UMEM Educational Pearls - By Bryan Hayes

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)
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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.
iPhone Screenshot 1

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Category: Pharmacology & Therapeutics

Title: Fidaxomicin vs. Vancomycin for Clostridium difficile infection

Keywords: vancomycin, c. diff, clostridium difficile, fidaxomicin (PubMed Search)

Posted: 4/4/2012 by Bryan Hayes, PharmD (Emailed: 4/7/2012) (Updated: 4/7/2012)
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In a recent  multicenter, double-blind, randomized, non-inferiority trial, vancomycin was compared to fidaxomixin for Clostridium difficile infection.

  • Location: 45 sites in Europe and 41 sites in the USA and Canada

  • Patients: Age 16 years or older with acute toxin-positive C difficile infection.

  • Treatment: Oral fidaxomicin (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days.

  • Endpoint: Clinical cure, defined as resolution of diarrhea and no further need for treatment. 

  • Results: 198 (91.7%) of 216 patients in the per-protocol population given fidaxomicin achieved clinical cure, compared with 213 (90.6%) of 235 given vancomycin (one-sided 97·5% CI -4·3%). Occurrence of treatment-emergent adverse events did not differ between groups. 

  • Author conclusions: Fidaxomicin could be an alternative treatment for infection with C difficile, with similar efficacy and safety to vancomycin.

  • Funding: Optimer Pharmaceuticals.

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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)
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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: Pharmacology & Therapeutics

Title: Egg Allergy and Influenza Vaccine: No more contraindication

Keywords: egg, influenza, vaccine (PubMed Search)

Posted: 3/2/2012 by Bryan Hayes, PharmD (Emailed: 3/3/2012) (Updated: 3/4/2012)
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The seasonal influenza vaccine is produced in chicken eggs. Ovalbumin, an egg protein, is often listed as a component of the purified vaccine on most drug-package inserts. The concentration of ovalbumin indicates the potential egg-allergen content of a vaccine.

Earlier ACIP guidelines recommended against giving the influenza vaccine to people with egg allergy, including those with a history of mild symptoms. However, several studies showed that influenza vaccine containing inactivated, or killed, virus is safe to give to people with egg allergy, especially those with a history of mild allergic reactions.

Influenza vaccines are now made with much lower ovalbumin concentrations than in the past; therefore, the level of potential egg protein allergens in a single dose of vaccine is extremely low.

The following are ACIP recommendations for the 2011 to 2012 influenza season:

  • Inactivated influenza vaccine (seasonal flu shot) is safe to give to people whose history of allergic reactions to egg has been limited to hives.
  • People with more severe allergic reactions to egg may receive the seasonal flu shot, but the vaccine must be given by a healthcare professional familiar with the signs and symptoms of an allergic reaction to egg and who has the ability to treat a severe reaction if one occurs.

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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)
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  • 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: Pharmacology & Therapeutics

Title: Droperidol as an alternative parenteral antiemetic

Keywords: droperidol, antiemetic, qt prolongation (PubMed Search)

Posted: 1/31/2012 by Bryan Hayes, PharmD (Emailed: 2/4/2012) (Updated: 2/4/2012)
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In the setting of critical drug shortages of ondansetron, prochlorperazine, and metoclopramide, consider droperidol as a viable option for the treatment of nausea and vomiting.

Although it is similar to haloperidol, it is actually FDA-approved for “prevention and/or treatment of nausea and vomiting from surgical and diagnostic procedures” (unlike haloperidol). Ironically, it is not approved for agitation, although it can be used for that indication.

Dosing for antiemesis is 1.25 to 2.5 mg IV/IM. Additional doses of 0.625 to 1.25 mg can be administered to achieve desired effect. Onset is 3-5 minutes and duration of effect is 2-4 hours. It should be administered via slow IV push over 2 minutes.

Why is it not commonly used? Black Box Warning for QTc prolongation. An ECG is a must prior to administration. Also be cautious in patients who are on other medications that can prolong the QT interval (

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)
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  • 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: Pharmacology & Therapeutics

Title: Updated Guidelines for Acute Uncomplicated Cystitis in Women

Keywords: cystitis, uti, nitrofurantoin, urinary tract infection (PubMed Search)

Posted: 1/3/2012 by Bryan Hayes, PharmD (Emailed: 1/7/2012) (Updated: 1/7/2012)
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In 2011, updated treatment guidelines were published for acute uncomplicated cystitis and pyelonephritis in women. The recommendations differ from the previous iteration due to increased E. Coli resistance. The good news is we have been ahead of the curve in changing our prescribing habits.

Cystitis (recommendations in order of preference)

  1. Nitrofurantoin 100 mg BID X 5 days
  2. Bactrim DS 1 tab BID X 3 days (not recommended when resistance rate is > 20% - UMMC is 32%)
  3. Fosfomycin (not currently available at UMMC)
  4. Fluoroquinolones not recommended as first-line therapy due to “propensity for collateral damage”
  5. Beta-lactam agents, including amoxicillin-clavulanate, cefdinir, cefaclor, and cefpodoxime-proxetil, in 3–7-day regimens are appropriate choices for therapy when other recommended agents cannot be used. Other beta-lactams, such as cephalexin, are less well studied but may also be appropriate in certain settings.

Take home points:

  • Be familiar with your institution’s antibiogram
  • Use nitrofurantoin first-line for uncomplicated cystitis in women (it is contraindicated with CrCl < 60 mL/min)
  • Consider beta-lactams such as Augmentin or Vantin (cefpodoxime) in patient’s with kidney injury

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Category: Toxicology

Title: Warfarin management of ED patients

Keywords: warfarin, INR (PubMed Search)

Posted: 11/29/2011 by Bryan Hayes, PharmD (Emailed: 12/8/2011) (Updated: 12/8/2011)
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A recent study highlighted the challenges we face managing ED patients on warfarin therapy. Some key observations about how we're doing: 

  • Only 71% of patients on warfarin had an INR checked
  • Nontherapeutic INRs were recorded for 49%; ED providers intervened to address these results in 21% of cases
  • 71% of patients with a supratherapeutic INR received an intervention compared with 9% of patients with a subtherapeutic INR
  • 30% of patients received or were prescribed potentially interacting medications
  • Recommendations for specific anticoagulation follow-up were documented for only 19% of all patients

Literature continues to show warfarin is the most dangerous medication for our patients. Meticulous monitoring and follow up will help us potentially avoid serious interactions and adverse events.

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Category: Pharmacology & Therapeutics

Title: Emergency Hospitalizations for ADEs in Older Americans

Keywords: older adult, adverse drug event, ade, elderly, warfarin (PubMed Search)

Posted: 11/29/2011 by Bryan Hayes, PharmD (Emailed: 12/3/2011) (Updated: 12/3/2011)
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A recent article estimated 100,000 emergency hospitalizations for adverse drug events in U.S. adults 65 years of age or older each year. Nearly half of these hospitalizations were among adults ≥80 years old and two-thirds were due to unintentional overdoses.

Four medications or medication classes were implicated alone or in combination in 67% of hospitalizations:

  • Warfarin (33.3%)
  • Insulins (13.9%)
  • Oral antiplatelet agents (13.3%)
  • Oral hypoglycemic agents (10.7%)

Opioids were #5. Digoxin was #7 and resulted in the highest percentage of hospitalizations per ED visit at 80%.

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Category: Toxicology

Title: Medication Causes of Idiopathic Intracranial Hypertension

Keywords: idiopathic intracranial hypertension, pseudotumor cerebri, tetracycline, vitamin a (PubMed Search)

Posted: 10/11/2011 by Bryan Hayes, PharmD (Emailed: 11/10/2011) (Updated: 11/10/2011)
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Several medications have been linked to causing idiopathic intracranial hypertension (pseudotumor cerebri). Be sure to record an accurate medication history in patients you suspect of having this diagnosis.

  • Excessive doses of vitamin A
    • Other retinoids too: retinol, isotretinoin, and tretinoin
  • Tetracyclines (tetracycline, doxycycline, minocycline)
  • Growth hormone

Withdrawal of the offending agent will generally resolve the symptoms.

Category: Pharmacology & Therapeutics

Title: Nicardipine vs Labetalol for Blood Pressure Management in the ED

Keywords: nicardipine, labetalol, blood pressure (PubMed Search)

Posted: 10/30/2011 by Bryan Hayes, PharmD (Emailed: 11/5/2011) (Updated: 11/5/2011)
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A recent randomized trial compared nicardipine as a continuous infusion to labetalol boluses to determine which one was more effective at lowering blood pressure to a target range within 30 minutes.

Median initial SBP for the 226 patients was 212 mm Hg. Within 30 minutes, nicardipine patients more often reached target range than labetalol (91.7 vs. 82.5%, P = 0.039). Of 6 BP measures (taken every 5 minutes) during the study period, nicardipine patients had higher rates of five and six instances within target range than labetalol (47.3% vs. 32.8%, P = 0.026).

What this means: Nicardipine is a reasonable choice for patients needing acute lowering of blood pressure (e.g., ischemic stroke with tPa).  Nicardipine seems to achieve faster and smoother lowering of blood pressure than labetalol therapy with less blood pressure readings outside the target range.

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Category: Pharmacology & Therapeutics

Title: Warfarin-Related Nephropathy

Keywords: warfarin, creatinine, nephropathy (PubMed Search)

Posted: 9/27/2011 by Bryan Hayes, PharmD (Emailed: 10/1/2011) (Updated: 10/1/2011)
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An acute increase in the INR over 3 in patients with chronic kidney disease (CKD) is often associated with an unexplained acute increase in serum creatinine and an accelerated progression of CKD.

Kidney biopsy in a subset of these patients showed obstruction of the renal tubule by red blood cell casts, and this appears to be the dominant mechanism of the acute kidney injury. This has been termed warfarin-related nephropathy (WRN).

In 15,258 patients who initiated warfarin therapy during a 5-year period, 4006 had an INR over 3 and creatinine measured at the same time. A presumptive diagnosis of WRN was made if the creatinine increased by over 0.3 mg/dl within 1 week after the INR exceeded 3 with no record of hemorrhage. WRN occurred in 20.5% of the entire cohort, 33.0% of the CKD cohort, and 16.5% of the no-CKD cohort. Other risk factors included age, diabetes mellitus, hypertension, and cardiovascular disease. The 1-year mortality was 31.1% in patients with WRN compared with 18.9% in those without WRN, an increased risk of 65%.

Take home message: Although the mechanisms are not clear, be very wary of even a small creatinine bump in patients presenting with an INR > 3 on warfarin therapy.  Yet another reason to fear warfarin...

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Category: Toxicology

Title: Adenosine in Patients with Only Central Line Access

Keywords: adenosine, central line (PubMed Search)

Posted: 8/29/2011 by Bryan Hayes, PharmD (Emailed: 9/8/2011) (Updated: 9/8/2011)
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Every so often a patient arrives in PSVT with their only intravenous access being through a hemodialysis port.

Initial dose of adenosine should be reduced to 3 mg if administered through a central line.  Remember a central line delivers the adenosine right where you need it.  This recommendation is supported by the 2010 ACLS guidelines.  Second and third doses should be 6 mg (instead of 12 mg).

Cases of prolonged bradycardia and severe side effects have been reported after full-dose adenosine through a central line.  Other situations to consider lower doses include patients currently receiving carbamazepine or dipyridamole or in those with a transplanted heart.

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Category: Toxicology

Title: Adenosine in Patients Using Caffeine

Keywords: adenosine, caffeine (PubMed Search)

Posted: 8/9/2011 by Bryan Hayes, PharmD (Emailed: 8/11/2011) (Updated: 8/11/2011)
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Caffeine can interfere with the successful reversion of paroxysmal supraventricular tachycardia (SVT) by adenosine.

Caffeine is an adenosine receptor blocker.

Ingestion of caffeine less than 4 hours before a 6-mg adenosine bolus significantly reduced its effectiveness in the treatment of SVTTheophylline is similar but not many patients are prescribed it anymore.

An increased initial adenosine dose may be indicated for these patients. A first dose of 12 mg (instead of 6), followed by 2nd and 3rd doses of 18 mg (instead of 12) may be indicated.

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Category: Pharmacology & Therapeutics

Title: Oral Phenytoin Loading

Keywords: phenytoin (PubMed Search)

Posted: 8/2/2011 by Bryan Hayes, PharmD (Emailed: 8/6/2011) (Updated: 8/6/2011)
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  • We often see seizure patients on phenytoin therapy who have subtherapeutic levels.  Most patients do not require intravenous loading and can be adequately managed with oral treatment.
  • To estimate what dose to prescribe, use the following equation: [0.7 x IBW x (15 - current level)].  For example if a 70 kg patient has a level of 8 mcg/mL (mg/L), we would need ~400 mg loading dose to achieve a level of 15.
  • Phenytoin is known for its erratic absorption and propensity for causing GI upset with doses too high.  The recommended strategy is to avoid administering more than 400 mg at one time and separate the doses by 2 hours.  This would take three doses over 4 hours for a 1 gm load.
    • In the ED, an effective strategy for a 1 gm oral load is 500 mg now and 500 mg in 2 hours at discharge.  Patients tolerate it well, it cuts down on ED length of stay, and still achieves therapeutic levels.  Remember that an oral suspension formulation is also available.

Category: Toxicology

Title: Fluoroquinolone-Induced Tendon Rupture

Keywords: fluroquinolone, tendon rupture (PubMed Search)

Posted: 7/28/2011 by Bryan Hayes, PharmD
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The incidence of tendon rupture related to fluoroquinolone use is reported to be in the range of 1 in 6000.

The risk of tendon rupture associated with FQ use is increased in those older than 60 years of age, those taking steroids, and in patients who have received heart, renal, or pulmonary transplants.

There is no evidence that tendon rupture is more likely for patients taking levofloxacin compared to other FQs.

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Category: Toxicology

Title: Levamisole Toxicity from Adulterated Cocaine and Heroin

Keywords: levamisole, cocaine, vasculitis, agranulocytosis, heroin (PubMed Search)

Posted: 6/23/2011 by Bryan Hayes, PharmD (Emailed: 7/14/2011) (Updated: 7/14/2011)
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Levamisole is an antihelminthic agent used in humans to treat certain parasitic infections and cancers.  It is more commonly used for veterinary purposes.  It has recently seen increasing use as a cutting agent for cocaine and heroin, found in up to 70% of cocaine sample seized by the DEA.  It adds bulk and weight to powdered cocaine and is even theorized to increase the stimulant effects.

Toxicity of levamisole includes agranulocytosis and vasculitis (see attached document for recent image from NEJM).

Trivia: Levamisole was found in DJ AM and Andrew Koppel (Ted Koppel’s son), who both died of drug overdoses.

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1106231638_levamisole.doc (526 Kb)

Category: Pharmacology & Therapeutics

Title: Argatroban in the ED patient

Keywords: argatroban, direct thrombin inhibitor, heparin, HIT (PubMed Search)

Posted: 6/6/2011 by Bryan Hayes, PharmD (Emailed: 7/2/2011) (Updated: 7/2/2011)
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Patients requiring anticoagulation for HIT or with a history of HIT may be initiated on argatroban.  We have recently been seeing increased utilization.  Here are some important points to remember.

  • MOA: Direct thrombin inhibitor – reversibly binds to the active thrombin site of free and clot-associated thrombin
  • Monitoring parameters:
    • aPTT prior to starting therapy (similar to heparin)
    • aPTT two hours after initiation of therapy or after dose change
    • Signs/symptoms of bleeding, LFTs, CBC, Hgb/Hct
  • Dosing (general): 2 mcg/kg/min (actual body weight)
  • Important notes:
    • Discontinue all heparin products including hep locks and coated catheters.  This includes all LMWH such as enoxaparin.
    • Causes false elevation of INR by cross-reacting with the INR assay

Category: Toxicology

Title: Beware These Medications as Summertime Approaches

Keywords: lithium, digoxin, colchicine, narrow therapeutic index (PubMed Search)

Posted: 6/6/2011 by Bryan Hayes, PharmD (Emailed: 6/9/2011) (Updated: 6/9/2011)
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Dehydration and subsequent prerenal acute kidney injury can result when temperatures begin to rise in the summer months.  As a result, medications with narrow therapeutic indices that are primarily renally excreted may accumulate.  Here are the specific ones to look out for:

  • Digoxin
  • Lithium
  • Colchicine
  • Phenobarbital and theophylline (partially eliminated unchanged by the kidneys)