UMEM Educational Pearls - Toxicology

Oseltamivir (Tamiflu)

  • Has low protein binding and does not inhibit CYP450 (resulting in a low incidence of drug interactions)
  • Requires dosage adjustment with creatinine clearance of < 30 ml/min
  • Does not require dosage adjustment in patients with liver failure or the elderly
  • Most common adverse effects are nausea and vomiting
  • Serious effects include anaphylaxis and skin reactions. Neuropsychiatric effects reported include hallucinations, delerium and abnormal behavior
  • It may be administered to infants and children due to the high potential morbidity associated with influenza

 

For complete indications and dosing: www.cdc.gov/h1n1flu/recommendations.htm

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Category: Toxicology

Title: Screening for Benzodiazepine Use/Abuse

Keywords: benzodiazepine, oxazepam, toxicology, urine, blood (PubMed Search)

Posted: 5/14/2009 by Bryan Hayes, PharmD (Updated: 12/7/2021)
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Your patient presents unresponsive with an empty bottle of alprazolam (Xanax). You order a urine and blood toxicology screen. The blood comes back negative for benzodiazepines but the urine test is positive. How do you interpret this result?

  • The benzodiazepine toxicology screen typically looks for oxazepam. If it is present in sufficient quantity, the test will be positive.
  • Three benzodiazepines are detected by this test: oxazepam (Serax), diazepam (Valium), and chlordiazepoxide (Librium); [diazepam and chlordiazepoxide are metabolized to oxazepam].
  • Other benzodiazepines such as clonazepam, lorazepam, and alprazolam will generally test negative unless there is cross-reactivity or large quantity.
  • The urine and blood immunoassays are exactly the same. For this patient, there was probably a low overall quantity of alprazolam in the blood but a concentrated amount in the urine. Therefore, the positive urine and negative blood.

Category: Toxicology

Title: Ethanol verses Fomepizole

Keywords: ethanol,fomepizole,toxic alcohols,ethylene glycol,methanol (PubMed Search)

Posted: 5/7/2009 by Ellen Lemkin, MD, PharmD (Updated: 12/7/2021)
Click here to contact Ellen Lemkin, MD, PharmD

  • Recently, a study was published which compared adverse drug events in patients who had received either fomepizole or ethanol for ethylene glycol or methanol poisoning.
  • Importantly, this is the first trial which has compared these events head to head.
  • Retrospectively, 172 charts over a 9 year period were reviewed. Toxicologists identified at least 1 ADR in 74 of 130 ethanol treated cases (57%) versus 5 of 42 fomepizole treated cases (12%).
  • Severe ADRs occurred in 20% of ethanol treated patients vs 5% fomepizole treated patients.
  • This adds further data to support the use of choosing fomepizole over alcohol for treatment of toxic alcohol poisonings
 

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Category: Toxicology

Title: Ondansetron (Zofran) in Pediatrics

Keywords: ondansetron, antiemetics (PubMed Search)

Posted: 4/23/2009 by Fermin Barrueto, MD (Updated: 12/7/2021)
Click here to contact Fermin Barrueto, MD

Ondansetron (Zofran) has been off patent and its price has dropped to the point that it has supplanted promethazine (Phenergan) and even metoclopramide (Reglan) as the antiemetic of choice. With its low side-effect profile and known efficacy it is now being utilized in hyperemesis gravidarum and in pediatric gastroenteritis. - A cochrane review showed ondansetron to be both safe and effective in the pediatric population. Consider it prior to attempting oral rehydration therapy to increase effectiveness. - Dose: 0.1 mg/kg - you can give the oral dissolvable tablet (ODT) - ages 4-11 you can give 4mg ODT - Above age 11 the dosing is the same as an adult.

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Category: Toxicology

Title: Colchicine

Keywords: colchicine, gout (PubMed Search)

Posted: 4/16/2009 by Fermin Barrueto, MD (Updated: 12/7/2021)
Click here to contact Fermin Barrueto, MD

Colchicine is a drug used for the treatment of acute gout attacks. It inhibits microtubule formation vital for cellular mitosis. It is also a drug with a narrow therapeutic index and lethal toxicity:

- Colchicine can be lethal at 0.5 mg/kg or even lower. Though this would be about 50 tablets and seems alot, remember it is prescribed 2 tablets initially then every hour until diarrhea presents (i.e. preliminary toxicity)

- Toxicity presents in 3 stages:

  1. 0-24hrs: Nausea, vomiting, diarrhea
  2. 1-7days: Sudden cardiac death, pancytopenia, renal failure, ARDS
  3. >7days: Alopecia, myopathy, neuropathy (if they survive)

- No antidote, supportive care only available.

- Presentation is similiar to that of a radiation exposure

 


Category: Toxicology

Title: Overdose of insulin glargine (Lantus)

Keywords: glargine, insulin, lantus (PubMed Search)

Posted: 4/9/2009 by Bryan Hayes, PharmD (Updated: 12/7/2021)
Click here to contact Bryan Hayes, PharmD

Overdoses of insulin glargine (Lantus) are rarely reported in the literature.  In fact, there are only 6 case reports.  We recently had a patient in our ED who was hypoglycemic from insulin glargine.  The hypoglycemic episode was quite prolonged (> 24 hours) in the ED before being the patient was transferred to the MICU.  Here are a few points to remember:

  • Insulin glargine does not peak; it was designed to mimic basal islet cell insulin secretion.
  • In the therapeutic setting, its effects can last up to about 24 hours.  In overdose the hypoglycemic effects have been reported to last up to 60-130 hours!
  • Be prepared to give IV dextrose 5% or 10% infusion for the duration of the patient's hypoglycemic effect.  This can be supplemented with food.
  • Octreotide will be ineffective for exogenous insulin poisonings because its effect comes from its ability to suppress insulin secretion from the pancreas.

Category: Toxicology

Title: Pediatric Substance Abuse

Keywords: overdose, precription drugs, pediatric, substance abuse (PubMed Search)

Posted: 4/1/2009 by Dan Lemkin, MD, MS (Emailed: 4/2/2009) (Updated: 5/24/2009)
Click here to contact Dan Lemkin, MD, MS

Classical illicit recreational drugs like cocaine, ecstacy, and marajuana are sometimes difficult for teens to acquire. As a result, many are turning to their parents medicine cabinets as a source for recreational drugs.

[From the website drugabuse.gov] In 2008, 15.4 percent of 12th-graders reported using a prescription drug nonmedically within the past year. This category includes:

  • amphetamines
  • sedatives/barbiturates
  • tranquilizers
  • opiates other than heroin
    • hydrocodone, oxycodone

When adolescent patient presents to the ED, consider the possibility of a poly-pharmacy overdose. Always query parents about the presence of OTC and Rx medications in their home, and what is within reach of their kids.

While sedatives and analgesics are concerning, be alert for overdoses of more mundane medications like beta blockers and calcium-channel blockers which often pose a much more lethal threat. Consider overdose in adolescent patients with:

  • GI or respiratory complaints
  • Altered mental status (combative or somnolent)
  • Abnormal vital signs
  • History of depression or psychiatric illness

Monitoring the Future Study: Trends in Prevalence of Various Drugs for 8th-Graders, 10th-Graders, and 12th-Graders

2005-2008 (in percent)*

 

8th-Graders

10th-Graders

12th-Graders

 

2005

2006

2007

2008

2005

2006

2007

2008

2005

2006

2007

2008

Any Illicit Drug Use

Lifetime
Past Year
Past Month

21.4
15.5
  8.5

20.9
14.8
  8.1

[19.0]
[13.2]
  7.4

19.6
14.1
  7.6

38.2
29.8
17.3

36.1
28.7
16.8

35.6
28.1
16.9

34.1
26.9
15.8

50.4
38.4
23.1

48.2
36.5
21.5

46.8
35.9
21.9

47.4
36.6
22.3

Full chart available by clicking link in references.

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Serotonin is a neurotransmitter that has central and peripheral effects. It regulates the secretion of ADH from the hypothalamus and also controls the chemoreceptive trigger zone (CTZ) which induces emesis. Here are a list of medications categorized by the way they affect serotonin. Remember, any combination of these agonists could precipitate serotonin syndrome:

Enhance 5-HT synthesis: L-tryptophan

Direct HT agonists: Ergots, metoclopramide, sumatriptan, buspirone

Increase 5-HT release: amphetamines, cocaine, dextromethorphan, MDMA, L-dopa

Inhibit 5-HT breakdown: MAOIs, Linezolid

Inhibit 5-HT re-uptake: SSRIs (paxil), amphetamines, carbamazapine, tramadol, TCAs, citalopram, trazodone, lamotrigine, meperidine

 


Category: Toxicology

Title: Diagnostic Odors

Keywords: acetone, cyanide, odor (PubMed Search)

Posted: 3/19/2009 by Fermin Barrueto, MD (Updated: 12/7/2021)
Click here to contact Fermin Barrueto, MD

Goldfrank's sniffing bar: no this is not a pub where toxicologist's hang out but rather a bar that assists with teaching the recognition of odors related to toxicology. Certain drugs and compounds have a distinct aroma.

The following is a list odors, see if you can name a medication or compound that has that odor - scroll down further to see the corresponding answers (if you really got all 5 email me and convince me):

1) Bitter Almond

2) Rotten Eggs

3) Wintergreen

4) Garlic

5) Sweet, Fruity (acetone)

 

Answers:

1) Cyanide; 2) N-acetylcysteine or Hydrogen Sulfide; 3) Methylsalicylate (like bengay); 4) Arsenic, organophosphate insecticides; 5) Chloroform, chloral hydrate


Category: Toxicology

Title: Black Box Warning for Metoclopramide

Keywords: metoclopramide, black box warning, tardive dyskinesia (PubMed Search)

Posted: 3/12/2009 by Bryan Hayes, PharmD (Updated: 12/7/2021)
Click here to contact Bryan Hayes, PharmD

Add metoclopramide (Reglan) to the laundry list of medications with black box warnings from the FDA. Why was a black box warning added?

  • Long-term metoclopramide use has been linked to tardive dyskinesia (involuntary and repetitive body movements) even after the drug is no longer being taken.
  • Risk factors: Long-term or high-dose use, elderly, female gender.
  • Recommended that metoclopramide treatment not exceed 3 months.
What implications does this have for our practice in the ED?
  • None really.
  • Just be aware of the dopamine antagonist effects (EPS - dystonic reactions) that are possible whenever you order metoclopramide in the acute setting.
  • These effects can be treated effectively with an anticholinergic agent, such as diphenhydramine or benztropine.

Category: Toxicology

Title: Clevidipine - A new IV calcium channel blocker

Keywords: Clevidipine, calcium channel antagonist, calcium channel blocker, antihypertensive (PubMed Search)

Posted: 3/5/2009 by Ellen Lemkin, MD, PharmD (Updated: 12/7/2021)
Click here to contact Ellen Lemkin, MD, PharmD

Clevidipine

  • A new intravenous antihypertensive agent
  • Has a very rapid onset (2-4 min) and offset (5-15 min), in contrast to the available IV calcium channel blocker nicardipine, which has a duration of action of 3-6 hours
  • Contraindicated in patients with soy or egg allergies, and in those with defective lipid metabolism
  • Most common ADR's reported were headache, nausea, and vomiting
  • Initiate at 1-2 mg/hr, most respond at doses between 4-6 mg/hr
  • Maximum recommended dose is 16 mg/hr
  • Costs between $86 to $140 per 50 mg vial

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Category: Toxicology

Title: Pharmacoeconomics

Keywords: ondansetron, albuterol (PubMed Search)

Posted: 2/26/2009 by Fermin Barrueto, MD (Updated: 12/7/2021)
Click here to contact Fermin Barrueto, MD

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: 12/7/2021)
Click here to contact Fermin Barrueto, MD

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: 12/7/2021)
Click here to contact Bryan Hayes, PharmD

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: 12/7/2021)
Click here to contact Ellen Lemkin, MD, PharmD

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.

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Category: Toxicology

Title: Fun Rodenticides

Keywords: brodifacoum, cholecalciferol, strychnine (PubMed Search)

Posted: 1/29/2009 by Fermin Barrueto, MD (Updated: 12/7/2021)
Click here to contact Fermin Barrueto, MD

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: 12/7/2021)
Click here to contact Fermin Barrueto, MD

 

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

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Category: Toxicology

Title: If you like sushi - Fugu

Keywords: tetrodotoxin, sushi (PubMed Search)

Posted: 1/15/2009 by Fermin Barrueto, MD (Updated: 12/7/2021)
Click here to contact Fermin Barrueto, MD

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

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: 12/7/2021)
Click here to contact Bryan Hayes, PharmD

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.

 


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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: 12/7/2021)
Click here to contact Ellen Lemkin, MD, PharmD

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

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