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magnesium sulfate in water for injection Clinical Pharmacology

CLINICAL PHARMACOLOGY

Magnesium (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.

Magnesium prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Magnesium is said to have a depressant effect on the central nervous system, but it does not adversely affect the mother, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal serum magnesium levels range from 1.3 to 2.1 mEq/liter.

As serum magnesium rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the serum level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower serum levels of magnesium.

Magnesium acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of magnesium poisoning are antagonized to some extent by intravenous administration of calcium.

With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter.

Pharmacokinetics:

Absorption: Intravenously administered magnesium is immediately absorbed.

Distribution: Approximately 1-2% of total body magnesium is located in the extracellular fluid space. Magnesium is 30% bound to albumin.

Metabolism: Magnesium is not metabolized.

Excretion: Magnesium is excreted solely by the kidney at a rate proportional to the serum concentration and glomerular filtration.

Special Populations:

Renal Insufficiency: Magnesium is excreted solely by the kidney. In patients with severe renal insufficiency, the dose should be lower and frequent serum magnesium levels must be obtained (see DOSAGE AND ADMINISTRATION).

Hepatic Insufficiency: Magnesium is excreted solely by the kidney. No dosing adjustments are necessary in hepatic insufficiency.

Drug-Drug Interactions: Drug induced renal losses of magnesium occur with the following drugs or drug classes:

     Aminoglycosides                                   Amphotericin B
     Cyclosporine                                         Diuretics
     Digitalis                                                 Cisplatin
     Alcohol

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