Calcium Gluconate: Properties, Medical Uses, Administration, Side Effects and Interactions

As a medicine, it is used by injection into a vein to treat the low toxicity of blood calcium, blood potassium, and magnesium.

Calcium gluconate is a mineral supplement and a medicine.

Generally, supplementation is only required when there is not enough calcium in the diet. Supplementation can be done to treat or prevent osteoporosis or rickets . It can also be taken orally, but injecting it into a muscle is not recommended.

Side effects when injected include slow heart rate, injection site pain, and low blood pressure . When taken by mouth, side effects can include constipation and nausea.

Blood calcium levels should be measured when used and special care should be taken in those with a history of kidney stones. In normal doses, use is considered safe during pregnancy and lactation.

Calcium gluconate is made by mixing gluconic acid with calcium carbonate or calcium hydroxide.

Calcium gluconate entered medical use in the 1920s. It is on the World Health Organization’s Essential Medicines List, the most effective and safest medicines needed in a healthcare system.

Calcium gluconate is available as a generic drug. The wholesale cost in the developing world is approximately $ 0.21 to $ 1.34 per 1 gram vial, 10 ml of 100 mg / ml (10% solution). In the UK, this amount costs the NHS around £ 0.65.

Description

This compound belongs to the class of organic compounds known as sugar acids and derivatives. These are compounds that contain a saccharide unit that carries a carboxylic acid group.

Properties of calcium gluconate

Calcium is an essential electrolyte for the body. It is necessary for the functional integrity of the nerve and muscle and is essential for muscle contraction, cardiac function, and blood clotting.

Calcium homeostasis is regulated mainly by three endocrine factors: parathyroid hormone is secreted in response to a drop in plasma calcium concentration and acts by accelerating calcium transfer from bone and increasing its intestinal absorption and renal reabsorption.

Calcitonin decreases plasma calcium by decreasing bone resorption and increasing renal ion excretion; vitamin D stimulates the intestinal absorption of calcium and decreases its renal excretion.

Oral calcium salts are used as supplemental dietary therapy for people who may not get enough calcium from their regular diet.

Calcium gluconate is used as a cardioprotective agent in high blood potassium. Calcium gluconate is the antidote to magnesium sulfate toxicity.

Parenteral administration of calcium is indicated when the pharmacological action of a high concentration of calcium ions is required, for example, in acute hypocalcemia, cardiac resuscitation and some cases of neonatal tetany.

Intravenous calcium injections have been used in the treatment of acute colic from lead poisoning, and as an adjunct in the treatment of acute fluoride poisoning. Also, for the prevention of hypocalcemia in exchange transfusions.

Pharmacodynamics

Calcium gluconate is the gluconate salt of calcium. Calcium is the most abundant mineral in the human body (approximately 1.5% of total body weight). More than 99% of the total calcium in the body is found in bones and teeth, approx. 1% dissolves in intracellular and extracellular fluid.

An element or mineral necessary for normal nerve, muscle, and heart function, calcium as the gluconate salt helps maintain calcium balance and prevents bone loss when taken by mouth.

This agent can also be chemopreventive for colon cancer and other cancers.

The physiological level of plasma calcium concentration is maintained at 2.25 – 2.75 mmol / l. As approximately 40-50% of plasma calcium is bound to albumin, total plasma calcium is coupled to plasma protein concentration.

The ionized calcium concentration is between 1.23 and 1.43 mmol / l, regulated by calcitonin and parathormone.

Hypocalcemia (total calcium below 2.25 mmol / l or ionized calcium below 1.23 mmol / l, respectively) can be caused by:

Renal failure, vitamin D deficiency, magnesium deficiency, massive blood transfusion, malignant osteoblastic tumors, hypoparathyroidism, or phosphate, oxalate, fluoride, strontium, or radium poisoning.

Hypocalcemia can be accompanied by the following symptoms: increased neuromuscular excitability up to tetany, paresthesia, carpopedal spasms, smooth muscle spasms.

For example, in the form of intestinal colic, muscle weakness, confusion, brain seizures, and cardiac symptoms such as a prolonged QT interval, arrhythmia, and even acute myocardial failure.

The therapeutic effect of parenteral calcium replacement is the normalization of pathologically low serum calcium levels and thus the relief of hypocalcemic symptoms.

Medical uses of calcium gluconate

After injection, the administered calcium shows the same distribution behavior as endogenous calcium.

About 45-50% of total plasma calcium is in the physiologically active ionized form, approximately 40-50% is bound to proteins, mainly albumin, and 8-10% is complexed with anions.

After injection, the administered calcium is added to the intravascular calcium pool and is handled by the body in the same way as endogenous calcium. Excretion of calcium occurs in the urine, although a large proportion undergo renal tubular reabsorption.

Low calcium in the blood

Calcium gluconate 10% solution (administered intravenously) is the most commonly used form of calcium in the treatment of low blood calcium.

This form of calcium is not as well absorbed as calcium lactate, and contains only 0.93% (930 mg / dl) of calcium ion (defined by 1 g of solute by weight in 100 ml of solution to obtain a solution at 1% w / v).

Therefore, if the hypocalcemia is acute and severe, calcium chloride is given.

High blood potassium

Calcium gluconate is used as a cardioprotective agent in people with high potassium levels in the blood, with an alternative being the use of calcium chloride.

It is recommended when potassium levels are high (> 6.5 mmol / L) or when the electrocardiogram (ECG) shows changes due to an increase in potassium in the blood.

Although it does not have an effect on potassium levels in the blood, it reduces the excitability of cardiomyocytes, which reduces the likelihood of cardiac arrhythmias.

Hydrofluoric acid burns

Calcium gluconate gel preparations are used to treat hydrofluoric acid burns. This is because calcium gluconate reacts with hydrofluoric acid to form non-toxic and insoluble calcium fluoride.

Black widow spider bite

Historically, intravenous calcium gluconate was used as an antidote for black widow spider poisoning, often in conjunction with muscle relaxants. This therapy, however, has proven to be ineffective.

Heart attack

Although intravenous calcium has been used in cardiac arrest, its general use is not recommended.

Cases of cardiac arrest in which it is still recommended include high blood potassium, low blood calcium, as can occur after blood transfusions, and calcium channel blocker overdoses.

There is a possibility that general use could worsen the results. If calcium is used, calcium chloride is generally the recommended form.

Dosage and method of administration

The normal concentration of calcium in plasma is within the range of 2.25 to 2.75 mmol or 4.5-5.5 mEq per liter. Treatment should be aimed at restoring or maintaining this level.

During therapy, serum calcium levels should be closely monitored.

Acute hypocalcemia : 10-20ml (2.2-4.4mmol).

Fluoride or lead poisoning : 0.3 ml / kg (0.07 mmol / kg).

Jezaniah neonatal : 0.3 ml / kg (0,07 mmol / kg).

Cardiac resuscitation : 7-15ml (1.54-3.3mmol). It should be noted that the absolute amount of calcium required for this indication is difficult to determine and can vary widely.

In hypocalcemic tetany, an initial intravenous injection of 10 ml of the 10% solution (2.25 mmol) should be followed by a continuous infusion of about 40 ml (9 mmol) per day. Plasma calcium must be monitored.

Pediatric population

Calcium gluconate injection is indicated for the treatment of neonatal tetany; It should not be used routinely in children under 18 years of age.

Elderly

Although there is no evidence that tolerance to calcium gluconate injection is directly affected by advanced age, factors that can sometimes be associated with aging, such as kidney failure and poor diet, can indirectly affect tolerance. and may require a dose reduction.

Renal function decreases with age and before prescribing this product to elderly patients, it should be considered that calcium gluconate injection is contraindicated for repeated or prolonged administration in patients with renal insufficiency.

Side effects of calcium gluconate

Side effects of calcium gluconate include nausea, constipation, and an upset stomach.

Rapid intravenous injections of calcium gluconate can cause hypercalcemia, which can lead to vasodilation, cardiac arrhythmias, low blood pressure, and bradycardia.

Its occurrence and frequency are directly related to the rate of administration and the dose administered.

Ceftriaxone-calcium salt precipitation

In rare cases, serious and in some cases fatal, adverse reactions have been reported in preterm and term infants (<28 days of age) who had been treated with intravenous ceftriaxone and calcium.

Ceftriaxone-calcium salt precipitations have been observed in the lungs and kidneys post mortem. The high risk of precipitation in newborns is due to their low blood volume and the longer half-life of ceftriaxone compared to adults.

Calcium gluconate extravasation can cause cellulite. Intramuscular injections can lead to local necrosis and abscess formation. If any of these effects persist or get worse, tell your doctor or pharmacist as soon as possible.

Reporting of suspected adverse reactions after authorization of the medicinal product is important. It allows continuous monitoring of the benefit / risk balance of the drug.

Tell your doctor right away if any of these unlikely but serious side effects occur:

  • Nausea, vomiting, loss of appetite, unusual weight loss, mental and mood changes, pain in bones, muscles, headache, increased thirst, urination, weakness, unusual tiredness.

If you notice other effects not listed above, contact your doctor or pharmacist.

Overdose

The symptoms

Symptoms of hypercalcemia may include: anorexia, nausea, vomiting, constipation, abdominal pain, polyuria, polydipsia, dehydration, muscle weakness, bone pain, kidney calcification, drowsiness, confusion, hypertension and, in severe cases, cardiac arrhythmia up to cardiac arrest. , and eat.

If the intravenous injection is too fast, symptoms of hypercalcemia may appear, as well as a chalky taste, hot flashes and hypotension .

Emergency treatment, antidotes

Treatment should be aimed at lowering the elevated plasma calcium concentration.

Initial treatment should include rehydration and, in severe hypercalcemia, it may be necessary to administer sodium chloride by intravenous infusion to expand the extracellular fluid. Calcitonin can be given to lower the elevated serum calcium level.

Furosemide can be given to increase calcium excretion, but thiazide diuretics should be avoided as they can increase renal calcium absorption.

Hemodialysis or peritoneal dialysis may be considered when other measures have failed and the patient continues to experience severe symptoms. Serum electrolytes should be carefully monitored during overdose treatment.

Contraindications

Calcium salts can form complexes with many drugs, and this can result in a precipitate. Calcium salts are incompatible with oxidizing agents, citrates, soluble carbonates, bicarbonates, phosphates, tartrates, and sulfates.

Physical incompatibility has also been reported with amphotericin, cephalothin sodium, cefazolin sodium, cepandandol naphate, ceftriaxone, novobiocin sodium, dobutamine hydrochloride, prochlorperazine, and tetracyclines.

Contraindicated in patients receiving cardiac glycosides. Patients with hypercalcemia (eg, in hyperparathyroidism, hypervitaminosis D, neoplastic disease with decalcification of the bone, renal failure, immobilization osteoporosis, sarcoidosis, milk-alkali syndrome).

Coadministration with ceftriaxone in : preterm infants up to a corrected age of 41 weeks (weeks of gestation + weeks of life) and / or full-term infants (up to 28 days of age) due to the risk of precipitation of ceftriaxone calcium.

Repeated or prolonged treatment, including intravenous infusion, in children (under 18 years) and in people with kidney failure, due to the risk of exposure to aluminum.

Metabolism

Calcium gluconate does not require hepatic metabolism for Ca ++ release and is as effective as calcium chloride in the treatment of ionic hypocalcemia in the absence of liver function.

Route of elimination

Renal (20%) : the amount excreted in the urine varies according to the degree of calcium absorption and whether there is excessive bone loss or failure of renal preservation.

Fecal (80%) – Consists primarily of unabsorbed calcium, with only a small amount of endogenous fecal calcium excreted.

Society and culture

Medical calcium gluconate shortages were reported in November 2012 and November 2015 in the United States.

Special warnings and precautions for use

Plasma calcium levels and calcium excretion should be monitored when calcium is administered parenterally, especially in children, in chronic renal failure, or when there is evidence of urinary tract stone formation.

If plasma calcium exceeds 2.75 mmol per liter or if 24-hour urinary calcium excretion exceeds 5 mg / kg, treatment should be stopped immediately, as cardiac arrhythmias may occur at these levels.

Calcium salts should only be used with caution and after careful establishment of the indication in patients with nephrocalcinosis, heart disease, sarcoidosis (Boeck’s disease), in patients receiving epinephrine, or in the elderly.

Calcium gluconate is physically incompatible with many other compounds. Care should be taken to avoid mixing calcium gluconate and incompatible drugs in game administration, or in circulation after separate administration.

Serious complications, including deaths, have occurred after microcrystallization of insoluble calcium salts in the body after separate administration of physically incompatible solutions or total parenteral nutrition solutions containing calcium and phosphate.

Renal insufficiency

Renal failure can be associated with hypercalcemia and secondary hyperparathyroidism. Therefore, in patients with renal impairment, parenteral calcium should be administered only after careful evaluation of the indication and the calcium-phosphate balance should be monitored.

Patients receiving ceftriaxone

Cases of fatal reactions with calcium-ceftriaxone precipitates in the lungs and kidneys have been described in premature and full-term newborns less than 1 month old.

In vitro studies demonstrated that newborns have an increased risk of ceftriaxone-calcium precipitation compared to other age groups.

In patients of any age, ceftriaxone should not be mixed or administered simultaneously with any intravenous solution containing calcium, even through different infusion lines or at different infusion sites.

However, in patients older than 28 days of age, the ceftriaxone and calcium solutions can be administered sequentially one after the other if infusion lines are used at different sites or if the infusion lines are replaced or washed completely between infusions with saline. physiological to avoid precipitation.

In hypovolaemia, sequential infusions of ceftriaxone and products containing calcium should be avoided.

Solutions containing calcium should be administered slowly to minimize peripheral vasodilation and cardiac depression.

Intravenous injections must be accompanied by monitoring of the heart rate or electrocardiogram, as bradycardia with vasodilation or arrhythmia can occur when calcium is administered too quickly.

Plasma levels and urinary calcium excretion should be controlled when high doses of parenteral calcium are administered. Calcium salts are irritating. The infusion site should be monitored regularly to ensure that an extravasation injury has not occurred.

Patients receiving calcium salts should be carefully monitored to ensure the correct calcium balance is maintained without tissue deposition. High intake of vitamin D should be avoided.

Interaction with other medicinal products and other forms of interaction

cardiac glucosides

The effects of digoxin and other cardiac glycosides can be potentiated by calcium, which can result in serious toxicity. Therefore, intravenous administration of calcium preparations to patients receiving cardiac glycosides is contraindicated.

Epinephrine

Co-administration of calcium and epinephrine attenuates the β-adrenergic effects of epinephrine in postoperative patients with cardiac surgery.

Magnesium

Calcium and magnesium mutually antagonize their effects.

Calcium antagonists

Calcium can antagonize the effect of calcium channel blockers (calcium channel blockers).

Thiazide diuretics

The combination with thiazide diuretics can induce hypercalcaemia since these drugs reduce the renal excretion of calcium.

Pregnancy and breastfeeding

The pregnancy

Calcium passes through the placental barrier and its concentration in fetal blood is higher than in maternal blood.

Calcium gluconate should not be used during pregnancy unless the clinical condition of the woman requires treatment with calcium gluconate.

The administered dose must be carefully calculated and the serum calcium level must be assessed regularly to avoid hypercalcaemia, which can be harmful to the fetus.

Lactation

Calcium is excreted in human milk. This should be taken into account when giving calcium to women who are breastfeeding their babies.

A decision must be made whether to discontinue breastfeeding or to suspend / abstain from calcium gluconate therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.