Loperamide abuse and cardiac dysrhythmia

header_3-3-imodium_a-d_diarrhea_caplets_oral_suspension3.5 out of 5 stars

Cardiac Dysrhythmias After Loperamide Abuse — New York, 2008-2016. Eggleston W et al. MMWR 2016 Nov 18;65:1276-1277.

Full Text

Last week we reviewed a new paper showing that the number of cases of loperamide abuse reported to the National Poison Data System increased by 91% from the years 2000 to 2015. For reasons detailed in that review and in my recent Emergency Medicine News article on the topic, massive doses of loperamide can alleviate opioid withdrawal symptoms and also produce opioid-like effects.

This very brief report has some interesting clinical and epidemiological nuggets. The authors looked at cases of intentional loperamide abuse reported to New York State’s two poison centers from January 2008 through March 2016. They identified 22 cases. Some of their findings include:

  • EKG abnormalities included QTc prolongation (15 cases,) QRS prolongation (9,) and ventricular dysrhythmia (8.)
  • Doses of loperamide ingested ranged from 34 to 1200 mg (average 358 mg.)
  • Serum loperamide levels measured in 4 patients raged from 77 – 210 mg/mL (therapeutic 0.24 – 3.1 mg/mL.)
  • In 179 cases of intentional loperamide abuse reported to the National Poison Data System, there were 16 cases of ventricular tachycardia or fibrillation.

The authors conclude that “These cases support the reported association between loperamide abuse and cardiac toxicity.” This is a developing topic in which there is increased interest. Worth reading.

Related posts:

Missing loperamide (Imodium) abuse can be a fatal mistake

Cardiac effects of loperamide abuse

Loperamide (Imodium) overdose can cause fatal cardiac toxicity

 

 

Treating “heroin” overdose: the past is no guide

naloxone-300x1741.5 out of 5 stars

Do heroin overdose patients require observation after receiving naloxone? Tillman MW et al. Clin Toxicol 2016 Nov 16:1-7 [Epub ahead of print]

Abstract

The stated goal of this study was to search the medical literature in an attempt to answer 3 main questions:

  1. “What are the medical risks to a heroin user who refuses ambulance transfer after naloxone?
  2. “If the heroin user is treated in the emergency department after naloxone, how long must the be observed prior to discharge?
  3. “How effective in heroin users is naloxone administered by first responders and bystanders?”

The authors searched Pubmed and Google Scholar for articles relevant to these questions, identifying literature going back to the 1990s. The paper does not report any stringent methods as to how relevant literature was selected, or how chosen papers were analyzed. Nevertheless, the authors concluded . . .

Screw it. By the time I was halfway through the paper, I really didn’t care what the conclusions were. It was clear to me that there was no way that this type of literature review — even if it had much better methods — could provide clinically useful answers to the questions asked. The fact is, first responders and emergency practitioners never deal with “heroin overdose patients.” They treat patients who may have taken an opioid that could be heroin, to some substance they thought was heroin, or something that was given or sold to them purported to be heroin. And “heroin” now may not be anything like the “heroin” on the street when much of the research reviewed by the authors was carried out. Today “heroin” may be some god-awful combination of U-47700, fentanyl, carfentanil, and who knows what else — maybe with some heroin thrown in.

We really don’t know the pharmacokinetics of many of these drugs, and there is no reason to believe that they will be the same as those of heroin. I would suggest that data from a decade or two ago have no certain relevance to what we’re seeing clinically today. Over the last several years we’ve entered a whole new world of street drugs, and unfortunately we can not rely on past experience to guide us.

Related posts:

Keys to the safe use of naloxone

Position statement on bystander naloxone

 

How to interpret urine drug tests for marijuana: a review

Linda Parton/shutterstock.com

Linda Parton/shutterstock.com

4 out of 5 stars

Interpretation of Workplace Tests for Cannabinoids. Kulig K. J Med Toxicol 2016 Sep 29 [Epub ahead of print]

Abstract

The interpretation of workplace urine drug tests for marijuana often becomes a point of contention in workman’s compensation cases or proceedings moving towards firing an employee. In may experience, the court or arbitrator not infrequently gets the science of these tests wrong. Such misinterpretation can be devastating for the employee who is at risk of losing his or her job and benefits. This concise review of the subject by Ken Kulig gets the science right, and will be a valuable reference to use when consulting in these cases.

Anyone who deals with occupational urine drug tests should read the entire article, which only takes about 10 minutes. But here are some pearls:

  • “A positive [qualitative screening test] result does not document impairment, or even recent use . . .” — this is a key point, one that is often missed.
  • The urine screening test for THC actually detects an inactive metabolite, THC-COOH.
  • The marijuana plant itself contains an inactive precursor of THC, THC acid (THCa):
THC acid

THC acid

  • Inactive THC acid is decarboxylated and transformed into psychoactive THC when it is heated or dried:
THC

THC

  • Of the 2 FDA approved prescription oral cannabinoids, Marinol® (dronabinol) will give a positive urine screening test for marijuana metabolic, whereas Cesamet® (nabilone) will not.
  • The prescriptiondrug Sativex ®— available in Europe — is an oral spray that contains equal amounts of THC and cannabidiol.
  • Synthetic cannabinoids such as “Spice” or “K2” will not be detected on a urine screening test for marijuana metabolites.

Related post:

Protonix (pantoprazole) can cause a false positive urine screening test for THC

Missing loperamide (Imodium) abuse can be a fatal mistake

Loperamide3 out of 5 stars

Epidemiologic Trends in Loperamide Abuse and Misuse. Vakkalanka JP et al. Ann Emerg Med 2016 Nov 4 [Epub ahead of print]

Abstract

This paper reviews loperamide exposures reported to the National Poison Data System  over the 6-year period from 2010 through 2015. Because of the well-recognized limitations involved in retrospective analysis of poison center data, there is not much clinically useful information revealed by their study. The authors did find — unsurprisingly — that reported exposures to loperamide went up from 2010 to 2015, increasing by 91%.

As we’ve discussed before, loperamide is an over-the-counter anti-diarrhea medication that in therapeutic doses acts as an agonist at the peripheral mu-opioid receptors but does not cross the blood-brain barrier. This lack of central effect is largely due to P-glycoprotein (P-gp), which acts prevent entry of loperamide (and other substances) into both the systemic circulation and central nervous system. However, opioid abusers have discovered that when taken in massive amounts (ten times the therapeutic dose or more) loperamide can overcome the protective effects of P-gp and reach the brain. As this paper notes, there is a growing use of huge-dose loperamide to relieve opioid withdrawal systems or to get high.

Unfortunately, loperamide can cause cardiotoxic effects, predominantly acquired prolonged QT syndrome. Last June, the FDA issued a Drug Safety Communication warning of serious heart problems from high-dose loperamide The authors this current study identified 1736 reports of intentional loperamide exposures, including 15 deaths. Previous case reports suggest that at least some of these deaths may have been from cardiac dysrhythmias precipitated by prolonged QT.

In this paper, Vakkalanka et al conclude:

“Health care providers should consider the potential for loperamide toxicity when managing patients with opioidlike toxicity.”

But they miss a key point. In at least one of the cases of fatal loperamide overdose reported in the literature, the patient had previously presented with syncope for which no cause was identified. So here’s the bottom line: if a patient comes in with unexplained syncope and/or a prolonged QT interval, consider massive loperamide abuse. If this is missed, the outcome can be deadly.

To read my Emergency Medicine News column on massive loperamide abuse, click here.

Related posts:

Cardiac effects of loperamide overdose

Loperamide (Imodium) overdose can cause fatal cardiac toxicity

 

 

 

 

Does exposure to marijuana cause myocardial infarction?

marijuana-heart-rate2 out of 5 stars

Prolonged cardiac arrest complicating a massive ST-segment elevation myocardial infarction associated with marijuana consumption. Orsini J et al. J Community Hosp Intern Med Perspect 2016 Sept 7;6(4):31695

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The medical literature contains scattered, rare case reports and series describing myocardial infarction, acute coronary syndrome, and cardiac arrest associated with exposure to cannabis. (Extreme emphasis on the word “associated.”) This literature is limited by a number of crippling problems, including failure to screen completely for presence of other drugs, failure to collect complete clinical data, and failure to establish causation rather than mere association. In addition, in many of these papers, exposure to marijuana is documented simply by the presence of a positive urine screen. Since this screen can be positive for days, weeks, or even months after last use, it is worthless for establishing acute exposure.

This case report illustrates these problems vividly. A previously healthy 40-year-old man had tonic-clonic seizures followed by cardiac arrest at a party. EMTs documented ventricular fibrillation which responded to ACLS measures. At hospital troponin I was 8.32 ng/ml (< 0.1) and EKG showed ST elevation in II, III, aVF, and V1 – V5. Urine drug screen was positive for THC but negative for cocaine and amphetamines as well as synthetic cannabinoids. (The authors don’t report on exactly what agents were included in the test.) The patient was admitted to the intensive care unit and ultimately declared brain dead. Autopsy revealed an acute anterior lateral, septal, and posterior wall myocardial infarction. Additional findings included a calcified left ventricular apical thrombus as well as hypertensive and atherosclerotic heart disease.

To their credit, the authors discuss many of the weaknesses of their report. The positive urine drug screen for THC does not establish acute exposure, and the fact that the patient collapsed at a “party” does not mean he was using cannabis at the time. The authors did not rule out possible exposure to other drugs, including the many varieties of bath salts and (most likely) all possible synthetic cannabinoids. In addition, the presence of a calcified mural thrombus as well as hypertensive and atherosclerotic cardiac changes disproves the authors claim that “[h]is past medical history was unremarkable . . .”  Rather, his extensive past cardiac history was undocumented.

 

Related posts:

Review: marijuana and health

Does smoking marijuana cause stroke?

Does cannabis cause acute coronary syndromes?