A new drug is coming onto the drug scene with some case reports beginning to build. The internet appears to have been a major driver or mode of distribution for this particular drug.
One study of users showed that this ketamine analog has more vivid hallucinations that would liken it to LSD. It has been theorized that this drug has the dissociative effects of ketamine but also has prominent serotninergic effects making additions more likely and hallucinations possible.
If you see a case in your ED, you can say you heard it here first!
Can acetaminophen concentrations < 100 mcg/mL obtained between 1-4 hours after acute ingestion accurately predict a nontoxic 4-hour concentration? NO!
Despite a high negative predictive value, a new study found there are still cases with toxic concentrations after 4 hours despite earlier levels < 100 mcg/mL.
The Rumack-Matthew nomogram is to be utilized starting at 4 hours after an acute acetaminophen ingestion. Unless the concentration is zero, a second level must be drawn at 4 hours if an earlier one is positive.
Reversal of the new anticoagulants rivaroxaban (Xarelto) and dabigatran (Pradaxa) has been challenging particularly in the ED setting with no definitive reversal agent. Intracerebral hemorrhage or critical GI bleed management becomes challenging and worsens mortality.
There is growing literature that states activated prothrombin complex concentrate or non-activated PCC may reverse these new anticoagulants. A volunteer study (1) showed its efficacy and concensus workgroups are now recommending aPCC as first line therapy(2). The search goes on for a reliable reversal agent for these new anticoagulants which were suppose to solve more problems instead of create new ones.
All benzodiazepines are metabolized by the liver. Some are just metabolized by pathways that are less dependent on global liver function.
The ‘LOT’ drugs are metabolized by conjugation, have no active metabolites, and have minimially affected half-lives even in the setting of liver disease.
L – Lorazepam
O – Oxazepam
T – Temazepam
The rest of the benzodiazepines are primarily metabolized via hepatic CYP-mediated oxidation and may have prolonged duration of effect in patients with marked liver impairment.
For a bit more detail and commentary by Dr. David Juurlink, please read my recent post on the Academic Life in Emergency Medicine blog: http://academiclifeinem.com/all-benzodiazepines-are-metabolized-by-the-liver/
You have a treat bag full of candy, which one can cause hypertension, hyopkalemia, metabolic alkalosis, rhabdomyolysis, low renin activity, thrombocytopenia and hypoaldosteronism. (scroll down for answer)
Licorice syrup or licorice extract contains glycyrrhizic acid which has a mineralcorticoid-like effect and can cause of all of the effects. Don't worry, Twizzlers and other usual licorice candies do not have true licorice extract in them. It is found in herbal remedies and some "natural" candies and licorice flavored cigars. Don't pick the licorice !
Yesterday's pearl generated several questions that I thought were worth answering briefly:
1) Why give it IM? Absorption rate is faster than SQ infiltration though theoretically could still cause necrosis
2) Is it only infilitration? Gangrene has occurred with inadvertent intra-arterial injection, SQ infiltration and even regular IV administration
3) Mechanism? Appears to be the drug and not diluent, diluting down the concentration as well as decreasing dose appears to help if you are going to give it IV
Here is a website if you wish to read more details:
https://www.ismp.org/newsletters/acutecare/articles/20060810.asp
If you are still using IV Phenergan, you need to be aware of the necrotic effect that occurs if it infiltrates. EDs have even removed it from their drug dispensing machines. It appears to be the drug and not the diluent. Mechanism is not completely understood. Below is a picture the plaintiff attorney will use about this well know adverse effect. If so many alternatives for IV antiemetic it is wise to reconsider IV phenergan.
Drugs that cause hearing loss:
Reversible - Chloroquine, erythromycin, quinine, CO, loop diuretics, NSAIDS, ASA
Irreversible - aminoglycosides, bleomycin, vincristine, vinblastine, cisplatin, lead, mercury, arsenic
Toxicologists should be aware of non-toxicological mimics of delirium, including anti-NMDA receptor encephalitis. It is an under-recognized progressive neurological disorder caused by antibodies against NMDA receptors.
Cases often present with altered mental status, autonomic instability, increased muscle tone, and movement disorders. It can easily be mistaken for neuroleptic malignant syndrome (NMS). A new case series describes two such patients for which toxicologists were consulted.
Must read links:
Dr. Leon Gussow provides a great review of the case series on his Poison Review blog.
Dr. Chris Nickson reviews the basics of the disease on the Life in the Fast Lane blog.
With several new diabetes medications available, it is important to know which ones are likely to cause hypoglycemia after overdose. Based on mechanism of action and reported cases, the likelihood of hypoglycemia after overdose is listed below by drug class.
Keep in mind that other drugs can interact with antidiabetics resulting in hypoglycemia. This table applies only to single agent ingestion/administration.
| Drug Class | Examples | Hypoglycemic Potential |
|---|---|---|
| Insulins | Glargine, Aspart, Detemir | High |
| Sulfonylureas | Glyburide, Glipizide | High |
| Meglitinides | Nateglinide, Repaglinide | High |
| Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists | Exenatide | Low-Moderate |
| Alpha-glucosidase inhibitors | Acarbose, Miglitol | Low |
| Thiazolidinediones | Rosiglitazone, Piaglitazone | Low |
| Biguanides | Metformin | Low |
| Dipeptidyl Peptidase 4 (DPP-4) Inhibitors | Sitagliptin, Saxagliptin | Low |
There are Type 1C Anti-Dysrhythmics, like propafenone and flecainide, that are utilized to suppress atrial fibrillation. They are called Type 1C due to their sodium channel blocking effects. Flecainide has a potent effect on the ECG and has caused significant and resistant widening of the QRS complex.
Typically, a sodium channel blocker like a TCA can be treated with hypertonic sodium bicarbonate but flecainide has been resistant to this at times and there is a reported overdose utilizing magnesium sulfate. (1) Keep that in mind if you were to see a widened QRS complex in the face of a flecainide ingestion.
There has been a Brugada ECG pattern also reported (I know Amal is smiling) (2) ontop of the widened QRS, PR intervals though minimal effect on the QT.
We will all see a patient that comes into the Emergency Department stating they have ingested some wild or self-picked mushrooms. Usually they will be actively vomiting and there will be no mushroom to identify. If there is, identification may still be difficult. There are no other clinical relevant symptoms that you can see until its too late. Amanita species is lethal and may require liver transplant. The most important question you can ask after trying to identify the mushroom is:
When did you eat the mushroom and how long after did the vomiting start?
As a general rule (with some exceptions), Amanita species cause vomiting and diarrhea in a delayed fashion 5-6 hours after ingestion. The other non hepatotoxic species usually cause vomiting within 1-3 hours.
Immediate vomiting <6 hrs from time of ingestion is good (usually).
There is minimal evidence of cross-reactivity between sulfonamide antibiotics and non-antibiotics [1-4]. Despite this, the U.S. FDA-approved product information for many non-antibiotic sulfonamide drugs contains warnings concerning possible cross-reactions.
Key Findings from a New Review Article [5]:
Bottom line: You can feel safe prescribing furosemide, glyburide, and hydrochlorothiazide to your patient with an allergy to sulfamethoxazole/trimethoprim.
Other blog reference on this topic: http://lifeinthefastlane.com/2011/04/sulfa-drug-discombobulation/
Naloxone can be administered via pretty much any route. One that has gained popularity in the past several years is nebulized naloxone. Although anecdotal reports tout the benefits of nebulized naloxone, what does the literature say?
Bottom Line: Many of the studied patients may not have needed naloxone in the first place (initial respiratory rate 13-14), with a few developing withdrawal symptoms. Nebulized naloxone may have a role in the not-too-sick opioid overdose in whom you want to prove your diagnosis and wake the patient up enough to obtain a history. It is not a therapy for the apneic opioid overdose.
A recent article was published in the Journal of Medical Toxicology reviewing the use of sodium acetate for treatment of overdoses and poisonings.
Acetate is metabolized to bicarbonate, causing a net increase in cations; this increased strong anion difference leads to alkalemia.
It has been used to treat acidosis in uremia, diarrhea, and in trauma patients.
Although no studies have been conducted using sodium acetate as an antidote, if bicarbonate is unavailable this is a viable option for management of salicylate overdose, and for qrs widening or arrhythmias due to overdoses.
Sodium acetate, if given rapidly (in animals and hemodialysis patients), causes myocardial depression, hypotension, and hypopnea.
The bolus dose should be given as 1-2 mEq/L given over 15-20 minutes. For the maintenance infusion, dilute 150 mEq diluted to 1 L in dextrose 5%, infuse at 2X the maintenance rate.
It must be diluted in dextrose 5% and NOT normal saline.
The internet has become a wealth of information and some books have now gained internet noteriety. A chemist and author of the book - TIKHAL: Tryptamines I Have Known and Loved is an excellent example.
Tryptamines include drugs like LSD and alpha-methyltryptamine (AMT). Vivid visual hallucinations and serotonin agonism, these drugs were glamorized by this author. He would synthesize a tryptamine and then "taste it". Take a look at the link below where he first describes the biochemical synthesis he performed then describes his dose response effect when he tried the drug.
If you run into a drug or slang term in the ED you are not familiar with, the website www.erowid.org will likely have the translation.
http://www.erowid.org/library/books_online/tihkal/tihkal48.shtml
In June 2013 the American College of Medical Toxicology (ACMT) released a Guidance Document on the Management Priorities in Salicylate Toxicity. Here are some key highlights:
The full document can be accessed here.
The Poison Review blog by Dr. Leon Gussow discusses the guidance document here.
Follow me on Twitter (@PharmERToxGuy)
When reviewing a patient's medication list, there are always some that should catch your eye. Digoxin is one since we can measure it, has a low therapeutic index and elimination is effected when renal function is diminished. Another drug that should catch your eye is SOTALOL. Renally cleared and affected by even a minimally lower than normal magnesium. The toxic effect even at therapeutic levels is torsades de pointes.
One study, in a 736 bed hospital, showed 89% of patients prescribed sotalol were on an inappropriate dose due to renal function and an odds ratio of 3.7 increased re-admission rate at 6 months for the patients on the inappropriate dose of sotalol.
We can catch this in the ED. Involve your pharmacist, ED pharmacist or local toxicologist for dosing calculations.
In the treatment of acetaminophen poisoning with N-acetylcysteine (NAC), the PT/INR can be slightly elevated even in the absence of hepatotoxicity. Considering Prothombin Time (PT) is one of the criteria used to assess severity of liver damage in this setting, it is important to know how much the PT/INR can be affected by NAC and if it has an actual effect on coagulation factor levels.
Clinical Practice Pearls