UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: Radiation and potassium iodide

Keywords: radiation, iodide, KI, thyroid, iodine-131 (PubMed Search)

Posted: 4/7/2011 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

·      In the event a nuclear power plant accident, people may be exposed to a mixture of radioactive products. The main radionuclides representing health risk are radioactive caesium and radioactive iodine.

·      Iodine-131 is concentrated in the thyroid gland and may eventually lead to development of thyroid nodules and thyroid cancer.

·      Radioiodine uptake by the thyroid can be blocked by taking potassium iodide (KI) pills or solution, preventing these effects.

·      KI should not be taken in the absence of a clear risk of exposure to a potentially dangerous level of radioactive iodine because KI can cause allergic reactions, skin rashes, salivary gland inflammation, hyperthyroidism or hypothyroidism.

·      Since radioactive iodine decays rapidly, current estimates indicate there will not be a hazardous level of reaching the United States from this accident.

·      There are three FDA approved KI products: Iosat, Thyrosafe and ThyroShield.

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Category: Toxicology

Title: Extravasation Injuries

Keywords: phenytoin, vinca alkaloids, (PubMed Search)

Posted: 3/31/2011 by Fermin Barrueto, MD (Updated: 1/18/2022)
Click here to contact Fermin Barrueto, MD

Extravasation from radiocontrast, phenytoin and promethazine have resulted in significant tissue necrosis sometimes requiring surgical debridement and reconstructive plastic surgery. 

Pearl: Keep the infiltrated peripheral IV in and inject hyaluronidase 3-5mL (150U/mL) into the same subcutaneous pocket of medication. Hyaluronidase will increase the systemic absorption of the drug, decreasing its time in the SQ tissue. Extremely safe drug (we have the enzyme in our body) and has been used in neonates as well as adults. Also used for SQ hydration in palliative care and pediatrics.

Controversy: Hot vs Cold - Heat will cause vasodilation and hopefully increase systemic absorption but will likely also increase SQ spread possibly increasing the surface area of injury. Cold will cause vasoconstriction and decrease size of injury however will concentrate drug and possibly worsen the local injury.

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Category: Toxicology

Title: DVT/PE and Antipsychotics

Keywords: antipsychotics, thromboembolism (PubMed Search)

Posted: 3/24/2011 by Fermin Barrueto, MD
Click here to contact Fermin Barrueto, MD

Could this be another risk factor for DVT/PE. Maybe not yet but it is worth mention. A recent observatioal study in BMJ showed that there was  an associated increase with DVT or PE. From a database of 25,532 patients over a 3 year period of time and finding match controls, the results were:

  1. 32% overall increase risk of DVT/PE in patient who were taking antipsychotics
  2. Recent initiation of therapy within 3 months increased risk 2-fold
  3. Risk was greater with atypical antipsychotics (Odds Ratio 1.73 Atypical vs 1.23 Old)
  4. Risk was greater with lower dose than higher dose

Limitations were this is was an observational study with missing data. BMI was missing in these records and it is always difficult to tease out the multiple medications these patients are on.  Also don't have a great biological mechanism (yet). Still makes you go hmm....

 

Antipsychotic drugs and risk of venous thromboembolism, Parker, BMJ, 2010.


Category: Toxicology

Title: Rocuronium vs Succinylcholine

Keywords: rocuronium, succinylcholine (PubMed Search)

Posted: 3/17/2011 by Fermin Barrueto, MD (Updated: 1/18/2022)
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Most have converted from succinylcholine to rocuronium for their choice of paralytic in RSI. Succinylcholine-induced hyperkalemia secondary to muscle fasciculations is considered usually clinically insignificant though there may be a hyperkalemic renal patient that this may tip them over. The fasciculations also may worsen traumatic long bone fractures.  Here is the argument in a head to head comparison:

 

 

Succinylcholine 

Rocuronium   Winner  
Onset 1-1.5min 1.5-3min

Tie

Duration

Recovery Index

3-7min

2min

 

30-40min

10min

Mild S

Fasciculations

Yes No Roc

Histamine 

Yes - Released None Roc
Pulse Rare Brady

Rare Tachy at high dose

Tie

Duration = injection of drug to 25% recovery of single twitch height (clinically relevant recovery in ED - essentially breathing may return)

Recovery Index = time from 25% to 75% recovery of single twitch height

The main reason succinylcholine was utilized was because of its fast onset and short duration. Rocuronium is comparable enough to succinylcholine in these characteristics tilting the overall benefits to rocuronium. If the FDA ever approves it, suggamadex is a possible reversal agent for rocuronium - currently used in Europe. Imagine having that in your RSI kit.
 


Category: Toxicology

Title: Xenobiotics That Cause Unusual or Idiosyncratic Reactions in Children

Keywords: benzyl alcohol, clonidine, ethanol, chloramphenicol (PubMed Search)

Posted: 3/9/2011 by Bryan Hayes, PharmD (Emailed: 3/10/2011) (Updated: 3/10/2011)
Click here to contact Bryan Hayes, PharmD

Several medications/chemicals can cause unique toxicologic reactions in pediatric patients.

  • Ethanol: hypoglycemia.  Reported with ethanol levels as low as 20 mg/dL.
  • Clonidine and imidazolines: central nervous system effects.  Agents such as tetrahydrozoline, oxymetazoline, naphazoline, and clonidine can cause CNS depression, respiratory depression, bradycardia, miosis, and hypotension.
  • Benzyl alcohol: gasping syndrome.  Preservative which has been removed from most medications and IV flush solutions used in neonates.  Syndrome includes severe metabolic acidosis, encephalopathy, respiratory depression, and gasping.
  • Chloramphenicol: gray baby syndrome.  Broad-spectrum antibiotic not used frequently in U.S.  Syndrome includes abdominal distension, vomiting, metabolic acidosis, progressive pallid cyanosis, irregular respirations, hypothermia, hypotension, and vasomotor collapse.

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Category: Toxicology

Title: Spider bite

Keywords: Brown Recluse,envenomation,spider,loxoscelism (PubMed Search)

Posted: 3/3/2011 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

 

Recently a case report was published in which a child was incorrectly diagnosed with MRSA. He actually had systemic loxoscelism from a Brown Recluse spider bite.

A patient who has been bitten by brown recluse spider bite may present with pruritis, pain and swelling. The classic lesion has a bluish-purple central region, surrounded by concentric rings of pale ischemia and erythema. (“red, white and blue”) Bites may progress over days to a bleb with necrosis and eschar formation, followed by ulceration.

Systemic loxoscelism presents with a scarlatiniform rash that spreads dependently. It may have the classic purple lesion surrounded by concentric rings of pale ischemia and erythema. The patient may be uncomfortable but is usually stable. Treatment is supportive care.

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Category: Toxicology

Title: Bath Salts

Keywords: mephedrone, bath salts (PubMed Search)

Posted: 2/24/2011 by Fermin Barrueto, MD (Updated: 1/18/2022)
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Continuing with the synthetic/designer drug theme. Last time we were discussing synthetic marijuana.  Another old drug making a resurgence under the designer drug category is mephedrone.This amphetamine-like drug has been purportedly the active substance in "bath salts". It has also been sold as "plant food" - still trying to figure that one out.

Sold in head shops under the name Bliss or Cloud 9 - they have been reported to be available in Baltimore, MD recently. They can also be bought over the internet. Crushed, snorted or ingested, the effect is similiar to cocaine with a largely sympathomimetic toxidrome. Mephedrone has been labeled an entactogen with users behaving similiar to an MDMA ingestion. A Baltimore news station incorrectly called it "synthetic cocaine" - though the effect may be similiar, completely different molecular structure.

Treatment is cooling, check lytes (especially sodium), check for rhabdomyolysis and sedation with benzodiazepines. Below is one link from a Denver News Station. Attached is a picture of a bath salt product.

The latest and greatest on the street - synthetic marijuana and bath salts!

http://www.thedenverchannel.com/news/26567376/detail.html


Attachments

bath-salts.jpg (38 Kb)


Category: Toxicology

Title: Synthetic Marijuana - What is it?

Keywords: THC, marijuana (PubMed Search)

Posted: 2/18/2011 by Fermin Barrueto, MD (Updated: 1/18/2022)
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Sold under the name of K2, Spice. Patients exposed to this will present with dry mouth, paranoia, tachycardia, hallucinations but will resolved rather quickly over several hours. Observation in the ED and supportive care is usually all that is needed. A little history about synthetic marijuana:

 

  • JWH-018 is a synthetic cannabinoid (SC) that acts at cannabinoid receptors.
  • Synthetic cannabinoids were created s in the 1960’s and continued to be developed as appetite stimulants (e.g., dronabinol).
  • The JWH series of SCs are named for the chemist who first synthesized them, John W. Huffman, Ph.D. (thus the JWH prefix).
  • SCs recently appeared for sale in smoke shops and other outlets (such as gas stations) as herbal incense.
  • These products contain plant material that mimics smell and appearance of marijuana but is adulterated with one or more SCs.

Attachments

Spice_drug.jpg (558 Kb)


Category: Toxicology

Title: Historical Figures in Toxicology: Paracelcus

Keywords: dose-response, paracelsus (PubMed Search)

Posted: 1/26/2011 by Bryan Hayes, PharmD (Emailed: 2/10/2011) (Updated: 2/10/2011)
Click here to contact Bryan Hayes, PharmD

Many consider Paracelsus (1493–1541) as the father of modern toxicology.

  • He was the first to emphasize the chemical nature of toxic agents.
  • He stressed the need for proper observation and experimentation regarding the true response to chemicals.
  • He underscored the need to differentiate between the therapeutic and toxic properties of chemicals when he stated in his Third Defense, "What is there that is not poison? All things are poison and nothing [is] without poison. Solely, the dose determines that a thing is not a poison."

The introduction of the dose–response concept might have been his most important contribution to toxicology, meaning that everything is toxic at the right dose (even oxygen and water).


Category: Toxicology

Title: Methemoglobinemia

Keywords: Methemoglobinemia,methylene blue (PubMed Search)

Posted: 2/3/2011 by Ellen Lemkin, MD, PharmD (Updated: 1/18/2022)
Click here to contact Ellen Lemkin, MD, PharmD

 

Suspect methemoglobinemia if you have a patient with persistent cyanosis, tachypnea, low pulse oximetry, and a lack of response to 100% oxygen therapy, or an elevated PaO2 on ABG and a low O2 sat on pulse ox.
 
Methemoglobin results from exposure to chemicals that oxidize the ferrous iron in hemoglobin to the ferric state, resulting in a functional anemia.  Usually a low level is reduced back to hemoglobin by cytochrome b5, NAD, G6PD, and glutathione reduction enzyme systems.  
 
Diagnose by confirmed by a methemoglobin level, although the most convenient and rapid test of choice is multiple wave co-oximetry. (not the standard 2 wave pulse ox).
 
Treat if they are symptomatic; use methylene blue, 1 mg/kg slow push. Patients should improve in one hour. Use with extreme caution in patients with G6PD disease (if at all).
 

Category: Toxicology

Title: Dabigatran (Pradaxa) concerns

Keywords: Dabigatran, anti-coagulation, toxicology, coumadin (PubMed Search)

Posted: 1/27/2011 by Fermin Barrueto, MD
Click here to contact Fermin Barrueto, MD

 

Dabigatran (Pradaxa), an antithrombin medication, was discussed in an earlier pearl and thought I would play devil's advocate and explain the possible concerns:

  • Yes you don't need INRs to evaluate therapeutic levels but the problem is also don't know if its subtherapeutic or supratherapeutic. This can be an issue during times of transition fromLWMH or coumadin. There are specific protocols to follow for "bridging".
  • Though not clinically significant, there was an increase in myocardial infarction in thedabigatran (Pradaxa) group when compared to coumadin - remember vioxx?
  • FDA approved dabigatran for stroke prevention, embolism, in AF patients. Though people will automatically translate all of the indications coumadin has that cannot be done yet.
  • No reversal agent so in an acute (ED) setting, you are in trouble and are depending on the relatively short half-life to get you out of trouble.

Toxicology Mantra: You never want to be the first person or the last person to use a drug


Category: Toxicology

Title: Utility of the Rumack-Matthew Nomogram

Keywords: acetaminophen, rumack-matthew nomogram (PubMed Search)

Posted: 1/13/2011 by Bryan Hayes, PharmD
Click here to contact Bryan Hayes, PharmD

The Rumack-Matthew nomogram is a well studied and validated tool to help assess the potential for liver toxicity following acute acetaminophen poisoning.  Here is a brief review of when it is best utilized.

  • Prior to 4 hours post-ingestion: Not helpful to determine likelihood for toxicity.  Only use is to confirm an ingestion took place.
  • Between 4 and 24 hours post-ingestion: Plot the patient's level vs. time after ingestion.  If above the toxicity line, treat with acetylcysteine.
  • More than 24 hours post-ingestion: Any elevated acetaminophen level is toxic and should be treated with acetylcysteine.

Outside-the-box situations:

  • Chronic exposures: Nomogram not indicated.
  • Overdoses with co-ingestants that slow GI motility (e.g., opioids, diphenhydramine) OR extended release products (e.g., Tylenol Arthritis): If the level at 4 hours post-ingestion is not toxic, repeat it at 8 hours post-ingestion.  If either level is toxic, treat with acetylcysteine.

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Category: Toxicology

Title: Intravenous vitamin K1

Keywords: Vitamin K1,anaphylaxis,coumadin,warfarin (PubMed Search)

Posted: 1/6/2011 by Ellen Lemkin, MD, PharmD (Updated: 1/18/2022)
Click here to contact Ellen Lemkin, MD, PharmD

  • Vitamin K can be used intravenously for management of the NON bleeding patient with a high INR (>9).
  • Although anaphylactoid reactions have been described, most cases occurred with large doses of vitamin K, administered rapidly, and with little dilution.
  • It is estimated that the incidence of anaphylaxis is 3:10,000 doses.
  • The subcutaneous route of administration is not recommended because of its delayed and unpredictable responses.

 

 

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Category: Toxicology

Title: Naloxone - Any Port In the Storm

Keywords: naloxone, opioids (PubMed Search)

Posted: 12/30/2010 by Fermin Barrueto, MD (Updated: 1/18/2022)
Click here to contact Fermin Barrueto, MD

Naloxone is the epitomy of an antidote with complete reversal of opioid toxicity within 60 seconds of administration. Remember your clinical endpoint should be respiratory effort. If you utilize "the vial" of either 0.4mg or 2mg and there is a higher probability of withdrawal and for acute lung injury. Here are some tips for administration:

1) IV Access: Try 0.1 mg or even 0.05 mg - anesthesiology typically doses naloxone in micrograms. Reversal is slower so you have to be patient. It is also not as dramatic so closely monitor respirations to see if you have improvement, that may be all that you get. These are probably patients that you don't want that awake anyways.

2) No IV Access: advantage of naloxone is it is bioavailable IV, intranasal and even by nebulizer.  Here you want the dose to be 0.4mg to start for intranasal. Nebulizer is difficult to measure and probably safe to start with 2mg in the nebulizer container.

There is a difference when you know it is an opioid overdose and are reversing apnea versus a diagnostic administration to determine if it is opioid toxicity. In the latter instance you can rationalize the large dose - just be ready and be sure you are not in line of the possible projectile vomiting.

 


Category: Toxicology

Title: Hydrofluoric Acid Burn

Keywords: HF (PubMed Search)

Posted: 12/23/2010 by Fermin Barrueto, MD (Updated: 1/18/2022)
Click here to contact Fermin Barrueto, MD

When you think of an acid or base causing a burn, you usually think of the local damage but there is one particular acid that causes systemic illness. Hydrofluoric Acid, found in your local Home Depot in brick/stone cleaning products, can cause severe illness despite a small total body surface area burn and exposure. A recent case report came out that illustrates how deadly HF can be. The reason is that this acid enters the body and chelates cations like calcium and potassium. The abstract is below but essentially hypocalcemia, hypokalemia leading to asystole 16hrs after exposure all from a 3% TBSA Burn - very impressive.

 

Background. Although hydrofluoric (HF) acid burns may cause extensive tissue damage, severe systemic toxicity is not common after mild dermal exposure. Case. A 36-year-old worker suffered a first-degree burn of 3% of his total body surface area as a result of being splashed on the right thigh with 20% HF acid. Immediate irrigation and topical use of calcium gluconate gel prevented local injury. However, the patient developed hypocalcemia and hypomagnesemia, hypokalemia, bradycardia, and eventually had asystole at 16 h post-exposure, which were unusual findings. He was successfully resuscitated by administration of calcium, magnesium, and potassium. Conclusion. This report highlights a late risk of HF acid dermal exposure.

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Category: Toxicology

Title: Fomepizole - Answer to Tox Pearl

Keywords: fomepizole, disulfiram (PubMed Search)

Posted: 12/17/2010 by Fermin Barrueto, MD (Updated: 1/18/2022)
Click here to contact Fermin Barrueto, MD

The answer was fomepizole would be the treatment for life-threatening disulfiram reaction. Blocks Alcohol Dehydrogenase and ironically prevent metabolism of ethanol and prolong intoxication.

I forgot how many see the pearls and the response was overwhelming. That was great and cost a me a little more. There were two winners:

Katie Baugher, PGY-1

Ari Keslter

Please email me how to best send you the gift certificate.

 


Category: Toxicology

Title: Can I drink Alcohol with this Med?

Keywords: disulfiram reaction (PubMed Search)

Posted: 12/16/2010 by Fermin Barrueto, MD (Updated: 1/18/2022)
Click here to contact Fermin Barrueto, MD

There are medications, if taken with ethanol, will cause a disulfiram reaction. This reaction results from inhibition of aldehyde dehydrogenase, the enzyme in ethanol metabolism that breaks acetaldehyde to acetic acid. The increase in acetaldehyde results in nausea, vomiting, diarrhea, flushing, palpitations and orthostatic hypotension. So if you prescribe a patient with any of these medications you must make certain to tell them NOT to drink any ethanol - that includes cough/cold preparations that have ethanol:

Antibiotics: Metronidazole(Flagyl), Trimethoprim-sulfamethoxazole (Bactrim)

Sulfonylureas: Chlorpropamide and tolbutamide

These have possible reactions: griseofulvin, quinacrine, procarbazine, phentolamine, nitrofurantoin

 

Bonus Question: $10 Starbuck's Gift Card for  first person that emails me with the answer to this question

What treatment could you give to someone suffering from a life threatening disulfiram reaction that biochemically should cure him? 


Category: Toxicology

Title: Toxin-Induced Causes of a Normal Anion Gap Metabolic Acidosis

Keywords: anion gap, metabolic acidosis (PubMed Search)

Posted: 12/8/2010 by Bryan Hayes, PharmD (Emailed: 12/9/2010) (Updated: 12/9/2010)
Click here to contact Bryan Hayes, PharmD

Most cases of normal anion gap metabolic acidosis result from either urinary (RTA) or gastrointestinal HCO3- losses (diarrhea).  A number of xenobiotics can also cause this disorder:

  1. Acetazolamide
  2. Acidifying Agents: Ammonium chloride, arginine hydrochloride, hydrochloric acid, lysine hydrochloride
  3. Cholestyramine
  4. Toluene
  5. Topiramate (Topamax)

Category: Toxicology

Title: Toxic Holiday Plants

Keywords: holly, berry, poinsettia, mistletoe, berries (PubMed Search)

Posted: 12/2/2010 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

Toxic Holiday Plants

Of the three plants listed, which is NOT poisonous?

1.     Holly plant

2.     Poinsettia

3.     Mistletoe

 

Poinsettia plants were once thought to be very poisonous. Contrary to popular belief, poinsettias are safe to have in the home during the holidays.

Although there are reported cases of death with ingestion of Holly plants in older literature, recent experience shows gastrointestinal effects in small doses, and serious toxicity such as CNS depression in large ingestions.

Mistletoe ingestion of few of the berries would, at most, produce mild gastroenteritis; however, ingesting concentrated extracts of the plant, including the berries, may produce serious effects such as seizures, mental confusion, drowsiness, and hallucinations.

Happy holidays!

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As we eat our turkey today and the myth that we are tired because of the tryptophan content is propagated further - nothing to do with the 2000kcals that we just ate - I would like to share an interesting and controversial study. 

Use of stimulants and and sedatives by EM residents. Incidence is as follows:

In a study of 485 residents with 47% response rate:

Prescription Stimulants: 3.1%

Sleep Aids (all):  89%

Use of Nonbenzodiazepines (zolpidem): 14%

Use of Melatonin: 10%

Benzodiazepines: 9%

Difficult job with difficult hours. What is the appropriate medication or is there a medication that truly assists with performance? Are they doing harm to themselves? to patients?

Disrupted circadian rhythm, addiction tendencies and the hardship of a stressful nightshifts are the price we pay for this specialty. Awareness and education are needed for the residents as well as the attendings.

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