A 12-year-old girl is being evaluated for recurrent episodes of self-limited colicky abdominal pain and nausea lasting several days. She was also recently hospitalized for an episode of difficulty breathing. The patient has no significant past medical history, but her mother has a history of attacks of severe abdominal pain and diarrhea. Physical examination is unremarkable. Laboratory evaluation reveals decreased serum complement C4 and C1 esterase inhibitor levels. Which of the following drugs is contraindicated in this patient?

Question

A 12-year-old girl is being evaluated for recurrent episodes of self-limited colicky abdominal pain and nausea lasting several days.  She was also recently hospitalized for an episode of difficulty breathing.  The patient has no significant past medical history, but her mother has a history of attacks of severe abdominal pain and diarrhea.  Physical examination is unremarkable.  Laboratory evaluation reveals decreased serum complement C4 and C1 esterase inhibitor levels.  Which of the following drugs is contraindicated in this patient?

Quizplus · Accepted Answer

11ec160b_3b6e_2c26_9249_038c938ff375_MD0001_00 Low serum levels of C1 esterase inhibitor (and its substrate C4) are diagnostic of hereditary angioedema, an inherited autosomal dominant condition that causes episodes of painless, non-pitting, well-circumscribed edema. The face, neck, lips, and tongue are most commonly affected, but internal organs may also be involved. Angioedema affecting the tracheobronchial tree can cause respiratory obstruction and is potentially fatal. Angioedema of the gastrointestinal tract manifests with abdominal pain, vomiting, and diarrhea. Normally, C1 esterase inhibitor suppresses activation of the C1 complement component and therefore the rest of the classic complement pathway. It also inactivates kallikrein, which catalyzes the conversion of kininogen to bradykinin. In hereditary angioedema, low C1 esterase inhibitor activity leads to an increase in active kallikrein and bradykinin levels. Bradykinin (along with C3a and C5a) mediate angioedema by increasing vasodilation and vascular permeability. Angioedema may also occur as a side effect of angiotensin-converting enzyme (ACE) inhibitor medications. ACE normally catalyzes the conversion of angiotensin I into angiotensin II. ACE also converts bradykinin into inactive metabolites. ACE inhibitors can therefore lead to bradykinin accumulation. These medications should not be used in patients with hereditary angioedema as they may precipitate disease episodes. (Choice B) Furosemide can cause hypokalemia, hyperuricemia, and hypovolemia. Ototoxicity may occur if furosemide is used with aminoglycosides. (Choice C) Methotrexate can cause hepatitis, pulmonary fibrosis, and bone marrow suppression. (Choice D) Metoprolol is a selective β1-adrenergic blocker with few side effects. It may cause heart block in patients with conduction system disease and bronchoconstriction in asthmatic patients (rare due to β1 selectivity but can still occur). (Choice E) The most common side effect of penicillin is hypersensitivity. Educational objective: Angioedema can be hereditary (autosomal dominant) or acquired (associated with angiotensin-converting enzyme [ACE] inhibitor treatment). In hereditary angioedema, low C1 esterase inhibitor activity leads to increases in bradykinin activity. ACE inhibitors should not be used in these patients.

A 12-Year-Old Girl Is Being Evaluated for Recurrent Episodes of Self-Limited