PRESENTED BY: PARTH DHANANI (10BPW618)

B.Pharm.Hons. BATCH E

BACKGROUND:

• Ten percent of all pregnancies are complicated by hypertension (HTN).Eclampsia and preeclampsia account for about half of these cases worldwide.

• In 1619, Varandaeus coined the term eclampsia in a treatise on gynecology.

• DEFINITION: Eclampsia is defined as the clinical presentation of an unexplained seizure, convulsion, or altered mental status in the setting of the signs and symptoms of preeclampsia. It is considered a complication of severe preeclampsia.

• A woman with preeclampsia develops:--- high blood pressure (>140 mmHg systolic or >90 mmHg diastolic)--- protein in the urine--- swelling (edema) of the legs, hands, face or entire body.

In eclampsia, placenta does not form a normal system of arteries [illness( diabetes or high blood pressure), genetic (inherited) factors and

the way the mother's immune system reacts to the growing placenta]↓

Placenta does not anchor itself as deeply as expected within the wall of the uterus↓

As the pregnancy progresses, a placenta creates an abnormal balance of enzymes (proteins) called growth factors(VEGF)

(placental production and secretion of antiangiogenic factors such as protein like tyrosine kinase 1 and activin A that antagonizes VEGF)

↓ANGIOGENESIS IMPEDANCE

↓Changes the way that arteries in the mother and the placenta

function- Arteries throughout the body can tighten (become narrower), ↑se BP Become "leaky" allowing protein or fluid to seep through their walls, which

causes tissues to swell →Edema Also react to the abnormal growth factor balance by forming clots Abnormal cerebral blood flow in the setting of extreme hypertension.

Vessels become dilated with increased permeability and cerebral edema occurs and results in ischemia and encephalopathy → Seizures

Many uterovascular changes occur due to the interaction between fetal and maternal allografts and result in systemic and local vascular changes. These system changes contribute to the brain pathology in eclampsia by inhibiting the regulation of cerebral perfusion.

Problems with the cells that line the insides of certain blood vessels

Overproduction, underproduction, or malfunction of proteins needed to grow new blood vessels in the placenta

Abnormal development of capillaries and certain types of muscles within the placenta

Increased immune system sensitivity which causes the mother’s immune system to attack certain molecules that are needed to regulate blood flow into the placenta

Increased overall sensitivity to hormones that regulate blood pressure and blood flow in different parts of the body

Family history of preeclampsia, prior preeclampsia and eclampsia

Poor outcome of previous pregnancy, including→ Intrauterine growth retardation→ Abruptio placentae→ Fetal death

Pre-existing medical condition – → Obesity → Chronic hypertension → Renal disease → Vascular and connective tissue disorders → Gestational diabetes → Systemic lupus erythematosus

Multifetal gestations (Carrying more than one baby) Teen pregnancy Patient older than 35 years Lower socioeconomic status

Ante partum haemorrhage Liver complications (liver encephalopathy) Kidney complications ( ARF) Jaundice Coma Fetal death - uncommon Maternal death - uncommon Premature delivery ( Small baby) Separation of placenta from uterus Damage to the brain due to seizures

In addition to swelling, protein in the urine, and high blood pressure, symptoms of eclampsia can include:

A change in reflexes (convulsions) Rapid weight gain caused by a significant increase

in bodily fluid Abdominal pain Severe headaches Reduced output of urine or no urine Blood in the urine dizziness Excessive vomiting and nausea

Laboratory Studies: Urinalysis to detect for proteinuria (>300 mg/24 h or > 1 g/L) The CBC may reveal the following:

Anaemia due to microangiopathic haemolysis Increased bilirubin >1.2 mg/dL Thrombocytopenia (<100,000) due to HELLP syndrome Elevated lactate dehydrogenase (LDH) levels (threshold of 180–600 U/L)

The serum creatinine level is elevated. Creatinine clearance (CrCl) may be less than 90 mL/min/1.73 m2.

Uric acid levels may be increased mildly Liver function test results may reveal the following :

Aspartate aminotransferase (SGOT) level higher than 72 IU/L Total bilirubin levels higher than 1.2 mg/d Elevated levels due to

hepatocellular injury and HELLP syndrome

LDH level higher than 600 IU/L .

Imaging Studies: Head CT scanning

CT scan is used to assess intracranial haemorrhage, subarachnoid haemorrhages, or cerebrovascular accidents.

Transabdominal ultrasonography Transabdominal ultrasonography is used to estimate gestational age. This may also be used to rule out abruptio placentae that can complicate eclampsia.

GOALS OF THERAPY: →Preventing low oxygen levels (hypoxia) in

the mother → Controlling maternal blood pressure

→ Preventing ongoing seizures → Deliver the baby by the safest method

possible The only real cure for eclampsia is the birth

of the baby.

Anticonvulsants: 1. MgSO4: 4 g IV initially, followed by 1-4 g IM q4h prn

Alternatively, 1-4 g/h continuous infusion 2. Diazepam: 5-10 mg IV q10-20min; repeat in 2-4 h prn

(Valium) not to exceed 30 mg in 8 h Antihypertensives: 1. Hydralazine: 5 mg IV initially, then 5-10 mg IV q20-30min prn;

not to exceed 30 mg 2. Labetalol: 20-30 mg IV over 2 min followed by 40-80 mg IV at

10-min intervals; not to exceed 300 mg/dose

3. Nitropruside: 0.3-0.5 mcg/kg/min IV, increase in increments of 0.5 mcg/kg/min

4. Diazoxide: 1-3 mg/kg IV as a single injection, not to exceed 150 mg/dose

Supportive treatment: Monitoring fluid intake( NS, D5%)

PATIENT’S DATA DOA:20/07/2010DOD:22/07/2010

PATIENT NAME:XYZ AGE:23 years SEX: Female ADDRESS: Bader district, Rajasthan

HEIGHT:5’3’’ WEIGHT:48kg

INVESTIGATION DAY 1 DAY 2

Hb 6.3 8.5

TC 26,200 26,000

DC 68/17/1/12/2 73/20/2/5/0

PC ↓se 82,000 1,66,000

PT ↑se Total Control

24 sec13.2 sec

---

RBS 120 mg/dL (75-115mg/dL)

---

Urea ↑se 193.47(10-20mg/dL)

---

Creatinine ↑se 8.88 (<1.5mg/dL)

---

Sodium 135.26 142.37

Potassium 4.7 4.1

S.Bilirubin ↑se 1.41 (0.3-1mg/dL)

---

SOPT ↑se 138.5 (0-35U/L) ---

S.Ammonia 39.59 ---

INVESTIGATION DAY 1 DAY 2

LDH ↑se 2835 (14-26%) ------

pH ↓se (7.38-7.44) 7.21 ---

pCO2 ↑se (35-45mmhg)

52 ---

PO2 ↑se (80-100mmhg)

67 ---

Bicarbonate ↓se (20-30mE/L)

11 ---

•NormalX-RAY

•Retain products

•ARF

USG

(Abdomen)

•Bilateral ischaemiaCT

SCAN(Brain)

ECLAMPSIA (leading cause of death) POST PARTAL ENCEPHALOPATHY SEPTICAEMIA ARF LIVER INJURY

DRUG

DOSE ROA

DURATION

GENERIC NAME

D1

D2

Inj. Pipzo 4.5 mg in 100ccNS

i.v. 12hrly Piperacillin+tazobactam

√ √

Inj. Metrogyl 100ml i.v. 8hrly Metronidazole √ √

Inj. Pantodac 40mg i.v. OD Pantoprazole √ √

Inj. Levepil 500mg in 100ccNS

i.v. 8hrly Levetiracetam √ √

Inj. Lasix 2amp i.v. BD Furosemide √ √

Inj. FFP 250ml i.v. 8hrly Fresh frozen plasma

√ √

Inj. Dopamine 2@ in 50ccNS i.v. 6hrly Dopamine √ √

Inj. Febrinil 1@ i.v. sos Paracetamol √ √

Inj. Falcigo 60mg i.v. OD Artesunate √ √

Inj. D25% 500ml i.v. 10ml/hr Dextrose √ √

Inj. Sodium bicarbonate

(0.6*wt*HCO3 def.)0.6*48*9 = 259.2mEq

i.v. 13@ straight &13@ 6hrly

Bicarbonate √ √

Pipzo dose claculation:

Cl cr = (140 – age yr) * Body wt. = (140-23) * 48 = 8.7872 * S.cr 72 * 8.88

DRUG

DOSE ROA DURATION

GENERIC NAME

D1 D2

Inj. Duphalac 15ml i.v. 8hrly Lactulose √ √

Inj. Vit K1 1@ in 100ccNS

i.v. OD Vit K1 √ √

Inj. Norad 2@ in 50ccNS

i.v. 6hrly Nor adrenaline

--- √

CreatineClearance

Dose Dose interval

20-80 4/0.5 8

<20 4/0.5 12

DRUGS INTERACTIONS MANAGEMENT

lactulose ↔ Artesunate( moderate)

Electrolyte loss and increase the risk of torsade de pointes ventricular arrhythmia. Electrolyte disturbances including hypokalemia and hypomagnesemia.

The recommended dosage and duration of use should not be exceeded. Electrolye supplements needed to be administered.

lumefantrine ↔ food(moderate)

Coadministration with grapefruit juice may increase the plasma concentrations of artemethe. The mechanism is decreased clearance due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

Avoid the consumption of grapefruits and grapefruit juice. To ensure maximal oral absorption, artemether-lumefantrine should be taken with food. Inadequate food intake can increase the risk for recrudescence of malaria.

DRUGS INTERACTIONS MANAGEMENT

furosemide ↔ lactulose(Moderate)

Potentiate the pharmacologic effects of diuretics. Laxatives can cause significant losses of fluid and electrolytes

In general, laxatives should only be used on a short-term, intermittent basis in recommended dosages. Contact physician if they experience signs and symptoms of fluid and electrolyte depletion such as dizziness, lightheadedness, dry mouth, thirst, fatigue, weakness, decreased urination, postural hypotension, and tachycardia.

http://en.wikipedia.org/wiki/Ischaemic_heart_disease

http://www.rxmed.com/b.main/b1.illness/b1.1.illnesses/Ischaemic%20Heart%20disease.html

http://www.drugs.com/interactions-check.php?drug_list

Patient’s case file at shrey hospital

THANK

YOU