UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: Drug-Induced Autoimmune Thrombocytopenia

Keywords: thrombocytopenia, sulfa, bactrim (PubMed Search)

Posted: 6/28/2012 by Fermin Barrueto, MD (Updated: 6/19/2024)
Click here to contact Fermin Barrueto, MD

Though an uncommon event, Drug-Induced Autoimmune thrombocytopenia occurs in a variety of drugs. Having recently diagnosed a patient that was receiving the "double-dose" bactrim for an MRSA abscess, it is worth mentioning the other drugs that have been reported to do it. Platelet count can go down to lethal levels and result in death due to the coagulopathy. Treatment is effective with platelets and no contraindication like in TTP.

Drugs that have been reported to do it:

abciximab, acetaminophen, amiodarone, amphotericin B

Carbamazepine, danazol, diclofenac, digoxin

Methyldopa, procainamide

Rifampin, trimethoprim-sulfamethoxazole, vancomycin



Category: Toxicology

Title: Transplant Drugs - Cyclosporine and Tacrolimus

Keywords: transplant, cyclosporine, tacrolimus (PubMed Search)

Posted: 6/21/2012 by Fermin Barrueto, MD (Updated: 6/19/2024)
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Transplant patients are the norm now in the ED. Their drug lists are immense and are usually on some form of immunosuppression to prevent rejection of the transplanted organ. Two common medications are cyclosporine and tacrolimus. They share many adverse effects like hepatotoxicity, nephrotoxicity and hypertension. Here is the mechanism of action and some unique adverse effects to these powerful immunosuppressants (there are many more so be wary):

1) Cyclosporine - suppresses T-cell activation and growth. Unique toxicity - painful neuropathy of the fingertips and toes, cortical blindness

2) Tacrolimus - simiar to cyclosporine but actually hampers T-cell communication/signal transduction. Unique toxicity - can also cause cortical blindness but is also known to cause diabetes/hyperglycemiad



Category: Toxicology

Title: Azithromycin and the Risk of Cardiovascular Death

Keywords: azithromycin, cardiovascular, death (PubMed Search)

Posted: 6/12/2012 by Bryan Hayes, PharmD (Emailed: 6/14/2012) (Updated: 6/15/2012)
Click here to contact Bryan Hayes, PharmD

  • Several macrolide antibiotics can cause QTc prolongation and dysrhythmias (e.g., erythromycin), but azithromycin is thought to have little cardiotoxicity.
  • A cohort of patients taking azithromycin was compared to those taking no antibiotics, amoxicillin, ciprofloxacin, or levofloxacin.
  • When compared to no antibiotics, amoxicillin, and ciprofloxacin, azithromycin was associated with a small but significant increased risk of cardiovascular death. Azithromycin was similar to levofloxacin.
  • Important points:
    • Increased risk translates to 47 additional deaths per 1 million prescriptions.
    • Increased risk only occurs during the 5 day course and does not carry on after discontinuation.
    • Patients most likely to die were in the highest risk category based on preexisting cardiovascular diseases (245 deaths per 1 million prescriptions).
  • Bottom line: Patients may start asking about this study finding when given a prescription for azithromycin. Although a small risk, it may be prudent to prescribe an alternative if patients have preexisting cardiovascular disease.

 

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Category: Toxicology

Title: Vitamin K: not necessary for INR 4.5 to 10?

Keywords: Warfarin,vitamin K,coagulation,INR,supratherapeutic (PubMed Search)

Posted: 6/7/2012 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

It may not be necessary to give oral vitamin K to patients that are not bleeding that have INRs between 4.5 and 10.

Patients who were supratherapeutic on warfarin were randomized to vitamin K 1.25 mg (n=355) versus placebo (n=369).

In the 90 days after enrollment, 15.8% of patients allocated to vitamin K and 16.3% allocated to placebo had a bleeding event. Major bleeding events occurred in 9 patients in the vitamin K group and 4 in the placebo.

Thromboembolic events occurred in 1.1% of patients in the vitamin K group, compared to 0.8% of patients in the placebo group. An equal number of patients died in each group (n=7).

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Category: Toxicology

Title: Nitrous Oxide

Keywords: Nitrous Oxide (PubMed Search)

Posted: 5/24/2012 by Fermin Barrueto, MD (Updated: 6/19/2024)
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Nitrous Oxide(N2O) is a common gas utilized to assist with procedural sedation especially in the pediatric population and dental offices. It has a long track history of safety but also has been abused.

N2O is 35x more solube in blood than N2. This means any air-filled space can have pressure increase thus complications like pneumothorax, TM rupture and bowel distention can occur.

When abused chronically can cause bone marrow suppression, B12 deficiency and resulting in polyneruopathy.

On the street, "whip its" are N2O from whipped cream containers. Balloons filled with N2O are inhaled which combine nitrous oxide and hypoxia effects.



Category: Toxicology

Title: Vitamins - Which Ones Have Toxicity?

Keywords: vitamins (PubMed Search)

Posted: 5/17/2012 by Fermin Barrueto, MD (Updated: 6/19/2024)
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More and more people are going to holistic medicine and "naturopaths". These have been an interesting source of toxicology case reports due to therapeutic misadventures. Vitamins have been an ever increasing adjunct to these health philosophies. The following are the vitamins and their related toxicity in overdose:

Vitamin A: Pseudotumor cerebri, increase ICH, hair thinning, hepatotoxicity

Vitamin D: Hypercalcemia

Vitamin E: can antagonize vitamin K particularly in vitamin K deficient people, could result in coagulopathy

Vitamin K: problem if supplement contains this and patient on coumadin, ask patient

Vitamin C: Association with increased kidney stones though controversial

 

 

 



Category: Toxicology

Title: Elevated Lactates in Ethylene Glycol Poisoning?

Keywords: lactate, lactic acid, ethylene glycol (PubMed Search)

Posted: 5/9/2012 by Bryan Hayes, PharmD (Emailed: 5/10/2012) (Updated: 6/15/2012)
Click here to contact Bryan Hayes, PharmD

  • Ethylene glycol can result in elevated lactate concentrations secondary to hypotension and organ failure in severely poisoned patients. However, lactate production by these mechanisms tends to result in serum concentrations less than 5 mmol/L.

  • Unfortunately, higher lactate levels don't necessarily rule out ethylene glycol. The glycolate metabolite causes a false-positive lactate elevation when measured by some analyzers, particularly with whole blood arterial blood gas analyzers. Specific models implicated include: ABL 625, Radiometer ABL 700, Beckman LX 20, Chiron 865, Bayer (formerly Chiron) 860, Rapidlab (Bayer) 865, Integra and to a lesser extent, Hitachi 911 analyzers, but not the Vitros 950 or Vitros 250.

  • The degree of lactate elevation directly correlates with the concentration of glycolate present, and the artifact probably results from the lack of specificity of the lactate oxidase enzyme used in these machines.

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Category: Toxicology

Title: Dexmedetomidine (Precedex)

Keywords: sedation, dexmedetomidine (PubMed Search)

Posted: 4/26/2012 by Fermin Barrueto, MD (Updated: 6/19/2024)
Click here to contact Fermin Barrueto, MD

Dexmedetomidine is an alpha2-agonist that has a similiar mechanism of action to clonidine. Short half-life and no respiratory depression make it possibly more effective than propofol in procedural sedation. Cost/Availability are the biggest barriers. Transient bradycardia is also possible but the actual incidence  of clinically significant bradycardia is not yet elucidated.

I am still awaiting the first emergency department study looking at dexmedetomidine for procedural sedation.

A recent article actually brought up the possibility of utilizing it intranasally which could have some tantalizing pediatric applications.

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Category: Toxicology

Title: Maternal Opioid Use and Breast-Fed Infants

Keywords: Opioid, breastfeeding, breast milk, newborn, infant (PubMed Search)

Posted: 4/5/2012 by Bryan Hayes, PharmD (Emailed: 4/12/2012) (Updated: 4/12/2012)
Click here to contact Bryan Hayes, PharmD

Over the last few decades, the rate of breastfeeding has increased steadily in the developed countries of the world. During this time, opioid  use in the general population has steadily increased as well. Despite this, clinicians remain unclear whether opioid use is safe during breastfeeding.

A recent article reviewed the production of breast milk, the transfer of xenobiotics from blood to milk, the characteristics that alter xenobiotic breast-milk concentrations, and the evidence of specific common opioids and infant toxicity.
 
Conclusion: The short-term maternal use of prescription opioids is usually safe and infrequently presents a hazard to the newborn.
 
 
Bonus app suggestion:
Continuing with the theme of the week, here is a nifty, free tox app for the iPhone called Emergency Toxicology. It is rudimentary and pretty basic, but it is a good starting tool.
http://itunes.apple.com/us/app/emergency-toxicology/id504893108?mt=8
iPhone Screenshot 1

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Protamine for enoxaparin overdose

  • Protamine may be used to treat severe cases of hemorrhage in enoxaparin overdose
  • Protamine reverses the prolonged aPTT, but fails to completely reverse the anti-Xa effect (reverses about 60%)
  • Administer protamine by slow IV to equal the dose of enoxaparin injected: (1:1 ratio) 
  • if < 8 hours after last dose enoxaparin, give 1 mg protamine per 1 mg enoxaparin;
  • if 8-12 hours after last dose enoxaparin, give 0.5 mg protamine per 1 mg enoxaparin;
  • if >12 hours after last dose of enoxaparin,  protamine is not required


Category: Toxicology

Title: Nebulized epinephrine for Smoke Inhalation

Keywords: epinephrine, carbon monoxide, smoke inhalation (PubMed Search)

Posted: 3/29/2012 by Fermin Barrueto, MD (Updated: 6/19/2024)
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Animal studies can pave the way for new clinical treatment modalities. In the setting of lung injury due to smoke inhalation, one of the problems (if you can get the ET tube in) are the elevated ventilatory pressures due to the massive edema. In this sheep model of smoke inhalation, nebulized epinephrine improved ventilatory pressures, PaO2/FiO2 ratio and pulmonary shunting.

We may have these sheep to thank for this new treatment.

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Category: Toxicology

Title: Had enough of coumadin and clopidogrel wannabe's?

Keywords: ticagrelor, brillinta, xarelto, pradaxa (PubMed Search)

Posted: 3/15/2012 by Fermin Barrueto, MD (Updated: 6/19/2024)
Click here to contact Fermin Barrueto, MD

Coumadin Wannabe's - have indication non-valvular atrial fibrillation

1) Dabigatran (Pradaxa) 

2) Rivaroxaban (Xarelto)

Clopidogrel Wannabe's - both are antiplatelets

1) Ticagrelor (Brilinta)

2) Prasugrel (Effient)

If you were looking for the first case reports of lethal hemorrhage due to pradaxa that could not be reversed - look no further. One patient fall from standing dies from ICH and another death in a spine trauma patient on pradaxa. I am waiting for the first epidural hematoma due to pradaxa, xarelto, etc in ED. Watch out! :

 

  1: Garber ST, Sivakumar W, Schmidt RH. Neurosurgical complications of direct  thrombin inhibitors-catastrophic hemorrhage after mild traumatic brain injury in  a patient receiving dabigatran. J Neurosurg. 2012 Mar 6.       2: Truumees E, Gaudu T, Dieterichs C, Geck M, Stokes J. Epidural Hematoma &  Intra-operative Hemorrhage in a Spine Trauma Patient on Pradaxa® [Dabigatran].  Spine (Phila Pa 1976). 2012 Feb 16. 

 



Category: Toxicology

Title: Pressure Immobilization for Crotalid snake envenomation

Keywords: crotalinae, snake, pressure immobilization, envenomation (PubMed Search)

Posted: 3/4/2012 by Bryan Hayes, PharmD (Emailed: 3/8/2012) (Updated: 3/8/2012)
Click here to contact Bryan Hayes, PharmD

Pressure immobilization involves wrapping the entire extremity with a bandage and then immobilizing the extremity with a splint. It is a technique routinely employed in the pre-hospital management of neurotoxic snakes in Australia.

A position statement was recently published by several international toxicology societies regarding the utility of pressure immobilization after North American Crotalinae snake envenomation (e.g., Copperheads, Timber rattlesnakes, Cottonmouths).

"Available evidence fails to establish the efficacy of pressure immobilization in humans, but indicates the possibility of serious adverse events arising from its use. The use of pressure immobilization for the pre-hospital treatment of North American Crotalinae envenomation is NOT recommended."

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Category: Toxicology

Title: Octreotide for sulfonylurea overdose- updated

Keywords: Octreotide, sulfonylurea, glucose, insulin (PubMed Search)

Posted: 3/1/2012 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

 

  • Sulfonyurea overdose is associated with hypoglycemia, which may be delayed and prolonged.
  • Treatment with dextrose results in hyperglycemia, which potentiates insulin release from the pancreas, resulting in recurrent hypoglycemia.
  • Octreotide mimics somatostatin, which suppresses the secretion of glucagon and insulin, among others.
  • Octreotide binds with somatostatin receptors, closing calcium channels, preventing the influx of calcium and subsequent insulin release.
  • The dose is 100 mcg SUBCUTANEOUSLY, repeated every 8 hours as needed.

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Category: Toxicology

Title: IM Midazolam vs IV Lorazepam for Seizure Pre-Hospital

Keywords: midazolam, lorazepam (PubMed Search)

Posted: 2/23/2012 by Fermin Barrueto, MD (Updated: 6/19/2024)
Click here to contact Fermin Barrueto, MD

You have seen the study comparing diazepam to lorazepam IV for the cessation of seizures. Lorazepam one that one. Now, for prehospital status epilepticus midazolam IM went head to head with IV lorazepam to see which would stop seizure more quickly.

This study was more about the practicality of starting an IV than it was of the pharmacokinetics or onset of action of a particular benzodiazepine. It was a large enough study to warrant publication in New Engl J Med last month and is worth noting.

Subjects whose seizures ceased before ED arrival (median):

Time to active treatment: 1.2 min IM Midazolam group;  4.8 min IV Lorazepam group

Median times active treatment to cessation of SZ:  3.3 min IM Midazolam and 1.6 min IV Lorazepam

Safety was equal in both groups. This study validates EMS initiating therapy with IM midazolam for the cessation of seizures while intravenous access is being attempted. 

 

 

 

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Category: Toxicology

Title: Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

Keywords: DRESS, anticonvulsant, eosinophilia, phenytoin, carbamazepine (PubMed Search)

Posted: 2/7/2012 by Bryan Hayes, PharmD (Emailed: 2/9/2012) (Updated: 2/19/2012)
Click here to contact Bryan Hayes, PharmD

  • Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, previously named “anticonvulsant hypersensitivity syndrome,” is a severe adverse drug reaction which occurs in approximately 1 of every 1,000–10,000 uses of anticonvulsants.

  • Characterized by triad of fever, rash, and internal organ involvement.

  • Usually involves aromatic anticonvulsants such as phenytoin, carbamazepine, phenobarbital, primidone, lamotrigine, and possibly oxcarbazepine.

  • DRESS occurs most frequently within the first 2 months of therapy and is not related to dose or serum concentration.

  • Treatment includes prompt discontinuation of the offending agent. Patients should be admitted to the hospital and receive methylprednisolone 0.5–1 mg/kg/d divided in four doses. Other promising therapies include use of IVIG.

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Category: Toxicology

Title: Succinylcholine

Keywords: paralytic, hyperkalemia, succinylcholine (PubMed Search)

Posted: 1/26/2012 by Fermin Barrueto, MD (Updated: 6/19/2024)
Click here to contact Fermin Barrueto, MD

As we go through the problems of national drug shortages it is important to remember the old drugs but to also remember why they became old and seldom used drugs. Prime example is many hospitals are beginning to develop shortages of rocuronium - the nondepolarizing paralytic that has a fast onset. This shortage has caused many to switch back to succinylcholine. The following case report should serve as reminder of how succinylcholine - due to its depolarizing nature and fasciculations - can cause a transient but significant hyperkalemia.

 

 

Succinylcholine-induced Hyperkalemia in a Patient with Multiple Sclerosis 
The Journal of Emergency Medicine, 12/13/2011

Levine M et al. – This case report describes a 38–year–old woman with multiple sclerosis who developed life–threatening hyperkalemia after the administration of succinylcholine during rapid sequence intubation. This case highlights the potential for iatrogenic hyperkalemia after succinylcholine in patients with neurologic diseases, including multiple sclerosis.






Category: Toxicology

Title: Pradaxa - Watch out

Keywords: pradaxa, myocardial infarction (PubMed Search)

Posted: 1/19/2012 by Fermin Barrueto, MD (Updated: 6/19/2024)
Click here to contact Fermin Barrueto, MD

Never be the first or last person to use a drug 

Vioxx was once touted to be the drug that would be the new standard for anti-inflammatories until it was found to increase your chance of MI by 33% and cause hypertension.

Dabigatran was recently pulled from Japan markets and now is dealing with an impressive meta-analysis by Uchino et al. It showed that dabigatran was significantly associated with higher risk of MI or ACS than other agents.

Control arms (included warfarin, enoxaparin or placebo): MI rate 83 per 10,514

Dabigatran arms: MI rate 237 per 20,000

OR 1.33; 95% CI, 1.03-1.71; p=0.03

The rush for what is perceived as a panaceae for all that is wrong with coumadin could actually cause an MI while it tries to prevent a stroke in nonvalvular a-fib.

Look at the study and decide for yourself and remember Vioxx:

http://archinte.ama-assn.org/cgi/content/full/archinternmed.2011.1666v1



Category: Toxicology

Title: Buprenorphine Poisoning in Children (submitted by Ashley Strobel, MD)

Keywords: buprenorphine, Suboxone, overdose, children (PubMed Search)

Posted: 1/10/2012 by Bryan Hayes, PharmD (Emailed: 1/12/2012) (Updated: 1/12/2012)
Click here to contact Bryan Hayes, PharmD

  • Suboxone = buprenorphine and naloxone in a 4:1 ratio, respectively. Formulated in 2 mg or 8mg tablets and film.

  • Buprenorphine acts as a partial agonist on the mu receptor and an antagonist at the kappa receptor.

  • If > 2 mg are ingested or age < 2 years old, these patients should be evaluated in an ED as ALL children with > 4 mg ingestion had symptoms.

  • There is a ceiling effect with respiratory depression however no ceiling with analgesia. This gives buprenorphine a better safety profile compared to methadone.

  • Onset of symptoms is about an hour and onset of respiratory depression is about 2-3 hours.

  • Increased doses of naloxone starting at 0.1 mg/kg may be needed to overcome high receptor affinity of buprenorphine. Remember, most children are opioid-naive and will not experience withdrawal symptoms. Repeat doses of naloxone and even infusions may be needed.

  • In the ED, a minimum of 6 hours observation is necessary. If no clinical effects are noted at 6 hours the patient can safely be discharged, although one small case series recommended 24 hours observation.

  • Unintentional overdose is common in toddlers, so advise family to keep prescriptions including family pet prescriptions locked (buprenorphine in the IV form is used for veterinary pain control).

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Category: Toxicology

Title: Rivaroxaban (Xarelto) - Another Pradaxa?

Keywords: pradaxa, xarelto (PubMed Search)

Posted: 12/29/2011 by Fermin Barrueto, MD (Updated: 6/19/2024)
Click here to contact Fermin Barrueto, MD

Another great example of the generic drug name being so difficult to pronounce you have no choice but to say - Xarelto. The drug touts ease of use and no need for hematologic monitoring like Pradaxa. This drug has the same indication for stroke prevention in nonvalvular atrial fibrillation. It also is being used in DVT prophylaxis in hip and knee surgeries.

Differences:

- Selective Factor Xa inhibitor unlike Pradaxa which is a competetive direct thrombin inhibitor

- Once a day dosing instead of twice a day for Pradaxa

Same concerns:

- No real reversal but can use FFP in a pinch

- Recommend waiting 24 hrs DC med to perform surgical procedure - this includes LP. I am personally waiting for the first case report of LP performed in ED on a patient taking either Xarelto or Pradaxa with subsequent epidural hematoma. Someone is bound to miss this on the med list. Be careful.

Even if your hospital has not added it to its formulary, you will see patients on this drug in the ED.