Dapsone

Dapsone(diamino-diphenyl sulphone) is an pharmacological medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy (MDT) for the treatment of Mycobacterium leprae infections (leprosy).

History
In the early 20th century the German chemist Paul Ehrlich was developing theories of selective toxicity based largely on the ability of certain dyes to kill microbes. Gerhard Domagk, who would later win a Nobel Prize for his efforts, made a major breakthrough in 1932 with the discovery of the antibacterial prontosil red. Further investigation into the active chemicals involved led to the discoveries both of dapsone and of the antibacterial sulfonamides.

Mechanism of action
As an antibacterial, dapsone inhibits bacterial synthesis of dihydrofolic acid. Though structurally distinct from dapsone, the sulfonamide group of antibacterial drugs also work in this way.

When used for the treatment of skin conditions in which bacteria do not have a role, the mechanism or action of dapsone is less well understood.

Indications
As well as being used in leprosy dapsone can also be used to treat dermatitis herpetiformis and other skin conditions including lichen planus. It is also sometimes used to prevent Pneumocystis pneumonia(PCP) in patients with HIV and to treat idiopathic thrombocytopenic purpura. It is used prophylactically to prevent Pneumocystis pneumonia and toxoplasmosis in patients unable to tolerate trimethoprim with sulfamethoxazole.

Administration
Dapsone is administered orally as a 100mg tablet or alternatively as 25mg tablets.

Effects on the blood
The most prominent side effects of this drug are dose-related hemolysis (which may lead to hemolytic anemia) and methemoglobinemia. Agranulocytosis occurs rarely when dapsone is used alone but more frequently in combination regimens for malaria prophylaxis. Abnormalities in white blood cell formation, including aplastic anaemia, are rare but the cause of the majority of deaths due to dapsone therapy.

Effects on the liver
Toxic hepatitis and cholestatic jaundice have been reported by the manufacturer. Jaundice may also occur as part of the dapsone reaction or dapsone syndrome (see below). Dapsone is also known to inhibit the Cytochrome P450 system.

Other adverse effects
Other adverse effects include nausea, headache, and rash, which are common, and insomnia, psychosis and peripheral neuropathy. Effects on the lung occur rarely and may be serious though are generally reversible.

Dapsone reaction
Hypersensitivity reactions occur in some patients. This reaction may be more frequent in patients receiving multiple drug therapy.

The reaction always involves a rash and may also include fever, jaundice, and eosinophilia. These symptoms will generally occur within the first six weeks of therapy or not at all, and may be ameliorated by corticosteroid therapy.

Specific considerations
Certain patients are at higher risks of adverse effects when using dapsone. Some specific issues which should be considered are:


 * Related to the blood (a full blood count should be obtained prior to initiating therapy):
 * Porphyria
 * Anaemia
 * Cardiac disease
 * Pulmonary disease
 * HIV infection
 * G6PD deficiency


 * Related to the liver (obtain liver function tests before starting therapy):
 * Liver impairment


 * Related to allergy:
 * Sulfonamide allergy is associated with dapsone allergy