This week's topic is panic disorder and relapse in patients with and without a history of substance abuse. Fun topic, really, and one close to my heart.

Case study:

[You are] working with a 32 year old man who comes to you for an evaluation of panic in August in Lowell. He meets the diagnostic criteria for panic disorder and has been experiencing untriggered episodes for the last 2 months. Name three factors that would guide your selection of medication and then discuss your pharmacologic plan for this unfortunate man.

One of the responses — by a prescriber in my area — was to encourage deep breathing, progressive relaxation, identifying triggers and avoiding the situation, CBT, and starting an SSRI. If panic continues, start a benzo.

This strikes me as fairly typical approach for a primary care provider in dealing with someone who presents during an acute panic attack, but I think that it's doing the patient a disservice. Perhaps it's also a typical response for a psychiatrist who is afraid to use benzodiazepines.

I'll post my response here, verbatim, because I think there's a deep (and common) misunderstanding of what panic is, and what having a panic attack is like.

It seems like you're thinking of panic as something that can be gotten out of, as though it's a normal fight-or-flight type response where removal from a stressful stimulus means no more panic.

This is dangerous thinking, and forgive me if I've read you wrong.

It can be harder than perhaps some practitioners think to identify a trigger. While triggers can often be identified, I think it's important to note that when a patient first presents, and you make a diagnosis of panic disorder, discovering these triggers will be more complex than simply avoiding a stressful situation, or simplifying and eliminating stressors from one's life. (Which is a very time-consuming process.)

You can't turn the ship on a dime.

Please don't fall victim to the idea that because you've been scared out of your wits a few times and your heartrate went up and your BP went through the roof that that is a panic attack. It's not. Panic attacks usually appear in a completely idiopathic manner, particularly the first time they hit. It's not an "Oh Gee, you scared me," type of thing, it's more of a "DEAR GOD I'M DYING, SOMEONE PLEASE DIAL 911" type of thing.* (The caps are appropriate there. )

Panic attacks can, and do hit without any warning in an otherwise comfortable, relaxed setting. Watching a movie in your living room, for example.

It's not like [situation] -> panic attack a few minutes or an hour later with a clear antagonist. It can come days after the stressors. It can also take a few weeks and lots of practice to build up an arsenal of effective coping mechanisms to return oneself to a calming state in the middle of an active attack.

Re: Deep breathing. This can also be problematic as at the point where one's lungs are fully inflated one can experience a PVC or PAC, which is VERY disconcerting to someone who's already acutely aware of what their heart is doing. I can actually trigger PVCs in myself by doing this.

–

I don't mean to lecture. I'm not the professor, and perhaps I've read too much between the lines of what you've written. As someone who didn't get out of bed for 3 weeks the first time I had a panic attack, I feel very strongly about the issue, and combatting it aggressively rather than taking a more laid back, it'll-fix-itself approach. Particularly this: "deep breathing, progressive relaxation, identifying triggers and avoiding the situation, CBT, [etc.]"

Those are all great long-term approaches, but the short-term is what someone with panic disorder in an active phase cares about most. Long term stuff can come after, just get me through right now.

And I am keenly aware that my personal experience should never cloud my clinical judgement inasmuch as that is humanly possible.

* I tried to dial 911 my first time, in the middle of a biochemistry lecture, no less. But I couldn't see well enough to dial the number. In retrospect, knowing what I know now, I'm glad I couldn't because that would have been a misuse of medical resources. :p

Early in panic, people are usually not capable of accessing the skills to use behavioral coping mechanisms. You usually need to halt the panic quickly and this is where BZDs are needed. Panic is such an uncomfortable and painful experience, the BZD's are in a way like pain medications in the early stages of treatment.

Onymnomycin 300mg
1 qid until finished
#40
0 refills

I love it when prescribers make shit up.

7 years ago:
WTF is lisinopril?
Time: instantaneous

6 years ago:
I know how to spell lisinopril!
Time: ~0.5 seconds

5 years ago:
Lisinopril is for blood pressure!
Time: ~1-2 seconds

4 years ago:
Have I seen this before? Yes… I have because Aleve is naproxen sodium, and I've seen people take Naprosyn with lisinopril.
Time: ~2-3 seconds

3 years ago:
Lisinopril is an ACE inhibitor, and I see this combination every day.
"Sure, that's fine."
Time: ~0.75 seconds

2 years ago:
*Visual, mental review of systems, picturing the RAAS pathway and envisioning how naproxen is metabolized to see where and how the two intersect.*
"Sure, that's fine."
Time: ~0.5 seconds or so

Most recently:
How old is she? What's her creatinine clearance? Might she be better off with diclofenac or celecoxib? Eh, it's probably okay on a short-term basis, and it's not a terrible choice, but it's probably not the best choice, either.
"Sure, that's fine."
Time: ~1-2 seconds

What's the next step, I wonder? Quicker processing? Maybe. Deeper comprehension? Hopefully.

This development of thought processes is the difference between these two residents. The ability to take in a situation in its entirety, process it efficiently, while remaining calm and friendly takes time and exposure, and has very little to do with intelligence or any other innate quality.

* Naproxen is considered an unacceptable agent in geriatric patients even though it is used in the elderly pretty regularly. (My grandmother, for instance.) Probably because most internists, orthopods, and others are often not terribly familiar with geropharmacology, which is why geriatrics is its own specialty both in Medicine and Pharmacy.

I called my GI doc three days ago to discuss my ongoing issues, and I was able to get an appointment for this afternoon(!). The nurse that did the preliminary vitals and whatnot stuff was unfamiliar to me. She told me that the GI folks were borrowing her for the day from Cardiology downstairs. For some reason she decided to listen to my heart… and she took a really long time doing so. I don't remember anyone listening to my heart before except at my PCP's, and never for so long.

"Hmm," she said.
"'Hmm'? What does 'hmm' mean?" I asked.
"I think you have a heart murmur… has anyone ever told you this before?"
"Uh, no. No one's told me that before."
"I see… let me listen again."

Another long pause while she listens.

"Yep, sounds like you have a murmur. Let me tell [Dr GI] so he can have a listen."

We then go on to have a five minute discussion about drugs, psychopharmacology, clinical pharmacy, and people with entitlement issues. (WTF)

My doc comes in, says hello, we talk about a great many things like we always do (last time we talked about the ins and outs of the laws governing anesthesia and CRNAs in the state of Massachusetts and this time we talked about Thanksgiving, travel, and energy efficiency and how it relates to electrical engineering. I love my GI doc — he's great.)

I was substantially less freaked out at this point, and we both almost forgot the murmur. He listens with me sitting up and lying down. He confirms it, suspects PVCs — something I've suspected I've had for about four years now — and we talk cardiologists. Turns out, one of the guys downstairs is an arrhythmia specialist, and does a lot of work with people my age.

–

I've been having mental battles with myself over the last couple of weeks whether I'm merely a hypochondriac, or if there's a real problem with whatever body part is letting me know it's there. I don't like to diagnose myself; I don't like to be one of those people. But I know that 1) I don't like going to the doctor every other week 2) I don't like taking pills and 3) I do my damnest not to be one of the people who taxes the system. I think that sort of rules out hypochondriasis.

Dropping a diagnosis on someone can be very disconcerting, even something relatively benign (most likely) like arrhythmia. Intellectually, I know that heart arrhythmia aren't a huge deal. I know millions of people have some kind of arrhythmia. I also know that most people have PVCs at some point during their life, and that rare is the person who has never had a skipped or extra beat. I have suspected that I have had some kind of heart trouble since the first time I walked up some stairs and I couldn't get my heart rate to drop for about five minutes.

I thought it was just the amphetamines I was taking at the time for ADHD. I'm certain those didn't help.

Since then, I've had four EKGs, and had my heart listened to by four doctors and countless nurses. They've all told me that I'm fine; there's nothing wrong. I heard it so many times, I believed it. I chalked it up to mere anxiety.

I'd just like to tell the world that I'm fucking tired of people ruling out something *actually* being wrong simply because I'm young. Delve deeper. Refer, if you must. Sitting here in my chair, sipping my decaf Columbian, this revelation explains a few things that I noticed were different about myself since since first grade.

I was always a pretty strong long-distance runner, but I suspect that's simply because walking was never (mentally) an option. I DID notice (and other parents noticed) that it took me longer to recover than the other kids. Where I might run a mile in 7 minutes or so, it would take me 45 minutes to an hour to get my breathing under control where other kids would be fine in 10 or 15 minutes.

Being in first grade, I thought nothing of it the first time someone said something to me about it. My chronic ear infections and multiple cases of severe poison ivy tended to be more pressing.

In junior high and early high school, I had a paper route, and despite biking 5-10 miles every day loaded down with newspapers, my CV endurance never really got beyond a certain point. When I played lacrosse in high school, my heart felt like it was going to explode pretty regularly. Moreso than the other kids.

More recently, while at the gym, I've hated cardio. There are days where I can run for 45 minutes to an hour and be fine, except for the very long recovery time afterwards. Other days, as soon as I move past a walk, I can feel my heart skipping beats. If I continue on, I get lightheaded and have to sit down. (Otherwise I'll fall down.) The more regular I am with cardio, the worse this problem is. It doesn't get better, it gets worse. Oh, and there's also the fact that about 10% of the time that I take a deep breath, my heart skips. (This is why deep breathing doesn't work for me when it comes to managing panic attacks.)

Of course, there's nothing wrong with me. I'm too young to have anything wrong with me. 19? 21? 25? Fuck it, it's all in your head. Maybe these R tards should read Groopman's book and try to take some of the principles to heart.

So while I was a little upset today at being informed that I have a heart murmur, I am somewhat comforted to know that I'm not mentally defective (at least not in that way ), and that perhaps I have an answer. At last. Yes, I know murmurs come and go. They're not always present while the provider is listening. But a Holter monitor was never discussed. Maybe I should have been more pushy. But like I said, I didn't want to be one of those people.

–

Back to diagnosis dropping before I close. Knowing something in your mind and reconciling it with the emotional reaction you have to this input are two completely different animals. In fact, logical reconciliation doesn't come until later, if at all.

I have been guilty of being somewhat dismissive when someone tells me something that's obviously bothering them. If I know it's trivial, or a problem that's easily managed, you tend to not think of it as a terribly big deal. Familiarity with and exposure to a disease state causes a recalibration of Normal. Perhaps even indifference.

But nothing is trivial, even if it's not serious or life-threatening. Not to the person receiving the news. Nothing. (Unless they're drugged out of their mind, like I was when they said "Hey dude you have Crohn's." I just didn't give a fuck at that point.)

Oh, and what takes the cake is that when I got home from work tonight, and informed my family of this revelation, my mom laughs and says "Oh yeah, I have a murmur, too." and my grandmother pipes up and tells me she's got one, too. What the fuck, people. TELL ME THESE THINGS so when I'm asked if there's any history of illness in my family I can give the correct answer. I know my grandfather died of a heart attack, but I always thought he was an isolated case and it was because he was a lifelong smoker and alcoholic. :rolleyes: But no, apparently most of my grandmother's brothers and sisters and my own aunts and uncles have murmurs, too.

The mind boggles. Apparently this information is trivial.

"I don't know what to do anymore. On the first day of school, he throws up. On the last day of school, he throws up. Waiting in line for a roller coaster, he throws up. If he gets really happy for any reason, he throws up. And he throws up because he throws up and worries that he's going to throw up again.

"Is there anything I can give him so he stops throwing up?"

Straight Face held firmly in place — with superhuman effort — I stopped to think about the problem.*

And lest you think me an insensitive clod, I can assure you that I did (and still do) feel awful for this kid. I wonder what his home life is like. I wonder if he's chemically imbalanced. I wonder if it's a phase he'll grow out of. I wonder how to help him in the short term, today, hopefully without robbing him entirely of the excitement that an amusement park brings. I wonder about abuse, too. I wonder if this behavior is conditioned in some way, and if it might be self-reinforcing, not unlike that destructive positive feedback loop that plagues those with panic disorder. I wonder if he'll grow up with anxiety problems. I wonder if he'll end up a well-adjusted adult, hopefully without the need to be on long-term psych meds.

Most of all, right now, I hope mom has a talk with the pediatrician about it.

Given that my options are severely limited by a lack of prescribing powers, the best solution OTC would be Benadryl to blunt the edge, with the side effect of probably making him very sleepy. Not optimal, for sure, but better than puking before you get on the ride, no? Some would think Emetrol, maybe, but that's a poor solution because that's not going after the actual problem. If the child is overexcited, better to take that down a notch than merely cover the side effects of being in that condition in the first place.

What do you guys think? What would you have done?

* When I was in junior high, my friends and I used to talk about the worst, most absurd "super power" to have. We decided it would be the superhuman ability to crap your pants every time you got excited. "Haha! Yay!… ohhhh…." This is where I coined the phrase "My bowels are aquiver with excitement."

I'd say this child's difficulty ranks right up there…

In the no sub box, this guy had scrawled "no substitution" in handwriting that looked like calligraphy done with a squiggle pen. And of course the ink was black.

Yeah okay, buddy. I mean, I don't really care if you want the brand name, just drive up the road to New Hampshire and request it. Don't alter the damn prescription and think I'm not going to notice. There are two parties that should be writing things on the prescription, and you are not one of them.

I didn't rake him over the coals for it. It wasn't worth the time and emotional energy, and he seemed like a nice enough fellow. I hope it doesn't happen again.

The ending is that the insurance (Tricare) wouldn't cover brand name if there was a generic available. Big surprise. So he ended up with his clonazepam, generic Sinemet CR, and generic something else. What a bunch of idiotic hoops to jump through to end up back at square one.

But seriously, what person — who knows they can't write due to a medical condition — alters their own prescription? In the wrong colored ink, no less?

Never ascribe to malice that which is adequately explained by stupidity.

Carlos Camejo, 33, was declared dead after a highway accident and taken to the morgue, where examiners began an autopsy only to realize something was amiss when he started bleeding. They quickly sought to stitch up the incision on his face.

"I woke up because the pain was unbearable," Camejo said, according to a report on Friday in leading local newspaper El Universal.

Ouchies. I guess they're not as thorough in other countries when it comes to pronouncing someone dead…

He should go as a vampire for Halloween.

(Images preserved in order to stave off the inevitable Reuters link rot.)

Baking soda is sodium bicarbonate, also available in tablet form for — you guessed it — heartburn. Certainly though, Tums (calcium carbonate) are far more common than soda bicarb tabs. I suspect this is due to marketing more than anything else.

I wonder if McPherson knew he was unintentionally close to a mark?

[tags]Lasagna, heartburn, cooking[/tags]

I believe that the continuing education (CE) requirements for U.S. pharmacists are woefully inadequate. They should be increased, in both number and difficulty.

To start with, the number of required CE hours should be doubled in every state. They have not been changed in 30 years. Also, at least half of these hours should be live, at least to get us to interact with educators, and, at most, to get us to interact with our peers in the profession.

I couldn't agree more. I think pharmacists should have to take a periodic exam to assure basic clinical competence as well. I've had pharmacists ask me to do their CEs for them, which I find appalling behavior. It is my opinion — and after 6 years behind the counter, I'm not as naive and enthusiastic as I once was — that you should take pride in your profession, and that you should want to keep up with developments in the field of medicine. Even non-drug therapies, in my non-humble opinion. You didn't go to school to learn to count to 30 and slap a label on a bottle. Any jackass can do that, and every jackass with half a clue learns the necessary behavioral tricks to survive standing behind that counter, too.

(Well, maybe you did go to school to learn to count to 30 because you thought that since you planned on standing behind that counter, you might as well make some money while doing it. That's alright, I guess, but I wouldn't want you as my pharmacist. No offense or anything.)

What boggled my mind were some of the comments left on TOP's entry. By pharmacists. The vitriol that follows isn't directed at these people specifically, but rather at the lackadaisical attitude in general that many pharmacists have towards keeping up with their profession.

Even if you cheat like I do and go straight to the questions without reading the program, you still get SOMETHING out of it because you still have to look for the answers.

Well I am a 63 YO RETIRED Pharmacist and honestly I never learned much, if anything, from any of the CE courses I have taken over the years…

All were a total WASTE of time..

Look, I know CEs are seen as an onerous chore. ("OMG! It's December and I haven't finished gotten all of my credits yet! … Will you do this CE for me?") Maybe you've got kids, and your family takes up your free time. In retail there's that fantastic work-home life divide. Work stops as soon as you leave the pharmacy, and the retail environment isn't the place to try to learn anything, unless you work in the slow store. Frankly, this divide between work and home is no excuse to not stay current. You're a professional, for fuck's sake, not a factory worker. This is one of the things that sets professionals aside from non-professionals — you have to make some effort on your own to stay current. Whether or not you are paid for the time you spend is not even a question. It's just something you do.

I don't believe for one minute that you actually retain anything that you "go back and find" to get the correct answers. Not for more than a day or two, in any meaningful detail.

I'm bringing this up now because one of the pharmacists I work with recently gave a patient the wrong answer. (Which may breed another entry for later about stepping on toes.) It was a basic question about statins — and she got it wrong. It wasn't even a hard question. It was "When is the best time to take simvastatin?" It doesn't matter how busy your pharmacy is. If you can't answer the most basic question someone could ask about the most popular HMG-CoA reductase inhibitor in America, you're doing something wrong. And she's in her early 30s — nowhere near retirement age.

I cringe at the thought of the 63 year old retired pharmacist who never learned anything doing CEs. Unless you're reading journals, and staying current of your own accord — which you're probably not — you probably didn't know much about modern medicine while you were still working. How many major classes of drugs came out since you graduated pharmacy school?

Well let's see. There'd be the PPIs, statins, quinolones and fluoroquinolones, macrolides (things have changed a lot since erythromycin), atypical antipsychotics, SSRIs, COX-2 inhibitors, AIDS drugs, the entire field of asthma management, ARBs, T2DM management… I could keep going. Without even going near the biologics. ALL of the drugs in these classes have their basic similarities, but equally importantly, their differences.

Wait a minute! That's basically the entire list of the top 200 drugs prescribed in America! You learned about all these things when you were in school? Are you up on them? Even the basics? Gee, a statin's for cholesterol… whoopty freakin' do. You're a goddamn genius.

Do you even know what cholesterol actually is?

And not to mention that our understanding of the mechanisms of action of some older drugs have changed since you were in school. Theophylline is an old drug that springs readily to mind as a drug about which our understanding has changed over time. Perhaps since you first learned about it all those years ago.

For shits and giggles last night, I went back to some older issues of the clinical publication my chain puts out. My mind was boggled at how much our understanding has changed about even "basic" problems like ADHD and depression in just 8 short years. Almost nothing is hammer -> nail anymore.

Just like formal schooling, you get out of CEs what you put into them. I have no doubt that a great many of them are useless. CEs may not be an ideal answer, but they do serve, if you make the effort. Some of the information is undoubtedly redundant. Some of it you undoubtedly learn by osmosis. But I guarantee you that if you pick up a CE and really read it, you will learn something.

Plagakis would probably say that "we're all clinical". The Ole' Apothecary asks if some are more worthy than others.

The answer is "yes" but it doesn't matter if the letters after your name are "RPh" or "PharmD". Some are inevitably more clinical than others — and that's okay. But there needs to be some basic standard of clinical competence, otherwise you're just a glorified pharmacy technician with some extra liability padding and a key to the safe who takes home a fat paycheck every other week.

And if you've never learned anything at a CE, you should be looking in the mirror for the reason instead of pointing a finger at the system.

The patient who you thought you filled that Rx correctly for ended up having another last name and the same birth-date as someone else in your system. Of course they don't tell you this until after they have received the Rx and loudly proclaim that you filled it for the wrong person with a store full of people. I mean aren't we supposed to know that her full name is Maria Consuelo Rodriguez Maravilla Hernandez Guadalupe AIAIAIAIA ARRIBA?

We have one patient in one of my pharmacies — yes, they're mine — that has two names.

Two completely different names. No motifs. No variations on a theme. One day she's Maria Gomez and the next day she's Elisa Rodriguez. It's fucked up. What's even more fucked up is that Maria doesn't know Elisa's name, and vice-versa. She has to read it from the bottle that she wants refilled, and God help you if she doesn't have the bottle that day. But even more mind-blowing than this is that I'm the only person in over a year to actually put the other name in each of her two profiles. Yeah. Wrap your brain around that one, if you can.

This woman takes an SSRI, but that's it in terms of psych meds, so I have no idea what her deal is. I wouldn't even want to guess. Naturally, she can't speak English except for "15 meenoo? O-K," so I'll never find out, but she is terribly nice, which does get her some brownie points. I'll take a nice idiot over a smart asshole any day of the week. Not that she's an idiot — I strongly suspect she has some untreated psych condition. (Surely it can't be undiagnosed? We can't be the only ones who haven't figured out that something's not quite right.)

Thankfully she is starting to prefer one name over the other, so I guess we're making some progress. Or maybe it's a seasonal thing? Now that it's after Labor Day she'll go back to being Elisa… :suicide:

That first phonecall is okay. But then there's the second. And the third. And sometimes the eighth.

"WHY HASN'T MY DOCTOR CALLED YOU YET??"

How in the seven hells should I know, lady? Yes, it is almost invariably women that ask this question; men, in general, seem to be more interesting in getting to the root of the problem than complaining about it. (Insert off-topic discussion about gender differences here.)

I DO know one thing, though. If you've called us twice, and your doctor hasn't gotten back to us, and it's been 24 hours, and oh my god you will absolutely die if you don't get your simvastatin five minutes ago, you need to start calling the right person. The gatekeeper. The person who — hold onto your socks now — writes your bloody prescription.

I am not your goddamn therapist.

I don't understand the mental disconnect between dialing the pharmacy versus dialing the doctor's office. Is it because you're calling a retail establishment where someone actually answers the phone? Somehow I think the answer is YES. In the last two days, I have waited on hold with a doctor's office for 10 minutes or longer six times. One of those times was actually 23 minutes(!).

But back to consumer idiocy for a moment: Pharmacies are not required to do refill requests for you. There's no law saying "Pharmacist must request refills for patient upon request." It's just something that's done as a service to remain competitive with the other retail pharmacy outlets. Way back in the day — before unlimited long-distance phone service — many pharmacies would add the price of that telephone call into the cost of the prescription. Back before there were third parties. The average person would shit a brick today if that was done. (Back in the Good Ol' Days, there was also the Asshole Tax, which I'd like to reinstate for the habitual offenders.)

Newsflash: the pharmacist doesn't decide whether or not to refill a prescription — we'd LOVE to fill it for you because you're being a pain in the ass, and it'll get you off our back. Not to mention that mo' scripts = mo' money. Maybe sometime down the road, when s/he has access to complete medical records and lab results, a one-time refill ability will be within the pharmacist's scope of practice. But as of now, it's not.

So why don't you go bother the person with that authority?

And incidentally, if you're a provider, I'm not particularly interested in why your customers — yes, customers — wait on hold for eons before they get to talk to someone. I don't care how busy you are. I don't care how busy your office staff are. I don't care that it takes you an hour to get a diagnostic test approved. I don't care that your reimbursement rates are declining, and gee wouldn't it be nice if you could bill for time wasted on the friggin telephone.*

I AM interested in not being the cathartic outlet for your patients' frustration at you and your office's inadequacy.

…I totally just went there, didn't I? Feel free to vent your frustrations at and about pharmacists and pharmacies in the comments — and yes, this post was very cathartic. You know I still love all of you.

* Actually, I do care quite a bit about that. Just not within this context.

So anyway, the bogus prescription was for extended-release lovastatin. Yeah, it really does exist, but hilariously enough, the prescribing doctor had never heard of it. And neither had the pharmacist, thankfully, because she might have ordered it, and then the patient would have gotten the wrong medication.

Christ, people. Proofread your goddamn prescriptions. To make sure that gibberish that your EMR spits out is REALLY what you want. And that you've actually heard of the drug you are prescribing. It ain't rocket science, and even if it were, I'm sure you'd be equal to the task.

Yeah, yeah. We all make mistakes. Proofreading a friggin' prescription shouldn't be one of them. But yet, somehow, I see anywhere from 4-20 crap prescriptions Every. Single. Day. All because they weren't proof-read before they were handed to the patient or sent to the pharmacy.

What's the most fun part of all this is that when you get the doctor on the line, he cops an attitude because he thinks he's the Second Coming of Christ even though he's the bonehead who made the mistake. Get over yourself, dude. <Internet toughguy>I swear, one of these days, I'm going to drive to a doctor's office and put my foot up someone's ass.</Internet toughguy>

No, I don't hate my job, but I do hate people sometimes. It gets tiresome saving other people's bacon when all you get is grief for your troubles. Grief from the patient because the prescription took more than 30 seconds to fill ("Well, can you just fill it anyway?"), and grief from the doctor because you deigned to bother him.

And no, not all doctors are like this. Many of them are awesome, nice people. But just as the vocal minority often gives the silent majority a bad name, the types of doctors that are most likely to come to the phone themselves are the ones who want to pick a fight. And they often do everything in their power to make you feel like a piece of shit, even when they are in the wrong. Needless to say, that does neither themselves, nor their profession any favors. The same holds true for bad behavior no matter who you are, or what you do.

Most of the people doing data entry are not pharmacists. They are technicians. And when they see "metoprolol" they immediately pick generic Lopressor, because that is what they are accustomed to. They don't know that there's a difference between succinate and tartrate, and if they do know there's a difference, they don't know what it means. Most of the time, if this error is made, it is caught by the checking pharmacist. But due to the sheer volume of Toprol scripts dispensed every day, some still slip through the cracks.

I know it's fun to start writing generic names when generics become available. When Zestril went generic, you all started writing lisinopril. Same for gabapentin and every other generic drug on the planet, I'm sure.

But please don't do this with Toprol. We're all on the same team, here, and the goal is to minimize errors regardless of who is technically at fault. And I can guarantee that it will minimize prescribing errors when those refill requests start coming in, and your office staff start leaving incorrect or incomplete voicemails, because they got it wrong, too.

Thank-you.

"Um, so why did you change this?" I ask, handing the QA pharmacist the hard copy and the edited label.

"Because it was wrong," she says.

"No, it wasn't," I say, handing over the script written by her hand. "2 qd means '2 tablets once daily'."

"You don't know that," she says. "What if the doctor means take 1 tablet in the morning and 1 tablet 4 hours later, or 1 tablet twice a day?"

"Well then the doctor should write that."

"Sometimes they don't."

"I see. *pause* I was always taught that 2 qd means '2 tablets once daily' and if the doctor wants twice daily dosing, the script should say 'BID' otherwise the doctor — not the pharmacist — has made a mistake. And that 2 qd absolutely means 2 tablets/capsules/whatever once daily, with no ambiguity."

"Well, I like to put 'Take 2 tablets every day as directed.'"

We argued a bit after that, but the trouble with sticking "as directed" on there is a nifty way of a pharmacist doing a little CYA, which isn't necessarily a bad thing. The script technically doesn't say it, and generally speaking, the patient hasn't been "directed" in how to do anything, so it's actually not correct to do that. What if the script is for meloxicam or nabumetone?

To aid in the discussion, here's a brief Latin recap for those that have forgotten it, or never learned what the abbreviations actually meant in the first place. Unfortunately, they're not much help, either:

• q: quaque: "every"
• qd: quaque die: "every day" which is generally understood to be "once a day" or "once daily"
• qX°: every X hours
• po: per os: "by mouth"
• od/os/ou: oculus dexter ("right eye"); oculus sinister ("left eye"); oculus uterque ("both eyes")

And so on.

For me, I will continue to write "Take 2 tablets once daily" when I see "2 qd". But to others, that means something different, and I think it's important that prescribers know that that it means something different to each pharmacist. I mentioned this phenomenon in my Chantix prescribing tutorial, and it applies here as well. There is indeed ambiguity, where there should ideally be none.

And it so happens that this presents the perfect opportunity to test out my new polling toy. So I've included 2(!) polls for finer-grained results. We'll pretend we're dealing with tablets for the sake of simplicity. If you are not in the medical field, please vote "Other medical personnel". The poll will open a new window for each poll which is annoying, but there doesn't seem to be a way around this. And feel free to elaborate in the comments — I really had no idea until yesterday that this was something not everyone agreed on.

"Heresy!" you shout. Well, hear me out…

You see, there's almost no data to support the assertion that alcohol and metronidazole combine to create a disulfiram-like reaction. It's crazy, I know. How could this age-old advice be wrong? The reason this is drilled into pharmacy and med students' heads is because the conventional wisdom is old. It got here because "everyone knows" that ethanol + metronidazole = A Bad Time. Even though there's no meaningful evidence to support this conclusion.

Regular readers know my distaste (hah!) for metronidazole. In fact, I missed out on my best friend's 21st birthday drunkfestcelebration because of it. As it turns out, I missed out for naught. Alas.

Exhibit A is a meta-analysis of published anecdotes, "Do Ethanol and Metronidazole Interact to Produce a Disulfiram-Like Reaction" published in The Annals of Pharmacotherapy. Exhibit B is a double-blind, placebo-controlled study out of Finland, also published in TAOP entitled "Lack of Disulfiram-Like Reaction with Metronidazole and Ethanol" which is a bit more science-y and a little less meta-analysis-y.

This is a long entry, so here's a ToC.

1. Bits and bobs from Exhibit A
2. Bits and bobs from Exhibit B
3. Final thoughts

Bits and bobs from Exhibit A (Back to top)

The first account of a metronidazole-ethanol interaction was noted in 1964. At that time, folks wondered if Flagyl could be used to curb alcohol abuse. A sort of proto-Antabuse, if you will. 8 of 17 studies found it to be marginally effective. But only marginally, and only 2 of the 8 positive studies were double-blind, and these 2 studies were statistically significant only when dropouts had been excluded.

My commentary after each quote.

revealed six case reports involving a total of eight patients. Tunguy-Desmerais reported on a two-year-old child taking acetaminophen and amoxicillin for pharyngitis. After a febrile seizure, ulcerative gingivostomatitis was diagnosed, phenobarbital–vitamin B6 syrup was added, and oral metronidazole was started. The next evening, the child was flushed but not febrile and, because both the analgesic and phenobarbital–vitamin B6 syrup contained ethanol, a metronidazole–ethanol reaction was considered likely.

I'm not an expert in pediatric liver function, but I do know that it takes longer for children to metabolize EtOH than it does for an adult. And the flushing is certainly a side effect of plain old alcohol consumption. Going right for the metronidazole-ethanol "reaction" seems a little too convenient, and more than a little irresponsible.

Another report involved three patients: a woman prescribed rectal metronidazole following hysterectomy, who became nauseous, pale, and dyspneic 36 and 60 hours postoperatively and was discovered to have taken a large amount of whiskey just prior to each episode; an 18-year old patient being treated with amoxicillin and metronidazole for pelvic inflammatory disease who experienced nausea, flushing, and headaches each evening after drinking ethanol; and a man who, after a 1g dose of metronidazole and a shared bottle of wine at his evening meal, vomited violently.

1. Taking whiskey in a post-operative state is probably not advisable regardless of the circumstance. Hysterectomy, while relatively common, isn't a walk in the park.
2. Metronidazole can nausea and even vomiting all by itself. It doesn't need any help from alcohol.
3. See #2. 1g is a lot of metronidazole all at once, especially if you're unused its GI effects. Would the man have vomited even if he'd not had a bottle of wine? We can't be sure, but you can bet that it wouldn't have been mentioned in the literature if it hadn't. It would have been chalked up to a bad reaction to the medication.

Plosker reported a reaction following intravaginal use of metronidazole. This case involved a female pharmacist who, after two or three cocktails (each contained ~1 oz of (vodka), inserted a single vaginal suppository of metronidazole 500 mg and went to sleep. She awakened an hour later with a burning sensation in her stomach, nausea, and a severe headache accompanied by a cold sweat, which she believed was a metronidazole–ethanol reaction.

I could go for the easy ad hominem attack here, but it doesn't serve any real purpose — and in any case, I am on my way towards showing that EtOH and metronidazole is not necessarily the End of the World. That said, the burning sensation and nausea could have been from the medication itself. Flagyl can cause this type of reaction, even when it's not administered orally.

A potentially serious reaction involved a 16-year-old male who, nine days after resection of an hepatic echinococcal cyst, developed a staphylococcal infection. He was treated initially with intravenous vancomycin, followed by a combination of intravenous nafcillin, clindamycin, and gentamicin. This regimen was then changed to intravenous trimethoprim/sulfamethoxazole (TMP/SMX) and intravenous metronidazole, in addition to his chronic therapy with albendazole, docusate sodium, and ferrous sulfate. After 12 hours and for the following 60 hours until the TMP/SMX was switched to oral therapy, he vomited and experienced flushing, which was attributed to a metronidazole interaction with the alcohol in intravenous TMP/SMX.

Attributing these side effects to the EtOH in the TMP/SMX is easy. It's also irresponsible, because a mechanism of action had been proposed by this point in time, but not substantiated. (Exhibit B will cover this more.) This reaction is not completely out of the question — metronidazole can indeed increase the levels of intracolonic alcohol dehydrogenase — but it's still irresponsible to put down, for certain, that this was the cause of the boy's distress. I wonder if the heavy antibiotics he was on could have contributed to this. It seems possible that by mowing down his normal intestinal flora, he's in a position to experience these effects anyway.

Another potentially serious reaction reported by Harries et al. also involved intravenous metronidazole, this time combined with cefotaxime and papaveretum in a patient who had been drinking heavily and stabbed in the chest and abdomen. A chest drain was inserted and 500 mL of blood was drained; peritoneal lavage produced clear fluid only and the patient was admitted for observation. Four hours after an initial improvement, he became short of breath and nauseous; he vomited, had a headache, and was profoundly acidotic. This metabolic disturbance was attributed to a metronidazole–ethanol interaction.

Drunken guy stabbed in the chest and abdomen. Chest drain removes half a liter of fluid, and four hours later the patient complains of nausea, vomits, has a headache, and is acidotic. And then it's attributed to a metronidazole-ethanol interaction.

I could think of a few things that're more likely to have caused this. Can you? He's been stabbed and he's probably developing a hangover spring readily to mind.

This last one is a real doozy:

Toxicity due to an ethanol–metronidazole interaction appeared on the death certificate of a 31-year-old woman. Cina et al. described the case of an alcohol abuser who had been in frail health for four years following a serious car accident involving severe chest, abdominal, and closed head injuries. After being assaulted by a man, the patient had collapsed and died. Medications found at the scene included propoxyphene, acetaminophen, naproxen, metaxalone, carisoprodol, amitriptyline, hydroxyzine, vitamins, and cough syrup. No metronidazole or empty metronidazole container was found and she had not recently been prescribed metronidazole by her doctor. Because high concentrations of ethanol and acetaldehyde were found, assays were performed for disulfiram and metronidazole. There was no discussion of the methodology that reportedly found metronidazole in her serum, despite the fact that this was not one of the drugs found at the scene. In addition, there was no discussion about whether any of the other drugs in her possession, for which she was apparently not tested, may have cross-reacted in the metronidazole assay. It was concluded that she had probably ingested metronidazole without the knowledge of her physician and had discarded the bottle before she died.

I think the idiocy here speaks for itself. "It was concluded that she had probably ingested metronidazole without the knowledge of her physician and had discarded the bottle" my ass. Flagyl ain't a drug people are likely to abuse.

Indeed the common thread throughout these cases has been the assumption that metronidazole and ethanol are the culprits without any real testing to verify whether or not this is the case. This study was published in 2000, and while there was a proposed mechanism of action for this EtOH-metronidazole reaction, there was no real evidence yet to support the proposed mechanism. There are also possible — and I would be so bold as to suggest more probable — causes for each of these adverse events, and I have done my best to explain them.

Now on to Exhibit B which talks about the science of the proposed alcohol-metronidazole interaction.

Bits and Bobs from Exhibit B (Back to top)

Disulfiram works its magic by inhibiting the hepatic low aldehyde dehydrogenase (ALDH) which increases blood acetaldehyde concentrations after alcohol is consumed. This is exactly like "Asian flush" — a common, genetic condition wherein those affected are unable to effectively metabolize alcohol completely leading to flushing, nausea, and a quickened pulse.

It was theorized that metronidazole may have a similar effect on ALDH. However, studies have shown that this is not true in rats. So, what about people?

Well, it doesn't do it in humans, either. In fact, it had the opposite effect. Metronidazole caused a reduction in acetaldehyde production, opposite to the effect of disulfiram(!). Indeed, in Exhibit B, the graphs show (probably clinically insignificant) that the participants in the double-blind, placebo-controlled, alcohol-metronidazole study that the blood alcohol levels for the participants taking metronidazole were slightly lower than their placebo-controlled counterparts between the 40 and 80 minute marks:

None of the participants noted any dyspnea, flushing, vertigo, or headache during the test. Interestingly, the heart rates for the metronidazole group tended to be about 10bpm lower than the control group throughout the test. I don't know that this is clinically significant, but it is interesting:

Final thoughts (Back to top)

So we've got some age-old advice that doesn't stand up when tested properly, and we have a proposed mechanism of action that doesn't hold up to closer scrutiny, either. Where does that leave us?

It leaves us with a couple things… Some people experience GI distress while on Flagyl. Sometimes they vomit. Sometimes they drink alcohol and vomit. Sometimes they drink alcohol and don't vomit. That tells us that:

1. Flagyl is hard on the stomach. It's a difficult medication to tolerate for a good percentage of folks, regardless of its effect on blood acetaldehyde levels.
2. Flagyl is not a disulfiram-like drug, and should not be referred to as such.
3. Flagyl will not absolutely cause the vomiting associated with Antabuse when consumed in conjunction with alcohol. Pharmacists should stop counseling that it will.
4. Adverse events are too often attributed to metronidazole because it is convenient, and "everyone knows" that alcohol and Flagyl are a recipe for disaster.
5. Flagyl remains an unpleasant drug to take; its side effects are real and often severe, and should not be downplayed.
6. Patients should be educated about these side effects, and how to minimize them. Avoiding alcohol is one way to do this. Taking it with food is probably more effective. Doing both is obviously better than doing just one of the two.

It is my suspicion that early researchers thought there was a link between metronidazole and alcoholism due to the medication's side effects. Taste perversion. Smell perversion. These things will cause folks to avoid certain foods for the duration of the drug therapy. Alcohol is one of those things. It's coincidental, and its usefulness in the real world is questionable.

Wonder no more. Medscape and Viread to the rescue!

All of the couples in the study wanted to have children; the men were already taking antiretrovirals that suppressed their serum HIV below the detectable level.

To further reduce the risk of infection in the female partners, the researchers gave each of them two doses of tenofovir, one to be taken 36 hours before intercourse and another 12 hours before.

After each of the couples had made three attempts, 11 of the 21 couples had conceived, Dr. Vernazza said, and after 10 attempts, 15 were pregnant. These are substantially higher rates than might be expected with artificial reproduction, Vernazza said.

All the women in the study tested negative for HIV, 3 months after the last exposure, the researchers report. "The risk of transmission in a couple with a fully treated male partner is low and can further be reduced by timed intercourse and a short pre-exposure prophylaxis with tenofovir," Dr. Vernazza said.

[...]

"Persuasion of the patients might sometimes be a problem, in which case we still offer them in vitro fertilization (with sperm washing)," he said. "But in general, an hour to explain all the data is enough."

An hour, eh? I wonder if there's a billing code for that?

[tags]HIV, AIDS, conception, tenofovir, Viread[/tags]

Oscar predicts — with 100% accuracy so far — when people are going to die. The following excerpt is from the NEJM essay mentioned in the AP article, for those who don't have access.

Oscar takes no notice of the woman and leaps up onto the bed. He surveys Mrs. T. She is clearly in the terminal phase of illness, and her breathing is labored. Oscar's examination is interrupted by a nurse, who walks in to ask the daughter whether Mrs. T. is uncomfortable and needs more morphine. The daughter shakes her head, and the nurse retreats. Oscar returns to his work. He sniffs the air, gives Mrs. T. one final look, then jumps off the bed and quickly leaves the room. Not today.

Making his way back up the hallway, Oscar arrives at Room 313. The door is open, and he proceeds inside. Mrs. K. is resting peacefully in her bed, her breathing steady but shallow. She is surrounded by photographs of her grandchildren and one from her wedding day. Despite these keepsakes, she is alone. Oscar jumps onto her bed and again sniffs the air. He pauses to consider the situation, and then turns around twice before curling up beside Mrs. K.

One hour passes. Oscar waits. A nurse walks into the room to check on her patient. She pauses to note Oscar's presence. Concerned, she hurriedly leaves the room and returns to her desk. She grabs Mrs. K.'s chart off the medical-records rack and begins to make phone calls.

Within a half hour the family starts to arrive. Chairs are brought into the room, where the relatives begin their vigil. The priest is called to deliver last rites. And still, Oscar has not budged, instead purring and gently nuzzling Mrs. K. A young grandson asks his mother, "What is the cat doing here?" The mother, fighting back tears, tells him, "He is here to help Grandma get to heaven." Thirty minutes later, Mrs. K. takes her last earthly breath. With this, Oscar sits up, looks around, then departs the room so quietly that the grieving family barely notices.

I think if I were dying, it might be nice to have an animal next to me. Even if I wasn't aware of it. Oscar has a plaque dedicated to him, as well, "For his compassionate hospice care, this plaque is awarded to Oscar the Cat."

Note: Since he was adopted by staff members as a kitten, Oscar the Cat has had an uncanny ability to predict when residents are about to die. Thus far, he has presided over the deaths of more than 25 residents on the third floor of Steere House Nursing and Rehabilitation Center in Providence, Rhode Island. His mere presence at the bedside is viewed by physicians and nursing home staff as an almost absolute indicator of impending death, allowing staff members to adequately notify families. Oscar has also provided companionship to those who would otherwise have died alone. For his work, he is highly regarded by the physicians and staff at Steere House and by the families of the residents whom he serves.

That's pretty amazing.

And it seems that I Can Has Cheezburger? has made a LOLCAT out of him.

What's not so nifty about Chantix are the horrific prescriptions we see for it. Directions that make no sense. Or make sense within a certain context, but probably not the context the prescriber was thinking of. This will become clear shortly.

This is a short post, but it's big because of all of the pictures.

Table of Contents:

1. How does Chantix come?
2. Normal Chantix Use: prescribing a course of Chantix
3. Normal Chantix Use: the first month (photos begin)
4. Normal Chantix Use: Month 2 and beyond
5. Abnormal Chantix Use and common missteps

How does Chantix come? (Back to top)

Chantix comes in four different packages, only three of which are of any consequence. The Starting Month Pak, the Continuing Month Pak, and bottles of 0.5mg tablets, which are only used when a patient cannot tolerate the side effects of the normal 1mg strength. The fourth package is a bottle of 56 tablets of the 1mg strength, which is exactly the same as the Continuing Month Pak, minus the fancy packaging. We don't use these.

You can think of Chantix almost like a Medrol Dose Pack: designed for ease-of-use, contained in packaging which explains itself to the patient in very simple terms, with pictures.

Normal Chantix Use: prescribing a course of Chantix (Back to top)

Chantix should ideally be prescribed for most people using two prescriptions:

Chantix starter pack
Sig: Take as directed
#1 package
0 refills

and

Chantix continuing pack
Sig: Take as directed
#X packages
_ refills

The continuing month pack prescription will be used after the patient has finished the starter pack. I have been counseling patients that when the time comes for a refill of their Chantix at the end of the first month to speak with the pharmacy staff to avoid the automated script refill request idiocy that I explained in Footnote #1 of this post.

Normal Chantix Use: the first month (Back to top)

The Starter Pack looks this:

Inside this main pack you'll find the following mini-packs:

The special pack there is the first week. The blue ones are what're inside the Continuing Month Pak, and they are all 1mg tablets (Photo). Inside that yellow first week pack you'll find the following blister tab of 0.5mg tablets:

The end of Week 1 is when the patient is supposed to stop smoking.

Normal Chantix Use: Month 2 and beyond (Back to top)

For the following months, that second prescription with X number of refills is used; inside are four blue packs, as I said before:

Closeup.

Abnormal Chantix Use and common missteps (Back to top)

50% of the time I see a prescription for Chantix, it's not done correctly. It'll be written for a Chantix Starter Pack with a bunch of refills, or a hand-written taper schedule that doesn't make any sense, some variation of these two problems. We smooth this out, but it is imperfect, and each pharmacist does it differently.

Every once in a while, we will come across an instance where a patient was prescribed a Starter Pack, and the followup prescription is for Chantix 0.5mg, 1 tablet twice daily, which makes no sense, given that 3 of the 4 packs in the Starter Pak are for 1mg tablets. Unfortunately, we cannot simply change the prescription to the Continuing Month Pack, even though when we call the prescriber's office 90% of the time we hear something like "Oh yeah, we meant the continuing month thing."

"Thing."

Not especially comforting. I've explained to more than one nurse exactly how Chantix comes, and how it's normally used. In some cases, this information is even relayed back to the prescriber, because I see prescriptions written correctly for someone else later on. It's a nice feeling.

But that 10% is the killer, which is why we have to call. GI upset is the most common side effect of varenicline, and often by reducing the dose to 0.5mg, these side effects are ameliorated, while retaining the efficacy of the drug. That's where that niche bottle of 0.5mg tablets is used. Ever so rarely.

In this RARE case, if you a prescriber, and you actually WANT the 0.5mg, and you are AWARE that this is the "wrong" way to use Chantix, write a brief note acknowledging that you know, and would like the 0.5mg tablets anyway. This will go a long way towards ensuring that your prescription will be filled the same everywhere, exactly the way YOU want it.

Not to mention it will save everybody time. Filling prescriptions is not a passive activity.

[tags]Chantix, pharmacy, medicine, varenicline, smoking, smoking cessation[/tags]

In fact, I'm not arguing how efficacious it is. I'm sure it works. If it didn't, it wouldn't be approved. I'm merely questioning its place in current treatment paradigms. To explain what I mean, I'm going to use a crude analogy to compare angiotensin II receptor blockers (ARBs) and aliskiren, the only direct renin inhibitor (DRI).

Think of a sink. For whatever reason, you want to keep liquid from going down the drain. Does it make more sense to keep the sink turned off, or to plug the drain directly?

Well obviously if the goal is keeping the drain dry, you'd plug the drain. This is what ARBs do. They prevent specific and non-specific binding at the angiotensin II receptor sites. Tekturna just keeps the sink from turning on and does nothing to block the drain directly. This means there's still going to be non-specific binding at the angiotensin II receptor site. (Incidentally, this non-specific binding is not merely theoretical; if it were, ACEis would be more effective as a class than the ARBs, but instead they are merely comparable.)

Back to my point: Tekturna is more expensive than the ARBs, and it will be for a long time. I don't think having aliskiren as an option is a bad thing. I just question how valuable the drug truly is with less expensive ACE inhibitors and ARBs. Sitting here, it doesn't seem to have a real niche. Would I try Tekturna if nothing else worked? Of course I would. If I were targeting the RAAS, would I reach for it as first-line therapy? Hell no I wouldn't. I'd go for an ACE inhibitor in most cases.

I'm not going to delve into the heated debates about reactive renin production and other similar topics because I suspect that the reality lies somewhere in the middle ground, as it usually does.

In the meantime, I think don't think Tekturna has a meaningful place in current drug therapy. If ARBs do not work, it is unlikely that a DRI will, either. The only time I see it perhaps being useful is if a patient cannot tolerate ACEis or ARBs.

[tags]Medicine, pharmacy, Tekturna, aliskiren, hypertension[/tags]

Medical resident contracts first reported case of Acute Wiiitis.

From Ars:

The case report reads very tongue-in-cheek, containing a description of the Wii controller that can only be described as clinical, and noting that, unlike in real tennis, the resident's level of fitness did not preclude his ability to overdo it: "Unlike in the real sport, physical strength and endurance are not limiting factors."

Apparently, Acute Wiiitis is actually a variant of a disease that was first described in 1990, Nintendinitis, but the presentation is distinct enough to warrant a specific term. Those curious about these sorts of ailments may also want to check out the description of Nintendo elbow and Ulcerative Nintendinitis.

Genius!