What is the best course of action for a patient with poorly controlled hypertension, impaired renal function (GFR of 68, creatinine of 1.31), and an A1C of 5.8, who has stopped taking their prescribed antihypertensive medications, lisinopril (angiotensin-converting enzyme inhibitor) and HCTZ (hydrochlorothiazide, a diuretic), and is experiencing drowsiness after taking amoxicillin (an antibiotic)?

Management of Poorly Controlled Hypertension with Medication Non-Adherence and Impaired Renal Function

Immediate Priority: Resume Antihypertensive Medications and Address Non-Adherence

The patient must immediately resume taking lisinopril and HCTZ as prescribed, as medication non-adherence is the most common cause of uncontrolled hypertension and significantly increases cardiovascular risk. 1

Critical Steps to Address Non-Adherence

• Counsel the patient that stopping antihypertensive medications to "save pills for a physical" is dangerous and defeats the purpose of treatment—uncontrolled hypertension increases risk of stroke, myocardial infarction, heart failure, and progressive kidney damage. 1, 2

• Verify medication adherence is the first step before any treatment intensification, as non-adherence affects 10-80% of hypertensive patients and is the most common cause of apparent treatment resistance. 1, 3

• Explain that the physical examination will be more meaningful with accurate assessment of blood pressure control on medications rather than off them. 1

Amoxicillin and Drowsiness Assessment

• Amoxicillin does not typically cause drowsiness or interact with lisinopril or HCTZ—the drowsiness is more likely related to the underlying infection, dehydration, or other factors rather than a drug interaction. 4

• NSAIDs can interfere with blood pressure control and should be avoided, but amoxicillin (a beta-lactam antibiotic) does not have this effect. 1, 4

• Monitor for signs of infection resolution and reassess drowsiness after completing the antibiotic course. 4

Renal Function Considerations with Current Medications

Lisinopril Dosing in Renal Impairment

• With a GFR of 68 mL/min (Stage 2 CKD), lisinopril can be continued at standard doses but requires closer monitoring—dose adjustment is typically not needed until GFR falls below 30 mL/min. 4, 5

• ACE inhibitors like lisinopril are actually preferred first-line agents in patients with CKD because they reduce albuminuria and slow progression of kidney disease. 1

• Monitor serum creatinine and potassium 1-2 weeks after resuming lisinopril, as ACE inhibitors can cause transient creatinine elevation (acceptable up to 30% increase) and hyperkalemia. 4, 1

HCTZ Appropriateness with GFR 68

• Thiazide diuretics like HCTZ become less effective when GFR falls below 30 mL/min, but at GFR 68 mL/min, HCTZ remains appropriate and effective. 1

• If GFR declines further to <30 mL/min, switch from HCTZ to a loop diuretic (furosemide or torsemide) for volume control. 1

Blood Pressure Target and Treatment Intensification

Target Blood Pressure

• Target blood pressure should be <140/90 mmHg minimum, ideally <130/80 mmHg given the presence of CKD (GFR 68). 1, 2

• For patients with CKD, the lower target of <130/80 mmHg is recommended to slow progression of kidney disease. 1

If Blood Pressure Remains Uncontrolled After Resuming Medications

• Reassess blood pressure 2-4 weeks after resuming lisinopril and HCTZ at full adherence—if BP remains ≥140/90 mmHg, treatment intensification is required. 1, 6

• Add a calcium channel blocker (amlodipine 5-10 mg daily) as the third agent to achieve guideline-recommended triple therapy (ACE inhibitor + thiazide diuretic + calcium channel blocker). 1, 3, 6

• This combination provides complementary mechanisms: renin-angiotensin system blockade, volume reduction, and vasodilation. 3, 6

Resistant Hypertension Protocol

• If blood pressure remains ≥140/90 mmHg despite triple therapy at optimal doses, add spironolactone 25 mg daily as the fourth agent (if serum potassium <4.5 mmol/L and GFR >45 mL/min). 1, 3

• Monitor serum potassium closely when adding spironolactone to lisinopril, as hyperkalemia risk is significant with dual renin-angiotensin system effects. 1, 4

Monitoring Parameters

Immediate Monitoring (Within 1-2 Weeks of Resuming Medications)

• Serum creatinine and potassium to detect hyperkalemia or acute kidney injury from ACE inhibitor. 4, 1

• Blood pressure measurement to assess response to resumed therapy. 1

Ongoing Monitoring

• Blood pressure reassessment every 2-4 weeks until target <140/90 mmHg (ideally <130/80 mmHg) is achieved. 1, 6

• Serum creatinine, potassium, and estimated GFR every 3-6 months to monitor kidney function. 1

• A1C monitoring annually (current 5.8 is normal, indicating no diabetes). 1

Critical Pitfalls to Avoid

• Never delay resuming antihypertensive medications—prolonged uncontrolled hypertension accelerates kidney damage and increases cardiovascular risk. 1, 2

• Do not attribute drowsiness to amoxicillin without considering other causes (infection itself, dehydration, sleep disturbance)—amoxicillin does not interact with lisinopril or HCTZ. 4

• Do not switch from HCTZ to a loop diuretic at GFR 68—thiazides remain effective until GFR <30 mL/min. 1

• Do not add multiple medications simultaneously without first ensuring adherence to the current regimen—non-adherence is the most common cause of apparent treatment resistance. 1, 3

• Do not combine lisinopril with an ARB—dual RAS blockade increases adverse events (hyperkalemia, acute kidney injury) without additional benefit. 4, 3

Lifestyle Modifications to Reinforce

• Sodium restriction to <2.3 g/day (ideally <2 g/day) can provide additional blood pressure reduction of 5-10 mmHg. 1, 3, 2

• Weight loss if overweight (BMI >25 kg/m²) and regular aerobic exercise (150 minutes/week of moderate intensity). 1, 2

• Limit alcohol consumption and maintain adequate hydration. 1, 2