What are the different classes of antihypertensive medications, their mechanisms of action, examples of drugs, safety during pregnancy, and contraindications?

Antihypertensive Medication Classes: Mechanisms, Examples, Pregnancy Safety, and Contraindications

1. Thiazide and Thiazide-Like Diuretics

Mechanism of Action:

• Promote sodium and water excretion by inhibiting sodium-chloride cotransporter in the distal convoluted tubule, leading to decreased intravascular volume 1
• Act as indirect vasodilators by depleting salt and water within the intramural portion of arterioles, diminishing responsiveness to catecholamines and angiotensin II 2

Examples:

• Hydrochlorothiazide 1
• Chlorthalidone 1

Pregnancy Safety:

• NOT recommended during pregnancy 1, 3
• May reduce normal plasma volume expansion and compromise uteroplacental perfusion 3
• Chronic use associated with restricted maternal plasma volume and reduced uteroplacental perfusion 1
• May increase risk of pre-eclampsia 3

Contraindications:

• Severe renal impairment/anuria 1
• Hypokalemia or hyponatremia 1

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2. ACE Inhibitors (Angiotensin-Converting Enzyme Inhibitors)

Mechanism of Action:

• Inhibit conversion of angiotensin I to angiotensin II, decreasing vasoconstriction and aldosterone production 2
• Reduce both preload and afterload through vasodilation 4

Examples:

• Lisinopril 4
• Enalapril 1

Pregnancy Safety:

• CONTRAINDICATED during pregnancy 1, 5
• May cause fetal renal dysplasia, oligohydramnios, intrauterine growth restriction, and fetal death 1
• Women who become pregnant must be transitioned immediately to safe alternatives 1

Contraindications:

• Pregnancy (all trimesters) 1, 4
• History of angioedema with prior ACE inhibitor use 4

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3. Angiotensin II Receptor Blockers (ARBs)

Mechanism of Action:

• Block angiotensin II at AT1 receptors, preventing vasoconstriction and aldosterone secretion 6
• Provide similar hemodynamic effects to ACE inhibitors without affecting bradykinin metabolism 6

Examples:

• Valsartan 6
• Losartan 7

Pregnancy Safety:

• CONTRAINDICATED during pregnancy 1, 5
• Cause severe fetotoxicity including renal dysplasia and fetal death 8
• Must be discontinued immediately upon pregnancy recognition 1

Contraindications:

• Pregnancy (all trimesters) 1, 6
• Concomitant use with ACE inhibitors or renin inhibitors (increases cardiovascular and renal risk) 1

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4. Calcium Channel Blockers (CCBs)

Mechanism of Action:

• Block L-type calcium channels in vascular smooth muscle and cardiac tissue, causing vasodilation and reduced peripheral resistance 9
• Dihydropyridines (e.g., nifedipine) are more selective for vascular smooth muscle 10

Examples:

• Nifedipine (dihydropyridine) 8
• Amlodipine (dihydropyridine) 1

Pregnancy Safety:

• SAFE for use during pregnancy 1, 8
• Extended-release nifedipine is a first-line option for hypertension in pregnancy 8
• Caution: Avoid concurrent use with magnesium sulfate due to risk of precipitous blood pressure drop 5

Contraindications:

• Severe aortic stenosis (for dihydropyridines) 1
• Acute myocardial infarction with pulmonary congestion 1

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5. Beta-Blockers

Mechanism of Action:

• Block beta-adrenergic receptors, decreasing cardiac output, heart rate, and renin release 2
• Inhibit prejunctional release of norepinephrine and may have central nervous system effects 2

Examples:

• Atenolol 11
• Labetalol (combined alpha/beta-blocker) 5

Pregnancy Safety:

• Labetalol is SAFE and preferred during pregnancy 1, 5, 8
• Atenolol should be avoided due to association with intrauterine growth restriction 1
• Labetalol has efficacy comparable to methyldopa with fewer side effects 5

Contraindications:

• Severe bradycardia or heart block (second or third degree) 11
• Decompensated heart failure 11

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6. Aldosterone Antagonists (Potassium-Sparing Diuretics)

Mechanism of Action:

• Block aldosterone receptors in the distal tubule and collecting duct, promoting sodium excretion while retaining potassium 1
• Reduce sodium reabsorption without causing hypokalemia 1

Examples:

• Spironolactone 1
• Eplerenone 1

Pregnancy Safety:

• Limited safety data; generally avoided during pregnancy 1
• Not recommended as first-line agents in pregnancy due to insufficient evidence 3

Contraindications:

• Hyperkalemia 1
• Significant renal dysfunction (risk of hyperkalemia) 1

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7. Alpha-1 Adrenergic Blockers

Mechanism of Action:

• Block alpha-1 receptors on vascular smooth muscle, causing vasodilation and reduced peripheral resistance 2
• Decrease blood pressure without reflex tachycardia 9

Examples:

• Prazosin 1
• Doxazosin 1

Pregnancy Safety:

• SAFE for use during pregnancy 1
• Prazosin is listed as an effective and safe option in pregnancy 1

Contraindications:

• Orthostatic hypotension 1
• Severe hepatic impairment 1

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8. Centrally Acting Agents

Mechanism of Action:

• Act on central alpha-2 receptors in the brainstem, decreasing sympathetic outflow from the vasomotor center 2
• Reduce peripheral vascular resistance and heart rate 2

Examples:

• Methyldopa 1, 5
• Clonidine 1, 8

Pregnancy Safety:

• SAFE and PREFERRED during pregnancy 1, 5, 8
• Methyldopa has the longest safety record and is considered first-line 5
• Clonidine is also safe and effective 1, 8

Contraindications:

• Active hepatic disease (for methyldopa) 1
• Severe coronary insufficiency 2

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Key Clinical Considerations

Primary Agents for General Hypertension: The ACC/AHA guidelines identify thiazide diuretics, ACE inhibitors, ARBs, and CCBs as primary agents with proven reduction in clinical events 1. Beta-blockers lack adequate evidence for initial use in uncomplicated hypertension 1.

Pregnancy-Safe Algorithm: For hypertensive pregnant women, the treatment hierarchy is: 1) Methyldopa or labetalol as first-line; 2) Nifedipine (extended-release) as second-line; 3) Avoid ACE inhibitors, ARBs, and diuretics unless specific indications exist 8, 5, 1.

Critical Pitfall: Simultaneous use of ACE inhibitors with ARBs or renin inhibitors is potentially harmful and increases cardiovascular and renal risk 1. This combination should never be used 1.