Thiacetazone

The antimicrobial activity of thiosemicarbazones against Mycobacterium tuberculosis in vitro was first reported by Domagk et al. [28] and later confirmed in vivo [29]. Screening revealed that only certain substituted be-nzaldehyde and heterocyclic thiosemicarbazones possess antitubercular activity [30-32]. The most widely used is p-acetamidobenzaldehyde thiosemicarbazone (trivial name = thiacetazone), 1. 

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]. 

Thiacetazone is active against many strains of M. tuberculosis. It is not marketed in the United States. However, because of its low cost, it is used as a first-line agent in East Africa, especially in combination with compounds such as isoniazid. The most common side effects of thiacetazone include GI intolerance and development of rashes. It causes significant ototoxicity, especially when coadministered with streptomycin. Life-threatening hypersensitivity reactions, such as hepatitis, transient marrow aplastic syndromes, neutropenia, and thrombocytopenia, have been reported. 

C. Pyrazinamide is known to cause hyperuricemia and precipitate gouty arthritis. Pyrazinamide-induced gouty arthritis does not respond to uricosuric therapy with probenecid but may respond to acetylsalicylic acid. Cycloserine (A) can cause headaches, confusion, tremors, and seizures, possibly secondary to low levels of magnesium in the cerebrospinal fluid cycloserine should be avoided in patients with epilepsy and mental depression. It is not associated with hyperuricemia. Thiacetazone (B) is an antibiotic that is rarely used in tuberculosis. The most common adverse reactions are general rashes and GI intolerance. Its use is not associated with hy-... 

Cimetidine, gentamicin, labetalol, meprobamate (grey-black), methallibure, salina-zid, thiacetazone... 

Adrenaline (— brown), benserazide (— brown), bitoscanate, captopril, carbi-dopa (— brown), carbimazole, disuliiram, dobutamine (— brown), ecothiopate, iso-etharine (— brown), levodopa (— brown), methallibure, methimazole, polythiazide, rimiterol, thiacetazone, thiopentone... 

Octamylamine Hydrochloride Arecoline Hydrobromide Isosorbide Dinitrate Carbazochrome Carbamazepine Cyclobarbitone Dropropizine Hexobarbitone Methazolamide Procaine Thiacetazone Tetrahydrozoline Hydrochloride Carbromal Cotarnine Viloxazine Ketamine Methyldopa Nitrofurantoin Proxyphylline Nealbarbitone Nomifensine Quinalbarbitone Isoetharine Methyldopate Salbutamol Benzphetamine Methacholine Bromide Danthron Cropropamide Hexethal... 

Therapeutic drug monitoring, 101-110 analytical techniques, 105 by immunoassay, 158 choice of drug, 103 choice of sample, 103 indications for, 102 interpretation of results, 106 timing of measurements, 104 Thermal conductivity detector, 183 Thiabendazole, 85,1012 Thiacetazone, 1013 Thiacyl, 978 Thialbarbital, 1014 Thialbarbitone, 1014 Thialbarbitone sodium, 1014 Thiamazole, 750 Thiambutosine, 1014 Thiamine, 1014 in sport, 99... 

Thiacetazone is tuberculostatic and is used with isoniazid to inhibit the emergence of resistance to the latter drug. It is absorbed from the gastrointestinal tract, partly metabolised and partly excreted in the urine (t) 13 h). 

Adverse reactions to all types of medication are more common in HIV-positive individuals skin reactions are especially frequent and often severe. Thiacetazone is well recognized as a cause of severe reactions, some of them fatal, but even in combination antituberculosis drug regimens that exclude thiacetazone, the incidence of adverse skin reactions is much higher in HIV-positive than HIVnegative patients 23% against 1% in one study from Cameroon (11). 

Kuaban C, Bercion R, Koulla-Shiro S. HIV seroprevalence rate and incidence of adverse skin reactions in adults with pulmonary tuberculosis receiving thiacetazone free... 

Thiacetazone (thioacetazone, thiosemicarbazone) was greeted enthusiastically in 1946 as one of the first synthetic agents against tuberculosis. However, its use rapidly diminished with the increasing observation of untoward effects. It is currently rarely used and then only for economical reasons. Dosages should never exceed 200 mg/day. 

Adverse effects of thiacetazone include bone marrow depression and hemolytic anemia. It can also cause serious skin rashes. Continuous laboratory and clinical observations are required (1). 

Adverse effects of thiacetazone include bone marrow depression, with anemia, leukopenia, agranulocytosis, and thrombocytopenia (2-4). Hemolytic anemia has also been described (5). 

Anorexia, nausea, and vomiting are not uncommon with thiacetazone (1). 

Adverse effects of thiacetazone on the skin are of various types, mainly erythematous and maculopapular rashes, angioedema, purpura (6), toxic epidermal necrolysis, Stevens-Johnson sjmdrome, and pigmentation (7). 

Of 50 cases of cutaneous adverse effects of thiacetazone, there were 48 cases of erythema multiforme (25 cases of Stevens-Johnson sjmdrome and 23 of toxic epidermal necrolysis), one case of erythrodermia, and one case of lichenoid toxidermia there were 20 deaths, 16 with toxic epidermal necrolysis and four with Stevens-Johnson syndrome (8). 

In a retrospective study, 38 cases of toxic epidermal necrolysis were observed in Dakar, and were attributed to thiacetazone in 24 cases 23 died, mainly because of hypovolemic shock during the first week and septic shock during the second (9). Those who died were generally aged over 50 years, had more than 50% skin involvement, and had evolving tuberculosis at the time of presentation or HIV infection. After-effects were vaginal synechia and two cases of blindness. 

Cutaneous allergic reactions to thiacetazone are very common in HIV-positive patients, in the order of 20%. Ethambutol should therefore be used instead of thiacetazone in these patients (10). 

Arguments have been advanced for the abandonment of thiacetazone as an antituberculosis drug (11,12), despite its cheapness, on the grounds that it often causes severe skin reactions, some rapidly fatal, in patients infected with HIV-1 (13). The WHO and lUATLD has recommended careful information and surveillance of possible adverse reactions, particularly cutaneous, in patients treated for tuberculosis in such countries and immediate replacement with ethambutol if there are any prodromal signs of toxicity. 

Anergy to tuberculin and lymphopenia have been associated with an increased risk of adverse reactions to thiacetazone. In a randomized study of rifampicin-and thiacetazone-containing regimens in HIV-positive adults with pulmonary tuberculosis, eight of 13 patients who developed adverse reactions were tubercuUn-aner-gic, compared with 12 of 77 patients who did not develop adverse reactions (13). An absolute lymphocyte count below 2.0 X 10 /1 was also associated with adverse reactions. 

Thiacetazone combined with isoniazid (and possibly thioacetazone alone) has been reported to damage chromosomes in cultured human Ijmphocytes (14). 

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