Wednesday, October 31, 2012


So I live in jersey city and Sandy decided my street belongs in the Hudson River. I'll be back up and running in a few days. Stay tuned!

Sunday, October 28, 2012

Pharmacy Consult: We accidentally just gave insulin aspart IV… Is that bad?

Open the Pyxis or Omnicell or fridge in your ED where insulin is stored. How many different vials are stocked? If you’re like most other EDs in the USA you’ll find a rapid acting insulin (aspart, glulisine, lispro) mainly used for hospital sliding scale regimens, insulin regular (fast acting) for IV use, an insulin mix (NPH or aspart/aspart protamine), and a long acting insulin (glargine or detemir) for maintenance.  With similar sounding, appearing and often stored next to each other products, it’s not surprising that insulin is the number 1 drug related to medication errors in US hospitals.  Consolidating the insulin products may be a solution, reducing the risk of grabbing the wrong vial. 

In pharmacy school and in residency, its rammed down your throat that your IV insulin is insulin regular. But there is no conceivable reason why rapid acting insulins (aspart, glulisine or lispro) cannot be given IV.  Right in the package insert of all places, IV administration is listed as a route of administration.

From an evidence-based perspective, there are two studies that compared the effects of IV aspart to IV regular and IV lispro to IV regular [1,2].  The two studies were methodologically similar.  Each conducted in healthy individuals, primarily measured glycemic threshold for onset of the clinically detectable autonomic reaction to hypoglycemia induced by aspart, lispro or regular human insulin and utilized the same dosing of 2 units/kg/min.  The blood glucose/time profiles were near identical between the different insulin products – practically speaking, this translates into a 1:1 dose conversion.

{From Frier BM, et al}

I have not yet been able to convince anyone in the hospital pharmacy to eliminate insulin regular from the formulary.  I suppose there are some valid reasons to have multiple insulin products stocked hospital wide, but at least in the ED, I think we could get away with keeping one (aspart or lispro) on hand. 

Aspart (Novolog)
Glulisine (Apidra)
Lispro (Humalog)
Regular (Humalin R/ Novolin R)
Mixes: (NPH, Humulin 50/50, Humulin 70/30…)
Glargine (Lantus)
Detemir (Levemir)

Fun pharmacy fact: NPH (neutral protamine hagedorn)

1. Frier BM, Ewing FM, Lindholm A, Hylleberg B, Kanc K. Symptomatic and counterregulatory hormonal responses to acute hypoglycaemia induced by insulin aspart and soluble human insulin in Type 1 diabetes. Diabetes Metab Res Rev. 2000 Jul-Aug;16(4):262-8.
2. McCrimmon RJ, Frier BM. Symptomatic and physiological responses to hypoglycaemia induced by human soluble insulin and the analogue Lispro human insulin. Diabet Med. 1997 Nov;14(11):929-36.

Thursday, October 25, 2012

ED Drug Shortage Showdown: Rabies Vaccine and Immune Globulin

By: Nadia Awad, Pharm.D.

It seems like nowadays, every ED drug and its mother is on a manufacturer shortage. Epinephrine? Check. Etomidate? Check. Succinylcholine? Check. Sodium bicarbonate? Check. Some are on shortage for only a short period of time and may seem like that they were never gone to begin with, while others may be on a critical long-term shortage for various reasons. Pharmacists and pharmacy buyers alike are literally pulling their hair out trying to keep up with the shortages and determine which alternative agents would be appropriate to keep in stock and utilize in the meantime.

On a Friday last month, when I was doing my regular residency duties down in the ED, we got word that both the rabies vaccine and immune globulin were on shortage due to the increase in demand in both products since the summer months as well as a manufacturing delay. The only indication that both products could be obtained from the manufacturer would be for the purposes of post-exposure prophylaxis, and an order form would have to be signed by the ED attending physician that indicates the number of patients (possibly) exposed to rabies, weight of the patients, the number of vials of immune globulin needed, and the total number of vaccines anticipated to complete the full course of treatment. This form would be sent directly to the manufacturer in order for both products to be shipped to us.

When we heard this, the dayshift ED pharmacist, my residency program director, and I quickly did a count of the current inventory of vaccines and immune globulin at our hospital, and we determined that we had enough to at least last us through the weekend. We then drafted an institutional protocol within an hour to define the conditions and steps necessary for our pharmacists in dispensing both the vaccine and immune globulin. The protocol that we have developed is outlined below:

•       ED attending physician enters an order for the rabies vaccine and immune globulin for a patient requiring post-exposure prophylaxis into our computer system.
•       Upon verification of the order by the pharmacist, both the assistant pharmacy director and pharmacy buyer are to be notified of the name of the patient and ordering physician regarding the request for rabies vaccine and immune globulin.
•       The pharmacist who verified the order is to complete the order form with all the patient information and have it signed by the ED attending physician.
•       The order form is forwarded to the pharmacy buyer so that both products are ordered for the next business day.
•       The first dose of the rabies vaccine is provided to the patient in the emergency department from the current pharmacy inventory.
•       Once all subsequent doses of vaccine and immune globulin for the patient have arrived, that supply is sequestered for that individual patient.
•       The pharmacist is to document their initials along with the name of the patient, name of the ED attending physician, and the date and time that vaccine and immune globulin are dispensed in the "Rabies Vaccine and Immune Globulin Dispensing Log" in the appropriate columns demarcating the days of therapy (days 0, 3, 7, and 14 for the rabies vaccine and days 0, 3, or 7 for rabies immune globulin).
•       A physical inventory of both the immune globulin and vaccine on hand will be maintained by the pharmacist each time a dose of rabies vaccine and/or immune globulin is provided to an individual patient and record the amount in the area provided on the log. 

Of course, there will be situations where a patient may require a shorter or longer course of therapy for post-exposure prophylaxis, and we indicated that that would need to be documented in the dispensing log as well to account for this.

We provided email communication to the ED attending physicians, physician assistants, and residents regarding the shortage to just give them a heads up about the shortage. In addition, we provided the protocol to the assistant director of the pharmacy and pharmacy buyer so that they knew how we would go about handling the shortage. We also provided a brief summary and a copy of the protocol to our pharmacists in our weekly departmental email bulletin.

So far, things have gone pretty smoothly and we have had not had any issues (knock on wood). I just cannot wait until we can go back to the days where we will no longer have to deal with the shortage. But that would make life less interesting, wouldn’t it?

Monday, October 22, 2012

Pharmacy Consult: Beta Blockers and Epinephrine

I had an interesting discussions in the ED the otherday when I was talking about the importance of administering epi via IM for anaphylaxis.  Is there a diminished response to epi if a patients is on a beta-blocker?

Let’s clarify: patients on chronic non-selective beta-blocker therapy may have a blunted effect of epinephrine in anaphylaxis but epinephrine administration may also result in profound hypertension and bradycardia or heart block.

Non-selective beta-blockers will blunt the bronchodilatory effects of epinephrine causing a sort of “resistance” to epinephrine in anaphylaxis. The same will hold true if epi is administered via nebulization or albuterol is given. If a patient is on chronic cardioselective beta-blocker therapy, this is generally not a concern, unless they’re on a high dose since these agents loose selectivity (for metoprololgreater than 100mg/day will do the trick). Alternatively, glucagon (1-5mg IV) can be given since it has sympathomimetic activity through cAMP, not alpha or beta receptor activation.

The mechanisms at play causing a significant blood pressure elevations and bradycardia share similarities. In this case, an unopposed alpha-adrenergic receptor activation causes profound vasoconstriction. Normally, epinephrine activates both alpha 1,2 and beta 1,2. Though the alpha activation leads to vasoconstriction, there is a balance of beta 2 mediated vasodilation. But by blocking this beta 2 activation you’ll have unchecked alpha 1 mediated vasoconstriction. The resulting effects are significant increases in blood pressure and subsequent reflex (vagally mediated) bradycardia. Again, in cases where the patients are on chronic cardioselective beta-blocker therapy, this effect is generally not observed if they’re on normal beta-blocker doses. Here is an interesting case report highlighting the concern.

Non-Selective (beta 1 and beta 2)
Cardioselective (beta 1)
Carvedilol (has additional α-blocking activity)
Labetalol (has additional α-blocking activity)
Sotalol (but really a class III antiarrhythmic)

Friday, October 19, 2012

Ticagrelor (Brilinta) and Aspirin Interaction - Fact or Fiction

When the literature behind ticagrelor hit, there seemed to be a short-lived cheer. Where prasugrel (Effient) fell short, this drug excelled - superior (composite endpoint of vascular death, MI and stroke) to clopidogrel (Plavix) with no excess bleeding. What followed was a resounding thud since 10% of the population in PLATO, who were from North America, did not see this benefit. But the confusion didn’t end there.  Especially for pharmacists…

In a mysterious turn of events, patients who received > 100mg of aspirin seemed to have no benefit (composite endpoint of vascular death, MI or stroke) with ticagrelor and more bleeding.  The mechanism of this interaction as theorized by the PLATO authors is that by administering aspirin at doses greater than 80 mg /day, the inhibition of prostacyclin production at these concentrations will offset the potent P2Y12 inhibition and additional prostacyclin release caused by ticagrelor (circa 1983). 

Although this makes sense, it’s not the whole story. We know that prostacyclin (specifically PGI2) inhibits platelet aggregation and causes vasodilation. Its production by COX-1 is readily inhibited by aspirin, however, its production by COX-2 is still maintained at normal daily aspirin doses. But at the end of the day, the suppression of PGI2 from higher doses of aspirin isn't enough to overcome the inhibitory effects of TXA2 to initiate or predispose a patient to thrombosis (unlike COX-2 inhibitors)

Moreover, if P2Y12 inhibition mediated prostacycline release was blunted in a clinically significant manner by aspirin, we should see this effect with clopidogrel and prasugrel – which we don’t.  There is a difference between showing no difference in clinical outcomes based on the dose of aspirin you use with clopidogrel (CURRENT-OASIS 7) and saying higher dose aspirin causes worse outcomes.

Or perhaps in everyone got aspirin 325mg daily in the region where ticagrelor did terribly (N. America) and virtually nobody received that dose elsewhere.
In the words of one of the ED pharmacists I work with, “I smell a fart with this one.” The FDA advisory panel regarding ticagrelor seems to agree.

Wednesday, October 17, 2012

Epinephrine IM for Anaphylaxis

Epinephrine dosing and administration for anaphylaxis can be a tricky situation. In a strange, non-conformist type of stubbornness, the concentration parenteral epinephrine products are listed as a ratio (1:1000 vs 1:10,000 vs 1:100,000), rather than a percentage. There have been numerous reports, and personal experiences, where patients end up getting a significant overdose, or underdose of epi from miscommunication, dosing error or picking the wrong ampule/vial/syringe.

An often-overlooked administration (won’t call it an error) issue is administering epinephrine for anaphylaxis SubQ. When epi is administered SubQ, its alpha agonist properties (vasoconstriction) predominate, limiting blood flow to the area and therefore absorption into systemic circulation.

When administered IM, on the other hand, the beta-2 agonist properties (vasodilation) predominate in skeletal muscle, allowing for rapid absorption.  Importantly, the site of IM administration plays a large role: the preferred site for IM administration being the vastus lateralis.

Monday, October 15, 2012

Amide and Ester Local Anesthetics

Ultrasound guided regional nerve block is an evolving trend in ED procedural sedation.  The thought being, local anesthetics could be used instead of benzodiazepines, ketamine or propofol, which could allow for earlier patient discharge from the ED and lower risk of complications (respiratory depression).
Navigating the library of local anesthetics can be complex, particularly if your patient reports some allergy to lidocaine or prilocaine or if the drug is on shortage (an evolving problem in the US).  Let’s just pretend it’s an allergy that you concerned enough about to not use that particular drug, but does that mean local anesthetics are off limits?
Not necessarily.
Local anesthetics are divided into two main groups based on their chemical structure: amides and esters.  Generally, allergy or hypersensitivity to an amide local anesthetic does not “cross react” with ester local anesthetics.
A quick way to remember which agent belongs in which category is that amides generally have two “I”’s and esters have one “I.” The one exception to this is procainamide, which is classified as an ester.


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