A 62-year-old homeless man comes to the clinic for evaluation after a resident in his shelter was diagnosed with active tuberculosis. The patient says that he is in good health and has no symptoms. He has been homeless for the last 10 years. He regularly drinks alcohol and smokes cigarettes but is unable to quantify the amount. The patient's temperature is 37 C (98.6 F), blood pressure is 110/74 mm Hg, pulse is 84/min, and respirations are 20/min. Examination shows multiple dental caries with the majority of his teeth missing. There are no skin rashes or lymphadenopathy. The chest is clear to auscultation. There is no organomegaly. Purified protein derivative testing shows 16 mm induration at 48 hours. Chest x-ray is unremarkable. HIV test is negative. He agrees to take both isoniazid 300 mg and pyridoxine 50 mg daily for the next 9 months. Which of the following therapeutic side effects is the patient most likely to experience?

Question

A 62-year-old homeless man comes to the clinic for evaluation after a resident in his shelter was diagnosed with active tuberculosis.  The patient says that he is in good health and has no symptoms.  He has been homeless for the last 10 years.  He regularly drinks alcohol and smokes cigarettes but is unable to quantify the amount.  The patient's temperature is 37 C (98.6 F), blood pressure is 110/74 mm Hg, pulse is 84/min, and respirations are 20/min.  Examination shows multiple dental caries with the majority of his teeth missing.  There are no skin rashes or lymphadenopathy.  The chest is clear to auscultation.  There is no organomegaly.  Purified protein derivative testing shows 16 mm induration at 48 hours.  Chest x-ray is unremarkable.  HIV test is negative.  He agrees to take both isoniazid 300 mg and pyridoxine 50 mg daily for the next 9 months.  Which of the following therapeutic side effects is the patient most likely to experience?

Quizplus · Accepted Answer

Explanation: Patients with purified protein derivative >5 mm are considered positive if they had close contact with an individual recently diagnosed with active tuberculosis. Isoniazid (INH) is typically indicated for latent tuberculosis in these patients. The most common side effect of INH is hepatotoxicity, which can occur within the first 2 months of therapy and range from mild hepatotoxicity to hepatitis. Risk factors include daily alcohol intake, HIV, underlying liver disease (eg, chronic viral hepatitis), age >50, and active intravenous drug use. Mild INH hepatotoxicity presents with increased transaminases (usually <100 IU/L). However, patients are usually asymptomatic. They typically have self-limited transaminitis and can continue INH with close monitoring. All patients should have baseline measurement of aminotransferases before starting INH and monthly monitoring during therapy. Patients with normal baseline aminotransferases should discontinue the drug if they have aminotransferases >5 times the upper limit of normal (ULN) or develop symptoms with aminotransferases >3 times the ULN. Patients with baseline elevated aminotransferases >3 times the ULN should discontinue the drug if they develop symptoms (eg, jaundice, mental status changes) or 2-3-fold increased aminotransferases from baseline. (Choice A) Asymptomatic hyperuricemia is more commonly associated with the active metabolite (pyrazinoic acid) of pyrazinamide, which competes with uric acid for elimination by the kidneys. (Choice B) INH rarely causes ocular toxicity, which typically presents as optic neuritis with blurred or diminished vision sometimes accompanied by eye pain. Ocular toxicity is more common with ethambutol. (Choice C) Drug-induced lupus can present with joint pain, malaise, and low-grade fever. However, this rarely occurs with INH and is more common with procainamide and hydralazine. (Choice E) INH can compete with vitamin B6 (pyridoxine), which acts as a cofactor in synthesizing various synaptic neurotransmitters. Susceptible individuals (eg, alcoholic patients, the malnourished, children, diabetic patients, HIV patients, those with chronic kidney disease) can develop ataxia, peripheral neuropathy, and paresthesias. However, giving vitamin B6 along with INH (as in this patient) typically prevents neurotoxicity. Educational objective: Hepatotoxicity due to isoniazid (INH) can occur within the first 2 months of therapy and range from mild hepatotoxicity to hepatitis. Patients should have baseline and monthly monitoring of aminotransferases. INH should be discontinued in patients who have aminotransferases >5 times the upper limit of normal (ULN) or develop symptoms with aminotransferases >3 times the ULN. References: An official ATS statement: hepatotoxicity of antituberculosis therapy. (http://www.ncbi.nlm.nih.gov/pubmed/17021358)

A 62-Year-Old Homeless Man Comes to the Clinic for Evaluation