4. MgSo4

many processes are dependent on magnesium (Mg2+), including the production and functioning of ATP (to which it is chelated) and the biosynthesis of DNA and RNA. It acts as a natural calcium (Ca2+) antagonist. High extracellular Mg2+ leads to an increase in intracellular Mg2+, which in turn inhibits Ca2+ influx through voltagedependent Ca2+ channels. It is this non-competitive inhibition that appears to mediate many of its effects. It also competes with calcium for binding sites on sarcoplasmic reticulum, thereby inhibiting its release. It acts as a physiological NMDA receptor antagonist. High concentrations inhibit both the presynaptic release of acetylcholine (Ach) as well as post-junctional potentials. — Mg2+ has an antiadrenergic action; release at all synaptic junctions is decreased and it inhibits catecholamine release.

magnesium is the fourth most abundant cation in the body, as well as being the second most important intracellular cation (after potassium). It activates at least 300 enzyme systems. It affects the activity of neurons, of myocardial and skeletal muscle fibres, and of the myocardial conduction system. It also influences vasomotor tone and hormone receptor binding.

Central and peripheral nervous systems: magnesium penetrates the blood–brain barrier poorly, but it nevertheless depresses the CNS and is sedating. It acts as a cerebral vasodilator, and it interferes with the release of neurotransmitters at all synaptic junctions. Deep tendon reflexes are lost at a blood concentration of around 8–10 mmol

magnesium reduces vascular tone via peripheral vasodilatation thought to be mediated at least partly by the endothelial nitric oxide pathway. It also causes sympathetic block and the inhibition of catecholamine release. It decreases cardiac conduction and diminishes myocardial contractile force. This intrinsic slowing is opposed partly by vagolytic action.

: magnesium has no effect on respiratory drive, but it may weaken respiratory muscles. It reduces bronchomotor tone

: it is a powerful tocolytic, which has implications for mothers who are being treated with the drug to control hypertensive disease of pregnancy prior to delivery

magnesium acts as a vasodilator and diuretic.

— 0.7–1.0 mmol l−1 – normal blood level. — 4.0–8.0 mmol l−1 – therapeutic level. — 15.0 mmol l−1 – respiratory paralysis. — 15.0 mmol l−1 – at these levels SAN and AV block is complete. — 25.0 mmol l−1 – cardiac arrest. — Magnesium crosses the placenta rapidly and so may exert similar effects in the neonate, which may be hypotonic and apnoeic.

magnesium sulphate decreases systemic vascular resistance and reduces CNS excitability. Following the Magpie Trial, its use in the UK to pre-empt eclamptic convulsions is now well established A loading dose of 4 g over 5–15 minutes is followed by an infusion at a rate of 1 g hr–1 for 24 hours

: it is effective at abolishing tachyarrhythmias (particularly ventricular), those induced by adrenaline, digitalis and bupivacaine, and torsade de pointes associated with a long QT interval. A prolonged QTc is itself associated with hypomagnesaemia. The ECG of hypermagnesaemia shows widening QRS with a prolonged P–Q interval. A typical dose regimen for the emergency treatment of arrhythmias is 2.0 g (8 mmol) infused over 10–15 minutes.

This may have endocrine and nutritional causes (normal intake is 0.4 mmol kg–1 daily). It may be caused by malabsorption and is also associated with critical illness. Acute decreases may follow subarachnoid haemorrhage.

Tetanus: this is rare in the UK, but magnesium sulphate by infusion is the primary treatment for the muscle spasm and autonomic instability caused by this condition.
Epilepsy: it can be used to control status epilepticus.
Subarachnoid haemorrhage: it has been used to prevent cerebral vasospasm following aneurysmal subarachnoid haemorrhage.
Asthma: magnesium sulphate is a bronchodilator that can be effective in severe refractory asthma. (Initial dose is 25 mg kg−1 by infusion, or up to 2 g intravenously over 20 minutes).
Analgesia: as a physiological NMDA receptor antagonist, it has been used as both an epidural and a subarachnoid adjunct to local anaesthetics for postoperative analgesia.
Constipation and dyspepsia: magnesium is a laxative and an antacid.