, A. 1990. Nutritional Medicine. Avon Books, New York. 509pp.

Facciola, S. 1998. Cornucopia – A Source Book of Edible Plants. Kampong Publications, Vista CA. 713 pp.

Pizzorno, J.E. and Murray, M.T. 1985. A Textbook of Natural Medicine. John Bastyr College Publications, Seattle, Washington (Looseleaf).

Werbach, M. 1993. Healing with Food. Harper Collins, New York, 443 pp.

Magnesium sulfuricum Urtinktur D1 – 20 ml DHU

Magnesium Sulfuricum Urtinktur D1 Hanosan

Transdermal Magnesium Therapy

Magnesium Deficiency

Symptoms of Low Magnesium

For Healthcare Professionals

 

Uses

The following is a list of the primary uses of magnesium.

Asthma and Chronic Obstructive Pulmonary Disease (COPD): Magnesium helps to promote relaxation of the bronchial smooth muscles, thus opening the airways and easing breathing.

Cardiovascular Disease (CVD): Magnesium is essential for proper functioning of the entire cardiovascular system.

Acute myocardial infarction: People dying of heart attacks have lower magnesium levels than people of the same age dying of other causes. IV magnesium is a valued treatment for acute myocardial infarction.

The benefits of using magnesium are it:

– improves production within the heart;

– dilates the coronary arteries, which results in improved delivery of oxygen to the heart;

– reduces peripheral vascular resistance, which creates reduced demand on the heart;

– inhibits platelets from aggregating and forming blood clots;

– reduces the size of the infarct (blockage);

– improves heart rate andarrhythmias.

Angina: angina is caused be a spasming of a coronary artery and usually responds to magnesium supplementation. IV magnesium supplementation can also help with angina due to atherosclerosis by the same mechanisms as described above for myocardial infarctions.

Cardiac arrhythmia: The current understanding of why magnesium helps to treat arrhythmia is due to magnesium’s role in properpotassium levels. When these two electrolytes are out of balance or deficient, proper nerve and muscle firing cannot occur.

Cardiomyopathy: Several studies have shown that magnesium supplementation produces improvements in heart functioning for individuals with a variety of cardiomyopathies.

Congestive Heart Failure: is characterized by an energy depleted state and many CHF patients are deficient in both magnesium and Co Q10. Magnesium supplementation is also beneficial because many conventional treatments for CHF cause magnesium depletion.

High Blood Pressure: Population studies have shown a correlation between higher magnesium intake and lower blood pressure. Studies which have used magnesium as an intervention to treat high blood pressure show mixed results. Cases in which magnesium supplementation has been shown to be helpful is, first, when a patient is taking a diuretic which depletes magnesium. Second, when high blood pressure is associated with high renin output. Finally, magnesium may be helpful when a patient has elevated intracellular sodium or decreased intracellular potassium (measured by red blood cells studies). A 4 week trial of magnesium supplementation is often recommended to see if magnesium supplementation is beneficial.

Intermittent Claudication: is a peripheral vascular disease. Atherosclerosis causes this condition, and like coronary artery disease, peripheral vascular disease is also associated with a magnesium deficiency.

Low HDL Cholesterol Levels: Magnesium deficiency is associated with an increase in both LDL (bad) cholesterol and triglycerides and a decrease in HDL. *Mitral Valve Prolapse: Research has shown that 85% of patients with mitral valve prolapse have magnesium deficiency.

Prevention of Strokes and Transient Ischemic Attacks (TIAs): Blood vessels supplying the brain are particularly sensitive to magnesium status. Vascular spasming can result from magnesium deficiency and this spasming can sometimes cause strokes orTIAs. Supplementation with magnesium can cause relaxation in the vessels and improve blood flow to the brain. Magnesium can also protect against strokes just as it may reduce risk of heart attack.

Diabetes and Hypoglycemia: Magnesium plays a key role in the secretion and action of insulin. Without adequate magnesium levels, it is impossible for the body to properly control blood sugar levels. Magnesium may also helps to prevent diabetic sequelae such as retinopathy and heart disease. Diabetics may actually require more than the RDA for magnesium. Vitamin B6 is also critical for the transport of magnesium into cells and therefore must also be considered in a comprehensive treatment.

Eosinophilia-Myalgia Syndrome: This syndrome was first recognized in 1989 and in most cases is caused by contaminated L-tryptophan. It is characterized by early peripheral eosinophilia, severe muscle pain, inflammation, and in some cases neural and visceral involvement. It has been found that individuals with EMS have a selective decrease in skeletal muscle ATP concentration, possibly due to a magnesium deficiency (recall that magnesium plays a key role in ATP manufacturing). In preliminary studies, it appears that magnesium injections may be helpful in treating this disease.

Fatigue: Magnesium deficiency, even if subclinical, can lead to chronic fatigue syndrome. Studies have shown improvement of symptoms for individuals suffering from CFS with intramuscular injection of magnesium sulfate and also with oral magnesium andpotassium aspartate.

Fibromyalgia: Intracellular magnesium deficiency may be a contributing factor to fibromyalgia. One study shows that magnesium malate supplementation helps to improve the number and severity of tender points. Others suggest using magnesium chelated to the entire family of Kreb cycle intermediates.

Glaucoma: Magnesium supplementation has been shown to improve peripheral circulation and has benefited those suffering fromglaucoma in terms of improvements in visual fields.

Hearing Loss: There is an association between low magnesium and noise-induced hearing loss.

Kidney Stones: Magnesium increases the solubility of calcium in the urine, thereby preventing stone formation and also prevents recurrent stone formation. Concomitant use of vitamin B6 actually increases magnesium’s effectiveness even more. Magnesium citrate is the most effective form for this purpose.

Migraine and Tension Headaches: Due to magnesium’s role in blood vessel tone, magnesium deficiency is linked to tension andmigraine headaches. In fact, low levels of magnesium are found in the serum, saliva, and red blood cells of migraine sufferers. In addition, migraines are also linked to mitral valve prolapse. Changes in blood platelets which result from mitral valve prolapse cause the platelets to release substances that cause expansion in blood vessels in the head leading to migraines.

Osteoporosis: Calcium and magnesium go hand-in-hand in terms of their importance in treating and preventing osteoporosis. Women with osteoporosis have indicators of magnesium deficiency including low bone magnesium. In addition, the conversion of vitamin D to its more active form relies on adequate magnesium levels.

Pregnancy: One’s need for magnesium increases during pregnancy. Adequate magnesium during pregnancy is critical for the prevention of pre-eclampsia, pre-term delivery, and fetal growth retardation and supplementation decreases one’s risk of developing these conditions.

Premenstrual Syndrome and Dysmenorrhea: Red blood cell magnesium levels in those suffering from PMS symptoms are significantly lower than those who do not have PMS. Magnesium supplementation has shown beneficial effects in treating PMSsymptoms such as emotional instability, generalized aches and pains and lower premenstrual pain threshold. Effects are even greater when vitamin B6 and other nutrients are added to treatment.

Attention Deficit or Hyperactivity Disorder (ADD/ADHD): Symptoms of ADHD look a lot like symptoms of magnesium deficiency such as excessive fidgeting, anxious restlessness, psychomotor instability, and learning disabilities. In one study, 95% of the ADHD patients had magnesium deficiency when levels were measure in their serum, red blood cells, and hair. In another study, individuals who were supplemented with magnesium showed improvement in terms of hyperactivity compared to the control group.

Cancer: Magnesium is important in controlling growth of cells and may be helpful in treating cancer.

 

Deficiency Symptoms

Magnesium deficiency is common in the geriatric population as well as in women during the premenstrual period. Deficiency is often secondary to conditions that reduce absorption or increase secretion such as: high calcium intake, alcohol, surgery, diuretics, liver and kidney disease, and oral contraceptive pill use. Signs and symptoms of deficiency include:

-fatigue

-mental confusion

-irritability

-weakness

-heart disturbances

-problems in nerve conduction and muscle contraction

-muscle cramps

-loss of appetite

-insomnia

-predisposition to stress

 

Excess Symptoms

Magnesium excess is rare and is typically iatrogenic from IV magnesium, from laxatives or antacids containing magnesium, or intramuscular injections. Signs and symptoms of excess or toxicity may include:

-diarrhea (most common, does not occur with parenteral administration)

-drowsiness

-weakness

-lethargy

-nausea and vomiting

-hypotension

-urinary retention

-bradycardia

-respiratory depression

-depressed mental status

-electrocardiographic (ECG) abnormalities

-possibly death

Assessment Procedure

Low serum magnesium reflects end-stage deficiency as most of the body’s magnesium concentrates in the cells and not in the serum. The best test to detect deficiency is the level of magnesium in the red blood cells.

Prescribing Considerations

The different types of magnesium include magnesium oxide, gluconate, sulfate, chloride, and carbonate.

-Taking magnesium supplements with food is less likely to cause diarrhea.

-The recommended dosages varies based on age and health status. To determine what your specific requirements are talk to your naturopathic doctor or other trained medical professional.

-Infant: 40mg (under 6 months); 60mg (6-12 months)

-Child: 80mg (1-3 years); 120mg (4-6 years); 170mg (7-10 years)

-Adolescent: 270mg/ 280mg (Males/ Females 11-14 years);

400mg/ 300mg (Males/ Females 15-18 years)

-Adult: 350mg/ 280mg (Males/ Females 19+ years)

-Pregnancy: 320mg

-Lactation: 280mg

Safety

Children: No problems have been reported with normal intake in infants and children.

Pregnancy and Breastfeeding: No problems have been reported with normal intake during pregnancy and nursing.

Contraindications: individuals with impaired kidney function can accumulate magnesium (some medications such as aminoglycosides and amphotericin-B cause both renal tubular damage and magnesium depletion patterns); individuals with high-grade atrioventricular blocks or bifascicular blocks must avoid magnesium supplementation because it can slow cardiac conduction.

Precautions: Due to magnesium’s effect on blood sugar, for individuals with diabetes or hypoglycemia, it should be introduced slowly to prevent complications.

Nutrient Interactions

Nutrient Interactions include:

Alcohol – Hypomagnesemia is common in alcoholics due to increased renal excretion.

Calcium – High intake may decrease magnesium absorption.

Manganese – Concomitant magnesium use may be necessary during manganese supplementation.

Phosphate – High intake may decrease magnesium absorption. Separate intake by 2 hours.

Potassium – and magnesium deficiency often occur together and need to be treated concomitantly.

Vitamin B1 – One case report indicates that a patient developed cardiac beriberi with polyneuritis after protracted use of large amounts of magnesium trisilicate.

Vitamin B6 – is necessary for magnesium to enter cells. Using these two nutrients together may increase the therapeutic efficacy of magnesium supplementation.

Vitamin D – enhances the bioavailability of magnesium.

Zinc – supplementation may increase magnesium intake needs.

Resources

-Murray Michael T (2005) Encyclopedia of Nutritional Supplements, The Essential Guide for Improving Your Health Naturally, Prima Publishing.

-Hoffer Abram, Prousky Jonathan (2006) Naturopathic Nutrition, A Guide to Nutrient-Rich Food & Nutritional Supplements for Optimum Health, CCNM Press

-Medlineplus

– Bralley J Alexander and Lord Richard S (2005) Laboratory Evaluations in Molecular Medicine, Nutrients, Toxicants, and Cell Regulators Institute for Advances in Molecular Medince, GA

-Stargrove Mitchell Bebell, Treasure Jonathan, McKee Dwight L (2008) Herb, Nutrient, and Drug Interactions, Clinical Implications and Therapeutic Strategies. Mosby

Izvor: www.ndhealthfacts.org

X X X X X X

http://www.sigmaaldrich.com/catalog/product/sial/13142?lang=en&region=SX

http://www.sigmaaldrich.com/catalog/product/sial/63145?lang=en&region=SX&gclid=CMCu1NT6tssCFdW4GwodZgMLCw

http://www.chemicalbook.com/ChemicalProductProperty_EN_CB9667185.htm

Magnesium Sulfate

In the US, Magnesium Sulfate (magnesium sulfate systemic) is a member of the following drug classes: laxatives, minerals and electrolytes, miscellaneous anticonvulsants and is used to treat Hypomagnesemia, Seizure Prevention and Ventricular Arrhythmia.

US matches:
Magnesium sulfate
Magnesium sulfate granules
Magnesium Sulfate-Sodium Chloride injection
Magnesium sulfate injection
Magnesium sulfate Oral, Topical application, Route Not Applicable
Magnesium Sulfate in Dextrose Injection

USP

ATC (Anatomical Therapeutic Chemical Classification)
A06AD04,A12CC02,B05XA05,D11AX05,V04CC02

Molecular Weight
120

Therapeutic Categories
Dermatological agent

Mineral supplement

Laxative, osmotically acting

Used in electrolyte solutions

Diagnostic agent, test for bilde duct patency

Chemical Name
Sulfuric acid magnesium salt (1:1), x hydrate (USP)
Magnesii sulfas heptahydricus (PH: Ph. Eur. 8)
Magnesium Sulfate (PH: USP 37)
Magnesium sulfate heptahydrate (PH: Ph. Eur. 8)
Magnesium Sulfate Heptahydrate (PH: BP 2015

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Open Heart Visit this article Submit a manuscript Receive email alerts Contact us BMJ
Open Heart. 2018; 5(2): e000775.
Published online 2018 Jul 1. doi: 10.1136/openhrt-2018-000775
PMCID: PMC6045762
PMID: 30018772

Magnesium for the prevention and treatment of cardiovascular disease

Introduction

Magnesium is an essential mineral found in the body. It is naturally present in many foods and is also available as a dietary supplement.1 It serves as a cofactor in more than 300 enzymatic reactions, such as those responsible for regulating blood pressure, glycaemic control and lipid peroxidation. It is therefore also critical to the cardiovascular system.1 The adult body contains approximately 24 g of magnesium, with 50% to 60% present in bones with the rest being contained in soft tissues. Serum magnesium represents less than 1% of total body magnesium.2 In industrialised western countries, a low intake of magnesium often predisposes to a high prevalence of magnesium deficiency increasing the risk of cardiovascular events and cardiovascular death.3 This article aims to review of effect of magnesium deficiency on the cardiovascular system.

Biochemical interactions of magnesium in cardiovascular diseases

In recent studies of hospitalised patients, 42% were shown to be hypomagnesaemic.4 However, physicians request magnesium testing in only 7% of these patients.4 In a study conducted among patients in the intensive cardiac care unit, 53% of patients had mononuclear cell magnesium content below the lowest normal control.5

Clinically, serum magnesium is usually measured despite the fact that less than 1% of magnesium exists extracellularly; hence, serum magnesium does not always accurately reflect total body magnesium stores. In fact, serum magnesium levels may be normal despite depletion of total body magnesium content.5 In experimental settings, total body magnesium stores can be estimated by measuring retention of an oral or intravenous magnesium load; however, measurement is cumbersome and requires a 24-hour urine collection.6 7 In many instances, intracellular levels of magnesium serve as a better indicator for total body magnesium content compared with serum magnesium levels with the most accurate test being blood mononuclear cell magnesium.8 Intracellular mononuclear magnesium content also correlates better with cardiac magnesium status.9–12

Magnesium plays diverse roles in the pathogenesis of cardiovascular diseases on the biochemical and cellular levels. First, magnesium activates adenosine triphosphatase (ATPase), which is essential for cell membrane functioning and is also the energy source of the Na+–K+ pump.13 In rat models, magnesium deficiency has been shown to decrease the activity of the Na+–K+ pump, leading to an increase in intracellular sodium, which alters the membrane potential.14 In studying the sodium kinetic and membrane potential in the aorta of magnesium-deficient rats, Madden et al also showed that magnesium deficiency caused the membrane potential to be less polarised as a result of intracellular sodium accumulation, suggesting Na+–K+pump inhibition.15 This change in membrane potential has been hypothesised as a potential mechanism for causing arrhythmias. Magnesium is also known to be a cofactor important for the functioning of the enzymes in cardiac mitochondria. Additionally, magnesium has been demonstrated to modulate the potassium-proton exchange. Cation selectivity in sodium and potassium exchange for protons is highly dependent on magnesium. Thus, magnesium also protects against potassium loss. Intracellular magnesium deficiency may also cause an increase in intracellular sodium and calcium, which predisposes to arterial vasospasm, increased catecholamine release, increased fatty acids and lipids, as well as intravascular hypercoagulability.13 16

Furthermore, magnesium deficiency has been shown to play a role in inflammation in the rat model. Weglicki et al showed that during progression of magnesium deficiency, there is an increase in the serum levels of inflammatory cytokines interleukin-1, interluein-6 and tumour necrosis factor after 3 weeks of magnesium-deficiency diet.17 Magnesium deficiency also leads to an exaggerated response to immune stress and oxidative stress through activation of neuroendocrinological pathways. This inflammatory response predisposes to proatherogenic changes in lipoprotein metabolism, endothelial dysfunction, thrombosis and hypertension, contributing to the pathogenesis of metabolic syndrome as well as cardiovascular diseases.3

Epidemiology

Despite the importance of magnesium for the proper functioning of the cardiovascular system, surveys and studies have shown that dietary magnesium intake is often inadequate in the USA, which is consistent with the pattern observed in North European countries. Several factors were thought to be contributory, including the loss of magnesium during food processing, low magnesium content of vegetarian diets, metabolic effects exerted by pregnancy, osteoporosis medication therapy, alcoholism, stress, as well as the differing magnesium content in water.18 Human dietary requirement for essential minerals such as magnesium is not precisely known. Based on earlier balance studies, recommended dietary magnesium intakes were 300 to 354 mg/day for American women and 420 to 483 mg/day for American men.19 However, other studies have indicated that around 180 mg of magnesium per day may be enough to maintain positive magnesium balance.8 Actual intakes in American women and men are approximately 228 mg/day and 331 mg/day, respectively.19

Interestingly, there may be an association between cardiovascular disease and drinking water hardness due to its differing magnesium content. A study by Catling et al systematically reviewed observational epidemiological studies investigating the association between levels of drinking water hardness and cardiovascular disease. Of the seven studies included that examined drinking water magnesium and risk of death from cardiovascular disease, a pooled OR of 0.75 (95% CI 0.68 to 0.82) showed a statistically significant inverse correlation between magnesium and cardiovascular mortality.20 Additionally, changes in water hardness and a change to soft water tended to predispose to increased death rates from cardiovascular diseases including heart attacks and strokes.21 Autopsies of patients in soft-water areas who died from non-cardiac causes were found to have lower levels of magnesium in cardiac tissues, more coronary atheroma and evidence of myocardial ischaemia compared with residents living in hard water areas.21 22 However, the results of these studies may be confounded by the presence of many other trace elements found in hard water, such as calcium, which have also been found to have beneficial effects in preventing cardiovascular diseases. The magnesium content also differed among the hard waters in the studies, representing another confounding factor. Other studies have found no difference in cardiovascular disease morbidity and mortality in hard-water versus soft-water regions.23–27

Hypertension

Hypertension is a complex, multifactorial, heterogeneous disorder for which the exact aetiology has yet to be elucidated. Clinical and experimental trials have suggested that magnesium may play a role in the pathogenesis of hypertension by affecting arterial smooth muscle contraction. Magnesium is found mainly at the inner surface of cell membranes. Therefore, it plays a role in cell membrane permeability for sodium and calcium.28 Magnesium activates the Na+–K+–ATPase pump, which plays a major role in regulating sodium and potassium transport by moving potassium into the cells and sodium out of the cells. Alterations in vascular membrane magnesium can also result in leaky arterial and arteriolar membranes, thus contributing to the intracellular reduction of potassium and the gain of calcium and sodium. Increased intracellular calcium can then lead to hypertension, vasospasm, as well as potentiation of vasoconstrictor agents.29

A number of observational and experimental studies have supported the role of magnesium depletion in the pathogenesis of hypertension. Hypertension has been shown to develop in magnesium-deficient rats.30 In humans, a similar effect of magnesium deficiency was observed. A study by Shibutani et al studying a group of 380 Japanese junior high school students found that higher systolic blood pressure was associated with positive family history of hypertension as well as lower serum and erythrocyte magnesium levels, suggesting that magnesium deficiency may at least be partially responsible for a rise in blood pressure in the students with positive family history of hypertension, and that a genetic predisposition of hypertension maybe closely related to magnesium deficiency.31

Multiple studies have analysed the effect of magnesium supplementation on blood pressure. The effect of water with added magnesium and natural mineral water on blood pressure have been studied by dividing a group of 70 subjects with borderline hypertension into consuming water low in minerals, magnesium-enriched water and natural mineral water for 4 weeks. Among persons with initial low excretion of magnesium (suggesting magnesium deficiency), the subjects consuming the two waters containing magnesium after 4 weeks had a significant decrease in blood pressure.32 In a meta-analysis conducted by Zhang et al including randomised double-blind placebo control trials, magnesium supplementation at a median dose of 368 mg/day for a median duration of 3 months was found to significantly reduce systolic blood pressure (SBP) by 2.00 mm Hg (95% CI 0.43 to 3.58) and diastolic BP (DBP) by 1.78 mm Hg (95% CI 0.73 to 2.82). Additionally, these reductions were accompanied by 0.05 mmol/L (95% CI 0.03 to 0.07) elevation of serum magnesium compared with placebo.33 Similarly, Kass et al also found that magnesium supplementation leads to a small but clinically significant reduction in both DBP and SBP (SBP of 3 to 4 mm Hg and DBP of 2 to 3 mm Hg).34 These studies suggest that magnesium supplementation may be beneficial for lowering blood pressure in certain patient populations.

The effect of magnesium supplementation on patients taking diuretics has been studied in several trials. Hattori et al looked at 20 patients with essential hypertension receiving long-term thiazide diuretic treatment and 21 age-matched untreated patients. The diuretic group received magnesium supplementation for 4 weeks. There were significant decreases in intra-erythrocyte sodium content and mean blood pressure, as well as increases in red cell magnesium content in the diuretic group who received magnesium supplementation. The effect of magnesium on blood pressure reduction was more evident in the nine patients who were unresponsive to diuretic therapy.35 In a meta-analysis involving 135 hypertensive subjects on antihypertensive medications, Rosanoff and Plesset found that oral magnesium supplementation decreases both systolic (mean change of −18.7 mm Hg (95% CI −14.95 to −22.45)) and diastolic blood pressures (−10.9 mm Hg (95% CI −8.73 to −13.1)).36

Cardiomyopathy

Magnesium deficiency has been implicated in the cause of cardiomyopathy in both animal models and studies involving humans. In animal models, hamsters fed a magnesium-deficient diet developed a cardiomyopathy with foci of myocardial necrosis, calcification and modest mononuclear and giant cell infiltration. Additionally, hamsters given nifedipine had a dose-dependent reduction in lesion abundance and diameter, while hamsters given digoxin produced a dose-dependent increase in lesion abundance and diameter. These results support the hypothesis that the lesions are secondary to calcium overload following an increase in myocardial sodium due to inhibition of the Na+–K+–ATPase and secondary sodium, calcium exchange in a magnesium-deficient state.37 In a different study involving Syrian male hamsters fed either a magnesium-deficient diet or identical diet supplemented with 100 mmol/kg of MgCl, animals were found more vulnerable to ischaemia-induced damage to the heart when magnesium deficient at the time the animals were sacrificed.38 The release and effects of catecholamines have been shown to intensify during cellular magnesium depletion. The detrimental effect of catecholamine excess and magnesium deficiency has been found to be synergistic in the myocardium. In rabbits, magnesium supplementation has been found to reduce the ultrastructural features of myocardial damage induced by epinephrine injection without an effect on changes in intracellular distribution of calcium induced by epinephrine.39

In humans, studies also support the role of magnesium in cardiomyopathy. Patients with hypoparathyroidism can manifest cardiomyopathy, which responds to magnesium supplementation.40 Cardiomyopathy and magnesium deficiency are commonly observed in patients with heavy alcohol consumption.41 Additionally, people who live in low magnesium equatorial areas, and those consuming a magnesium-deficient diet, have developed spontaneous endomyocardial fibrosis of undetermined aetiology.41–43

Congestive heart failure

Magnesium deficiency is commonly found in patients with congestive heart failure due to various mechanisms. Patients with congestive heart failure may have an increased urinary excretion of magnesium, secondary to decreased tubular absorption of magnesium as a result of increased extracellular volume and the effects of secondary hyperaldosteronism found in heart failure. Medications, such as diuretics and digoxin, can also worsen the problem and decrease tubular reabsorption of magnesium. Hyperactive renin–angiotensin system may further elevate aldosterone levels in the body, further exacerbating a state of magnesium deficiency. Additionally, norepinephrine in a state of heart failure has been shown to reduce magnesium through increased fatty acids.44–52 Adding to the vicious cycle, magnesium deficiency may worsen hyperaldosteronism, which may lead to fluid retention.

In patients with heart failure, hypomagnesaemia also predisposes to hypokalaemia, therefore increasing the chance of developing ventricular arrhythmias and haemodynamic derangements. Finally, magnesium depletion may worsen cardiac contractility, increase vasoconstriction and deplete cardiac energy stores.53 Magnesium deficiency has even been shown to worsen clinical outcomes in patients with congestive heart failure. Micronutrient deficiency is found to be independently predictive of poor health-related quality of life (HRQoL) and shorten cardiac event-free survival in patients with heart failure.54 Storm and Zimmerman reported a case of cardiogenic shock developing after cardiopulmonary bypass that was initially unresponsive to therapeutic intervention, which resolved promptly after magnesium administration.55 Gottlieb et al found that patients with normal versus low magnesium levels had 2-year survival rates of 61% and 42%, respectively. It was hypothesised that hypomagnesaemia lead to deaths due to ventricular arrhythmias.56

Because electrolyte abnormalities are a frequent and potentially hazardous complication in patients with heart failure, magnesium likely improves outcomes in patients with congestive heart failure by preventing ventricular arrhythmias. Bashir et al investigated the effect of oral magnesium supplementation in a randomised, double-blind, cross-over trial involving 21 patients with stable congestive heart failure secondary to coronary artery disease and who were receiving long-term loop diuretics. Oral magnesium supplementation was found to lower mean arterial pressure, systolic vascular resistance and the frequency of isolated ventricular premature complexes, couplets and non-sustained ventricular tachyarrhythmia.57 However, more studies are needed to establish whether routine supplementation of magnesium in patients with heart failure is warranted. In fact, Ralston et al showed that the prevalence of hypomagnesaemia in ambulatory patients with dilated cardiomyopathy is relatively low (9%); however, magnesium is 99% intracellular and hence there is a poor correlation between serum, mononuclear cells, skeletal muscles cells and cardiac muscle cell magnesium levels.58

Cardiac arrhythmia

The importance of magnesium supplementation in preventing arrhythmias in patients with congestive heart failure has long been established. Magnesium deficiency can lead to QT interval prolongation, ST-segment depression and low amplitude T waves.59–61 Magnesium also influences the movement of other ions such as potassium, sodium and calcium across the cell membranes. The association between magnesium and potassium is probably best demonstrated in that magnesium deficiency is often accompanied by potassium deficiency. In patients with congestive heart failure, both magnesium and potassium are depleted with thiazide diuretics, particularly in patients requiring high doses of thiazide diuretics.62–65 It has been shown that the level of potassium in muscle will not normalise unless magnesium is replaced, even though serum potassium rises with repletion.62 66 67 The ominous role of magnesium depletion in predisposing to arrhythmias in patients with congestive heart failure is perhaps best demonstrated in a recent prospective study showing that among the 66% of patients with cardiac arrest who had magnesium abnormalities, none were successfully resuscitated.68

Supraventricular tachycardia

A large percentage of patients with supraventricular arrhythmias have an intracellular magnesium deficiency despite having normal serum magnesium concentrations, and this may explain the rationale for magnesium’s benefits as an atrial antiarrhythmic agent.69 Magnesium enhances atrial antiarrhythmic efficacy when used as monotherapy.69 Maurat et al found that in vitro, changes in atrial action potential can be induced experimentally by a fall in extracellular potassium or by digoxin overdose. Increasing magnesium concentration in the medium can correct these changes in atrial action potential. Magnesium does not seem to act on the Na+–K+–ATPase activity but rather exert its effect through moderating the calcium inflow into the cell, which is favoured by hypomagnesaemia.70 In the Framingham Heart Study, individuals in the lowest quartile of serum magnesium were 50% more likely to develop atrial fibrillation compared with those in the upper quartiles. Results were similar after the exclusion of individuals on diuretics. As a result, low serum magnesium is moderately associated with development of atrial fibrillation in individuals without cardiovascular disease.71 To make matters worse, hypomagnesaemia is common among patients with symptomatic atrial fibrillation,72 and replacement of magnesium deficiency may be beneficial in patients with symptomatic atrial fibrillation who are receiving digoxin therapy. Similarly, a study by Lewis et al suggested that treatment with magnesium may be associated with a decreased prevalence of ventricular ectopy in some patients receiving digoxin with chronic atrial fibrillation and mild–moderate hypomagnesaemia.73

However, not all studies find a clinically significant association between hypomagnesaemia and improved outcomes in atrial fibrillation. Eray et al assessed the effect of magnesium supplementation on lowering the rate in patients with atrial fibrillation with rapid ventricular response and evaluated the effect of this therapy in magnesium-deficient and non-deficient patients. The decrease in the ventricular rate was statistically significant at 15, 30 and 60 min after magnesium therapy; however, there was no difference in the response to magnesium between magnesium-deficient and non-deficient patients. The authors concluded that magnesium supplementation had a statistically significant but clinically limited effect on ventricular rate and its effect did not differ between patients with and without magnesium deficiency.74

In addition to atrial fibrillation, the effect of hypomagnesaemia has also been studied in other forms of supraventricular dysrhythmias. Cohen et al studied two groups of patients with multifocal atrial tachycardia treated with intramuscular and continuous intravenous magnesium and found that both routes of administration were successful in reverting patients back to sinus rhythm. However, the intramuscular regimen attains higher and more sustained serum concentrations.75 In a separate study, seven patients with congestive heart failure receiving long-term diuretics as well as digoxin experienced idional tachycardia. Intravenous administration of magnesium followed by intramuscular magnesium repletion was noted to abolish the arrhythmias. Interestingly, decreased lymphocyte magnesium and potassium content but normal serum magnesium levels were found in five patients, again suggesting that normal serum magnesium does not preclude total body magnesium deficiency, and a decreased cellular magnesium level predisposes to digitalis-induced arrhythmias.76

Ventricular arrhythmia

Magnesium therapy has also been shown to be effective in patients with ventricular tachycardia. Magnesium supplementation may be a viable therapeutic option when other antiarrhythmic agents fail to suppress ventricular tachycardia and ventricular fibrillation.77 In animal models, magnesium-deficient dogs showed increased pressor sensitivity to epinephrine as determined by the dose of epinephrine required to cause a maximum pressor response. Magnesium-deficient dogs also had a significantly lower threshold for triggering ventricular premature beats. Administration of magnesium in these dogs restored the pressor sensitivity level and abolished premature ventricular beats.78 In humans, a significant increase in cellular potassium content and likewise a significant decrease in frequency of ventricular ectopic beats were noted after magnesium infusions.63 Magnesium may be exerting its antiarrhythmic effects by preventing prolonged QTc. Krasner et al studied 24 patients scheduled electively for mitral valve replacement and found that all patients who developed arrhythmias postoperatively had not been pretreated with oral magnesium and had abnormal QTc intervals both before and after operation.79

The role of intravenous magnesium supplementation has also been studied in patients with acute myocardial infarction who received thrombolytic therapy. Ventricular arrhythmias were less in the experimental group supplemented with magnesium, suggesting that magnesium supplementation may be a safe and effective adjuvant to thrombolytic therapy in reducing the short-term mortality and ventricular arrhythmias after acute myocardial infarction.80 Magnesium depletion has long been associated with severe ventricular arrhythmias such as torsades de pointes. Papaceit et al reported a case of a patient with chronic magnesium depletion who developed torsades de pointes and had good response to magnesium supplementation.81 However, magnesium supplementation has not been shown to reduce implantable cardioverter-defibrillator (ICD) firing rates. The trial, however, was underpowered. More prospective, large, randomised controlled trials are needed to further elucidate the effect of magnesium supplementation on ventricular arrhythmias in ICD patients.

Sudden cardiac death

A link between magnesium deficiency and sudden cardiac death has been suggested by a number of studies published over the past few decades. Data from epidemiological, autopsy, clinical and animal studies suggest that sudden cardiac death is more common in areas where community water supplies are low in magnesium content. Additionally, myocardial magnesium content is found to be low in patients who died of sudden cardiac death. Sudden cardiac death secondary to magnesium deficiency may be secondary to cardiac arrhythmias and coronary artery vasospasm. Finally, repletion of magnesium has been found to reduce the risk of arrhythmias and death after an acute myocardial infarction.82

Magnesium likely predisposes to sudden cardiac death through several mechanisms. First, magnesium deficiency sensitises the myocardium to toxic effects of various drugs as well as to hypoxia. Therefore, magnesium supplementation may have significant cardioprotective effects. Second, magnesium activates the Na–K–ATPase, which may be inhibited by non-glucose fuels such as lactate and free fatty acid in the setting of ischaemia. Third, deficiency in magnesium may also lead to chronic electrical instability of the myocardium by affecting the sodium and calcium flow into the cells.83 A fourth potential mechanism is via the effect of hypomagnesaemia on vascular tone. In in vitro experiments, extracellular magnesium ions have been found to exert a profound beneficial influence on the contractility and reactivities of the arteries, arterioles and veins from a number of regional vasculatures and in several mammalian species, including humans. Hypomagnesaemia has also been observed to increase the contractile activity of a variety of neurohumoral substances and to potentiate vasospasm, likely by controlling the entry and distribution of calcium ions into the cells. Coronary vasospasm has thus been suggested as a possible mechanism of sudden cardiac death.84 Other experiments have taken isolated coronary arteries from dogs and exposed them to different concentrations of magnesium in the medium. High concentrations of magnesium were found to decrease the basal tension of the coronary arteries, whereas sudden withdrawal of magnesium increased the contractile function of both small and large coronary arteries.85 Similarly, Altura also found that lowering the magnesium contents around perfused arterioles can lead to spontaneous vasoconstriction as well as increased arteriolar resistance, tissue ischaemia and reduced venous outflow. Lastly, the concentration of circulating vasoconstrictor hormones, such as angiotensin, serotonin and acetylcholine, are increased when extracellular magnesium is lower than normal.86 It is possible that hypomagnesaemia produces progressive vasoconstriction and vasospasm, which then leads to ischaemia, giving rise to sudden cardiac death overtime.

Ways to supplement magnesium as a possible method to reduce sudden cardiac death include changing dietary habits to include magnesium-rich foods, adding magnesium to community water supplies, fortifying foods with magnesium as well as oral supplementation.82 More prospective, large-scale studies are needed to study the effect of magnesium supplementation as a means of primary prevention for sudden cardiac death.

Atherosclerosis

Magnesium deficiency has been shown to play a role in lipoprotein metabolism and may be contributing to atherosclerosis as a cardiovascular risk factor. Endothelial cells cultured in low magnesium have been found to activate nuclear factor-kappa beta, which may in turn trigger the downstream cytokine network. Low magnesium levels in culture also increases the endothelial cell secretion of RANTES (regulated on activation, normal T cell expressed and secreted), interleukin 8 and platelet-derived growth factor-BB. All play an important role in atherogenesis. Additionally, endothelial cells when exposed to low magnesium increase the secretion of matrix metalloprotease-2 and matrix metalloprotease-9 and their inhibitor, tissue inhibitor of metalloproteinases (TIMP-2). All of these pathways lead to endothelial dysfunction by promoting the expression of inflammatory cytokines in a state of magnesium deficiency.87

In rats fed a short-term magnesium-deficient diet, there is a reduction in the serum magnesium level, sphingomyelin level, phosphatidylcholine, high-density lipoprotein (HDL) cholesterol and the phosphatidylcholine:cholesterol ratio, concomitant with decreases in tissue levels of glutathione, leakage of cardiac creatine kinase (CK) and lactic dehydrogenase (LDH), as well as activation of nitric oxide synthetase (e-NOS and n-NOS) in all chambers of the heart. In addition, the changes in these parameters are dose dependent on the degree of magnesium deficiency, and they can lead to oxidative stress. Reductions in glutathione content as well as activation of e-NOS and n-NOS in various chambers of the heart have been hypothesised to produce early cardiac damage characterised by leakage of CK and LDH. Additionally, rats exposed to low dietary magnesium had de novo synthesis of ceramide, which was attenuated by inhibition of sphingomyelinase and serine palmitoyl CoA transferase. Hence, the activation of the sphingomyelin–ceramide pathway in a state of magnesium deficiency may also play a role in the pathogenesis of atherosclerosis.88 Low magnesium concentrations may also reversibly inhibit endothelial proliferation and alter endothelial migration via significant downregulation of CDC25B and an upregulation of interleukin-1 (IL-1), vascular cell adhesion molecule-1 and plasminogen activator inhibitor-1 after magnesium deficiency leading to a pro-atherosclerotic state.89

In one study, the effects of thiamine, magnesium and sulfate salts on the growth, thiamine levels and serum lipid level were tested in rats. Deficiency of both magnesium and sulfate salts in thiamine-supplemented groups decreased body weight gain and liver thiamine content, but elevated serum triglycerides.90 Animals given cyclophosphamide or methotrexate also had greater cardiac damage while on a low magnesium diet via its effect on blood lipid levels and atherogenesis.91 In humans, long-term magnesium deficiency has been found to lower serum magnesium levels and increase levels of lipids as well as serum glucose. In young, apparently healthy athletes, persistent magnesium deficiency as a result of strenuous physical activity was found to correlate with long-term increases in cholesterol, triglycerides and blood sugar.92 These studies suggest that magnesium supplementation may be beneficial as treatment for the primary prevention of atherosclerosis.

Coronary vasospasm

Multiple studies have suggested a link between magnesium deficiency and coronary artery spasm. Magnesium controls the movement of calcium into smooth muscle cells, leading to smooth muscle contraction. In dogs, coronary arteries incubated in low magnesium solutions are predisposed to vasospasm.85 Additionally, low magnesium solution can significantly increase the potential for contractile responses of both small and large arteries to norepinephrine.85 Experiments of intact dogs93 and isolated coronary arteries of pigs also showed similar results.94 Low magnesium levels have been associated with variant angina in humans, and measurement of erythrocyte magnesium content is useful to determine how easily vasospasm may occur.95 Guo et al also evaluated the intracellular and extracellular magnesium status in 12 women with variant angina and found that the 24-hour magnesium retention rate and intracellular concentrations of magnesium in erythrocytes correlated well with the activity of variant angina.96 Teragawa et al demonstrated that magnesium infusion can produce non-site-specific basal coronary dilatation and suppresses acetylcholine-induced coronary spasm in patients with vasospastic angina. Magnesium infusion was also effective in reducing the severity of chest pain and ST-segment deviations during coronary spasm. After the magnesium infusion, the per cent change in the diameter of the spastic segments improved from −62.8±2.6% to −43.7±4.7% during coronary spasm.97 These studies suggest that magnesium may be beneficial for symptom control in patients with variant angina.

Oxidative stress and myocardial injury

Evidence suggests that magnesium deficiency plays a role in myocardial infarction via increased oxidative stress. Magnesium deficiency has been associated with the production of reactive oxygen species, cytokines, as well as vascular compromise in vivo.98 Magnesium deficiency has also been shown to produce myocardial lesions in different animal models. In rats fed a diet deficient in magnesium, there is a significant lowering of superoxide dismutase and catalase in the rat heart, leading to depressed antioxidant defence in the heart and increased myocardial susceptibility to oxidative injury.99 Hans et al also demonstrated that magnesium deficiency is associated with increased oxidative stress through reductions in plasma antioxidants and increased lipid peroxidation, suggesting that the increased oxidative stress may be due to increased susceptibility of body organs to free radical injury.100 In Syrian hamsters placed on a magnesium-deficient diet, oxidation (isoprenaline)-induced injury was dramatically increased in magnesium-deficient rats.101 This finding suggests that magnesium deficiency increases the susceptibility of the cardiovascular system to oxidative damage. In humans, similar findings were reported. Kharb and Singh estimated serum malonaldehyde (MDA), magnesium, vitamin E and total glutathione levels (GSH) in 22 patients with acute myocardial infarction and 15 healthy controls. Low levels of magnesium, GSH, vitamin E and elevated levels of MDA were observed in patients with acute myocardial infarction. The findings suggest that magnesium deficiency can potentiate oxidative injury in post-ischaemic myocardium.102

Patients with acute myocardial infarction also tend to have lower magnesium content, particularly in the early hours after infarction. Urdal et al studied mononuclear cell magnesium and retention of magnesium after intravenous loading in patients with acute myocardial infarction compared with healthy volunteers. The study found that mononuclear cell magnesium concentrations before magnesium retention test were slightly higher in patients with acute myocardial infarction compared with healthy volunteers indicting no magnesium depletion in the acute myocardial infarction group. However, when magnesium retention test was performed 4–11 days after admission in the subjects with acute myocardial infarction, the retention of magnesium was 45±23% of the 30 mmol given intravenously (retention of more than 20% generally represents magnesium deficiency). It is unclear what caused the increased retention of magnesium during the acute phase of myocardial infarction, but it may be due to increased concentrations of circulating catecholamines during the early hours of myocardial infarction.103 Rasmussen et al also found that patients with ischaemic heart disease both with and without acute myocardial infarction retained significantly more magnesium than did the control group of healthy volunteers. The increase in magnesium retention points to a state of magnesium deficiency in patients with ischaemic heart disease. Unsurprisingly, when the patients with ischaemic heart disease were subgrouped according to long-term diuretic treatment, the patients receiving long-term diuretic treatment had a 39% retention of magnesium (11.6 mmol/L (28.2 mg/dL)) compared with a 29% retention (8.7 mmol/L (21.1 mg/dL)). This study indicates that patients with ischaemic heart disease may be severely magnesium deficient and that long-term diuretic treatment may contribute to this deficiency.104 The beneficial effect of intravenous magnesium treatment in acute myocardial infarction has also been demonstrated in regards to reducing both mortality and early cardiac insufficiency. Besides antiarrhythmic and vasodilatator effects, magnesium also seems to protect cardiac cells against the harmful effects of ischaemia.70

Thrombosis

In both animals and human models, magnesium deficiency has been linked to a prothrombotic state. In an uncontrolled study in 1954, Parsons et al found that patients with angina or myocardial infarction had a reduced death rate, from 30% to 1%, if they were treated with magnesium sulfate intramuscularly. The improvement was thought to be secondary to favourable effects in reducing the inhibition of plasmin, an enzyme that plays an essential role in fibrinolysis and responsible for the degradation of fibrin clots.105 A more recent study in 1986 demonstrated that bleeding time increased with magnesium infusion in patients with acute myocardial infarction.106 Magnesium has been shown to inhibit ADP-induced platelet aggregation.107 In patients with pre-eclampsia, treatment with magnesium infusion has been shown to reduce certain clotting factors.108 In a 1989 paper, Paolisso et al found that magnesium administration can reduce platelet hypercoagulability in patients with non-insulin-dependent diabetes.109 Shecter also found that low intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease by exposing porcine aortic media to their flowing un-anticoagulated venous blood for 5 min by using an ex vivo perfusion chamber.110 These studies suggest that magnesium may play a role in thrombosis and supplementation with magnesium may be beneficial in certain population of patients.

Magnesium and mitral valve prolapse

The mechanism of mitral valve prolapse has not been fully elucidated. However, magnesium deficiency has been proposed to be related to mitral valve prolapse syndrome. In a study comparing 49 subjects with mitral valve prolapse to age-matched and gender-matched subjects without mitral valve prolapse, both groups were found to have similar serum magnesium levels. However, subjects with mitral valve prolapse had lower magnesium levels in the lysate of their lymphocytes. The results suggest that lymphocyte magnesium deficiency may play a role in mitral valve prolapse.111 In a separate study by Licholdziejewska et al, serum magnesium levels in 141 subjects with heavily symptomatic mitral valve prolapse and 40 healthy subjects were compared. The group found that many patients with heavily symptomatic mitral valve prolapse have low serum magnesium, and magnesium supplementation leads to improvement in most symptoms such as chest pain, dyspnoea, weakness, palpitations and anxiety along with a decrease in catecholamine excretion.112 Further studies are needed to further elucidate the relationship between magnesium deficiency and mitral valve prolapse syndrome.

Diabetes and glycaemic control

Magnesium deficiency has also been implicated in the pathogenesis of diabetes and poor glycaemic control. In animal models, magnesium deficiency as well as excess sucrose intake has been shown to be associated with the generation of reactive oxygen species. When male Wistar rats were divided into groups fed control, low-magnesium, high-sucrose and low-magnesium high-sucrose diet for a period of 3 months, the rats fed high sucrose and low magnesium diet were found to have significantly higher levels of lipid peroxidation in the plasma and liver tissue; however, the same effect was not observed in the other groups. These findings suggest that a diet low in magnesium and high in sucrose causes oxidative stress in rats, as reflected by increased lipid peroxidation and reduced antioxidant potential.113 In humans, randomised double-blind placebo-controlled trials have been done to study the effect of magnesium deficiency in diabetic patients. In a study conducted by Simental-Media et al, 62 men and non-pregnant women with a diagnosis of pre-diabetes and hypomagnesaemia were enrolled in the double-blind, placebo-controlled trial to receive either magnesium supplementation or placebo. At the end of the trial, subjects receiving magnesium supplementation were found to have higher levels of serum magnesium, as well as lower levels of high-sensitivity C reactive protein.114 In a separate randomised controlled trial, Guerrero-Romero et al showed that supplementation of oral magnesium in subjects with pre-diabetes and hypomagnesaemia improved glycaemic control. At the end of the follow-up period, subjects in the treatment group had significantly lower fasting and post-load glucose, homeostatic model assessment for insulin resistance indices and triglycerides, whereas HDL cholesterol and serum magnesium levels were significantly increased in those receiving magnesium supplementation. Remarkably, a total of 50.8% of those in the magnesium treatment group improved their glycaemic level compared with only 7% in the placebo group.115

Stroke

Hypomagnesaemia has also been found to be a risk factor for cerebrovascular events and complications. Szabo et al found that a slight decrease in extracellular magnesium from 1.2 to 0.8 mM resulted in sustained relaxation when the endothelium was intact; however, when the endothelium was interrupted, the slight reduction in magnesium resulted in elevation of vascular tone. These results suggested that magnesium modules human cerebra-arterial tone through an endothelium-derived relaxing factor rather than by altering smooth muscle tone directly, and magnesium deficiency appears to drive endothelial dysfunction and hence atherosclerosis.116 Amighi et al investigated the prognostic impact of magnesium serum levels with respect to the occurrence of neurological events in patients with advanced atherosclerosis in 323 patients with symptomatic peripheral artery disease and intermittent claudication. Compared with patients in the highest tertile of magnesium serum levels (>0.84 mmol/L), patients with magnesium serum values <0.76 mmol/L (lowest tertile) exhibited a 3.29-fold increased adjusted risk (95% CI 1.34 to 7.90; p=0.009) for neurological events. However, patients with magnesium serum values of 0.76 mmol/L to 0.84 mmol/L (middle tertile) had no increased risk (adjusted HR 1.10; 95% CI 0.35 to 3.33; p=0.88). Hence, low serum magnesium levels appear to correlate with an increased risk for neurological events, defined as ischaemic stroke and/or carotid revascularisation.117 In a different study involving 40 patients with acute ischaemic strokes, low serum magnesium concentration was found to correlate with the intensity of neurological deficit at 48 hours after the onset of ischaemic stroke, as measured by the National Institute of Health Stroke Scale. Severity of paresis was also higher in patients with low serum magnesium levels.118 In summary, these studies seem to suggest that magnesium plays an important role in the pathogenesis of acute ischaemic stroke. However, more studies are necessary to further elucidate the mechanism by which magnesium exerts these effects in the cerebral–vascular system.

Conclusion

Magnesium plays an important role in cardiovascular health. It is instrumental for the proper maintenance of cellular membrane potential, functioning of the mitochondria and plays a key role in the body’s antioxidative pathways. As a result, magnesium deficiency can lead to serious morbidity and mortality, and has been implicated in multiple cardiovascular diseases such as hypertension, cardiomyopathy, cardiac arrhythmia, atherosclerosis, dyslipidaemia and diabetes. Unfortunately, the western diet is often low in magnesium due to the refining and processing of foods, and hypomagnesaemia is often underdiagnosed in hospitalised patients. Studies have suggested that prompt diagnosis and timely supplementation of magnesium may be beneficial in patients with certain cardiac conditions. However, more prospective, randomised controlled trials are needed to be able to further elucidate the value of magnesium as a therapy to prevent or reverse some of the aforementioned cardiovascular conditions.

Footnotes

Contributors: All authors contributed to the final manuscript.

Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests: JJD is the author of The Salt Fix and operates the website thesaltfix.com.

Patient consent: Not required.

Provenance and peer review: Not commissioned; internally peer reviewed.

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Articles from Open Heart are provided here courtesy of BMJ Publishing Group

 

Magnesium sulfuricum Bundesanzeiger Nr. 190 a vom 10.10.1985
Monographie BGA/BfArM (Kommission D)

 

ZDRAVLJE u 3 minute – Opasnost deficijencije magnezija

X X X X X

MAGNEZILUM HLORID I MAGNEZIJUM SULFAT

Adverse Effects

Excessive parenteral doses of magnesium salts lead to the development of hypermagnesaemia, important signs of which are respiratory depression and loss of deep tendon reflexes, both due to neuromuscular blockade. Other symptoms of hypermagnesaemia may include nausea, vomiting, flushing of the skin, thirst, hypotension due to peripheral vasodilatation, drowsiness, confusion, slurred speech, double vision, muscle weakness, bradycardia, coma, and cardiac arrest.

Hypermagnesaemia is uncommon after oral magnesium salts except in the presence of renal impairment. Ingestion of magnesium salts may cause gastrointestinal irritation and watery diarrhoea.

Effects on the gastrointestinal tract.

There are isolated reports of paralytic ileus in patients receiving magnesium salts.1,2 Delayed intestinal transit has also been reported in a neonate who received an intramuscular overdose of magnesium.3 See also Pregnancy, under Precautions, Go to Pregnancy..

  1. Hill WC, et al. Maternal paralytic ileus as a complication of magnesium sulfate tocolysis. Am J Perinatol 1985; 2 47–8. PubMed
  2. Golzarian J, et al. Hypermagnesemia-induced paralytic ileus. Dig Dis Sci 1994; 39 1138–42. PubMed
  3. Narchi H. Neonatal hypermagnesemia more causes and more symptoms. Arch Pediatr Adolesc Med 2001; 155 1074. PubMed

Hypersensitivity.

Hypersensitivity reactions characterised by urticaria were described in 2 women after receiving magnesium sulfate intravenously.1

  1. Thorp JM, et al. Hypersensitivity to magnesium sulfate. Am J Obstet Gynecol 1989; 161 889–90. PubMed

Treatment of Adverse Effects

The management of hypermagnesaemia is reviewed on Go to Hypermagnesaemia..

Hypermagnesaemia.

A patient with hypermagnesaemia of a degree that is normally fatal was successfully treated using assisted ventilation, calcium chloride administered intravenously, and forced diuresis with mannitol infusions.1 In another report, a 7-year-old boy given an Epsom salt (magnesium sulfate) enema for abdominal cramping, developed asystole and died, despite aggressive attempts at resuscitation. Such enemas should be avoided because of the risk of significant, unpredictable rectal absorption, leading to toxic hypermagnesaemia.2

  1. Bohman VR, Cotton DB. Supralethal magnesemia with patient survival. Obstet Gynecol 1990; 76 984–6. PubMed
  2. Tofil NM, et al. Fatal hypermagnesaemia caused by an Epsom salt enema a case illustration. South Med J 2005; 98 253–6. PubMed

Precautions

Parenteral magnesium salts should generally be avoided in patients with heart block or severe renal impairment. They should be used with caution in less severe degrees of renal impairment and in patients with myasthenia gravis. Patients should be monitored for clinical signs of excess magnesium (see Adverse Effects, Go to Adverse Effects), particularly when being treated for conditions not associated with hypomagnesaemia such as eclampsia. An intravenous preparation of a calcium salt should be available in case of toxicity. When used for hypomagnesaemia, serum-magnesium concentrations should be monitored.

Magnesium crosses the placenta. When used in pregnant women, fetal heart rate should be monitored and use within 2 hours of delivery should be avoided (see also Pregnancy, Go to Pregnancy.).

Oral magnesium salts should be used cautiously in patients with renal impairment. Taking with food may decrease the incidence of diarrhoea. Chronic diarrhoea from long-term use may result in electrolyte imbalance.

Breast feeding.

In breast milk samples from 10 pre-eclamptic women given magnesium sulfate, mean magnesium concentrations 24 hours after delivery were about 6.4 mg per 100 mL, and significantly higher than those in control subjects. However, by 48 and 72 hours after delivery, values were not significantly different. In both treated and control subjects, milk-magnesium concentrations were about twice those of maternal plasma concentrations. Although total doses of magnesium given to mothers may differ, the authors considered any increased magnesium load to a breast-fed infant to be quite small, about 1.5 mg of additional magnesium daily, and unlikely to significantly alter magnesium clearance from the neonate.1 Based on this, the American Academy of Pediatrics considers that use of magnesium sulfate is therefore usually compatible with breast feeding.2

  1. Cruikshank DP, et al. Breast milk magnesium and calcium concentrations following magnesium sulfate treatment. Am J Obstet Gynecol 1982; 143 685–8. PubMed
  2. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108 776–89. PubMed Correction. ibid.; 1029. Also available at online (accessed 180504)

Hepatic disorders.

Severe hypermagnesaemia and hypercalcaemia developed in 2 patients with hepatic encephalopathy given magnesium sulfate enemas; both patients died, one during and one after asystole. It was recommended that patients with liver disease who might develop renal impairment, or in whom renal failure is established, should not be prescribed enemas containing magnesium for treatment of hepatic encephalopathy as serious magnesium toxicity can occur, which may contribute to death.1

  1. Collinson PO, Burroughs AK. Severe hypermagnesaemia due to magnesium sulphate enemas in patients with hepatic coma. BMJ 1986; 293 1013–14. PubMed Correction. ibid.; 1222.

Pregnancy.

The meconium-plug syndrome (abdominal distention and failure to pass meconium) has been described in 2 neonates who were hypermagnesaemic after their mothers had received magnesium sulfate for eclampsia.1 It was believed that the hypermagnesaemia may have depressed the function of intestinal smooth muscle. See also Effects on the Gastrointestinal Tract, Go to Effects on the gastrointestinal tract.. In 36 hypermagnesaemic infants born to pre-eclamptic mothers treated with magnesium sulfate, significant neurobehavioural impairment persisted for over 24 hours after birth. Impairment was manifest by prolonged weakness in activities such as head lag, ventral suspension, suck reflex, and cry response; improvement corresponded to the decrease in plasma-magnesium concentrations.2

In studies in women with3 and without4 pre-eclampsia there were decreases in short-term fetal heart rate variability when women were given intravenous magnesium sulfate; however, although variability is considered a sign of fetal well-being the decrease was considered clinically insignificant.

  1. Sokal MM, et al. Neonatal hypermagnesemia and the meconium-plug syndrome. N Engl J Med 1972; 286 823–5. PubMed
  2. Rasch DK, et al. Neurobehavioral effects of neonatal hypermagnesemia. J Pediatr 1982; 100 272–6. PubMed
  3. Atkinson MW, et al. The relation between magnesium sulfate therapy and fetal heart rate variability. Obstet Gynecol 1994; 83 967–70. PubMed
  4. Hallak M, et al. The effect of magnesium sulfate on fetal heart rate parameters a randomized, placebo-controlled trial. Am J Obstet Gynecol 1999; 181 1122–7. PubMed

Interactions

Parenteral magnesium sulfate potentiates the effects of competitive and depolarising neuromuscular blockers (Go to Magnesium salts.). The neuromuscular blocking effects of parenteral magnesium and aminoglycoside antibacterials may be additive. Similarly, parenteral magnesium sulfate and nifedipine have been reported to have additive effects (Go to Magnesium salts.).

Oral magnesium salts decrease the absorption of tetracyclines and bisphosphonates, and doses should be separated by a number of hours.

Pharmacokinetics

About one-third of magnesium is absorbed from the small intestine after oral doses and even soluble magnesium salts are generally very slowly absorbed. The fraction of magnesium absorbed increases if magnesium intake decreases. In plasma, about 25 to 30% of magnesium is protein bound. Parenteral magnesium salts are excreted mainly in the urine, and oral doses are eliminated in the urine (absorbed fraction) and the faeces (unabsorbed fraction). Small amounts are distributed into breast milk. Magnesium crosses the placenta.

Human Requirements

Magnesium is the second most abundant cation in intracellular fluid and is an essential body electrolyte which is a cofactor in numerous enzyme systems.

The body is very efficient at maintaining magnesium concentrations by regulating absorption and renal excretion, and symptoms of deficiency are rare. It is therefore difficult to establish a daily requirement.

Foods rich in magnesium include nuts, unmilled grains, and green vegetables.

UK and US recommended dietary intake.

In the United Kingdom dietary reference values (DRV—see Go to Human requirements.)1 and in the United States recommended daily allowances (RDA)2 have been published for magnesium. In the UK the estimated average requirement (EAR) is 200 mg (or 8.2 mmol) daily for adult females and 250 mg (or 10.3 mmol) daily for adult males; the reference nutrient intake (RNI) is 270 mg (or 10.9 mmol) daily for adult females and 300 mg (or 12.3 mmol) daily for adult males; no increment is recommended during pregnancy but an increment of 50 mg (or 2.1 mmol) daily in the RNI is advised during lactation. In the USA under the new dietary reference intakes an EAR of 330 to 350 mg daily has been set in adult males and 255 to 265 mg daily in adult females; the corresponding RDAs are 400 to 420 mg and 310 to 320 mg daily.2 An increase in RDA to 350 to 360 mg is recommended during pregnancy but the standard RDA is considered adequate during lactation. A tolerable upper intake level of 350 mg daily has been set for adults.2

  1. DoH. Dietary reference values for food energy and nutrients for the United Kingdom report of the panel on dietary reference values of the committee on medical aspects of food policy. Report on health and social subjects 41. London HMSO, 1991. PubMed
  2. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board. Dietary Reference Intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC National Academy Press, 1999. Also available at online (accessed 180406)

Uses and Administration

Some magnesium salts are given as a source of magnesium ions in the treatment of magnesium deficiency and hypomagnesaemia (Go to Hypomagnesaemia.). Doses may be expressed in terms of mmol or mEq of magnesium, mass (mg) of magnesium, or mass of magnesium salt. In acute or severe hypomagnesaemia, magnesium may be given parenterally, usually as the chloride or sulfate. One suggested regimen is 20 mmol of magnesium in 1 litre of infusion solution (glucose 5% or sodium chloride 0.9%) given intravenously over 3 hours. Alternatively, 35 to 50 mmol of magnesium in 1 litre of infusion solution may be given over a period of 12 to 24 hours. Up to a total of 160 mmol may be required over 5 days. In those receiving parenteral nutrition, doses of about 12 mmol magnesium daily may be given to prevent recurrence of the deficit. Magnesium sulfate can also be given intramuscularly for severe magnesium deficiency. A recommended dose is 1 mmolkg of magnesium, given over a period of 4 hours; this route is stated to be painful. Careful monitoring of plasma-magnesium and other electrolyte concentrations is essential. Doses should be reduced in renal impairment. Other salts which are, or have been, used parenterally include magnesium ascorbate, magnesium aspartate hydrochloride, and magnesium pidolate.

In simple deficiency states magnesium salts may be given by mouth in doses adjusted according to individual requirements. For preventing recurrence of hypomagnesaemia, doses of 24 mmol daily in divided doses have been recommended. Salts that are, or have been, used orally include magnesium aspartate, magnesium chloride, magnesium citrate, magnesium gluceptate, magnesium gluconate, magnesium glycerophosphate, magnesium lactate, magnesium levulinate, magnesium orotate, and magnesium pidolate.

Magnesium salts such as the carbonate, hydroxide, oxide, and trisilicate are widely used for their antacid properties (Go to Antacids). Magnesium salts also act as osmotic laxatives (see Constipation, Go to Constipation); the salts generally used for this purpose are magnesium sulfate (an oral dose of 5 to 10 g in 250 mL of water being given for rapid bowel evacuation) and magnesium hydroxide (Go to Magnesium Hydroxide).

Parenteral magnesium sulfate has some specific uses. It is used for the emergency treatment of some arrhythmias such as torsade de pointes (see Go to Arrhythmias.) and those associated with hypokalaemia (Go to Hypokalaemia.). The usual dose is 2 g of magnesium sulfate (8 mmol of magnesium) given intravenously over 10 to 15 minutes and repeated once if necessary.

Parenteral magnesium sulfate is also used for the prevention of recurrent seizures in pregnant women with eclampsia (see Go to Eclampsia and pre-eclampsia.). Debate continues as to which dosage regimen is most appropriate. Typically an intravenous loading dose of 4 g of magnesium sulfate (16 mmol of magnesium) is given over 10 to 15 minutes. This is then followed by either an infusion of 1 g (4 mmol magnesium) per hour (for at least 24 hours after the last seizure) or by deep intramuscular injection of 5 g (20 mmol magnesium) into each buttock then 5 g intramuscularly every 4 hours (for at least 24 hours after the last seizure). Should seizures recur under either regimen, then an additional intravenous dose of 2 to 4 g can be given. It is essential to monitor for signs of hypermagnesaemia, and to stop magnesium dosage should this occur. Doses should be reduced in renal impairment.

The use of magnesium sulfate in acute myocardial infarction and premature labour is discussed below (see Go to Myocardial infarction. and Go to Premature labour., respectively).

Dried magnesium sulfate has been used in the form of Magnesium Sulphate Paste (BP 2005) as an application to inflammatory skin conditions such as boils and carbuncles, but prolonged or repeated use may damage the surrounding skin.

General references.

  1. McLean RM. Magnesium and its therapeutic uses a review. Am J Med 1994; 96 63–76. PubMed
  2. Fawcett WJ, et al. Magnesium physiology and pharmacology. Br J Anaesth 1999; 83 302–20. PubMed
  3. Fox C, et al. Magnesium its proven and potential clinical significance. South Med J 2001; 94 1195–1201. PubMed
  4. Gums JG. Magnesium in cardiovascular and other disorders. Am J Health-Syst Pharm 2004; 61 1569–76. PubMed

Anaesthesia.

Magnesium sulfate has been used to prevent the undesirable haemodynamic response sometimes associated with intubation (Go to Anaesthesia). It has also been tried in the treatment of postanaesthetic shivering (Go to Shivering and its treatment.).

Arrhythmias.

Parenteral magnesium is used for the treatment of some arrhythmias such as torsade de pointes (Go to Cardiac arrhythmias). However, for the suggestion that it did not have an antiarrhythmic effect in patients with myocardial infarction see Myocardial Infarction, Go to Myocardial infarction..

Further references.

  1. Frick M, et al. The effect of oral magnesium, alone or as an adjuvant to sotalol, after cardioversion in patients with persistent atrial fibrillation. Eur Heart J 2000; 21 1177–85. PubMed
  2. Stuhlinger HG, et al. Der Stellenwert von Magnesium bei Herzrhythmusstorungen. Wien Med Wochenschr 2000; 150 330–4. PubMed
  3. Piotrowski AA, Kalus JS. Magnesium for the treatment and prevention of atrial tachyarrhythmias. Pharmacotherapy 2004; 24 879–95. PubMed
  4. Shiga T, et al. Magnesium prophylaxis for arrhythmias after cardiac surgery a meta-analysis of randomized controlled trials. Am J Med 2004; 117 325–33. PubMed
  5. Alghamdi AA, et al. Intravenous magnesium for prevention of atrial fibrillation after coronary artery bypass surgery a systematic review and meta-analysis. J Card Surg 2005; 20 293–9. PubMed
  6. Miller S, et al. Effects of magnesium on atrial fibrillation after cardiac surgery a meta-analysis. Heart 2005; 91 618–23. PubMed

Eclampsia and pre-eclampsia.

Magnesium sulfate has become the preferred treatment for seizures associated with eclampsia (Go to Eclampsia and pre-eclampsia.). Studies and systematic reviews have shown it to be more effective than phenytoin,1,2 diazepam,1,3 or lytic cocktail,4 as well as causing fewer adverse effects. Its advantages included a rapid effect and lack of sedation in the mother or the infant.5 It was also considered to have a wide safety margin with the added security of calcium gluconate being an easily available antidote should overdose occur. Subsequent meta-analysis6 and systematic review2-4 reinforced this favourable view.

Magnesium sulfate may also be used to prevent eclampsia in pre-eclamptic patients; trials have shown it to be more effective than phenytoin,7 or nimodipine.8 A randomised placebo-controlled trial9 involving over 10 000 women in 33 countries found that treatment with magnesium sulfate approximately halved the risk of developing eclampsia; the number of maternal deaths was also less in the treatment group although the differences in risk between this group and the placebo group were not significant.

Despite some concerns about the effects of early use of magnesium sulfate on the fetus (see Premature Labour, Go to Premature labour.), many,10,11 including WHO, consider magnesium sulfate the drug of choice for both treatment and prevention of eclampsia.

  1. The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia evidence from the Collaborative Eclampsia Trial. Lancet 1995; 345 1455–63. PubMed Correction. ibid.; 346 258.
  2. Duley L, Henderson-Smart D. Magnesium sulphate versus phenytoin for eclampsia. Available in The Cochrane Database of Systematic Reviews; Issue 3. Chichester John Wiley; 2003 (accessed 210605). PubMed
  3. Duley L, Henderson-Smart D. Magnesium sulphate versus diazepam for eclampsia. Available in The Cochrane Database of Systematic Reviews; Issue 3. Chichester John Wiley; 2003 (accessed 210605). PubMed
  4. Duley L, Gulmezoglu AM. Magnesium sulphate versus lytic cocktail for eclampsia. Available in The Cochrane Database of Systematic Reviews; Issue 3. Chichester John Wiley; 2000 (accessed 210605). PubMed
  5. Saunders N, Hammersley B. Magnesium for eclampsia. Lancet 1995; 346 788–9. PubMed
  6. Chien PFW, et al. Magnesium sulphate in the treatment of eclampsia and pre-eclampsia an overview of the evidence from randomised trials. Br J Obstet Gynaecol 1996; 103 1085–91. PubMed
  7. Lucas MJ, et al. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med 1995; 333 201–5. PubMed
  8. Belfort MA, et al. A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med 2003; 348 304–11. PubMed
  9. The Magpie Trial Collaborative Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate The Magpie Trial a randomised placebo-controlled trial. Lancet 2002; 359 1877–90. PubMed
  10. Roberts JM, et al. Preventing and treating eclamptic seizures. BMJ 2002; 325 609–10. PubMed
  11. WHO. Managing complications in pregnancy and childbirth a guide for midwives and doctors headache, blurred vision, convulsions or loss of consciousness, elevated blood pressure. Available at online (accessed 180504)

Hypokalaemia.

Potassium and magnesium homoeostasis are linked, and hypokalaemia with increased urine potassium excretion may occur in patients with hypomagnesaemia. In this situation, correction of potassium deficit usually requires magnesium to be given as well. Magnesium sulfate at doses greater than those required to correct hypomagnesaemia has been associated with greater improvements in potassium balance than doses just sufficient to correct hypomagnesaemia.1

  1. Hamill-Ruth RJ, McGory R. Magnesium repletion and its effect on potassium homeostasis in critically ill adults results of a double-blind, randomized, controlled trial. Crit Care Med 1996; 24 38–45. PubMed

Migraine.

Low magnesium concentrations are thought to be important in the pathogenesis of migraine (Go to Migraine), but the precise role of magnesium supplementation in the disorder remains to be determined.1 In a double-blind study,2 24 mmol magnesium daily (in the form of magnesium citrate) reduced the incidence of migraine headache by 42% compared with a reduction of 16% with placebo. However, in another similar study,3 20 mmol magnesium daily (in the form of magnesium aspartate hydrochloride) was no more effective than placebo in producing a 50% reduction in migraine frequency or intensity. Intravenous magnesium sulfate has shown benefit in the treatment of migraine attacks,4 especially in those with aura,5,6 or in patients with low serum-magnesium levels.7

  1. Mauskop A, Altura BM. Role of magnesium in the pathogenesis and treatment of migraines. Clin Neurosci 1998; 5 24–7. PubMed
  2. Peikert A, et al. Prophylaxis of migraine with oral magnesium results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 1996; 16 257–63. PubMed
  3. Pfaffenrath V, et al. Magnesium in the prophylaxis of migraine a double-blind placebo-controlled study. Cephalalgia 1996; 16 436–40. PubMed
  4. Demirkaya Ş, et al. Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache 2001; 41 171–7. PubMed
  5. Bigal ME, et al. Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura a randomized, double-blind, placebo-controlled study. Cephalalgia 2002; 22 345–53. PubMed
  6. Bigal ME, et al. Eficácia de três drogas sobre a aura migranosa um estudo randomizado placebo controlado. Arq Neuropsiquiatr 2002; 60 406–9. PubMed
  7. Mauskop A, et al. Intravenous magnesium sulphate relieves migraine attacks in patients with low serum ionized magnesium levels a pilot study. Clin Sci 1995; 89 633–6. PubMed

Myocardial infarction.

Magnesium has an important physiological role in maintaining the ion balance in muscle including the myocardium. Magnesium might have an antiarrhythmic effect (see also Arrhythmias, Go to Arrhythmias.) and protect the myocardium against reperfusion injury including myocardial stunning (delayed recovery of myocardial contractility function). Intravenous magnesium salts have been used for cardiac arrhythmias and in an overview of studies in patients with suspected myocardial infarction their use, generally within 12 hours of the onset of chest pain, reduced mortality.1 The beneficial effect on mortality appeared to be confirmed by the LIMIT-2 study2 in which 8 mmol of magnesium was given by intravenous injection before thrombolysis and followed by a maintenance infusion of 65 mmol over the next 24 hours. Benefit was confirmed at follow-up an average of 2.7 years later;3 however, there was no evidence of an antiarrhythmic effect. These beneficial effects were not borne out by the larger ISIS-4 study,4 although there were slight differences in the magnesium regimen and its timing which might have played a part in these contradictory results. In an attempt to resolve the controversy, the MAGIC trial5 was designed to test the hypothesis that early use of magnesium in a similar dose to that used in the LIMIT-2 study would reduce short-term mortality in patients with ST elevation myocardial infarction. No benefit or harm of magnesium was observed, and at present the routine use of magnesium in myocardial infarction (Go to Myocardial infarction) cannot be recommended.

Patients with acute myocardial infarction may have magnesium deficiency and long-term treatment with oral magnesium has been tried, but in one study was associated with an increased risk of adverse cardiac events and could not be recommended for secondary prevention.6

  1. Teo KK, et al. Effects of intravenous magnesium in suspected acute myocardial infarction overview of randomised trials. BMJ 1991; 303 1499–1503. PubMed
  2. Woods KL, et al. Intravenous magnesium sulphate in suspected acute myocardial infarction results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). Lancet 1992; 339 1553–8. PubMed
  3. Woods KL, Fletcher S. Long-term outcome after intravenous magnesium sulphate in suspected acute myocardial infarction the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). Lancet 1994; 343 816–19. PubMed
  4. Fourth International Study of Infarct Survival Collaborative Group. ISIS–4 a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction. Lancet 1995; 345 669–85. PubMed
  5. The Magnesium in Coronaries (MAGIC) Trial Investigators. Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) trial a randomised controlled trial. Lancet 2002; 360 1189–96. PubMed
  6. Galløe AM, et al. Influence of oral magnesium supplementation on cardiac events among survivors of an acute myocardial infarction. BMJ 1993; 307 585–7. PubMed

Porphyria.

Magnesium sulfate is one of the drugs that has been used for seizure prophylaxis in patients with porphyria (Go to Porphyria.) who continue to experience convulsions while in remission.

Premature labour.

Pulmonary hypertension of the newborn.

Preliminary studies have suggested that intravenous magnesium sulfate may be effective in treating persistent pulmonary hypertension of the newborn, as mentioned on Go to Pulmonary hypertension.

Respiratory disorders.

Magnesium sulfate, given intravenously over 20 minutes in doses of 1.2 g to patients with acute exacerbations of chronic obstructive pulmonary disease (Go to Chronic obstructive pulmonary disease) who had received inhaled salbutamol, appeared to have moderate efficacy.1

Infusion of magnesium has been reported to be of benefit in some patients with acute asthma (Go to Asthma), but results have been conflicting;2-5 meta-analyses of these and other studies concluded that its routine use was not justified, but that it may benefit some patients with severe exacerbations.6,7 A meta-analysis of 5 trials in children concluded that intravenous magnesium sulfate is likely to be an effective adjunct to standard therapy in the symptomatic treatment of moderate to severe acute childhood asthma.8 Inhalation of magnesium has also been investigated, either alone or with salbutamol; another meta-analysis considered that it improved pulmonary function, particularly in combination with a beta2 agonist, with the best results seen in more severe cases.9

  1. Skorodin MS, et al. Magnesium sulfate in exacerbations of chronic obstructive pulmonary disease. Arch Intern Med 1995; 155 496–500. PubMed
  2. Skobeloff EM, et al. Intravenous magnesium sulfate for the treatment of acute asthma in the emergency department. JAMA 1989; 262 1210–13. PubMed
  3. Green SM, Rothrack SG. Intravenous magnesium for acute asthma failure to decrease emergency treatment duration or need for hospitalization. Ann Emerg Med 1992; 21 260–5. PubMed
  4. Ciarallo L, et al. Intravenous magnesium therapy for moderate to severe pediatric asthma results of a randomized, placebo-controlled trial. J Pediatr 1996; 129 809–14. PubMed
  5. Silverman RA, et al. IV magnesium sulfate in the treatment of acute severe asthma a multicenter randomized controlled trial. Chest 2002; 122 489–97. PubMed
  6. Rowe BH, et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Available in The Cochrane Database of Systematic Reviews; Issue 1. Chichester John Wiley; 2000 (accessed 210605). PubMed
  7. Alter HJ, et al. Intravenous magnesium as an adjuvant in acute bronchospasm a meta-analysis. Ann Emerg Med 2000; 36 191–7. PubMed
  8. Cheuk DKL, et al. A meta-analysis on intravenous magnesium sulphate for treating acute asthma. Arch Dis Child 2005; 90 74–7. PubMed
  9. Blitz M, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Available in The Cochrane Database of Systematic Reviews; Issue 3. Chichester John Wiley; 2005 (accessed 051005). PubMed

Stroke.

Intravenous magnesium sulfate has been investigated for a neuroprotective effect in stroke (Go to Stroke), but results have been largely disappointing.1

  1. Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators. Magnesium for acute stroke (Intravenous Magnesium efficacy in Stroke trial) randomised controlled trial. Lancet 2004; 363 439–45. PubMed

 Tetanus.

Magnesium sulfate has been found to minimise autonomic disturbance in ventilated patients and control spasms in non-ventilated patients when used in the treatment of tetanus (Go to Tetanus).

References.

  1. Attygalle D, Rodrigo N. Magnesium as first line therapy in the management of tetanus a prospective study of 40 patients. Anaesthesia 2002; 57 811–17. PubMed
  2. William S. Use of magnesium to treat tetanus. Br J Anaesth 2002; 88 152–3. PubMed

Preparations

Single-ingredient Preparations

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

IIzvor:

 

X X X X X 

Literatur:
Arzneimittel-Patienteninformation (CH, USA)
Burger A., Wachter H. (Hrsg.) Hunnius. Pharmazeutisches Wörterbuch. Berlin, New York: de Gruyter, 1998
Europäisches Arzneibuch PhEur
Hagers Handbuch der Pharmazeutischen Praxis
Pharmacopoea Helvetica V
Quellen
Reynolds J. (Hrsg.) Martindale. The Extra Pharmacopoeia. London: The Pharmaceutical Press, 1989
Tofil N.M., Benner K.W., Winkler M.K. Fatal hypermagnesemia caused by an Epsom salt enema: a case illustration. South Med J, 2005, 98(2), 253-6 Pubmed Externer Link












Pakovanje mL/ g:
 10 20 30 50 100 250 500 1000

Količina:
1 2 3 više 

 

vrh