A 47-year-old man comes to the emergency department due to fever and fatigue. He has a history of HIV and has not been taking his antiretrovirals consistently. His temperature is 38.3 C (100.9 F), blood pressure is 110/70 mm Hg, pulse is 104/min, and respirations are 20/min. Physical examination is notable for hepatosplenomegaly and multiple erythematous papules. Laboratory studies show pancytopenia. Histoplasma antigen testing is positive. Intravenous amphotericin B therapy is initiated for disseminated histoplasmosis. A day later, the patient develops palpitations and weakness. An ECG reveals frequent premature ventricular beats. If these new signs and symptoms are caused by drug toxicity, they are most likely related to which of the following?

Question

A 47-year-old man comes to the emergency department due to fever and fatigue.  He has a history of HIV and has not been taking his antiretrovirals consistently.  His temperature is 38.3 C (100.9 F), blood pressure is 110/70 mm Hg, pulse is 104/min, and respirations are 20/min.  Physical examination is notable for hepatosplenomegaly and multiple erythematous papules.  Laboratory studies show pancytopenia.  Histoplasma antigen testing is positive.  Intravenous amphotericin B therapy is initiated for disseminated histoplasmosis.  A day later, the patient develops palpitations and weakness.  An ECG reveals frequent premature ventricular beats.  If these new signs and symptoms are caused by drug toxicity, they are most likely related to which of the following?

Quizplus · Accepted Answer

This patient with HIV has fever, fatigue, hepatosplenomegaly, skin lesions, and pancytopenia; these are consistent with disseminated histoplasmosis, as evidenced by the positive Histoplasma antigen test. Amphotericin B is the drug of choice to treat many systemic mycoses. It is also the most toxic antifungal medication. The most dangerous adverse effect of amphotericin B is its nephrotoxicity; this is due to both a decrease in glomerular filtration rate and direct toxic effects on the tubular epithelium. Nephrotoxicity can lead to anemia (decreased erythropoietin production) and electrolyte abnormalities. Hypokalemia and (less often) hypomagnesemia are common due to an increase in the membrane permeability of the distal tubule. Hypokalemia can cause weakness and arrhythmias. ECG findings in hypokalemia include T wave flattening, ST-segment depression, prominent U waves, and premature atrial and ventricular contractions. Profound hypokalemia can cause ventricular tachycardia or fibrillation. (Choice A) Bone marrow suppression is associated with many chemotherapeutic agents, chloramphenicol, zidovudine, and gold-containing medications. Bone marrow suppression would not cause ECG changes. (Choice B) Doxorubicin and daunorubicin are associated with irreversible dose-dependent cardiotoxicity, which is not a side effect of amphotericin B. (Choice C) Acetaminophen and halothane are examples of medications that can cause liver necrosis. Amphotericin B can lead to liver toxicity, not necrosis. Arrhythmias and palpitations are more likely caused by electrolyte abnormalities due to renal tubular dysfunction. (Choice D) Busulfan and bleomycin are examples of drugs that cause pulmonary fibrosis and can lead to pulmonary hypertension. Educational objective: Hypokalemia and hypomagnesemia are common electrolyte disturbances in patients undergoing treatment with amphotericin B and reflect an increase in distal tubular membrane permeability.

A 47-Year-Old Man Comes to the Emergency Department Due to Fever