Diuretics and

C8H10N4O2. An alkaloid occurring in tea, coffee and guarana, from which it may be prepared by extraction, It is also manufactured by the methylation of theobromine and by the condensation of cyanoacetic acid with urea. Crystallizes with H2O or anhydrous from organic solvents. M.p. (anhydrous) 235"C, sublimes at 176 C. Odourless, and with a very bitter taste. Caffeine acts as a stimulant and diuretic, and is a constituent of cola drinks, tea and coffee. 

C7HgN402. Occurs to a small extent in tea, but is chiefly prepared synthetically. Like caffeine, it is a very weak base which forms water-soluble compounds with alkalis. It has a similar pharmacological mechanism to that of caffeine and is used, in combination with ethy-lenediamine. as a diuretic and a bron-chodilator. 

C4H4N2O2. Colourless crystalline powder, turning brown at 280 C and melting at 338 C (decomp.). Uracil is a constituent of ribose nucleic acid. Used as a diuretic and derivatives have pharmaceutical importance. 5-Fluorouracil is used in cancer treatment. 

Diuretics. The diuretic and antihypertensive agent bendrodumethia2ide [73 8-3] is a ben2otriduoride-based pharmaceutical. 

For fluorine-free products, the labiUty of fluorine in fluoronitrobenzenes and other activated molecules permits it to serve as a handle in hair-dye manufacturing operations, high performance polymers such as polyetheretherketone (PEEK), production of dmgs such as diuretics, and fiber-reactive dyes. Labile fluorine has also been used in analytical appHcations and biological diagnostic reagents. 

Hydroxyhyda.ntoins. Some 5-hydroxyhydantoins such as (24) and (25) have shown antidiabetic activity (108). In some cases they are also diuretics and hypolipemics. These properties are probably related to the urea moiety found in these compounds. 

Pharmaceuticals. A variety of mercury compounds have had pharmaceutical appHcations over the years, eg, mercury-containing diuretics and antiseptics. Whereas some mercury compounds remain available for use as antiseptics such as merbromin [129-16-8] mercuric oxide, and ammoniated mercury [10124-48-8] or as preservatives such as thimerosal [54-64-8] in dmgs and cosmetics, most have been supplanted by more effective substances. A detailed discussion of mercury-containing antiseptics is available (37). Many hospitals use mercury metal to serve as weight for keeping nasogastric tubes in place within the stomach. 

Many 1,2,3,5-benzenetetrol derivatives are used mediciaaHy. For example, khellin [82-02-0] (65), which is a naturally occurring benzopyranone, is used as a coronary vasodilator and bronchodilator (233). Derivatives of khellin are effective local anesthetics and antiarrythmics (234). Similarly, amine derivatives (68) that are prepared from khellinone oxime (66) exhibit hypnotic, sedative, anticonvulsant, antiinflammatory, cardiac analeptic, diuretic, and antiulcerous activity (235) (see Analgesics, antipyretics, and antiinflammatory agents). 

Eupatin (69, R = H) and Eupatoretin (69, R = CH3), which are isolated from thistle perennials, show moderate cytotoxicity against human carcinoma of the nasopharynx (236). Baicaleia (70) salts exhibit antiallergic and antiinflammatory activity. 3,4,5-Trimethoxyphenoxyacetamides are hypotensives and diuretics and are useful for controlling arrhythmia duting anesthesia (237). 

Sodium sulfate in moderation is used as a diuretic and cathartic for humans and animals (14) (see Gastrointestinal agents). It is also used in consumer products such as laxatives, antacids, and as a natural filler it is used extensively in powdered laundry detergents (see Detergency). 

Mineralocorticoids. Aldosterone [6251-69-0] (32), the most potent natural rnineralocorticoid, also possesses a A -3-one group, an oxygen substituent at Clip, and a C17P-2-hydroxyethan-l-one side chain. In addition, the C18 of aldosterone is oxidized to an aldehyde. Mineralocorticoids, particularly aldosterone, act to retain sodium and to prevent the retention of excess potassium. Antimineral ocorticoids have been used therapeutically as diuretics and as agents that regulate blood pressure (63—65). 

Indapamide has been shown to possess diuretic and iadependent vasodilatory effects (16). It lowers the elevated blood pressure and reduces total peripheral resistance without an iacrease ia heart rate. ladapamide antagoni2es the vasocoastrictiag effects of the catecholamiaes and angiotensin II (16), a property not shared by other thia2ide-type diuretics. Tripamide is also reported to have direct vasodilatory effects (13). 

Chloro-6-sulfonamido-4(3 f)quinazo]inones are more effective than the mercury diuretics and can be administered orally. The 1,2-dihydro derivatives are even more effective and one (59) has been marketed under the name "Quinethazone. ... 

ACE inhibitors are approved for the treatment of hypertension and cardiac failure [5]. For cardiac failure, many studies have demonstrated increased survival rates independently of the initial degree of failure. They effectively decrease work load of the heart as well as cardiac hypertrophy and relieve the patients symptoms. In contrast to previous assumptions, ACE inhibitors do not inhibit aldosterone production on a long-term scale sufficiently. Correspondingly, additional inhibition of aldosterone effects significantly reduces cardiac failure and increases survival even further in patients already receiving diuretics and ACE inhibitors. This can be achieved by coadministration of spironolactone, which inhibits binding of aldosterone to its receptor. 

In the treatment of hypertension, ACE inhibitors are as effective as diuretics, (3-adrenoceptor antagonists, or calcium channel blockers in lowering blood pressure. However, increased survival rates have only been demonstrated for diuretics and (3-adrenoceptor antagonists. ACE inhibitors are approved for monotherapy as well as for combinational regimes. ACE inhibitors are the dtugs of choice for the treatment of hypertension with renal diseases, particularly diabetic nephropathy, because they prevent the progression of renal failure and improve proteinuria more efficiently than the other diugs. 

When either drug is administered with diuretics and other hypotensives, an increased hypotensive effect may occur. When labetalol is administered with cimetidine, the effects of labetalol are increased. Halothane increases the effects of labetalol. When carvedilol is administered with the antidiabetic drugs, there is an increased effectiveness of the antidiabetic drugs. There is an increased effectiveness of clonidine when carvedilol is administered with clonidine There is an increased serum level of digoxin when digoxin is administered with carvedilol. 

Initiate diuretics and ACE inhibitors add digoxin, if symptoms persist add p blocker (when the patient is no longer overloaded with fluid)... 

Initiate ACE inhibitors add p blocker add diuretics and digoxin as needed for persistent or new symptoms... 

Fhtients taking a diuretic and a digitalis glycoside must be monitored closely. Thiazide and loop diuretics (see Chap. 46) may increase the risk and effects of toxicity. 

The hypotensive effects of most antihypertensive dru are increased when administered with diuretics and other antihypertensives. Many dnigp can interact with the antihypertensive drugs and decrease their effectiveness (eg, antidepressants, monoamine oxidase inhibitors, antihistamines, and sympathomimetic bronchodilators). When the ACE inhibitors are administered with the NSAIDs, their antihypertensive effect may be decreased. Absorption of the ACE inhibitors may be decreased when administered with the antacids. Administration of potassium-sparing diuretics or potassium supplements concurrently with the ACE inhibitors may cause hyperkalemia. When the angiotensin II receptor agonists are administered with... 

The effects of warfarin may increase when administered with acetaminophen, NSAIDs, beta blockers, disulfiram, isoniazid, chloral hydrate, loop diuretics, aminoglycosides, cimetidine, tetracyclines, and cephalosporins. Oral contraceptives, ascorbic acid, barbiturates, diuretics, and vitamin K decrease the effects of warfarin. Because die effects of warfarin are influenced by many drugp, die patient must notify die nurse or die primary healdi care provider when taking a new drug or discontinuing... 

Diuretics are used in a variety of medical disorders. The primary health care provider selects the type of diuretic diat will most likely be effective for treatment of a specific disorder. In some instances, hypertension may be treated with the administration of an antihypertensive drug and a diuretic. The diuretics used for this combination tiierapy include the loop diuretics and the thiazides and related diuretics. The specific uses of each type of diuretic drug are discussed in the following sections. 

Additional adverse reactions of these drugs are listed in tiie Summary Drug Table Diuretics. When a potassium-sparing diuretic and a thiazide diuretic are given together, tiie adverse reactions associated with both drugp may be seen. 

Diuretics are used to treat many different types of conditions. Therefore promoting an optimal response to dierapy for patients taking diuretics will often depend on die specific diuretic and die patient s condition. 

Older adults are particularly prone to fluid volume deficit and electrolyte imbalances (see Display 46-1) while taking a diuretic. The older adult is carefully monitored for hypokalemia (when taking the loop or thiazide diuretic and hyperkalemia (with the potassium-sparing diuretics... 

CARD IAC ARRHYTH MI AS AN D DIZZIN ESS. Patients receiving a diuretic (particularly a loop or thiazide diuretic) and a digitalis glycoside concurrently require frequent monitoring of the pulse rate and rhythm because of the possibility of cardiac arrhythmias. Any significant changes in the pulse rate and rhythm are immediately reported to the primary health care provider. 

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