Leprostatic agent

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A leprostatic agent is a drug that interferes with proliferation of the bacterium that causes leprosy. [1] [2]

Contents

The following agents are leprostatic agents: [3]

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Host defenses are crucial in determining the patient's response to the disease, the clinical presentation, and the bacillary load. These factors also influence the length of therapy and the risk of adverse reactions to medication.

M. leprae cannot be grown on routine laboratory culture media, so drug sensitivity testing in vitro is not possible. Growth and drug susceptibility testing are done by injecting into animal models. One description of a clinical picture that results from tuberculoid leprosy is characterized by intact cell-mediated immunity, a positive lepromin skin reaction, granuloma formation, and a relative paucity of bacilli.

At the other extreme, lepromatous leprosy is characterized by depressed cell-mediated immunity, numerous bacilli within the tissues, no granulomas, and a negative skin test for lepromin. Within these two extremes are the patients with an intermediate or borderline form of leprosy who show a variable lepromin reaction and few bacilli; they may progress to either tuberculoid or lepromatous leprosy.

Kinds of antileprotic drugs

Current recommendations for the treatment of leprosy suggest multidrug regimens rather than monotherapy because such a regimen has proven to be more effective, delays the emergence of resistance, prevents relapse, and shortens the duration of therapy. Established agents used in the treatment of leprosy are dapsone, clofazimine, and rifampicin. Treatment of tuberculoid leprosy is continued for at least 1 to 2 years, while patients with lepromatous leprosy are generally treated for 5 years. In addition to chemotherapy, patients with leprosy need psychosocial support, rehabilitation, and surgical repair of any disfiguration.

Dapsone and Sulfones

The sulfones are structural analogues of PABA and are competitive inhibitors of folic acid synthesis. Sulfones are bacteriostatic and are used only in the treatment of leprosy. Dapsone (Avlosulfon) is the most widely used sulfone for the long-term therapy of leprosy. Although the sulfones are highly effective against most strains of M. leprae, a small number of organisms, especially those found in lepromatous leprosy patients, are less susceptible and can persist for many years, resulting in relapse. Before the introduction of current multidrug regimens, resistance rates were as high as 20% with dapsone monotherapy.

Sulfones, such as dapsone and sulfoxone (Diasone), are well absorbed orally and are widely distributed throughout body fluids and tissues. Peak concentrations of dapsone are reached within 1 to 3 hours of oral administration and have a half-life of 21 to 44 hours; about 50% of administered dapsone is bound to serum proteins. The sulfones tend to remain in the skin, muscle, kidney, and liver up to 3 weeks after therapy is stopped. The concentration in inflamed skin is 10 to 15 times higher than that found in normal skin. The sulfones are retained in the circulation for a long time (12–35 days) because of hepatobiliary drug recirculation. The sulfones are acetylated in the liver, and 70 to 80% of drug is excreted in the urine as metabolites. Dapsone, combined with other antileprosy agents like rifampicin and clofazimine, is used in the treatment of both multibacillary and paucibacillary M. leprae infections.

Dapsone is also used in the treatment and prevention of Pneumocystis carinii pneumonia in AIDS patients who are allergic to or intolerant of trimethoprim–sulfamethoxazole. Acedapsone is a derivative of dapsone that has little activity against M. leprae but is converted to an active dapsone metabolite. It is a long-acting intramuscular repository form of dapsone with a half-life of 46 days. It may prove useful in leprosy patients who cannot tolerate long-term oral dapsone therapy.

The sulfones can produce non-hemolytic anemia, methemoglobinemia, and sometimes acute hemolytic anemia in persons with a glucose-6-phosphate dehydrogenase deficiency. Within a few weeks of therapy some patients may develop acute skin lesions described as sulfone syndrome or dapsone dermatitis. Some rare side effects include fever, pruritus, paresthesia, reversible neuropathy, and hepatotoxicity.

Clofazimine

Clofazimine is a weakly bactericidal dye that has some activity against M. leprae. Its precise mechanism of action is unknown but may involve mycobacterial DNA binding. Its oral absorption is quite variable, with 9 to 70% of the drug eliminated in the feces. Clofazimine achieves significant concentrations in tissues, including the phagocytic cells; it has a plasma half-life of 70 days. It is primarily excreted in bile, with less than 1% excretion in urine.

Clofazimine is given to treat sulfone-resistant leprosy or to patients who are intolerant to sulfones. It also exerts an antiinflammatory effect and prevents erythema nodosum leprosum, which can interrupt treatment with dapsone. This is a major advantage of clofazimine over other antileprosy drugs. Ulcerative lesions caused by Mycobacterium ulcerans respond well to clofazimine. It also has some activity against M. tuberculosis and can be used as last resort therapy for the treatment of MDR tuberculosis. The most disturbing adverse reaction to clofazimine is a red-brown discoloration of the skin, especially in light-skinned persons. A rare but serious adverse reaction is acute abdominal pain significant enough to warrant exploratory laparotomy or laparoscopy. Other infrequent side effects include splenic infarction, bowel obstruction, paralytic ileus, and upper GI bleeding.

Ethionamide and Prothionamide

Ethionamide and prothionamide are weakly bacteriocidal against M. leprae and can be used as alternatives to clofazimine in the treatment of MDR leprosy. Both cause GI intolerance and are expensive.

Related Research Articles

<span class="mw-page-title-main">Leprosy</span> Chronic infection caused by mycobacteria leprae or lepromatosis

Leprosy, also known as Hansen's disease (HD), is a chronic infection caused by the bacteria Mycobacterium leprae or Mycobacterium lepromatosis. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damage may result in a lack of ability to feel pain, which can lead to the loss of parts of a person's extremities from repeated injuries or infection through unnoticed wounds. An infected person may also experience muscle weakness and poor eyesight. Leprosy symptoms may begin within one year, but, for some people, symptoms may take 20 years or more to occur.

<i>Mycobacterium leprae</i> Bacterium that causes leprosy

Mycobacterium leprae, is one of the two species of bacteria that cause Hansen’s disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves and targets the skin, eyes, nose, and muscles.

<span class="mw-page-title-main">Dapsone</span> Antibiotic medication

Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment and prevention of pneumocystis pneumonia and for the prevention of toxoplasmosis in those who have poor immune function. Additionally, it has been used for acne, dermatitis herpetiformis, and various other skin conditions. Dapsone is available both topically and by mouth.

<span class="mw-page-title-main">Rifampicin</span> Antibiotic medication

Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), Mycobacterium avium complex, leprosy, and Legionnaires’ disease. It is almost always used together with other antibiotics with two notable exceptions: when given as a "preferred treatment that is strongly recommended" for latent TB infection; and when used as post-exposure prophylaxis to prevent Haemophilus influenzae type b and meningococcal disease in people who have been exposed to those bacteria. Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended. Rifampicin may be given either by mouth or intravenously.

The lepromin skin test is used to determine what type of leprosy a person is infected with. It involves the injection of a standardized extract of the inactivated "leprosy bacillus" under the skin. It is not recommended as a primary mode of diagnosis.

<span class="mw-page-title-main">4-Aminosalicylic acid</span>

4-Aminosalicylic acid, also known as para-aminosalicylic acid (PAS) and sold under the brand name Paser among others, is an antibiotic primarily used to treat tuberculosis. Specifically it is used to treat active drug resistant tuberculosis together with other antituberculosis medications. It has also been used as a second line agent to sulfasalazine in people with inflammatory bowel disease such as ulcerative colitis and Crohn's disease. It is typically taken by mouth.

<span class="mw-page-title-main">Clofazimine</span> Medication

Clofazimine, sold under the brand name Lamprene, is a medication used together with rifampicin and dapsone to treat leprosy. It is specifically used for multibacillary (MB) leprosy and erythema nodosum leprosum. Evidence is insufficient to support its use in other conditions though a retrospective study found it 95% effective in the treatment of Mycobacterium avium complex (MAC) when administered with a macrolide and ethambutol, as well as the drugs amikacin and clarithromycin. However, in the United States, clofazimine is considered an orphan drug, is unavailable in pharmacies, and its use in the treatment of MAC is overseen by the Food and Drug Administration. It is taken orally.

<span class="mw-page-title-main">Lupus vulgaris</span> Human disease

Lupus vulgaris are painful cutaneous tuberculosis skin lesions with nodular appearance, most often on the face around the nose, eyelids, lips, cheeks, ears and neck. It is the most common Mycobacterium tuberculosis skin infection. The lesions may ultimately develop into disfiguring skin ulcers if left untreated.

<span class="mw-page-title-main">Febrile neutrophilic dermatosis</span> Medical condition

Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is a skin disease characterized by the sudden onset of fever, an elevated white blood cell count, and tender, red, well-demarcated papules and plaques that show dense infiltrates by neutrophil granulocytes on histologic examination.

<span class="mw-page-title-main">Ethionamide</span>

Ethionamide is an antibiotic used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, to treat active multidrug-resistant tuberculosis. It is no longer recommended for leprosy. It is taken by mouth.

Leprosy was said to be first recognized in the ancient civilizations of China, Egypt and India, according to the World Health Organization (WHO). Leprosy, also known as Hansen's disease, was officially eliminated at the national level in China by 1982, meaning prevalence is lower than 1 in 100,000. There are 3,510 active cases today. Though leprosy has been brought under control in general, the situation in some areas is worsening, according to China's Ministry of Health. In the past, leprosy sufferers were ostracized by their communities as the disease was incurable, disfiguring and wrongly thought to be highly infectious.

The Fernandez reaction is a reaction that occurs to signal a positive result in the lepromin skin test for leprosy. The reaction occurs in the skin at the site of injection if the body possesses antibodies to the Dharmendra antigen, one of the antigens found in Mycobacterium leprae, the bacteria that causes leprosy. The reaction occurs via a delayed-type hypersensitivity mechanism. This reaction occurs within 48 hours of injection of lepromin and is seen in only tuberculoid forms of leprosy. In contrast, the Mitsuda reaction occurs 3–4 weeks after injection of lepromin and is only seen in patients with the tuberculoid form of leprosy. In terms of mechanism of action and appearance, the reaction is similar to the tuberculin reaction of a positive Mantoux test for tuberculosis.

<span class="mw-page-title-main">Acedapsone</span> Antimicrobial drug

Acedapsone (INN) is an antimicrobial drug, which also has antimalarial activity.

<span class="mw-page-title-main">Lepromatous leprosy</span> Medical condition

Lepromatous leprosy is a form of leprosy characterized by pale macules in the skin.

Leprosy stigma is a type of social stigma, a strong negative feeling towards a person with leprosy relating to their moral status in society. It is also referred to as leprosy-related stigma, leprostigma, and stigma of leprosy. Since ancient times leprosy instilled the practice of fear and avoidance in many societies because of the associated physical disfigurement and lack of understanding behind its cause. Because of the historical trauma the word "leprosy" invokes, the disease is now referred to as Hansen's disease, named after Gerhard Armauer Hansen who discovered Mycobacterium leprae, the bacterial agent that causes Hansen's disease. Those who have suffered from Hansen's disease describe the impact of social stigma as far worse than the physical manifestations despite it being only mildly contagious and pharmacologically curable. This sentiment is echoed by Weis and Ramakrishna, who noted that "the impact of the meaning of the disease may be a greater source of suffering than symptoms of the disease".

<span class="mw-page-title-main">Kensuke Mitsuda</span>

Kensuke Mitsuda was a Japanese leprologist and director of the Tama Zenshoen Sanatorium (1914–1931) and the National Sanatorium Nagashima Aiseien (1931–1957). He had been at the frontier of leprosy policy of Japan. He was given the Order of Cultural Merits (1951) and Damien-Dutton Award (1961). He has been the cause of admiration from one side, and the target of criticism from the other.

Lucio's phenomenon is an unusual reaction seen almost exclusively in patients from the Caribbean and Mexico with diffuse lepromatous leprosy, especially in untreated cases. It is characterised by recurrent crops of large, sharply demarcated, ulcerative lesions, affecting mainly the lower extremities, but may generalise and become fatal as a result of secondary bacterial infection and sepsis.

The diffuse leprosy of Lucio and Latapí, also known as diffuse lepromatous leprosy or "pretty leprosy" is a clinical variety of lepromatous leprosy. It was first described by Lucio and Alvarado in 1852 and re-identified by Latapí in 1936. It is common in Mexico and in Costa Rica and very rare in other countries.

<span class="mw-page-title-main">Promin</span> Chemical compound

Promin, or sodium glucosulfone is a sulfone drug that was investigated for the treatment of malaria, tuberculosis and leprosy. It is broken down in the body to dapsone, which is the therapeutic form.

<span class="mw-page-title-main">History of leprosy</span> Aspect of history

The history of leprosy was traced to its origins by an international team of 22 geneticists using comparative genomics of the worldwide distribution of Mycobacterium leprae. Monot et al. (2005) determined that leprosy originated in East Africa or the Near East and traveled with humans along their migration routes, including those of trade in goods and slaves. The four strains of M. leprae are based in specific geographic regions where each predominantly occurs:

References