Amlodipine Overdose

Abstract

We describe the case of a 24-year-old woman who intentionally ingested between 400 and 600 mg of amlodipine along with a large number of simvastatin and trazodone tablets. CASE HISTORY A 24-year-old white woman with a past history of depression being treated with sertraline presented to the emergency department with nausea, vomiting, and diarrhea after ingesting 400 to 600 mg of amlodipine and unknown quantities of simvastatin and trazodone. Th e quantities ingested were deduced based on the last refi ll date and contacting the pharmacy. Th e patient had one previous suicide attempt while in high school. She reported a recent altercation with her estranged husband and a history of alcohol abuse and rehabilitation. She was sober until the night of the overdose, when she had a beer. She smoked 30 cigarettes each day and denied the use of any illicit drugs. In the emergency department, she was euthermic with a heart rate of 99 beats/minute, in no distress, but with a blood pressure of 72/34 mm Hg. Her skin was cold and clammy. Her laboratory results at presentation are shown in Table 1. She received 3 L of normal saline and 1 L of 5% dextrose in normal saline in the emergency department. Because the hy-potension remained refractory, vasopressor agents were initiated with dopamine and norepinephrine followed by vasopressin and phenylephrine. Th e patient was intubated for airway protection. Glucagon was started with a 10 mg bolus followed by a continuous infusion at 10 mg/h. A 20% fat emulsion (Intralipid) was started with a 1.5 mg/kg bolus over 10 minutes followed by 0.25 mL/kg/h. A calcium gluconate drip was started at a rate of 1 g/h. In addition, an intravenous insulin infusion was started at a rate of 70 units/h along with 10% dextrose. Th e patient started developing metabolic acidosis in spite of an intravenous isotonic bicarbonate infusion. Continuous venovenous hemodi-alysis without any ultrafi ltration was started for the worsening metabolic acidosis and the anuria. Intravenous hydrocortisone was administered at a dose of 50 mg every 8 hours. On the second day of hospitalization, a chest radiograph showed worsening bilateral pulmonary infi ltrates. With numerous catecholamines, the heart rate was up to 140 beats per minute and the respiratory rate increased to 35 breaths per minute. A fractional inspired oxygen concentration (FiO 2) at 100% was). instituted. Ultrafi ltration was started with continuous veno-venous hemodialysis. Dopamine and lipid emulsion infusions were discontinued as hemodynamic stability improved. By the third hospital day, the patient's heart rate had slowed, but leukocytosis developed. Meropenem and levofl oxacin were added. Phenylephrine was tapered, and albumin 25 g every 8 hours was started to aid in vasopressor tapering. By the fourth day of hospitalization, the FiO 2 was reduced to 60% with maintenance of good oxygen saturation. A chest radiograph showed improvement in the pulmonary infi ltrates. Th e high-dose insulin drip was discontinued and the calcium gluconate drip was decreased to 0.5 g/hour. Vancomycin was started for methicillin-resistant Staphylococcus aureus coverage and the intravenous bicarbonate was stopped. Th e following day, vasopressin and norepinephrine were tapered off. Two days later, glucagon and calcium gluconate were discontinued. Th e patient was extubated on the ninth day of admission and transitioned to intermittent hemodialysis. Th e patient's continued kidney failure was attributed to acute tubular necrosis from hypotension and rhabdomyolysis. Th e rhabdomyolysis reached a peak creatine phosphokinase of 5035 U/L 50 hours after ingestion. Th is eventually resolved without the need for continued hemodialysis 17 days after continuous venovenous hemodialysis was fi rst initiated. Her creatinine at the time of discharge was 1.7 mg/dL. She was discharged home 23 days after admission. DISCUSSION Amlodipine, a dihydropyridine calcium channel blocker, has a half-life of approximately 30 to 50 hours and a large volume of distribution (2 L/g). Its slower and longer (up to 72 hours) duration of action, relative lack of negative inotropy, and once-daily dosing has made it preferred over other calcium channel blockers (CCBs) such as verapamil or nifedipine. CCBs such as amlodipine reduce calcium fl ux through voltage-gated slow