Ethionamide is a synthetic derivative of thio-isonicotinamide. The initial oral dosage for adults is 250 mg/day, slowly increasing up to 15-20 mg/kg/day (maximum 1 g/day).
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Clofazimine is weakly bactericidal against Mycobacterium leprae. It is active in chronic skin ulcers (Buruli ulcer) and partly against Mycobacterium avium intracellulare.
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Nalidixic acid, the first quinolone, first introduced in 1962, is now only rarely used and has been supplanted by the fluoroquinolones. It is almost completely absorbed from the gastrointestinal tract and is rapidly eliminated by the kidneys, resulting in urinary concentrations 4-6 times higher than plasma concentrations.
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Griseofulvin was originally isolated in 1939 as a natural product of Penicillium griseofulvum. It interferes with fungal microtubule formation, disrupting the cell’s mitotic spindle formation and arresting the metaphase of cell division. Griseofulvin is a fungistatic compound and is active against Trichophyton, Microsporon, and Epidermophyton species.
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Headache is the most common adverse effect of griseofulvin. It occurs in about 50% of patients and can be severe. Drowsiness, dizziness, fatigue, confusion, depression, irritability, and insomnia have also been observed. Impaired co-ordination and unsteadiness while walking have been reported in some cases when there was confusion.
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The tetracyclines are a closely related group of antibiotics with comparable pharmacological properties but different pharmacokinetic characteristics. They have both the advantages and disadvantages of broad-spectrum antibiotics. Tetracyclines are effective not only against bacteria and spirochetes, but also against some forms of Mycoplasma, Chlamydia, and Rickettsia, as well as protozoa.
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Co-administration of tetracyclines with antacids or other drugs containing divalent or trivalent cations, such as calcium, magnesium, or iron, is contraindicated. Tetracyclines form complexes with such cations, which are very poorly or not at all absorbed.
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Cardiovascular reactions to tetracyclines have often been associated with other symptoms of hypersensitivity, such as urticaria, angioedema, bronchial obstruction, and arterial hypotension. Such reactions occurred in patients who had tolerated tetracyclines previously and were therefore considered as anaphylactic. Tetracyclines rarely cause benign intracranial hypertension. This syndrome has primarily involved children, although it has also been observed in adults.
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Mild gastrointestinal disturbances are common. A common and nearly unique feature of all tetracyclines is the formation of drug-melanin complexes, resulting in pigment deposition at various sites. Except for enamel defects and presumable disturbances of osteogenesis these deposits do not give rise to abnormalities of organ function. In view of tooth discoloration and enamel hypo-plasia, with a tendency to caries formation, tetracyclines should be avoided in children under 8 years of age and in women after the third month of pregnancy.
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The synthetic triazole nucleoside, ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, tribavirin, virazole), has a broad spectrum of antiviral activity, including DNA as well as RNA viruses. Ribavirin closely resembles guanosine and is converted intracellularly to mono-, di-, and triphosphate derivatives, which inhibit the virally induced enzymes involved in viral nucleic acid synthesis by different mechanisms that are not fully understood. Of the DNA viruses, ribavirin is active against Herpes simplex virus and hepatitis B virus; among the RNA viruses, good activity has been observed against hepatitis C virus, orthomyxoviruses, paramyxoviruses, arenaviruses, and bunyaviruses.