Drugs used in pregnancy

1. CVS Drugs in Pregnancy
Chairperson:
Prof. Dr. Manzoor Mahmood
Professor,Department of Cardiology
BSMMU.
Presenter:
Dr. Swapan Kumar Sur
D-Card 2nd year student
Department of Cardiology , BSMMU.

3. FDA Category X drugs
• ACE inhibitors
• ARB
• Renin inhibitors
• Endothelin receptor inhibitors
• Statin
• Warfarin
• Amiodarone (Cat D)

4. Common agents for anticoagulation
 Warfarin (Cat X)
• Unfractionated heparin (UFH) (Cat C)
• Low-molecular-weight heparin (LMWH) (cat B )

5. Warfarin
• Crosses the placenta
• FDA class X in 1st trimester & class B in 2nd and 3rd trimester
• first trimester may cause fetal embryopathy.
• Warfarin dose<5mg risk of embryopathy is low
• 2 weeks before birth cause risk of fetal & maternal bleeding
• Safe during breast feeding
• A/E: spontaneous abortion, prematurity, still birth, Warfarin
embryopathy syndrome

6. warfarin embryopathy syndrome
• facial abnormalities
• optic atrophy
• microencephaly
• spasticity
• Hypotonia
• digital abnormalities
• epithelial changes
• mental impairment
Risk of embryopathy is low 0.45 to 0.9% with low dose(<5mg) warfarin but
0.6 to 10% in >5mg warfarin

7. • Use of warfarin in 2nd and 3rd trimester may cause fetopathy like
• Ocular and CNS abnormality
• Intracranial hemorrhage

8. Unfractioned heparin (UFH)
• Does not cross placenta
• FDA class C
• Administrated parenterally
• Appropriate dose based on (aPTT) of 2 to 3 times the control level
• Adverse effect
• maternal osteoporosis
• hemorrhage,
• thrombocytopenia,
• heparin-induced thrombocytopenia with thrombosis[HITT] syndrome
• In Event of preterm labour , spontaneous hemorrage, or significant
bleeding during delivery, UFH reversed with protamine sulfate

9. Low-molecular-weight heparin (LMWH)
• Does not cross placenta
• FDA class B
• Not secreated in breast milk.
• Safer to fetus
• low molecular weight heparin (LMWH; e.g., enoxaparin 1 mg/kg
subcutaneously every 12 hours)
• More predictable anticoagulant response
• Lower incidence of HITT and osteoporosis
• Monitor by anti-Xa levels

10. 2nd and 3rd trimester upto 35wk
• All patients should be
switched to Warfarin
• INR twice weekly
At 36 week
• Switch to LMWH /UFH

11. Labor and post partum
1. 36 hour prior to planned delivery switch to IV UFH
2. 6 hours prior to deliver stop UFH
3. 6 hours after delivery restart IV UFH if no obs bleeding risk
4. Bridging should be done with warfarin once safe

12. Anticoagulation option during pregnancy

15. Management of ACS/MI with pregnancy-
Reperfusion
• Primary PCI is recommended as preferred reperfusion therapy in
STEMI and also as primary PCI strategy in NSTE-ACS when indicated
• The effect of ionizing radiation should not prevent primary PCI
• Streptokinase pregnancy category C and does not cross placenta
• When administered near delivery,it may cause severe postpartum
hemorrhage
• Insufficient data on use of tissue plasminogen activator,pregnancy
category C and does not cross placenta

16. ACS management in pregnancy
Pharmacotherapy-
aspirin safe ( non classified)
Clopidogrel can be used for shortest duration (Cat B)
Potent P2Y12 inhibitors/Biva/ GPIIb-IIIa inh --- not recommended
Short term heparinization during PCI (Cat C)
Revasculariztion :
Indication-as per guideline
Primary PCI preferred than thrombolysis

18. Antiplatelet medication
• aspirin (Cat N)
• Crosses the placenta and secreted in breast milk
• Low dose aspirin is safe during pregnancy and breast feeding
• Should be stopped at 36 week due to its effect on fetal prostaglandin which
prevents closure of ductus arteriosus
• Clopidogrel
• Pregnancy category B but limited data
• Must be discontinued 7 days prior to delivery
• Prasugrel and ticagrelor
• Not recommended

19. Statins
• Statins contraindicated (cat X) during pregnancy and breast feeding
• Cholesterol is essential for fetal development

20. ACE/ARB/ARNI/Renin inhibitor
• FDA category D/X(contraindicated in pregnancy)
• Adverse effect
 Renal failure
 Oligohydramnios
 IUGR
 Fetal death

21. Beta blocker
• FDA class C/D
• Crosses placenta but not teratogenic
• Adverse effect
• Fetal bradycardia
• Fetal hypoglycemia
• IUGR
• Low birth wt
• Hypospadias
• Birth defect

22. Hypertensive drugs in Pregnancy
• The definition of hypertension in pregnancy is based on absolute BP
values (SBP ≥140 mmHg or DBP ≥90 mmHg)
• mild hypertension in pregnancy - (140–159/90–109 mmHg)
• Severe hypertension in pregnancy - (≥160/ 110 mmHg)

25. Management of chronic hypertension in
pregnancy
• Labetalol should be considered to treat chronic hypertension in
pregnant women.
• Nifedipine should be considered for women in whom labetalol is not
suitable, or Methyldopa if both labetalol and nifedipine are not
suitable.
• Pregnant women with chronic hypertension should be offered
aspirin 75–150 mg once daily from 12 weeks
• Placental growth factor (PlGF)-based testing should be offered to
help rule out preeclampsia between 20-35weeks of pregnancy

26. Management of pregnancy with severe
gestational hypertension
• Blood pressure measurement every 15–30 minutes until BP is less
than 160/110mmHg
• treatment with i.v. labetalol, or oral methyldopa, or nifedipine
should be initiated
• The drug of choice in pre-eclampsia associated with pulmonary
oedema is nitroglycerine (glyceryl trinitrate)

28. Chronic heart failure in pregnancy
• Drugs can be used
• Beta blocker
• Diuretic
• Digoxin
• Hydralazine
• Nitrate
• Drugs contraindicated
• ACEI/ARB
• ARNI
• Direct renin inhibitor
• MRA
• Ivabradine

29. Peri partum cardiomyopathy (PPCM)
Management
1. Afterload reduction –hydralazine/ nitrates
2. Rate control-- blocker/ digoxin
3. Diuretics
4. Other oral heart failure therapy(according to pregnancy status)
5. Anticoagulation– LV thrombus
6. Bromocriptine—2.5mg once daily for at least 1 week , must be prescribed
with LMWH
7. Contraindicated– ACE inhibitors, Spironolactone
8. Delivery – NVD under E/A, expedited C/S in severe HF

30. PPCM
• PPCM councilling
• Deterioration in LV function is reported in up to 50% of cases despite optimal
medical treatment
• A subsequent pregnancy carries a recurrence risk for PPCM of 30–50%.
• When the EF has not normalized, a subsequent pregnancy should be
discouraged

31. Pulmonary Arterial hypertension
• Extreme high risk, thus pregnancy is contraindicated
• Maternal mortality 30-56%
• Death may occur due to RV failure
•  risk in last trimester, labor and postpartum
• Counselling to avoid pregnancy
• Endothelin receptor antagonist (ERA) like bosentan,ambrisartan is
contraindicated in pregnancy

32. Management
1. High dose CCB continued if patient was vasoreactive
(idiopathic/heritable/drug) (FDA Cat C)
2. IV prostanoids—epoprostenol, teprostanil are best
agent in pregnancy (cat B)
3. PDE 5 inhibitors are safe in pregnancy (Cat B)
4. Combination therapy – better
5. Close follow up with Echo
6. Mode of delivery– VD is preferred than C/S (less volume
shift in VD)

33. Anti-arrhythmic drugs in pregnancy
• Unstable arrhythmia should be treated with electrical cardioversion
• SVT can be treated initially by vagal maneuver and adenosine
• Pre-excitation – more likely to develop orthodromic AVRT
• Amiodarone should be avoided due to fetal thyroid and neurodevelopmental
complications
• Most of the antiarrhythmic drug can be used like
• Adenosine
• Beta blocker
• Verapamil
• Digoxin
• Flecainide
• Procainamide
• Propafenone
• Sotalol

35. Cardiovascular contraindication of Pregnancy
 Pulmonary arterial hypertension of any cause
 Eisenmenger physiology
 Congenital cyanotic heart disease
 Severe systemic ventricular dysfunction (LVEF <30% NYHA III-IV
 Marfan syndrome with aorta dilated >45 mm
 Aortic dilatation >50 mm in aortic disease associated with bicuspid aortic valve
• Native severe coarctation
• Severe symptomatic left ventricular outflow tract obstruction (LVOTO)
• Previous peripartum cardiomyopathy with any residual impairment of left
ventricular function
• Severe mitral stenosis, severe symptomatic aortic stenosis

36. Well tolerated CVS disease pregnancy
• Uncomplicated, small or mild - pulmonary stenosis
• patent ductus arteriosus
• mitral valve prolapse
• Successfully repaired simple lesions
• atrial or ventricular septal defect
• patent ductus arteriosus
• anomalous pulmonary venous drainage
• Atrial or ventricular ectopic beats, isolated

37. Indication of Cesarian section due to CV
disease
• patient on oral anticoagulants (OACs) in pre-term labour
• patients with Marfan syndrome and an aortic diameter >45 mm,
• patients with acute or chronic aortic dissection
• those in acute intractable heart failure
• Cesarean delivery may be considered in Marfan patients with an aortic
diameter 40–45 mm.
• severe aortic stenosis (AS)
• patients with severe forms of pulmonary hypertension (including
Eisenmenger syndrome)
• acute heart failure.

38. Valvular hear disease-Mitral stenosis
• In patients with symptoms or pulmonary hypertension, restricted activities
and β1-blockers are recommended.
• Diuretics are recommended when congestive symptoms persist despite β-
blockers.
• Therapeutic anticoagulation is recommended in the case of atrial
fibrillation, left atrial thrombosis, or prior embolism.
• Patients with severe MS should undergo intervention before pregnancy.
• PTMC should be considered in pregnant patients with severe symptoms or
systolic pulmonary artery pressure >50 mmHg despite medical therapy

39. Valvular heart disease-Aortic stenosis
• Limited role of medical management

40. • Patients with severe aortic or mitral regurgitation and symptoms or
impaired ventricular function or ventricular dilatation should be
treated surgically pre-pregnancy.
• Medical therapy is recommended in pregnant women with
regurgitant lesions when symptoms occur.

41. Important Cardiovascular drugs which may
adversely affect the embryo
ACE inhibitors
ARBs
Ambrisartan
Bosentan
Renin inhibitors
Warfarin(in 1st trimester)
 statin groups
Amiodarone
Phenytoin
Spironolactone

42. Relatively safe drugs
• Adenosine
• Aspirin
• Amiloride
• Beta blocker(except atenolol)
• Calcium channel blocker
• Digoxin
• Fenofibrate
• Furosemide
• Flecainide
• Heparin
• Hydralazine
• Hydrochlorothiazide

43. Relatively safe drugs
• methyldopa
• Nitrate
• Phosphodiesterase inhibitor
• Lidocaine
• Mexiletine
• Procainamide
• Quinidine
• Sotalol

44. Drugs not recommended as status unknown
• NOAC
• Apixaban
• Dabigratan
• Edoxaban
• Rivaroxaban
• Ezetimibe
• Levosimendan
• Fondaparinux
• Ivabradine
• Ranolazine
• Ticagrelor
• Prasugrel
• Sacubitril/Valsartan

46. STAY SAFE