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September 16, 2019

The human body is approximately 60 percent water [1]. The water in the body is divided into extracellular and intracellular fluids. The amount of extracellular fluid must stay almost constant for the cells to function properly. Human fluids contain a variety of salts in concentrations that are carefully regulated. If the salts become too concentrated or too diluted, metabolic disorders may follow. [2]. Of the blood salts of humans, the most important ones are sodium and potassium. Extracellular fluid contains mainly sodium while intracellular fluid contains potassium. Both are essential for the normal functioning of the cell. The salt balance of the body can be easily measured from plasma. [3, 4]. Normally, the quantity of sodium in plasma is approximately 3.2 grams per litre, or approximately 140 millimoles per litre (mmol/l) [4]. The quantity of potassium in plasma is relatively low (0.15 g per litre), but its significance is high for the metabolism. The normal potassium reference values are 3.3–4.9 mmol/l [3].The role of the kidneys is to remove foreign substances and impurities from the blood and to keep the body’s fluid and electrolyte balance stable. Accordingly, the kidneys are the main regulator of the fluid and electrolyte balance concentration. Per day, they produce approximately 180 litres of extremely mild primary urine consisting of water and electrolytes. Some of this primary urine is absorbed back into the blood stream while the rest is eliminated from the body as urine. Diuretics are pharmaceutical substances with a mechanism of action that prevents the electrolytes and water from being reabsorbed in the kidneys. As a consequence of this, the secretion of water and salts in the urine increases. [5].

Diuretics differ from one another, for instance, by their chemical structures and their mechanisms of action. Diuretics are classified into thiazide diuretics and their derivatives, short-acting salt diuretics, potassium-sparing diuretics, and other diuretics [5].

For example, hydrochlorothiazide belongs to the thiazide group of diuretics. Furosemide and bumetanide are short-acting salt diuretics, or loop diuretics. Spironolactone, triamterene and amiloride are potassium-sparing diuretics. Some examples of other diuretics include carbonic anhydrase inhibitors, such as acetazolamide and dorzolamide, as well as osmotic diuretics, such as water diuresis-inducing mannitol. [5]

Medical use

Diuretics are used in the treatment of hypertension, cardiac failure, and states of edema, as well as other conditions [5, 6]. The pharmaceutical treatment of hypertension employs all diuretics, which increase the excretion of sodium and chloride in urine [3]. When treating cardiac failure, the use of diuretics aims to reduce the body’s water and salt content. This also reduces the amount of blood.

Salt diuretics are used especially in situations that require rapid and effective diuresis: for example, in the treatment of pulmonary edema, hypertensive crises, and toxicosis. [5] Salt diuretics are also used in the treatment of cardiac failure [6].

In comparison with other diuretics, the efficacy of potassium-sparing diuretics is weaker, so these are used alongside thiazide diuretics in the treatment of hypertension. Potassium-sparing diuretics are used as the primary treatment, for example, in the treatment of cirrhosis.

Properties and mechanism of action

The properties of the various diuretics differ from one another [5]. Salt diuretics are more effective than thiazide diuretics, whereas potassium-sparing diuretics are less effective than other diuretics [3]. There are also differences between the groups of diuretics in terms of the mechanism of action [5].

However, as a general rule, it can be said that diuretics prevent the re-absorption of electrolytes and water in the kidneys and therefore the excretion of urine and electrolytes increases.

Thiazide diuretics increase the excretion of sodium, potassium, chloride and water. Salt diuretics increase the excretion of all of the above in urine, but also potassium. Of the potassium-sparing diuretics, spironolactone increases the excretion of sodium and water in urine, but decreases the excretion of potassium. Triamterene and amiloride inhibit the re-absorption of sodium from the kidneys and decrease the excretion of potassium in urine.

Desired effects

Diuretics remove water and salts [5] from the body; therefore, they are used for losing weight in competitive sports involving weight categories [7].

With the help of diuretics, one can also seek to hide the presence of doping substances in urine because diuretics increase the amount of urine so that the concentration of other substances in urine decreases. Certain diuretics can also change the pH of urine so that doping substances will not necessarily be excreted in urine.

Adverse effects

When using high doses of diuretics, severe dehydration and hypovolemia may develop in the body, meaning that the blood volume can fall abnormally low [5, 6].

The adverse effects induced by thiazide diuretics include, among others, fluid and electrolyte imbalances [2]. The most remarkable adverse effect of thiazide diuretics is hypokalemia, which refers to blood potassium content that is lower than normal. High doses of thiazide diuretics may cause dehydration and hypotonia, meaning an excessive decrease in blood pressure.

Because thiazide diuretics can weaken glucose tolerance and increase the re-absorption of uric acid from the kidneys, their use may sometimes also aggravate diabetes and lead to an increased propensity for gout [5]. The glucose and uric acid concentrations can thereby increase during thiazide treatment. [5]. Some of the other adverse effects include various nervous system symptoms (vertigo, headaches, and fatigue) and alimentary canal symptoms (nausea and vomiting). These are rare, however. [5].

In addition to body dehydration, the adverse effects of short-acting salt diuretics include fluid and electrolyte imbalances, especially hypokalemia [5]. Like thiazide diuretics, short-acting salt diuretics possibly also aggravate diabetes and increase the risk of gout.

The most important adverse effect of potassium-sparing diuretics is hyperkalemia, a condition where the blood potassium level is too high [5]. Hyperkalemia can lead to death.

Salla Ruuska
Doctor of Philosophy (PhD), Pharmacist

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[1] Haug E, Sand O, Sjaastad Ø & Toverud KC (1999): Ihmisen fysiologia. ss. 423-470. WSOY, Porvoo.

[2] Mustajoki P. (2018): Veren suolapitoisuuksien muutoksia. Duodecim.

[3] Mustajoki P. (2018): Hypokalemia. Duodecim.

[4] Mustajoki P. (2018): Hypernatremia. Duodecim.

[5] Ruskoaho (2019): Diureetit. Kirjassa: Farmakologia ja toksikologia, ss. 553-572. Eds. Ruskoaho, H, Hakkola, J. Duodecim, Keuruu.

[6] Ylitalo P (2007): Verenpainetaudin, angina pectoriksen ja sydämen vajaatoiminnan lääkehoito. In Farmakologia ja toksikologia, ss. 567-594. Eds. Koulu M, Tuomisto J. Medicina, Kuopio.

[7] Cadwallander  AB, de la Torre X, Tieri A & Botrè F (2010): The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: pharmacology, toxicology and analysis. Review. British Journal of Pharmacology 161, 1-16.