Calcium Salts, Parenteral

CALCIUM SALTS: PARENTERAL

General Monograph,

Calcium Therapy

Pharmacology: Calcium is the most abundant mineral in the human body and is essential for maintaining the functional integrity of nervous and musculoskeletal systems as well as cell membrane and capillary permeability. The majority (99%) of body calcium is contained in bone with the remainder equally distributed between intra- and extracellular fluids. Calcium is an activator in many enzymatic reactions and is necessary for nerve impulse transmission, renal function, respiration and blood coagulation.

Pharmacokinetics: Once absorbed into the bloodstream, most calcium is rapidly incorporated into skeletal muscle; the remainder is equally distributed between intra- and extra- cellular fluids. Normal total serum calcium concentrations range from 2.2 to 2.6 mmol/L, although only the ionized fraction is physiologically active. Of the total serum calcium, 50% is ionized, 5% is complexed with anions such as phosphates or citrates and 45% is protein bound. Hyperproteinemia is associated with an increase in total calcium; hypoproteinemia has the opposite effect. Acidosis favors an increase in ionic calcium concentration, while alkalosis leads to a decrease in the ionized fraction.

CSF calcium concentrations tend to be similar to the serum concentration of ionized calcium, i.e., approximately 50% of total serum calcium.

Calcium crosses the placenta, reaching higher levels in fetal blood than in the mother, and is excreted in breast milk.

Calcium is excreted mainly in the feces, either as a result of passing through the gut unabsorbed or through biliary or pancreatic secretion into the gut lumen. Very small amounts of calcium are excreted in the urine as most renally filtered calcium is reabsorbed. Urinary excretion of calcium is promoted by growth hormone, calcitonin and nonthiazide diuretics, whereas parathyroid hormone, Vitamin D, thiazide diuretics or a decrease in ionized calcium concentration tend to decrease the amount of calcium excreted in the urine. Calcium is also excreted in sweat.

Indications: The treatment of hypocalcemia for those conditions requiring a prompt increase in blood plasma calcium concentrations, such as neonatal tetany and tetany due to parathyroid deficiency, vitamin D deficiency and alkalosis. The prevention of hypocalcemia during exchange transfusions of citrated blood. In the treatment of hyperkalemia when there is ECG evidence of secondary cardiac toxicity.

Calcium salts have also been administered as adjunctive therapy in a number of conditions, including the following: insect bites or stings (e.g., black widow spider), sensitivity reactions characterized by urticaria or angioedema, magnesium sulfate overdosage, or lead colic.

The use of calcium is not recommended in cardiac arrest except in cases of calcium channel blocker overdose, hyperkalemia or severe hypocalcemia. For more information on the role of calcium in CPR, see Drugs Used in Cardiac Arrest in the Clin-Info section.

Contraindications: Hypercalcemia and hypercalciuria (e.g., in hyperparathyroidism, vitamin D overdosage, decalcifying tumors such as plasmocytoma, bone metastases); severe renal or cardiac disease; calcium loss due to immobilization.

Precautions: In mild hypercalciuria (exceeding 300 mg/24 hours) as well as in chronic renal failure, or where there is evidence of stone formation in the urinary tract, adequate checks must be kept on urinary calcium excretion. If necessary, the dosage should be reduced or calcium therapy discontinued.

Because concurrent use of i.v. calcium with digitalis glycosides may increase the risk of cardiac arrhythmias, the use of i.v. calcium in digitalized patients should be avoided. If absolutely necessary, i.v. calcium should be given slowly and in small amounts with ECG monitoring.

When severe hypocalcemia co-exists with hyperphosphatemia (>6 mmol/L), patients should be treated for hyperphosphatemia prior to the administration of i.v. calcium; the aim is to achieve a proper calcium/phosphate ratio in order to prevent extraskeletal deposition of calcium. Correction of hyperphosphatemia may require measures such as discontinuing exogenous phosphate, administration of oral aluminum hydroxide, or dialysis.

High dose calcium therapy by any of the parenteral routes should always be accompanied by very careful monitoring of serum concentration and urinary calcium excretion, particularly in children. Serum calcium concentrations should generally be maintained between 2.25 and 2.60 mmol/L. Cardiac monitoring is also recommended.

Drug Interactions: Digitalis glycosides (see Precautions). Parenteral calcium is precipitated by carbonates, bicarbonates, phosphates, sulfates and tartrates in addition to i.v. solutions containing various drugs. Specialized references should be consulted for compatability information.

Adverse Effects: Cardiovascular: Hypotension, bradycardia, cardiac arrhythmias, syncope and cardiac arrest may occur with too rapid i.v. administration.

Local: Tissue irritation and necrosis may occur with i.m. or s.c. injection, or if extravasation occurs during i.v. administration, particularly with the chloride salt.

Symptoms: Markedly elevated plasma calcium level, weakness, lethargy, intractable nausea and vomiting, coma and sudden death.

Treatment: To rapidly lower serum calcium to safe levels, administer sodium chloride by i.v. infusion plus a potent natriuretic agent, e.g., furosemide, to increase renal clearance of calcium and reduce hypercalcemia.

Dosage: Table I lists the elemental calcium content of the available parenteral calcium salts.

I.V.: Calcium injections must be administered slowly, through a small needle into a large vein to minimize venous irritation. The rate of administration should not exceed 0.35 to 0.9 mmol/minute. Injection should be stopped if patient complains of discomfort. Patients should remain recumbent for a short period following injection.

I.M.: Calcium chloride should never be injected i.m. as it may cause severe necrosis and sloughing when injected into tissue. Other calcium salts should only be administered i.m. when i.v. access cannot be established.

Intracardiac: 1.35 to 5.4 mmol (as Cl into the ventricle cavity. Not to be injected into the myocardium.

CALCIUM SALTS: PARENTERALGeneral Monograph,Calcium Therapy

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