Isoniazid

Snapshot

• A 21-year-old man presents to his primary care physician for a wellness visit. The patient currently has no acute complaints. He says that there are some medical forms he wants filled so he can start volunteering in the hospital. He denies any fevers, chills, night sweats, or unexpected weight loss. He recently returned from India for a medical mission. He immigrated from Mexico when he was young. He said that he cannot get the purified protein derivative skin test since he received the Calmette-Guerin vaccination when he was an infant. An interferon-gamma release assay returns positive. A chest radiograph is unremarkable. He is started on isoniazid and vitamin B6 for 9 months. (Latent tuberculosis)

Introduction

• Mechanism of action
  • impairs mycolic acid synthesis 
    • requires catalase-peroxidase (encoded by KatG) in order to convert the drug into an active metabolite 
      • slow and fast acetylators result in isoniazid having different half-lives
• Mechanism of resistance
  • mutations in the KatG gene 
• Clinical use
  • tuberculosis (as a component of RIPE therapy)
    • RIPE therapy – rifampin, isoniazid, pyrazinamide, ethambutol
  • latent tuberculosis
• Adverse effects
  • vitamin B6 deficiency 
    • peripheral neuropathy
    • sideroblastic anemia
    • seizures
  • optic neuropathy and color vision changes
  • P-450 inhibition
  • drug-induced systemic lupus erythematosus
  • hepatotoxicity