UMEM Educational Pearls - Pharmacology & Therapeutics

Category: Pharmacology & Therapeutics

Title: Tranexamic Acid in Anterior Epistaxis

Keywords: anterior epistaxis, tranexamic acid, antifibrinolytic (PubMed Search)

Posted: 2/6/2014 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

Tranexamic Acid (TXA) topically applied was compared to anterior nasal packing in 216 patients with acute anterior epistaxis. Cotton pledgets (15 cm) soaked in injectable TXA (500 mg/5 ml) were inserted into the bleeding nostril and removed after bleeding had arrested. This was compared to standard anterior packing.


                                                                   TXA            Anterior packing

% pts bleeding stopped in 10 min:           71%           31.2%                

Discharge after 2 hours                           95.3%           6.4%

Rebleeding in 24 h hours                          4.7%        11%

Satisfaction scores                                    8.5               4.4


Bottom line: topical tranexamic acid looks promising for control of uncomplicated anterior epistaxis.

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Category: Pharmacology & Therapeutics

Title: Minimum Methadone Dose to Prevent Withdrawal

Keywords: methadone, withdrawal (PubMed Search)

Posted: 1/23/2014 by Bryan Hayes, PharmD (Emailed: 2/1/2014) (Updated: 2/1/2014)
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In most situations (dependant on state laws and institutional policies), methadone-maintained patients enrolled in a drug abuse program are best managed by continuing methadone at the usual maintenance levels with once-a-day oral administration.

Pearl: In the event the methadone clinic is closed and/or the dose cannot be verified, 30-40 mg (10-20 mg IM) is generally enough to prevent withdrawal in most patients.

This is only a short-term measure and some patients may require additional methadone. Full doses of methadone should be reinstituted as soon as possible.

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Category: Pharmacology & Therapeutics

Title: High-Dose Droperidol: Little, if any, Risk for QT Prolongation

Keywords: droperidol, QT prolongation (PubMed Search)

Posted: 12/31/2013 by Bryan Hayes, PharmD (Emailed: 1/4/2014) (Updated: 8/15/2014)
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46 patients treated with high-dose droperidol (10-40 mg) were studied prospectively with continuous holter recording.

What they did

Patients initially received 10 mg droperidol as part of a standardized sedation protocol (for aggression). An additional 10 mg dose was given after 15 min if required and further doses at the clinical toxicologist's discretion.

Continuous 12-lead holter recordings were obtained for 2-24 hours. QTc > 500 msec was defined as abnormal (with heart rate correction - QTcF).

What they found

Only 4 patients had abnormal QT measurements, three given 10 mg and one 20 mg. All 4 had other reasons for QT prolongation. No patient given > 30 mg had a prolonged QT. There were no dysrhythmias.

What it means

There was little evidence supporting droperidol being the cause and QT prolongation was more likely due to pre-existing conditions or other drugs.

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Tranexamic acid (TXA) is an antifibrinolytic that prevents clot breakdown by inhibiting plasminogen activation and plasmin activity

The CRASH-2 trial enrolled 20,211 adult trauma patients with significant hemorrhage (SBP <90 or HR 110) or at significant risk of hemorrhage

Patients were randomized to 1 gram TXA over 10 minutes followed by an infusion of 1 gm over 8 hours vs placebo

There was a significant reduction in the relative risk off all cause mortality of 9% (14.5% vs 16%, RR 0.91, CI 0.85-0.97, p = 0.0035)

The patients that benefited most were those most severely injured, and in those treated in less than 3 hours of injury.

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Category: Pharmacology & Therapeutics

Title: JNC 8 Recommendations for Hypertension

Keywords: Hypertension, treatment (PubMed Search)

Posted: 12/21/2013 by Michael Bond, MD (Updated: 9/27/2023)
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JNC8 (the Eigth Joint National Commission) released their recommendations for blood pressure management this week. The full article as published in JAMA can be found at

Highlights from this report are

  • Older adults do not need to be placed on antihypertensive medications unless their SBP > 150 or DBP > 90. 
  • Younger patients should still be started if their SBP > 140 or DBP > 90.
  • Firstline drug treatment recommendations are:
    • Non-black patients: start with thiazide diuretics, calcium channel blockers, angiotension converting enzyme (ACE) inhibitors, or angiotension-receptor blockers (ARBs).
    • For black patients start with thiazide diuretics or calcium channel blockers.
    • Patients with chronic kidney disease should be on an ACE or ARB.

General Pearl:  Remember to be cautious in acutely lowering the blood pressure in asymptomatic patients.  Acute lowerings can cause watershed ischemia leading to strokes.

Category: Pharmacology & Therapeutics

Title: Add Atypical Coverage for Healthcare-Associated Pneumonia Patients

Keywords: healthcare-associated pneumonia, HCAP, atypical, macrolide, fluoroquinolone (PubMed Search)

Posted: 12/2/2013 by Bryan Hayes, PharmD (Emailed: 12/7/2013) (Updated: 12/7/2013)
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In a potentially ground breaking study of healthcare-associated pneumonia (HCAP) patients, atypical pathogens were identified in 10% of cases!

Application to clinical practice: Add atypical coverage with a macrolide or respiratory fluoroquinolone for HCAP patients who have been in the community for any length of time.

The study also identified HCAP patients who may not require 3 'big gun' broad-spectrum antibiotics. This is a practice changing article for ED providers. For more analysis of the study, please note the bonus reading links below.

Bonus reading:

Dr. Emily Heil (@emilylheil) analyzes the full study in more depth at Academic Life in Emergency Medicine:

Dr. Ryan Radecki (@emlitofnote) critiques the study at Emergency Medicine Literature of Note:

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Category: Pharmacology & Therapeutics

Title: Edoxaban, a new Xa inhibitor

Keywords: oral anticoagulant,edoxaban,atrial fibrillation,stroke,Xa (PubMed Search)

Posted: 12/5/2013 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

It has linear, predictable pharmacokinetics, achieves maximal concentration within 1-2 hours, is 50% renally excreted, and has a half life is 9-11 hours.

Edoxaban was evaluated in a recent trial comparing warfarin in patients with atrial fibrillation.

The primary end point or first stroke or systemic pulmonary embolic event occurred in 1.5% with warfarin, compared with 1.18% in the high dose edoxaban (HR 0.79; 97.5% CI 0.63-0.99, P<0.001). In the intention to treat there were trends favoring high dose edoxaban and unfavorable trends with the lower dose.

The principal safety end point of major bleeding occurred in 3.43% with warfarin versus 2.75% with high dose edoxaban (HR 0.86; 95% CI 0.71-0.91, P<0.001). 

Bottom line: Both high dose (60 mg) and low dose (30 mg) edoxaban were non-inferior to warfarin with prevention of stroke or systemic emboli, and were associated with significantly lower rates of bleeding and death from cardiovascular causes.

Currently it is approved for use in Japan.

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Category: Pharmacology & Therapeutics

Title: Cephalosporin Side Chains and Allergies

Keywords: Cephalosporin,penicillin,anaphylaxis,urticaria,cross sensitivity (PubMed Search)

Posted: 11/7/2013 by Ellen Lemkin, MD, PharmD (Updated: 9/27/2023)
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When patients with severe allergies to penicillin (urticarial, bronchospasm, anaphylaxis, angioedema) are excluded, the cross reactivity to cephalosporins is very low (approximately 0.1%)

The reaction is related to structures in the side chain, not the cyclical structure as thought in the past.

There are several cephalosporins with IDENTICAL side chains that should not be given to patients with allergies to specific penicillins, namely:

  • Penicillin:   do not give cefoxitin
  • Ampicillin:   do not give cefaclor or cephalexin
  • Amoxicillin: do not give cefadroxil or cefprozil

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Category: Pharmacology & Therapeutics

Title: Nail in the NAC Coffin for Prevention of Contrast-Induced Nephropathy

Keywords: contrast-induced nephropathy, n-acetylcysteine, NAC (PubMed Search)

Posted: 10/31/2013 by Bryan Hayes, PharmD (Emailed: 11/2/2013) (Updated: 11/2/2013)
Click here to contact Bryan Hayes, PharmD

A recent meta-analysis has called into question whether contrast-induced AKI even occurs after an IV dye load for radiologic imaging. [1] This conclusion is most certainly up for debate.

Irrespective of that conclusion, prevention of contrast-induced nephropathy is still important. Is there any benefit to using N-acetylcysteine over normal saline in the ED? Probably not according to a new study. [2]

  • The primary outcome was contrast-induced nephropathy, defined as an increase in creatinine level of 25% or 0.5 mg/dL, measured 48 to 72 hours after CT.
  • The authors found no reduction in contrast-induced nephropathy in patients who received NAC vs normal saline (about 7% in each group).
  • The important finding is that the contrast-induced nephropathy rate in patients receiving less than 1 L IV fluids in the ED was 13% compared to 3% for more than 1 L.


  1. Contrast-induced AKI does happen after emergency CT.
  2. NAC does not provide additional benefit over saline alone.
  3. Giving more than 1 L of normal saline markedly reduces the risk.

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Category: Pharmacology & Therapeutics

Title: Initiating Treatment for Cryptococcal Meningitis in the ED (submitted by Ryan Spangler, MD)

Keywords: cryptococcal, meningitis, amphotericin, flucytosine (PubMed Search)

Posted: 9/25/2013 by Bryan Hayes, PharmD (Emailed: 10/5/2013) (Updated: 10/5/2013)
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Treatment of patients with HIV/AIDS can frequently mean consideration for, and need to treat cryptoccocal meningitis.

Since 1997, studies have demonstrated that high-dose Amphotericin B combined with flucytosine has improved outcomes compared to low dose treatment or monotherapy.

A recent 2013 study reiterated this approach, showing significant decrease in deaths at 70 days post-treatment and increased rates of yeast clearance with combination therapy of Amphotericin B plus flucytosine. 


Antifungal treatment of cryptococcal meningitis should start with Amphotericin B at 0.7-1 mg/kg IV daily plus concurrent flucytosine 25 mg/kg orally q6 hours. Fluconazole can be substituted in place of flucytosine if it is not available or not tolerated.

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Category: Pharmacology & Therapeutics

Title: Procainamide Dosing

Keywords: procainamide,atrial fibrillation,prolonged QT,monomorphic VT (PubMed Search)

Posted: 10/3/2013 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

ACLS recommendation for procainamide in tachycardic rhythms is:

Loading dose 20 mg/minute (up to 50 mg/minute for more urgent situations) until:

  • Arrhythmia is controlled
  • Hypotension occurs
  • QRS complex widens by 50% of its original width
  • or total of 17 mg/kg is given

Maintenance infusion is 1 to 4 mg/min.


An easier method for dosing acute onset atrial fibrillation in stable patients was used in the Ottawa Aggressive Protocol, in which they administered 1 gm over 60 min, which was interrupted if BP < 100 mmHg; if corrected by a 250 ml IV bolus, the infusion was resumed. This was not used, however if the patient was to be admitted.


A strategy for treating stable monomorphic VT with procainamide used:

100 mg IV over 1-2 minutes, repeat as necessary until an endpoint of

  • Termination of tachycardia
  • Drug induced hemodynamic deterioration
  • Completion of 800 mg maximal dose

If no slowing of the tachycardia occurred with a dose of 400 mg, the administration was ceased.

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Category: Pharmacology & Therapeutics

Title: How to Dose Antibiotics in the Critically Ill Obese Patient

Keywords: antibiotic, obese, obesity, critically ill, antimicrobial (PubMed Search)

Posted: 8/31/2013 by Bryan Hayes, PharmD (Emailed: 9/7/2013) (Updated: 9/7/2013)
Click here to contact Bryan Hayes, PharmD

Although there is a paucity of data to guide dosing of antimicrobials in the critically ill obese patient, we can draw some conclusions from existing kinetic studies. Assuming normal renal and hepatic function, here's what to do:

Penicillins: Use the high end of dosing range. For example, if the plan is to use piperacillin/tazobactam 3.375 gm IV every 6 hours for a complicated intra-abdominal infection, use 4.5 gm instead.

Cephalosporins: Use the high end of the dosing range.

Carbapenems: Use the high end of the dosing range.

Quinolones: Use the high end of the dosing range.

Aminoglycosides: Dose using adjusted body weight. ABW (kg) = IBW + 0.4 X (actual body weight - IBW)

Vancomycin: 15-20 mg/kg actual body weight every 8 to 12 hours. Adjust based on trough level.

When dosing most antibiotics in critically ill obese patients, use the high end of the dosing range (if not more).

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Category: Pharmacology & Therapeutics

Title: Fluids are Drugs

Keywords: fluid, saline, chloride (PubMed Search)

Posted: 7/22/2013 by Bryan Hayes, PharmD (Emailed: 8/3/2013) (Updated: 8/2/2013)
Click here to contact Bryan Hayes, PharmD

A recent review identified 5 key points to consider when prescribing fluids.

  1. Fluids should be prescribed as drugs, recognizing that any fluid can be harmful if dosed incorrectly.
  2. The differences in efficacy between administering a 'crystalloid versus colloid' are modest; however, the cumulative differences in safety appear more significant.
  3. The qualitative toxicity associated with hydroxyethyl starch (HES) and isotonic saline remains a concern.
  4. The differences in chloride load and strong ion difference between cystalloid solutions, such as isotonic saline compared with physiologically more balanced solutions, appear to have clinical relevance.
  5. The 'default' resuscitation fluid for acutely ill patients should likely be physiologically balanced crystalloid solutions (eg, PlasmaLyte or Ringer's lactate ).

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A recent, randomized study evaluated two approaches for treating acute pain in an inner-city ED.

  • Group 1 received hydromorphone 2 mg. Group 2 received hydromorphone 1 mg (with the option of a second 1 mg dose 15 minutes later).
  • 1 hour after the dose, patients were asked if they wanted more pain medication.
  • Both groups had an equal proportion of patients decline more pain medication at one hour (67%). 61% of patients in the 1 + 1 group only needed the initial dose of hydromorphone!
  • Secondary outcomes and safety measures were also similar between the groups.
  • Patients with chronic pain, age >64, weight <150 pounds, or opioid use within last 7 days were excluded. 

Application to clinical practice: For most patients with acute, severe pain in the ED, start with hydromorphone 1 mg. It may be all the patient needs and can potentially avoid giving them extra opioid they don't need.

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  • Hold metformin if the patient is at risk for dehydration (eg. vomiting, diarrhea) due to the risk of lactic acidosis
  • Medications that stimulate insulin secretion (eg. sulfonylureas, repaglinide, or nateglinide) should be held if the patient is at risk for hypoglycemia
  • Patients usually should continue their basal insulin, but may decrease or hold their bolus dosing.
  • Finger sticks should be checked every 2-4 hours for those on insulin, or 2-4 times per day for type II diabetics not on insulin.

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Category: Pharmacology & Therapeutics

Title: Add Strep Coverage to Outpatient Cellulitis Treatment Regimens

Keywords: cellulitis, cephalexin, sulfamethoxazole/trimethoprim, Bactrim, streptococcus (PubMed Search)

Posted: 5/20/2013 by Bryan Hayes, PharmD (Emailed: 6/1/2013) (Updated: 5/31/2013)
Click here to contact Bryan Hayes, PharmD


In the current era of community-acquired MRSA (CA-MRSA), most of our outpatient treatment options for cellulitis aim to cover MRSA. Choices include sulfamethoxazole/trimethoprim (SMZ-TMP), doxycycline, linezolid, and clindamycin (depending on local susceptibility patterns).

A New Study

  • In a double-blind, placebo-controlled trial 146 patients with cellulitis were randomized to receive cephalexin alone or cephalexin + SMZ-TMP for 7-14 days
  • Lots of exclusion criteria basically narrowed the patient population to uncomplicated cellultits with no history of diabetes or other immunocompromising conditions
  • Cure rates up to 30 days post-treatment were the same between the two groups (>80%)

Take Home Clinical Points

  • Even in communities with high prevalence of MRSA, uncomplicated cellulitis cases without pus generally seem to be strep species.
  • Therefore, make sure to include an anti-streptococcal component (such as cephalexin) to the MRSA agent (doxycycline or SMZ-TMP). Clindamycin has sufficient strep coverage by itself (but may not adequately cover MRSA).
  • Given the potential for MRSA infections to deteriorate quickly and the inability to differentiate staph from strep without cultures, MRSA coverage should still be considered.

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Category: Pharmacology & Therapeutics

Title: Hyperphosphatemia from Fosphenytoin?

Keywords: phosphate, fosphenytoin, phenytoin, hyperphosphatemia (PubMed Search)

Posted: 4/29/2013 by Bryan Hayes, PharmD (Emailed: 5/4/2013) (Updated: 5/2/2013)
Click here to contact Bryan Hayes, PharmD


Fosphenytoin is a prodrug and is metabolized quickly to phenytoin after administration. The conversion of fosphenytoin to phenytoin involves the release of phosphate. In fact, each mmol of fosphenytoin releases 1 mmol of phosphate.

Clinical Question

Are patients at risk for hyperphosphatemia after fosphenytoin loading?


There are only two cases of reported hyperphosphatemia.

  • A 17-year old African-American male with end-stage renal disease developed acute hyperphosphatemia to 3.9 mmol/L (12.1 mg/dL) following the IV administration of 1000 mg of fosphenytoin for an idiopathic complex partial seizure
  • An infant in status epilepticus had marked hyperphosphatemia 8.4 mmol/L (25.9 mg/dL) after a 5-10 fold dosing error.

Bottom Line

Despite the phosphate load from fosphenytoin administration, hyperphosphatemia is very rare and probably associated with renal insufficiency and dosing errors.

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Category: Pharmacology & Therapeutics

Title: Prothrombin Complex Concentrate Approved by FDA

Keywords: Prothrombin Complex Concentrate, warfarin, coumadin, vitamin K antagonist, anticoagulant, PCC (PubMed Search)

Posted: 5/2/2013 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD


  • Prothrombin Complex Concentrate (PCC) Kcentra™ has been approved for urgent reversal of major bleeding in patients taking vitamin K antagonists (e.g. warfarin).
  • It contains factors 2,7,9 and 10, and antithrombotic Proteins C and S.
  • Both fatal and non-fatal arterial and venous thromboembolic complications have occurred with Kcentra™. Thrombotic events occurred more frequently in the PCC group compared to plasma, although the differences were not statistically significant.
  • Volume overload occurred less frequently in the PCC group, as there is a smaller volume  administered with PCC compared to that of plasma.
  • Percentage of INR ≤ 1.3 at 30 minutes was 62% in the PCC group and 9.6% in the plasma group.

Approval of Kcentra™ may open the door for studying treatment of the bleeding patient on newer oral anticoagulants.

Category: Pharmacology & Therapeutics

Title: tPA Use in Patients on New Oral Anticoagulants: Recommendations from the 2013 Ischemic Stroke Guidelines

Keywords: alteplase, tPA, dabigatran, anticoagulant, apixaban, rivaroxaban (PubMed Search)

Posted: 4/3/2013 by Bryan Hayes, PharmD (Emailed: 4/6/2013) (Updated: 4/5/2013)
Click here to contact Bryan Hayes, PharmD

A new recommendation in the 2013 Ischemic Stroke Guidelines provides guidance on what to do in patients taking new oral anticoagulants who are deemed eligible for IV fibrinolysis. Here is what the guidelines say:

"The use of IV rtPA in patients taking direct thrombin inhibitors (dabigatran) or direct factor Xa inhibitors (rivaroxaban, apixaban) may be harmful and is not recommended unless sensitive laboratory tests such as aPTT, INR, platelet count, and ECT, TT, or appropriate direct factor Xa activity assays are normal, or the patient has not received a dose of these agents for >2 days (assuming normal renal metabolizing function)." (Class III; Level of Evidence C)
Additional points:
  • The most helpful lab tests are not widely available.
  • A detailed history is important, but not always obtainable.

Until further data are available, a history consistent with recent use of new oral anticoagulants generally precludes use of IV tPA.

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Category: Pharmacology & Therapeutics

Title: Levetiracetam (Keppra) for Status Epileptics

Keywords: Status epilepticus, Keppra, seizures, valproic acid, levetiracetam (PubMed Search)

Posted: 4/4/2013 by Ellen Lemkin, MD, PharmD (Updated: 9/27/2023)
Click here to contact Ellen Lemkin, MD, PharmD


  • Although Keppra has been used more frequently in clinical practice, there is little evidence for its use in status epilepticus.
  • It has a wide spectrum of action and few drug interactions.
  • Initially, case series appeared to be highly successful in terminating seizures as an add-on agent.
  • A review of 2 prospective studies found efficacies of 44% as an add- on agent, and 75% as a primary agent. The studies had markedly different populations.
  • In a retrospective study, the treatment failure rates were 3X higher than that of intravenous valproic acid as an add-on agent in terminating status epilepticus.
  • Therefore, although it is used frequently, the evidence for use is limited and inconclusive in terminating status epilepticus.

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