►ANTICONVULSANTS USED IN ANTICONVULSANTS USED IN ECLAMPSIAECLAMPSIA

►Magnesium sulphateMagnesium sulphate►Lytic cocktail regimenLytic cocktail regimen►Phenytoin Phenytoin ►DiazepamDiazepam►Thiopentone sodiumThiopentone sodium

►Magnesium sulphate is also known as Magnesium sulphate is also known as Epsom salt .Epsom salt .

► It is MgSO4.7H2O.USP.It is MgSO4.7H2O.USP.► It has a molecular weight of 246&1g of It has a molecular weight of 246&1g of

salt contains 98mg of elemental salt contains 98mg of elemental magnesium.magnesium.

► It has been called the ‘forgotten It has been called the ‘forgotten mineral’ &the 5cent mineral.mineral’ &the 5cent mineral.

Mechanism of actionMechanism of action

►Blockade of NMDA subtypeof Blockade of NMDA subtypeof glutamate channel receptor in voltage glutamate channel receptor in voltage dependant manner.dependant manner.

►Peripheral action-at NMjunction Peripheral action-at NMjunction causing blockade of calcium entering causing blockade of calcium entering the cell and blocking calcium at the the cell and blocking calcium at the intracellular sites ,reducing the intracellular sites ,reducing the presynaptic acety choline release at presynaptic acety choline release at the end plate,reducing motor end the end plate,reducing motor end plate sensitivity to acetyl choline.plate sensitivity to acetyl choline.

►Central action:preferential uptake by Central action:preferential uptake by the hippocampus and cerebral cortex the hippocampus and cerebral cortex rich in NMDA receptors.rich in NMDA receptors.

► Inhibits platelet activation.Inhibits platelet activation.►Decreases systemic vascular resistance.Decreases systemic vascular resistance.►Dilates the orbital vessels ,increases Dilates the orbital vessels ,increases

cardiac output,renal blood cardiac output,renal blood flow,uteroplacental blood flow.flow,uteroplacental blood flow.

PharmacokineticsPharmacokinetics

►Only 0.3% of total body magnesium is Only 0.3% of total body magnesium is found in serum of which 33% is protein found in serum of which 33% is protein bound ,5%are complexed to anions like bound ,5%are complexed to anions like citrate and phosphate,62%in ionised citrate and phosphate,62%in ionised form.form.

►Normal serum levels vary from 1.6-Normal serum levels vary from 1.6-2.1mEq/l.2.1mEq/l.

►Magnesium is not absorbed orally.Magnesium is not absorbed orally.► kidneys excrete magnesium.kidneys excrete magnesium.

Magnesium sulphate toxicityMagnesium sulphate toxicity

► Maternal side effects:Maternal side effects:► Disappearence of patelar reflex is the first Disappearence of patelar reflex is the first

sign of impending toxicity(8-10mEq/l)sign of impending toxicity(8-10mEq/l)► Dry mouth ,flushing,drowsiness,blurred vision Dry mouth ,flushing,drowsiness,blurred vision

,slurred speech, nausea,vomiting(9-12mEq/l),slurred speech, nausea,vomiting(9-12mEq/l)► Respiratory depression 12mEq/lRespiratory depression 12mEq/l► Cardiotoxicity-prolonged PR,QT,QRS(10-Cardiotoxicity-prolonged PR,QT,QRS(10-

15mEq/l)15mEq/l)► Cardiac arrest-30mEq/lCardiac arrest-30mEq/l

►Fetal effect:Fetal effect:►Neurological,neuromuscular Neurological,neuromuscular

depression.depression.►Protective effect against cerebral Protective effect against cerebral

palsy.palsy.►Hyporeflexia.Hyporeflexia.►Decreases FHR variability.Decreases FHR variability.►Disturbed fetal calcium hemostasis.Disturbed fetal calcium hemostasis.

►Management of magnesium sulphate Management of magnesium sulphate toxicity is by calcium.toxicity is by calcium.

► Intravenous calcium as 10ml of 10%calcium Intravenous calcium as 10ml of 10%calcium gluconate infusion is given slowly over 3 gluconate infusion is given slowly over 3 minutes .minutes .

► It increases the acetylcholine liberated at It increases the acetylcholine liberated at the neuromuscular junction .the neuromuscular junction .

► If respiratory failure ensues prompt If respiratory failure ensues prompt endotracheal intubation & ventilation are life endotracheal intubation & ventilation are life saving. saving.

Magnesium sulphateMagnesium sulphate

►The use of MgSO4 in managing The use of MgSO4 in managing eclampsia was first suggested by Horn eclampsia was first suggested by Horn in Germany in 1906 who injected it in Germany in 1906 who injected it intrathecally.intrathecally.

► In 1925 Lazard &in 1926 Dorsett In 1925 Lazard &in 1926 Dorsett recommended the intravenous recommended the intravenous &intramuscular route of MgSO4 &intramuscular route of MgSO4 theraphy.theraphy.

►Pritchard gets the credit of Pritchard gets the credit of popularising MgSO4 for eclampsia in popularising MgSO4 for eclampsia in modern obstetrics by his famous modern obstetrics by his famous parkland hospital regimen popularly parkland hospital regimen popularly known as the Pritchard regimen.known as the Pritchard regimen.

► In 2002 the results of Magpie trial In 2002 the results of Magpie trial another multicentric trial was another multicentric trial was published which showed beyond any published which showed beyond any resonable doubt the efficacy of MgS04 resonable doubt the efficacy of MgS04 in reducing the risk of eclampsia.in reducing the risk of eclampsia.

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

Pritchard MgSO4 regimen Pritchard MgSO4 regimen

Loading dose:Loading dose:

4g (20ml of 20%) 4g (20ml of 20%) IV over not less IV over not less than 3 min than 3 min followed by 10g followed by 10g (20ml of 50%)IM in (20ml of 50%)IM in each buttock.each buttock.

If convulsion If convulsion persists over 15 persists over 15 min 2g (10ml of min 2g (10ml of 20%) is given over 20%) is given over 2 min.2 min.

Maintenance dose:Maintenance dose:

5g (10ml of 50%)is 5g (10ml of 50%)is given every 4 given every 4 hours & alternate hours & alternate sites after assuring sites after assuring

1)Presence of 1)Presence of knee reflexknee reflex

2)Respiratory rate 2)Respiratory rate >14/min>14/min

3)Urine output 1003)Urine output 100

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

Loading Loading dose:dose:

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

maintenamaintenance dosence dose

(20g of (20g of 50%)adde50%)added to d to 1000ml of 1000ml of dextrose dextrose given as given as IV IV infusion infusion as 100ml as 100ml per /hr.per /hr.

Dosing shedule of other Dosing shedule of other regimenregimen

loadingloading maintenancmaintenancee

Zuspan Zuspan 4gIV over 5-4gIV over 5-10hrs10hrs

1-2g/hr as IV 1-2g/hr as IV infusioninfusion

Charles Charles FlowersFlowers

4g IV in 4g IV in 250ml of 5% 250ml of 5% DD

5g every4-5g every4-6hrs as IM6hrs as IM

Chesley -Chesley -TepperTepper

5g every 45g every 4thth hour given hour given as IMas IM

5g every 45g every 4thth hour given hour given as IMas IM

EastmanEastman 5g every 45g every 4thth hour given hour given as IMas IM

5g every 45g every 4thth hour given hour given as IMas IM

►Hall Anderson and Hall Anderson and Herbert :2%magnesium sulphate Herbert :2%magnesium sulphate solution at 140 drops /min in first solution at 140 drops /min in first hour ,80 drops /min in 2hour ,80 drops /min in 2ndnd hour ,40 hour ,40 drops /min in the 3drops /min in the 3rdrd hour. hour.

►Cruink shant et al :4g given as IV Cruink shant et al :4g given as IV (loading dose) followed by 2g /hour.(loading dose) followed by 2g /hour.

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

Loading Loading dosedose

MaintenaMaintenance dosence dose

4g MgSO4 4g MgSO4 given given both as IV both as IV &IM&IM

2g given 2g given as IV /IM as IV /IM every every 3hrs.if 3hrs.if convulsioconvulsions ns recurred recurred after 15 after 15 min min additional additional dose of dose of MgSo4 MgSo4 givengiven

►Begum et al used low dose Dhaka Begum et al used low dose Dhaka regimen comprising of 10g of loading regimen comprising of 10g of loading dose ,following which 2.5g was given dose ,following which 2.5g was given intramuscularly 4intramuscularly 4thth hourly-she hourly-she concluded that half the standard dose concluded that half the standard dose was sufficient to prevent convulsion.was sufficient to prevent convulsion.

►Mahajan et al used 6g of loading dose Mahajan et al used 6g of loading dose &4g maintenance dose with &4g maintenance dose with recurrence of 1.05%.recurrence of 1.05%.

► Therapeutic levels Therapeutic levels to prevent to prevent convulsions from convulsions from different studies.different studies.

regimenregimen TherapeutTherapeutic levels ic levels {mEq/l}{mEq/l}

PritchardPritchard 4.8-8.44.8-8.4

ZuspanZuspan 3-43-4

Chesley Chesley &Tepper&Tepper

4-74-7

Cruink Cruink shantshant

3.3-4.73.3-4.7

EastmanEastman 3-63-6

Hall,AnderHall,Anderson son &herbert&herbert

6-86-8

Lytic cocktail regimenLytic cocktail regimen

► Popularised in India by Dr.Krishna Menon in Popularised in India by Dr.Krishna Menon in 1961.1961.

► Intial dose -25mg of chlorpromazine Intial dose -25mg of chlorpromazine +100mg of pethidine in 20ml of 5%dextrose +100mg of pethidine in 20ml of 5%dextrose given IV along with 50mg of chlorpromazine given IV along with 50mg of chlorpromazine +25mg of phenergan given IM.+25mg of phenergan given IM.

►Maintenance dose-50mg of chorpromazine Maintenance dose-50mg of chorpromazine +25mg phenergan given IM in alternate +25mg phenergan given IM in alternate buttocks 4buttocks 4thth hourly till 24 hrs after last hourly till 24 hrs after last convulsionconvulsion

Phenytoin regimenPhenytoin regimen

► It’s a drug only for prevention and not It’s a drug only for prevention and not for treatment of convulsions.for treatment of convulsions.

►Mechanism of action :membrane Mechanism of action :membrane stabilizing effect on neuronal stabilizing effect on neuronal membranes.membranes.

►GABA concentration is increased –GABA concentration is increased –inhibiting the activity.inhibiting the activity.

►Sodium concentration is reduced.Sodium concentration is reduced.

►Side effects: Side effects: ►PhlebitisPhlebitis►Peripheral neuropathyPeripheral neuropathy►Blood dyscrasiasBlood dyscrasias►Megaloblastic anemiaMegaloblastic anemia►Cardiac dysarrythmia,cardiovascular Cardiac dysarrythmia,cardiovascular

collapse ,hypotensionand severe CNS collapse ,hypotensionand severe CNS depression.depression.

►Differrent regimens are followed most Differrent regimens are followed most notable is Lucas .notable is Lucas .

► Initial dose :1g IV slow infusion over Initial dose :1g IV slow infusion over 20minutes followed by 100mg every 20minutes followed by 100mg every 66thth hourly for next 24 hours . hourly for next 24 hours .

►Diazepam :It was introduced and Diazepam :It was introduced and popularized by Lean et al.popularized by Lean et al.

►Mechanism of action:by depressant Mechanism of action:by depressant action on CNS increasing the seizure action on CNS increasing the seizure threshold& facilitates the inhhibitory threshold& facilitates the inhhibitory action of GABA.action of GABA.

►Side effects: respiratory depression,risk Side effects: respiratory depression,risk of aspiration pneumonia due to of aspiration pneumonia due to prolonged sedation.prolonged sedation.

►FLABBY BABY syndromeFLABBY BABY syndrome

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

during the next 24 hrs an infusion of during the next 24 hrs an infusion of 20mg diazepam in 500ml NS given.20mg diazepam in 500ml NS given.

►Thiopentone sodium:0.5mg dissolved Thiopentone sodium:0.5mg dissolved in 20ml of 5% D given IV very slowly in 20ml of 5% D given IV very slowly by expert anaesthetist .by expert anaesthetist .

► If the above therapy fails complete If the above therapy fails complete anaesthesia with assisted ventilation anaesthesia with assisted ventilation can be employed.can be employed.