1. Buprenorphine Induced Acute Precipitated Withdrawal in the Setting of Loperamide Abuse
William Eggleston, PharmD1, Nicholas Nacca, MD3, and Jeanna M. Marraffa, PharmD, DABAT1,2
1SUNY Upstate Medical University, Upstate NY Poison Center, Syracuse, NY 2SUNY Upstate Medical University, Department of Emergency Medicine, Syracuse, NY 3University of Vermont Medical Center, Department of Surgery, Burlington, VT
DISCUSSION
We report a case of buprenorphine induced acute precipitated withdrawal in the setting of loperamide toxicity
Patient became increasingly agitated with hallucinations shortly after 12 mg of sublingual buprenorphine
Approximately 2 hours after administration the patient developed ventricular tachycardia with a pulse that progressed to PMVT
During the resuscitation the patient received:
6 mg lorazepam IV
10 mg diazepam IV
150 mg amiodarone IV bolus  continuous infusion
2 g magnesium sulfate IV
Loperamide is a mu-opioid agonist
Large doses required to overcome P-glycoprotein efflux
Addiction properties likely similar to other opioids
Google trend suggests the popularity of loperamide use may be increasing
Accessible and affordable alternative agent to mitigate withdrawal symptoms in opioid addicted patients
Cardiac abnormalities due to effect on delayed-rectifying potassium channels (Ikr) and likely sodium channels
ECG abnormalities may be a surrogate marker of elevated serum level
Administration of buprenorphine (mu-receptor partial agonist) at induction doses likely precipitates withdrawal in patients with elevated serum concentrations of loperamide
Similar to other opioids
Prolonged elimination has been reported in overdose
Elevated serum loperamide concentration of 41 ng/mL at the time of buprenorphine administration
Consider prolonged drug effect in overdose
INTRODUCTION
Loperamide is an antidiarrheal that exhibits mu-opioid receptor agonism
It is a piperidine derivative
Abused in large doses for opioid-like effects
Cardiac conduction disturbances reported after abuse
We report a case of buprenorphine induced acute precipitated withdrawal in a patient presenting with loperamide toxicity
Relative Interest
Time (years)
Figure 1: Google trends result for “loperamide” interest based on web-search history from 2004 to present (8/25/15)
Loperamide Fentanyl Morphine
Figure 1: Structural relationship between loperamide, fentanyl, and morphine
CASE
A 30 year-old male with a history of opioid addiction and loperamide abuse resulting in previous episodes of PMVT presented to an Emergency Department with syncope. His electrocardiogram (ECG) demonstrated sinus rhythm with a prolonged QRS and QT/QTc. He left against medical advice and was later found pulseless and apneic. CPR was performed with return of spontaneous circulation. He had multiple ventricular dysrhythmias, including polymorphic ventricular tachycardia (PMVT). He was successfully treated with magnesium sulfate and a repeat ECG was performed after transfer (Figure 2). He admitted to abusing approximately 400 mg of loperamide daily for 7 days. Twelve hours after admission his ECG demonstrated a QRS duration of 172 ms and a QTc of 659 ms. Within 24 hours of presentation he complained of withdrawal symptoms. A 12 mg dose of sublingual buprenorphine was administered. He became agitated and combative with hallucinations. Lorazepam was given without effect. He then had multiple episodes of non-sustained ventricular tachycardia, which ultimately deteriorated to PMVT (Figure 3). He was resuscitated, sedated with propofol, and intubated. The serum loperamide concentration (reported after the fact) was approximately 41 ng/mL (therapeutic range ng/mL) at the time of buprenorphine induction. The conduction blocks slowly normalized to a QRS of 96 ms and QTc of 489 ms on hospital day 9.
Figure 2: ECG completed on presentation to the Emergency Department after transfer; ventricular rate 60, PR interval 192 ms, QRS duration 192 ms, QT/QTc 704 ms.
CONCLUSION
Toxicologists should be aware of the increasing trend of loperamide abuse
ECG abnormalities suggest elevated serum loperamide concentration
Administration of high-dose buprenorphine in patients actively intoxicated with loperamide can acutely precipitate opioid withdrawal
Figure 3: Rhythm strip obtained during arrhythmia, approximately two hours after buprenorphine administration.