ANTICONVULSANTS USED IN ECLAMPSIA Magnesium sulphate Lytic cocktail regimen Phenytoin Diazepam Thiopentone sodium

Magnesium sulphate is also known as Epsom salt . It is MgSO4.7H2O.USP. It has a molecular weight of 246&1g of salt contains 98mg of elemental magnesium. It has been called the forgotten mineral &the 5cent mineral.

Mechanism of action
Blockade of NMDA subtypeof glutamate channel receptor in voltage dependant manner. Peripheral action-at NMjunction causing actionblockade of calcium entering the cell and blocking calcium at the intracellular sites ,reducing the presynaptic acety choline release at the end plate,reducing motor end plate sensitivity to acetyl choline.

Central action:preferential uptake by the hippocampus and cerebral cortex rich in NMDA receptors. Inhibits platelet activation. Decreases systemic vascular resistance. Dilates the orbital vessels ,increases cardiac output,renal blood flow,uteroplacental blood flow.

Pharmacokinetics
Only 0.3% of total body magnesium is found in serum of which 33% is protein bound ,5%are complexed to anions like citrate and phosphate,62%in ionised form. Normal serum levels vary from 1.61.62.1mEq/l. Magnesium is not absorbed orally. kidneys excrete magnesium.

Magnesium sulphate toxicity

Maternal side effects: Disappearence of patelar reflex is the first sign of impending toxicity(8-10mEq/l) toxicity(8Dry mouth ,flushing,drowsiness,blurred vision ,slurred speech, nausea,vomiting(9-12mEq/l) nausea,vomiting(9Respiratory depression 12mEq/l CardiotoxicityCardiotoxicity-prolonged PR,QT,QRS(10-15mEq/l) PR,QT,QRS(10Cardiac arrest-30mEq/l arrest-

Fetal effect: Neurological,neuromuscular depression. Protective effect against cerebral palsy. Hyporeflexia. Decreases FHR variability. Disturbed fetal calcium hemostasis.

Management of magnesium sulphate toxicity is by calcium. Intravenous calcium as 10ml of 10%calcium gluconate infusion is given slowly over 3 minutes . It increases the acetylcholine liberated at the neuromuscular junction . If respiratory failure ensues prompt endotracheal intubation & ventilation are life saving.

Magnesium sulphate
The use of MgSO4 in managing eclampsia was first suggested by Horn in Germany in 1906 who injected it intrathecally. In 1925 Lazard &in 1926 Dorsett recommended the intravenous &intramuscular route of MgSO4 theraphy.

Pritchard gets the credit of popularising MgSO4 for eclampsia in modern obstetrics by his famous parkland hospital regimen popularly known as the Pritchard regimen. In 2002 the results of Magpie trial another multicentric trial was published which showed beyond any resonable doubt the efficacy of MgS04 in reducing the risk of eclampsia.

Cochrane review of 2002 which analysed the data from most of the studies available on MgSO4 concluded MgSO4 as being the superior to other anticonvulsant.

Pritchard MgSO4 regimen

Loading dose: 4g (20ml of 20%) IV over not less than 3 min followed by 10g (20ml of 50%)IM in each buttock. If convulsion persists over 15 min 2g (10ml of 20%) is given over 2 min. Maintenance dose: 5g (10ml of 50%)is given every 4 hours & alternate sites after assuring 1)Presence of knee reflex 2)Respiratory rate >14/min 3)Urine output 100

Baha M.Sibai at the university of Tennessee introduced guidelines for MgSO4 administration.

Loading dose: 6g IV (30ml of 20%)in 100 ml of 5% dextrose over 10-15 10minutes.

maintenanc e dose (20g of 50%)adde d to 1000ml of dextrose given as IV infusion as 100ml per /hr.

Dosing shedule of other regimen

Zuspan Charles Flowers Chesley Tepper Eastman loading 4gIV over 5510hrs 4g IV in 250ml of 5% D 5g every 4th hour given as IM 5g every 4th hour given as maintenance 1-2g/hr as IV infusion 5g every4every46hrs as IM 5g every 4th hour given as IM 5g every 4th hour given as

Hall Anderson and Herbert :2%magnesium sulphate solution at 140 drops /min in first hour ,80 drops /min in 2nd hour ,40 drops /min in the 3rd hour. Cruink shant et al :4g given as IV (loading dose) followed by 2g /hour.

In 1997 Suman sardesai from VM medical college Sholapur popularised low dose regimen.

Loading dose 4g MgSO4 given both as IV &IM

Maintenanc e dose 2g given as IV /IM every 3hrs.if convulsions recurred after 15 min additional dose of

Begum et al used low dose Dhaka regimen comprising of 10g of loading dose ,following which 2.5g was given intramuscularly 4th hourlyhourly-she concluded that half the standard dose was sufficient to prevent convulsion. Mahajan et al used 6g of loading dose &4g maintenance dose with recurrence of 1.05%.

Therapeutic levels to prevent convulsions from different studies.

regimen

Pritchard Zuspan Chesley &Tepper Cruink shant Eastman

Therapeutic levels {mEq/l} 4.8-8.4 4.83-4 4-7 3.33.3-4.7 3-6

Lytic cocktail regimen

Popularised in India by Dr.Krishna Menon in 1961. Intial dose -25mg of chlorpromazine +100mg of pethidine in 20ml of 5%dextrose given IV along with 50mg of chlorpromazine +25mg of phenergan given IM. Maintenance dose-50mg of chorpromazine +25mg dosephenergan given IM in alternate buttocks 4th hourly till 24 hrs after last convulsion

Phenytoin regimen
It s a drug only for prevention and not for treatment of convulsions. Mechanism of action :membrane stabilizing effect on neuronal membranes. GABA concentration is increased inhibiting the activity. Sodium concentration is reduced.

Side effects: Phlebitis Peripheral neuropathy Blood dyscrasias Megaloblastic anemia Cardiac dysarrythmia,cardiovascular collapse ,hypotensionand severe CNS depression.

Differrent regimens are followed most notable is Lucas . Initial dose :1g IV slow infusion over 20minutes followed by 100mg every 6th hourly for next 24 hours .

Diazepam :It was introduced and popularized by Lean et al. Mechanism of action:by depressant action on CNS increasing the seizure threshold& facilitates the inhhibitory action of GABA. Side effects: respiratory depression,risk of aspiration pneumonia due to prolonged sedation. FLABBY BABY syndrome

Loading dose 10mg slow IV over 2 min ,repeated if convulsion recurred followed by IV infusion of 40mg in 500ml NS for 24hrs,titrated against the levels of consciousness with the aim to keep woman sedated bit arousable. during the next 24 hrs an infusion of 20mg diazepam in 500ml NS given.

Thiopentone sodium:0.5mg dissolved in 20ml of 5% D given IV very slowly by expert anaesthetist . If the above therapy fails complete anaesthesia with assisted ventilation can be employed.