Continuing Education Activity

Magnesium use is indicated for a variety of diseases. This is due to the variety of effects magnesium has within the body. Administration of magnesium can be divided into FDA versus non-FDA approved. Also, magnesium is commonly used in over-the-counter products. This activity will highlight the mechanism of action, adverse event profile, pharmacology, monitoring, and relevant interactions of magnesium, pertinent for interprofessional team members in treating patients with conditions where magnesium is indicated.

Objectives:

• Identify the physiological processes in which magnesium is involved.
• Summarize the indications for endogenously administered magnesium therapy.
• Explain the contraindications and toxicity of magnesium therapy.
• Describe some interprofessional team strategies for improving care coordination and communication to properly use magnesium to improve patient outcomes in the varied scenarios where magnesium is effective.

Indications

Magnesium use is indicated for a variety of diseases. This is due to the variety of effects magnesium has within the body. Administration of magnesium can be divided into FDA versus non-FDA approved. Also, magnesium is commonly used in over-the-counter products.[1][2][3][4] Normal serum blood magnesium levels are between 1.8 and 2.2 mg/dL.

Hypomagnesemia: Magnesium Concentration of Less Than 1.8 mg/dL

• Magnesium depletion can result from inadequate intake, decreased renal absorption, or impaired gastrointestinal (GI) absorption.
• Risk factors for hypomagnesemia include those with GI disease, chronic diarrhea, proton pump inhibitor therapy, alcohol use disorder, and diuretic use, both loop and thiazide. It is common to see hypomagnesemia along with low levels of other electrolytes, such as hypokalemia and hypocalcemia. In patients with refractory hypokalemia or hypocalcemia, hypomagnesemia may be the reason. It is difficult to correct these electrolyte imbalances without first treating the magnesium imbalance.[5]
• Symptoms of hypomagnesemia correlate with the development of concurrent hypocalcemia. The signs include Trousseau sign, Chvostek sign, hyperreflexia, tremor, and muscle fasciculations. Patients may also experience vague symptoms such as nausea, vomiting, lethargy, and weakness. Severe hypomagnesemia, less than 1.25 mg/dL, can result in generalized tonic-clonic seizures.[5]

Eclampsia or Severe Pre-Eclampsia

• Magnesium is given to those with severe pre-eclampsia to prevent seizures and those with eclampsia to control seizures.[6]

Constipation

• Over-the-counter laxatives, such as Milk of Magnesia, commonly contain magnesium.

Pre-Term Labor (Off-Label Use)

• Magnesium can be given as a tocolytic to stop the progression of pre-term labor.[5]

Arrhythmias (Off-Label Use)

• Administration of magnesium is recommended in certain arrhythmias such as torsades de pointes, digoxin-associated arrhythmia, ventricular arrhythmias like ventricular fibrillation, and ventricular tachycardia.[7]

Asthma: Acute Severe Exacerbation (Off-Label Use)

• Magnesium is recommended as adjunctive therapy for patients with severe, life-threatening exacerbation or refractory cases after 1 hour of intensive conventional therapy. Magnesium allows bronchial smooth muscle relaxation, which aids in patients with status asthmatics.

Migraines: Over the Counter Supplementation 

• The use of magnesium in migraines is limited at this moment. Hypomagnesemia has been found in patients with migraines. Supplemental magnesium is considered an inexpensive, simple preventive treatment option for some. However, the dosage required is above the daily requirement, thus potentially leading to hypermagnesemia. The American Academy of Neurology and the American Headache Society have stated that magnesium therapy is “probably effective” for migraine prevention.[8]

Mechanism of Action

As with other electrolytes, magnesium's role in the body is diverse and complex. The mechanism of action of magnesium is dependent on which organ system is involved and the formulation used.Physiology of Magnesium

• Magnesium is the fourth most common cation in the body. The majority of magnesium is intracellular; it is the second most common intracellular cation following potassium. Magnesium plays a vital role in over 300 reactions involving metabolism. It is involved with hormone receptor binding, muscle contraction, neural activity, neurotransmitter release, vasomotor tone, and cardiac excitability. It is necessary for the active transport of potassium and calcium across the cell membrane. ATP is dependent on magnesium for proper functioning.[5]

Effects of Magnesium

Gastrointestinal

• Oral magnesium promotes defecation via osmotic retention of fluids. It is also used in over-the-counter antacids.[5]

Cardiovascular

• Magnesium acts as a natural calcium channel blocker, and it is a cofactor of the Na-K-ATP pump. Magnesium helps control atrioventricular node conduction. Therefore, hypomagnesemia can cause myocardial excitability resulting in arrhythmias such as ventricular tachycardia and torsades de pointes.[5]

Neurological System

• Magnesium depresses the central nervous system (CNS) while producing anticonvulsant effects. At neuromuscular junctions, it inhibits the release of acetylcholine, thus blocking peripheral neuromuscular transmission.[5]

Reproductive System

• Magnesium is used as a tocolytic during pre-term labor. Magnesium stimulates calcium reuptake by the sarcoplasmic reticulum, which promotes relaxation of muscle and vasodilation. For pre-term labor, magnesium decreases the calcium within the uterine muscle.[5]

Musculoskeletal System

• Magnesium is a cofactor of parathyroid hormone (PTH) synthesis. With hypomagnesemia, concurrent hypoparathyroidism will ensue. Hypoparathyroidism can lead to decreased calcium and eventually lead to osteopenia or osteoporosis.[5]

Respiratory System

• Magnesium administration can cause bronchial smooth muscle relaxation. The cause of smooth muscle relaxation is unclear. It is thought to be either by inhibiting calcium, histamine, or acetylcholine release. There may also be a synergist effect with the concurrent use of beta-agonists.[5]

Hemostasis of Magnesium

• Roughly 50% of magnesium is located within the bone, 25% is within the muscle, and the remainder is in soft tissue, serum, and red blood cells (RBC). Like other electrolytes, it can be classified as ionized, protein-bound, or bound to anions. Ionized magnesium is the most biological activity.
• The intestine, bone, and kidney maintain magnesium homeostasis. Similar to calcium, magnesium is absorbed via the intestine, stored in the bone, excreted via the kidneys. The absorption of magnesium is inversely proportional to the concentration within the body; if there are low magnesium levels within the body, more magnesium will be absorbed.

Administration

Administration of magnesium can occur in various ways. Dietary intake is the primary source of magnesium for a healthy individual. The recommended daily intake varies with gender and age. Green leafy vegetables, fish, legumes, and whole grains are good sources of magnesium.

Magnesium comes in various salts and forms, including magnesium oxide, magnesium citrate, magnesium sulfate, magnesium hydroxide, and magnesium gluconate.

• Treatment can be via oral magnesium salts or intravenous (IV) or intramuscular (IM) magnesium sulfate. IV or IM magnesium sulfate is given for severe hypomagnesemia or those unable to tolerate or adhere to oral therapy.
• Patients with alcohol use disorder are treated empirically to avoid hypomagnesemia. For patients with renal insufficiency, the clinician must increase the dose to adjust for the increase in renal loss.[5]
• The clinician must also address concurrent hypokalemia or hypocalcemia.

Adverse Effects

Adverse reactions are associated with magnesium’s effect on the neuromuscular and cardiovascular systems and can vary depending on the exact formulation. Effects can include the following:

• Serious adverse events:
  • Cardiovascular collapse
  • Respiratory depression or paralysis
  • Hypothermia
  • Depressed cardiac function
  • Pulmonary edema

• Common adverse events:
  • Flushing
  • Hypotension
  • Vasodilation
  • Impaired reflexes
  • Abdominal pain
  • Diarrhea
  • Flatulence
  • Nausea/vomiting
  • Respiratory depression
  • Electrolyte disorders (hypocalcemia, hyperkalemia)
  • Hypermagnesemia[9] 

Hypermagnesemia can be a serious adverse event, particularly as it pertains to cardiology effects; see the Toxicity section for more information. 

Contraindications

For contraindications, factors to consider are renal function, pregnancy, and neuromuscular disease.

• It is crucial to assess renal function before giving magnesium. Renal failure can cause decreased magnesium excretion leading to toxicity. Closely monitor magnesium levels in patients with reduced renal function.[2]
• Patients with neuromuscular disease, such as myasthenia gravis need to be closely monitored if they are given magnesium. Magnesium inhibits the release of acetylcholine which can cause deterioration.
• Magnesium is considered class D for pregnancy. Skeletal demineralization, hypocalcemia, and hypermagnesemia are seen with long-term use, more than 5 to 7 days, of magnesium, which is necessary for pre-term labor treatment.
• There are no contraindications for magnesium supplements with other prescriptions. However, various drugs increase or decrease the concentration of either magnesium or the prescribed medication.
• Magnesium may be used in pregnancy and lactation; there is no expected risk of fetal or infant harm based on limited data in humans.

Monitoring

Hypermagnesemia may occur from overdose. Monitoring magnesium level is necessary while administering magnesium. Monitoring can be done on serum magnesium levels, as well as other electrolytes such as calcium and potassium.

Toxicity

Hypermagnesemia: Serum Magnesium Concentration Greater Than 2.6 mg/dL

• Hypermagnesemia is a potential effect of administering magnesium. If too much magnesium is administered too quickly, hypermagnesemia may ensue.
• Symptoms include vasodilation causing flushing, hypotension, hyporeflexia, and respiratory depression. With a magnesium concentration above 6 mg/dL, ECG changes can consist of PR prolongation, widening of QRS, and peaked T waves. Cardiac arrest occurs whenever levels are above 15 mg/dL.[7][9][5]
• Hypermagnesemia is less common than hypomagnesemia. The most significant cause of hypermagnesemia is renal failure causing increased retention of magnesium. It can also occur in the overuse of magnesium-containing laxatives and antacids.[2]
• Treatment for hypermagnesemia includes calcium gluconate, diuresis, or dialysis. It is important to maintain circulatory and respiratory support for those with severe hypermagnesemia. IV furosemide is the diuretic of choice, as it increases magnesium excretion.[10][5]

Enhancing Healthcare Team Outcomes

Magnesium is a vital mineral for many bodily functions. However, unless patients are diagnosed with hypomagnesemia, this mineral should not be empirically recommended by the prescribing clinicians, including MDs, DOs, NPs, and PAs. These days many people consume magnesium supplements because of a false understanding of correcting the condition. Excessive magnesium intake is not safe either, as it can lead to hypotension, hyporeflexia, and respiratory depression. With a magnesium concentration of above 6 mg/dL, ECG changes can include PR prolongation, widening of QRS, and peaked T waves. Cardiac arrest occurs whenever levels are above 15 mg/dL. When IV magnesium is administered, the nurse should constantly monitor the vital signs, especially blood pressure.[10] 

While magnesium is generally safe, given the potential for severe issues in specific cases, the entire interprofessional team needs to be aware of the patient's intake of supplemental magnesium and record such in the patient's health record. This way, the whole team can make medical decisions based on complete and accurate data. It is incumbent on each interprofessional team member to provide input based on their area of expertise and counsel the patient on the appropriate use of the drug. Pharmacists need to examine the possibility of drug-drug interactions and report to the prescriber as appropriate. An interprofessional approach involving clinicians, mid-level practitioners, pharmacists, and nursing staff, collaborating the activities, and openly sharing case information will provide the safest and most successful patient care. [Level 5]