Sulfonamides long-acting

Finally, attachment of a rather complex side chain to the para position of the benzene ring on the sulfonamide leads to the very potent, long-acting oral antidiabetic agent, glyburide (215). Preparation of this compound starts with the chlorosul-fonation of the acetamide of 3-phenethylamine (209). The resulting sulfonyl chloride (210) is then converted to the sulfonamide (211) and deacylated (212). Reaction with the salicylic acid derivative, 213, in the presence of carbodiimide affords the amide, 214. Condensation of that with cyclohexylisocyanate affords glyburide (215). ... 

Newbould and Kilpatrick (N3) found that addition of plasma to the fluid perfusing a rabbit liver preparation reduced the rate of acetylation of two long-acting sulfonamides and that the rate of metabolism was dependent on the concentration of unbound drug. Anton and Boyle (A8) and Wiseman and Nelson (W15) using data from both in vitro and in vivo techniques reported a correlation between the rate of metabolism of a sulfonamide and the extent of protein binding. 

The use of the long-acting sulfonamides such as sulfadimethoxine and sulfadoxine is limited because of a high rate of hypersensitivity reactions. Sulfadoxine in combination with pyrimethamine is indicated for chloroquine-resistant falciparum malaria. 

Ultra long acting sulfonamides in combination with pyrimethamine are used. The effect is supraadditive due to sequential block. It may be employed as a clinical curative. Another advantage of the drug combination is that the development of resistance is retarded. 

Sulfonamides can be divided into three major groups (1) oral, absorbable (2) oral, nonabsorbable and (3) topical. The oral, absorbable sulfonamides can be classified as short-, intermediate-, or long-acting on the basis of their half-lives (Table 46-1). They are absorbed from the stomach and small intestine and distributed widely to tissues and body fluids (including the central nervous system and cerebrospinal fluid), placenta, and fetus. Protein binding varies from 20% to over 90%. Therapeutic concentrations are in the range of 40-100 mcg/mL of blood. Blood levels generally peak 2-6 hours after oral administration. 

Sulfadoxine is the only long-acting sulfonamide currently available in the USA and only as a combination formulation with pyrimethamine (Fansidar), a second-line agent in treatment for malaria (see Chapter 52). 

Sulfadimethoxine is a low-dose, rapidly absorbed, long-acting sulfonamide that is effective in reducing mortality due to bacterial infections and coccidiosis in poultry and ruminants (212, 213). The drug is highly protein-bound (80-85%) and this probably contributes to its slow excretion. 

The aminopyrazole made available by this method was converted to the sulfonamide (1) sold under the name Orisul and patented in Switzerland as one of the best long-acting sulfonamides.371... 

Sulfones — Potential long-acting sulfone and sulfonamide derivatives have been synthesized - to provide substances that (l) in combination... 

From the clinical point of view, kidney blockade during sulfonamide therapy is much less a problem now than it was years ago. This is mostly due to the discovery of agents which are highly soluble at the pH of the urine (pH 4.8 to 7.4) and the development of long-acting sulfas which can be given... 

Peters, J. H., Clinical Experience with a New Long-Acting Sulfonamide, in preparation. 

Many of the adverse reactions seen with sulfonamides are due to hypersensitivity reactions, which include dermatitis, leukopenia, hemolytic anemia, and drug fever. Stevens-Johnson syndrome is a very severe, but rare hypersensitivity reaction that occurs only with some of the long-acting sulfonamide preparations. 

The sulfonamides are classed based on the extent or rapidity with which they are absorbed and excreted (1) agents that are absorbed and excreted rapidly, such as sulfisoxazole and sulfadiazine (2) agents that are absorbed very poorly when administered orally and hence are active in the bowel lumen, such as sulfasalazine , (3) agents that are used mainly topically, such as sulfacetamide, mafenide, and silver sulfadiazine , and (4) long-acting sulfonamides, such as sulfadoxine, that are absorbed rapidly but excreted slowly. 

Among the isoxazoles, many biologically active compounds are found. Some of them are important as drugs or biocides, e.g. the long-acting sulfonamide sulfamethoxazole 10, the anti-inflammatory isoxi-cam 11, the antiarthritic and antirheumatic leflunomide 12 and the fungicide 3-hydroxy-5-methylisoxazole. 

For sulfadiazine, Nouws et al. reported long elimination half-lives in carp of 47.1 h at 10°C and 33.0 h at 20°C. However, as for sulfadimine, the elimination half-life of sulfadiazine in calves was in the range of 3.4-7.0 h, with no apparent relationship to age. " Sulfadimethoxine is a long-acting sulfonamide, with an elimination half-life of... 

Sulfadoxine A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections. [NIH]... 

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