Hypertension for USMLE Step 1

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Antihypertensives: USMLE Step 1 Review

VITAL FOR USMLE STEP 1

Pathophysiology & Treatment Goals

1. Hypertension mechanism: Elevated blood pressure due to increased cardiac output and/or total peripheral resistance 2. Treatment target: BP < 130/80 mmHg (current guidelines) 3. First-line treatment: Often includes lifestyle modifications via DASH diet (emphasizes whole grains, fruits, vegetables, low-fat dairy, reduced sodium) 4. Resistant hypertension: BP remains elevated despite concurrent use of three or more medications (including a diuretic)

Thiazide and Thiazide-like Diuretics

1. Mechanism: Inhibit Na⁺/Cl⁻ cotransporter in distal convoluted tubule → ↓ sodium & water reabsorption → ↓ blood volume 2. Clinical use: First-line, especially in salt-sensitive patients 3. Chronic effects: Vasodilation (exact mechanism uncertain) 4. Key adverse effect: Hypokalemia

ACE Inhibitors

1. Mechanism: Block ACE → ↓ angiotensin II formation → ↓ vasoconstriction & ↓ aldosterone 2. Additional effect: ↑ bradykinin levels (ACE normally degrades bradykinin) 3. Clinical use: First-line therapy 4. Key adverse effects:

Dry cough (due to ↑ bradykinin)
Angioedema (due to ↑ bradykinin)
Hyperkalemia
Contraindicated in pregnancy

Angiotensin Receptor Blockers (ARBs)

1. Mechanism: Block AT₁ receptors → prevent angiotensin II effects 2. Clinical use: Alternative to ACE inhibitors 3. Advantage over ACEIs: No effect on bradykinin → no cough or angioedema 4. Key adverse effect: Hyperkalemia

Calcium Channel Blockers

1. Mechanism: Block L-type calcium channels → ↓ Ca²⁺ influx → ↓ vascular smooth muscle contraction & ↓ cardiac contractility 2. Effects:

Heart: ↓ conduction velocity, ↓ contractility, ↓ heart rate
Vasculature: ↓ vasoconstriction

3. Clinical use: First-line, particularly effective in African Americans 4. Key adverse effects: Lower extremity edema, rash, flushing, dizziness

Beta Blockers

1. Mechanism: Block β-adrenergic receptors → prevent catecholamine binding 2. Effects:

Heart: ↓ contractility, ↓ heart rate, ↓ conduction
Kidney: ↓ renin secretion → ↓ angiotensin II
Vasculature (3rd generation): Vasodilation

3. Key adverse effects: Fatigue, cold extremities, depression, sleep disturbances, erectile dysfunction, bronchospasm (in asthma/COPD patients)

Alpha Blockers

1. Mechanism: Block α₁-adrenergic receptors → prevent norepinephrine binding 2. Effect: ↓ vasoconstriction 3. Key adverse effect: Orthostatic hypotension (especially in elderly)

HIGH YIELD

Thiazide Diuretics

1. Most effective in salt-sensitive individuals 2. Long-term therapy leads to vasodilation 3. Metabolic side effects: Hypokalemia, hyperglycemia, hyperlipidemia, hyperuricemia

Renin-Angiotensin System

1. Key pathway: Angiotensinogen (liver) → Angiotensin I (via renin) → Angiotensin II (via ACE) → vasoconstriction 2. ACE is primarily located in vascular endothelium, especially in pulmonary circulation 3. ACEIs vs ARBs: Both cause hyperkalemia, but only ACEIs cause cough and angioedema

Beta Blockers

1. Third-generation agents (carvedilol, nebivolol) have additional vasodilatory properties 2. Contraindicated in patients with asthma or COPD due to bronchospasm risk 3. Should be tapered gradually when discontinuing (to prevent rebound hypertension)

Population-Specific Considerations

1. African Americans: Often less responsive to ACEIs/ARBs; more responsive to CCBs and thiazides 2. Elderly: At higher risk for orthostatic hypotension with alpha blockers 3. Pregnant women: ACEIs/ARBs contraindicated (teratogenic); methyldopa and labetalol preferred

Cross-Drug Concepts

1. Drug combinations: Often more effective than monotherapy at lower doses 2. First-line agents: Thiazides, ACEIs, ARBs, and CCBs 3. Renal protection: ACEIs and ARBs particularly beneficial in diabetic patients

BEYOND THE BASICS

Resistant Hypertension

1. Definition: BP remains elevated despite concurrent use of ≥3 drugs (including a diuretic) 2. Management: Consider secondary causes, optimize medication adherence, add mineralocorticoid receptor antagonist

DASH Diet

1. Key components: Rich in fruits, vegetables, whole grains, low-fat dairy, reduced sodium 2. Effectiveness: Can lower systolic BP by 8-14 mmHg

Secondary Hypertension

1. Renovascular: Consider in young females (fibromuscular dysplasia) or older patients with atherosclerosis 2. Primary aldosteronism: Consider in hypokalemic hypertension 3. Pheochromocytoma: Consider in episodic hypertension with headache, sweating, palpitations

Special Populations

1. Diabetic patients: ACEIs/ARBs preferred for renoprotective effects 2. Heart failure patients: Beta blockers, ACEIs/ARBs, and aldosterone antagonists have mortality benefit 3. Post-MI patients: Beta blockers and ACEIs have mortality benefit

Additional Agents

1. Mineralocorticoid receptor antagonists (spironolactone, eplerenone): Effective in resistant hypertension 2. Direct renin inhibitors (aliskiren): Block conversion of angiotensinogen to angiotensin I 3. Centrally acting agents (clonidine, methyldopa): Reduce sympathetic outflow

Hypertension for USMLE Step 1

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