UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: aPCC for rivaroxaban and dabigatran

Keywords: rivaroxaban, dabigatran (PubMed Search)

Posted: 11/21/2013 by Fermin Barrueto, MD (Updated: 1/18/2022)
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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: http://academiclifeinem.com/all-benzodiazepines-are-metabolized-by-the-liver/

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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: 1/18/2022)
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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: 1/18/2022)
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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:

https://www.ismp.org/newsletters/acutecare/articles/20060810.asp

 


Category: Toxicology

Title: Intravenous Phenergan

Keywords: Promethazine (PubMed Search)

Posted: 10/24/2013 by Fermin Barrueto, MD (Updated: 1/18/2022)
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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.


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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: 1/18/2022)
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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: http://lifeinthefastlane.com/2011/04/sulfa-drug-discombobulation/

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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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Category: Toxicology

Title: Tihkal - What does that mean

Keywords: lsd, alpha-methyltryptamine, AMT (PubMed Search)

Posted: 7/18/2013 by Fermin Barrueto, MD (Updated: 1/18/2022)
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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


Category: Toxicology

Title: Highlights from the new Salicylate Toxicity Management Guideline

Keywords: salicylate, aspirin, toxicity, sodium bicarbonate (PubMed Search)

Posted: 7/10/2013 by Bryan Hayes, PharmD (Emailed: 7/11/2013) (Updated: 7/11/2013)
Click here to contact Bryan Hayes, PharmD

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:

  • Continuous IV infusion of sodium bicarbonate is indicated even in the presence of mild alkalemia from the early respiratory alkalosis.
  • Euvolemia is important.
  • If intubation is required, administration of sodium bicarbonate by IV bolus at the time of intubation in a sufficient quantity to maintain a blood pH of 7.45-7.5 over the next 30 minutes is a reasonable management option during this critical juncture.
  • Once airway control has been established, it is imperative that the increased minute ventilation and low PCO2 usually seen with salicylate intoxication are maintained.
  • A salicylate concentration approaching 100 mg/dL warrants consideration of hemodialysis in the acute toxicity setting (40 mg/dL for chronic toxicity). Consult nephrology well before these threshold levels.

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) 


Category: Toxicology

Title: Sotalol - watch out, review med list

Keywords: sotalol, torsade de pointes (PubMed Search)

Posted: 6/27/2013 by Fermin Barrueto, MD (Updated: 1/18/2022)
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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.

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Category: Toxicology

Title: Effect of N-Acetylcysteine on Prothrombin Time and Coagulation Factors

Keywords: acetylcysteine, NAC, INR, PT, prothrombin time (PubMed Search)

Posted: 6/12/2013 by Bryan Hayes, PharmD (Emailed: 6/13/2013) (Updated: 6/13/2013)
Click here to contact Bryan Hayes, PharmD

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.

  1. N-acetylcysteine has been shown to slightly increase the PT) by up to 3.5 seconds in healthy volunteers.
  2. A more recent study by the same authors demonstrated a reduction in vitamin K-dependent clotting factor activity (II, VI, IX, and X) after NAC administration in healthy volunteers.

Clinical Practice Pearls

  • The elevation in PT/INR after NAC administration is real, not simply laboratory interference.
  • However, the PT/INR elevation and decrease in coagulation factors is modest and not likely clinical signficant.
  • Many poison center guidelines allow for an INR up to 2 to be considered 'normal' to account for this phenomenon in this setting.

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Category: Toxicology

Title: Opioid Induced Hyperalgesia

Keywords: Opioid, methadone, pain management, tolerance, analgesia (PubMed Search)

Posted: 6/6/2013 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

 
  • Opioid analgesia can actually INCREASE sensitivity to pain in some cases
  • The exact cause is unclear, but may be due to up-regulation of NDMA receptors in spinal cord dorsal horn neurons
  • Pain tends to be DIFFERENT and DIFFUSE from the underlying condition for which the narcotics were prescribed
  • Switching from shorter acting opiates to methadone may be effective, as it is a weak NDMA antagonist and has only partial cross tolerance with other opioids

 

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Category: Toxicology

Title: DKA Deaths Due to 2nd Generation Antipsychotics

Keywords: quetiapine, olanzapine, risperidone (PubMed Search)

Posted: 5/30/2013 by Fermin Barrueto, MD (Updated: 1/18/2022)
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Hyperglycemia in the setting of antipsychotic use has been reported mostly with olanzapine (Zyprexa) but does occur with other antipsychotics. A recent study from the NYC medical examiner's office details 17 deaths of DKA due to antipsychotics and found that (from highest to lowest incidence) quetiapine > olanzapine > risperidone were the atypical antipsychotics found with these deaths.

Remember hyperglycemia occurs with patients on antipsychotics and can lead to hyperglycemia hyperosmolar coma or DKA. Both can be lethal.

 

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Category: Toxicology

Title: Lipid Emulsion Therapy - Increasing Evidence

Keywords: intralipid, arrest, lipid (PubMed Search)

Posted: 5/23/2013 by Fermin Barrueto, MD (Updated: 1/18/2022)
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Utilizing 20% lipid emulsion at a dose of 1.5 mL/kg (100 mL Bolus) IV with repeat in 15 minutes in no response is being recommended in patients hemodynamic instabiity due to poisoning.

Probably more effective in lipophilic drugs is a current theory for the mechanism of action - the "lipid sink". The idea is that the lipids envelope the drug pulling it off its receptors or sequestering it in the intravascular space. A recent paper has added another mechanism - direct inotropic and lusiptropic effects.(1)

Also, if you think the therapy is experimental, think again. Another recent paper surveyed Poison Control Centers and found 30/45 Poison Centers in the US have a defined protocol for utilization of lipid emulsion therapy. The PCCs are recommending it more.(2)

What was once considered just a purely experimental therapy only used at the very end of code is becoming more mainstream. Comfort with its safety profile and anectodotal effiicacy continues to mount.

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