Category: Toxicology
Keywords: rivaroxaban, dabigatran (PubMed Search)
Posted: 11/21/2013 by Fermin Barrueto, MD
(Updated: 3/22/2023)
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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.
1) Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011 Oct 4;124(14):1573-9. 2) Pernod G, Albaladejo P, Godier A, Samama CM, Susen S, Gruel Y, Blais N, Fontana P, Cohen A, Llau JV, Rosencher N, Schved JF, de Maistre E, Samama MM, Mismetti P, Sié P; Working Group on Perioperative Haemostasis. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP) - March 2013. Arch Cardiovasc Dis. 2013 Jun-Jul;106(6-7):382-93.
Category: Toxicology
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/
Mihic SJ, Harris RA. Chapter 17. Hypnotics and Sedatives. In: Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12nd ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=16663643. Accessed November 7, 2013.
Lee DC, Ferguson KL. Chapter 74. Sedative-Hypnotics. In: Lee DC, Ferguson KL, eds.Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=6520459. Accessed November 7, 2013.
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Category: Toxicology
Keywords: glycyrrhizic acid, licorice (PubMed Search)
Posted: 10/31/2013 by Fermin Barrueto, MD
(Updated: 3/22/2023)
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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
Keywords: promethazine (PubMed Search)
Posted: 10/25/2013 by Fermin Barrueto, MD
(Updated: 3/22/2023)
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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
Keywords: Promethazine (PubMed Search)
Posted: 10/24/2013 by Fermin Barrueto, MD
(Updated: 3/22/2023)
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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.
Category: Toxicology
Keywords: Hearing loss (PubMed Search)
Posted: 10/17/2013 by Fermin Barrueto, MD
(Updated: 3/22/2023)
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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
Adapted from Goldfranks Toxicological Emergencies 8th ED, p. 344
Category: Toxicology
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)
Click here to contact Bryan Hayes, PharmD
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.
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis: an etiology worth considering in the differential diagnosis of delirium. Clin Toxicol 2013;51(8):794-7. [PMID 23962100]
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Category: Toxicology
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 |
Bosse GM. Chapter 48. Antidiabetics and Hypoglycemics. In: Bosse GM, ed. Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=6514172. Accessed September 10, 2013.
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Category: Toxicology
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.
1: Cabrera Ortega M, Gell Aboy J, Díaz Berto E, Monagas Docasal V. [Acute flecainide overdose]. An Pediatr (Barc). 2011 Jan;74(1):56-8. 2: Martínez-Mateo V, Arias MA, Rodríguez-Padial L. [Brugada electrocardiographic pattern elicited by flecainide overdose]. Med Clin (Barc). 2011 Mar 19;136(7):320.
Category: Toxicology
Keywords: Mushroom, vomiting (PubMed Search)
Posted: 8/22/2013 by Fermin Barrueto, MD
(Updated: 3/22/2023)
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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
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]:
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
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?
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.
1. Mycyk MB, et al. Nebulized naloxone gently and effectively reverses methadone intoxication. J Emerg Med 2003;24(2):185-7. [PMID 12609650]
2. Weber JM, et al. Can nebulized naloxone be used safely and effectively by emergency medical services for suspected opioid overdose? Prehosp Emerg Care 2013;16(2):289-92. [PMID 22191727]
3. Baumann BM, et al. Use and efficacy of nebulized naloxone in patients with suspectd opioid intoxication. Am J Emerg Med 2013;31(3):585-8. [PMID 23347721]
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Category: Toxicology
Keywords: bicarbonate, acetate, TCA, salicylate, poisoning, alkalinization (PubMed Search)
Posted: 8/1/2013 by Ellen Lemkin, MD, PharmD
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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.
Neavyn MJ, Boyer EW, Bird SB, Babu KM. Sodium Acetate as a Replacement for Sodium Bicarbonate in Medical Toxicology: a Review. Published online 30 April 2013. J. Med. Toxicol.
Category: Toxicology
Keywords: lsd, alpha-methyltryptamine, AMT (PubMed Search)
Posted: 7/18/2013 by Fermin Barrueto, MD
(Updated: 3/22/2023)
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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
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:
The full document can be accessed here.
The Poison Review blog by Dr. Leon Gussow discusses the guidance document here.
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Category: Toxicology
Keywords: sotalol, torsade de pointes (PubMed Search)
Posted: 6/27/2013 by Fermin Barrueto, MD
(Updated: 3/22/2023)
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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.
Assessment of sotalol prescribing in a community hospital: opportunities for clinical pharmacist involvement. Finks SW, Rogers KC, Manguso AH. Int J Pharm Pract. 2011 Aug;19(4):281-6.
Category: Toxicology
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.
Clinical Practice Pearls
1. Pizon AF, et al. The in vitro effect of n-acetylcysteine on prothrombin time in plasma samples from healthy subjects. Acad Emerg Med 2011;18:351-4. [PMID 21496136]
2. Jang DH, et al. In vitro study of n-acetylcysteine on coagulation factors in plasma samples from healthy subjects. J Med Tox 2013;9:49-53. [PMID 22733602]
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Category: Toxicology
Keywords: Opioid, methadone, pain management, tolerance, analgesia (PubMed Search)
Posted: 6/6/2013 by Ellen Lemkin, MD, PharmD
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Gussow, L. Toxicology Rounds. When Opioids Increase Pain. Emergency Medicine News Feb 2013. 35(2):6.
Category: Toxicology
Keywords: quetiapine, olanzapine, risperidone (PubMed Search)
Posted: 5/30/2013 by Fermin Barrueto, MD
(Updated: 3/22/2023)
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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.
Fatal Diabetic Ketoacidosis and Antipsychotic Medication.
Ely SF, Neitzel AR, Gill JR.
J Forensic Sci. 2012 Dec 27. doi: 10.1111/1556-4029.12044.
Category: Toxicology
Keywords: intralipid, arrest, lipid (PubMed Search)
Posted: 5/23/2013 by Fermin Barrueto, MD
(Updated: 3/22/2023)
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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.
1. Fettiplace MR, Ripper R, Lis K, Lin B, Lang J, Zider B, Wang J,
Rubinstein I, Weinberg G. Rapid Cardiotonic Effects of Lipid Emulsion
Infusion. Crit Care Med. 2013 Mar 25. [Epub ahead of print]
2. Christian MR, Pallasch EM, Wahl M, Mycyk MB. Lipid Rescue 911: Are
Poison Centers Recommending Intravenous Fat Emulsion Therapy for
Severe Poisoning? J Med Toxicol. 2013 May 10. [Epub ahead of print]