W-18, a synthetic opiate 100 times more potent than fentanyl

W-18

W-18

Last August, Canadian police seized 110 illegal fentanyl pills at a home in Alberta province. Yesterday, Global News reported that some of the pills have tested positive for an extremely potent opioid called W-18.

This is certainly a disturbing development, since W-18 is a μ-receptor agonist 100 times more potent than fentanyl. According to B.C. Centre for Disease Control, W-18 is one of a series of 32 synthetic opioids discovered in the 1980s at the University of Alberta. W1 thru W19 are pure μ-receptor agonists; W20 thru W32 are agonist-antagonists (as is buprenorphine.)  W-18 seems to be the most powerful agonist of the group.

The ‘W’ compounds have never been used clinically, and there has been virtually no scientific study of their actions, adverse effects, or reversibility. The B.C. Centre for Disease Control points out that since some of these drugs — especially W-18 — are so potent, they will likely required high doses of naloxone to reverse their effects.

Coronary artery vasospasm induced by cocaine (maybe)

2.5 out of 5 stars

Cocaine-Induced Coronary Artery Vasospasm. Almaddah N, Ajayi TO. N Engl J Med 2016 Feb 4;374:e5

Full Text with video

In a series of amazing studies that are now about three decades old, Richard Lange and his colleagues at Parkland Hospital in Dallas investigated the cardiovascular effects of administering intranasal cocaine to patients to patients during cardiac catheterization for routine workup of chest pain. In an initial study, the group demonstrated that cocaine produced coronary artery vasoconstriction that was relieved by nitroglycerin and exacerbated by smoking a cigarette and also by administering a beta-blocker.

This brief case report in the New England Journal of Medicine’s “Images in Clinical Medicine” series could be an excellent real-life illustration of Lange’s discoveries, if it weren’t for some critical flaws (more on these in a minute.) A 58-year-old woman comes to the emergency department complaining of chest pain on and off for 2 days. The pain goes away after she is given nitroglycerin SL and acetaminophen with hydrocodone (!). A recent coronary angiogram was unremarkable. Her initial troponin level was minimally elevated at 0.04 ng/ml (reference range 0.0 – 0.03 ng/ml). At 6 hours the troponin level increased to 5.7 ng/ml and a transthoracic echocardiogram showed a small pericardial effusion and normal cardiac function without wall motion abnormalities.

She was admitted with a diagnosis of myoparicarditis and treated with steroids with resolution of symptoms.

On hospital day 3 she developed ventricular fibrillation that resolved after 5 minutes of ACLS. EKG showed new anterior ST elevation with reciprocal changes. Emergency coronary angiography revealed severe coronary vasospasm of the left main, LAD, and circumflex arteries; the spasm resolved after administration of intracoronary nitroglycerin. The EKG, echo, and angiographic findings are nicely illustrated in the clips accompanying the case report.

The authors state that the patient’s urine drug screen (UDS) was positive for cocaine, so: “It appears that this patient used cocaine during hospitalization, which led to active coronary spasm.” This conclusion is not at all clear from the evidence presented. As any toxicologist could have told them, the UDS can be positive for 3 days (or more) after last exposure to cocaine, long after the acute effects of the drug have passed. It’s certainly possible that the coronary vasospasm could have been the result of something other than cocaine, such as Prinzmetal’s angina. However, the visuals nicely illustrate the cardiac effects of cocaine even if they were not, in fact, caused by cocaine.

 

Tox Tunes #105: How Can a Poor Man Stand Such Times and Live (Ry Cooder)

Well the doctor comes around with a face all bright,
And he says in a little while you’ll be all right.
All he gives is a humbug pill,
A dose of dope and a great big bill —
Tell me how can a poor man stand such times and live?

“How Can a Poor Man Stand Such Times and Live” was written by Blind Alfred Reed (1880-1956), who recorded it about a month after the stock market crash in 1929 that heralded the Great Depression. This great cover by Ry Cooder features a first-rate band including the legendary Flaco Jiménez on accordion.

This cut was taken from a 1987 concert at The Catalyst in Santa Cruz. The entire set is fabulous and can be viewed here:

Saturday with SMACC: Strayer on how to use opioids (and how not to use opioids)

smacc-dublin

The 3rd (and final) release of registrations for the 2016 Social Media and Critical Care (SMACC) conference in Dublin (June 13-16) will take place on February 3 at 09:00 Sydney time — or 4 pm Tuesday February 2 Chicago time. The 2nd release early December sold out in just one hour (!) after being posted,  so if you’re interested in attending plan accordingly. The program and registration details for the conference can be accessed at the smaccDUB website.

To get a taste of what’s in store for Dublin, here’s a talk from last year’s smaccCHICAGO — Reuben Strayer’s excellent talk on how the current epidemic of opioid abuse developed, and some steps emergency practitioners can take to deal with it and minimize harm. To listen to the talk and access the accompanying slides, click here.

Cannabis psychopharmacology: it’s more complex than you might imagine

Yarygin/shuttershock.com

Yarygin/shuttershock.com

3.5 out of 5 stars

The Cannabis sativa Versus Cannabis indica Debate: An Interview with Ethan Russo, MD. Cannabis and Cannabinoid Research 2016 Jan;1:44-46

Full Text

This short interview with Ethan Russo MD should be of interested to toxicologists and other clinicians who might counsel patients on issues regarding medical marijuana. It contains some interesting information about the different biologically active chemicals contained in cannabis plants, and their effects. These chemicals include:

  • Δ9-tetrahydrocannabinol (THC) – main psychoactive chemical in Cannabis
  • cannabinol – breakdown product of THC with approximately 25% of its potency
  • tetrahydrocannabivarin (THCV)CB1-receptor antagonist at low doses, agonist at high doses
  • cannabidiol (CBD) – component with anti-depressant and anti-inflammatory effects

There are also many additional components of cannabis that may increase or modify the effects of these major chemicals. These include terpenes such as myrcene — a strong sedative that may be responsible for the couch-lock effect caused by some strains of cannabis — and alpha-pinene, a component that may counter the tendency of THC to impair short-term memory.

Dr. Russo argues that while Cannabis sativa and Cannabis indica strains are morphologically different, the common notion that sativa is “uplifting and energetic” while indica is sedating is completely wrong:

“. . .almost all Cannabis on the market has been from high-THC strains. The differences in observed effects in Cannabis are then due to their terpenoid content, which is rarely assayed, let alone reported to potential consumers. The sedation of the so-called indica strains is falsely attributed to CBD content when, in fact, CBD is stimulating in low and moderate doses!”

The psychopharmacology of Cannabis is turning out to be much more complex than initially. As the use of medical and recreational marijuana expands, it is important for clinicians to have a basic familiarity with the basic science involved. This informative open-access interview is a quick read and worth looking at.

Related post:

Effects of marijuana on driving ability

Extracorporeal treatment for digoxin toxicity: just say no

digoxin53 out of 5 stars

Extracorporeal treatment for digoxin poisoning: systematic review and recommendations from the EXTRIP Workgroup. Mowry JB et al. Clin Toxicol 2016 Feb;54:103-14.

Abstract

“Forced diuresis, and hemodialysis are ineffective in enhancing the elimination of digoxin because of its large volume of distribution (4-10 L/kg), which makes it relatively inaccessible to these techniques.” Goldfrank’s Toxicologic Emergencies (Tenth Edition, 2015)

That one sentence from the latest edition of Goldfrank’s tells you all you need to know about the use of extracorporeal treatment (ECTR)  in digoxin poisoning, and makes this current paper from the EXTRIP workgroup somewhat superfluous. To cut to the chase (no spoiler alert needed), the conclusions here agree completely:

ECTR, in any form, is not indicated for either suspected or proven digoxin toxicity, regardless of the clinical context, and is not indicated for removal of digoxin-Fab complex.

As usual with the EXTRIP papers, the discussion is worth reading as a review of the topic. Some points made by the authors:

  • less than 0.5% of body burden of digoxin is in the blood
  • it is important not to confuse the short-term plasma clearance effected by hemodialysis with significant reduction in total body burden of digoxin
  • hemodialysis in patients with digoxin poisoning may still be indicated for reasons other than drug removal, such as renal failure, hyperkalemia that does not reverse with administration of Fab fragments, or fluid overload

Related posts:

Hemodialysis in lithium poisoning: there is no evidence. Full stop.

Recommendations for staring hemodialysis in salicylate toxicity

Excellent guidelines for managing salicylate overdose

Hemodialysis in metformin poisoning

Hemodialysis in acute methanol poisoning: is there really good evidence?

Hemodialysis in lithium poisoning: what is the evidence?

Must-read: consider hemodialysis in cases of massive acetaminophen overdose

What enhanced elimination techniques are useful in critical toxicology patients

Hemodialysis and other extracorporeal modalities in toxicology cases