A 48-year-old woman with metastatic cervical cancer is brought to the emergency department due to worsening lethargy for the past several days. A year ago, the patient was diagnosed with cervical cancer, which has progressed despite chemotherapy treatment and metastasized to the liver and lungs. She has also developed bilateral hydronephrosis and renal failure due to ureteral compression by the tumor. The patient is receiving palliative care, and her pain has been adequately controlled with a stable dose of oral morphine. Temperature is 36.7 C (98 F), blood pressure is 110/62 mm Hg, pulse is 92/min, and respirations are 10/min. On physical examination, the patient is somnolent and responds to painful stimuli only. The pupils are small and sluggish to react. The lungs are clear to auscultation, and heart sounds are normal. The abdomen is soft and nondistended. Arterial blood gas analysis shows respiratory acidosis. Which of the following medication-related events most likely precipitated her current condition?

Question

A 48-year-old woman with metastatic cervical cancer is brought to the emergency department due to worsening lethargy for the past several days.  A year ago, the patient was diagnosed with cervical cancer, which has progressed despite chemotherapy treatment and metastasized to the liver and lungs.  She has also developed bilateral hydronephrosis and renal failure due to ureteral compression by the tumor.  The patient is receiving palliative care, and her pain has been adequately controlled with a stable dose of oral morphine.  Temperature is 36.7 C (98 F), blood pressure is 110/62 mm Hg, pulse is 92/min, and respirations are 10/min.  On physical examination, the patient is somnolent and responds to painful stimuli only.  The pupils are small and sluggish to react.  The lungs are clear to auscultation, and heart sounds are normal.  The abdomen is soft and nondistended.  Arterial blood gas analysis shows respiratory acidosis.  Which of the following medication-related events most likely precipitated her current condition?

Quizplus · Accepted Answer

Morphine stimulates mu opioid receptors to provide the desired effect of analgesia, but in doing so can also precipitate many undesired effects. This patient has multiple signs of opioid toxicity, including miosis (ie, pinpoint pupils), respiratory depression (evidenced by slow respiratory rate and respiratory acidosis), and CNS depression (eg, somnolence, coma). Morphine is primarily metabolized by the liver via glucuronidation to form 2 major metabolites. These metabolites, morphine-3-glucoronide and morphine-6-glucoronide, then undergo renal elimination via excretion in the urine. Because the metabolites are metabolically active, renal dysfunction can lead to metabolite accumulation and opioid toxicity. Morphine-6-glucoronide is particularly responsible for toxicity, acting as a more potent mu opioid receptor agonist than morphine itself. Due to its metabolically active and renally cleared metabolites, morphine requires careful monitoring when used in patients with renal dysfunction. When opioid pain control is needed in such patients, fentanyl or hydromorphone is often preferred as these drugs are predominantly hepatically cleared. (Choice A) Decreased first-pass metabolism occurs with drugs that are given by a route other than orally, allowing the drug to reach the systemic circulation without passing through the portal circulation and the liver. Examples include drugs that are administered sublingually, rectally, or intravenously. (Choice B) Decreased hepatic metabolism is common in the elderly or in patients with advanced liver disease (eg, cirrhosis). Although this patient has metastatic disease to the liver, accumulation of morphine metabolites is a more likely cause of toxicity in the setting of known renal failure. (Choice C) Enterohepatic circulation occurs when a drug undergoes biliary excretion into the small intestine, where it is then reabsorbed back into the bloodstream. Such drugs typically demonstrate a prolonged half-life. Although the phenomenon may account for a prolonged duration of therapeutic effect, it rarely accounts for toxicity. (Choice E) Drugs with a high volume of distribution (eg, amiodarone) are well distributed in the tissues and have a long half-life. These drugs may demonstrate prolonged therapeutic and/or adverse effects after discontinuation. Educational objective: Morphine generates 2 major metabolites that are metabolically active and renally cleared. These metabolites can accumulate in the bloodstream of patients with renal dysfunction and lead to opioid toxicity, evidenced by miosis, respiratory depression, and CNS depression. __________ References: Relationships among morphine metabolism, pain and side effects during long-term treatment: an update. (http://www.ncbi.nlm.nih.gov/pubmed/12565191)

A 48-Year-Old Woman with Metastatic Cervical Cancer Is Brought to the Emergency