≡ Menu

Hi-Yield Tox Flashcards

Flashcards aid in memory repetition of difficult to memorize things that may show up on boards and in-service exam. This list will grow as I distill my readings and notes into only the highest yield memorization points.

note: all images used are public domain, unless otherwise cited within the flashcard

Iron(II,III) hexacyanoferrate(II,III)
File:HexacyanidoferratIII 2.svg
Click to View the Answer
Click to View the Question

The IUPAC name for Iron(II,III) hexacyanoferrate(II,III)  is Prussian Blue. This form of Prussian blue is insoluble and administered orally.

Enhances elimination of cesium (Cs) from the GI tract, which is useful for radioactive fallout.

Prussian blue is also the treatment for thallium (Th) toxicity, via a similar mechanism.

Constipation is also commonly reported, and stools may be blue in color. The medication should be taken with food to enhance biliary secretion of Cs.

Adult dosing is 3 grams PO taken 3 times a day with food.

Although pregnancy category C, pregnant patients should likely still be treated as the benefits likely outweigh the risks.

Iron(II,III) hexacyanoferrate(II,III)
Toxicology of the Pancreatic Beta Cell

Describe the cellular mechanism of sulfonylureas, octreotide, and calcium channel blockers on the pancreatic beta cell.

Click to View the Answer
Click to View the Question

    Toxicology of the pancreatic beta cell, demonstrating the effect of sulfonylureas, octreotide, and calcium channel blockers. PDB file = 1zni
Toxicology of the Pancreatic Beta Cell
tear gas

Active ingredient? Mechanism? Treatment?

Click to View the Answer
Click to View the Question
  • -Aerosolized liquids or solids (not actually a gas), 2-chlorobenzalmolonotrile is an example, but there are many other related compounds.
  • -Activates TRP receptors and induce substance P release leading to pain and mucosal irritation
  • -Complications include ocular irritation, keratitis. Requires very high concentrations to cause life threatening injury.
  • -Extraction from environment, decontamination and supportive care?
tear gas
Chlorine Gas

Symptoms? Fatal dosing? Mechanism? Treatment?

Click to View the Answer
Click to View the Question
  • Humans can smell at 3 ppm, this causes mild mucus membrane
  • As concentration increases, smell strength increases, which is associated with worse lung injury
  • -@400 ppm; 30 minutes is fatal, @>1000ppm, instantly fatal.
  • Creates HOCl leading to direct injury of the lung tissue
  • Supportive, nebulized Bicarb is a safe approach
Chlorine Gas
Phosgene
  • -Mechanism of action? Structure? Clinical effects? Treatment? History?
Click to View the Answer
Click to View the Question
  • -Causes a delayed ARDS type picture and respiratory irritation (typically around ppm>4.8).
  • -Causes acylation of cells in the alveoli as well as formation of ROS.  It is not readily water soluble so production of HOCl is less likely.
  • -Supportive care, high dose steroids, ARDS net protocol, but theoretically antioxidant support with NAC maybe of benefit, ECMO for complete lung failure
  • -History: chemical weapon used during World War 1

 

Phosgene
Serum Osmolarity
What is the formula to calculate serum osmolarity?
Click to View the Answer
Click to View the Question
normal is < 10

 

Serum Osmolarity
Enterohepatic recirculation
  • What are 5 important enterohepatically recirculated drugs?
  • And what should you give in a significant overdose?

Click to View the Answer
Click to View the Question

  • Phenobarbital
  • Theophylline
  • Carbamazepine
  • Dapsone
  • Quinine
  • Colchicine
  • They need MDAC to bind xenobiotic before it is recirculated
Enterohepatic recirculation
Naloxone for non-opioid overdoses

Off-label use for Naloxone to reverse non-opioid overdose has been substantiated at the case series/report level for which xenobiotics?

Click to View the Answer
Click to View the Question

Valproic acid (PMID=17711961; theoretical mechanism: empiric evidence, no theory)

Ace-inhibitor overdose (PMID=1928887; theoretical mechanism: inhibition of digestion of endogenous endorphins)

Imidazolines (PMDI=29544366; higher dose, theoretical mechanism: reversal of brain stem Beta-endorphin release)

 

Naloxone for non-opioid overdoses
Beta Blockers for Tox induced Tachycardia
For which poisonings that result in tachycardia might Beta Blockade be a good idea?

Click to View the Answer
Click to View the Question
methyl xanthines (caffeine, theophylline, aminophylline; they increase beta1&2 signaling as a downstream effect of phosphodiesterase activity and adenosine antagonism )
albuterol, clenbuterol (iatrogenic) 
glucagon (iatrogenic) 
halogenated hydrocarbons (huffers) 
Beta Blockers for Tox induced Tachycardia
CroFab
  • What are the common and scientific names of the 4 species used to produces CroFab?

  • What structure does Fab have?

Click to View the Answer
Click to View the Question
  • Mohave Rattlesnake (Crotalus scutulatus)

  • Diambondback Rattlesnake (Crotalus atrox)

  • Eastern Diamonback Rattlesnake (Crotalus adamanteus)

  • Cottonmouth/Water moccasin (Agkistrodon piscivorus)

  • Ovine papain digested Ab results in cleavage at the hinge site resulting in 2 linear Fab’s per antibody. This is comparison to pepsin cleavage resulting in a v-shaped Fab.

CroFab
{ 0 comments }

Drug Dose Estimator

Use this calculator to estimate the initial dose of xenobiotic, assuming taken at 1 time, and the serum sample is at tmax. It is not a perfect calculator, but can give the clinician a rough estimate. Future mathematical modeling will involve incorporating approximate metabolism and give variable for time of ingestion and kinetic order. Please note that µg/mL = mg/L.

D=C_0*V_d*Wt

{ 0 comments }

Drug Serum Concentration Estimator

This calculator will let you estimate a theoretical xenobiotic serum concentration at the Tmax using a reported dose . Use this with a grain of salt because in massive overdose, standard kinetics no longer apply. Please note that µg/mL = mg/L.

D=C_0*V_d*Wt
C_0=\cfrac{D}{{(V_d*Wt)}}

{ 0 comments }

TEG learning case:  
 
We had a patient on warfarin and plavix who had a GI bleed and was found to have INR>9.9. Prior to the start of my shift, her vital signs were stable so the decision overnight was to give vitamin K because she did not have yet have a diagnosed life threatening bleed. However, she became increasingly altered, and subsequent head CT showed spontaneous subarachnoid hemorrhage. By this time nearly 8 hours had passed and her INR was about 4. We ran a TEG platelet mapping assay before she received any reversal agents, which utilizes a green top (heparinized tube).
 
You can see the HKH (heparinized kaolin heparinase) TEG tracing in pink has a prolonged R time, indicating severe hypocoagulability. Furthermore, even though the patient was reported to be on plavix, you can see that the maximum amplitude (MA) of the platelet ADP tracing in green and the MA of the HKH tracing are approximately the same; both the green and pink curves approximate an MA of 60 mm. This indicates that she does not have significant antiplatelet effect. 
 
  
For whatever reason, the TEG machine does not report R time as a numerical value on the platelet mapping assay; however, you can see it is just under 15 minutes (pink tracing), and is far outside of reference values, which are posted on the wall by the machine.

 
She then got 4 factor PCC, and we gave DDAVP anyway given the life threatening nature of her bleed. However, I would not rush to transfuse platelets given her normal platelet mapping assay. 
 
2 hours after she got 4 factor PCC and DDAVP, we then ran a standard TEG (CK, CRT, CKH, CFF), which uses a blue top tube. We ran this test because we already knew her platelet function from the previous assay. Here you see that that R time has now normalized. The MA is high normal and the functional fibrinogen (CFF) channel is high normal. This indicated to us that our reversal during the resuscitation was sufficient. She definitely does not need more factors, lest she become hypercoagulable.  


 
 
She had stable hematocrit and stable interval head CT and was subsequently dispositioned. 
 
Thanks for reading !

{ 0 comments }

Ebola Virus Disease

One reason I know that I went into the right speciality is that we HAVE to know about Ebola. Virology is uber fascinating, and we aim to hammer out everything the EP provider needs to know regarding this Ebola virus disease (EVD). 

Aside from being an interesting topic, there is currently a budding outbreak of ebola in the congo. See news article below. 

https://www.beckershospitalreview.com/quality/101-dead-in-congo-s-ebola-outbreak-as-safety-risks-mount-for-health-workers.html

(note: I wrote this for a departmental memo in 2018)

Now the outbreak is worsening: https://www.apnews.com/49fcb435740b4c5b88bab2a1c873b763

So it is even more important for the EP to keep this disease on their radar.

If you recall from the last outbreak, there were several notable US cases, one of which  received treatment in NYC. 

It is thought that there is animal reservoir (likely fruit bats) and the animal to human transmission of the virus may come from individuals handling bushmeat. 

Ebola is a filovirus (meaning it looks like a string). It is a negative sense single stranded RNA virus. 

Below is a colorized scanning electron microscope image of the virus (curtesy wikimedia commons)

Transmission is via contact of viral particles to mucus membranes or broken down skin.  

Incubation time is 9-11 days.

The ebola virus is one of the most infectious agents known to man. A single ebola virion is enough to be infectious. This is in stark contrast to most other infectious agents which typically require a large inoculum to cause clinically significant disease. 

Symptoms typically develop by infection day 5: 

  • -fever, fatigue
  • GI upset: vomiting, watery diarrhea, abdominal pain
  • this can progress to seizures and cerebral edema
  • renal failure
  • hepatic failure
  • ecchymoses and petechial rash are also possible
  • hemorrhage is uncommon, but reported in 18% of patients (typically GI)

Patients with severe disease typically die within 6-16 days. Mortality rate in west Africa was ~40-70%. Of 27 patients treated in the United States, the fatality rate was 18.5%.

The mechanism for the hemorrhagic fever is thought to be massive activation of macrophages and other immune cells causing a cytokine storm, which then leads to break down of the vascular endothelium and results in leaking. Other research suggests the virus itself has proteins which lead to endothelial dysfunction and leakage.

You can utilize ELISA, PCR, or virus isolation to test for the disease. These tests are only available in consultation with a governmental health agency. 

Mainstay of treatment is supportive. However, you can transfuse convalescent serum from recovered and now immune individuals. A more elegant and certainly more expensive treatment is ZMapp, which is a mix of “3 humanized monoclonal antibodies” against Ebola.  There also several vaccines including rVSV-ZEBOV which have been experimentally deployed in west Africa. 

As per the CDC, travelers from endemic outbreak regions should self monitor their health for 21 days. Febrile patients who may had contact with ebola, should be placed on contact precautions and NYDOH should be immediately contacted. 

Hopefully this is something we never see. But preparedness is critical for our specialty. Thank you for taking the time to read and have a great day. 

References: 

Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med. 2015;372(1):40-7.

Cantoni D, Rossman JS. Ebolaviruses: New roles for old proteins. PLoS Negl Trop Dis. 2018;12(5):e0006349.

https://www.cdc.gov/vhf/ebola/healthcare-us/preparing/clinicians.html

https://commons.wikimedia.org/wiki/File:Ebola_virus_virion.jpg

Sanford guide, app on iOS

Zwart MP, Hemerik L, Cory JS, et al. An experimental test of the independent action hypothesis in virus-insect pathosystems. Proc Biol Sci. 2009;276(1665):2233-42.

{ 0 comments }

Toxicology Art

I put together is piece as part of collaboration with Department of Toxicology at Mother Theresa hospital in Skopje, MK (Болница Мајка Тереза, Скопје МК). It features Cyrilic script reading Toxicology in Macedonian (Токсикологиа), the caduceus, a laboratory flask and the ekg rhythm strip. This version is a lowish quality version to save on web space and also has my signature on the bottom (the original does not).

There is, after all, an art to medicine as well. Regardless, it prints quite nice at 40 cm x 30 cm.

{ 0 comments }

EtOH dose estimator

I have been tinkering around with some dose calculators, my own code of course!

input measured serum etoh and body weight, the output will be approximate to the dose if the patient had taken a 1 time chug of etoh and ended up in your ED. Derivations are also available below for your own education.

D=C_0*V_d

now converting for units, here is the full equation resulting in g of EtOH

D=(C_o\;mg/dL)(0.72\:L/kg)(weight\;in\;kg)(10\;dL/1\;L)(1\;g/1000\;mg)

So, say now we have a patient with a toxic alcohol ingestions and no fomepizole is available. We need to get them drunk!

Modifying the previous equation we get:

D=\cfrac{(100\;mg/dL)(0.72\;L/kg)(10\;dL/1\;L)(1\;g/1000\;mg)}{(EtOH\;fraction)}

Inputting pt weight and the concentration of alcohol you have available (0.01-1) will give you appropriate loading dose.

I plan to expand this to include steady state elimination over a number of hours so that you can calculate estimated times of metabolization, allowing for redosing if appropriate.

references:

Cowan JM, Weathermon A, Mccutcheon JR, Oliver RD. Determination of volume of distribution for ethanol in male and female subjects. J Anal Toxicol. 1996;20(5):287-90.

Mcmartin K, Jacobsen D, Hovda KE. Antidotes for poisoning by alcohols that form toxic metabolites. Br J Clin Pharmacol. 2016;81(3):505-15.

{ 0 comments }

Measles Infographic

Use this infographic on your peds shifts to teach about measles. There is a current outbreak originating near to where I live in Brooklyn. We have seen several cases at our hospital. Given the high infectivity and crowding in our inner city ED’s, it is critical to become familiar with the natural course of the disease.

https://www.cdc.gov/measles/cases-outbreaks.html

{ 0 comments }

Fluid and Insulin Management in Pediatric DKA

Here is a quick guide to dosing of fluids and insulin in pediatric dka. Infants have a slightly different management strategy that is not covered here.

insulin drip: 0.05 -0.1 units/kg/hr

Fluids: Start off with a 10-30 mL/kg bolus of NS (I’d recommend the lower end)

K <5.5

INSTRUCTIONS FOR IVF:
BAG 1: 75meq Na-acetate/75 meq NaCL with 20 meq KCl/20 meq KPhos 
BAG 2: D10 75meq Na-acetate/75 meq NaCL with 20 meq KCl/20 meq KPhos 

Maintenance rate=M=***

BGM >350: Bag 1 100%M
BGM 250-350: Bag 1 50%M + Bag 2 50%M
BGM < 250: Bag 2 100%M

Adultish child with K >5.5

INSTRUCTIONS FOR IVF:
BAG 1: 75meq Na-acetate/75 meq NaCL 
BAG 2: D10 75meq Na-acetate/75 meq NaCL 

Maintenance rate=M=***

BGM >350: Bag 1 100%M
BGM 250-350: Bag 1 50%M + Bag 2 50%M
BGM < 250: Bag 2 100%M

{ 0 comments }

Thromboelastography

Thromboelastography (TEG) is coming to an emergency department near you. For those who rotated at Shock, TEG is utilized to guide administration of blood products during massive transfusion protocol in a bleeding patient. For us, this test will likely be most useful for bleeding in patients on anticoagulation and/or antiplatelet agents.

INR and aPTT only measure the enzymatic clotting time, which means they only measure clotting cascade up until fibrin. Utilizing these tests, it is impossible to know the causes(s) of coagulopathy in intracranial hemorrhage or GI bl er the last time the took their meds.

TEG is a whole blood test and assays clot formation, mechanical strength and stability across time. This allows interpretation of the curve to determine the cause of coagulopathy.  Old TEG machines measured the mechanical elasticity and strength of the clot by physically interacting with whole blood. The TEG output across time is measured in maximum amplitude, which is a function of dynes of force generated by the elastic clot. This an example of what a TEG curve looks like (Trepani, et al).

pastedGraphic.png

Traditional clotting cascade 

Reaction Time R is the time to activation, ending in thrombin. Theoretically any deficiency can cause prolonged R time (eg thrombophilia), but in the setting of trauma, it is most commonly associated with thrombin deficiency. R will also be long with anticoagulation. If R is long, you need praxbind, PCC or FFP depending on the etiology.  

Polymerization

Clot Kinetics K is dependent on fibrinogen function and fibrin cross linking 

αº is the angle formed between R and the tangent line to the curve at point K. 

If either αº or K are low, you can give cryoprecipitate which contains the fibrinogen necessary to correct this coagulopathy. 

Clot features

Maximum amplitude (MA in mm) or G (dynes) represents clot strength at its peak. The lower the amplitude, the lower the platelet function. If this is low and patient is bleeding, you need DDAVP or platelets. 

LY30 is the amount of clot lysis 30 minutes after MA is achieved, and represents the amount of thrombolysis due to factors in the patient’s blood sample. 

Here is a diagram with each of the variables as they relate to the coagulation cascade. Abnormalities in these values suggest the possible cause of their coagulopathy:  

TEG 6s

Previous machines analyzed the thromboelastic properties of the clot across time using physical forces. This new generation of machine sends sound waves through 4 channels and measures motion of the sample optically across the clotting time. All 4 tests occur simultaneously in the microfluidic test cartridges. A 5th channel assays platelet function, which we may or may not use. 

4 channels: 

Kaolin TEG: kaolin is used as an initiation of coagulation cascade. This is channel gives you the classic TEG graph.

Rapid TEG: this channel’s coagulation cascade is rapidly initiated by tissue factor (extrinsic pathway).  R will be dramatically shortened because the coagulation cascade is activated faster in this channel. 

Heparinase TEG: as the name suggests, this microfluidic channel contains an enzyme that breaks down heparin, which effectively analyzes a heparinized patient’s blood as if they were not on heparin. If the patient is not on heparin the Kaolin TEG and Heparinase TEG should be the same. 

Functional Fibrinogen: this specific assay determines whether fibrinogen should be repleted.

The 4 channel readout will come off the machine as below. CK=Kaolin; CRT=Rapid TEG; CKH=Herapinase TEG; CFF=Functional Fibrinogen

pastedGraphic_1.png

Each channel’s specific values can be displayed, which give you reference assay result in black with reference ranges in light grey. The caveat here is that reference ranges are established by the device manufacturer’s database of normals. 

pastedGraphic_2.png

Long R time = you need to replete factors

Low K or alpha angle = cryoprecipitate for fibrinogen 

Low MA = need ddavp, or platelets

High Ly30 = TXA

Low Ly30, low R, high K and alpha angle = hypercoagulable state. 

Whewww…. Let’s take a breather. We do not have to take a super deep dive into the physics. Rather, as Emergency Medicine providers, we should focus on pattern recognition.

Here is a modified table  from EMdocs.com with different TEG patterns, their clinical significance and possible intervention for bleeding: 

Theoretically, in early DIC or other hypercoagulable states, the tracing will show that the clot does not lyse. Therefore, heparin may be indicated. Dosing of heparin can be titrated to normalization of the TEG curve, but this is case report level at the moment and the literature is sparse. We have more than a few patients in DIC progressing from hypercoagulable to hypocoagulable as all of their factors and platelets are consumed.

The most common utilization of TEG at our institution will likely be determining pharmacologic interventions for bleeding patients on antiplatelets and/or anticoagulation. Imagine a patient on dual anti-platelet and anti-factor-Xa agent who presents with a GI bleed but did not take his or her medicine in 2 days. If a bleeding patient has a normal TEG, it could indicate we do not need to reverse a patient, give them blood product, or DDAVP. In this particular patient reversal of antiplatelet, transfusion, of 4-factor PCC administration may make them dangerously hypercoagualable. 

Finally, TEG is only an in vitro assay and it does not take into account host factors such as anatomic defects, endothelial damage, etc. Furthermore, very little data is available regarding RCT’s for patient centered outcomes utilizing TEG to manage patients. No test is perfect, but hopefully this will be a tool to better guide interventions we make on bleeding or clotting patients. 

Sources:

Anzoletti, M. B., Cressoni, M., D’Angelo, A., Bader, R., L’Acqua, C., Panigada, M., … Protti, A. (2015). Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified Thromboelastography. Plos One, 10(8), e0136463. https://doi.org/10.1371/journal.pone.0136463

Gill, M. (2017). The TEG®6s on Shaky Ground? A Novel Assessment of the TEG®6s Performance under a Challenging Condition. The Journal of Extra-Corporeal Technology, 49(1), 26–29. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28298662%0Ahttps://www.ncbi.nlm.nih.gov/pmc/PMC5347215/

Stammers, A. H., Willett, L., Fristoe, L., Merrill, J., Stover, T., Hunt, A., … Newberry, J. (1995). Coagulation monitoring during extracorporeal membrane oxygenation: the role of thrombelastography. J Extra Corpor Technol, 27(3), 137–145.

Trapani, L. M. (2013). Thromboelastography: Current Applications, Future Directions. Open Journal of Anesthesiology, 03(01), 23–27. https://doi.org/10.4236/ojanes.2013.31007

[x] non primary sources fact checked

[x] http://www.emdocs.net/thromboelastogram-teg-five-minute-primer-emergency-physician/

[x] https://teg.haemonetics.com/en-gb

[x] https://www.youtube.com/watch?v=-4d9buDGXAo by Julie Wegener, PhD

[x] https://www.youtube.com/watch?v=us89Srum8KE by Dr. Johannigman

[x] https://www.slideshare.net/claudegindrey/teg-6s-presentation

{ 0 comments }