Urinary tract

NHCOCH3. White crystals, m.p. 18l-l83"C. Soluble sulphacetamide is the sodium salt which is soluble in water. Il is prepared by acetylating sulphanilamide and hydrolysing one acetyl group. Being more soluble than most of the sulphonamides it is used in treating infections of the urinary tract and of the conjunctiva. 

Health and Safety Factors. Isophthahc acid has a low order of toxicity. Inhalation by rats for 4 h at 11.4 g/m showed no toxicity. The LD -level for rats is high at 10.4 g/kg (96). As with terephthahc acid, isophthahc acid was found to form urinary tract calcuh in rats in 90 d when it constituted 3% of their diet. This led to some cancer owing to the presence of the calcuh. Some mild eye irritation is possible, so eye protection should be worn. Otherwise, normal precautions used in handling industrial chemicals should be observed with isophthahc acid. 

Nitrofurantoin. The urinary tract antibacterial, l-[(5-nitro-2-furanyl)-methyleneamino]-2,4-imidazohdinedione, is prepared by reaction of 5-nitro-2-furancarboxaldehyde with l-anaino-2,4-imidazohdinedione (19,40). Crystallization of the material from nitromethane provides a macrocrystalline form (41) which continues to be employed clinically. 

Nifurtoinol. Treatment of nitrofurantoin with formaldehyde gives nihirtoinol, 3-hydroxymethyl-l-[5-nitro-2-furanyl)methyleneamino]-2,4-imidazohdinedione, a urinary tract antibacterial (46). The kinetics of decomposition of this dmg and its potential as a prodmg of nitrofurantoin have been reported (47). 

The sulfa dmgs are stiH important as antimicrobials, although they have been replaced in many systemic infections by the natural and semisynthetic antibiotics. They are of great value in third world countries where problems of storage and lack of medical personnel make appropriate use of antibiotics difficult. They are especially useful in urinary tract infections, particularly the combination of sulfamethoxazole with trimethoprim. Their effectiveness has been enhanced by co-adniinistration with dihydrofolate reductase inhibitors, and the combination of sulfamethoxazole with trimethoprim is of value in treatment of a number of specific microbial infections. The introduction of this combination (cotrimoxazole) in the late 1960s (1973 in the United States) resulted in increased use of sulfonamides. 

Sulfonamides in combination with dihydrofolate reductase inhibitors are of continuing value. Pyrimethamine [58-14-0] (5) in combination with sulfonamides is employed for toxoplasmosis (7), and a trimethoprim (6)-sulfamethoxa2ole preparation is used not only for urinary tract infections but also for bmceUosis, cholera, and malaria. 

Table 3. Representative Minimum Inhibitory Concentrations for Urinary Tract Organisms by Sulfamethoxazole (SMX), Trimethoprim (TMP), and Their Combination...

Mixtures of sulfas (eg, the tri-sulfapyrimidines) have also been used for this purpose. Resistant organisms frequently result after a urinary tract infection has been treated with sulfonamides, however. 

Also includes antiproto2oan agents and other urinary tract antiinfectives, but does not include the antileprotic sulfones. 

L-Dopa and Trimethoprim are two other dmgs that can be made from vanillin. u-Dopa is used for the treatment of Parkinson s disease Trimethoprim is an antiinfective agent used mainly for urinary tract infections and certain venereal diseases. Also, Mebeverine, an antispasmodic agent, and Verazide, a generic antitubercular agent, are dmgs that can be made from vanillin or its derivatives. 

Cefuroxime (35) is effective against community-acquired pneumonia in which ampicillin-resistant Haemophilus influence is the probable etiologic agent. Cefoxitin (23) is used to treat mixed aerobic—anaerobic infections including pelvic infections, intra-abdorninal infections, and nosocomial aspiration pneumonia. Cefonicid (31), because of its long half-life has been used in a once-a-day regimen to treat a variety of mild to moderate infections including community-acquired pneumonias, urinary tract infections, and infections of the skin and soft tissue (132,215). 

A number of disinfectants apparentiy owe their activity to formaldehyde, although there is argument on whether some of them function by other mechanisms. In this category, the dmg with the longest history is hexamethylenetetramine (hexamine, urotropin) [100-97-0] which is a condensation product of formaldehyde and ammonia that breaks down by acid hydrolysis to produce formaldehyde. Hexamine was first used for urinary tract antisepsis. Other antimicrobials that are adducts of formaldehyde and amines have been made others are based on methylolate derivations of nitroalkanes. The apphcations of these compounds are widespread, including inactivation of bacterial endotoxin preservation of cosmetics, metal working fluids, and latex paint and use in spin finishes, textile impregnation, and secondary oil recovery (117). 

Chlorhexidine has found other medical appHcations, eg, in urology in preventing urinary tract infections (217), in obstetrics and gynecology (218), in controlling infection in bums and wounds (219), and in the prevention of oral disease (220). Hypersensitivity to chlorhexidine has been reported in Japan (221) but 0.05% concentration is considered to be safe. 

X-ray structure, 3, 158-159 Phenazin-l(2H)-one, 3,4-dihydro-synthesis, 2, 69 Phenazopyridine, 1, 145 as urinary tract analgesic, 2, 517 Phenbenzamine as antihistamine, 1, 177 Phencyclidine... 

Carcinogens Cancer-producing agents Skin Respiratory Bladder/urinary tract Liver Nasal Bone marrow Coal tar pitch dust crude anthracene dust mineral oil mist arsenic. Asbestos polycyclic aromatic hydrocarbons nickel ore arsenic bis-(chloromethyl) ether mustard gas. p-naphthylamine benzidine 4-am i nodi pheny lam ine. Vinyl chloride monomer. Mustard gas nickel ore. Benzene. 

France plastic diseases of the lower urinary tract Printing worker (ever) M 7/3 3.0 0.7-13.8 ... 

More then a dozen representatives of the above ring systems were introduced into the human therapy. Actisomide (2) and trequinsin (3) are used as antiarrhytmic and antihypertensive agents, respectively. Sunepitron (4), a a 2-adrenoceptor antagonist, is under clinical trials for the treatment of anxiety and depression. Representatives of the third generation of antibacterial quinolone-3-carboxylic acids the blockbluster ofloxacin (5), its levorotatory enantiomer, levofloxacin (6), and rufloxacin (7) have gained wide acceptance for the treatment of bacterial infections of the respiratory and urinary tracts, skin, and soft tissues, as well as sexually transmitted diseases, and pazufloxacin (8) is under development. Praziquantel (9) is widely applied for the treatment of schistosomes- and cestode-caused infection in both veterinary and human therapies (Scheme 4). 

In an unusual variant on the Chichibabin reaction, treatment of 3-hydroxypyridine with sodium amide at 200° affords 2,6-di-aminopyridine (21). Coupling of the product with benzenediazo-nium chloride gives phenazopyridine (22). This drug is used as an analgesic for the urinary tract in conjunction with antibacterial agents for treatment of urinary infections. 

A 1,8-naphthyridine, nalidixic acid (39), shows clinically useful antibacterial activity against Gram-negative bacteria as such, the drug is used in the treatment of infections of the urinary tract. Condensation of ethoxymethylenemalonate with 2-amino-6-methylpyridine (36) proceeds directly to the naphthyri-dine (38) the first step in this transformation probably involves an addition-elimination reaction to afford the intermediate, 37. W-Ethylation with ethyl iodide and base followed by saponification then affords nalidixic acid (39). 

Urinary lithiasis is a disease in which calculi form in the kidney and urinary tract. Roughly 5 % of the human population suffers to some degree from urinary lithiasis. A number of severely afflicted patients (e.g. ca. 60,000 in West Germany and more than 100,000 in the U.S.) are hospitalized yearly for major surgical treatment. Obviously, nephrolithiasis is not only a common ailment but also an issue of great social and economic consequence. 

Litholytic agents in current use are classified as direct or indirect. Indirect type drugs decrease the C.P. of urine, thus inhibiting calculus formation. An example is citrate which helps prevent insoluble salts from crystallizing in the urinary tract. Potassium citrate is administered in pill form as a preventive drug. Direct type drugs dissolve renal calculi which have already formed. 

---