4. MgSo4 Flashcards
Mode of action
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.
Physiology:
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:
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
Cardiovascular
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.
Respiratory
: magnesium has no effect on respiratory drive, but it may weaken
respiratory muscles. It reduces bronchomotor tone
Uterus
: 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
Renal:
magnesium acts as a vasodilator and diuretic.
Magnesium Toxicity
— 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.
Clinical Uses of Magnesium Sulphate
Pre-eclampsia and eclampsia:
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
Acute arrhythmias
: 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.
Hypomagnesaemia
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.
Other uses
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.
