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Tuberculosis and antituberculous therapy have ever increasing global implications. More and more people are exposed to more combinations of antituberculous and antiretroviral drugs throughout the world. Vigilance for depression and suicide risk are particularly important to evaluate as complications of the diseases under treatment and as complications of the therapy. Isoniazid remains the most commonly used and the most consequential in overdose.

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The global burden of tuberculosis is enormous. Approximately two billion people, one-third of the total population of the world, are infected with Mycobacterium tuberculosis. An estimated 8.8 million new cases of disease are diagnosed and 1.6 million persons die from tuberculosis annually.3 In 2007, the incidence of tuberculosis (TB) in the United States was the lowest recorded (13,000 cases) since the inception of national reporting in 1953.22 The introduction of isoniazid (INH) into clinical practice in 1952 produced a steady decline in the number of TB cases in the United States over the subsequent 30 years. However, between 1985 and 1991, there was a resurgence in TB cases in the United States resulting primarily from the effects of human immunodeficiency virus (HIV), homelessness, deterioration in the healthcare infrastructure, and an increased presence of foreign-born persons. With the initiation and implementation of containment strategies, the spread of the infection has been slowed by aggressive case identification and patient-centered management, including directly observed therapy, social support, housing, and substance abuse treatment. These methods have decreased the incidence rate in the United States as well as worldwide. In 2005, the tuberculosis incidence was stable or declining worldwide, although the total number of new TB cases continues to increase slowly. Also in that year, extensively-drug-resistant tuberculosis (XDR-TB) was recognized, with between 4% and 19% of multidrug resistant tuberculosis (MDR-TB) strains being resistant to both INH and rifampin, all fluoroquinolones, and at least one of three injectable drugs (capreomycin, kanamycin, and amikacin).7,21,94 At present, populations that remain at risk for tuberculosis include HIV-positive patients, the homeless, injection drug users, healthcare workers, prisoners, prison workers, and Native Americans. In addition, the tuberculosis rate in foreign-born persons is nearly 10 times higher than in US-born persons. In the US population, countries of birth generating the highest number of tuberculosis cases are Mexico, the Philippines, India, and Vietnam.7,21 The use of second-line (reserve) drugs and multidrug antituberculous regimens for MDR-TB and XDR-TB resulted in an increased incidence of adverse drug effects, increasing to 40-70% and sometimes requiring discontinuation of the treatment. Hepatotoxicity, peripheral neuropathy, and ocular neuropathy are often irreversible and potentially fatal. Psychosocial conditions, chronic illness, and adverse drug effects involving anxiety, depression, and psychosis all contribute to an escalated risk of suicidality, intentional overdose, and noncompliance with therapy.128

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Pharmacology

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Isoniazid (INH, or isonicotinic hydrazide) is structurally related to nicotinic acid (niacin, or vitamin B3), nicotinamide-adenosine dinucleotide (NAD), and pyridoxine (vitamin B6) (...

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