Hypertension Drug Selection

Hypertension Drug Selection

Master hypertension drug selection with free flashcards and evidence-based clinical strategies. This lesson covers first-line agent selection, compelling indications for specific drug classes, and patient-specific factors that guide antihypertensive therapy—essential competencies for NAPLEX success and optimal cardiovascular care.

Welcome to Hypertension Drug Selection 🩺

Selecting the right antihypertensive agent requires integrating multiple factors: patient demographics, comorbidities, contraindications, and evidence-based guidelines. The 2017 ACC/AHA guidelines lowered the threshold for hypertension diagnosis (≥130/80 mmHg), making early, appropriate pharmacotherapy more critical than ever. This lesson equips you with a systematic approach to drug selection that balances efficacy, safety, and individualized patient care.

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Core Concepts: The Foundation of Drug Selection 💊

Understanding First-Line Agents

The JNC 8 and ACC/AHA guidelines identify four primary drug classes as first-line therapy for most patients:

Drug Class	Mechanism	Primary Benefits	Key Considerations
ACE Inhibitors (ACEIs)	Block conversion of angiotensin I → II	Renoprotection, cardioprotection, mortality reduction in HF	Dry cough (10-15%), hyperkalemia, contraindicated in pregnancy
Angiotensin Receptor Blockers (ARBs)	Block AT1 receptors	Similar to ACEIs but lower cough incidence	Hyperkalemia, contraindicated in pregnancy, avoid with ACEIs
Calcium Channel Blockers (CCBs)	Block L-type Ca²⁺ channels	Effective in Black patients, ISH in elderly, no metabolic effects	Peripheral edema (DHPs), constipation (non-DHPs), negative inotropy
Thiazide Diuretics	Block NaCl reabsorption in DCT	Low cost, effective, reduce CV events	Hypokalemia, hyponatremia, hyperuricemia, hyperglycemia, dyslipidemia

💡 Tip: Think "ACT" for first-line therapy: ACEIs/ARBs, CCBs, Thiazides.

The Compelling Indications Framework 🎯

Certain comorbidities create compelling indications for specific drug classes based on outcome data:

┌────────────────────────────────────────────────────────────┐
│         COMPELLING INDICATIONS ALGORITHM                   │
└────────────────────────────────────────────────────────────┘

    Patient presents with HTN
           │
           ↓
    Does patient have compelling indication?
           │
      ┌────┴────┐
      ↓         ↓
    YES        NO
      │         │
      │         ↓
      │    Standard first-line:
      │    - Thiazide OR
      │    - ACEI/ARB OR
      │    - CCB
      │
      ↓
   Select based on condition:
   │
   ├─→ 💓 HFrEF → ACEI/ARB + β-blocker + diuretic + aldosterone antagonist
   │
   ├─→ 🫀 Post-MI → β-blocker + ACEI/ARB + aldosterone antagonist
   │
   ├─→ 🩺 CKD → ACEI/ARB (if proteinuria present)
   │
   ├─→ 🧠 Stroke (recurrent risk) → ACEI/ARB + thiazide
   │
   └─→ 👤 Diabetes → ACEI/ARB preferred

⚠️ Critical Distinction: Compelling indications are NOT the same as preferred agents. They represent scenarios where specific drug classes have proven mortality/morbidity benefits in clinical trials.

Patient-Specific Factors: The Decision Matrix 🧩

Race and Ethnicity Considerations

Black patients exhibit:

• Reduced response to ACEI/ARB monotherapy (due to lower renin profiles)
• Enhanced response to CCBs and thiazide diuretics
• Recommendation: Initiate with CCB or thiazide; add ACEI/ARB if needed for CKD or DM

Non-Black patients:

• Can initiate with any first-line agent
• ACEI/ARB often preferred for younger patients and those with DM

Age-Related Selection 👴👵

Age Group	Preferred Agents	Rationale	Cautions
<60 years	ACEI/ARB, CCB, thiazide	Any first-line appropriate	Consider pregnancy potential (avoid ACEI/ARB)
≥60 years	CCB or thiazide preferred	Isolated systolic HTN common; CCBs highly effective	Orthostatic hypotension risk with α-blockers, central agents
≥80 years	Thiazide, CCB; lower BP target (controversial)	HYVET trial showed benefit; individualize based on frailty	Fall risk, polypharmacy, renal function decline

Comorbidity-Driven Selection 🏥

Diabetes Mellitus:

• First choice: ACEI or ARB (reduce proteinuria, delay nephropathy progression)
• Evidence: HOPE, RENAAL, IDNT trials
• Target BP: <130/80 mmHg
• Add-on: CCB or thiazide if needed (monitor for hyperglycemia with thiazides)

Chronic Kidney Disease (CKD):

• With proteinuria (UACR ≥30 mg/g): ACEI or ARB required regardless of race
• Without significant proteinuria: Any first-line agent acceptable
• Monitor: SCr increase up to 30% acceptable; check K⁺ within 2-4 weeks
• Avoid: If bilateral renal artery stenosis or SCr >3 mg/dL (relative)

Coronary Artery Disease (CAD):

• Stable angina: β-blocker + ACEI/ARB ± CCB
• Post-MI: β-blocker + ACEI/ARB (improve survival)
• β-blockers reduce: Myocardial O₂ demand, heart rate, contractility

Heart Failure:

HFpEF (EF >50%):

• Focus on: BP control, rate control if AFib, diuretics for volume
• Less established: ACEI/ARB benefit (use for HTN control)

Atrial Fibrillation:

• Rate control: β-blocker (metoprolol, carvedilol) or non-DHP CCB (diltiazem, verapamil)
• BP control: Continue ACEI/ARB if indicated
• Avoid: DHP CCBs alone (insufficient rate control)

🧠 Mnemonic - "ABCD" for HFrEF:

• ACEI/ARB/ARNI
• Beta-blocker
• Continue diuretics (loop)
• Daldosterone antagonist (spironolactone)

Contraindications and Cautions ⚠️

Drug Class	Absolute Contraindications	Relative Contraindications/Cautions
ACEI/ARB	• Pregnancy (Category D) • History of angioedema • Bilateral RAS	• Hyperkalemia (K⁺ >5.5) • Acute kidney injury • SCr >3 mg/dL
β-blockers	• Decompensated HF • High-grade AV block • Severe bradycardia • Acute asthma	• COPD • Peripheral artery disease • Depression • Diabetes (masks hypoglycemia)
CCB (non-DHP)	• HFrEF • 2nd/3rd-degree AV block • Sick sinus syndrome	• Concurrent β-blocker (additive negative chronotropy)
Thiazides	• Anuria • Sulfa allergy (cross-reactivity)	• Gout • Hypokalemia • CKD (GFR <30: ineffective)
Aldosterone antagonists	• Hyperkalemia (K⁺ >5.0) • CKD stage 4-5 (GFR <30) • Concurrent ACEI + ARB	• Male patients (gynecomastia with spironolactone)

💡 Clinical Pearl: The "triple whammy" (ACEI/ARB + diuretic + NSAID) significantly increases acute kidney injury risk. Counsel patients to avoid NSAIDs when possible.

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Clinical Examples: Applying the Framework 📋

Example 1: The Uncomplicated Patient

Case: 52-year-old White male, newly diagnosed HTN (BP 142/94 mmHg), no comorbidities, BMI 27, labs normal.

Analysis:

• No compelling indications
• Non-Black patient → any first-line acceptable
• Young, no CKD/DM → ACEI/ARB good choice for long-term renoprotection

Selection: Lisinopril 10 mg daily (ACEI)

• Rationale: Cost-effective, once-daily dosing, favorable metabolic profile, established CV benefit
• Alternative: Amlodipine 5 mg daily (CCB) or chlorthalidone 12.5 mg daily (thiazide)
• Monitoring: BP recheck in 2-4 weeks, titrate to goal <130/80 mmHg

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Example 2: The Complex Patient with Multiple Comorbidities

Case: 68-year-old Black female, HTN (BP 158/98), type 2 diabetes (A1C 7.8%), CKD stage 3 (eGFR 48, UACR 120 mg/g), K⁺ 4.8 mEq/L.

Analysis:

• Compelling indications: DM + CKD with albuminuria → ACEI/ARB mandatory
• Race is overridden by compelling indication
• CKD stage 3: ACEI/ARB safe; monitor renal function
• Likely needs combination therapy (BP 28/18 above goal)

Selection:

1. Losartan 50 mg daily (ARB) - addresses DM and CKD
2. Amlodipine 5 mg daily (CCB) - effective in Black patients, no metabolic effects

Rationale:

• ARB provides renoprotection (reduce proteinuria, slow GFR decline)
• CCB adds complementary mechanism, highly effective for BP reduction
• Avoid thiazide alone initially due to potential hyperglycemia
• Monitor: K⁺ and SCr in 2 weeks (acceptable if SCr rises <30%)

Follow-up Plan:

• Titrate losartan to 100 mg if BP not at goal
• Add low-dose thiazide (chlorthalidone 12.5 mg) if still above goal
• Target BP <130/80 mmHg

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Example 3: The Post-MI Patient

Case: 60-year-old male, recent STEMI (2 months ago), EF 35%, BP 136/88, on aspirin, atorvastatin.

Analysis:

• Multiple compelling indications: Post-MI + HFrEF
• Requires GDMT for HFrEF
• BP slightly above goal but not severely elevated

Selection:

1. Carvedilol 6.25 mg BID (β-blocker) - proven mortality benefit post-MI and in HFrEF
2. Lisinopril 5 mg daily (ACEI) - reduce remodeling, improve survival
3. Furosemide 20 mg daily (loop diuretic) - volume management
4. Consider adding: Spironolactone 25 mg daily (EF <35%, NYHA class evidence)

Rationale:

• β-blocker is non-negotiable post-MI (reduce reinfarction, sudden death)
• ACEI reduces ventricular remodeling and mortality in HFrEF
• Start low, titrate slowly to target doses (carvedilol 25 mg BID, lisinopril 20-40 mg)
• Aldosterone antagonist adds significant mortality benefit (RALES, EPHESUS trials)

Monitoring:

• Heart rate (target 50-60 bpm)
• BP (avoid excessive reduction <110 systolic)
• K⁺ (risk with ACEI + spironolactone)
• Volume status (daily weights)

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Example 4: The Elderly Patient with Isolated Systolic Hypertension

Case: 78-year-old female, BP 164/72 mmHg (isolated systolic HTN), history of osteoporosis, no other comorbidities, takes calcium/vitamin D.

Analysis:

• Isolated systolic HTN (SBP ≥130, DBP <80) - common in elderly
• Wide pulse pressure suggests arterial stiffness
• Fall risk consideration
• Thiazides may help prevent osteoporosis (reduce urinary calcium)

Selection: Amlodipine 5 mg daily (DHP CCB)

• Rationale:
  • CCBs extremely effective for isolated systolic HTN in elderly
  • No orthostatic hypotension risk
  • Once-daily dosing improves adherence
  • May provide some bone-protective effect
• Alternative: Chlorthalidone 12.5 mg daily (reduces bone resorption)

Special Considerations:

• Start low, go slow (avoid rapid BP reduction)
• Monitor for peripheral edema (common with DHP CCBs)
• Assess for orthostatic BP changes
• Consider lower BP goal individualization (frailty assessment)

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Common Mistakes and How to Avoid Them ⚠️

Mistake 1: Using β-Blockers as First-Line in Uncomplicated HTN

Why it's wrong: β-blockers (except in compelling indications) are no longer recommended as first-line due to:

• Inferior stroke prevention vs. other agents
• Metabolic adverse effects (weight gain, DM risk)
• Less effective BP reduction
• Not included in JNC 8 first-line recommendations

Correct approach: Reserve β-blockers for CAD, post-MI, HFrEF, or rate control needs.

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Mistake 2: Avoiding ACEI/ARB in Black Patients with Diabetes or CKD

Why it's wrong: While Black patients respond less to ACEI/ARB monotherapy for BP, they still receive the renoprotective and cardioprotective benefits when CKD or DM is present.

Correct approach:

• Use ACEI/ARB in Black patients with DM or CKD with proteinuria (compelling indication overrides race)
• Combine with CCB or thiazide for optimal BP control

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Mistake 3: Combining ACEI + ARB

Why it's wrong: The ONTARGET trial showed dual RAAS blockade increases adverse events (hyperkalemia, hypotension, AKI) without additional benefit.

Correct approach:

• Use ACEI or ARB, not both
• If inadequate response, add different class (CCB, thiazide)
• Exception: Some HF protocols use ARNI (which replaces ACEI, not adds to it)

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Mistake 4: Not Monitoring Potassium with ACEI/ARB + Spironolactone

Why it's wrong: Dual RAAS blockade dramatically increases hyperkalemia risk (K⁺ >5.5 mEq/L can cause fatal arrhythmias).

Correct approach:

• Check K⁺ and SCr at baseline, 2 weeks, 4 weeks, then quarterly
• Hold if K⁺ >5.5 or SCr increases >30%
• Counsel on low-potassium diet
• Avoid salt substitutes (often contain potassium)

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Mistake 5: Using Short-Acting Nifedipine

Why it's wrong: Short-acting DHP CCBs cause reflex tachycardia and sudden BP drops, increasing adverse CV events.

Correct approach:

• Use only long-acting/extended-release CCBs (amlodipine, felodipine ER, nifedipine XL)
• Never use immediate-release nifedipine for chronic HTN

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Mistake 6: Discontinuing Effective Therapy Due to "Tachyphylaxis"

Why it's wrong: True tachyphylaxis to antihypertensives is rare. Apparent loss of control usually indicates:

• Medication nonadherence
• Excessive sodium intake
• Weight gain
• NSAIDs or other interfering drugs
• Progression of hypertension (age, renal decline)
• White coat effect

Correct approach:

• Investigate reasons for BP increase before switching medications
• Assess adherence (ask open-ended questions, check refill records)
• Review diet, weight changes, new medications
• Consider ambulatory BP monitoring if white coat suspected

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Key Takeaways 🎯

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🤔 Did You Know?

The "polypill" concept—a single pill combining multiple antihypertensives (e.g., ACEI + CCB + thiazide)—has been shown in trials to improve adherence by 30-40% compared to multiple separate medications. While not yet standard in the US, polypills are increasingly used in low-resource settings for primary prevention.

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📚 Further Study

1. 2017 ACC/AHA Hypertension Guidelines: https://www.acc.org/guidelines/high-blood-pressure - Comprehensive resource for BP classification and treatment algorithms

2. SPRINT Trial Full Publication (NEJM): https://www.nejm.org/doi/full/10.1056/NEJMoa1511939 - Landmark trial establishing intensive BP targets

3. Pharmacist's Letter: Hypertension Treatment Comparison: https://pharmacistsletter.therapeuticresearch.com - Regularly updated comparative effectiveness data and patient counseling guides

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You've completed Hypertension Drug Selection! 🎉 You now have the framework to systematically approach antihypertensive therapy, integrate compelling indications, and avoid common prescribing pitfalls. Practice applying these principles to diverse patient cases to solidify your NAPLEX readiness.