A 78-year-old woman is brought to the hospital due to 2 days of nausea, vomiting, abdominal pain, and headache. She was recently hospitalized due to a stroke, and the hospitalization was complicated by a urinary tract infection and delirium. The patient has a history of chronic obstructive pulmonary disease and her treatment regimen includes theophylline. Temperature is 37 C (98.6 F), blood pressure is 110/70 mm Hg, pulse is 118/min, and respirations are 22/min. On physical examination, the patient appears agitated and restless. There is a coarse tremor of the outstretched arms. Chest auscultation reveals mild expiratory wheezing. Serum theophylline levels are markedly elevated. Treatment with which of the following agents most likely precipitated this patient's current symptoms?

Question

A 78-year-old woman is brought to the hospital due to 2 days of nausea, vomiting, abdominal pain, and headache.  She was recently hospitalized due to a stroke, and the hospitalization was complicated by a urinary tract infection and delirium.  The patient has a history of chronic obstructive pulmonary disease and her treatment regimen includes theophylline.  Temperature is 37 C (98.6 F), blood pressure is 110/70 mm Hg, pulse is 118/min, and respirations are 22/min.  On physical examination, the patient appears agitated and restless.  There is a coarse tremor of the outstretched arms.  Chest auscultation reveals mild expiratory wheezing.  Serum theophylline levels are markedly elevated.  Treatment with which of the following agents most likely precipitated this patient's current symptoms?

Quizplus · Accepted Answer

11ec160b_3c65_851a_9249_dba8786a8bff_MD0001_00 This patient was most likely treated with ciprofloxacin (a fluoroquinolone) for her urinary tract infection and experienced subsequent theophylline toxicity. Theophylline is an adenosine receptor antagonist and phosphodiesterase inhibitor that is sometimes used as an alternate therapy for asthma and chronic obstructive pulmonary disease. It causes bronchodilation primarily by increasing intracellular cyclic AMP levels (similar to beta-adrenergic agonists) and also has mild anti-inflammatory effects. Theophylline is metabolized predominantly by hepatic cytochrome oxidases. Inhibition of these enzymes by concurrent illness (eg, infection with fever) or ingestion of certain drugs or substances (eg, ciprofloxacin) can raise serum concentrations and cause theophylline toxicity due to the drug's narrow therapeutic index. Toxicity presents with excessive CNS stimulation (eg, tremor, insomnia, seizures), gastrointestinal disturbances, and cardiovascular abnormalities (eg, hypotension, tachycardia, cardiac arrhythmias). (Choices A, B, and E) Amoxicillin and cephalexin are beta-lactams that inhibit bacterial cell wall synthesis. Nitrofurantoin inactivates or alters bacterial ribosomal proteins to inhibit protein and cell wall synthesis. These antibiotics do not interact significantly with the hepatic cytochrome oxidase system. (Choice D) Haloperidol blocks postsynaptic dopamine (D2) receptors in the brain but does not interact significantly with theophylline to cause toxicity. Chronic haloperidol use can cause neuroleptic malignant syndrome presenting with fever, mental status changes, muscle rigidity, and autonomic instability. Educational objective: Theophylline is an adenosine receptor antagonist and indirect adrenergic agent with a narrow therapeutic index. It is predominantly metabolized by the hepatic cytochrome oxidases. Inhibition of these enzymes by concurrent illness (eg, infection with fever) or ingestion of certain drugs or substances (eg, ciprofloxacin) can raise serum theophylline concentrations and cause toxicity (eg, seizures, cardiac arrhythmias). __________ References: Ciprofloxacin-induced theophylline toxicity: a population-based study. (http://www.ncbi.nlm.nih.gov/pubmed/21234553) Pharmacokinetic drug interactions with theophylline. (http://www.ncbi.nlm.nih.gov/pubmed/6147220)

A 78-Year-Old Woman Is Brought to the Hospital Due to 2