N-Bomb: a potent psychedelic stimulant

EPSON MFP image3.5 out of 5 stars

2C-I-NBOMe, an “N-bomb” that kills with “Smiles”. Toxicological and legislative aspects. Nikolaou P et al. Drug Chem Toxicol 2014 May 1 [Epub ahead of print]

Abstract

Despite the confusing title, this is a well done comprehensive review of 2C-I-NBOMe, an extremely  potent hallucinogenic stimulant that has been associated with deaths and severe toxicity.

The NBOMe structure drugs have a 2-methoxybenzyl group attached to the nitrogen of a 2C psychedelic phenethylamine:

 

nbome_article1-1

This substitution gives the drug enhanced activity at the 5-HT2A  serotonin receptor, a main target of many serotonergic agents such as LSD.

Major common effects of 2C-I-NBOMe include tachycardia, agitation, visual and auditory hallucinations, hypertension and seizures. A number of deaths have been reported in association with 2C-I-NBOMe.

Street names for 2C-I-NBOMe include:

  • N-Bomb
  • 25I
  • Bom-25
  • Cimbi-5
  • Legal Acid (it is, of course, neither legal nor LSD)
  • Mr. Happy
  • Solaris
  • Smiles
  • Smiley Paper

This review is comprehensive and up-to-date, with 40 references (some as recent as this year). Worth reading for those with any interest in the topic.

 

Related posts:

NBOME — it’s not your father’s LSD

Case series: 7 patients with confirmed exposure to hallucinogenic stimulant 25I-NBOMe (“N-bomb”)

25I-NBOMe: a dangerous new hallucinogen

 Case report: toxicity from designer drug 25I

Seizures, hyperthermia, and serotonin syndrome following use of designer drug 2C-I (“Smiles”)

 

Must-read: marketing vs. medicine in the case of Pradaxa (dabigatran)

Pradaxa34 out of 5 stars

Dabigatran: how the drug company withheld important analyses. Cohen D. BMJ 2014 Jul 23;349:g4670. doi: 10.1136/bmj.g4670.

Full Text

As TPR has reported before, there has long been reason to doubt the claim that the anticoagulant dabigatran (Pradaxa) can be safely and effectively used for prevention of strokes in patients with non-valvular atrial fibrillation without laboratory monitoring.

This must-read investigative report uses internal company documents released in association with multiple lawsuits — recently settled for a total of $650 million — to suggest that Boehringer Ingelheim, the drug’s manufacturer, suppressed evidence that using a laboratory test to adjust dosing could reduce the incidence of major bleeds associated with the drug.

As the BMJ report points out, the claim that monitoring levels and/or anticoagulation effect was not necessary when using Pradaxa was a key talking point in marketing the drug. However, a company study had determined that blood levels of dabigatran were unpredictable, varying five-fold from patient to patient. One cardiologist who advised the FDA noted:

“I’m struck by what my eyeball tells me about a five-fold variability [in plasma levels] within the 90% confidence [interval] of the 150-dose. That seems awfully big to me in a drug that we’re proposing to use without therapeutic monitoring.”

This unpredictability was especially important because there was no available and effective way to reverse the anticoagulant effect in the event of significant hemorrhage. The Institute for Safe Medication Practices reported that in 2011 there were 3781 serious adverse effects and 542 patient deaths reported in the United States in association with dabigatran. In comparison, warfarin (Coumadin) was associated with only 72 deaths during that same time period.

The BMJ report cites the internal company documents to argue that for marketing purposes the company suppressed recommendations for monitoring and did not share all their analyses with regulatory agencies:

“In the end, the final recommendations simply stressed the need to monitor renal function and patient characteristics before and during treatment and ‘make dose reductions in certain patients’ — and not routinely measure plasma concentrations of anticoagulant activity.”

This is an important report. It’s a must-read.
Related posts:

Maybe Pradaxa (dabigatran) does need blood monitoring after all

Dabigatran-related bleeding: a case series

Pearl: estimating renal function in patients on dabigatran (Pradaxa)

Massive bleeding associated with dabigatran

Case report: hemodialysis for dabigatran overdose

The many potential problems with using dabigatran

New York Times on dabigatran

Case series: four patients with dabigatran-associated bleeding

Guidelines for reversing overdose of dabigatran (Pradaxa) and other new anticoagulants

Care Report: fatal GI bleed 6 days after one dose of dabigatran (Pradaxa)

Dabigatran: is laboratory monitoring really unnecessary?

Dabiagtran and the trauma patient

Dabigatran Toxicity: The Top 10 Questions

Review: the bleeding patient on dabigatran

Dabigatran and the elderly

Dabigatran etexilate: a new challenge for emergency physicians and toxicologists

 

 

 

 

 

 

 

Fatal caffeine overdose: useful paper despite BuzzFeed-worthy title

KFDA – NewsChannel 10 / Amarillo News, Weather, Sports

2.5 out of 5 stars

Fatal Caffeine Intoxication: A Series of Eight Cases from 1999 to 2009. Banerjee P et al. J Forensic Sci 2014 May;59:865-868.

Abstract 

This article is classic example of scientific bait and switch, a deceptive tactic not dissimilar to the use of “click bait” by websites like BuzzFeed. The subtitle promises “Fatal Caffeine Intoxication: A Series of Eight Cases . . .” But by the end of the introduction this has been walked to back “eight fatal cases of caffeine intoxication-related deaths,” a concept that is hopelessly vague and undefined. The way the authors use the term, a man who gets hit by a truck leaving Starbucks after drinking two Vente cappuccinos could be considered a caffeine-related death. The authors’ attitude seems to be: Causation? We don’t need no stinkin’ causation!

In fact, a careful analysis of these cases, from the Office of the Chief Medical Examiner of Maryland, reveals that only 3 of these 8 cases (numbers 5,6 and 8) are convincingly caused by caffeine overdose. In the others, the caffeine level was lower than the generally accepted lethal concentration of 80 mg/L and/or other drugs were possibly involved (case #4 had a lethal level of butalbital).

However, the paper is worth perusing since, as illustrated by the clip above, the availability of concentrated caffeine powders may mean that we will be seeing more cases of significant overdose. Here are some key take-home points from the discussion section:

  • Caffeine is rapidly and completely absorbed from the GI tract, with peak levels 30-60 minutes after ingestion.
  • Through its action blocking adenosine receptors, increased peripheral vascular resistance and raises blood pressure.
  • Caffeine increases the risk of cardiac arrhythmias in a dose-related fashion.
  • Presenting signs and symptoms of caffeine toxicity include: weakness, vomiting, fever, altered mental status, seizures, cardiac arrhythmias, hypokalemia, hyperglycemia, and coma.
  • Although treatment of caffeine toxicity is generally supportive, hemodialysis can be beneficial in massive overdose.

The authors don’t mention that the antidotes-of-choice to treat cardiotoxic effects of caffeine (tachydysrhythmias and blood pressure alteration) are β-blockers.

Earlier this year, 18-year-old Ohio high school senior Logan Stiner died from an overdose of caffeine powder:

http://www.youtube.com/watch?v=JE95w8tPSQY

[ADDENDUM 7/21/14]: The FDA’s warning about powdered pure caffeine can be read here. The release makes the points that this product is essentially pure caffeine, and that one teaspoon equals the amount of caffeine in approximately 25 cups of coffee. (HT @Jldorazio)

Related posts:

Toxicity of high-caffeine “energy” drinks

Fatal caffeine overdose

 

Two cases of laboratory-confirmed exposure to 25B-NBOMe

25I-NBOMe blotter paper

25I-NBOMe blotter paper

3 out of 5 stars

Two cases of severe intoxication associated with analytically confirmed use of the novel psychoactive substances 25B-NBOMe and 25C-NBOMe. Tang MHY et al. Clin Toxicol 2014 Jun;52:561-565.

Abstract

The NBOMe series of drugs are substituted phenethylamines. They act as agonists at both the 5-HT2A receptors and the α-receptors. Because of these actions, they can cause both hallucinations (5-HT2A  effects) and sympathomimetic toxidrome (α effects.) Since these drugs are so potent, they are often sold in the form of impregnated blotter paper.

This paper, from Hong Kong, describes 2 laboratory-confirmed cases of 25B-NBOMe toxicity. One patient also had 25C-NBOMe in his urine. Given the basic toxicology of these compounds, the patients’ signs and symptoms were not surprising. Both ad mydriasis, agitation, hypertension, tachycardia, hyperthermia, diaphoresis, and altered mental status, One patient had seizure activity and was intubated. The other developed rhabdomyolysis and renal impairment.  Treatment included basic supportive care, fluids, and benzodiazepines.

[Photograph of blotter paper, seized in Austria in April 2013, from Belgian Early Warning System on Drugs. The blotter paper had been sold as LSD but found to contain 25I-NBOMe]
Related posts:

NBOME — it’s not your father’s LSD

Case series: 7 patients with confirmed exposure to hallucinogenic stimulant 25I-NBOMe (“N-bomb”)

25I-NBOMe: a dangerous new hallucinogen

 Case report: toxicity from designer drug 25I

Seizures, hyperthermia, and serotonin syndrome following use of designer drug 2C-I (“Smiles”)

 

 

Case report: guanfacine overdose

Intuniv (Guanfacine)

Intuniv (Guanfacine)

3 out of 5 stars

Prolonged Bradycardia and Hypotension Following Guanfacine Extended Release Overdose. Walton J et al. J Child Adolesc Psychopharmacol 2014 Jul 10 [Epub ahead of print]

Reference 

Guanfacine is a central α2-agonist with a mechanism of action similar to that of clonidine. Originally marketed as an antihypertensive agent, it is now available as an extended-release preparation (Imtuniv) for treating children ages 6-17 with attention-deficit hyperactivity disorder (ADHD). It is thought the mechanism of action in that condition may involve stimulation of α2-receptors in the prefrontal cortex.

As with clonidine, guanfacine can cause initial hypertension (from peripheral α-agonist activity) followed by prolonged bradycardia and hypotension (from central α2 effects.

This short case report describes a 9-year-old boy with ADHD who was taking dexmethylphenidate and risperidone, as well as extended-release guanfacine (3 mg in the morning.) Inadvertently, the child received an extra dose of guanfacine-ER at around noon. Four hours later he was lethargic and drowsy but arousable. On arrival at hospital, he was bradycardic (40-50 bpm) and hypotensive (~80/40 mm Hg.) He was admitted for observation and given IV fluids. He recovered uneventfully over the next 24 hours.

In their discussions, the authors suggest that — as illustrated by their case — a prolonged hypotensive response can follow even a mild overdose of guanfacine, and any overdose of this agent should mandate medical evaluation.

To read my Emergency Medicine News column discussing the toxicology of newer ADHD drugs, click here.