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Deventer buying coke

Official websites use. Share sensitive information only on official, secure websites. E-mail: francesco. 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. For as long as sporting events have existed, the desire to gain a competitive edge has been present as well. With the huge financial incentives and the subsequent pressures to excel associated with the international sporting industry, attempts to achieve a competitive edge especially with the use of performance-enhancing drugs have only been increasing Barroso et al. Despite centuries of reports of using substances to enhance athletic performance, testing athletes for the use of performance-enhancing drugs began only in Barroso et al. Compounds and methods included on the list are those that can be used by an athlete to provide an unfair advantage WADA, b. The objective of this paper is to review the pharmacology of diuretics and the applications of diuretics to sports doping, as well as detail the analytical methodologies currently described to detect and identify diuretics in urine. All the classes of diuretics detailed later in this paper are banned in sport. Diuretics are therapeutic agents that are used to increase the rate of urine flow and sodium excretion in order to adjust the volume and composition of body fluids or to eliminate excess of fluids from tissues Jackson, Diuretics were first banned in sport both in competition and out of competition in because they can be used by athletes for two primary reasons. First, their potent ability to remove water from the body can cause a rapid weight loss that can be required to meet a weight category in sporting events. Second, they can be used to mask the administration of other doping agents by reducing their concentration in urine primarily because of an increase in urine volume. The urine dilution effect of diuretics also allows them to be classified as masking agents and precludes their use both in and out of competition. Some diuretics also cause a masking effect by altering the urinary pH and inhibiting the passive excretion of acidic and basic drugs in urine Ventura and Segura, ; Goebel et al. In , diuretics represented 7. All classes of diuretics were represented in the positive cases; hydrochlorothiazide was the most common diuretic detected, with cases. Table 1 summarizes the statistics of positive diuretic findings by all WADA laboratories from to the present. In all six of the past years, all classes of diuretics have been represented in the positive findings WADA, ; ; ; ; a ; a ;. Over the years, the total number of occurrences has been increasing; this trend of increasing positive findings may be due not only to an increase in abuse, but is likely due to improved methods of detection. This pharmacological class of drugs includes compounds with a variety of pharmacological and physicochemical properties. Because of the variety of diuretic compounds, classification of these drugs can be based on different criteria. The most common classification categories are by site of action in the nephron, relative efficacy, chemical structure, effects on potassium excretion, similarity to other diuretics and mechanism of action Jackson, In the following section, this review will briefly summarize the pharmacology and toxicology of diuretic classes based on mechanism of action. Figure 2 details the site and mechanism of the diuretic classes in the nephron Figure 2A. Examples of diuretic structures grouped by mechanism of action. Site and mechanism of action of diuretics. A The nephron with major divisions labelled. B Mechanism of carbonic anhydrase inhibitors in the proximal tubule. Aldo, aldosterone; CA, carbonic anhydrase; MR, mineralocorticoid receptor. Figure modified from Jackson Historically, the detection of diuretics in biological samples was achieved using high-performance liquid chromatography HPLC with ultraviolet-diode array detection UV-DAD. Therefore, mass spectral methodology is required for confirmation according to international anti-doping regulations Trout and Kazlauskas, ; Thevis and Schanzer, ; WADA, c. Ventura and Segura published a comprehensive review of diuretic analysis in Ventura and Segura, This review will mainly focus on the developments and techniques that have been developed since that time. Carbonic anhydrase inhibitors Figure 1A by definition are a class of substances that act as inhibitors of CA carbonate dehydratase, carbonate hydrolase, E. Type IV CA, a membrane-bound isoenzyme, is found in the luminal and basolateral membranes. In addition, bicarbonate is kept in the lumen with the consequent increase of urinary pH to approximately 8 and subsequential development of a metabolic acidosis. Phosphate excretion is also increased by a mechanism not fully clarified. Currently, there are three main CA inhibitors available as diuretics see Figure 1A for structures , acetazolamide the prototype of the class, a sulphonamide without antibacterial activity , dichlorphenamide and methazolamide. Acetazolamide and dichlorphenamide are excreted by the kidneys as intact drugs while methazolamide is extensively metabolized. The major therapeutic indication of CA inhibitors is open-angle glaucoma. Acetazolamide is often used for the prevention of high-altitude mountain sickness AMS , a pathological effect of high altitude on the body caused by acute exposure to low partial pressure of oxygen at high altitude that can progress to high-altitude oedema pulmonary and cerebral. Acetazolamide increases bicarbonate excretion in urine, making the blood more acidic and increasing ventilation, thus aiding in acclimatization to high altitude. Acetazolamide is also used for the treatment of oedema. CA inhibitors may also be used therapeutically for the treatment of pre-menstrual fluid retention. Carbonic anhydrase is present in a number of extrarenal tissues, including the eye, gastric mucosa, pancreas, central nervous system and erythrocytes. Because of the varied location around the body, CA inhibitors are typically used for non-diuretic indications, such as glaucoma, to decrease the rate of formation of aqueous humour and consequently reduce intraocular pressure. It has been demonstrated that topical administration of dorzolamide, a CA inhibitor abolishing the enzymatic activity in the ciliary body, does not produce any diuretic effect Mazzarino et al. CA inhibitors are also used as antiepileptic drugs due in part to the production of metabolic acidosis. Most adverse effects, contraindications and drug interactions are a consequence of urinary alkalinization or metabolic acidosis. Infrequent adverse effects are similar to those of sulphonamides. The diversion of ammonia of renal origin from urine into the systemic circulation, calculus formation and ureteral colic causing precipitation of calcium phosphate salts in alkaline urine, worsening of metabolic or respiratory acidosis and reduction of the urinary excretion rate of weak organic bases are also adverse effects of CA inhibitors. The efficacy of CA inhibitors as single agents is low and the long-term usefulness of CA inhibitors is often compromised by the development of compensatory processes such as metabolic acidosis. Additionally, the continuous use of CA inhibitors may result in the diminution of the desired therapeutic effect. Acetazolamide accounted for 1. Uric acid excretion is also increased with acute administration while chronic administration has the converse effect. These symport inhibitors undergo partial metabolism hepatic for bumetanide and torsemide, renal glucuronation for the others with renal excretion as intact drugs Shankar and Brater, Because of their sulphonamide-based structure, some loop diuretics have weak CA-inhibiting activity that further increases the diuretic effect of these drugs. Moreover, they have direct vascular effects Dormans et al. This effect, particularly evident for furosemide, benefits patients with pulmonary oedema even before diuresis ensues. A major indication of loop diuretics is in the treatment of acute pulmonary oedema. They are also used for the treatment of chronic congestive heart failure. This leads to a significant reduction in mortality, a decrease in the risk of worsening heart failure and an improvement in exercise capacity Faris et al. Loop diuretics are also widely used for the treatment of hypertension van der Heijden et al. Adverse effects are all correlated to fluid and electrolyte imbalance. Furthermore, they increase plasma levels of low-density lipoprotein cholesterol and triglycerides while decreasing plasma levels of high-density lipoprotein cholesterol. Loop diuretics can cause ototoxicity, especially ethacrynic acid. This class of diuretics has drug—drug interactions with several substances including aminoglycosides, anticoagulants, digitalis glycosides, lithium, propranolol, sulphonylureas, cisplatin, probenecid and amphotericin B. The synergism of diuretic activity of associated loop and thiazide diuretics leads to profound diuresis. Furosemide was the second most frequently detected diuretic with samples testing positive In addition, some thiazide diuretics also are weak inhibitors of CA. Some examples of the drugs included in this class are the following see the structure in Figure 1C : bendroflumetazide, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methyclothiazide, polythiazide, trichlormethiazide, chlortalidone, indapamide, metolazone and quinethazone. They are partially metabolized by unknown pathways and are partially excreted as intact drugs by the kidney. Plasma protein binding varies considerably among the class. The wide ranges of half-lives vary from 1. Thiazide diuretics are the most widely used diuretics. They are employed as a first-line therapy for hypertension either alone or in combination with other antihypertensive medications Chobanian et al. They are also used for the treatment of oedema associated with heart, liver and renal diseases. Thiazide diuretics are frequently used because of their low cost, high tolerance, good compliance once daily administration , few contraindications, efficacy comparable to other classes of antihypertensive agents and proven benefits in reducing cardiovascular morbidity and mortality. Thiazide and thiazide-like diuretic drug—drug interactions cause a diminished effect of anticoagulants, uricosuric agents, sulphonylureas and insulin and increase the effects due to synergism of action between anaesthetics, diazoxide, digitalis glycosides, lithium, vitamin D and loop diuretics. Hydrochlorothiazide was the most detected diuretic, found in Osmotic diuretics are a class of non-metabolizable low-molecular-weight compounds. Only four compounds are included in this diuretic class, glycerin, isosorbide, mannitol and urea. The molecular structures are shown in Figure 1D. These compounds are relatively pharmacologically inert, freely filterable by the glomerulus and non-diffusible across the nephron. They are administered in large doses, not only orally glycerine, isosorbide but also intravenously mannitol, urea. Osmotic diuretics act both in the proximal tubule and the loop of Henle, with the latter being the primary site of action. These diuretics also work via an osmotic effect in the tubules and by reducing medullary tonicity. The half-lives range from less than 1 h in the case of glycerin and mannitol to almost 10 h for isosorbide. By extracting water from intracellular compartments, osmotic diuretics expand the extracellular fluid volume, decrease blood viscosity and inhibit renin release. Their use is limited to well-defined clinical situations, for instance, mannitol is used to reduce cerebral oedema and brain mass before and after neurosurgery, in acute tubular necrosis as a renal protector Levinsky and Bernard, , and for the treatment of dialysis disequilibrium syndrome. Because osmotic diuretics extract water from the eye and brain, they are all used to control intraocular pressure during acute attacks of glaucoma and in ocular surgery. Osmotic diuretic therapy can cause hypernatremia and dehydration due to the loss of water in excess of electrolyte loss. Conversely, their use can lead to hyponatremia, which is responsible for the common adverse effects headache, nausea and vomiting. Hyperglycaemia can occur as a result of glycerin metabolism. The only two drugs of this class in clinical use are triamterene and amiloride structures pictured in Figure 1E. Typically, they are used in combination with other diuretics to offset their severe kaliuretic effects and preserve potassium levels in patients at risk of hypokalaemia. The route of elimination is predominantly renal for intact amiloride while triamterene is extensively metabolized into the active 4-hydroxytriamterene sulphate and excreted in urine. Triamterene can also reduce glucose tolerance and induce photosensitization. Mineralocorticoid receptor antagonists Figure 1F are competitive inhibitors of aldosterone that bind to and inhibit cytosolic MRs found in the epithelial cells of the late distal tubule and collecting duct of the nephron Figure 2E. The MR is a member of the steroid superfamily of nuclear receptors. Normally, aldosterone enters the epithelial cell and binds to MRs. The MR—aldosterone complex then translocates to the nucleus where it binds to specific sequences of DNA hormone responsive elements and thereby regulates the expression of multiple gene products called aldosterone-induced proteins. Unlike the MR—aldosterone complex, the MR—antagonist complex is not able to induce the synthesis of aldosterone-induced proteins. The compounds belonging to this class see Figure 1F for molecular structures are spironolactone, canrenone, potassium canrenoate and eplerenone. Canrenone is an active metabolite of spironolactone with a fold greater half-life Canrenoate is not active, but is converted to canrenone in the body. Eplerenone has good oral availability and is extensively metabolized. The clinical efficacy of MR antagonists strictly depends on endogenous levels of aldosterone; higher levels cause greater effects. This group of diuretics is very useful as an alternative to potassium replacement therapy. Usually, they are employed in cases of high-aldosterone concentrations. Spironolactone is useful in the treatment of primary hyperaldosteronism and refractory oedema associated with secondary aldosteronism Ouzan et al. Because of its molecular structure Figure 1F , spironolactone has some affinity for progesterone and androgen receptors that causes some side effects such as gynecomastia, impotence and menstrual irregularities. Chronic administration of spironolactone can induce malignant tumours; in particular, breast cancer has been observed. With regard to drug—drug interactions, salicylates reduce the tubular secretion of canrenone and decrease the diuretic efficacy of spironolactone, while spironolactone alters the clearance of digitalis glycosides. Canrenone and spironolactone together accounted for 4. As previously mentioned, diuretics are commonly prescribed in clinical medicine to treat hypertension and other cardiovascular disorders. These compounds are also frequently encountered illicitly in sports. Diuretics are banned in all sports because they can cause rapid weight loss and can act as masking agents to hide the effects of other prohibited substances both in and out of competition. For diuretics, the primary permitted therapeutic use is for hypertension WADA, b. It should be noted that a TUE is not valid if an athlete's urine contains a diuretic in association with a threshold or sub-threshold level of another exogenous substance included on the Prohibited List. Because of the TUE, some athletes do use diuretics for legitimate medicinal purposes; in many cases, however, diuretic use is illicit Clarkson and Thompson, Reasonably, the most effective use of diuretics in sport doping would be before an anti-doping test. Diuretics increase urine volume and dilute any doping agents as well as their metabolites present in the urine and make their detection more problematic by conventional anti-doping analysis. Although there is little evidence of athletic performance enhancement following diuretic administration, their abuse is widespread among athletes who want to lose weight quickly. For example, diuretic s use can allow an athlete to transiently reduce body weight, which is a clear advantage in wrestling, boxing, judo and weight-lifting as well as in general sports where weight categories are involved and among athletes who want to maintain a low body weight, such as female gymnasts and ballet dancers. Skiers and mountain climbers, however, make legitimate use of acetazolamide a CA inhibitor that also acts on sites different than the kidney in preventing AMS. In both cases and discussed in more detail below, the diuretic administration can be acute or chronic with administered doses that can markedly exceed therapeutic levels. In general, athletes can use diuretics in a single dose some hours before a competition i. It is important to note that the diuretics most abused by athletes furosemide, hydrochlorothiazide and triamterene have a short half-life and are therefore undetectable in urine if samples are not collected within 24—48 h after the last administration. In an attempt to assess the significance of diuretic use in weight loss, Caldwell et al. The results showed a decrease of 2. Additionally, diuretics are abused simultaneously with androgenic-anabolic steroids by bodybuilders to accentuate muscle definition and body tone. In the same study reported by Caldwell et al. Diuretics can have variety of physiological effects on exercise physiology, including effects on metabolism thermoregulation, potassium homeostasis , the cardiovascular system and the respiratory system \[pulmonary actions, oxygen uptake VO 2 \]. Most of the effects are related to the consequences of volume depletion and electrolyte imbalance and depletion. Exercise can affect the action of diuretics as well, with consequences on both pharmacology and pharmacokinetics. At the level of the nephron, exercise can both complement and antagonize the effects of diuretics. Exercise acutely induces a negative water balance and long-term regular exercise lowers blood pressure, augmenting pharmacological properties of diuretics Zappe et al. Exercise also influences specific actions of diuretics; it can cause an acute shift of intracellular potassium into the intravascular space Young et al. While thiazide diuretics are associated with insulin resistance Moser, , exercise potentiates the opposite effect Plasqui and Westerterp, This reduces blood insulin levels and consequently increases hepatic glucose release and decreases muscle utilization of insulin Bonen et al. Although there is little information on how exercise affects diuretic pharmacokinetics, chlorothiazide, hydrochlorothiazide and triamterene have an elimination half-life short enough 1. Therefore, these substances are not always detected in urine samples collected post-competition or at the end of an intense training session. It is notable that both exercise and diuretics can independently cause fluid and electrolyte loss. Table 2 , adapted from Caldwell et al. Effects of exercise and diuretics on renal physiology \[adapted from Caldwell and Reents \]. It is known that during exercise skeletal muscle temperature exceeds core temperature within several minutes, and alteration of the body's thermoregulatory systems is a major risk of diuretic abuse. The marked dehydration following diuretic intake exerts a detrimental effect on the cardiovascular and thermoregulatory systems of the body during exercise and can lead to exhaustion, irregular heartbeat, heart attack and death. Both acetazolamide Brechue and Stager, , a mild diuretic, and furosemide Claremont et al. Diuretics affect potassium homeostasis in exercising muscle; intracellular potassium and the resting membrane potential of the cell both decrease. All diuretics except the potassium-sparing agents increase kaliuresis, accelerating the depletion of intracellular potassium. On the other hand, overuse of potassium-sparing diuretics such as spironolactone, triamterene and amiloride can lead to hyperkalaemia and consequently may expose athletes to malignant arrhythmias Appleby et al. Moreover, the interference of most diuretics with uric acid metabolism can cause a gout attack, which can be very painful Koutlianos and Kouidi, Diuretic-induced dehydration influences exercise heart rate. In particular, at lower exercise intensity a higher heart rate results, while during maximal exercise exertion, the effect is lower or almost absent Stager et al. This is especially true for acetazolamide Brechue and Stager, and to a lesser extent, furosemide abuse Claremont et al. Studies performed on CA inhibitors and thiazide diuretics demonstrated that after administration of acetazolamide Brechue and Stager, or a hydrochlorothiazide—triamterene combination Nadel et al. Loss of plasma volume and stroke volume disrupts thermoregulation via peripheral vasodilation radiation cooling and perspiration evaporative cooling , impairing both the acute and the long-term physiological vasodilatory response to aerobic exercise. Furthermore, aldosterone antagonists, in particular spironolactone, interfere with the increase in aldosterone receptor sensitivity due to exercise-induced hypervolemia a consequence of normal adaptation to regular exercise. Because CA plays a key role in the acid-base regulation mechanisms, CA inhibitors are the only class of diuretics that can affect pulmonary function. Acetazolamide has been shown to impair CO 2 elimination during exercise Scheuermann et al. In AMS, acetazolamide enhances alveolar oxygenation by increasing arterial oxygen pressures and lowering arterial carbon dioxide pressures Bradwell et al. The cellular metabolic effects of acetazolamide may override its pulmonary effects and cause an inhibition of VO 2 during maximal exercise Stager et al. Furosemide decreases tidal volume, minute ventilation and the respiratory exchange ratio at aerobic threshold Caldwell et al. Conversely, clinical data indicate that inhaled furosemide reduces the exercise-induced bronchoconstriction in asthmatic children Munyard et al. The effects of diuretics on VO 2 are variable. Furosemide causes a dose-dependent effect; furosemide has no influence on VO 2 at low doses Armstrong et al. Acetazolamide affects VO 2 only during maximal exercise Stager et al. Acetazolamide effects on performance depends on altitude; at sea level Heigenhauser et al. Finally, thiazide diuretics are derivatives of sulphonamides and can cause photosensitivity if exercising outdoors during midday hours. Caldwell et al. In this study, VO 2 max maximum oxygen uptake and workload while cycling decrease in athletes after furosemide intake. Even after rehydration, muscular endurance and performance are greatly compromised by diuretic use Caldwell et al. Additional studies performed on middle-distance runners Armstrong et al. Although insufficient data are available to establish the effect of long-term diuretic treatment on exercise capacity, it has been clearly shown that both single dose and short-term diuretic treatment adversely affect maximal exercise capacity and the duration of prolonged submaximal exercise Fagard et al. For the multitude of reasons mentioned above, the drawbacks related to diuretic administration outweigh the potential advantages of lowering of weight and urine dilution; dehydration drastically impairs aerobic capacity and muscular strength and decreases metabolic efficiency. This results in a detrimental effect on overall sport and exercise ability and especially on athletic performance Caldwell et al. In addition, a potential effect of diuretics abuse is the possible alteration of the glomerular filtration size, which depends on a series of parameters Edwards et al. Finally, it should be noted that disqualification from competition as well as the other, previously mentioned detrimental effects of diuretic abuse offset any perceived benefits. Although many of the studies highlighted above were published in the s and s, diuretics are still widely abused in sport and among the most prescribed therapeutic agents. Few studies of the effects of diuretics on athletes have been published recently because in recent times, most studies assessing doping agents and exercise and sport have focused on newer drugs and methods of performance enhancement. Diuretic use for the masking of other prohibited substances remains a serious problem, however. Lower dosages of diuretics are likely to be insufficient at causing the masking effect or dramatic and acute weight loss abusers seek. Properties of diuretics important for analytical method development \[adapted from Ventura and Segura and Jackson \]. However, in some instances, the target analyte may not be the parent compound or its metabolites, but one or more degradation products formed after the hydrolysis of the diuretics in aqueous media. This is the case of thiazide diuretics, and primarily among them hydrochlorthiazide and althiazide. This phenomenon is more relevant when there is a delay between collection of the sample and the laboratory analysis Thieme et al. Basically, the critical steps are represented by the extraction of the diuretics from the biological matrix and the chemical derivatization performed to increase volatility and thermal stability of the target compounds. SPE can allow the recovery of diuretics with higher yields, but at the same time the use of disposable cartridges increases the overall cost of the pretreatment procedure, especially in the case of more complex supports, like internal surface reversed-phase supports ISRP-size exclusion. Commercially available pre-activated columns have been tested for their efficacy and the best choice should depend on the characteristics of the matrix and on the expected composition of the sample \[reviewed by Ventura and Segura in Ventura and Segura, \]. Anhydrous sodium sulphate can be added to promote a salting-out effect. Particular care has to be dedicated to the study of potential degradation processes that could involve target compounds. Oxidation of thiazides althiazide, benzthiazide and polythiazide has been demonstrated in the presence of ethyl acetate, so the efficacy and the non-reactivity of different extraction solvents has to be preliminarily assessed. In some instances, two or more pretreatment steps can be combined, as in the case of extractive methylation in which both the extraction and the derivatization steps are combined in a single procedure. The most common derivatization procedures are silylation and methylation, but the latter is usually preferred as it allows sufficient yields of more stable derivatives for most diuretics to be obtained \[reviewed by Carreras et al. When methylation is performed by a stand-alone process, the time can be drastically reduced by microwave irradiation, either in combination or as an alternative to thermal incubation Amendola et al. Drastically shorter times can be obtained by fast-GC systems, in which last generation columns and mass spectrometric detection relying on fast electronics are successfully coupled. Fast-GC systems provide a fold reduction of the overall chromatographic run Morra et al. The mass spectra of the methyl derivatives of diuretics have been described by different authors, and the fragmentation profiles have been also interpreted by comparison with the deuterated methyl derivatives Yoon et al. When diuretics were introduced on the list of forbidden substances by the International Sports Authorities, the first attempts to create a screening method for their detection were based on HPLC. At that time, UV diode array was used as detector as it facilitated peak identification Ventura and Segura, The lack of robustness of the equipment did not permit a daily running screening method based on these instruments. Thieme et al. Additionally, both positive and negative ionization modes can by used simultaneously permitting the detection of both acidic and basic compounds included among diuretics. The analysis by tandem MS with triple stage quadrupoles were selective and sensitive enough compared with previous methods and made simplification of sample preparation possible as the cleanness of the urinary extracts was less critical compared with previously designed LC-UV methods. Even more recently, the need for more universal strategies for doping agents analysis introduced the use of time-of-flight analysers Georgakopoulos et al. The selectivity and sensitivity of these techniques allowed the inclusion of additional non-diuretic drugs, also forbidden in sports, in the same screening procedures Deventer et al. Additionally, different approaches for sample preparation have been explored. In the past, classical double extractions with organic solvents at acidic and basic pH were used to permit the recovery of diuretics presenting different physicochemical properties. The new features of the instruments and the extension of the screening methods to other compounds expand the possibilities of sample preparation. Specific SPE procedures can be performed in robotic systems Goebel et al. Currently, there are analyses that includes diuretics among other doping substances where more than different compounds can be analysed in less than 10 min Thorngren et al. The members of the diuretic class of drugs vary greatly in structure, physicochemical properties and site and mechanism of action. Future goals of diuretic analysis include developing more efficient and more economical detection methods. Increasing the sensitivity of the methods and the number of compounds in the screen while decreasing the analysis time and cost to laboratories would be welcome improvements. Additionally, the development of methods that combine the detection of diuretics with other prohibited substances will enhance the ability of laboratories to monitor abuse and doping in sports. As a library, NLM provides access to scientific literature. Br J Pharmacol. Find articles by Amy B Cadwallader. Find articles by Xavier de la Torre. Find articles by Alessandra Tieri. Open in a new tab. One arrow indicates a moderate effect; two arrows indicate a profound effect. Unknown Indapamide 8. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Mineralocorticoid receptor antagonists aldosterone antagonists and some potassium-sparing diuretics.

Deventer buying coke