Adverse effect of hydrochlorothiazide
Pro Research Analysisby 
Searched over 200M research papers
Adverse Effects of Hydrochlorothiazide: A Comprehensive Review
Introduction to Hydrochlorothiazide and Its Usage
Hydrochlorothiazide (HCTZ) is a commonly prescribed thiazide diuretic used to manage hypertension and edema. Despite its efficacy in lowering blood pressure, HCTZ is associated with several adverse effects that can impact metabolic, renal, and cardiovascular health.
Metabolic Adverse Effects of Hydrochlorothiazide
Impact on Glucose and Lipid Metabolism
Hydrochlorothiazide has been shown to adversely affect glucose and lipid metabolism. In a study comparing HCTZ with captopril, HCTZ decreased insulin-mediated glucose disposal and increased basal insulin concentration, suggesting a reduction in insulin sensitivity. Additionally, HCTZ significantly increased serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels1. These metabolic changes may elevate the risk for diabetes mellitus and coronary heart disease1.
Effects on Serum Potassium and Lipoproteins
High doses of HCTZ can lead to significant reductions in serum potassium levels, which is a concern for patients with hypertension. Even at low doses, HCTZ has been associated with adverse changes in serum lipids, including increases in total cholesterol, LDL cholesterol, and apolipoprotein B, while reducing apolipoprotein A14. These lipid alterations can contribute to an increased risk of cardiovascular events.
Influence of Abdominal Obesity
Patients with abdominal obesity are particularly susceptible to the adverse metabolic effects of HCTZ. Studies have shown that these patients are more likely to develop impaired fasting glucose, elevated triglycerides, and new-onset diabetes mellitus when treated with HCTZ10. This suggests that abdominal obesity exacerbates the metabolic risks associated with HCTZ therapy.
Renal Adverse Effects
Renal Function and Structure
The addition of HCTZ to angiotensin-converting enzyme (ACE) inhibitors in rats with myocardial infarction has been shown to detrimentally affect renal function and structure. This combination led to increased plasma creatinine levels, severe renal interstitial lesions, tubular dilatation, and fibrosis, indicating significant renal damage2. These findings highlight the potential for HCTZ to exacerbate renal impairment, particularly in patients with pre-existing cardiovascular conditions.
Severe Allergic Reactions
Hypersensitivity and Pulmonary Edema
Hydrochlorothiazide can cause severe allergic reactions, including noncardiogenic pulmonary edema and hypersensitivity reactions mimicking septic shock. Cases have been reported where patients developed acute respiratory failure, multiple-organ dysfunction, and severe fatigue shortly after taking HCTZ3 5 6. These reactions are rare but can be life-threatening, necessitating immediate medical attention.
Conclusion
While hydrochlorothiazide is effective in managing hypertension, its use is associated with several adverse effects, particularly on metabolic and renal health. Patients with abdominal obesity and those on combination therapy with ACE inhibitors are at higher risk for these adverse outcomes. Clinicians should carefully consider these risks when prescribing HCTZ and monitor patients closely for any signs of metabolic disturbances, renal impairment, or severe allergic reactions.
Sources and full results
Most relevant research papers on this topic
A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension.
Hydrochlorothiazide has adverse effects on glucose and lipid metabolism, while captopril shows beneficial or no effects, potentially reducing the risk for diabetes and coronary heart disease.
RCT
Highly CitedAdverse renal effects of hydrochlorothiazide in rats with myocardial infarction treated with an ACE inhibitor.
Adding hydrochlorothiazide to ACE inhibitors in rats with myocardial infarction negatively affected renal function and structure, potentially impacting long-term prognosis.
RCT
Animal Study
Rigorous JournalSevere Allergic Reaction to Hydrochlorothiazide Mimicking Septic Shock
A severe allergic reaction to hydrochlorothiazide may mimic septic shock, potentially due to a predisposition to drug allergies rather than sulfonamide cross-sensitivity.
Case ReportThe Effect of Low‐Dose Hydrochlorothiazide on Blood Pressure, Serum Potassium, and Lipoproteins
Low doses of hydrochlorothiazide can effectively reduce blood pressure in mild hypertension, but may cause adverse changes in serum lipids.
RCTHydrochlorothiazide‐Induced Noncardiogenic Pulmonary Edema: An Underrecognized Yet Serious Adverse Drug Reaction
Hydrochlorothiazide-induced noncardiogenic pulmonary edema is a rare but potentially life-threatening complication, with 90% of cases occurring in women.
Case ReportRecurrent hydrochlorothiazide-induced pulmonary edema
Hydrochlorothiazide-induced pulmonary edema is a rare but life-threatening adverse reaction, with a potential mechanism of production being idiosyncratic.
Case Report[Hypotensive and metabolic effects of small doses of hydrochlorothiazide in the long-term treatment of elderly patients with systolic arterial hypertension].
Small doses of hydrochlorothiazide effectively lower blood pressure in elderly patients with systolic arterial hypertension, with minimal adverse effects.
Non-RCTAssociation between Concomitant Use of Hydrochlorothiazide and Adverse Chemotherapy-Related Events among Older Women with Breast Cancer Treated with Cyclophosphamide
Concomitant hydrochlorothiazide use does not show a significant association with adverse chemotherapy-related events in older women with breast cancer treated with cyclophosphamide.
Observational StudyEffects of antihypertensive therapy on blood pressure control, cognition, and reactivity. A placebo-controlled comparison of prazosin, propranolol, and hydrochlorothiazide.
Prazosin has the most beneficial profile for blood pressure control, cognitive and psychomotor effects, lipid levels, and side effects compared to propranolol and hydrochlorothiazide.
RCTImpact of Abdominal Obesity on Incidence of Adverse Metabolic Effects Associated With Antihypertensive Medications
Abdominal obesity increases the risk of adverse metabolic effects and new-onset diabetes mellitus when using hydrochlorothiazide and atenolol short-term.
RCT
Large Human TrialHighly Cited