What is the best course of treatment for a 56-year-old patient with hypertension, headache, leukocytosis, and elevated alkaline phosphatase level, currently prescribed amlodipine?

Management of Leukocytosis and Elevated Alkaline Phosphatase in a Hypertensive Patient on Amlodipine

Primary Recommendation

The amlodipine you ordered is appropriate for initial hypertension management, but you must immediately investigate the elevated alkaline phosphatase (176 IU/L) and mild leukocytosis (11.7 x10³/μL with neutrophilia) before simply continuing antihypertensive therapy alone. 1

Immediate Diagnostic Workup Required

Alkaline Phosphatase Elevation Investigation

The isolated elevation of alkaline phosphatase (176 IU/L, normal 49-135 IU/L) with normal transaminases requires fractionation to determine the source:

• Order alkaline phosphatase isoenzymes or GGT to differentiate hepatic from bone origin, as this patient's normal AST (27 IU/L) and ALT (26 IU/L) suggest a non-hepatocellular source 1
• If bone origin is confirmed, obtain calcium, phosphate, vitamin D levels, and consider bone imaging to evaluate for Paget's disease, osteomalacia, or bone metastases 1
• If hepatic origin is confirmed, obtain hepatitis serologies, autoimmune markers (ANA, anti-smooth muscle antibody), and abdominal ultrasound to evaluate for biliary obstruction or infiltrative liver disease 1

Leukocytosis Evaluation

The mild leukocytosis (WBC 11.7 x10³/μL) with absolute neutrophilia (8.5 x10³/μL, normal 1.4-7.0) requires assessment:

• Review for infectious symptoms: fever, cough, urinary symptoms, or recent illness that could explain reactive leukocytosis 1
• Assess for inflammatory conditions: check ESR and CRP if clinical suspicion exists for underlying inflammatory or autoimmune disease 1
• If persistent without clear cause, repeat CBC in 2-4 weeks to determine if this represents a transient reactive process or requires hematology referral 1

Hypertension Management Strategy

Current Amlodipine Prescription Assessment

Your choice of amlodipine as initial therapy is guideline-concordant, as calcium channel blockers are first-line agents for hypertension 1, 2

• Amlodipine provides smooth 24-hour blood pressure control with once-daily dosing due to its long half-life (35-50 hours) 3
• The typical starting dose is 5 mg daily, which can be titrated to 10 mg if needed for blood pressure control 2, 4

Adding a Second Agent When Needed

If blood pressure remains uncontrolled (≥140/90 mmHg) after 2-4 weeks on amlodipine monotherapy, add either an ACE inhibitor/ARB or a thiazide-like diuretic as the second agent 1, 5

The choice between these options depends on patient characteristics:

• For patients with chronic kidney disease (eGFR 67 mL/min/1.73 suggests early CKD stage 2), an ACE inhibitor or ARB is preferred as the second agent due to renoprotective effects 1, 5
• The combination of amlodipine plus an ACE inhibitor/ARB provides complementary mechanisms—vasodilation through calcium channel blockade and renin-angiotensin system inhibition—demonstrating superior blood pressure control compared to either agent alone 5, 6
• Monitor for peripheral edema, which occurs in 10.8% of patients on amlodipine 10 mg but may be attenuated by adding an ACE inhibitor or ARB 2, 5

Triple Therapy if Needed

If blood pressure remains uncontrolled on dual therapy, add a thiazide-like diuretic (chlorthalidone 12.5-25 mg or hydrochlorothiazide 25 mg daily) as the third agent 1, 5

• This creates the guideline-recommended triple therapy combination: ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic 1, 5
• Check serum potassium and creatinine 2-4 weeks after initiating diuretic therapy to detect hypokalemia or changes in renal function 5

Blood Pressure Targets and Monitoring

Target blood pressure is <140/90 mmHg minimum for most patients, with consideration for <130/80 mmHg for higher-risk patients 1, 5

• Reassess blood pressure within 2-4 weeks after initiating or adjusting antihypertensive therapy 5
• The goal is to achieve target blood pressure within 3 months of treatment initiation or modification 5
• Confirm elevated readings with home blood pressure monitoring (target <135/85 mmHg) or 24-hour ambulatory monitoring (target <130/80 mmHg) to rule out white coat hypertension 5

Critical Pitfalls to Avoid

Do not ignore the laboratory abnormalities while focusing solely on blood pressure management—the elevated alkaline phosphatase and leukocytosis require investigation as they may represent underlying conditions that could influence treatment choices or prognosis 1

Do not combine an ACE inhibitor with an ARB, as dual renin-angiotensin system blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit 1, 5

Do not add a beta-blocker as second or third-line therapy unless there are compelling indications (heart failure, post-myocardial infarction, angina), as beta-blockers are less effective than other agents for stroke prevention 1, 5

Lifestyle Modifications

Reinforce non-pharmacological interventions that provide additive blood pressure reductions of 10-20 mmHg 5:

• Sodium restriction to <2 g/day (provides 5-10 mmHg systolic reduction) 5
• Weight management if overweight (BMI target 18.5-24.9 kg/m²) 1
• Regular aerobic exercise (30-60 minutes most days) 1
• Alcohol limitation (≤2 drinks/day for men, ≤1 drink/day for women) 5
• DASH diet (rich in vegetables, fruits, low-fat dairy products) 1