Tuberculostatic agents

In many other cases, hydrolysis results in drug inactivation, as with the tuberculostatic agent pyrazinamide (4.69). In humans and rats, the metabolism of this compound involves deamidation to produce pyrazinoic acid (4.70). Ring oxidation is another major pathway, leading to 5-hydroxypyrazinamide (4.71), which, in turn, is hydrolyzed to 5-hydroxypyrazinoic acid (4.72). The rates of hydrolysis were found to determine the apparent half-life of pyrazinamide [42] [43]. 

Thioacetazone is a tuberculostatic agent with limited activity but still used on a large scale for the first-line management of tuberculosis in developing countries because it is extremely cheap. 

Cycloserine This orally effective tuberculostatic agent appears to antagonize the steps in bacterial cell wall synthesis involving D-alanine. It distributes well throughout body fluids, including the CSF. Cycloserine [sye kloe SER een] is metabolized, and both parent and metabolite are excreted in urine. Accumulation occurs with renal insufficiency. Adverse effects involve CNS disturbances epileptic seizure activity may be exacerbated. Peripheral neuropathies are also a problem. 

Several hundred semisynthetic derivatives have been prepared in an effort to obtain substances with better biological activities (for references see Ref.s)). Particularly positions 3 and 4 of the naphthoquinone ring system (numbering system as proposed by Prelog7 8) have been extensively substituted, since it has been shown that structural changes in these two positions do not critically affect the action of the substance on the target enzyme, the bacterial RNA polymerase (cf. Chapter 3.). They can, however, influence other parameters such as its ability to penetrate into cells, its pharmacokinetic properties and resorption, which are all important for clinical use as an antibiotic. Rifampicin (U.S. rifampin), which is a widely used orally active tuberculostatic agent, is a 3-(4-methyl piperazinyl)-iminomethyl derivative of rifamycin SV, synthesized via the 3-formyl derivative (Fig. 5)10 ... 

Cycloserine is an aminoisoxazolidone that shows no crossresistance with other tuberculostatic agents (1). Because of its high toxicity, it should only be used when microorganisms are resistant to other drugs (relapse or primary resistance). It is usually given orally. 

Council on Drugs. Ethionamide. A tuberculostatic agent (Trecator). JAMA 1964 187(7) 527. 

Ethambutol The (S,S)-form of ethambutol is a tuberculostatic agent the (i ,i )-form causes optical neuritis that can lead to blindness... 

The antidepressant drugs were derived via the process of molecular modification from the sympathomimetic agents, antihistamines, antispasmodics (anticholinergics), tranquilizers, and tuberculostatic agents. 

The biological activity of rifamycins has been described [179b]. Rifamycin S (102) results from the oxidation of rifamycin B (98) to rifamycin O (101) and final hydrolysis, and rifamycin SV (103) is given by reduction of rifamycin S (98) to the corresponding hydroquinone. The biological activity is retained by all compounds. Rifampicin, a hydrazone derivative of 3-formyl rifamycin SV, is a widely used orally active tuberculostatic agent [182]. 

Viomycin is used in combination with other tuberculostatic agents in the treatment of tuberculosis. Because of its toxic side effects its use is not recommended for patients who respond to the classical forms of treatment. 

Cycloserine inhibits M. tuberculosis in concentrations of 5-20 jlg/mL in vitro. There is no crossresistance between cycloserine and other tuberculostatic agents. 

Syvalahti E, Pihlajamaki K, lisalo E. Effect of tuberculostatic agents on the re onse of serum growth hormone and immunoreactive insulin to intravenous tolbutamide, andonthehalf-life of tolbutamide, IntJ Clin Pharmacol Biopharm ( 916) 13, 83-9. 

Orally administered tuberculostatic agent used in combination with isoniazid or with isoniazid and streptomycin. 

Tuberculostatic agent, available in oral and injectable forms, used in front-line combination therapy with rifampin against Mycobacterium tuberculosis. 

C2iH39NtO,2 581.579 Aminoglycoside antibiotic. Isol. from Streptomyces griseus. Clinically used broad spectrum antibacterial (tuberculostatic) agent. Neuromuscular blocking agent. Phospholipase D inhibitor. Sol. H2O fairly sol. MeOH poorly sol. butanol, hexane. Log P -7.17 (uncertain value) (calc). Indefinite Mp. 

Virtanen, O. E. (1955). Derivatives ofusnic acid with the most important tuberculostatic agents. Suom. Kemistilehti B 28, 125-126. 

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