The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: pharmacology, toxicology and analysis

Abstract

Diuretics are drugs that increase the rate of urine flow and sodium excretion to adjust the volume and composition of body fluids. There are several major categories of this drug class and the compounds vary greatly in structure, physicochemical properties, effects on urinary composition and renal haemodynamics, and site and mechanism of action. Diuretics are often abused by athletes to excrete water for rapid weight loss and to mask the presence of other banned substances. Because of their abuse by athletes, diuretics have been included on The World Anti-Doping Agency's (WADA) list of prohibited substances; the use of diuretics is banned both in competition and out of competition and diuretics are routinely screened for by anti-doping laboratories. This review provides an overview of the pharmacology and toxicology of diuretics and discusses their application in sports. The most common analytical strategies currently followed by the anti-doping laboratories accredited by the WADA are discussed along with the challenges laboratories face for the analysis of this diverse class of drugs.

Figure 2

Site and mechanism of action of diuretics. (A) The nephron with major divisions labelled. (B) Mechanism of carbonic anhydrase inhibitors in the proximal tubule. (C) Mechanism of the Na⁺/K⁺/2Cl^- symporter inhibitors in the thick ascending limb of the loop of Henle. (D) Mechanism of the Na⁺/Cl^- symporter inhibitors in the distal tubule. (E) Mechanism of renal epithelial Na⁺ channel inhibitors and mineralocorticoid receptor antagonists in the collecting duct. Aldo, aldosterone; CA, carbonic anhydrase; MR, mineralocorticoid receptor. Figure modified from Jackson (2006).

Figure 1

Examples of diuretic structures grouped by mechanism of action. (A) Carbonic anhydrase inhibitors; (B) inhibitors of the Na⁺/K⁺/2Cl^- symporter (loop diuretics); (C) inhibitors of the Na⁺/Cl^- symporter (thiazide and thiazide-like diuretics); (D) osmotic diuretics; (E) inhibitors of renal epithelial Na⁺ channels (some potassium-sparing diuretics); (F) mineralocorticoid receptor (MR) antagonists (aldosterone antagonists and some potassium-sparing diuretics).

Figure 1

Examples of diuretic structures grouped by mechanism of action. (A) Carbonic anhydrase inhibitors; (B) inhibitors of the Na⁺/K⁺/2Cl^- symporter (loop diuretics); (C) inhibitors of the Na⁺/Cl^- symporter (thiazide and thiazide-like diuretics); (D) osmotic diuretics; (E) inhibitors of renal epithelial Na⁺ channels (some potassium-sparing diuretics); (F) mineralocorticoid receptor (MR) antagonists (aldosterone antagonists and some potassium-sparing diuretics).

Figure 1

Examples of diuretic structures grouped by mechanism of action. (A) Carbonic anhydrase inhibitors; (B) inhibitors of the Na⁺/K⁺/2Cl^- symporter (loop diuretics); (C) inhibitors of the Na⁺/Cl^- symporter (thiazide and thiazide-like diuretics); (D) osmotic diuretics; (E) inhibitors of renal epithelial Na⁺ channels (some potassium-sparing diuretics); (F) mineralocorticoid receptor (MR) antagonists (aldosterone antagonists and some potassium-sparing diuretics).