Patients abuse this laxative for an opiate-like high
Key Takeaways
Loperamide can be purchased OTC and is abused in high doses by some patients looking for the opiate-like high.
QTc prolongation is evident in cases of loperamide abuse, with other signs and symptoms including syncope, fainting, Torsade de Pointes, ventricular arrhythmias, and cardiac arrest.
Short-term treatment is symptomatic, while patients with chronic abuse require referral to a treatment center for substance use disorder.
Laxatives serve a very specific purpose—most people wouldn't think there would be any potential to use laxatives recreationally to get "high." The truth is, some of your patients may be doing just that.
When loperamide (Imodium) was first introduced in 1977, the FDA gave it a Schedule 5 designation, joining antidiarrheals and cough medicines with less than 200 mg of codeine.[] This placement on the controlled substances was determined by animal studies that showed loperamide yielded opioid-like effects but exhibited very low physical or psychological dependence. In 1988, after clinical and epidemiologic studies suggested its abuse potential in humans was low, the FDA removed it from the Schedule V list.[]
During the past decade, however, an alarming number of case reports and state poison-control calls document loperamide misuse and abuse, primarily involving teens and young adults.[]
A cheap high
Loperamide is a µ opioid receptor agonist used for acute diarrhea.[] It activates opiate receptors at the level of the intestinal tract, thus reducing peristalsis. At therapeutic doses (ie, <16 mg daily), the drug has poor bioavailability, rapid first-pass hepatic metabolism, and low central nervous system penetration—and thus a presumed low abuse potential.
This low abuse potential arises secondary to the P-glycoprotein pump that regulates the transportation of loperamide at the gastrointestinal tract and the blood-brain barrier (BBB).
Loperamide, however, can cross the BBB at higher doses (ie, 100mg–400 mg), thus resulting in euphoria or withdrawal avoidance. Accordingly, the drug has become the “poor man’s methadone,” and its use has skyrocketed as the opioid epidemic rages on.
“Loperamide is not normally included in drug screens and routine reporting is not required,” write authors in Cureus.[] “This leads to delayed diagnosis, decreased awareness, and increased mortality. It is projected to increase in the absence of regulation, and with low cost and vast availability.”
A visit to the ED
A case report by UK researchers illustrates what can happen with chronic loperamide overdose.[]
A 30-year-old woman with a history of non-epileptic seizures, ADHD, and PTSD presented to the ED after two episodes of syncope. She complained of palpitations and light-headedness before temporarily losing consciousness. A witness corroborated that the patient lost consciousness for a few seconds and experienced jerking movements. The patient quickly recovered.
ECG exhibited a dangerously prolonged QTc between 553 ms and 567 ms, as well as first-degree AV block and right bundle-branch block. A more detailed history revealed the patient had struggled with loperamide dependency for the past year, which she developed following codeine dependency.
The only other medication she was using was methylphenidate. Her physical exam was unremarkable, with standing and lying blood pressures equivalent. Blood values, including electrolytes, were normal.
The case study authors’ takeaway was that “Loperamide overdose should be considered in patients with a history of opiate addiction who present with syncope and preceding palpitations.”
A particular concern in the diagnosis of loperamide abuse is that false-positive screening results for fentanyl or buprenorphine could result.[] Researchers testing the hypothesis of cross-reaction with immunoassay drug screens used drug-free urine spiked with loperamide or its principal metabolite, dLop, which was then assessed on multiple fentanyl and buprenorphine assays. At concentrations >5.72 mg/L and 23.7 mg/L, and on certain assays, loperamide yielded positive results for fentanyl, and dLop, at >6.9 mg/L and 35.7 mg/L, did the same, also giving positive results for buprenorphine on one assay at concentrations over 12.2 mg/L.
Although the case study patient did not exhibit them, other signs and symptoms of loperamide abuse include Torsade de Pointes after further QT prolongation and cardiac arrest.[]
Focus on symptomatic treatment
The treatment of loperamide misuse depends on presentation and is largely supportive.[] Activated charcoal can be used to treat acute toxicity within 2–4 hours of ingestion. In cases of respiratory depression and airway compromise, naloxone at the lowest effective dose is administered to obviate withdrawal.
Patients administered naloxone should be monitored, as the half-life of loperamide can be prolonged.
Lipid emulsion therapy might reverse toxicity in cases of overdose; it is hypothesized that loperamide might bind to the lipid-rich emulsion, although further elucidation of this potential mechanism is required.
Other reversible causes of QTc prolongation should be ruled out, including hypokalemia or hypomagnesemia. It should be stressed that Torsades de Pointes due to loperamide toxicity may not respond to magnesium or sodium bicarbonate and instead requires cardiac pacing, electrical cardioversion, or IV isoproterenol to inhibit ventricular ectopy and prevent arrhythmias from recurring. Ventricular dysrhythmias (eg, polymorphic ventricular tachycardia) can be treated using magnesium sulfate and sodium bicarbonate.
Hypertonic saline increases sodium concentrations to surmount sodium-channel blockade secondary to loperamide. Cardiopulmonary resuscitation and advanced cardiac life support are first-line treatments for cardiac arrest.
Guidance for clinicians
The Consumer Healthcare Products Association (CHPA) offers valuable resources on helping patients who abuse loperamide, including fact sheets for HCPs.[]
Specifically, the CHPA admonishes that some patients who experience opioid withdrawal use loperamide to ease withdrawal symptoms. Therefore, it’s a good idea to screen these patients with associated signs and symptoms of loperamide toxicity.
Some patients combine loperamide with other drugs to boost absorption and penetration of the BBB.
Physicians should choose their words wisely when talking about loperamide abuse, as patients may not know that loperamide can be abused to achieve a high or to treat withdrawal. The long-term treatment of loperamide abuse necessitates referral to a treatment center for substance-use disorder.
What this means for you
Although not always ranking high on a list of differential diagnoses, loperamide abuse is becoming increasingly common—especially as the opioid epidemic wears on. Physicians should treat the condition supportively and direct patients to treatment centers for long-term care.