THE ROLE OF ISONIAZID IN THE TREATMENT OF TUBERCULOSIS: MECHANISMS, EFFICACY AND CLINICAL CHALLENGES: A REVIEW

Chekwube A. Ezegbe; Obioma R. Emeka-Obi; Ezinne C. Okorafor; Chikaodi G. Onuaja; Nkesi A. Amadi; Ruhuoma G. Amadi

doi:10.22270/ujpr.v11i4.1633

Chekwube A. Ezegbe Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka, Nigeria.
Obioma R. Emeka-Obi Department of Haematology, School of Basic Clinical Sciences, College of Medicine, Federal University of Technology, Owerri, Imo State, Nigeria.
Ezinne C. Okorafor Department of Pharmacology, School of Basic Clinical Sciences, College of Medicine, Federal University of Technology, Owerri, Imo State, Nigeria.
Chikaodi G. Onuaja Department of Environmental Science and Resource Management, National Open University of Nigeria, Abuja, Nigeria.
Nkesi A. Amadi Centre for Occupational Health and Safety, University of Port-Harcourt, Choba, Rivers State, Nigeria.
Ruhuoma G. Amadi University of Regina, 3737, Wascana Parkway, Regina Saskatchewan S4S0A2, Canada.

10.22270/ujpr.v11i4.1633

Keywords:

drug delivery, drug resistance, isoniazid, hepatotoxicity, Mycobacterium tuberculosis

Abstract

Tuberculosis (TB) remains one of the leading causes of mortality from infectious diseases worldwide, with Mycobacterium tuberculosis (Mtb) infecting one-quarter of the global population. Isoniazid (INH), a cornerstone of first-line anti-TB therapy for over 70 years, continues to play a central role in both treatment of active TB and preventive therapy for latent infection. This review provides an analysis of the mechanisms of action, clinical efficacy, pharmacological properties, and emerging challenges associated with isoniazid in modern TB management. Isoniazid is a prodrug that requires activation by the mycobacterial catalase-peroxidase enzyme KatG to form reactive species that inhibit InhA, an essential enoyl-acyl carrier protein reductase involved in mycolic acid biosynthesis. This inhibition disrupts the mycobacterial cell wall and leads to bactericidal activity, particularly against actively replicating bacilli. The review further evaluates the clinical efficacy of isoniazid within standard 6-month regimens for drug-susceptible TB, as well as its role in 3HP and 6H preventive therapy regimens. Despite its potency and low cost, the widespread emergence of INH resistance, primarily mediated by mutations in katG and inhA, poses a significant threat to TB control programs. The molecular basis of resistance, diagnostic approaches, and current World Health Organization (WHO) recommendations for managing INH-resistant TB was elaborated. Additional clinical challenges addressed include hepatotoxicity, drug-drug interactions, and adherence issues linked to long treatment durations. Finally, future directions, including novel drug delivery systems, combination therapies, and strategies to overcome resistance while preserving the utility of isoniazid in TB elimination efforts was highlighted.