UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: Pharmacoeconomics

Keywords: ondansetron, albuterol (PubMed Search)

Posted: 2/26/2009 by Fermin Barrueto, MD (Updated: 5/27/2024)
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As the economy worsens and our patients pay for more prescriptions out of pocket, here are some tips that may help you better serve your patients: 1) Ondansetron (zofran) is now off patent. Write generic on your script for zofran - for pediatrics the ODT (dissolving tablets) - are all much cheaper ($0.50 to $1.00 per pill or ODT). IV formulation is now cheaper than phenergan. Reglan is probably still the cheapest in most pharmacies. 2) Typical $4 antibiotics are the following: SMP-TMZ (Bactrim), Cephalexin, Amoxicillin, Penicillin, Ciprofloxacin. 3) Albuterol MDIs are now much more expensive because they have to be CFC free. Unfortunately, after this federal regulation, patients will have difficulty getting these inhalers which can be quite expensive. If you write a script and the patient is self-pay, they are going to have difficulty. Hospitals are beginning to discourage "to go" inhalers and even pills due to the fact that insurance companies DO NOT reimburse these costs - only IV meds.

Category: Toxicology

Title: Rocuronium vs Succinylcholine

Keywords: rocuronium, succinylcholine (PubMed Search)

Posted: 2/19/2009 by Fermin Barrueto, MD (Updated: 5/27/2024)
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Rocuronium is fast becoming the agent of choice for RSI in the Emergency Department. Here is a head to head comparison of the two drugs to understand why:

  Rocuronium Succinycholine

Dose

 1-1.2mg/kg

1mg/kg

Onset

1-1.5min

1min

Duration

7-12min

30-40min

Histamine Release

No

Minimal Yes

CVS Effect

Tachycardia rare

Severe Brady rare

Other Adverse Effect

No fasciculations, No ICP effect, No Rhabdo

Fasciculations, increase ICP, rhabdo, movement of displaced Fxs 

 



Category: Toxicology

Title: Phentolamine Use in Hypertensive Crisis

Keywords: phentolamine, tyramine, pheochromocytoma (PubMed Search)

Posted: 2/12/2009 by Bryan Hayes, PharmD (Updated: 5/27/2024)
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You have a 44 y/o female patient with an arterial line monitoring her blood pressure which is reading 302/156 mm Hg.  Her heart rate is 140 bpm.  Her history reveals she is taking a monoamine oxidase inhibitor (MAOI) and has inadvertantly ingested tyramine at her friend's cheese/wine party.   What do you do?

  • Conditions producing hypertensive crisis from catecholamine surges (phenylephrine overdose, cocaine, tyramine interactions, pheochromocytoma) can be treated with phentolamine
  • Phentolamine is a nonspecifc alpha blocking agent which produces peripheral vasodilation with a resultant fall in blood pressure in most patients.
  • Other uses include extravasation of some vasopressors (e.g. norepineprhine)
  • May see an increase in HR after administration (once alpha blockade is established, beta-blocker can be administered)
  • Dose: 5-15 mg IV/IM
  • Duration: 30-45 minutes


Category: Toxicology

Title: Clopidogrel and Thrombosis

Keywords: Clopidogrel, DVT, thrombosis, stents (PubMed Search)

Posted: 2/5/2009 by Ellen Lemkin, MD, PharmD (Updated: 5/27/2024)
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There have been multiple case reports of patients who have had coronary stents who have been on clopidogrel for > 1 year who have developed coronary thrombosis after clopidogrel cessation. There are also reports of patients who have developed DVTs likewise after clopidogrel cessation. In vivo studies in diabetics have demonstrated increased platelet and inflammatory markers after clopidogrel withdrawal. It appears that abrupt discontinuation of clopidogrel may lead to a thrombotic state in susceptible patients.

Show References



Category: Toxicology

Title: Fun Rodenticides

Keywords: brodifacoum, cholecalciferol, strychnine (PubMed Search)

Posted: 1/29/2009 by Fermin Barrueto, MD (Updated: 5/27/2024)
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Rodenticides have taken many forms. The following is a list of some of the more interesting ones either due to the mechanism of toxicity or how it is lethal. All of these are also toxic to people.

1) Strychnine - Glycine Antagonist at the post-synaptic spinal cord neurons - patient or rat will have convulsion of the extremeties but will be awake, alert and in extreme pain. Essentially look like generalized seizure except awake. Treatment: Benzodiazepines, Analgesia, Supportive

2) Brodifacoum - Long Acting Coumarin - rat eats, later develops elevated INR then tries to run through thin cracks in the wall or takes a little too high of a jump, then boom - subdural or some other internal hemorrhage. In human, they can stay anticoagulated for weeks after an overdose. Treatment: Vitamin K and large padded room

3) Cholecalciferol - Vitamin D precursor - there are big blocks of this drug in the NY and other subway systems. Rat nibbles, gets hypercalcemic, then gets thirsty because of this. Rat runs out into middle of subway to drink out of puddle then - splatt - the M train to Brooklyn comes along. Treatment: IVF, Loop Diuretics, Bisphosphonates



Category: Toxicology

Title: Octreotide - The Antidote for Sulfonylurea Toxicity

Keywords: octreotide, sulfonylurea, hypoglycemia (PubMed Search)

Posted: 1/22/2009 by Fermin Barrueto, MD (Updated: 5/27/2024)
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Octreotide

  • Somatostatin-analog that supresses insulin secretion but also treats acromegaly, esophageal varices and secretory diarrhea
  • Sulfonylurea-induced hypoglycemia requires frequent monitoring and administration of intravenous dextrose
  • Octreotide is considered antidotal therapy since it turns off insulin secretion that is caused by sulfonylureas
  • Recent article by Fasano et al Ann Emerg Med 2008 showed that octreotide 75 mcg SQ one-time in the ED was superior to "traditional" therapy with fewer recurrent hypoglycemic episodes during the patient's hospitalization.
  • Excellent article worth reading, even if its just the abstract

Show References



Category: Toxicology

Title: If you like sushi - Fugu

Keywords: tetrodotoxin, sushi (PubMed Search)

Posted: 1/15/2009 by Fermin Barrueto, MD (Updated: 5/27/2024)
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Tetrodotoxin - Sodium Channel blocker - Extremely toxic causes paresthesias, dysrhythmias and paralysis - Found in the sushi called Fugu (From the Pufferfish) - Eating the sushi is considered a delicacy and goal is to get just enough of the toxin to get perioral paresthesias after eating. - Also found in the blue-ringed octopus, angelfish and parrot fish. Enjoy your seafood and take a look at the attached pic of actual fugu.


Attachments

0901152329_fugu_0111.jpg (145 Kb)



Category: Toxicology

Title: Methadone-induced QT prolongation

Keywords: methadone, QT prolongation, torsade de pointes, magnesium (PubMed Search)

Posted: 1/7/2009 by Bryan Hayes, PharmD (Emailed: 1/8/2009) (Updated: 5/27/2024)
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A few previous pearls have touched on identifying drugs that cause QT prolongation.  In our patient population, methadone is one of the more common causes of drug-induced prolonged QT syndrome.  Of 692 physicians surveyed (35% family practitioners, 25% internests, 22% psychiatrists, and 8% self-identified addiction specialists) only 41% were aware of methadone's QT-prolonging properties and just 24% were aware of methadone's association with torsade de pointes.

 

Now that you know, what do you do when a patient on methadone presents with a QTC of 580 msec and intermittent runs of vtach and torsade de pointes?

 

The answer is... the exact same thing you would do with any other patient who presents this way, regardless of the cause.

  • Give magnesium sulfate 2 gm IV for torsade de pointes
  • Check magnesium and potassium levels.  If low (which they often are), replete.
  • Monitor continuous EKG.

Buprenorphine, an alternative to methadone, is not associated with prolonged QT syndrome.

 


Show References



Category: Toxicology

Title: Non-Cardiac Cocaine Toxicity

Keywords: Cocaine, stroke, crack lung, headache, seizures, hyperthermia, stroke (PubMed Search)

Posted: 1/1/2009 by Ellen Lemkin, MD, PharmD (Updated: 5/27/2024)
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Although we tend to think of ACS with cocaine use, there are many other serious complications, including:

  • Agitation, psychosis, and anxiety
  • Hyperthermia
  • Vascular headache of withdrawal
  • Seizures
  • Hemorrhagic stroke (many of these patients have an underlying vascular abnormality)
  • Ischemic stroke
  • Acute Renal Failure
  • Crack Lung: acute pulmonary syndrome that occurs after inhaling freebase cocaine presents as fever, dyspnea, hypoxemia, diffuse alveolar infiltrates, and respiratory failure
  • Intestinal perforations

Show References



Category: Toxicology

Title: Toxicology - Happy Holidays

Keywords: adverse drug reaction (PubMed Search)

Posted: 12/25/2008 by Fermin Barrueto, MD (Updated: 5/27/2024)
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Watch out for tradename and generic name's of medications.

They can get the patient and yourself into trouble:

  • coumadin: warfarin, jantoven
  • diphenhydramine: unisom, benadryl, tylenol PM

Classic example is my own case: Insert a central line in a patient - subclavian - and shortly after completion am alerted the patient's INR is 25. No adverse outcome but when I reviewed the med list, I did not see coumadin or warfarin and assumed I was in the clear. Patient was on jantoven.

Happy Holidays



Category: Toxicology

Title: Fat emulsion for treating local anesthetic toxicity

Keywords: Fat emulsion, intralipid, local anesthetic (PubMed Search)

Posted: 12/25/2008 by Ellen Lemkin, MD, PharmD (Updated: 5/27/2024)
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  • Local anesthetics work through reversible binding of sodium channels
  • If inadvertantly administered intravenously or as an overdose, serious CNS and cardiac toxicities can occur, including seizures, arrhythmias, and cardiovascular collapse
  • Fat emulsion has been shown to increase the lethal dose of bupivicaine required, and also resuscitate animals that have local-anesthetic induced cardiac collapse
  • There have been successful case reports of patiets treated with fat emulsion that had cardiac arrest, seizures, and EKG changes. All patients recovered successfully with no neurologic sequale
  • Regimens used in these cases have included bolus doses between 1.2 -2 ml/kg followed by continuous infusions of 0.25 -0.5 ml/kg/min
  • Toxicity may be ameloriated by extracting lipophilic anesthetics from plasma or tissue, or by countering inhibition of myocardial fatty acid oxygenation

Show References



Category: Toxicology

Title: LABAs

Keywords: serevent, foradil (PubMed Search)

Posted: 12/19/2008 by Fermin Barrueto, MD (Updated: 5/27/2024)
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The FDA has ruled that Long-Acting Beta Agonists (LABAs) are not worth the risk with increased hospitalization and increased mortality. Serevent has largely been replaced by Advair now. Unfortunately, for the children, it took 3 years to look at the data and finally come to this conclusion. Advair (LABA + fluticasone) has escaped the ruling with lack of evidence.

Category: Toxicology

Title: Naloxone for non-opioid overdoses?

Keywords: naloxone, clonidine, valproic acid, captopril (PubMed Search)

Posted: 12/1/2008 by Bryan Hayes, PharmD (Emailed: 12/11/2008) (Updated: 5/27/2024)
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A search of the toxicology literature will reveal that naloxone has been tried in many different overdose situations.  It is thought that the endogenous opioid system mediates several physiologic and pharmacologic pathways.

  • Captopril – naloxone reverses hypotension (Ann Emerg Med 1991;20(10):1125-7)
    • Evidence: One case report.
  • Valproic Acid  naloxone reverses CNS depression possibly through GABA attenuation
    • Evidence: Two case reports demonstrated effectiveness in patients with minimally elevated VPA levels.  Other reports showed no effect in patients with much higher concentrations.
  • Clonidine – naloxone reverses coma, bradycardia, and hypotension
    • Evidence: Several case reports suggest positive response while others demonstrate no benefit.  Anecdotal experience estimates a response in about 50% of cases.

Bottom line: In none of these instances was improvement as dramatic or consistent as in the reversal of the toxic effects of an opioid.  Naloxone can certainly be tried in non-opioid overdoses but should not be considered a first-line antidote.  The most benefit appears to be with clonidine.



Category: Toxicology

Title: Carbon Monoxide (CO) Poisoning

Keywords: carbon monoxide, CO, hyperbarics, HBO (PubMed Search)

Posted: 12/4/2008 by Ellen Lemkin, MD, PharmD (Updated: 5/27/2024)
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CO is formed from the incomplete combustion of carbon materials, eg. fires, stoves, portable heaters CO reversibly binds hemoglobin, producing carboxyhemoglobin (HbCO). This causes oxygen to bind more tightly to hemoglobin, releasing less in the tissues. Because of this, it affects the organs with the highest oxygen requirements most profoundly (eg. brain and heart).

Symptoms are mainly neurological and cardiovascular, but may include a wide variety of non-specific symptoms. The initial symptoms of CO poisoning may include headache and flu-like illness progressing to confusion, agitation, lethargy, seizures and coma.

Place patients on 100% oxygen to decrease the half-life of HbCO. Though controversial, HBO therapy is thought to decrease the incidence of neurologic sequelae. HBO therapy should be considered for patients with a HbCO level above 20%, severely symptomatic patients with lower levels, and pregnant patients. Remember that pulse oximetry will not be accurate.

Show References



Category: Toxicology

Title: Thanksgiving Toxicology

Keywords: tryptophan (PubMed Search)

Posted: 11/28/2008 by Fermin Barrueto, MD (Updated: 5/27/2024)
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Tryptophan - a precursor to melatonin, it is often blamed for the post prandial coma that many go into after a big turkey dinner. Never mind the 5000 kcals that was consumed during the meal. The supplement really doesn't help with sleeping. Interestingly, turkey isn't even in the top 10 or 20 of foods that contain tryptophan. The top five are:

1) Game meat (Elk): 746 mg of tryptophan

2) Seaweed (Spirulina): 736 mg of tryptophan

3) Spinach: 690 mg of tryptophan

4) Egg White: 673 mg of tryptophan

5) Soy protein: 630 mg of tryptophan

Supplements of L-tryptophan have been contaminated with a compound that has been associated with eosinophilia myalgia syndrome.

 



Category: Toxicology

Title: Bupivacaine

Keywords: cardiotoxicity, marcaine, bupivacaine (PubMed Search)

Posted: 11/20/2008 by Fermin Barrueto, MD (Updated: 5/27/2024)
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Local Anesthetic - Bupivacaine (Marcaine) - Sodium channel blocker with duration of action 2-4 hrs (w/epi 3-7 hrs) - Toxic dose is > 2.5 mg/kg or > 175 mg total dose (Infiltrating into SQ) - Bupivacaine 0.25% = 2.5 mg/mL - Inadvertent intravenous injection can result in toxicity - Lethally cardiotoxic with widened QRS, V-tach and neurotoxic with inebriation and seizures - Anesthesia literature reports successful use of Intralipid as an antidote

Category: Toxicology

Title: Opioid Allergies and Cross-reactivity

Keywords: opioid, opiate, allergy, hypersensitivity (PubMed Search)

Posted: 11/5/2008 by Bryan Hayes, PharmD (Emailed: 11/13/2008) (Updated: 5/27/2024)
Click here to contact Bryan Hayes, PharmD

How many times have you had a patient with an allergy to codeine described as stomach upset?  Or how about a rash with morphine (probably secondary to histamine release)?  True anaphylactic reactions to opioids are very rare (< 1%).  But what happens when you have a patient with a true allergy, but still need to give an opioid?  No problem, you just need to choose one that is structurally different.

  • Group 1 (aka opiates) - Naturally occurring agents derived from the opium plant
    • Morphine, codeine, thebaine
  • Group 2 - Semi-synthetics
    • Hydrocodone, oxycodone, hydromorphone, oxymorphone, buprenorphine (heroin is also in this group)
  • Group 3 - Synthetics
    • Fentanyl (alfentanil, sufentanil, etc.), methadone, tramadol, propoxyphene, meperidine

All of the group 1 and 2 agents are structurally very similar to each other and should not be given if a true allergy exists to any other natural or semi-synthetic derivative.  Group 3 agents have structures different enough that they can be given to a patient intolerant to the natural or semi-synthetics without fear of cross reactivity.  They are also very different from others in this same group.

The bottom line is that most of our patients don’t have true opioid allergies.  Just as an example, you will many times see a patient listed as having a percocet or morphine allergy and yet they tolerate hydromorphone without a problem. Go figure…


Category: Toxicology

Title: Salvia Divinorum

Keywords: Drugs of abuse, salvia, sage (PubMed Search)

Posted: 11/6/2008 by Ellen Lemkin, MD, PharmD (Emailed: 11/7/2008) (Updated: 5/27/2024)
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This is a psychoactive herb which can induce strong dissociative effects by stimulation of the kappa receptor. It has become increasingly well known and available in modern culture, and popularized by YouTube Salvia (also known as Sage, Diviner's Sage, Magic Mint, or Sally D) is usually smoked, but can be chewed or ingested.

The high it produces is very intense, but lasts only approximately 10 minutes. Currently many states have enacted legislation against it, including Fla, IL, KA, MI, MO, ND, OK and VA, but it is available over the internet.

  

The following video demonstrates clinical effects of drug.
Although it is amusing, this is not meant to condone use.

(if you can not view the embeded video here is the link)

http://www.youtube.com/watch?v=w6dgXX0ytSo



Category: Toxicology

Title: MDMA and SIADH

Keywords: siadh, mdma, ecstasy (PubMed Search)

Posted: 10/30/2008 by Fermin Barrueto, MD (Updated: 5/27/2024)
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Methylenedioxymethamphetamine (MDMA) or "Ecstasy"

A designer club drug that has been classified as a "hallucinogenic" amphetamine though it does not cause visual hallucinations like are reported with LSD. It has many of the sympathomimetic effects like other amphetamines but its main mechanism of action which both causes the euphoria and toxicity is serotonin agonism. Since Anti-diuretic hormone is released by the hypothalamus under the direct regulation of serotonin, there is a transient but dangerous episode of Syndrome of Inappropriate ADH (SIADH). Combined with the club culture and fear of dehydration while taking MDMA, patients ingest MDMA concomitantly with free water through the night further exacerbating the hyponatremia. The time sequence of events for these patient is (women appear genetically predisposed to this phenomena):

  • Friday Night: Ingestion of MDMA (even one pill is enough) +/- free water
  • Saturday Morning: headache, nausea, vomiting
  • Saturday Afternoon: (Realizes its not a hangover) patient becomes confused progressing to unresponsive and eventually seizures
  • Saturday Evening: Presents to ED with seizures

Treatment: Fluid restriction - this is the one time that the 1L NS Bolus can kill a patient with cerebral edema. If you must give fluid give 3% NaCl if there is symptomatic hyponatremia. Remember the patient has dropped their sodium in about 24 hours so you can replenish in about the same time quite safely and even faster in severe cases. Treated correctly, patients improve rapidly - within 24-48 hours. Read a great case report in the reference below.

Show References



Category: Toxicology

Title: Olanzapine - Know the Adverse Effects

Keywords: anticholinergic, olanzapineA (PubMed Search)

Posted: 10/24/2008 by Fermin Barrueto, MD (Updated: 5/27/2024)
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 Olanzapine (Zyprexa)

This is an atypical antipsychotic that gained popularity because it caused less sedation and fewer extrapyramidal effects. However, there are many other adverse effects that need to be emphasized. Some of these may contribute to a patient's condition in the ED:

  • Hyperglycemia: has been reported to even cause hyperglycemic hyperosmolar nonketotic coma as well as DKA in patients that were not diabetic prior to initiation of olanzapine.
  • Anticholinergic: one of the most anticholinergic antipsychotics, watch for polypharmacy. Perhaps the patients urinary retention and mild confusion is due to the many anticholinergic medications the patient is taking.
  • Serotonin Syndrome: again a problem with polypharmacy and in overdose.