Diuretics sulfonamide type

Unwanted effects of sulfonamide-type diuretics (a) hypokalemia is a consequence of excessive 1C loss in the terminal segments of the distal tubules where increased amounts of Na are available for exchange with 1C (b) hyperglycemia and glycosuria (c) hyper-uricemia-increase in serum urate levels may precipitate gout in predisposed patients. Sulfonamide diuretics compete with urate for the tubular organic anion secretory system. 

In the last ten years, the sulfonamide type of diuretic has yielded spectacularly to intensive study. The recognition that certain sulfonamides could have a useful influence upon renal electrolyte excretion is scarcely 15 years old The basic observations for this diuretic development arose from the sulfa drug era, from observations on the side effects of the first sulfa drug, sulfanilamide. Tishler (62) gives a chart depicting the many new drug fields where valuable... 

Each era of medicinal chemistry has been marked by intensive concentration on some structural type in a large number of laboratories. One need only look back in this book to the tables of sulfonamides, barbiturates, and thiazide diuretics, noting the small time span covered by the references to each list. The benzodiazepines have provided such a focus for the past decade. 

The thiazide diuretics are contraindicated in patients with known hypersensitivity to the thiazides or related diuretics, electrolyte imbalances, renal decompensation, hepatic coma, or anuria. A cross-sensitivity reaction may occur with the thiazides and sulfonamides. Some of the thiazide diuretics contain tartrazine, which may cause allergic-type reactions or bronchial asthma in individuals sensitive to tartrazine. 

All sulfonamides, including antimicrobial sulfas, diuretics, diazoxide, and the sulfonylurea hypoglycemic agents, have been considered to be partially cross-allergenic. Flowever, evidence for this is not extensive. The most common adverse effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, diarrhea, and difficulties referable to the urinary tract (see below). Stevens-Johnson syndrome, although relatively uncommon (ie, < 1% of treatment courses), is a particularly serious and potentially fatal type of skin and mucous membrane eruption associated with sulfonamide use. Other unwanted effects include stomatitis, conjunctivitis, arthritis, hematopoietic disturbances (see below), hepatitis, and, rarely, polyarteritis nodosa and psychosis. 

The sulfonamide diuretics cause problems through excessive excretion of potassium which diffuses into the urine as Na+ is removed in the distal tubule. This cation exchange is prevented by a different type of diuretic, triamterene (198), which was developed by following the observation that xanthopterin (199) affects renal function. The pyrazine amiloride (200) also increases Na+ output and spares K+, and is used in conjunction with chlorothiazide. It has been shown to reduce the electrical potential gradient along which K+ migrates into the lumen of the tubule. 

The drug most commonly used in clinical practice that can produce immune thrombocytopenic purpura is heparin. Other examples are sulfonamides, thiazide diuretics, chlorpropamide, quinidine, and gold. These types of immune thrombocytopenic purpura are reversed when the drug is withdrawn. Molecular mechanisms for the formation of specific drug-dependent antibodies appear to be very similar. The glycoproteins on the platelet surface interact with the drugs to form neo-epitopes. Subsequent... 

When hybrid micellar eluents were first used, they were severely criticized. It has been argued that when organic modifiers are used, this type of chromatography loses some of its appeal [25], However, most reported procedures in MLC, since 1985, utilized these eluents. The experience acquired in our laboratories on the development of analytical procedures for the determination of different drugs (c.g., P-blockers, diuretics, narcotics, steroids, stimulants and sulfonamides) has shown that, in most instances, the retention of solutes with pure micellar eluents is excessive, which forces one to add a modifier to achieve adequate retention times. 

Some of the synthetized compounds were found 2500 times more active than sulfanilamide. One of these, 2-acetylammo-l,3,4-thiadiazol-5-sulfonamide, acet-azolamide (Diamox ), was studied in detail and reported in 1954 by T. Maren, and became the first clinically effective carbonic anhydrase inhibitor-type diuretic [69]. 

Chloro-3-(dunethylamino)-2,4-(l/f,3//)-quinazolinedione 50 by heating with excess chlorosulfonic acid at 100 °C afforded the 6-sulfonyl chloride 51, which on subsequent reaction with ammonia gave the sulfonamide 52 (Equation 12). Some of the substituted derivatives of type 52 showed diuretic properties. ... 

I), a new, clinically useful sulfonamide diuretic, briefly mentioned in the previous review, have been reported. Mefruslde belongs to the class of benzene-1,3-dlsulfonamides of the chlorphenamide type, which has thus far received relatively little attention. It differs from chlorphenamide, however, in that it does not Increase bicarbonate excretion at therapeutic doses, but predominantly promotes Che excretion of water and sodium accompanied by chloride. 

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