Drugs sulfonamides

The phenomenon of bacterial resistance to antibiotics was already known by the pioneers of the era of antibiotics, like Paul Ehrlich, who coined the term selective toxicity as the basic principle of antimicrobial therapeutics, as well as Gerhard Domagk, the inventor of the sulfonamide drugs, and Sir Alexander Fleming, the discoverer of the penicillins. When penicillin G was introduced into clinical practice in 1944, as many as 5% of the isolates of Staphylococcus aureus were resistant to penicillin, while 5 years later the percentage was 50%. 

Promoting an Optimal Response to Therapy The patient receiving a sulfonamide drug almost always lias an active infection. Some patients may be receiving one of Hiese drugs to prevent an infection (prophylaxis) or as part of Hie management of a disease such as ulcerative colitis. 

Oral administration of mesalamine may cause abdominal pain, nausea, headache dizziness, fever, and weakness. The adverse reactions associated witii rectal administration are less than those seen witii oral administration, but headache abdominal discomfort, flu-like syndrome, and weakness may still occur. Olsalazine administration may result in diarrhea, abdominal discomfort, and nausea Sulfasalazine is a sulfonamide witii adverse reactions the same as for the sulfonamide drugs (see Chap. 6). 

Sulfonamide Drugs and Pneumococcus Capsular Polysaccharides, M. Stacey and E. Schliichterer, Nature. 143 (1939)724. 

Figure 1. HPLC separation of four sulfonamide drugs on a CN-NH2 bonded polar phase (1) Sulfadiazine (2) sulfapyridine (3) sulfanilamide (4) sulfathiazole. Mobile phase 95% methylene chloride-5% methanol flow rate 1 ml/min. Detection 254 nm. Amount injected 0.2 ]ig each (as the free acids obtained from Sigma Chemical Co.).

Code of Federal Regulations, 1985. Antibiotic, Nitrofuran, and Sulfonamide Drugs in the Feed of Animals. Section 558.15 484-497. 

Nucleophilic attack on a nitrile rather than a carbonyl has also provided aminopyrimidines as reported by Hassanien and co-workers in their efforts to discover new sulfonamide drugs <99JCR(S)8>. The reactions of sulfonamides 12 with a variety of nitrogen-based nucleophiles produced aminopyrimidines 13. 

Administration of streptomycin intramuscularly is the method of choice for treating systemic infections. Oral forms of streptomycin or dihydrostreptomycin, frequently combined with sulfonamide drugs and other compounds, are also used in animals for treatment of enteric infections. In addition, streptomycin is used as a feed additive for growth promotion purposes. In some countries, the combination of streptomycin with procaine penicillin is used as an initial nonspecific therapy in farm animals, and in intramammary applications for treatment of mastitis. Intramuscular dosages are in the range 5-10 mg/kg bw, while oral dosages are 20 mg/kg bw. Dihydrostreptomycin is also used in veterinary medicine in intramammary and topical treatments. 

Diaveridiiie, a pyrimidine derivative (Fig. 5.7), is a compound used primarily as a synergist with sulfaquinoxaline or other sulfonamide drugs. 

Diethylstilbestrol (DES) Sulfonamide drugs in lactating dairy cattle (except approved use of... 

Fru thermore, 156,078 samples from cattle, sheep/lambs, goats, swine, and other animals were screened for antibiotics and sulfonamide drug residues using the fast antimicrobial screen test (FAST) developed in 1991 to replace CAST and STOP. There were 1022 violations for cattle and 2 for swine samples. In cattle, violative cases included 335 for penicillin, 142 for streptomycin, 128 for tetracycline, 28 for erythromycin, 48 for neomycin, 174 for oxytetracycline, 17 for chlortetracycline, 109 for gentamicin, 87 for sulfamethazine, 22 for sulfamethoxazole, 141 for sulfadimethoxine, 7 for sulfachlorpyridazine, 2 for tylosin, and 19 for sulfathiazole. In swine, violative samples were limited to one for oxytetracycline and one for penicillin. Analogous surveys conducted in 1995 showed 804 violative specimens of the 68,139 samples tested. 

Aromatic amides, sometimes referred to as aryiamides, exhibit the same relationship. Note the relationship of benzoic acid Cg H5 COOH with benzamide Q H5 CONH2. Thiamides are derived from amides in which there is substitution of the O atom by a sulfur atom. Thus, acetamide NHa- CO- CH3, becomes thiacetamide NH2- CS- CH3 or acetanilide C6 H5- NH- CO- CH3 becomes thiacetanilide C6 H5- NH- CS- CH3. Sulfonamides arc derived from the sulfonic acids. Thus, bcnzcnc-sulfonic acid Cg H5 SO2- OH becomes benzene-sulfonamide Cg Hs- SOv NH2. See also Sulfonamide Drugs. 

Aminosalicylic acid (Paser, PAS) exerts its effects in a manner similar to the sulfonamide drugs that is, aminosalicylic acid is structurally similar to para-aminobenzoic acid (PABA) and inhibits folic acid synthesis by competing with PABA in tuberculosis... 

Dapsone (Avlosulfon) is a member of a class of chemical agents known as the sulfones. Dapsone is especially effective against M. leprae and is used with rifampin as the primary method of treating leprosy. Dapsone appears to exert its antibacterial effects in a manner similar to that of the sulfonamide drugs that is, dapsone impairs folic acid synthesis by competing with PABA in bacterial cells. Primary adverse effects associated with dapsone include peripheral motor weakness, hypersensitivity reactions (skin rashes, itching), fever, and blood dyscrasias, such as hemolytic anemia. 

The sulfonamides include sulfadiazine, sulfamethizole, and similar agents (see Table 33-4). Sulfonamides interfere with bacterial nucleic acid production by disrupting folic acid synthesis in susceptible bacteria. Sulfonamide drugs are structurally similar to PABA, which is the substance used in the first step of folic acid synthesis in certain types of bacteria (see Fig. 33-2). Sulfonamides either directly inhibit the enzyme responsible for PABA utilization or become a substitute for PABA, which results in the abnormal synthesis of folic acid. In either case, folic acid synthesis is reduced, and bacterial nucleic acid synthesis is impaired. 

The problems encountered most frequently with sulfonamide drugs include gastrointestinal distress, increased skin sensitivity to ultraviolet light, and allergic reactions. Serious disturbances in the formed blood elements, including blood dyscrasias such as agranulocytosis and hemolytic anemia, may also occur during systemic sulfonamide therapy. 

Pyrimethamine may also be combined with other antimalarials such as artemisinin derivatives, but these regimens should only be used if the malarial parasites are not resistant to the specific drugs in the regimen.13 Pyrimethamine can also be combined with a sulfonamide drug such as dapsone, sulfadiazine, or sulfamethoxazole to treat protozoal infections that cause toxoplasmosis, or fungal infections that cause Pneumocystis pneumonia.These agents are administered orally. 

Clinical Use. Sulfasalazine (Azulfidine, other names) has unique properties, with some antibacterial characteristics similar to sulfonamide drugs (see Chapter 33) and some of anti-inflammatory characteristics similar to the salicylates (see Chapter 15). This drug is primarily used to suppress the immune response associated with rheumatoid arthritis and inflammatory bowel disease.38,61... 

The occurrence of salt forms and cocrystal systems between six sulfonamide drug substances and carboxylic acids was studied, with the... 

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