What are the long-term side effects of hydrochlorothiazide
Pro Research Analysisby 
Searched over 200M research papers
Long-Term Side Effects of Hydrochlorothiazide
Hydrochlorothiazide (HCTZ) is a commonly prescribed diuretic for managing hypertension. While effective in lowering blood pressure, its long-term use is associated with several adverse effects on metabolic, renal, and cardiovascular health.
Metabolic Side Effects: Glucose and Lipid Metabolism
Impact on Glucose Metabolism
Long-term use of hydrochlorothiazide has been shown to negatively affect glucose metabolism. Studies indicate that HCTZ decreases insulin sensitivity, leading to increased basal insulin concentrations and a heightened late insulin response to glucose . This reduction in insulin sensitivity can potentially elevate the risk of developing diabetes mellitus over time .
Impact on Lipid Metabolism
Hydrochlorothiazide also adversely affects lipid profiles. Research has demonstrated significant increases in serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides with prolonged HCTZ use 13. These changes in lipid levels can contribute to an increased risk of coronary heart disease, undermining the cardiovascular benefits of blood pressure reduction 13.
Renal Side Effects: Function and Structure
Renal Function
The addition of hydrochlorothiazide to angiotensin-converting enzyme (ACE) inhibitors in patients with myocardial infarction has been shown to impair renal function. Studies in rats have revealed that HCTZ can lead to a 40% increase in plasma creatinine levels, indicating reduced kidney function . This impairment is associated with increased mortality in patients with the highest plasma creatinine levels .
Renal Structure
Long-term HCTZ use has also been linked to detrimental changes in renal morphology. These include severe renal interstitial lesions, tubular dilatation, fibrosis, and increased interstitial inflammation . Such structural damage can exacerbate renal dysfunction and negatively impact long-term prognosis after myocardial infarction .
Cardiovascular Side Effects: Electrolyte Imbalance and Arrhythmias
Hydrochlorothiazide can induce hypokalemia, a condition characterized by low potassium levels, which is potentially arrhythmogenic. This electrolyte imbalance can increase the risk of malignant ventricular arrhythmias, especially during acute myocardial infarction . The combination of HCTZ with other cardiovascular drugs may further aggravate these risks .
Comparative Studies: Hydrochlorothiazide vs. Other Antihypertensives
Hydrochlorothiazide vs. Captopril
Comparative studies between hydrochlorothiazide and captopril, an ACE inhibitor, have shown that captopril has a more favorable impact on glucose and lipid metabolism. While captopril increases insulin sensitivity and has minimal effects on lipid levels, HCTZ decreases insulin sensitivity and significantly raises cholesterol and triglyceride levels .
Hydrochlorothiazide vs. Amlodipine
In a long-term study comparing HCTZ with amlodipine, a calcium antagonist, both drugs effectively reduced blood pressure. However, the incidence of treatment-related side effects was higher with amlodipine. Despite this, HCTZ's adverse metabolic effects remain a concern .
Conclusion
Hydrochlorothiazide, while effective in managing hypertension, has several long-term side effects. These include adverse impacts on glucose and lipid metabolism, renal function and structure, and an increased risk of arrhythmias due to electrolyte imbalances. These side effects necessitate careful consideration and monitoring in patients undergoing long-term HCTZ therapy.
Sources and full results
Most relevant research papers on this topic