Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other mineral supplements, magnesium sulfate ATC code: A12CC02
Magnesium is the second most abundant cation in intracellular fluid and is an essential body electrolyte.
The body contains about 25 g of magnesium (about 14 mmol per kg body weight), approximately 60% of which is found in the skeleton. The daily amount of magnesium required by an adult is of the order of 270 to 350 mg (about 11 to 14 mmol). Symptomatic hypomagnesaemia is associated with a deficit of 0.5 – 1.0 mmol/kg.
Mechanism of action
It is a cofactor in numerous enzyme systems and is involved in phosphate transfer, muscle contractility and neuronal transmission.
Clinical efficacy and safety
The normal concentration of magnesium in plasma is around 0.65 to 1.0 mmol/L. Serum magnesium levels in the range 1.5 – 2.5 mmol/L cause vasodilatation in the peripheral and coronary circulation and corresponding increases of 20 – 25% in cardiac output and coronary blood flow. There is little change in heart rate or blood pressure.
Animal studies suggest that the effect of magnesium ions on cardiac muscle is to slow the rate of the sinoatrial node impulse formation and prolong conduction time. Limited data on patients with no evidence of heart disease indicate that intravenous magnesium prolongs PR interval, H (atria-His bundle) interval, antegrade AV nodal effective refractory period and sinoatrial conduction time. Within this concentration range there are no detectable effects on CNS function or neuromuscular transmission.
When given intravenously, magnesium sulfate has an immediate onset of action and its duration of activity is about 30 minutes. The onset of action of intramuscular magnesium sulfate is about one hour and its duration of action 3 – 4 hours.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
The amount of elemental magnesium provided by each 1 g of magnesium sulfate heptahydrate is 4.1 mmol; therefore 2 mL of a 50% solution will provide approximately 4 mmol of magnesium ions.
Distribution
Infused magnesium is distributed rapidly throughout the entire extracellular fluid space and some is taken up by bone but none by red blood cells.
About 40% of plasma magnesium is protein bound and is not ultrafiltrable. Most of the plasma Mg is bound with albumin, globulin and proteins and therefore not filterable at the glomerulus. The injected magnesium sulfate is promptly bound to plasma proteins to the same degree as that of endogenous magnesium.
Biotransformation
Magnesium sulfate is not metabolized.

Elimination
The major excretory pathway is renal and parenteral loads are rapidly eliminated in this way. Faecal loss is very limited.
Renal impairment
In renal impairment, there may be accumulation of magnesium.