Leprosy, treatment

Since the causative organism of leprosy, one of the world s six major diseases, Mycobacterium leprae, is closely related to Mycobacterium tuberculosis, thio-semicarbazones have also been used as second-line drugs in the chemotherapy of leprosy [38]. The most widely used in leprosy treatment has been thiacetazone, and structure-activity relationships for it are similar to those observed for antitubercular thiosemicarbazones [39, 40]. 

Alves-Rodrigues EN, Ribeiro LC, Silva MD,Takiuchi A, Fontes CJ. Dapsone syndrome with acute renal failure during leprosy treatment case report. Braz J Infect Dis. 2005 Feb 9(l) 84-6. 

Analogous para-isomers are obtained from p-chioronitrobenzene (29b). Thus animation with aqueous ammonia at 180 °C and 40 atmospheres gives p-nitroaniline (15a), a useful dye intermediate, manufactured by batch or continuous processes. With sodium sulfide, 4,4 -diaminodiphenyl sulfone (4,4 -sulfonyldianiline), also known as dapsone (32), is obtained, a product used in leprosy treatment and in the manufacture of aramides. 15a... 

Samson JG, Limkako G. 1923. Preliminary report on creosote as an adjuvant in leprosy treatment. Philippine J Sci 23 515-529. 

Used properly, the sulfones may be given safely for many years in doses adequate for the successful therapy of leprosy. Treatment should be initiated with a small dose and then increased gradually. Patients must be under consistent laboratory and clinical supervision. The reactions induced by the sulfones, especially those related to the sulfone syndrome, may require the cessation of treatment as well as the institution of specific measures to reduce the threat to life. 

Uses Epoxy resin curing agent (composite aircraft bodies/components) hardener for adhesives, PWB laminates, prepregs, composites, powd. coatings exc. high temp, and chem. resist. antibacterial in treatment of dermatitis herpetiformis leprosy treatment drug veterinary medicine... 

Constituent of obaulmoo a oil in. form of glyceride and from oil of Oncola echinata and Uydnocarpusakaloe. Leaflets. M.p.68-5 . B.p. 247-8 /20.mm. Sol. EtjO, CHCI3. [a]o + 62 in CHGI3. Derive, used in leprosy treatment. 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

The sulfas also remain clinically useful in the treatment of chancroid, lymphogranuloma venereum, trachoma, inclusion conjunctivitis, and the fungus-related nocardiosis (7). In combination with pyrimethamine, they are recommended for toxoplasmosis (8) and have been used for chloroquine-resistant falciparium malaria (4,9). There has also been some use of sulfas for the prophylaxis of rheumatic fever. The sulfone, dapsone, remains an accepted treatment for all forms of leprosy (4). 

Antituberculin Agents. Rifampin [13292-46-17, a semisynthetic derivative of rifamycin SV, is a most valuable dmg for treatment of tuberculosis, an infection caused by mycobacteria, leprosy, and an expanding range of other infections (23). Cycloserine [64-41-7] has been used to a limited extent for treatment of tuberculosis as a reserve dmg. Although cycloserine inhibits bacteria by interfering with their cell wall biosynthesis, it has toxic side effects in humans in the form of neurotoxicity. Capreomycin [11003-38-6] and to a much lesser extent viomycin [32988-50-4] both of which are peptides, have also been used for treatment of this disease. 

Rifampicin has also shown antiviral activity but at levels 500—1000 times greater than required for antibacterial activity (130,140—142). Rifampicin shows promise in the treatment of leprosy (130,143). A large number of rifampicinlike derivatives are potent inhibitors of reverse transcriptase (123,144-148). 

Leprosy is a chronic, communicable disease spread by prolonged, intimate contact with an infected person. Peripheral nerves are affected, and skin involvement is present. Lesions may be confined to a few isolated areas or may be fairly widespread over the entire body. Treatment with the leprostatic drugs provides a good prospect for controlling the disease and preventing complications. 

Mr. Winters is very anxious about his newly diagnosed leprosy and his treatment regimen with dapsone. Discuss what you could do to decrease his anxiety. Determine what information you would include when educating Mr. Winters about the treatment regimen. 

Dapsone (diaminodiphenylsulphone Fig. 5.16F) is used specifically in the treatment of leprosy. However, because resistance to dapsone is unfortunately now well known, it is recommended that dapsone be used in conjunction with rifampicin and clofazimine. 

The answers are 484-k 485-j. (tlardman, pp 1061-1062, 1682-1685.) Sulfonamides can cause acute hemolytic anemia. In some patients it mayr be related to a sensitization phenomenon, and in other patients the hemolysis is due to a glucose-6-phosphate dehydrogenase deficiency Sulfamethoxazole alone or in combination with trimethoprim is used to treat UTls. The sulfonamide sulfasalazine is employed in the treatment of ulcerative colitis. Daps one, a drug that is used in the treatment of leprosy, and primaquine, an anti mala rial agent, can produce hemolysis, particularly in patients with a glucose-6-phosphate dehydrogenase deficiency. 

Because of its antiviral and anticancer effects, IFN-a is used in the treatment of hepatitis and various forms of cancer, such as Kaposi s sarcoma, non-Hodgkin s lymphoma, and hairy cell leukemia. Exhibit 4.8 describes the treatment of hepatitis C with IFN- . IFN-jS is used for treating multiple sclerosis, a chronic disease of the nervous system. The medical application of IFN-y is for cancer, AIDS, and leprosy. 

Dapsone (p. 280) has several therapeutic uses besides treatment of leprosy, it is used for prevention/prophylaxis of malaria, toxoplasmosis, and actinomycosis. 

Rifampin inhibits the bacterial enzyme that catalyzes DNA template-directed RNA transcription, i.e DNA-de-pendent RNA polymerase. Rifampin acts bactericidally against mycobacteria (M. tuberculosis, M. leprae), as well as many gram-positive and gram-negative bacteria It is well absorbed after oral ingestion. Because resistance may develop with frequent usage, it is restricted to the treatment of tuberculosis and leprosy (p. 280). 

Mycobacteria are responsible for two diseases tuberculosis, mostly caused by M. tuberculosis, and leprosy due to M. leprae. The therapeutic principle applicable to both is combined treatment with two or more drugs. Combination therapy prevents the emergence of resistant mycobacteria Because the antibacterial effects of the individual substances are additive, correspondingly smaller doses are sufficient Therefore, the risk of individual adverse effects is lowered. Most drugs are active against only one of the two diseases. 

FDA information on their approval of thalidomide for treatment of leprosy. 

In 1998, the FDA approved the use of thalidomide for the treatment of lesions associated with erythema nodosum leprosum. Because of thalidomide s potential for causing birth defects, the distribution of thalidomide was permitted only under tightly controlled conditions. Nevertheless, because of its use for patients with leprosy thalidomide has been identified again as a current teratogen, now in South America. 

Thalidomide is approved for use in the United States for the treatment of cutaneous manifestations of erythema nodosum leprosum, a potentially life-threatening systemic vasculitis that occurs in some patients with leprosy. Although not approved for other indications, thalidomide has also been shown to be very effective in the management of Behget s disease, HIV-related mucosal ulceration (aphthosis), and select cases of lupus erythematosus. 

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