UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: Ondansetron Induced Dystonia

Keywords: ondansetron, dystonia (PubMed Search)

Posted: 2/6/2014 by Fermin Barrueto, MD (Updated: 6/17/2024)
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Ondansetron (Zofran) is a great anti-emetic that, since it has gone generic, is also inexpensive. High dose ondansetron has been reported to cause QT prolongation and that practice is largerly discontinued now in the oncology world. Another uncommon adverse drug reaction may be dystonia. Though we think of ondansetron as a 5-HT3 blocker and should not cause the dystonic reaction like we see in metoclopramide, there are case reports of this reaction occurring.






Ondansetron-induced dystonia, hypoglycemia, and seizures in a child.
Patel A, Mittal S, Manchanda S, Puliyel JM.
Ann Pharmacother. 2011 Jan;45(1):e7.

Category: Toxicology

Title: Resistant Etoh Withdrawal - Try Dexmedetomidine (Precedex)

Keywords: dexmedetomidine, alcohol withdrawal (PubMed Search)

Posted: 1/30/2014 by Fermin Barrueto, MD (Updated: 6/17/2024)
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If you are treating an alcohol withdrawal patient and benzodiazepines are not working, try dexmedetomidine (precedex). This centrally acting alpha-2 agonist was utilized in 18 ICU patients and was shown to be safe. Average diazepam dose was 193 mg IV and lorazepam dose was 9 mg IV in these patients. Haloperidol was utilized in 3 of these patients which is not an effective therapy for alcohol withdrawal (could worsen due to QT prolongation, decrease seizure threshold and anticholinergic effects).
Still requires further research and not sure about the physiologic mechanism dexmedetomidine would actually treat alcohol withdrawal aside from sedating. There is the added benefit of maintaining airway reflexes versus propofol. This case series shows the experience with this drug regimen.
1. Tolonen J et al. Dexmedetomidine in addition to benzodiazepine-based
sedation in patients with alcohol withdrawal delirium. Eur J Emerg
Med. 2013. 20:425-427.

Category: Toxicology

Title: Bioaccumulation and the "Therapeutic" Overdose

Keywords: pharmacology (PubMed Search)

Posted: 1/23/2014 by Fermin Barrueto, MD (Updated: 6/17/2024)
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Everyone has admitted an altered mental status, patient or bradycardic patient and all of your test results are coming back normal except for a mild increase in creatinine. Take a look at the medication list. Creatinine is a poor indicator of renal function and GFR may be severely impaired even with a mild elevation of creatinine. If you have a predominantly renally excreted drug, you can see toxic effects of a drug even if administered at therapeutic levels.

Common bradycardia inducing medication that is renally cleared: atenolol (very high renal excretion) and digoxin (70%).

Altered Mental Status and on Keppra? Keppra is 100% renally cleared!

Ask your pharmacist for help with the medication list with renal or hepatic insufficiency.

Category: Toxicology

Title: Antivenin Only for North American Crotalinae Snake Envenomation

Keywords: copperhead, snake, envenomation, antivenin, crotalinae, fasciotomy (PubMed Search)

Posted: 1/7/2014 by Bryan Hayes, PharmD (Emailed: 1/9/2014) (Updated: 1/9/2014)
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Current evidence does not support the use of fasciotomy or dermotomy following North American Crotalinae envenomation with elevated intracompartmental pressures. [1]

A new case report of a 17-month old bitten by a copperhead snake reinforces that early and adequate administration of crotaline Fab antivenin is the treatment of choice. [2]

Many experts recommend against measuring compartement pressures altogether; we know it will be elevated.

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Category: Toxicology

Title: Pink Disease - Acrodynia

Keywords: mercury (PubMed Search)

Posted: 12/26/2013 by Fermin Barrueto, MD (Updated: 6/17/2024)
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Though an uncommon exposure, it can occur from chronic mercury exposure. One mode of exposure that I have seen is with elemental mercury thermometers that were broken to collect the beads of mercury - for entertainment. This occurred in a child's room and were forgotten.  One child presented with personality changes and pink hands and feet. The patient suffered from severe mercury poisoning and acrodynia due to prolonged exposure to the mercury vapor. 

Acrodynia or Pink Disease includes:

Irritability, shyness, photophobia, pink discoloration of the hands and feet and polyneuritis.


Category: Toxicology

Title: Methoxetamine - A New "Legal" High from the Internet

Keywords: ketamine, methoxetamine (PubMed Search)

Posted: 12/19/2013 by Fermin Barrueto, MD (Updated: 6/17/2024)
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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!

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Category: Toxicology

Title: Utility of Pre-4 Hour Acetaminophen Levels

Keywords: acetaminophen, Rumack-Matthew nomogram (PubMed Search)

Posted: 12/7/2013 by Bryan Hayes, PharmD (Emailed: 12/12/2013) (Updated: 12/12/2013)
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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.

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Category: Toxicology

Title: aPCC for rivaroxaban and dabigatran

Keywords: rivaroxaban, dabigatran (PubMed Search)

Posted: 11/21/2013 by Fermin Barrueto, MD (Updated: 6/17/2024)
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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.

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Category: Toxicology

Title: All Benzodiazepines are Metabolized by the Liver

Keywords: benzodiazepine, lorazepam, liver (PubMed Search)

Posted: 11/11/2013 by Bryan Hayes, PharmD (Emailed: 11/14/2013) (Updated: 11/14/2013)
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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:

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Category: Toxicology

Title: Halloween Candy - Which one is toxic?

Keywords: glycyrrhizic acid, licorice (PubMed Search)

Posted: 10/31/2013 by Fermin Barrueto, MD (Updated: 6/17/2024)
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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 !



Category: Toxicology

Title: Follow Up on Phenergan IV - Why Not IM

Keywords: promethazine (PubMed Search)

Posted: 10/25/2013 by Fermin Barrueto, MD (Updated: 6/17/2024)
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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:


Category: Toxicology

Title: Intravenous Phenergan

Keywords: Promethazine (PubMed Search)

Posted: 10/24/2013 by Fermin Barrueto, MD (Updated: 6/17/2024)
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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.


1310241854_image.jpg (29 Kb)

Drugs that cause hearing loss:

Reversible - Chloroquine, erythromycin, quinine, CO, loop diuretics, NSAIDS, ASA

Irreversible - aminoglycosides, bleomycin, vincristine, vinblastine, cisplatin, lead, mercury, arsenic

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Category: Toxicology

Title: Beware anti-NMDA receptor encephalitis mimicking NMS

Keywords: nms, neuroleptic malignant syndrome, anti-NMDAR encephalitis (PubMed Search)

Posted: 10/4/2013 by Bryan Hayes, PharmD (Emailed: 10/10/2013) (Updated: 10/10/2013)
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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.

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Category: Toxicology

Title: Which Antidiabetics are Likely to Cause Hypoglycemia in Overdose?

Keywords: hypoglycemia, overdose, diabetes, antidiabetic (PubMed Search)

Posted: 9/10/2013 by Bryan Hayes, PharmD (Emailed: 9/12/2013) (Updated: 9/12/2013)
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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


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Category: Toxicology

Title: Flecainide Toxicity

Keywords: flecainide, overdose, sodium channel (PubMed Search)

Posted: 8/29/2013 by Fermin Barrueto, MD
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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.

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Category: Toxicology

Title: Mushroom Ingestion - When Do You Worry

Keywords: Mushroom, vomiting (PubMed Search)

Posted: 8/22/2013 by Fermin Barrueto, MD (Updated: 6/17/2024)
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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).

Category: Toxicology

Title: Mythbuster: No Cross-Reactivity Between Sulfonamide Antibiotics and Non-Antibiotics

Keywords: sulfonamide, antibiotic, cross-reactivity (PubMed Search)

Posted: 8/15/2013 by Bryan Hayes, PharmD (Updated: 1/29/2014)
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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]:

  • An estimated 3-6% of the general population is allergic to sulfonamides.
  • Structurally, none of the non-antibiotic sulfonamides exhibit both of the features shown to be responsible for sulfonamide reactions (i.e., an N-containing ring attached to the N1 nitrogen of the sulfonamide group and an arylamine group at the N4 position).
  • A comprehensive literature search (1966-December 2011) identified only 9 case reports indicating possible cross-reactivity to sulfonamide medications; however, in most cases, adequate patient testing was not conducted to firmly establish either sulfa allergy or sulfonamide cross-sensitivity.

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:

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Category: Toxicology

Title: Nebulized Naloxone: What Does the Literature Say?

Keywords: naloxone, nebulized, opioid (PubMed Search)

Posted: 7/30/2013 by Bryan Hayes, PharmD (Emailed: 8/8/2013) (Updated: 8/8/2013)
Click here to contact Bryan Hayes, PharmD

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?

  • Case report of 46 y/o f with initial oxygen saturation of 61%. Naloxone was administered by nebulizer and within 5 min oxygen saturation was 100% and mental status was normal. [1]
  • Retrospective analysis of prehospital adminstration in 105 patients. 22% had "complete response" and 59% had "partial response." Problem is the initial respiratory rate was 14 bpm with GCS of 12. [2]
  • Prospective analysis of 26 patients in an inner-city, academic ED. Pre-naloxone respiratory rate was 13 with GCS of 11. Post-naloxone respiratory rate was 16 with GCS of 13. Three patients (12%) experienced moderate-to-severe agitation and 2 (8%) were diaphoretic. [3]

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.

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Category: Toxicology

Title: If bicarbonate is in short supply: what to do

Keywords: bicarbonate, acetate, TCA, salicylate, poisoning, alkalinization (PubMed Search)

Posted: 8/1/2013 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

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.



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