Antituberculosis drugs hepatotoxicity

Adrenaline hypertension Anticoagulants, oral skin necrosis Antituberculosis drugs hepatotoxicity Pseudoephedrine toxic epidermal necrolysis SSRIs suicidal behavior Statins acute pancreatitis Ximelagatran liver damage... 

Iproniazid 24, an alkyl analog of the antituberculous drug isoniazid 25 (Figure 2.8), surprisingly showed mood-improving activity in several depressed tuberculosis patients, which turned out to result from a monoamine oxidase (MAO) inhibitory activity. Since the compound was already registered as an antituberculosis drug and since it constituted the very first effective treatment of depression, more than 400 000 patients received it within only one year after the first announcement of its antidepressant activity [2, 33], Later it was withdrawn from therapy, due to hepatotoxic side effects. 

Underlying liver disease can cause diagnostic confusion, e.g. the alcoholic patient receiving antituberculosis drugs. It is wise to measure liver function tests before starting treatment with any drug which has documented hepatotoxic potential. 

Hepatotoxicity is the most important adverse effect of antituberculosis drug therapy. Isoniazid, rifampicin, and pyrazinamide are the main culprits. There is wide variability in the risk of hepatotoxic reactions reported from different parts of the world or in different populations (for example African-American women in the postpartum period) (SEDA-24, 353). 

The risks of hepatotoxicity differ with different antituberculosis drug combinations. 

A case-control study has suggested that there is also an increased risk of antituberculosis drug-induced hepatotoxicity in individuals with a glutathione-5-transferase Ml null mutation (23). Reduced glutathione transferase activity could theoretically predispose individuals to adverse effects of toxic metabohtes and xenobiotics. These observations need to be confirmed. 

One of the most important predictors of hepatotoxicity during antituberculosis drug therapy is an abnormal hver function test at basehne. It is reasonable to avoid potentially hepatotoxic drugs in the management of patients with pre-existing hver disease. 

The use of ofloxacin instead of rifampicin in antituberculosis drug regimens for patients with underlying chronic hver disease has been reported to be associated with a significantly lower risk of hepatotoxicity (27). Similar observations have been reported among carriers of hepatitis B and hver transplant recipients by other investigators. 

There are four issues related to the management of patients who develop hepatotoxicity during treatment with antituberculosis drugs ... 

Pande JN, Singh SP, Khilnani GC, Khilnani S, Tandon RK. Risk factors for hepatotoxicity from antituberculosis drugs a case-control study. Thorax 1996 51(2) 132-6. 

Roy B, Chowdhury A, Kundu S, Santra A, Dey B, Chakraborty M, Majumder PP. Increased risk of antituberculosis drug-induced hepatotoxicity in individuals with glutathione S-transferase Ml null mutation. J Gastroenterol Hepatol 2001 16(9) 1033-7. 

Ungo JR, Jones D, Ashkiu D, Hollender ES, Bernsteiu D, Albanese AP, Pitcheuik AE. Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus. Am J Respir Crit Care Med 1998 157(6 Pt l) 1871-6. 

Antischistosomal drugs, 12.261 Antithyroid drugs, pregnancy, 13.377 Antituberculosis drugs, 16.341, 31.500 children, 32.557 genetic susceptibility, 28.342 hepatotoxicity, 25.363, 26.339, 31.495, 32.555 Mycobacterium avium-complex infection, 20.278... 

There is a lack of consensus on the best re-treatment protocol for patients who develop hepatotoxicity during treatment with standard antituberculosis agents. Investigators from Turkey have reported a high risk of recurrence of hepatitis (in six of 25 patients) on re-introduction of all drugs in full doses after recovery from hepatitis (31). This risk was less when rifampicin and isonia-zid were re-introduced sequentially in increasing doses and when pyrazinamide was replaced by streptomycin. 

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