DrPullen.com – Medical and Health Blog

Generic Boniva: A Welcome Addition to our Generic Drug Options

March 19, 2012 Dr. Pullen

The bisphosphonates have been very popular for treatment of osteoporosis. On March 19th the FDA approved several manufacturers to sell generic Boniva, ibandronate, at the 150 mg monthly dosage that is commonly used. Unlike many drugs that go generic Boniva has been approved for several manufacturers from the start, so we should expect prices to drop as soon as this gets to market. Boniva has the primary advantage over the other commonly used drugs in its class of needing to be used only once monthly vs. once weekly. This may not seem like a big advantage until you understand how the drug has to be taken. All of the bisphosphonates need to be taken on an empty stomach the first thing in the morning with a large glass of water, and then the patient has to neither eat nor lie down for at least 30 minutes. The reason for this is that these drugs are very caustic to the lower esophagus lining cells if the pill refluxes back up into the esophagus and that if taken with food absorption is very poor. This means that for the first hour after taking the pill a patient has to remain upright and not eat nor drink.

Having to plan their morning around this ritual once a month is less of a hassle than once a week. In addition one of the common side effects of Fosamax, Actonel and Boniva, the three drugs in this class approved for use in the U.S. is dyspepsia or reflux esophagitis. These symptoms are usually most severe for a day or so after taking the medication, and having Boniva side effects for a day a month is more likely to be tolerated than having Fosamax or Actonel side effects every week.

I expect that if the cost of generic Boniva approaches the cost of generic Fosamax or Actonel many patients will prefer the monthly generic Boniva. It will be interesting to see how generic Boniva is positioned in comparison to the other drugs in the class regarding pricing.

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Generic Lexapro Finally: Understanding Isomers

March 15, 2012 Dr. Pullen

With the FDA approval yesterday of Teva’s generic Lexapro (escitalopram) I’m taking this opportunity to remember my years as a chemistry major at Bowdoin College and talk about a subject that is fascinating and not really that complicated. The movement toward the use of isolated isomers (also called sterioisomers or enantiomers ) as medication seems to be an accelerating trend in recent years.
A compound is defined by its chemical structure. The number of each type of ato, and the bonds between the atoms define the compound. For many drugs every molecule is shaped the same. For others the shape of the molecule can assume mirror image conformations, i.e. a left-handed and a right-handed shape. In medications the useful isomers are those with an asymmetric (chiral) center where there are two mirror image options for the shape of the chemical bonds to assume. These are technically called enantiomers, but are most commonly called R and S isomers. S stands for the Latin “sin” for left, R for the Latin rectus for right. (There are two other nomenclature methods for designating isomers, one using +/-, another using D/L, but these are seldom used in medicine and are mentioned so if you see them you won’t wonder if I am making all this stuff up.) A mixture of both the L and S isomers is called a racemic mixture. The FDA has developed a detailed approach to isomers that makes an interesting read for those of you with a scientific interest.

Fits great

Wrong Hand to Fit

The way most drugs work in the body is that they attach to a receptor site. If the receptor site is shaped in way that the left or right handed molecule fits well, and the other shape does not fit well, the one that fits well is going to the active drug. Think of this like hands and a glove. Your right hand fits nicely into a right-handed glove. Your left hand does not easily fit. The same is true for your left hand and a left-handed glove.

For other things like your head, any hat the right size fits because our heads are symmetric (relatively), with no isomeric variations.

In some cases the less active isomer is truly inactive. In other cases it appears that the “pure” active isomer has advantages as a medication. The not-so-surprising observation that drug companies somehow seem to discover that one isomer of their blockbuster drug is really the active isomer just before the patent expires on the original isomer mix leads some of us to be skeptical about the benefits of isomers. Still the trend toward isomers as medications seems to be real, so it is useful to understand what an isomer is, and why sometimes it may not be worth the added expense of buying the brand name isomer when the isomeric mix product is an inexpensive generic. Here are a few of the more popular isomers used as medication with a little Dr. Pullen commentary:

Lexapro vs citalopram: Lexapro was brought to market by Forest Laboratories just prior to the patent expiration of Celexa, the racemic citalopram product. The argument that Lexapro has less side effects and works faster is much harder to define than with a product like Nexium where more objective endpoints like ulcer healing, gastric pH, etc are available, but in my experience most patients to equally well on generic $4./month citalopram vs. Lexapro at $138.24/ month (Costco pricing). With the approval of Teva to exclusively market generic Lexapro for 6 months their price will be somewhat lower than brand name Lexapro, but in 6 months expect much lower prices from competitors. If the price approaches the $4. cost of citalopram generic Lexapro is likely to be very commonly used.

Nexium vs Omeprazole: Nexium has been a blockbuster drug for AstraZenica for years. This was a brilliant marketing move, by AstraZenica, again just prior to Prilosec (the original brand name for omeprazole) going generic. In order to market a “better” drug, Nexium was marketed as a 40 mg esomepraxole (left handed isomer) and compared to the 20 mg dose of omeprazole. It was shown to be very slightly faster acting. Now that you understand isomers does it surprise anyone that by taking the active isomer or omeprazole and using 4 times the dose of esomeprazole that is in racemic omeprazole the it is slightly faster acting? Not me. Is it worth the cost premium (Costco omeprazole 20 mg = $11.75/ 30 capsules vs. Nexium 40 mg = $202.75 / 30 capsules). Probably never.

Albuterol vs Xopenex: Unlike the prior two isomers, Xopenex is the R isomer not the S isomer of albuterol. There are some patients where the racemic mixture in albuterol causes more cardiac stimulation like racing heartrate than the R-albuterol isomer in Xopenex. This makes Xopenex preferable for some patients, but most patients do just fine on albuterol.

There are lots of other drugs sold as isomers, but this is enough to give you examples, and hopefully enough reason to be skeptical of claims of superiority for isomers sold as new expensive branded drugs.

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How Good Is Peyton Manning Going To Be?

March 11, 2012 Dr. Pullen

Does Muscle Weakness Improve After Disc Surgery?

For an NFL fan arguably the best thing that could happen to your team is to sign Peyton Manning and have him perform at or near his pre-injury level. The corollary is that one of the worst things to happen to your team would be to take a huge salary cap hit to get a Peyton Manning with such weak throwing arm that even with his experience and determination he is unable to excel or that he is re-injured and unable to play. The opportunity to get a superbowl champion, 4-time MVP, and future hall of fame quarterback who suddenly has become available to lead your team to a championship makes it easy to overlook the nature of spinal nerve injuries and cervical spine surgery.

The excitement and media heyday surrounding Peyton Manning neck surgery and his recent free agency prompted me to post about the nature of weakness from spinal nerve injury, and what can be expected in terms of recovery of strength and function. The real issues come down to two questions:

Is the nerve injury he has sustained to his cervical nerve root significant enough to cause irreversible weakness that will render him unable to perform at a level close to his previous superstar status. How much more recovery of strength can he expect.
Is he going to be able to hold up to the trauma he will be subject to as an NFL quarterback?

Let’s look at these one at a time.

How much of Manning’s arm weakness can he recover?: The real key to how successful Mr. Manning is going to be in his comeback hinges on the degree of chronic nerve injury he has sustained. Most of the time once a spinal nerve had been injured leading to muscle weakness, if the weakness persists for very long the damage is permanent. It is not clear how long Manning had been having weakness prior to his single-level fusion procedure, but it is certainly concerning that he had undergone at least 2 prior microdiscectomy procedures and that with a player as valuable to his team and generally competitive as Manning it seems unlikely that he chose to stop playing and have surgery at the first sign of weakness.

So what is the chance of a full recovery of motor function, i.e. strength, for Manning and how is this likely to affect his effectiveness as at throwing a football? I expect it to be more significant than may be widely appreciated. I cannot find it reported anywhere just which cervical level Manning had fused, so I don’t know which cervical nerve root is damaged. The most common cervical levels for disc injury are the C5-6 and the C6-7 levels. The cervical discs and nerves are labeled for the two vertebrae they are between. There are 7 cervical vertebrae, so the C6 nerve root exits

Brachial Plexus Diagram

between the C5 and the C6 vertebrae, and the C7 nerve root exits between the C6 and the C7 vertebrae. The anatomy is further complicated because the nerves to each muscle in the shoulder and arm get stimulation from several spinal nerve roots. This is because the cervical nerves come together in a complicated conglomeration of nerves called the brachial plexus. The nerve roots enter the plexus and fibers from several nerve roots joint to exit the plexus as peripheral nerves. Each muscle gets stimulation from one of these peripheral nerves. Key muscles in the throwing process include the triceps, the pectoralis major and minor, the latissimus dorsi, the deltoid, the biceps, the biceps radialis, and others. Each of these muscles in innervated by a specific peripheral nerve, and most of these receive varying amounts of innervations from the C5, 6, 7 and 8 nerve roots.

Certainly Manning has had access to the best available therapy to try to regain muscle strength. Still muscles just don’t work without nerve stimulation. This is called trophy, or trophic stimulation. Muscles that lose their innervations undergo atrophy (no trophy) and become smaller and lose their function. (think of polio and spinal cord injury victims) No amount of exercise, therapy or effort can make a muscle without innervations work. So if Manning still has arm weakness six months after his fusion surgery it is likely he will be left with at least some degree of muscle weakness. Six months post surgery he is not likely to get much more strength back. Certainly therapy can help other muscles become stronger and assume some of the roll of the muscles that have lost strength, but for Manning to function at a level required of a top level NFL quarterback I predict he will need to be able to throw the a football at very close to his prior strength.

How Vulnerable Is Manning To Recurrent of Further Injury?: How serious are the concerns that Peyton Manning will be at risk of additional levels of disc injury due to already existing disc injuries and the additional stress on the disc levels adjacent to a fusion. I expect that the fusion is going to hold up pretty well, and not itself be highly vulnerable to becoming unstable. The issue is really whether he develops disc herniations at the levels above and below the fusion, and whether he develops narrowing of the spinal canal (spinal stenosis) related to scar tissue or exuberant bone growth in the area of the fusion or at adjacent disc levels. NFL quarterbacks are sacked an average of twice a game, an although Manning is very experienced and may be able to minimize the number or sacks and hits he receives, undoubtedly he will be hit and his neck will be put in harm’s way in the course of an NFL season. I anticipate that these are going to be future issues for Manning, but that they are not likely to be the reason he is or is not successful in his short term comeback.

I anticipate that Peyton Manning’s success or lack of success at his comeback is going to hinge on how much arm strength he has remaining. This will be apparent to fans by the time the season comes, and he really has had enough time to strengthen his muscles by now. Teams expecting him to become a great deal stronger than he is right now are likely to be disappointed.

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Post Hoc Ergo Propter Hoc: All Is Not As It Appears

March 10, 2012 Dr. Pullen

I like some Latin phrases that have become part of our language. See an earlier post Carpe Diem. ”Ad hoc” is a commonly used moniker meaning literally “for this”, but the term “post hoc,” or more properly “post hoc ergo propter hoc,” (Latin for after the fact, therefore because of the fact) is used to describe the tendency to infer a causal relationship to what happens after something to the preceding event or action. The whole debate about MMR and autism is because the MMR vaccine is given to 1-year-old children and the first signs of autism are usually noticed in the few months after the usual time to give MMR. This post hoc ergo propter hoc assumption is a big part of the reason that when you look at the list of side effects of any medication on the manufacturer’s prescribing guideline nearly every commonly encountered symptom is listed. When you look at the comparison of side effects of the drug being tested and compare this to the incidence of the side effects of placebo control, it is amazing how commonly “side effects” of placebo occur. I jokingly tell patients who come in for evaluation of a problem just as it seems to be resolving that I wish I had seen them yesterday. Then I could have taken credit for a cure. The tendency to assume that what happens in the period of time shortly after an intervention is the direct result of and caused by the intervention is natural although not always correct.

This same issue occurs with everything from surgeries to chiropractic care. I remember in medical school that one student in our class was traumatized by the sudden death of his patient right in the middle of his first time alone with a patient for a physical exam. Did he do something to cause her death? Almost certainly not, but still he was likely pretty anxious the next few times he did a physical exam.

The natural course of many self-limited illnesses makes post hoc ergo propter hoc relationships very common. If you have a sinus infection that is going to last 10 days, but you see the doctor on day 8 and get an antibiotic, are told the medication should help within 2-3 days, when you recover in 2 days it is natural to credit the recovery to the antibiotic. If you get a headache the day after you start a new medicine, or a rash when you have been on the medication for a few days then post hoc. The relationship is assumed.

This issue is discussed very nicely in a recent article in Forbes by Henry Miller:

The Data on Drugs’ Side Effects Must be Reliable

As a medical resident at a major cancer center some years ago, I was responsible for administering a 4 a.m. intravenous dose of a drug that was part of the patient’s treatment protocol. I stood by the patient’s bedside, groggily flicking and tapping the syringe to get the last tiny air bubble out of the drug before injecting it.

Just as I was about to push the plunger to administer the drug, the patient died — just stopped breathing and expired. There was a “do not resuscitate” order, so sadly, that was that. The time was 4:01 a.m.

Had I more quickly removed the air bubbles and administered the drug at exactly 4 a.m., the patient would have died within seconds of receiving it. As a result, the investigators on the treatment protocol, the maker of the drug, federal regulators and I would all have suspected that the drug was the proximate cause of death. Read more

This post hoc issue plays havoc with everything from medication side effects reporting to patient’s expectations for treatment. I think it is an import concept to keep in mind when we try make sense of what we observe in live and medicine.

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Why Patient’s Don’t Have Advance Directives?

March 5, 2012 Dr. Pullen

I was reading my American Family Physician at the YMCA this weekend, and found an article “Implementing Advance Directives” that prompted me to come home and write this post. I have to admit that I should need to more often and earlier with many of my patients. I need to have a better plan for helping patients successfully and confidently choose to complete both a living will and a durable power of attorney. A living will outlines you preferences for decisions you want made on your behalf in various circumstances if you are unable to verbalize you own preferences. A durable power of attorney legally authorizes someone to make health care decisions for you in the circumstances where you are unable to make them for yourself. These two documents complement each other. I’ve too often tried to maneuver the minefield of coming to decisions for a patient’s care when they have failed to make their preferences clear and implement a durable power of attorney giving one individual the power to execute those choices. Then an out of town relative shows up to save the day, or a sibling dispute over how to deal with Dad’s terminal illness care happens. This type of thing is all too common, and makes a stressful time for everyone. Making your preferences known, putting it in writing, and designating a legal power of attorney helps your loved ones avoid this unnecessary messy and at times ugly scenerio. Both of these documents are crucial to both you and your family to assure that your wishes for decision making about your health are carried out according to your wishes.

Why don’t I do a better job? I suspect it is a combination of factors. I think the first is that this is rarely high on a patients list of topics they want to discuss at an office visit. It is easy to put off this discussion when seemingly more pressing issues are the patient’s expressed reason for the office visit. Even at physical exam visits, or in the medical coding lingo “preventative care” or “health maintenance” visits, it is alluring to focus on topics that lead to a longer or healthier life rather than a better death experience. Here is the list of the physician-related barriers to completion of an advance directive listed in the AFP article:

Discomfort with the topic.
Lack of institutional support.
Lack of reimbursement.
Lack of time.
Waiting for the patient to initiate the discussion.

In my case it is certainly not discomfort with the subject, and I am not intentionally waiting for the patient to bring up the subject, but lack of time and reimbursement undoubtedly play a role.

In addition most patients really don’t need my help in working through this decision process if they address the issue before there is a crisis. Although there are cultural, personal and ethnic variables that shape our decision making, most of my patients can really quite quickly and easily work through the process of completion of both a very functional living will and a durable power of attorney without my assistance. So why doesn’t everyone just do it themselves? Here are the barriers listed in the AFP article that are patient related:

Fear of burdening others, i.e. family or friends.
Health Literacy
Lack of interest or knowledge of the subject.
Spiritual, cultural or racial traditions.
Waiting for their physician to initiate the discussion.

So how can you just “Do it yourself?” It’s really easy. Obvoiusly since you are reading this article you have access to the internet, and everything you need is just a few clicks away. I encourage you, if you have not already completed these documents, to DO IT NOW:

Down load your state’s Advance Directives at the caringinfo.org site. This is really easy and you can get everything you need by selecting your state from the list here.
Many states have a form called a POLST form. This stands for physician orders for live sustaining treatment. If you use a search engine like Google, and you type in your state + POLST form you will easily find a form to download if your state has a POLST form. You can get the Washington State form to download easily at WA POLST download. Many physician offices have these available, just ask your doctor.
For some people a form to help you ascertain your values on this subject and to make your values clear to the individual you choose to have your medical power of attorney is helpful. The University of New Mexico Institute for Ethics has published online a non-copyright protected form for you to download. Some patients will find it helpful to attach this to their advance directive as guidance to their proxy in making decisions in line with their values.

There you have it. You have no more valid excuses to keep you from completing your own advance directive and living will. Once you complete it be sure to not keep it a secret. Give a copy to your physician, to the person you choose as your DPA, and keep a copy handy at your home. Don’t be a victim of your own procrastination or discomfort with this topic. If you find it helpful ask questions on the subject up with your personal physician. Be sure to let them know you have these documents completed.

In my best cheer-leading mantra: You can do it! Go – Go – Go!

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Selfishness and Suicide

March 5, 2012 Dr. Pullen

Is suicide the epitome of selfishness? I was initially taken aback when a person I completely respect told me how angry he was about a colleague who had committed suicide, telling me how selfish he though the person had been. I had not thought of suicide as a selfish act previously, but have thought a good deal about it since.

I see patients, parents, grandparents, siblings, friends and lovers concerned about suicide in the office from time to time. Other times I am the one concerned about suicide in patients I think may be at risk. Suicide is I a big and growing concern in the U.S. these days and I thought this would be a good time to write about this topic to share some statistical information and some thoughts. I hope to stimulate a forum for comments and sharing of thoughts in the comments below.

First some thoughts:

I think of suicide as the ultimate in selfish behavior most of the time. The purported victim leaves behind many other victims of their act. Family, loved ones, friends, associates and their whole community are left to grieve, often filled with guilt over the lost soul. Don’t ever think of suicide as leaving the world better off without out your presence, you will leave far more sadness and grief behind that if you live.
Never be afraid to ask anyone if suicide is a concern. They may lie and say no, but often people with suicidal intent will admit their concern if directly and empathetically asked.
If you have concerns about suicide for yourself or someone else ask for help. There are 24-hour crisis lines available, your physician, pastor, or other professional is obliged and usually happy to try to help.
Never think of a half-hearted suicide attempt as a way to find help. Miscalculations or other mishaps can make a suicidal gesture (not really meaning to kill yourself, but really asking for help) into a successful suicide all too often.

First some thoughts:

I think of suicide as the ultimate in selfish behavior most of the time. The purported victim leaves behind many other victims of their act. Family, loved ones, friends, associates and their whole community are left to grieve, often filled with guilt over the lost soul. Don’t ever think of suicide as leaving the world better off without out your presence, you will leave far more sadness and grief behind that if you live.
Never be afraid to ask anyone if suicide is a concern. They may lie and say no, but often people with suicidal intent will admit their concern if directly and empathetically asked.
If you have concerns about suicide for yourself or someone else ask for help. There are 24-hour crisis lines available, your physician, pastor, or other professional is obliged and usually happy to try to help.
Never think of a half-hearted suicide attempt as a way to find help. Miscalculations or other mishaps can make a suicidal gesture (not really meaning to kill yourself, but really asking for help) into a successful suicide all too often.

Next some statistics that I find interesting and informative:

N 2007 suicide was the 10^th leading cause of death in the U.S.
Although persons of all ages may commit suicide young men and the elderly are by far at highest risk. The incidence of suicide in adolescents ages 15-19 is 6.9/100,000, in young adults 20-24 is 12.7/100,000 and in adults 65 and older 14.3/100,000. In the age range 15-19 males are 5x as likely as females, and in 20-24 males are 6x as likely as females to die of suicide.
Access to firearms is a major risk for successful suicide. Children in homes with firearms are 10x as likely to die of suicide as children in homes without firearms.
Both men and women die of firearms related suicide but males are especially at risk. 56% of male suicides involve firearms vs. 30% of females. Males are also more likely to die of suffocation than females at 24 vs.21%.
Females are far more likely to die of poisoning at 40% vs. 13% than males.
Gay young men are especially at risk for suicide. See comments below.

Risk factors for suicide include:

Prior suicide attempts
Mental health problems
Drug or alcohol abuse
Separation or divorce
Physical or sexual abuse
Being young and gay. Several studies show higher risks of suicide in gay male adolescents. Risk estimates range from 2-10x. (1,2)
Returning veterans of the recent Iraq and Afghanistan wars are at risk.

So what can we do to keep suicide from affecting those near us? I suggest a few things.

If you choose to have firearms in your home, take rigorous precautions to keep them away from adolescents. Recognize this as a major risk factor.
Even if you do not suspect any concern, make the topic a regular subject to bring up with your child. Be sure they understand that suicide is not acceptable, and that you are very willing to help them in any way if suicide becomes remotely a concern.
Take any suicidal hints or references very seriously.
Keep prescription and non-prescription medications well away from youth. Buy non-prescription drugs in small quantities or keep larger quantities locked away.
Never think of suicide as beneficial to others. It is strictly a selfish exit from life, and leave behind others to struggle with your loss as well as all of their own problems. It makes nothing better.

I’d love to hear comments from readers. Leave a comment below.

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The Grapefruit and Medication Dilemma

March 1, 2012 Dr. Pullen

Grapefruit has a flavor that is unique and refreshing. There is something about sitting down to a half grapefruit, carefully separating the segments, enjoying each one and then squeezing out the

juice to sip that just makes a breakfast seem civilized and elegant. One problem, often in apparent to the casual grapefruit lover, is that there is something else special about grapefruit. It contains a substance that is an irreversible competitive inhibitor of the CYP 3A4 intestinal isoenzyme that breaks down a wide variety of medications. You may think Dr. Pullen has lost it, getting this technical on this blog intended for patients not scientists. Bear with me; it is an interesting and possibly important story.

Many medications are metabolized in the liver through a number of different enzyme mediated steps using what are called the cytochrome P450 (CYP 450) enzymes. There are several different variations of this enzyme, each with a alphanumeric moniker, like 3A4, 2D1 and so on. One of the most important is the 3A4 isoenzyme. It is located in the liver primarily, but also on what is called the brush border of the small intestinal cells. The brush border is where nutrients and medications are broken down into tiny molecules by various digestive enzymes to be absorbed into the blood that goes to the liver. The CYP 450 3A4 enzyme at this intestinal brush border functions to inactivate significant amounts of some medications before they can get absorbed into the bloodstream.

Grapefruit (and a few other uncommonly eaten fruits) contain high amounts of something called furanocoumarin derivatives, which irreversibly bind to the intestinal brush border CYP 3A4 isoenzymes, and prevent the breakdown of many medications. By irreversible I mean this binding prevents an enzyme from functioning until the brush border cell dies and is replaced by another cell with new enzymes, often a period of a few days. When a person who takes one of the medications normally metabolized by the CYP 3A4 isoenzyme eats grapefruit or drinks grapefruit juice a higher percentage of that medication is absorbed into the bloodstream and becomes bioavailable. In the case of some medications this can be significant, and lead to the potential for toxicity or a higher incidence of dose related side effects.

As consumers of medical care it is important to know whether any medications you are taking have a significant grapefruit interaction potential or not. Your pharmacist will often counsel you regarding this issue, and it is usually mentioned in the drug handout information at the pharmacy, but this is easy information to overlook. Here is a list of the medications I think is most relevant to patients (not intended to be complete):

Statins: Simvastatin, Atorvastatin (Lipitor) and lovastatin (Mevacor) use the 3A4 pathway, but pravastatin, rosuvastatin (Crestor) and pitavastatin (Livalo) do not. This may be significant especially at higher doses of these drugs with the potential for dose related myalgias.

Dihydropyridine Calcium Channel Blockers: Several of the CCBs including fleldipine, nifedipine, nicardipine (Cardene). In addition verapamil, an non dihydropyridine CCB uses this pathway.

Carbamazepine: An anticonvulsant with a fairly narrow therapeutic window.

Sertraline (Zoloft) an SSRI type of antidepressant

Methadone: an opioid used for pain control and in some cases at methadone clinics for heroin addicts.

Omeprazole: a proton pump inhibitor used for stomach acid related disorders like reflux esophagitis

Cyclosporine: An important immunosuppressant.

Many of the HIV medications: In the early days of HIV therapy, to contain costs of branded drugs some physicians had patients routinely take their HIV drugs with grapefruit juice to allow lower doses of the medications. (don’t try this at home with your medications)

Losartin (Cozaar): a blood pressure medication

Colchicine: a gout medication

In many cases this interaction is not clinically significant, but in some cases it may be. If you use eat grapefruit or grapefruit juice you should consider asking your pharmacist about any medications you use to see if there is a significant concern. If there is be aware that this is not just an issue if the grapefruit and the drug are ingested at the same time, but for several days after eating/drinking the grapefruit.

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Asthenia

February 27, 2012 Dr. Pullen

Of the names we use to describe symptom in medicine the term asthenia is among the most descriptive. Somehow I am enamored by the term. Asthenia is an interesting word, beautiful in some way to me, but asthenia is not a symptom I look forward to using to describe my patient’s condition. Asthenia is almost a synonym for weakness, but implies a more serious connotation. Asthenia is usually used to describe a generalized weakness, as is noted in conditions like chronic wasting diseases like advanced HIV disease, cancer, advanced heart, kidney or liver disease, or some neuromuscular diseases. Asthenia is often associated with other symptoms like malaise, fatigue and dizziness. I usually think of asthenia being associated with weight loss, especially muscle mass loss.

Weakness that I don’t think of as being asthenia on the other hand is usually used to describe a loss of muscle strength that is localized or if generalized is not associated with overall wasting or other symptoms of advanced disease. Weakness can be associated with neuromuscular disease like a nerve root impingement, a stroke or other brain lesion and other causes that lead to true loss of power in one or more muscles, or can be more a perceived weakness where patients feel they need to exert more force than normal, but on testing muscle strength is normal. Disorders like chronic fatigue syndrome and depression can lead to perceived weakness

A specific disorder called myasthenia gravis is a condition where strength at rest is normal, but with repeated use muscle strength decreases. It is due to an autoimmune disorder where antibodies against the post-synaptic acetylcholine receptors at the neuromuscular junction are blocked.

Numerous medications have asthenia as a potential side effect. The HIV drug Ritonavir which functions as a protease inhibitor has been associated with asthenia. This has to be somewhat of a dilemma as progression of HIV itself is a potential cause of asthenia. Chronic opioid use for pain management has been linked to asthenia in some individuals. Alcoholism is a common cause of asthenia, as are other types of drug abuse. The list of potential medication causes of asthenia is long, and medication use always needs to be considered in a patient presenting with undiagnosed asthenia.

Still in my practice, admittedly a suburban practice where neglected disease is relatively uncommon and HIV is not a major part of my practice, advanced age, end stages of serious illnesses, and cancer are the most common causes of asthenia. As patients become very old it is common for them to lose strength and body mass and whether this is asthenia or not may be up for debate. Asthenia associated with weight loss is a fairly common presentation of undiagnosed cancer. Asthenia is fairly common with end stage cirrhosis and liver failure, with very severe congestive heart failure and with COPD as respiratory failure approaches. In most cases unless a diagnosis can be made with good treatment options asthenia is a serious if not ominous symptom.

I have to say I rarely describe a patient as having asthenia, but when I do it is with the intent of trying really hard to find an underlying cause that can be treated or at least discovered, because asthenia in my mind is usually something that needs to be figured out.

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Benign Neglect

February 23, 2012 Dr. Pullen

Benign neglect is a concept that comes into play more often than you might think in my office. As I mused about this over lunch today it led me to look at the genesis of the term, which I was surprised to find is attributed to Patrick Moynihan when he was in the Nixon white house. (I was most surprised to hear that this famously liberal democrat was in the Nixon white house, but he was in 4 consecutive administrations from JFK through Gerald Ford) The term was used to refer to a policy recommendation that the issue of race in the late 1960’s could benefit from a period of “benign neglect.”

I think of benign neglect in my office primarily in dealing with patients who are more likely to benefit from not investigating or treating a condition or complaint than by actively managing the condition. A good example is a woman in her mid 80’s with mild dementia and multiple chronic medical conditions, maybe longstanding diabetes and who has had a coronary bypass surgery 12 years ago who asks if she should have a mammogram. In this case her life expectancy is relatively short, maybe 2-5 years, and the benefit of an early diagnosis of breast cancer is minimal. In addition the diagnosis is going to force difficult decisions to be made. Is no treatment, minor treatment, or moderately aggressive treatment best for her situation? Is she competent to make the choice herself? The dilemma expands. Maybe the best approach is to not test for the condition in the first place. In her case most of the time it is an easy consensus to choose not to do the mammogram.

Benign neglect can also apply to situations where leaving relatively harmless conditions alone is better than aggressive treatment. Examples I see are molluscum contagiosum, where the lesions usually resolve with no therapy in a year or so vs. painful ablative therapy that is far from uniformly successful on the child with the lesions. Another example is with seborrheic keratoses ( the brownish waxy pasted on lesions so common on our skin as we age) or small lipomas (benign fatty tumors) of the skin. These generally don’t go away, and often very slowly grow, but usually never bother the patient except cosmetically. If the y need to be removed later it is not especially more difficult on larger lesions. If patients are comfortable ignoring these, then benign neglect is a great option. Benign neglect is a key to successful parenting too. It is more widely called ignoring, and involves not rising to the lure of a child’s minor misbehavior. Often the misbehavior is an attention gaining behavior, and ignoring the behavior will more likely lead to dissipation of it than confrontation or punishment. Examples in early childhood are temper tantrums, and in teens door slamming or a minor cursing. Bringing attention to the behavior may be just the attention the child consciously or subconsciously desired, and the benign neglect of ignoring can be effective at reducing the behavior.

It’s important to understand what you are doing when you choose benign neglect as the best tactic. It is not appropriate when it simply makes your life easier. In order to be truly benign the choice must in it total consequences have a neutral or better impact. Most of the time when I choose benign neglect I anticipate the likelihood of negative consequences of active intervention to outweigh the likelihood of negative consequences of choosing no active intervention. Benign neglect is an important part of good primary care, yet needs to be used consciously and carefully.

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Scope of Practice: Advantage of Seeing a Family Doctor First

February 20, 2012 Dr. Pullen

Early in my fourth year of med school, when I was trying to decide what type of residency to apply for, I realized that I enjoyed the breadth of the scope of practice a family physician embraces. I tell my patients that I specialize in what they walk through the door with. As a family physician I have to be comfortable and competent at seeing nearly any patient for any problem and helping them access the care that they need for the problem they present asking for help with. In addition I have to try to recognize problems or health risks that they may not recognize, and have to find a way to let my patients accept what I feel is appropriate preventative care and disease management. I need to be familiar with a vast array of medications, from psyllium to pradaxa, and problems from PSVT to psychogenic cough.

I often am asked by patients if they should come see me or if they should just go directly to the specialist they feel is going to be able to definitively address their concern. I don’t mean to sound pompous here, but often patients are way off base in choosing the specialist best suited to their problem. Seeing a specialist in an arena of healthcare different from your problem has several risks. These include significant delay in receiving appropriate care, incurring the expense of extensive testing in their area of interest prior to reaching the specialist appropriate to your circumstances, overdiagnosis, and missing related or unrelated problems that a family physician may recognize but a sub-specialist may not notice. Let’s go through these in more detail:

Delay in Receiving Appropriate Care: This can be the result of various causes. The one most concerning to me is when a patient makes a self-diagnosis and sees a specialist in that field. Often symptoms that seem related to one area expertise are caused by a disorder not apparent to the patient. Epigastric pain and nausea may be the result of heartburn and a gastroenterologist may be suited to evaluate and treat the pain. On the other hand it may be related to coronary ischemia and need urgent intervention. Seeing a gastroenterologist is not only not going to help, but may delay care, either because of a longer time to get an appointment for evaluation or because specialists often extensively evaluate issues in their area of concern prior to referral to another specialist. The time to have a trial of a medication for acid reflux and have an endoscopic exam of the esophagus and stomach may be detrimental to the care of a patient with coronary disease.
Incurring Expensive Testing: When a patient sees a family physician they are likely evaluated for the most serious or most likely problems causing their symptoms. The list of potential concerns often extends across several areas of sub-specialty interest. By looking at the most serious and most likely issues first a family physician is more likely to avoid expensive tests for very unlikely problems. An example might be a patient with groin pain. If this patient sees a family doctor, they will probably be evaluated by history and physical exam for things like inguinal hernia, urologic causes like kidney stone and infection, hip pathology, in women ovarian-gynecologic issues including ectopic pregnancy, gastrointestinal causes and neurologic causes. If they see a urologist they are likely to have extensive evaluation for urologic problems, and may get a correct diagnosis of a kidney stone or UTI. If their problem very likely a gynecologic problem, they are still likely to have extensive evaluation for the urologic issues because no specialist wants to miss a diagnosis in their field of expertise no matter how low the likelihood may be. This holds true for most specialists. If you see a sub-specialist you are very likely to have an extensive evaluation for problems in their scope of practice whether or not they think you likely have a problem in their realm. A family physician is more likely to go through a process of looking for problems they consider important and likely, and put off extensive evaluation for very unlikely diagnoses. The cost savings of the latter approach can be huge.
Overdiagnosis: I’ll be brief here, but if you have imaging like an MRI, CT scan, ultrasound or even many lab tests abnormalities are often noted that can lead to extensive testing which has its own risks, or diagnosis of a problem that does not now nor will ever bother you. The latter is called overdiagnosis. See a prior post on overdiagnosis for more information on this topic. Overdiagnosis may lead to medication side effects, risks of unnecessary procedures, and emotional distress.
Missing related or unrelated Problems: A specialist while highly trained in their scope of practice may not be focused on related or unrelated important health care issues. If you see a cardiologist it is unlikely that they are going to recognize that you are due for a mammogram and urge you to get a preventative care visit for this and other preventative services you are due. If you see a dermatologist it is unlikely you will bring up your “Oh doctor, by the way I am having these odd numbness and weakness symptoms,” that may lead your family physician to consider a TIA and make interventions to prevent stroke. The list of similar situations is nearly endless.

I feel pretty strongly that the first point of care for most health concerns should be either your family physician or the emergency department for life threatening emergencies. The scope of practice of your family physician gives you the best chance of efficient, timely and effective care.

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