How Nexium took down Prilosec and how Pharma changed our stomachs forever

Once upon a time, during the height of acid wash, shoulder pads, and the side pony tail, there was a great plague tormenting the people of the developed world. It started as a burning sensation in the solar plexus--right below the sternum--then churned its way up the esophagus, often leaving behind a sour taste in the mouth. It was born of over-sized meals, greasy fast food, and acidic ingredients (e.g. tomato sauce, orange juice, onions), fed by alcohol, cigarettes, and anti-inflammatory medications (e.g. ibuprofen, naproxen and aspirin), and showed up most often during post-meal naps and late-night bouts of insomnia. It seemed  to get worse with stress.

It was heartburn.

Other terms often used interchangeably for heartburn include acid reflux, dyspepsia, and indigestion. We doctors call it "gastro-esophageal reflux disease" or GERD,

(Okay, the term "heartburn" is derived from the Ancient Greek kardialgia (heart-pain), having first appeared in English literature in the 13th century, so to be perfectly honest, heartburn was a recognized plague long before acid wash. BUT what came next did actually happen in the '80s. . .).

http://www.adelle.com.au/wp-content/

How Pharma changed our stomachs
In  1989-- the very year of the peak of Paula Abdul and the fall of the Berlin Wall-- a most remarkable event occurred: Prilosec came on the market.

Prilosec was the first of a new drug class--a proton pump inhibitor-- designed to change the way our stomachs digest food forever. Its generic name was omeprazole. It has since been joined by brothers Prevacid (lansoprazole), Protonix (pantoprazole), Nexium (esomeprazole) and a gang of other inbred siblings whose generic names all end in -prazole. Prilosec was also the first to go over the counter in 2003.

Though Prilosec was the first of its kind, its little bro Nexium, released in 2001, has become the superstar. Between 2001 and 2012, Nexium (known to anyone who watches TV as "the purple pill") has grossed $48 billion. Yes, that's $48,000,000,000. That makes it #2 in all time drug sales (see here for more drug details). Oh, health care costs, where art thou going?

You should know that Prilosec and Nexium are made by the same pharmaceutical company (AstraZeneca), AND they are almost the same exact chemical compound. (Think identical twins with different haircuts). For those of you with any interest in organic chemistry, esomeprazole (Nexium) is simply the s-isomer of omeprazole. Who says o-chem isn't worth anything?!

The big differences between the two medications are the following: Nexium is always purple (Prilosec is sometimes pink), Nexium is still on patent (but generic will be available mid-2014) and Nexium costs five to ten times as much as Prilosec.


Okay, enough tangent.

How do proton pump inhibitors work?
Proton pump inhibitors (PPIs) decrease acid production in our stomachs, thereby lessening the discomfort caused by said acid. They accomplish this by blocking the proton pump in the parietal cells of the stomach lining (hence the name). Details on the nitty gritty mechanism can be found here.

Interestingly, these pumps are constantly being turned on, off, and over, so there is never complete inhibition of acid.  We need acid, in fact, to digest our food and absorb many nutrients, including iron, calcium, magnesium and Vitamin B12. PPIs are considered stronger than any other family of acid-blocking medicines on the market, and studies show they bring relief to 85-90% of people.

PPIs work best in the fasting (not-eating) state, so people are usually instructed to take them  first thing in the morning before breakfast. A single dose may bring some relief but tends to leave too many acid pumps around to do their thing, which is why taking a PPI on occasion ("as needed") doesn't often do the trick.  PPIs reach  maximum efficacy around day 5-7 of continuous use. Most over-the-counter formulations instruct patients to take the med for a total of 14 days before consulting a physician. The FDA recommends that PPIs be taken in the lowest dose for the shortest duration possible-- in most cases 4-8 weeks is probably sufficient.

Heartburn is a common and uncomfortable health condition, and for people experiencing acute discomfort, PPIs work remarkably well. I prescribe them with some regularity to a range of patients including the elderly, pregnant women and even children (for all these groups I have some serious reservations and a few caveats). When I personally had a bout of severe esophagitis during my Peace Corps years, I took a PPI for several months. It was miraculous.

PPIs serve an important purpose: they do what is asked of them, and they make people feel better.

The challenge comes when trying to get patients OFF of them.
You see, PPIs are pretty darn addictive. Addictive, you say, no way. How could anyone get addicted to a medicine that suppresses acid?!  If you object to the word addiction (see a prior post for discussion of chemical addiction versus chemical dependence), then you must at least concede that PPIs lead to a level of dependence. This is likely because our brilliant bodies try to circumvent the acid blockage by creating new acid pumps.

If you take a PPI for a short time (let's say 1-2 weeks for a bout of really bad heartburn), you probably won't have a problem, but if you take a PPI for longer than a few months, there is a good chance you will have a hard time stopping cold turkey. This is because, when you stop, your solar plexus will burn, your stomach will churn, and your heartburn comes back with such a vengeance that you find yourself popping another PPI just to get through the night. For all intents and purposes, you are now hooked.

PPIs also do nothing to encourage you to address why you might have GERD in the first place.
I have a large number of patients who are extremely attached to their PPIs-- so attached that they refuse to discontinue or taper, even as an experiment.  In sharing this, I am airing my own dirty doctor laundry-- it is with more than a touch of shame that I continue to refill medications for people when I know that in doing so, I may not be fulfilling my solemn promise to "do them no harm".

As you might have guessed, PPIs don't actually do anything to correct the underlying problem of acid reflux. They are a temporary fix-- a band-aid of sorts for your GERD-- making you feel better tonight or this week without helping you recover for the long-haul. There are some exceptions: in patients with known ulcer disease, PPIs promote actual healing of the gastric lining. And in specific combinations with other medications (e.g. for treatment of helicobacter pylori), they can be used to help eradicate disease.

It was thought for some time that PPIs were pretty harmless even if taken over long periods of time. Doctors and patients alike dismissed the dependence issue as unimportant. After all, you could always taper and eventually get off them. But the longer the PPIs have been out on the market, the more concerns have been raised about potential long-term effects on many other organ systems.

Here is a partial list of PPI-associated problems:

PPIs:

• inhibit absorption of important nutrients
• magnesium: taking PPIs for prolonged time (over a year) can deplete magnesium levels, leading to muscle spasms, irregular heartbeats, and convulsions (reference)
• vitamin B 12: people on PPI have a 65% increased risk of B12 deficiency compared to people not on a PPI. B12 is important vitamin that is involved our red blood cell production, which is important to get oxygen to all our tissues.  (reference)
• iron (reference)
• increase risk of osteoporosis and osteoporotic fractures: increased risk of fractures of the wrist, hip and spine. 25% increase in overall fractures, 47% increase in spinal fractures in postmenopausal women (reference)
• increase risk of clostridium difficile infection (antibiotic associated diarrhea) likely because decreased acid leads the bacteria to have a better environment to party (reference)
• increased risk of pneumonia: 30% increased risk for developing pneumonia (reference)
• drug interactions
• increased risk of atrophic gastritis, which could theoretically lead to increased risk for gastric cancer

As you can see, PPIs are clearly associated with serious harm--  especially when taken long term. While PPIs might enable us to keep on chug chug chugging on, eating like crap, drinking like fish, being lazy lumps, smoking cigarettes, and ignoring our own bodies' attempts to communicate with us, we will pay at some point. Are you willing to pay with your bones? Or your blood cells? What about your pocket book? We should not disregard potential long-term health effects because we are so tied to relief from our momentary discomfort.

We know better, don't we?


I would challenge you to consider simple ways in which you could change your life that will actually make you feel better now and for the duration.  Here are a few lifestyle modifications to consider to treat and/or prevent GERD:

1. Slow down your eating
2. Lose weight (only if you are overweight or obese)
3. Eat small frequent meals
4. Stop smoking
5. Decrease your alcohol intake
6. Avoid trigger foods ( trigger foods are different for different folks but consider cutting back on the following to see if you feel better: chocolate, coffee, cow's milk, orange juice, spicy foods, tea, tomato sauce/juice. Maybe even try one at a time.)
7. Exercise (Exercise actually helps the sphincter between your stomach and your esophagus work better! How cool is that?!)
8. If you have predominantly night-time symptoms, elevate the head of your bed 4-6 inches 
9. Herbal remedies: If you are considering herbal treatments, try licorice, slippery elm, marshmallow (the herb, not the white sugary puff) or chamomile 

And please don't misunderstand me-- if you need a PPI for a few weeks, go for it. It will probably help. Just remember that you have some more work to do than continuously pop the purple pill. If you do the work, you will feel better.  This I can attest to both personally and professionally.

May your solar plexus be healthy.

A

http://graphics8.nytimes.com/images/2007/02/08/fashion/08fitness.1.600.jpg

Additional References:
http://www.healthandwelfare.idaho.gov/Portals/0/Medical/PrescriptionDrugs/PPI%20Educational%20Information.pdf
http://www.fammed.wisc.edu/sites/default/files//webfm-uploads/documents/outreach/im/module_gerd_clinician.pdf
http://well.blogs.nytimes.com/2012/06/25/combating-acid-reflux-may-bring-host-of-ills/?_php=true&_type=blogs&_r=0

Can doctors have tattoos?

A few months ago, a patient (about my age) asked me whether or not I had a tattoo. Before I had a chance to answer, he interrupted himself by asking whether or not doctors were allowed to have tattoos. He asked the questions pretty spontaneously-- in the context of his being restarted on a blood thinner after a period of time without it. Mostly, he was mourning the realization that he wouldn't be able to get a long-coveted tattoo now that he was back on the medicine.  He was curious, then embarrassed, and ultimately, the conversation returned to his health care situation.

I don't think I ever answered him.

Ever since that visit, though, his questions have been doing somersaults in my head. I don't believe it's the personal nature of the inquiry that bothered me (I tend to be a pretty self-disclosing doctor). Initially, in fact, I found it pretty amusing. But after several days of chuckling, I moved from a place of amusement, to one of deeper consideration. It's some of the issues implied in his questions that have lingered. Does having a tattoo take something away from a doctor being a doctor? and Is it okay for doctors to be regular people? 

http://www.neatorama.com/2007/09/23/the-tattooed-doctor/#!r30u6

What do you think?

http://thedo.osteopathic.org/?p=86631

1) Does having a tattoo take something away from a doctor being a doctor?
This is a tricky one. I briefly did some Internet research on the topic of physicians with tattoos and came across a plethora forums in which applicants who were interviewing for medical school and residency training were discussing the need to "cover up" tattoos during the interview process. These forums made it quite clear-- in the land of auditions and under the guise of professionalism, doctors shouldn't have tattoos. Many universities and hospitals, in fact, have dress codes prohibiting display of potentially offensive tattoos and promoting the covering of all tattoos "when feasible".

Of course, there are the distinguished doctors who get tattoos to honor their patients (see article here). Or those who tattoo themselves with their end of life wishes (see article here).  Definitely interesting twists on a different story.

But then I came across this, an article right up my alley. This article even features a picture of a young hip osteopathic doctor with a pretty sweet sleeve tattoo (look right: she looks a lot like one of the characters from Grey's Anatomy). The story quotes a 2006 study from The Journal of Dermatology that 36% of  people born between the years 1975-1986 have tattoos. That's my generation! The article theorizes that if one-third of people in this age range have tattoos, a certain number of those tattooed people will become physicians.

And while the article did commend this tattooed student doctor for her many successes, it seemed to imply that her successes came in spite of her beautiful tattoos rather than because of them. And it wrapped back around to the idea of "professionalism" as the crux of the matter. This begs the question, are tattoos inherently unprofessional? And if so, why? Is this mutable?

Despite my own secret desire to be a rebel, I must admit that I, too, hold onto some pretty traditional ideas around professionalism. Though I don't often wear skirts or a white coat to work, I do believe in dressing professionally for my patients' sakes. I believe patients expect their doctor to look a certain way-- namely, forgettable. By this I mean that the best dressed doctor is literally dressed in something the patient doesn't remember (not flashy, not sexy, not odd, not ostentatious, not ugly or offensive). The outfit that puts the patient at ease is most likely the outfit that that he/she doesn't even recall. This, I would argue, is because the clinical encounter is really about the patient, not the doctor.

And yet, what might a tattoo say about one's doctor? Is a tattoo too out there? Too memorable? Or might it be healing?

I can imagine that some of my patients (especially the ones that sport their own beautiful body art) would just LOVE having a decorated physician. A tatted-out doctor would make them feel more kinship than otherness. That always feels good, no matter who we are. And feeling better is the essence of healing. But many of my older and/or more traditional patients would certainly frown upon a visible tattoo-- tattoos might distract certain patients so much that they wouldn't be able share comfortably, listen to medical advice, or even want to see that doctor (I can almost hear one special patient of mine saying something like "I don't want to see that tattooed person ever again.").

To what extent is it the responsibility of the physician to have appearance that puts patients at ease versus an appearance that the physician feels good about?

I would like to believe that most patients would prefer a brilliant loving doctor with tattoos to a dumb cold one without-- certainly, as I groused about in a prior post, what I really yearn for in my own provider is someone who knows something, listens to me, and cares about me. What he/she looks like doesn't have much correlation with any of these essentials. Or does it?

2) Is it okay for doctors to be regular people?
This question is a pretty easy one for me to answer. The answer is a resounding YES. It has to be, in fact because we are. . . well. . .people. My family knows this (very well), my friends know this, and plenty of my patients know this (I hope).

Yes, physicians happen to have completed medical school and residency training (all of which took many years and a lot of effort), but just like our fellow humans, we have diverse strengths and weaknesses, unique hopes and dreams, fears, fallibility, and yes, even tattoos. And yet, perhaps, this "realness" is a relatively new concept, as medicine goes. In the footsteps of a generation of physicians who worked 100+ hours per week, completely and singularly focused on their patients, my generation of physicians is trying to be more than career physicians-- we are also hoping to be spouses and parents and friends and political activists, musicians, and scholars, and athletes, and dreamers, and community advocates.

I do intentionally share with my patients important pieces of my human self: why I work part-time (to be able to take my three-year-old to preschool and take him swimming), when I don't know something (I believe strongly in transparency when I don't have a good answer for why something is happening or what a patient should do), and even some of my own personal challenges (sharing my struggles with infertility, only when it seems relevant). Obviously, my patients' clinic visits are sacred space-- long-awaited appointments are definitely not about me-- so I don't share or expect to share all of my personal self, but I do disclose the parts that seem helpful for my patients' journeys.

Here are few examples (that I don't necessarily share with patients) of how I am regular person:
I pick up my dog's poop.
I do laundry.
I lose my temper with my son.
I eat ice cream from the carton.
I have sex.
I worry.
I sometimes feel depressed and watch mindless TV to improve my mood.
I get zits.
I argue with my mom (sometimes in that snarky seventh grade way)
My underwear drawer is a disaster.
I get anxious.
I am often wrong.
And I make mistakes. Yup, plenty.

Since many of my closest friends are doctors, I can also vouch that THEY are regular people too.  Though they have uniquely different human traits than the ones I listed for myself above, they are regular nonetheless. I would espouse that all this makes us better doctors-- most of the time. After all, the human experience is what empowers us to ask questions when we are unsure, to admit to misunderstanding when communication is imperfect, to relate personally to our patients' struggles, to ask for help when we need it, and to apologize when we make mistakes.

And that's the kind of family doctor I want to be. I hope it's the kind of doctor you want to have.


Back to my inquisitive patient. . .
I didn't answer my patient right there in the moment because I wasn't quite sure how to answer him. Should I flash him my own stamp? (Not appropriate). Share with him how I got my little tattoo in the midst of an intense break-up with a college boyfriend? (Definitely not appropriate). Should I take the opportunity to talk about clean needles and infectious disease (Very doctorly, for sure). Should I divert the conversation? (Always a good tactic) Should I reassure him that we were all 21 at some point? (Duh). I guess what I would say to him now after months of pondering is just the following,

"Yes, actually, I do have a small tattoo, I've had it for 15 years. And no, there is no explicit rule about doctors not having tattoos. After all, we're all human. We come in all varieties. Mostly, I am just sorry that you aren't going to be able to get your dream tattoo this month, but hey, let's be optimistic and hope that one day, you will be well enough to get the tattoo of your dreams."

Please don't make me pee my pants

Ladies, raise your hands if you have ever peed your pants. And, by peed your pants, I mean coughed out a few drops, sneezed out a squirt or two, emitted an undisclosed volume as you stood in line at a public restroom, or maybe even lost your entire bladder in a fit of laughter.

http://lerablog.org/wp-content/uploads/2013/09/Urinary-Incontinence.jpg

Take heart. Wherever you happen to be reading, either your seatmates won't realize why in the world you are raising your hand, or those that do will feel in good company. And men, well, please keep quiet. Most of you with a Y chromosome happen to have much longer urethras than those of us XXers. Lucky you. You also cannot birth babies. And you don't live as long as we do. Lucky us.  (Oh, and in case you're a man thinking a post about pants-peeing might be irrelevant for you, turns out that men and women who live past 80 have the same rates of incontinence. So read on if you're planning to live a long life).

Urinary incontinence-- the involuntary loss of urine--is one of those hush hush taboo topics that even over-sharing women don't like to discuss. It is right up there with bowel movements, vaginal discharge, depression, and sexual dysfunction.  In fact, most of my female patients are happier to discuss the shape and color of their poop than the fact that they cannot always hold onto their own urine. Studies show that half of people who suffer from incontinence never bring it up with their primary care provider.

However, urinary incontinence is extremely common. (This probably explains the plethora of adult diaper commercials featuring grandmothers running through fields of flowers). Because so many people keep their situation private, it's hard to get perfect data, but studies estimate between 25-50% of adult women have lost their urine at least once in the last year. One study found 10% of women experience this problem at least weekly. That means that up to half of women reading this post have peed their pants this year, and 1 in 10 did it in the last week. And it's not limited to those women who have had babies. While 30-60% of pregnant women have peed their pants, 12.6% of women between the ages of 16 and 30 who had never been pregnant reported incontinence.

Unfortunately, as alluded to above, the problem gets worse with age: while 7% of women ages 20-39 report having had some incontinence, the percentage increases to 17% for women 40-59, 23% of those 60-79, and 32% for women over 80.

Ugh.

Urinary incontinence can have a seriously negative impact on a woman's quality of life, potentially complicating and/or interfering with everyday activities like work (frequent pad changes or limited physical activity for fear of being far from a bathroom when the time comes), exercise (especially anything that involves jumping up and down), household activities (e.g. heavy lifting), travel (who wants to be stuck on a bus without a toilet?), sexuality (it's hard to feel sexy when you cannot keep your undies dry), social interactions (embarrassment about look/smell), sleep (frequent night wakings), self-esteem, and even clothing choice.

While many women with incontinence can get by wearing a panty liner in their underwear to catch unanticipated droplets or make sure to take themselves to the toilet on a scheduled basis, other women can be so severely affected that they feel they must abandon activities they love. Incontinence can be so severe, in fact, that women feel confined to their house, for fear of an embarrassing accident. I have had patients who've memorized bathroom stops along a 500 mile drive, who've stopped playing tennis with their spouses, and who no longer walk in the mornings with their friends for fear of wetting themselves.

Triple ugh.

The process of peeing (in doctor-speak micturition)--filling and emptying the bladder--seems simple, but it is much more complicated than filling and emptying a water bottle. Micturition is an intricate dance involving our central, peripheral, and autonomic nervous systems. It also depends on well-functioning muscles down there. Our central nervous system (aka brain and spinal nerves) control the when and when not; our peripheral and autonomic nervous systems control the how. To not pee, we have to maintain relaxation of the smooth muscles of the bladder and then simultaneously inhibit and contract the muscles of the sphincters. Then, to pee we must do the opposite: contract the smooth bladder muscles, followed by disinhibition and relaxation of the sphincter muscles. 

Ask any potty-training toddler-- keeping one's pants dry is not easy. Just getting to the potty can be a challenge! (By the way, same goes for older adults, where limited mobility plays an important role in increasing rates of incontinence).

For women who experience incontinence, the problem comes in one of five flavors: stress, urge, mixed, overflow and functional incontinence. By far, stress incontinence is the most common.

1) Stress incontinence: anything that puts stress (added pressure) on your bladder. This includes coughing, sneezing, jumping, weight lifting. This often causes intermittent and/or episodic incontinence. Please note, that while stress incontinence may cause you psychological stress, it is not being "stressed out" that causes women to lose control of their bladders.
2) Urge incontinence (overactive bladder): involuntary contraction of the bladder muscles causing you to feel an intense "urge" to go to the bathroom right away, leaving you little time to get yourself there.
3) Mixed incontinence: a mixture of 1 and 2.
4) Overflow incontinence: as you might imagine, when the bladder reaches a certain level of fullness, the sphincter just quits doing its job and the urine overflows (aka leaks) uncontrollably.
5) Functional incontinence: mental or physical disabilities that limit a person's ability to get to the toilet in time, to get their pants on, to realize and respond to bodily cues, etc

We know that childbearing, obesity and functional impairment (e.g. cognitive issues after stroke, mobility issues after a fall, inability to plan and execute) are the three main risk factors for incontinence. There is a lot more controversy about other things that may contribute to urinary incontinence, including: childhood bed-wetting, high impact physical activities, diabetes, stroke, depression, vaginal deliveries, episiotomies, low estrogen levels, female surgeries (e.g. hysterectomy), and radiation.

So, for women who are overweight or obese, there is really good evidence that losing weight helps reduce frequency and severity of incontinence. If you could lose a few pounds (or more), one more reason to be motivated to do it! You might also hear advice to lay off caffeine, alcohol, carbonated beverages, and sugary foods. There isn't much data behind this advice, but it doesn't hurt to try.

But what if you aren't overweight? What if you've abandoned Starbucks, wine, and your favorite chocolate, and you are still wetting your pants. What can you do? Incontinence is super frustrating, and there are no quick fixes. However, there are interventions that have been shown to help. Yes, here are the options. The goal is to start with 1, 2, and 3 before moving onto medications because the behavioral changes actually work a good percentage of the time!

1) Bladder retraining: boot camp for the bladder. Works particularly well for urge incontinence. See an example of a bladder retraining program here. It's not rocket science but definitely can work!

http://www.cardiodesign.com.au/page6.html

2) Pelvic floor muscle exercises: often called "Kegel exercises", have been shown to be helpful in both stress and urge incontinence, despite popular belief that they only help with stress incontinence. One 1998 study found that these exercises worked better than medications! See an example of Kegel exercises here. And I know many of you are Kegeling right now as you read-- just seeing the word makes those exercises involuntary-- you go, ladies!

Random sidebar: Dr. Kegel was a gynecologist who invented an instrument called a perineometer, for measuring the strength of those very exercises he invented in 1948. 

3) Neuromodulation devices that can either be inserted in the vagina or external on the leg. See weird contraption above. See video example here. Studies show they help in 75% of urge in continence. Not too bad!

4) Medications: used mostly to treat urge incontinence. There are several different medications out on the market, most of which target the nervous system and belong to a group of medicines called antimuscarinics. None have been shown to help much with stress incontinence, and as for urge incontinence, studies found that only 1 in 5 women will achieve continence using this type of medication. Not great odds, unless you happen to be that 1.

5) Electrical stimulation: either electrodes placed on the thigh and/or implanted under the skin of the buttocks (sacral nerve stimulation). I've never actually met anyone who has done this-- would love feedback from any readers who have had success or failure.

6) Vaginal inserts/urethral plugs: Most commonly an insert called a "pessary". Looks like an over-sized diaphragm (if any of you remember those from old school birth control days), placed inside the vagina to literally help hold things up. You have to be fitted by a physician, but can be a simple fix especially for someone who doesn't want to go through surgery. They are pretty easy to get in, don't hurt, and can really help!

7) Surgery: I have been witness to some great success in several women who struggled for a long time with incontinence and finally decided to go for surgery, which is, of course, both invasive and scary. Generally, surgery should be considered if the behavioral changes discussed above don't really work and after a woman is done having children. Something to ponder, especially for women whose lives are being impacted negatively.

Now that you've been slogging through this post for at least the last fifteen minutes and you've done your requisite Kegel exercises, it's probably time to get up and pee. Hopefully you learned a little something!
_________________________________________________
References:
http://www.aafp.org/afp/2013/0415/p543.html
http://www.aafp.org/afp/2005/0115/p315.html
http://guidance.nice.org.uk/CG171/KingsHealthQuestionnaire
uptodate.com: Epidemiology, risk factors, and pathogenesis of urinary incontinence
http://www.iciq.net/ICIQ.LUTSqolmodule.html