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Abdulaziz Dhafer Algarni et al, 2020;4(2):509–512.

International Journal of Medicine in Developing Countries

Uses of diuretics in heart failure: a brief review

Abdulaziz Dhafer Algarni1*, Wejdan Talal Almutairi2, Asawir Mohammed AlQurashi3, Esraa Abdulrahman Alshehrani3, Wijdan Turki Almrzouqi3, Hussain Ali Alhazmi4

Correspondence to: Abdulaziz Dhafer Algarni

*Al-Maarefa University, Al Khalidiyah, Saudi Arabia.

Email: azizdg2222 [at] gmail.com

Full list of author information is available at the end of the article.

Received: 18 December 2019 | Accepted: 24 December 2019


ABSTRACT

Heart failure (HF) is a disorder that affects at least a minimum of 26 million humans over the world, and its prevalence keeps growing. HF health expenses are large and will elevate dramatically with an older populace. Despite the progress in treatment strategies and prevention, death rate and morbidity remain rising. This study included all the studies which focused and reported the uses of diuretics in HF. A filtration procedure was used to remove duplicates, irrelevant publications. The online databases PubMed and Google Scholar and Research gate were used to perform a literature search for publications published between 1995 and 2019, without any date or language restrictions. We used a combination of relevant search terms “treatment of heart failure by using diuretics, the role of diuretics in the treatment of heart failure, loop diuretic therapy in heart failure, etc.” to discover articles regarding the matter. We independently identified publications and systematically screened titles, abstracts, and full texts of the collected publications. However, the studies available on extensive use of diuretics and its capability to control HF-related mortality and morbidity are very limited. Diuretics are a valuable and diverse class of agents for the controlling of hypervolemic cases. This review summarizes the essential characteristics of diuretics, involving their mode of action and significances.


Keywords:

Heart failure, diuretic therapy, loop diuretics, thiazide diuretics, potassium-sparing diuretics, diuretic resistance.


Introduction

Heart failure (HF) is a disease identified by the decreased heart strength to pump the blood into body arteries [1]. HF can also be known as an inappropriate cardiac product to meet metabolic demands or adequate cardiac output after the activation of compensatory neurohormonal [1]. HF is the frequent reason for staying in the hospital in elderly patients (more than 65 years) [1]. The main symptoms are caused by vascular obstruction, such as breathing shortness, gastric insufflation, and edema development. HF syndrome has commercial value, and in the ADHERE research, signs and symptoms of obstruction were the most prevalent reason for hospitalization [2]. Congestion often occurs before the entrance, and various cases may have increased left ventricular pressures when congestion is missing [3]. HF has been categorized into HF with decreased ejection fraction, HF with maintained ejection fraction, and HF mid-range ejection fraction, in agreement with the ejection fraction, natriuretic levels of peptide and the residence of heart illness and diastolic abnormalities [4]. HF has been described as a global pandemic since it influences about 26 million people all over the world [5]. Diuretic medications and particularly loop diuretic drugs are the common method of treating congestion, particularly in excess volume patients [6]. Loop, thiazides, and potassium-sparing diuretics are the most common drugs used in HF treatment [6]. This paper aimed to review the using of diuretics in the controlling and treatment of heart failure diseases.


Data Search

This study included all the studies which focused and reported the uses of diuretics in HF. A filtration procedure was used to remove duplicates, irrelevant publications. The online databases PubMed and Google Scholar and Research gate were used to perform a literature search for publications published between 1995 and 2019, without any date or language restrictions. We used a combination of relevant search terms “treatment of heart failure by using diuretics, the role of diuretics in the treatment of heart failure, loop diuretic therapy in heart failure, etc.” to discover articles regarding the matter. We independently identified publications and systematically screened titles, abstracts, and full texts of the collected publications.


Mode of Action and Classification of Diuretics Used in HF Treatment

Thiazides

The collection usually mentioned as “thiazide” diuretics are not all benzothiadiazole derivatives. Thiazides more effectively decreased the reabsorption of chloride and sodium than loop diuretic. The thiazides co-carrier is not sensitive to loop diuretics. Consequently, a higher concentration of sodium ions enters the distal tubules to stimulate the replacement with potassium ions, especially in the stimulated renin-angiotensin-aldosterone system [7]. Thiazides can further improve the active secretion of potassium ions in the distal kidney tubule. Thiazides are immediately soaked up from the Gastrointestinal tract (GIT), giving diuresis within 2 hours maximally and continues for 6–12 hours. Their strength is intermediate between the loop and K+-sparing agents, which affect the distal tubules. Metolazone (thiazide-similar diuretic) appears to affect the proximal tubule plus its extra distal effect [8]. It is active in kidney diseases, while other thiazides, for their distal and consequently less effective, are of restricted or don’t use. Indapamide showed vasodilatory outcomes in shorter doses, and it acts as a weak diuretic in proportionately higher doses [9]. The most prevalent side effects related to thiazides are dermatitis, interstitial nephritis, pancreatic inflammations, gout, blood alkalosis, volume deficiency, decreasing the blood concentration of potassium and magnesium, increasing the cholesterol and triglycerides concentrations, hyperglycemia in diabetics, and azotemia [10].

Loop diuretics

Loop diuretics repress the Na+/2Cl/K+ co-carrier of the thick ascending loop of Henle, wherever about 30% of infiltrated sodium is reabsorbed into the blood circulation. This causing decreasing the sodium and chloride reabsorption and elevated diuresis [8]. Loop diuretics further stimulate prostaglandin formation, which causes venous and kidney dilatation, and illustrates some of the heart effects, like the decrease in pulmonary artery occlusion pressure [11]. Nevertheless, it is crucial to recognize that the concomitant use of non-steroidal anti-inflammatory drugs decreased the diuretic effects of loop diuretics, causing inhibition in the synthesis of kidney prostaglandin. Loop diuretics involve torsemide, bumetanide, furosemide, and ethacrynic acid, whereas the oral furosemide bioavailability varies between 40% and 80 %, and this of bumetanide and torasemide more than 80%; therefore, these two diuretics are more efficient in managing HF cases [12]. A threshold model of dose-response curve supplies loop diuretics. Furosemide is begun with 20 mg and can be increased to 40 mg, depending on the response to diuretic medications. Furosemide’s highest doses for HF cases with healthy glomerular filtration rate vary from 40 to 80 mg orally, and the highest dose is 600 mg per day. If the highest dose has previously been supplied, it is prescribed to improve the incidence of the daily dose to 2 or 3 times. Bumetanide is administered at a dose ranging from 2 to 3 mg per day, whereas torsemide is administered at 20 to 50 mg per day [13]. It was investigated that bumetanide and torsemide are more efficient than furosemide in HF therapy. These medications showed an advantage in decreasing manifestations, such as fatigue and dyspnea and leading to enhanced weight loss. A critical reduction in hospital readmission rates and all-cause death was also observed [14].

K+-sparing diuretics

K+-sparing diuretic medications are the third type of diuretic that is assigned to as potassium-sparing diuretic drugs [15]. Unlike thiazide and loop diuretics, some of potassium-sparing diuretics do not work on sodium transport. Some medications are aldosterone receptor antagonists at the distal segment of the distal tubule, which leads to higher sodium and water to reach the collecting tube and be discharged in the urine. They are known as potassium-sparing diuretics because they do not provide hypokalemia similar to the thiazide and loop diuretics [16], this is because by inhibiting the reabsorption of aldosterone-sensitive sodium, less hydrogen and potassium ions are replaced for sodium, and hence less hydrogen and potassium are urinary excreted. Other K+-sparing diuretics immediately repress channels of sodium ions correlated with the pump of aldosterone-sensitive sodium and hence have alike impacts on hydrogen and potassium ions as the aldosterone antagonists. Their mode of action relays on the production of kidney prostaglandin. As this category of diuretic medications has limited impacts on the balance of sodium ions, it is frequently used in connection with the loop or thiazide diuretics to control hypokalemia [15].

Carbonic anhydrase inhibitors

Carbonic anhydrase inhibitors repress the bicarbonate transport away from the proximal convoluted tubule within the interstitium, causing decreased sodium reabsorption at this position, consequently high urinary loss of sodium, water, and bicarbonate [15]. These have weak effects and rarely used in the treatment of heart diseases. Their principal application is in the treatment of glaucoma [15].

Combination diuretic therapy (CDT)

This therapy comprising of a loop and thiazide diuretic is suggested for controlling the resistance of diuretic in HF cases with volume overload, reflects a sufficient dosage of an intravenous loop diuretic (Intravenous furosemide daily dose of 160 to 320 mg) [16]. This method provides a diuretic agonist effect through “sequential nephron blockade.” Thiazide diuretics prevent distal tubule sodium reabsorption and can antagonize the kidney adaptation to chronic loop diuretic treatment. This enhances diuretic resistance secondary to rebound sodium maintenance. The CDT side effects including weight loss, enhancement of the symptomatic system, limiting hospital discharge, systemic congestion, and limitation of readmission. Nevertheless, accurate investigation and regular monitoring of electrolytes and kidney function tests are necessary with the starting of CDT as this treatment protocol can cause severe hypokalemia. The first dose of Metolazone is 2.5 mg daily is recommended for two to three times weekly for the outpatient. While for inpatients, a 10 mg initial daily dose of metolazone is recommended with a 3-day limit to the drug plan [16].

Diuretic Rrsistance

The resistance to diuretic is a basic issue in patients suffering from HF. Elimination of extreme fluid is obtained by a combination of loop diuretics and salt restriction although in some patients, congestion perseveres notwithstanding sufficient diuretic treatment. The diuretic resistance prevalence in the HF patients is obscure as a result of the differences among studied groups, the common comorbidity, the various medication strategies, in addition to the several definitions used in different clinical studies [17]. Diuretic resistance was correlated with total, sudden, and pumps failure death. Loop diuretics are “threshold drugs.” HF is causing the dose-response curve for loop diuretics to shift down and to the right (Figure 1). Consequently, a higher outset dose of loop diuretics is required to obtain a similar level of sodium excretion [18].

Figure 1. The dose-response curve for loop diuretics [19].

Excretion of diuretics

All diuretics except osmotic ones are actively excreted in the urine by the proximal tubule. The organic-acid pathway is the way for excretion of thiazides, loops, and acetazolamide diuretics, while the organic-based pathway is the way for excretion of amiloride and triamterene [19].


Conclusion

Thiazide diuretics work by blocking the sodium-chloride carrier [8]. Loop diuretics repress the Na+/2Cl-/K+ co-carrier of the thick ascending loop of Henle, wherever about thirty percent of infiltrated sodium is reabsorbed into the blood circulation [8]. All diuretics except spironolactone enter these luminal transportation positions via the tubular fluid. Spironolactone competitively connects receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted kidney tubule. Diuretic resistance was associated with total, sudden, and pumps failure death [19,20].


List of Abbreviations

CDT Combination diuretic therapy
HF Heart failure

Conflict of interest

Not applicable.


Funding

None.


Consent for publication

Not applicable.


Ethical approval

Not applicable.


Author details

Abdulaziz Dhafer Algarni1, Wejdan Talal Almutairi2, Asawir Mohammed AlQurashi3, Esraa Abdulrahman Alshehrani3, Wijdan Turki Almrzouqi3, Hussain Ali Alhazmi4

  1. Al-Maarefa University, Al Khalidiyah, Saudi Arabia
  2. King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
  3. King Abdulaziz University, Jeddah, Saudi Arabia
  4. Hunan Normal University, Changsha, China

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How to Cite this Article
Pubmed Style

Algarni AD, Almutairi WT, AlQurashi AM, Alshehrani EA, Almrzouqi WT, Alhazmi HA. Uses of diuretics in heart failure: a brief review. IJMDC. 2020; 4(2): 509-512. doi:10.24911/IJMDC.51-1576053352


Web Style

Algarni AD, Almutairi WT, AlQurashi AM, Alshehrani EA, Almrzouqi WT, Alhazmi HA. Uses of diuretics in heart failure: a brief review. https://www.ijmdc.com/?mno=77573 [Access: October 15, 2021]. doi:10.24911/IJMDC.51-1576053352


AMA (American Medical Association) Style

Algarni AD, Almutairi WT, AlQurashi AM, Alshehrani EA, Almrzouqi WT, Alhazmi HA. Uses of diuretics in heart failure: a brief review. IJMDC. 2020; 4(2): 509-512. doi:10.24911/IJMDC.51-1576053352



Vancouver/ICMJE Style

Algarni AD, Almutairi WT, AlQurashi AM, Alshehrani EA, Almrzouqi WT, Alhazmi HA. Uses of diuretics in heart failure: a brief review. IJMDC. (2020), [cited October 15, 2021]; 4(2): 509-512. doi:10.24911/IJMDC.51-1576053352



Harvard Style

Algarni, A. D., Almutairi, . W. T., AlQurashi, . A. M., Alshehrani, . E. A., Almrzouqi, . W. T. & Alhazmi, . H. A. (2020) Uses of diuretics in heart failure: a brief review. IJMDC, 4 (2), 509-512. doi:10.24911/IJMDC.51-1576053352



Turabian Style

Algarni, Abdulaziz Dhafer, Wejdan Talal Almutairi, Asawir Mohammed AlQurashi, Esraa Abdulrahman Alshehrani, Wijdan Turki Almrzouqi, and Hussain Ali Alhazmi. 2020. Uses of diuretics in heart failure: a brief review. International Journal of Medicine in Developing Countries, 4 (2), 509-512. doi:10.24911/IJMDC.51-1576053352



Chicago Style

Algarni, Abdulaziz Dhafer, Wejdan Talal Almutairi, Asawir Mohammed AlQurashi, Esraa Abdulrahman Alshehrani, Wijdan Turki Almrzouqi, and Hussain Ali Alhazmi. "Uses of diuretics in heart failure: a brief review." International Journal of Medicine in Developing Countries 4 (2020), 509-512. doi:10.24911/IJMDC.51-1576053352



MLA (The Modern Language Association) Style

Algarni, Abdulaziz Dhafer, Wejdan Talal Almutairi, Asawir Mohammed AlQurashi, Esraa Abdulrahman Alshehrani, Wijdan Turki Almrzouqi, and Hussain Ali Alhazmi. "Uses of diuretics in heart failure: a brief review." International Journal of Medicine in Developing Countries 4.2 (2020), 509-512. Print. doi:10.24911/IJMDC.51-1576053352



APA (American Psychological Association) Style

Algarni, A. D., Almutairi, . W. T., AlQurashi, . A. M., Alshehrani, . E. A., Almrzouqi, . W. T. & Alhazmi, . H. A. (2020) Uses of diuretics in heart failure: a brief review. International Journal of Medicine in Developing Countries, 4 (2), 509-512. doi:10.24911/IJMDC.51-1576053352