Dapsone block

Dapsone, which was first proposed in 1941, possesses both bactericidal as weU as bacteriostatic activity with respect to Mycobacterium leprae and Mycobacterium tuberculosis. It is used to treat patients with herpetiform dermatitis. It is believed that the mechanism of its action consists of competitive inhibition of the enzyme dihydroprotease synthetase, which blocks synthesis of folic acid in microorganisms, allowing it to also be viewed as an analog of p-aminobenzoic acid. Synonyms of this drug are avosulfon, croysulfon and others. 

Considering the drugs in relation to modes of action, dapsone and the sulphonamides block the biosynthesis of tetrahydrofolate by inhibiting di-hydropteroate synthetase, while the 2,4-diamino-pyrimidines (proguanil and pyrimethamine) block the same pathway but at a later step catalysed by dihydrofolate reductase. 

Drugs used in prophylaxis. These block a stage in the life cycle, e.g. chloroquine, dapsone, doxycycline, mefloquine, proguanil and pyrimethamine, and often in combinations. 

FIGURE 107 Patients with a clinical diagnosis of AIDS should undergo long-term therapy with zidovudine (AZT, 1200 mg q. 4 hrs). Acyclovir may potentiate the beneficial effects of AZT. In addition, patients should be treated prophylactically for Pneumocystis carinii pneumonia such regimens include sulfadoxine and pyrimethamine (Fansidar), dapsone, or aerosolized pentamidine. Dextran sulfate is also useful because it blocks the binding of HIV to target cells. 

Dapsone (4,4 -diaminodiphenylsulfone) is used in dermatology for its anti-inflammatory properties, particularly in sterile (noninfectious) pustular diseases of the skin. Dapsone prevents the respiratory burst from myeloperoxidase, suppresses neutrophil migration by blocking integrin-mediated adherence, inhibits adherence of antibodies to neutrophils, and decreases the release of eicosanoids and blocks their inflammatory effects aU these actions are hkely to be important in autoimmune skin diseases. 

Probenecid inhibits renal tubular reabsorption of water and by this meehanism enhanees the urinary excretion of uric acid. This lowers the level of urate in the serum. It thus serves as a potent uricosuric agent in the treatment of gout. Probenecid also blocks the renal tubular seeretion of penicillins and cephalosporins. It is, therefore, used as an adjuvant therapy with penicillin V or G, ampicillin, cloxacillin, oxacillin, methicillin and naficillin to increase and prolong their plasma levels. Besides it also enhances the plasma levels of anti-inflammatory agents like naproxen and indomethacin, and a host of medicinal compounds such as sulphonamides, sulphonylureas, dapsone, etc. 

An example of sequential blocking is the use of a sulfadiazine with pyrimethamine 9.31) in toxoplasmosis, a protozoal disease (Wettingfeld, Rowe and Eyles, 1956). In this sequence, the sulfonamide blocks the incorporation of / -aminobenzoic acid into dihydrofolic acid, and the pyrimethamine prevents the reduction of this pteridine to tetrahydrofolic acid (Sections 9.3.2 and 9.3.3). In malaria, as early as 1959, Hurly made the observation that pyrimethamine and sulfadiazine potentiated one another to such a degree that the combination could actually cure Pl.falciparum infections. Thus, less than 0.1 m.e.d. (minimal effective dose) of pyrimethamine and 0.25 m.e.d. of sulfadiazine were, together, as effective as 1.0 m.e.d. of either drug separately. In current tropical medicine, Maloprim , a combination of pyrimethamine and dapsone 9.17) (the latter chosen because of its slow rate of excretion which matches that of pyrimethamine), forms an excellent replacement for chloroquine in cases of Pl.falciparum... 

Cardiovascular Complete atrioventricular block has been reported in the context of dapsone hypersensitivity [44 ]. 

A 45-year-old woman took dapsone 150 mg/ day for 5 weeks for pustular palmoplantar psoriasis and developed dyspnea, numbness of all four limbs, and syncope. She had multiple enlarged mobile cervical and retroauricu-lar lymph nodes measuring 1.5-3.0 cm and an itchy maculopapular rash. Her liver enzymes were raised but urea and electrolytes were normal. An electrocardiogram showed sinus rhythm and left anterior fascicular block. She had three further episodes of syncope, on each occasion associated with bradycardia. Dapsone was withdrawn and she was given atropine, dopamine, and isoprenaline, but her heart rate and blood pressure remained low and eventually a pacemaker was inserted. 

It is not clear whether dapsone could be incriminated in the heart block that occurred in this case. 

Zhu KJ, He FT, Jin N, Lou JX, Cheng H. Complete atrioventricular block associated with dapsone therapy a rare complication of dapsone-induced h5fpersensitivity syndrome. J Clin Pharm Ther 2009 34(4) 480-92. 

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