What is the safety of Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blockers (ARBs), Calcium Channel Blockers (CCBs), Thiazide Diuretics, Beta-Blockers, Alpha-Blockers, Direct Renin Inhibitors, and Vasodilators during pregnancy?

Safety of Antihypertensive Medications During Pregnancy

Contraindicated Medications (DO NOT USE)

ACE inhibitors, ARBs, and direct renin inhibitors are absolutely contraindicated during pregnancy due to severe fetotoxicity and teratogenicity. 1, 2

1. Angiotensin-Converting Enzyme Inhibitors (ACEIs): UNSAFE

• Contraindicated throughout pregnancy - must be discontinued immediately upon pregnancy planning or confirmation 1, 3
• Associated with fetal teratogenicity, oligohydramnios, renal dysfunction, and fetal death in second and third trimesters 1, 2, 4
• First trimester exposure may cause congenital malformations, though evidence is conflicting 5
• Women taking ACEIs must be transitioned to safe alternatives (methyldopa, nifedipine, or labetalol) before conception 1, 2

2. Angiotensin Receptor Blockers (ARBs): UNSAFE

• Contraindicated throughout pregnancy - same fetotoxic profile as ACEIs 1, 2
• Case reports document oligohydramnios that resolved within 8 days of discontinuation, but fetal risks remain significant 6
• Must be stopped immediately when pregnancy is confirmed or planned 3
• Should be replaced with methyldopa, labetalol, or long-acting nifedipine 3

7. Direct Renin Inhibitors: UNSAFE

• Contraindicated during pregnancy - grouped with ACEIs and ARBs due to effects on the renin-angiotensin system 1
• Should be discontinued before conception 2

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Safe Medications (First-Line Options)

3. Calcium Channel Blockers (CCBs): SAFE

• Extended-release nifedipine is recommended as first-line therapy during pregnancy 2
• Nifedipine has the strongest safety record among CCBs with established long-term data 2
• Long-acting formulation should be used for maintenance therapy; short-acting reserved only for acute severe hypertension 2
• Offers once-daily dosing advantage for adherence 2
• Beta blockers and CCBs appear superior to methyldopa in preventing preeclampsia 1
• Caution: Avoid concurrent use of nifedipine with magnesium sulfate due to risk of severe hypotension, neuromuscular blockade, and cardiac depression 4
• Nifedipine showed lowest risk of persistent hypertension compared to hydralazine and labetalol in meta-analysis 7

5. Beta-Blockers: SAFE (with exceptions)

• Labetalol is safe and recommended as first-line therapy during pregnancy 1, 2, 8
• Main contraindication is history of reactive airway disease 2
• Labetalol IV is first-line for acute/severe hypertension: 20 mg initial bolus, then 40 mg after 10 minutes, then 80 mg every 10 minutes (maximum 220 mg) 3
• Metoprolol (beta-1 selective) is preferred over non-selective agents - lower incidence of fetal growth retardation compared to atenolol 8
• Atenolol should NOT be used - increased risk of fetal growth restriction and intrauterine growth impairment 1, 8
• Potential fetal effects include transient bradycardia and neonatal hypoglycemia (monitoring recommended after delivery) 8
• Short-term use (<6 weeks) is well tolerated if no signs of intrauterine growth impairment 4

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Safe Medications (Alternative Options)

6. Alpha-Blockers: LIMITED DATA

• Methyldopa (centrally-acting alpha-2 agonist) has the longest safety record with long-term infant outcome data 2
• Recommended dosage: 250-500 mg twice daily 3
• Should be used with caution in women at risk of developing depression 2
• Must be avoided postpartum due to risk of postnatal depression 1
• Methyldopa is initial drug of choice for long-term oral therapy, with no adverse effects in short or long-term use 4, 9

8. Vasodilators: SAFE (specific agents)

• Intravenous hydralazine is widely used for rapid reduction of severely elevated blood pressure 4, 7
• Infusion: 5 mg/min initially, gradually increased every 3-5 minutes to maximum 100 mg/min 1
• Nifedipine showed lower risk of persistent hypertension compared to hydralazine 7
• Diazoxide should probably be avoided due to risk of hypotension with standard dosing, though may be used for acute severe hypertension with careful dosing 8

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Medications to Avoid or Use with Caution

4. Thiazide Diuretics: GENERALLY AVOID

• Should generally be avoided during pregnancy due to risk of reducing uteroplacental perfusion 2
• May cause hypokalemia and hyponatremia (more common in women than men) 1
• Not recommended for new initiation during pregnancy 2

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Blood Pressure Targets and Monitoring

Target BP during pregnancy: 110-135/85 mmHg - balances reduction of maternal hypertensive complications while minimizing fetal growth impairment 2, 3

Treatment Thresholds:

• SBP ≥170 mmHg or DBP ≥110 mmHg is an emergency requiring hospitalization 1
• Initiate treatment at BP 140/90 mmHg in women with gestational hypertension, pre-existing hypertension with gestational hypertension, or hypertension with subclinical organ damage 1
• In other circumstances, initiate treatment if SBP ≥150 mmHg or DBP ≥95 mmHg 1

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Critical Clinical Pitfalls to Avoid

• Failing to transition from ACEIs/ARBs before conception causes severe fetal harm 2, 3
• Never use atenolol - highest risk of fetal growth restriction among beta-blockers 8
• Avoid nifedipine + magnesium sulfate combination - risk of severe hypotension and cardiac depression 4
• Stop methyldopa postpartum - risk of postnatal depression 1
• Women with hypertension during pregnancy have increased lifelong cardiovascular risk requiring continued monitoring 1, 2