SAQ. In the third trimester, a pregnant woman develops jaundice, thought to be caused by antihypertensive drugs.

1. Which is the most likely drug that may cause jaundice? What is the mechanism 

• Likely drug: Alpha methyldopa

Mechanism of Hepatotoxicity: 

• Autoimmune mechanism
• Metabolic studies suggest that methyldopa may induce an autoimmune liver injury (perhaps via a toxic metabolic intermediate serving as an antigenic hapten presented on the surface of hepatocytes) in susceptible hosts.

1. How will you investigate to support your diagnosis?

Investigations : 

The acute liver injury within 2 -12 weeks of starting therapy.

Management of hypertension in pregnancy:

Non- pharmacological

• Regular exercise may be continued
• For obese women: advised to avoid weight gain of more than 6-8 kg

Pharmacological:

• Drugs of choice (Contraindicated: ACEI, ARB, Diuretics)
  • Methyldopa
  • Beta blockers (Labetalol)
  • CCB (Nifedipine, amlodipine)
  • Doxazosin

• Prevention of HTN and pre-eclampsia:

• High or moderate risk of pre-eclampsia: 100-150 mg of Aspirin daily from week 12 to weeks 36-37 of pregnancy

• Calcium supplementation: 1.5-2 gm/day is recommended for prevention of pre-eclampsia in women with low dietary intake of calcium (<600 mg/day), to be commenced at the first antenatal clinic.

• For prevention & Rx of eclampsia: IV MgSO4 (but not with CCB)

• Rx of severe HTN

• Hospitalization is indicated 

• Anti-HTN drug & route of administration depends on expected time of delivery

• IV Labetalol/oral Methyldopa/Nifedipine should be initiated

• Na-nitroprusside is the drug of last choice, due to risk of fetal cyanide poisoning

• Preeclampsia associated with pulmonary oedema: nitroglycerine IV infusion

• Delivery: Indicated in 

1. Pre-eclampsia with visual disturbances or hemostatic disorders
2. At 37 weeks in asymptomatic woman

Preeclampsia:

• Control of blood pressure, 
• IV magnesium sulfate as prophylaxis against seizures.
• Correction of coagulation abnormalities 
• Monitoring of fluid balance. 
• If these measures are ineffective and eclampsia supervenes  
  • urgent delivery 

Eclampsia 

• It usually presents with seizures on a background of pre-eclampsia but rarely can occur before the onset of hypertension and proteinuria. 
• Treatment: 
  • Anti hypertensives
  • IV magnesium sulfate (Inf. Nalepsin 4 gm/100 ml) 4 g, over 15 mins followed by an infusion of 1 g/hr titrated to serum magnesium for 24 h. 
  • Correction of coagulation abnormalities.
  • Monitoring of fluid balance. 
  • Delivery of the fetus as soon as possible. 

Prognosis:

• Women with pre-eclampsia are more likely to develop HTN, CKD, IHD, cerebrovascular in later life.