What are the contraindications of beta blockers (beta-adrenergic blocking agents) and diazoxide in pregnancy?

Beta Blockers and Diazoxide in Pregnancy: Contraindications and Mechanisms

Beta Blockers Are NOT Contraindicated in Pregnancy

Beta blockers are actually recommended for use during pregnancy and are not contraindicated. 1 The key considerations are selecting the appropriate agent and understanding potential fetal effects.

Recommended Beta Blockers in Pregnancy

• Labetalol is a first-line antihypertensive agent during pregnancy, recommended by multiple major guidelines 1, 2
• Beta-1 selective agents (like metoprolol) are preferred because they avoid beta-2 effects on uterine relaxation 1
• Metoprolol has lower incidence of fetal growth retardation compared to atenolol and is the preferred beta blocker 1

Beta Blockers to AVOID in Pregnancy

• Atenolol should NOT be used due to increased risk of fetal growth restriction 1, 2
• Non-selective beta blockers may cause uterine effects through beta-2 blockade 1

Potential Fetal Effects (Not Contraindications)

While beta blockers can be used safely, clinicians should monitor for:

• Fetal bradycardia - transient and generally not harmful 1
• Neonatal hypoglycemia - monitor after delivery 1
• Small for gestational age - primarily with atenolol, less with labetalol/metoprolol 1

Clinical Use During Pregnancy

• Beta blockers are used for rate control in arrhythmias during pregnancy 1
• Effective for hypertension management throughout pregnancy 1
• Can be continued for primary or secondary prophylaxis of variceal bleeding in patients with portal hypertension 1
• Should be continued in women with long QT syndrome throughout pregnancy and postpartum 1

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Diazoxide: Significant Concerns But Not Absolutely Contraindicated

Diazoxide is NOT formally contraindicated in pregnancy, but it carries substantial risks and should be avoided except in specific emergency situations. 3

FDA Label Contraindications (Actual)

The FDA label lists only two absolute contraindications 3:

• Functional hypoglycemia
• Hypersensitivity to diazoxide or thiazides

Pregnancy is NOT listed as an absolute contraindication 3

Why Diazoxide Should Generally Be Avoided in Pregnancy

Fetal and Neonatal Risks

• Crosses the placental barrier and appears in cord blood 3
• Causes degeneration of fetal pancreatic beta cells in animal studies 3
• Produces fetal hyperbilirubinemia, thrombocytopenia, and altered carbohydrate metabolism when given before delivery 3
• Alopecia and hypertrichosis lanuginosa reported in infants whose mothers received diazoxide during last 19-60 days of pregnancy 3
• Pulmonary hypertension reported in neonates and young infants treated with diazoxide 3

Maternal Risks During Labor

• Causes cessation of uterine contractions when given intravenously during labor 3
• Oxytocic agents may be required to reinstate labor 3

Dosing-Related Hypotension

• High-dose diazoxide (75mg bolus) causes profound maternal hypotension requiring treatment 4, 5, 6
• This is why standard bolus dosing is problematic 7, 4

When Diazoxide May Be Considered

Mini-bolus diazoxide (15mg doses) can be used for hypertensive emergencies when other agents fail 7:

• A 2007 randomized trial showed mini-bolus diazoxide (15mg) was safe and effective compared to hydralazine 7
• Achieved blood pressure control faster than hydralazine (19 minutes vs 34 minutes) 7
• No episodes of hypotension occurred with 15mg mini-bolus dosing 7
• Fewer episodes of persistent severe hypertension compared to hydralazine (16% vs 38%) 7

Guideline Recommendations

• Cochrane reviews conclude diazoxide should probably be avoided due to hypotension risk with standard dosing 4, 5, 6
• May be used for acute severe hypertension but only with careful dosing 8
• Not a first-line choice - hydralazine, labetalol, or nifedipine preferred 1, 2

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Common Pitfalls to Avoid

• Do not confuse beta blocker safety with ACE inhibitor teratogenicity - these are completely different drug classes with different risk profiles 1
• Do not use atenolol - it has the highest risk of fetal growth restriction among beta blockers 1, 2
• Do not give standard 75mg bolus doses of diazoxide - use mini-bolus 15mg dosing if diazoxide must be used 7, 4
• Do not administer diazoxide during active labor due to risk of stopping uterine contractions 3
• Monitor neonates for hyperbilirubinemia and hypoglycemia if mother received diazoxide near delivery 3