Side Effects of Thiazide Diuretics and Amlodipine
Thiazide diuretics and amlodipine have distinct side effect profiles that clinicians should carefully consider when prescribing these medications for hypertension.
Thiazide Diuretic Side Effects
Metabolic Effects
- Hypokalemia - can lead to cardiac arrhythmias, glucose intolerance, and may contribute to insulin resistance 1, 2
- Hyponatremia - particularly in elderly patients 1
- Hyperglycemia - may precipitate diabetes or worsen glycemic control in diabetic patients 1, 3, 2
- Hyperuricemia - can exacerbate or precipitate gout 1
- Hyperlipidemia - may cause unfavorable lipid profile changes 2, 4
Renal Effects
- Pre-renal azotemia - especially with excessive diuresis 1
- Reduced diuretic response when creatinine clearance <30 mL/min 1
- May precipitate azotemia in patients with impaired renal function 3
Cardiovascular Effects
- Orthostatic hypotension - can lead to falls, especially in elderly 1
- Volume depletion - can cause dehydration 1
Other Effects
- Sleep disturbances and nocturia 1
- Acute transient myopia and acute angle-closure glaucoma - idiosyncratic reaction requiring immediate discontinuation 3
- Photosensitivity reactions 5
Amlodipine Side Effects
Cardiovascular Effects
- Peripheral edema - most common side effect, due to vasodilation 1, 6
- Flushing and headache 1, 6
- Reflex tachycardia 1
- Hypotension - can lead to falls 1, 6
- Palpitations and irregular heartbeat 6
Neurological Effects
Gastrointestinal Effects
- Stomach pain and nausea 6
Serious but Rare Effects
- Worsening angina or heart attack when first starting or increasing dose 6
Comparative Safety Considerations
Elderly Patients
- Thiazides are potentially inappropriate medications (PIMs) in elderly patients with:
- Dihydropyridine calcium channel blockers like amlodipine may cause greater antihypertensive effects in elderly due to decreased baroreceptor response and age-related increase in drug exposure 1
Combination Therapy
- When combined, amlodipine and thiazide diuretics show enhanced antihypertensive effects 7, 8
- Amlodipine may have favorable effects on lipid profiles when combined with thiazides 7
- The combination is generally well-tolerated 7, 8
Monitoring Recommendations
For Thiazide Diuretics
- Monitor renal function and electrolytes (particularly potassium, sodium) 1, 5
- Monitor blood pressure for excessive reduction 1
- Monitor blood glucose in diabetic patients and those at risk 3, 2
- Monitor uric acid levels in patients with history of gout 1
For Amlodipine
- Monitor blood pressure 1, 6
- Monitor for peripheral edema, especially in elderly 1, 6
- Monitor for symptoms of heart failure in susceptible patients 1
Clinical Implications
- Potassium supplementation or potassium-sparing diuretics may be necessary to prevent thiazide-induced hypokalemia and its associated complications 2
- Low-dose thiazides may minimize metabolic side effects while maintaining antihypertensive efficacy 5
- Amlodipine is generally well-tolerated but peripheral edema may limit its use in some patients 1, 6
- Both medications require special caution in elderly patients due to increased risk of falls from orthostatic hypotension 1
When choosing between these medications, clinicians should consider the patient's comorbidities, risk factors, and the distinct side effect profiles of each medication to optimize treatment while minimizing adverse effects.