Effects of hydrochlorothiazide: A Synthesis of Findings from 14 Studies

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Original Abstract of the Article

Major Research Findings

Hydrochlorothiazide (HCTZ) is a diuretic widely used to treat hypertension. Various studies have investigated the effects and side effects of HCTZ. 5 examined the dose-dependent effects of HCTZ in seven hypertensive patients receiving the dihydropyridine calcium channel blocker nicardipine. The results showed that blood pressure decreased by approximately 7/3 mmHg regardless of the dose, but potassium, glucose, and uric acid increased in a dose-dependent manner. The hypokalemic and hyperglycemic responses at 50 mg were greater than those usually seen with HCTZ. 4 examined the effects of HCTZ and amiloride on salt excretion (intake) and taste in 73 normotensive adults (aged 18 to 56) who were randomly assigned to receive 50 mg/day of HCTZ (n = 24), 5 mg twice daily of amiloride (n = 24) or placebo (n = 25) for 8 weeks. The results showed that significant increases in sodium excretion (intake) of 31%, 53% and 30% were observed in subjects receiving HCTZ after 2, 4 and 8 weeks of treatment, respectively. 6 investigated the effects of thiazide diuretics on plasma lipoproteins in 16 hypertensive patients in a double-blind, placebo-controlled, crossover study. The results showed that 4 weeks of 50 mg hydrochlorothiazide twice daily, caused significant elevations in total plasma cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, very low density lipoprotein (VLDL)-cholesterol and triglycerides. 7 studied the antihypertensive and biochemical effects of different doses of hydrochlorothiazide alone or in combination with triamterene in 26 patients with essential hypertension. The results showed that 25 mg of hydrochlorothiazide is as effective in lowering blood pressure as higher doses of the diuretic. 1 compared the effects of ticrynafen (TCNF) with hydrochlorothiazide (HCTZ) on blood pressure (BP), renal function, serum uric acid (UA) and electrolytes, and body fluid spaces in 25 hypertensive subjects in a double-blind, randomized study. The results showed that BP was similarly lowered by TCNF and HCTZ. 14 compared chlorthalidone (CTD) and hydrochlorothiazide (HCTZ) for major cardiovascular events, blood pressure, left ventricular mass, and adverse effects. The results showed that CTD may be more effective in reducing major cardiovascular events than HCTZ. 13 examined the effects of hydrochlorothiazide on oxidative stress and pulse pressure in hypertensive patients with chronic stroke in a randomized, multicenter study. The results showed that hydrochlorothiazide did not provide any additional benefits over non-diuretic antihypertensive drugs in terms of antioxidant effects or reducing pulse pressure. 9 compared the hypocalciuric and potential side-effects of hydrochlorothiazide (HCT) to indapamide (IND; a thiazide-like drug) in patients with idiopathic hypercalciuria. The results showed that IND was at least as effective as HCT in controlling hypercalciuria. 3 compared the antihypertensive and metabolic effects of captopril combined with hydrochlorothiazide (C+HCTZ) versus chlorthalidone (CT) in mild and moderate primary hypertensive patients. The results showed that captopril combined with low diuretic dose normalize the blood pressure in 69% mild to moderate primary hypertensive patients, and acts faster than chlorthalidone in this control. 12 compared the effectiveness of losartan/hydrochlorothiazide and telmisartan/hydrochlorothiazide in patients with hypertension. The results showed that LOS + HCTZ did not influence UA metabolism as well as glucose metabolism, likely because of inhibitory action of losartan on URAT1, although TEL + HCTZ were accompanied with impairment of the UA metabolism and glucose metabolism. 10 examined the effects of three years of low-dose thiazides on mineral metabolism in healthy elderly persons. The results showed that the urine calcium showed significant decreases from placebo in men at one year, but the effects had waned by 3 years. 8 evaluated the effects of 12.5-mg and 112.5-mg daily doses of hydrochlorothiazide (HCTZ) administered for 1 month to nine postmenopausal black female hypertensives. The results showed that both regimens produced significant reductions in sitting diastolic blood pressure. 11 conducted a meta-analysis of dose-response characteristics of hydrochlorothiazide and chlorthalidone. The results suggested that chlorthalidone is more effective in lowering blood pressure at lower doses than hydrochlorothiazide. 2 compared the efficacy of a combination of methyldopa with hydrochlorothiazide with that of its components, methyldopa and hydrochlorothiazide. The results showed that the combination was found to be more efficacious than either of its components.

Benefits and Risks

Benefit Summary

HCTZ is effective in lowering blood pressure and is widely used to treat hypertension. 5 , 7 , 1 , 3 , 12 showed that HCTZ significantly reduces blood pressure. In addition, 10 suggests that HCTZ may have beneficial effects on the skeleton.

Risk Summary

HCTZ may cause side effects such as hypokalemia, hyperglycemia, and hyperuricemia. 5 , 4 , 7 , 1 , 14 , 13 , 9 , 3 , 12 reported these side effects. 6 , 8 also showed that HCTZ may increase blood lipids.

Comparison Across Studies

Commonalities Across Studies

Many studies have shown that HCTZ is effective in lowering blood pressure. It is also consistently reported that HCTZ may cause side effects such as hypokalemia, hyperglycemia, and hyperuricemia.

Differences Across Studies

Studies have reported different degrees of blood pressure lowering effects and side effects of HCTZ. In addition, the effects of HCTZ on blood lipids, its effects on the skeleton, and its combined effects with other drugs vary depending on the study.

Consistency and Inconsistencies of Results

While there is consistency in the research findings regarding the effects and side effects of HCTZ, there are also inconsistencies. For example, the blood pressure lowering effect of HCTZ has been shown to vary depending on the dose, the drug used in combination, and the patient's condition. Furthermore, the side effects of HCTZ have been reported differently depending on the study. These inconsistencies may be explained by differences in research design, subjects, and other factors.

Important Considerations for Real-World Application

HCTZ is an effective drug for treating hypertension, but the risk of side effects should also be considered. Particular caution should be exercised when using HCTZ in elderly patients, patients with kidney disease, and diabetic patients. Regular monitoring of blood pressure, blood potassium levels, and blood sugar levels is important when taking HCTZ. There are various drugs used to treat hypertension besides HCTZ. It is important to consult with your doctor to find the right treatment for you.

Limitations of Current Research

Many studies on HCTZ are small and have a limited number of subjects. In addition, many studies have not been conducted on specific populations (e.g. elderly patients, patients with kidney disease, diabetic patients). Further research is needed to assess the effects and side effects of HCTZ in these populations.

Future Research Directions

Further research on HCTZ should include larger studies and involve diverse populations. More research is also needed on the long-term effects and side effects of HCTZ, as well as its combined effects with other drugs.

Conclusion

HCTZ is effective in lowering blood pressure and is widely used to treat hypertension. However, HCTZ may cause side effects such as hypokalemia, hyperglycemia, and hyperuricemia. It is important to consider the risk of side effects when taking HCTZ and to follow your doctor's instructions. There are various drugs used to treat hypertension besides HCTZ. It is important to consult with your doctor to find the right treatment for you.

Literature analysis of 14 papers
Positive Content
10
Neutral Content
3
Negative Content
1
Article Type
12
2
0
0
14
1.

Comparative effects of ticrynafen and hydrochlorothiazide on blood pressure, renal function, serum uric acid and electrolytes, and body fluid spaces in hypertensive man.

Author: BauerJ H, BrooksC S

Blood pressure reduction
Hypouricemic effect
Electrolyte disturbance

Ticrynafen and hydrochlorothiazide both effectively lowered blood pressure and caused similar electrolyte disturbances. Ticrynafen lowered serum uric acid, while hydrochlorothiazide increased it.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

2.

Efficacy of an antihypertensive agent. Comparison of methyldopa and hydrochlorothiazide in combination and singly.

Author: McMahonF G

Hypertension treatment
Mild side effects

A combination of methyldopa and hydrochlorothiazide was more effective than either of its components in reducing blood pressure in patients with hypertension. Side effects were mild.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

3.

[An open comparative study of captopril + hydrochlorothiazide versus chlorthalidone for the treatment of mild and moderate primary hypertension].

Author: FrancoR J, SampaioM, BalbiA L, MartinL C, LunaR L

Blood pressure normalization
Cholesterol reduction
Potassium reduction

Captopril combined with hydrochlorothiazide normalized blood pressure in 69% of mild to moderate primary hypertensive patients, acting faster than chlorthalidone. The combination also reduced cholesterol levels without affecting potassium levels.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : Portuguese

4.

Effects of hydrochlorothiazide and amiloride on salt taste and excretion (intake).

Author: MattesR D, ChristensenC M, EngelmanK

Increased sodium intake
Potassium wasting

This study examined the effects of hydrochlorothiazide (HCTZ) and amiloride on salt excretion in 73 healthy adults. HCTZ significantly increased sodium excretion, which may partially counteract its intended effects and increase the risk of potassium loss. Amiloride did not increase sodium excretion, but it did increase salt taste sensitivity. The study suggests that the increased sodium intake observed with HCTZ may need to be addressed to optimize its therapeutic effect and minimize potential side effects.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

5.

Dose response to hydrochlorothiazide in hypertensives receiving a calcium channel blocker.

Author: ZieglerM G, LernhardtE, Solt-BuzsakiV

Modest blood pressure reduction
Hyperglycemia
Hypokalemia
Increased uric acid

Hydrochlorothiazide, when combined with nicardipine, a calcium channel blocker, provided a modest antihypertensive effect at low doses. However, higher doses resulted in unusually large metabolic side effects.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

6.

The effects of thiazide diuretics upon plasma lipoproteins.

Author: JohnsonB F, SaundersR, HicklerR, MarwahaR, JohnsonJ

Hypertension treatment
Glucose elevation
Insulin elevation
Lipid elevation

Hydrochlorothiazide caused significant elevations in total plasma cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, and triglycerides. However, the ratio between LDL- and HDL-cholesterol remained unchanged, suggesting that coronary risk may be unchanged.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

7.

Antihypertensive and biochemical effects of different doses of hydrochlorothiazide alone or in combination with triamterene.

Author: KohvakkaA, SaloH, GordinA, EisaloA

Hypertension treatment
Magnesium reduction
Potassium reduction
Urate increase

Hydrochlorothiazide (25 mg) was as effective as higher doses in lowering blood pressure. Triamterene was effective in preventing the fall in serum potassium and magnesium associated with higher doses of thiazides.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

8.

The effect of low-dose hydrochlorothiazide on blood pressure, serum potassium, and lipoproteins.

Author: McKenneyJ M, GoodmanR P, WrightJ T, RifaiN, AycockD G, KingM E

Hypertension treatment
Hypokalemia
Lipid changes

Low doses of hydrochlorothiazide were more effective than high doses in treating hypertension without causing hypokalemia. However, both doses caused similar increases in serum lipids.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

9.

Indapamide (Natrilix): the agent of choice in the treatment of recurrent renal calculi associated with idiopathic hypercalciuria.

Author: MartinsM C, MeyersA M, WhalleyN A, MargoliusL P, BuysM E

Reduces hypercalciuria
Safe for hypercalciuria
Increased serum urate
Lower serum potassium

Indapamide was found to be at least as effective as hydrochlorothiazide in controlling hypercalciuria. Indapamide is preferred due to its safety profile and lack of effects on urinary citrate excretion.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Effects of three years of low-dose thiazides on mineral metabolism in healthy elderly persons.

Author: OttS M, LaCroixA Z, ScholesD, IchikawaL E, WuK

Bone health

Hydrochlorothiazide can reduce urine calcium and increase serum bicarbonate, potentially benefiting the skeleton.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Meta-analysis of dose-response characteristics of hydrochlorothiazide and chlorthalidone: effects on systolic blood pressure and potassium.

Author: ErnstMichael E, CarterBarry L, ZhengShimin, GrimmRichard H

Reduce cardiovascular events

Low-dose thiazide-based regimens are known to reduce cardiovascular events, but most studies used chlorthalidone, while hydrochlorothiazide (HCTZ) is more widely prescribed. This study compared the dose-response relationships of chlorthalidone and HCTZ for changes in systolic blood pressure and potassium levels.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

12.

A comparative study on the effectiveness of losartan/hydrochlorothiazide and telmisartan/hydrochlorothiazide in patients with hypertension.

Author: HamadaToshihiro, KuwabaraMasanari, WatanabeArisa, MizutaEinosuke, OhtaharaAkira, OmodaniHiroki, WatanabeMasashi, NakamuraHiroki, HirotaYutaka, MiyazakiSatoshi, KatoMasahiko, OginoKazuhide, KosakaHiroki, HaruakiNinomiya, TaniguchiShin-ichi, YamamotoKazuhiro, KotakeHiroshi, HisatomeIchiro

Blood pressure control
Glucose metabolism impairment
UA metabolism impairment

Losartan/hydrochlorothiazide (LOS+HCTZ) did not influence uric acid (UA) metabolism or glucose metabolism in hypertensive patients, while telmisartan/hydrochlorothiazide (TEL+HCTZ) was associated with impaired UA and glucose metabolism.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

13.

Effects of hydrochlorothiazide on oxidative stress and pulse pressure in hypertensive patients with chronic stroke: the EMINENT study.

Author: NakaneHiroshi, KamouchiMasahiro, HataJun, IbayashiSetsuro, KusudaKenji, OmaeTsuyoshi, NagaoTetsuhiko, AgoTetsuro, KitazonoTakanari,

No additional benefit

Hydrochlorothiazide treatment did not provide any additional benefits over non-diuretic antihypertensive drugs in terms of antioxidant effects or reducing pulse pressure (PP) in stroke patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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