Diuretics are medications that increase urine flow and sodium excretion to adjust the volume and composition of body fluids. There are several main categories of this class of drugs, and the compounds vary widely in structure, physicochemical properties, effects on urinary composition and renal hemodynamics, and location and mechanism of action. Diuretics are often abused by athletes to excrete water in order to lose weight quickly and mask the presence of other prohibited substances. Due to their abuse by athletes, diuretics have been added to the World Anti-Doping Agency`s (WADA) list of prohibited substances. The use of diuretics is prohibited in-competition and out-of-competition, and diuretics are regularly studied by anti-doping laboratories. This review provides an overview of the pharmacology and toxicology of diuretics and discusses their use in sport. The most common analytical strategies currently followed by WADA-accredited anti-doping laboratories will be discussed, as well as the challenges faced by laboratories in the analysis of this diverse class of drugs. Diuretics can have a variety of physiological effects on exercise physiology, including effects on metabolism (thermoregulation, potassium homeostasis), cardiovascular system, and respiratory system (pulmonary actions, oxygen (VO2) uptake). Most of the effects are related to the consequences of volume depletion and electrolyte imbalance and depletion. Exercise can also affect the action of diuretics, with implications for pharmacology and pharmacokinetics. At the level of the nephron, exercise can both complement and antagonize the action of diuretics. Exercise acutely induces negative water balance and regular, long-term exercise lowers blood pressure and improves the pharmacological properties of diuretics (Zappe et al., 1996). Exercise also affects the specific effects of diuretics; It can cause acute displacement of intracellular potassium in the intravascular space (Young et al., 1992) and enhance the caliuretic effect of diuretics.
While thiazide diuretics are associated with insulin resistance (Moser, 1998), exercise potentiates the opposite effect (Plasqui and Westerterp, 2007). In most cases, exercise is used as a therapy for insulin resistance because it activates pancreatic β cells via the neuroadrenergic system (Bordenave et al., 2008). This lowers insulin levels in the blood and, as a result, increases glucose release in the liver and decreases muscle use of insulin (Bonen et al., 2006). Although there is little information on how exercise affects diuretic pharmacokinetics, chlorothiazide, hydrochlorothiazide and triamterene have an elimination half-life short enough (1.5-4 h) to be affected by 1 hour or more of sustained exercise (Somani, 1996), thereby decreasing renal and hepatic blood flow. As a result, these substances are not always detected in urine samples taken after competition or at the end of an intense training session. It should be noted that exercise and diuretics can independently cause a loss of fluid and electrolytes. Table 2, adapted by Caldwell et al. (1984) and Reents (2000), summarizes the effects of exercise and diuretics on renal physiology. In contrast, potassium-sparing diuretics can cause potassium levels to be too high. This can potentially lead to dangerous cardiac arrhythmias or cardiac arrest. If diuretics aren`t enough to lower your blood pressure, your doctor may add other blood pressure medications to your treatment plan.
Loop diuretics such as furosemide are used to treat high blood pressure (high blood pressure), fluid in the lungs (pulmonary edema), generalized swelling and hyperkalemia (dangerously high potassium levels). As an off-label use, they may be prescribed for hypercalcemia or high calcium levels. Na+/Cl inhibitors were the most widely used class of diuretics in 2008, accounting for 38.7% of positive samples, according to WADA statistics. Hydrochlorothiazide was the most commonly detected diuretic, found in 31.4% (137) of positive samples (AMA, 2009a). The diuretics listed above should all be prescribed by your doctor. But you may have heard of diuretics that you can buy over-the-counter. These are sometimes called «natural diuretics». These are herbs or supplements that claim to have a mild diuretic effect, thus treating «water retention.» Some people use them for water retention associated with their periods. But there is no evidence that they work.
Diuretics are used to lower blood pressure and reduce symptoms of fluid overload such as edema. There are many classifications of diuretics. We will discuss loop diuretics, thiazides and potassium-sparing agents. Other diuretics, such as osmotic diuretics, are used to decrease cerebrospinal fluid and the brain. Osmotic diuretics attract water by osmosis. Osmosis is the transition of water from a less concentrated solution to a more concentrated solution. Amiloride blocks the reabsorption of water in your body. Like spironolactone, amiloride is often used to counteract potassium loss caused by other diuretics.
When diuretics were added to the list of banned substances by international sports authorities, the first attempts to create a screening method for their detection were based on HPLC. At that time, the UV diode array was used as a detector because it facilitated peak identification (Ventura and Segura, 1996). According to IOC and WADA requirements, the confirmation procedures required to support a positive case must be based on MS. For this reason, a GC/MS method after methylation of compounds was the technique of choice in most cases. For the reasons explained in the previous sections, significant changes were introduced in diuretic detection strategies in the doping field in the late 1990s as more robust, reliable and affordable LC/MS instruments became available. The first attempts to use LC/MS for diuretic detection began in the early 1990s with thermospray or particle beam interfaces (Ventura et al., 1991) in confirmatory analyses.