I've covered generic drugs and their supposed inferiority to brand-name drugs before. But something came up at work the other day that made me want to take a second look at the topic.
Scenario: Male patient, age I forget, military (so he has Tricare insurance, which pays for everything except for the things that it doesn't). A middle-aged woman is driving him around and apparently in charge of his care (wife? mother? again, I forget the guy's age).
Four new prescriptions. Metoprolol XL (beta-blocker), raniditine (antacid), warfarin (Coumadin, anticoagulant/"blood thinner"), furosemide (diuretic/fluid mobilizer). All new meds for him. I guessed post-heart attack or maybe heart failure, but didn't actually ask what was wrong.
Doctor signed the Coumadin script dispense as written. Tricare won't pay for brand-name Coumadin for this patient. Other three drugs come back $0. Zero, zip, nothing, free. Coumadin comes back $55. The patient has two options: Wait for someone to call the doc tomorrow and get authorization to dispense generic or pay for the brand. For $55, I'll tell you what I'd do. He didn't; he paid the $55. Why?
"His doctor is very particular, and he has a lot of allergies, so he's going to go with the brand name. He might be allergic to one of the fillers in the generic, you know."
To the credit of the woman managing his care, she was actually pretty smart. She asked a lot of good questions and knew a thing or two about the medicines she and some of her family members were on. Best kind of patient. But here was an example of what she knew getting her in trouble, and she wouldn't be talked out of it. I had previously explained to her that it didn't matter whether he went brand or generic as long as he stuck with his choice (warfarin is a fickle mistress, and you want to be consistent).
I'd heard this line of reasoning before--once from a patient and once from a tech I used to work with. "I might be allergic to the fillers in the generic."
News flash. You might be allergic to the fillers (excipients) in the brand, too. There are probably only about two dozen different ingredients that you can put into tablets and have them still do what they're supposed to do. The brand and the generic probably differ by only one or two excipients. If you've never taken either one, you are just as likely to be allergic to a component of the brand as the generic. Generic drugs are not made with ingredients that are somehow more likely to be immunogenic.
So. Unless you know you're allergic to something (a dye, for example) and you know the brand or generic version of a particular drug contains that something there's no reason to assume you are "less likely" to be allergic to something in the brand name drug.
Another day, another victory. Generics are still the way to go, 99.999% of the time.
Showing posts with label patient education. Show all posts
Showing posts with label patient education. Show all posts
Monday, October 6, 2008
Friday, September 26, 2008
But Doctor, I NEED Antibiotics!
How often do you go to the doctor? What prompts you to seek care?
For many people, the answer to that question is "at least once a year" and the reason is upper respiratory tract infection (URTI). Because of the amount of time and effort involved in isolating precisely what is causing an upper respiratory tract infection, doctors quite frequently prescribe unneeded antibiotics:
It is a well-established fact that a huge percentage of antibiotic prescriptions are dispensed for conditions where they will have no effect, such as the common cold, simply because doctors feel that they have some obligation to write patients a prescription--or because the patients pressure the doctor and insist that they need an antibiotic.
But statistics released in this month's Pharmacist's Letter make the issue very clear. Overtreating with antibiotics does more harm than good.
Now, as always, I encourage readers who believe that they might be suffering from any illness to consult their physicians. But think about those numbers for a second. There's only a 0.025% chance that it's going to do you any good to beg your doctor for an antibiotic prescription. The odds that you will wind up in the ER because of a bad antibiotic reaction are higher than the odds that the antibiotic is going to do you any good.
This does not mean that you should avoid antibiotics at all costs, believing that the risks always outweigh the benefits, because that is patently untrue. Keep in mind that these numbers only pertain to (generally non life-threatening) respiratory infections. What this really mean is that you should ask your doctor to be straight with you, especially if you are going to the doctor because you're coughing up phlegm or have a stuffy head. "Do you really think I need an antibiotic?" Make it very clear that you will take no for an answer if it is that physician's professional opinion that you don't need one. They didn't go to school for nothing.
For many people, the answer to that question is "at least once a year" and the reason is upper respiratory tract infection (URTI). Because of the amount of time and effort involved in isolating precisely what is causing an upper respiratory tract infection, doctors quite frequently prescribe unneeded antibiotics:
Various bacterial respiratory infections were diagnosed during 6.5% of physician office visits in 1999. One or more antibiotics were prescribed during 51.0% of those visits. The probabilities of resistance to the most frequently prescribed antibiotics varied from 20% to 40% and showed a weak positive correlation with the frequencies of antibiotic prescriptions.
It is a well-established fact that a huge percentage of antibiotic prescriptions are dispensed for conditions where they will have no effect, such as the common cold, simply because doctors feel that they have some obligation to write patients a prescription--or because the patients pressure the doctor and insist that they need an antibiotic.
But statistics released in this month's Pharmacist's Letter make the issue very clear. Overtreating with antibiotics does more harm than good.
There's only a 1 in 4000 chance that an antibiotic will help most acute upper respiratory infections.
But there's a 1 in 4 chance of diarrhea...a 1 in 50 chance of a skin reaction...and a 1 in 1000 chance it'll cause an ER visit.
...antibiotics [overuse] can also lead to more resistant infections that are harder to treat.
Now, as always, I encourage readers who believe that they might be suffering from any illness to consult their physicians. But think about those numbers for a second. There's only a 0.025% chance that it's going to do you any good to beg your doctor for an antibiotic prescription. The odds that you will wind up in the ER because of a bad antibiotic reaction are higher than the odds that the antibiotic is going to do you any good.
This does not mean that you should avoid antibiotics at all costs, believing that the risks always outweigh the benefits, because that is patently untrue. Keep in mind that these numbers only pertain to (generally non life-threatening) respiratory infections. What this really mean is that you should ask your doctor to be straight with you, especially if you are going to the doctor because you're coughing up phlegm or have a stuffy head. "Do you really think I need an antibiotic?" Make it very clear that you will take no for an answer if it is that physician's professional opinion that you don't need one. They didn't go to school for nothing.
Monday, September 22, 2008
It's Ozone Action Day: Don't Use Your Inhaler
Do you remember the CFC reduction efforts that went into effect in the latter half of the 20th century? CFCs, or chlorofluorocarbons, are a class of compounds that were traditionally used as refrigerants, solvents, or propellants in aerosol spray cans. When scientists determined that CFCs were contributing to the hole in the ozone layer. CFCs participate in a reaction with ozone where they act as a catalyst--i.e., they are not used up--that breaks ozone down into oxygen gas. Because individual CFC molecules are not used up in the reaction, a single CFC molecule may continue to break down thousands of ozone molecules over its lifetime.
What does this have to do with inhalers? By the end of 2008, CFC-containing inhalers will no longer be sold.
Traditional inhalers used to treat respiratory diseases like asthma used CFC-based propellants to deliver an aerosolized spray of medication directly to the lungs. But the time has come to phase out the old inhalers and replace them with new, more environmentally-friendly alternatives. The replacements, HFA inhalers, are just as effective as the old standbys without causing damage to the ozone layer or contributing to greenhouse gas production. The switch is a good thing, on the whole.
For once, Pharma is releasing a bunch of variations on their old products that aren't just a scam to extend their patents. They're actually doing something to help the environment. Y'know, aside from the fact that they're doing so because of Federal mandate.
There are a few minor issues that must be addressed. The new inhalers are just as good as the old ones, but FDA regulations consider them to be different, non-equivalent drug formulations. This means that you can't simply switch back and forth from CFC to HFA--in most states, the physician who writes the prescription must specify that the inhaler to be dispensed is an HFA inhaler. HFA inhalers are also going to cost slightly more--about $50 versus $30 for the old inhalers. But many manufacturers are distributing coupons that might help reduce costs for patients making the switch.
So if you use an inhaler, be prepared--you're going to have to switch, and soon. But the sooner the better, really. With every puff you're taking on an HFA inhaler instead of a CFC inhaler, you're contributing to the efforts to repair the ozone layer. That's like saving the world, one inhalation at at time.
What does this have to do with inhalers? By the end of 2008, CFC-containing inhalers will no longer be sold.
Traditional inhalers used to treat respiratory diseases like asthma used CFC-based propellants to deliver an aerosolized spray of medication directly to the lungs. But the time has come to phase out the old inhalers and replace them with new, more environmentally-friendly alternatives. The replacements, HFA inhalers, are just as effective as the old standbys without causing damage to the ozone layer or contributing to greenhouse gas production. The switch is a good thing, on the whole.
For once, Pharma is releasing a bunch of variations on their old products that aren't just a scam to extend their patents. They're actually doing something to help the environment. Y'know, aside from the fact that they're doing so because of Federal mandate.
There are a few minor issues that must be addressed. The new inhalers are just as good as the old ones, but FDA regulations consider them to be different, non-equivalent drug formulations. This means that you can't simply switch back and forth from CFC to HFA--in most states, the physician who writes the prescription must specify that the inhaler to be dispensed is an HFA inhaler. HFA inhalers are also going to cost slightly more--about $50 versus $30 for the old inhalers. But many manufacturers are distributing coupons that might help reduce costs for patients making the switch.
So if you use an inhaler, be prepared--you're going to have to switch, and soon. But the sooner the better, really. With every puff you're taking on an HFA inhaler instead of a CFC inhaler, you're contributing to the efforts to repair the ozone layer. That's like saving the world, one inhalation at at time.
Thursday, April 17, 2008
Just Pissing It Away
It's been quiet in my corner of the blogosphere, but I lay the blame squarely on the fact that my latest round of exams has kept me extremely busy. Ths plus side of all this is that I get to come back to lots of news, all ripe for comment!
Like this article published today analyzing a couple studies from early 2000 about certain drugs prescribed for high blood pressure being potentially tied to bone loss, particularly in older men.
Most of the time, our sound bite-focused media doesn't get the whole story out there. This article is no exception.
Diuretics are commonly called "water pills," particularly by older people. I really, really hate that term. It isn't even remotely appropriate for describing how diuretics function. I suppose that the analogy comes from the idea that drinking more water causes increased urination, and taking diuretics causes increased urination; hence, diuretics are "water in pill form," except that that totally fails to explain how they work to lower blood pressure. Normally I don't think it's necessary for patients to know the mechanisms of action for the drugs they take--such details are excessively complicated. But we strive to explain things in the simplest way we can without sacrificing accuracy. Antidepressants, for example, are said to "balance or correct problems in brain chemistry." This is simple, but true at the base level.
Diuretics don't add anything to your body, and they certainly don't hydrate you. They have varying mechanisms of action, but what they really do is increase the body's excretion of certain elements that float around in the body in ion form. Sodium, potassium, and calcium are three good examples--they are commonly called "electrolytes," especially if you like reading the labels on your sports drinks. Generally, sodium loss is desirable in patients with high blood pressure. All of these ions must be present in proper concentrations for the body's various functions to work properly. Too much and too little are both bad. Diuretics are a convenient way to get rid of excess electrolytes.
The diuretic the article is talking about is furosemide, though there are other diuretics in the same family that have the same effect. Furosemide flushes out sodium, potassium, and calcium by preventing the kidneys from re-absorbing it at a specific point (the loop of Henle, if you're curious). Many patients on furosemide are also prescribed potassium supplements to counter the potassium loss. The calcium loss is not as frequently addressed, but it really should be; then again, most people don't get enough calcium anyway.
But saying diuretics in general are responsible for worsening bone loss is not only alarmist, it's false. Hydrochlorothiazide, or HCTZ, actually results in calcium retention. Sometimes this is a problem, as it can cause calcium levels in the blood to get too high. But for some patients with high blood pressure who are also at risk for osteoporosis, HCTZ is a great drug; it helps them retain extra calcium, improving bone density! This doesn't mean that everyone at risk for osteoporosis should be on HCTZ; increasing dietary calcium and vitamin D are a much better idea. But when treating patients with high blood pressure, it is often best to use drugs that "kill two birds with one stone." Likewise, it doesn't mean that patients at risk for bone loss shouldn't get furosemide. This is what trained physicians and pharmacists are for--evaluating the complicated mess of risks, benefits, and drug interactions that make modern medical therapy so difficult to manage.
And that's the bottom line--medicine is complicated. One 200-word article in a newspaper is never going to explain all the ins and outs of any particular treatment or drug; that's why scholarly journal articles are long, detailed, and extensively referenced. So consider very carefully where you get your information; chances are that if it was packaged for the general public and sold at the newsstand, you're not getting the whole story.
Like this article published today analyzing a couple studies from early 2000 about certain drugs prescribed for high blood pressure being potentially tied to bone loss, particularly in older men.
Most of the time, our sound bite-focused media doesn't get the whole story out there. This article is no exception.
Diuretics are commonly called "water pills," particularly by older people. I really, really hate that term. It isn't even remotely appropriate for describing how diuretics function. I suppose that the analogy comes from the idea that drinking more water causes increased urination, and taking diuretics causes increased urination; hence, diuretics are "water in pill form," except that that totally fails to explain how they work to lower blood pressure. Normally I don't think it's necessary for patients to know the mechanisms of action for the drugs they take--such details are excessively complicated. But we strive to explain things in the simplest way we can without sacrificing accuracy. Antidepressants, for example, are said to "balance or correct problems in brain chemistry." This is simple, but true at the base level.
Diuretics don't add anything to your body, and they certainly don't hydrate you. They have varying mechanisms of action, but what they really do is increase the body's excretion of certain elements that float around in the body in ion form. Sodium, potassium, and calcium are three good examples--they are commonly called "electrolytes," especially if you like reading the labels on your sports drinks. Generally, sodium loss is desirable in patients with high blood pressure. All of these ions must be present in proper concentrations for the body's various functions to work properly. Too much and too little are both bad. Diuretics are a convenient way to get rid of excess electrolytes.
The diuretic the article is talking about is furosemide, though there are other diuretics in the same family that have the same effect. Furosemide flushes out sodium, potassium, and calcium by preventing the kidneys from re-absorbing it at a specific point (the loop of Henle, if you're curious). Many patients on furosemide are also prescribed potassium supplements to counter the potassium loss. The calcium loss is not as frequently addressed, but it really should be; then again, most people don't get enough calcium anyway.
But saying diuretics in general are responsible for worsening bone loss is not only alarmist, it's false. Hydrochlorothiazide, or HCTZ, actually results in calcium retention. Sometimes this is a problem, as it can cause calcium levels in the blood to get too high. But for some patients with high blood pressure who are also at risk for osteoporosis, HCTZ is a great drug; it helps them retain extra calcium, improving bone density! This doesn't mean that everyone at risk for osteoporosis should be on HCTZ; increasing dietary calcium and vitamin D are a much better idea. But when treating patients with high blood pressure, it is often best to use drugs that "kill two birds with one stone." Likewise, it doesn't mean that patients at risk for bone loss shouldn't get furosemide. This is what trained physicians and pharmacists are for--evaluating the complicated mess of risks, benefits, and drug interactions that make modern medical therapy so difficult to manage.
And that's the bottom line--medicine is complicated. One 200-word article in a newspaper is never going to explain all the ins and outs of any particular treatment or drug; that's why scholarly journal articles are long, detailed, and extensively referenced. So consider very carefully where you get your information; chances are that if it was packaged for the general public and sold at the newsstand, you're not getting the whole story.
Wednesday, March 19, 2008
The Great Generic "Controversy"
The short version of this post is that there is no controversy. 99% of generic drugs are safe and effective. Given available data and a long history of positive results, there is simply no reason for your pharmacist (or your doctor) to recommend against use of a generic in 99% of all cases.
Let's start off the post with a list of comments I hear from patients on a fairly regular basis on the subject of generic drugs.
•"I want the 'real thing.'"
•"My doctor told me that generics don't work."
•"I'm allergic to generics."
•"How can the generic be as good if it's cheaper?"
•"No one is willing to guarantee that the generic and the brand are exactly the same, so I want the brand."
For starters, generics are "the real thing." They contain the same drug molecule that is responsible for changing your body's function as the brand. They are not cheap imitations. A technician I once worked with explained that people's objection to generic drugs was frequently because of their experience with generic foods; generic Oreos don't taste like "real" Oreos, after all. But unlike drug laws that mandate generics to be the same as brands, there's no law saying that generic Oreos have to taste just like real Oreos.
You aren't "allergic to generics." You just aren't. It isn't possible. An allergy to some component of a specific drug formulation (a dye, a flavoring, whatever) is totally possible. Saying you are allergic to generics is like saying you are allergic to fruit. The category is too big to be plausible.
If you think your doctor told you never to get generics, your doctor either failed to explain the difference between generic and brand adequately, or you are an idiot. A third possibility is that your doctor is a dermatologist. Some huge percentage of dermatologists advocate marking prescriptions for acne creams and similar products as "brand medically necessary" because they claim there is a huge difference. Hm. I'd think that if there were any product where a little bit of variation wouldn't matter much to my health would be my cosmetic face cream. Who knew?
The FDA has already answered the cost question. I won't answer it again.
Pharmacy colleague Abel Pharmboy has already elaborated on the basics of generic drugs. Patients are often confused by the 80-125% rule, so I rarely bring it up in clinical practice, but what it boils down to is this. It has nothing to do with the amount of drug in the tablet. It has nothing to do with the potency of the drug. Generics are equal to the brands in this respect. What differs between brands and generics, in most cases, are the "inert" fillers and binders that hold a tablet together or comprise the granules contained inside a capsule.
You rarely get the full dose of a drug. If you put a 100 mg tablet of drug X in your mouth and swallow it, there is a good chance that only a small percentage of drug X is absorbed (anywhere from 5% to 95%, depending on the drug). The big, technical word for this is bioavailability.
Suppose taking 100 mg of drug X means you have blood levels of 10 nanograms (ng) per deciliter (dL). What the 80-125% rule means is that if you take 100 mg of generic drug X your blood levels could be anywhere from 8 to 12.5 ng/dL and the drug would still be considered acceptable by FDA standards.
And that's the thing. For most drugs, it doesn't matter where you are in that range as long as you're above some minimum and below some toxic maximum, both of which are typically pretty far from the ideal range. Generic ibuprofen versus brands? Not gonna matter. Antibiotics? You're more likely to get sub-therapeutic blood levels because the patient isn't taking the drug properly than you are some bioavailability issue. Blood pressure meds? Your goal BP is based on averages, so it's all going to even out over time. Going generic is not going to cause your blood pressure to fluctuate wildly.
The whole thing only becomes an issue if this is not the first time a patient has taken a drug. If you have never taken a particular drug before, your blood level of that drug is obviously zero. You will start taking the drug, and after a set period of time, your blood level of the drug will reach a "steady" concentration as long as you continue taking your medication appropriately. It is only if you are suddenly switched from brand to generic that you might see a change--and you'd have the same issue if you started on generic and then switched to the brand.
For most drugs, as I mentioned above, there's no difference between our hypothetical 8 and 12 ng/dL. For others--those said to have a narrow therapeutic index--8 ng/dL may mean "no effect" and 12 ng/dL might mean "liver failure."
Of course, with drugs like this, patients must be closely monitored--using blood tests, in many cases--to make sure that they're getting just the right amount of drug. But that doesn't mean that the brand is superior. It means that the patient's therapy should be consistent. If the patient starts on the brand, they should stay on the brand, and if they start on the generic, they should stay on the generic, with no flip-flopping back and forth between the two. Most pharmacists are loathe to switch people back and forth repeatedly on drugs like Synthroid, Dilantin, or Lanoxin. And some states explicitly forbid it in their pharmacy law codes. Seizures in particular are all-or-nothing, so I totally agree with these sentiments.
Some people want to extend this no-substitution issue to all psychoactive drugs. Antidepressants are the big one; some patients really, really want the branded Paxil over the generic (generic brands just don't know how to act), for example (nevermind that brand name Paxil has not been on the market for a few years now).
It's easy to see why this might happen, drug efficacy aside. More expensive medicine makes patients feel better. I'm not saying antidepressants are placebos; the jury is still out on that one, though most evidence favors efficacy, even if it is slight (the drugs would never have been approved otherwise). But paying more for a drug--or a placebo--results in a better outcome for most patients. Perhaps paying more for the drug raises their expectations and subtly influences their mood. With largely subjective disorders like depression, subjective improvements are real improvements.
The case of the Wellbutrin scenario is somewhat unique in that we are talking about an extended-release product.
The process of making a tablet can be extremely simple or extremely complex. It is possible to make aspirin tablets by compressing crystalline aspirin with corn starch and water. At the other end of the spectrum are tablets that are designed with microscopic pores designed to release their contents at a constant (and precise) rate as the tablet passes through the intestinal tract, with the empty tablet shell being excreted with the next bowel movement. Extended-release formulations are generally on the complicated end of the scale, and the design process for these tablets is a great deal more involved. Many drug companies even patent their own extended-release mechanisms, like the OROS mechanism.
Because a generic manufacturer cannot simply use the same extended-release mechanism as the brand-name manufacturer (remember, these mechanisms are often patented), they must design their own tablet designed to release the drug at a similar rate. According to the ConsumerLabs data, the generic buproprion XL tablets released their drug more rapidly than Wellbutrin XL tablets. But the same amount of drug did get released, and the full dose was delivered.
Honestly, this doesn't surprise me in the least. The question is whether or not the increased rate of release is significant. For that, I'm going to have to go to Lexi-Comp's Drug Information Handbook, online edition. This could get a bit technical, but don't worry, I'll sum it up at the end.
The half-life of bupropion is greatly dependent on the person's liver function, ranging from 12 to 30 hours with an average of 21 hours. Bupropion's metabolites, i.e. the by-products of breakdown by the liver, are also active drugs, though they are less potent than bupropion (20-50% potency). These metabolites have half-lives similar to or longer than the primary drug, one of them having a half-life of anywhere from 30 to 40 hours.
What all these numbers ultimately mean is that bupropion hangs around in the body for a long time, and generic tablets releasing the drug over 2 and 1/2 hours instead of 5 hours is not going to significantly effect the "lower bound"--the lowest blood level measured in the peaks and valleys produced by daily administration. Remember that blood levels of a drug look kind of like a normal distribution curve, only flatter or shifted up, depending on the drug. To continue the math analogy, what the more rapid release is going to do is increase the slope of the curve.
This is not going to effect treatment of depression if the benchmark we're looking at is "is the patient maintaining minimum drug levels?" The more likely outcome is that the patient is going to experience a slight increase in side-effects compared to the brand name (if they've been switched from generic to brand recently) due to the fact that their blood levels are climbing more rapidly after administration. Whether or not this is going to be a problem depends on the patient. Last I checked, however, no one was complaining that patients switched to generic Wellbutrin XL were having seizures (which would be extremely unlikely unless the patient had an existing seizure disorder, which is a NO-NO when it comes to prescribing this drug). The specific issue probably never would have come up if it weren't for ConsumerLabs doing a bunch of assays.
Like with most brand-generic issues, the complaint from patients was most likely that the drug "wasn't working" or that they "just didn't feel right." These are the same complaints that come up all the time. That doesn't mean that they shouldn't be investigated; it just means that it's hard for heathcare professionals to filter things out given the poor signal to noise ratio.
I'm still not convinced that the differences between brand and generic Wellbutrin XL are clinically significant, but then, I'm just a pharmacy student. What's troubling is that this information didn't come out sooner, and, as Abel mentioned, the fact that it was kept under wraps until an independent lab started poking around seriously undermines both the generic drug companies and the FDA's trustworthiness in the eyes of the public. That's the true tragedy here; patients are going to think that this failure to disclose information is indicative of serious problems with the generic drug industry when in fact the complete opposite is true. The generic drug industry has a long record of producing safe and effective drugs. Most community pharmacies dispense generic alternatives for over 90% of the prescriptions they fill without any hitches--I know mine does.
Generic drugs are a great thing for patients. Let's not let one little slip--a slip of questionable significance from a clinical perspective--ruin that.
Let's start off the post with a list of comments I hear from patients on a fairly regular basis on the subject of generic drugs.
•"I want the 'real thing.'"
•"My doctor told me that generics don't work."
•"I'm allergic to generics."
•"How can the generic be as good if it's cheaper?"
•"No one is willing to guarantee that the generic and the brand are exactly the same, so I want the brand."
For starters, generics are "the real thing." They contain the same drug molecule that is responsible for changing your body's function as the brand. They are not cheap imitations. A technician I once worked with explained that people's objection to generic drugs was frequently because of their experience with generic foods; generic Oreos don't taste like "real" Oreos, after all. But unlike drug laws that mandate generics to be the same as brands, there's no law saying that generic Oreos have to taste just like real Oreos.
You aren't "allergic to generics." You just aren't. It isn't possible. An allergy to some component of a specific drug formulation (a dye, a flavoring, whatever) is totally possible. Saying you are allergic to generics is like saying you are allergic to fruit. The category is too big to be plausible.
If you think your doctor told you never to get generics, your doctor either failed to explain the difference between generic and brand adequately, or you are an idiot. A third possibility is that your doctor is a dermatologist. Some huge percentage of dermatologists advocate marking prescriptions for acne creams and similar products as "brand medically necessary" because they claim there is a huge difference. Hm. I'd think that if there were any product where a little bit of variation wouldn't matter much to my health would be my cosmetic face cream. Who knew?
The FDA has already answered the cost question. I won't answer it again.
Pharmacy colleague Abel Pharmboy has already elaborated on the basics of generic drugs. Patients are often confused by the 80-125% rule, so I rarely bring it up in clinical practice, but what it boils down to is this. It has nothing to do with the amount of drug in the tablet. It has nothing to do with the potency of the drug. Generics are equal to the brands in this respect. What differs between brands and generics, in most cases, are the "inert" fillers and binders that hold a tablet together or comprise the granules contained inside a capsule.
You rarely get the full dose of a drug. If you put a 100 mg tablet of drug X in your mouth and swallow it, there is a good chance that only a small percentage of drug X is absorbed (anywhere from 5% to 95%, depending on the drug). The big, technical word for this is bioavailability.
Suppose taking 100 mg of drug X means you have blood levels of 10 nanograms (ng) per deciliter (dL). What the 80-125% rule means is that if you take 100 mg of generic drug X your blood levels could be anywhere from 8 to 12.5 ng/dL and the drug would still be considered acceptable by FDA standards.
And that's the thing. For most drugs, it doesn't matter where you are in that range as long as you're above some minimum and below some toxic maximum, both of which are typically pretty far from the ideal range. Generic ibuprofen versus brands? Not gonna matter. Antibiotics? You're more likely to get sub-therapeutic blood levels because the patient isn't taking the drug properly than you are some bioavailability issue. Blood pressure meds? Your goal BP is based on averages, so it's all going to even out over time. Going generic is not going to cause your blood pressure to fluctuate wildly.
The whole thing only becomes an issue if this is not the first time a patient has taken a drug. If you have never taken a particular drug before, your blood level of that drug is obviously zero. You will start taking the drug, and after a set period of time, your blood level of the drug will reach a "steady" concentration as long as you continue taking your medication appropriately. It is only if you are suddenly switched from brand to generic that you might see a change--and you'd have the same issue if you started on generic and then switched to the brand.
For most drugs, as I mentioned above, there's no difference between our hypothetical 8 and 12 ng/dL. For others--those said to have a narrow therapeutic index--8 ng/dL may mean "no effect" and 12 ng/dL might mean "liver failure."
Of course, with drugs like this, patients must be closely monitored--using blood tests, in many cases--to make sure that they're getting just the right amount of drug. But that doesn't mean that the brand is superior. It means that the patient's therapy should be consistent. If the patient starts on the brand, they should stay on the brand, and if they start on the generic, they should stay on the generic, with no flip-flopping back and forth between the two. Most pharmacists are loathe to switch people back and forth repeatedly on drugs like Synthroid, Dilantin, or Lanoxin. And some states explicitly forbid it in their pharmacy law codes. Seizures in particular are all-or-nothing, so I totally agree with these sentiments.
Some people want to extend this no-substitution issue to all psychoactive drugs. Antidepressants are the big one; some patients really, really want the branded Paxil over the generic (generic brands just don't know how to act), for example (nevermind that brand name Paxil has not been on the market for a few years now).
It's easy to see why this might happen, drug efficacy aside. More expensive medicine makes patients feel better. I'm not saying antidepressants are placebos; the jury is still out on that one, though most evidence favors efficacy, even if it is slight (the drugs would never have been approved otherwise). But paying more for a drug--or a placebo--results in a better outcome for most patients. Perhaps paying more for the drug raises their expectations and subtly influences their mood. With largely subjective disorders like depression, subjective improvements are real improvements.
The case of the Wellbutrin scenario is somewhat unique in that we are talking about an extended-release product.
The process of making a tablet can be extremely simple or extremely complex. It is possible to make aspirin tablets by compressing crystalline aspirin with corn starch and water. At the other end of the spectrum are tablets that are designed with microscopic pores designed to release their contents at a constant (and precise) rate as the tablet passes through the intestinal tract, with the empty tablet shell being excreted with the next bowel movement. Extended-release formulations are generally on the complicated end of the scale, and the design process for these tablets is a great deal more involved. Many drug companies even patent their own extended-release mechanisms, like the OROS mechanism.
Because a generic manufacturer cannot simply use the same extended-release mechanism as the brand-name manufacturer (remember, these mechanisms are often patented), they must design their own tablet designed to release the drug at a similar rate. According to the ConsumerLabs data, the generic buproprion XL tablets released their drug more rapidly than Wellbutrin XL tablets. But the same amount of drug did get released, and the full dose was delivered.
Honestly, this doesn't surprise me in the least. The question is whether or not the increased rate of release is significant. For that, I'm going to have to go to Lexi-Comp's Drug Information Handbook, online edition. This could get a bit technical, but don't worry, I'll sum it up at the end.
The half-life of bupropion is greatly dependent on the person's liver function, ranging from 12 to 30 hours with an average of 21 hours. Bupropion's metabolites, i.e. the by-products of breakdown by the liver, are also active drugs, though they are less potent than bupropion (20-50% potency). These metabolites have half-lives similar to or longer than the primary drug, one of them having a half-life of anywhere from 30 to 40 hours.
What all these numbers ultimately mean is that bupropion hangs around in the body for a long time, and generic tablets releasing the drug over 2 and 1/2 hours instead of 5 hours is not going to significantly effect the "lower bound"--the lowest blood level measured in the peaks and valleys produced by daily administration. Remember that blood levels of a drug look kind of like a normal distribution curve, only flatter or shifted up, depending on the drug. To continue the math analogy, what the more rapid release is going to do is increase the slope of the curve.
This is not going to effect treatment of depression if the benchmark we're looking at is "is the patient maintaining minimum drug levels?" The more likely outcome is that the patient is going to experience a slight increase in side-effects compared to the brand name (if they've been switched from generic to brand recently) due to the fact that their blood levels are climbing more rapidly after administration. Whether or not this is going to be a problem depends on the patient. Last I checked, however, no one was complaining that patients switched to generic Wellbutrin XL were having seizures (which would be extremely unlikely unless the patient had an existing seizure disorder, which is a NO-NO when it comes to prescribing this drug). The specific issue probably never would have come up if it weren't for ConsumerLabs doing a bunch of assays.
Like with most brand-generic issues, the complaint from patients was most likely that the drug "wasn't working" or that they "just didn't feel right." These are the same complaints that come up all the time. That doesn't mean that they shouldn't be investigated; it just means that it's hard for heathcare professionals to filter things out given the poor signal to noise ratio.
I'm still not convinced that the differences between brand and generic Wellbutrin XL are clinically significant, but then, I'm just a pharmacy student. What's troubling is that this information didn't come out sooner, and, as Abel mentioned, the fact that it was kept under wraps until an independent lab started poking around seriously undermines both the generic drug companies and the FDA's trustworthiness in the eyes of the public. That's the true tragedy here; patients are going to think that this failure to disclose information is indicative of serious problems with the generic drug industry when in fact the complete opposite is true. The generic drug industry has a long record of producing safe and effective drugs. Most community pharmacies dispense generic alternatives for over 90% of the prescriptions they fill without any hitches--I know mine does.
Generic drugs are a great thing for patients. Let's not let one little slip--a slip of questionable significance from a clinical perspective--ruin that.
Monday, March 17, 2008
All Antibiotics Are Equal
...but some are more equal than others. Or so patients seem to think.
Here's the bottom line. If you take nothing else away from this post: Antibiotics are not "strong" or "weak." They are targeted.
Patients ask me some questions about antibiotics that sound truly strange if you know anything at all about microbiology and antimicrobial agents. Granted, most patients don't have that background, and it would be unfair for me to expect them to know the difference between Gram-negative and Gram-positive bacteria or to know anything about activity spectra. Probably the most common question, in some form or another, is "is this a good one?"
The answer is not as simple as yes or no. Are the antibiotics on the market effective for treating bacterial infections? Yes. Will this antibiotic be effective against your bacterial infection? I don't know. And, chances are, neither does your doctor, at least, not for certain. Are the risks of taking this antibiotic going to outweigh the benefits? Probably, unless you're taking telithromycin for acute bacterial sinusitis (which is not an acceptable use of the drug).
That bit about telithromycin was a bit of pharmacy dark humor. If you didn't get the joke, forget I mentioned it and move on with your life.
The only way to know if a given antibiotic will be effective in treating a particular infection is to culture the microorganism causing the disease. This means taking a sample from the patient, growing the sample on a petri dish, and then trying to grow the sample in the presence of various antibiotics that are released by little discs inserted into the growth medium. The bacterial growth results are then compared to a table for each antibiotic to determine whether or not the antibiotic sufficiently inhibited bacterial proliferation to say that the antibiotic will be effective against an infection in a living person.
This process takes anywhere from three days to a week to get right. Most patients are not willing to wait that long, and the lab tests are both costly and time-intensive. Most doctor's offices are not equipped to do a lot of lab testing. As a result, most doctor's visits where patients complain of what sounds like an infection result in the patient being sent out the door with a prescription for some antibiotic that the doctor thinks will be appropriate.
You can't blame physicians for not taking the time to culture everything, though I imagine most infectious disease specialists would bite your head off for suggesting that it's acceptable to start throwing around prescriptions without doing a culture. My microbiology professor would have a heart attack if I showed him the script I transcribed from a phone conversation on Saturday; Tamiflu and an antibiotic. Tamiflu kills influenza A viruses, but not bacteria. Antibiotics kill bacteria, but not viruses. You could argue that the physician is just covering his bases and trying to help the patient.
You could also argue that this is a little bit like using a blunderbuss to kill a mosquito.
The point of culturing bacteria is that antibiotics are not like a set of progressively bigger guns. They're specific tools in a toolbox. Using the wrong antibiotic is like using a hammer instead of a screwdriver. The problem is not that the tool isn't "strong" enough, it's that it isn't specific enough. Even healthcare professionals throw around terminology that makes it sound like some antibiotics are explicitly more "powerful" than others, but what they're really talking about is antibiotics that are used as last resorts. There are certain antibiotics that are used after everything else has failed--not because they're better and the others are "weaker," but because bacteria are less likely to resist them.
Which brings me to my second point. Bacterial resistance.
Bacterial resistance is a matter of evolution, i.e., natural selection. Suppose that 99% of all bacteria exposed to genericillin die. The 1% of the population that survives does so because it has randomly developed a means to protect itself from genericillin; perhaps it breaks down genericillin by secreting enzymes before the drug can affect the bacteria. That 1% of the population goes about its life and continues to reproduce, so that 1% of the old population is now billions of bacteria. The population rebuilds itself rapidly (due to lack of competition for resources), so we expose the bacteria to genericillin again. But this time, it doesn't work, because these bacteria are immune to genericillin. They were never susceptible to genericillin. What we have done is selectively bred the organisms most fit to survive in a genericillin-laden environment and killed off all of their competition, permitting their population to explode.
You do not become "immune" to an antibiotic because antibiotics don't do anything to "you" (at least, not ideally). This is probably the biggest misunderstanding of antibiotic resistance that I encounter--patients who think that they have become "immune" to genericillin because they took too much of it.
This is a little like expecting to be immune to bullets because you've shot too many people.
Unfortunately, the situation is much worse than that. You aren't the only one who has to deal with the consequences of resistant bacteria. We all do. And we have no one to blame but ourselves. Every unnecessary antibiotic prescription, every antibiotic that someone stops taking halfway through their therapy or that they "save for later," every "borrowed" medication--all of these contribute to resistant bacteria. The resistant bacteria already exist, for the most part, results of genetic mutations. But we're selectively breeding them by killing off their competition. Curing syphilis today requires eight times the dose that was required in 1960.
I've said it before, and I'll say it again. I would rather see physicians overprescribe narcotics than antibiotics. Drug addiction and substance abuse are bad, from a public health perspective, but breeding "superbugs" is a great deal worse. Addicts are, as a rule, only hurting themselves; overuse of antibiotics hurts everyone.
Here's the bottom line. If you take nothing else away from this post: Antibiotics are not "strong" or "weak." They are targeted.
Patients ask me some questions about antibiotics that sound truly strange if you know anything at all about microbiology and antimicrobial agents. Granted, most patients don't have that background, and it would be unfair for me to expect them to know the difference between Gram-negative and Gram-positive bacteria or to know anything about activity spectra. Probably the most common question, in some form or another, is "is this a good one?"
The answer is not as simple as yes or no. Are the antibiotics on the market effective for treating bacterial infections? Yes. Will this antibiotic be effective against your bacterial infection? I don't know. And, chances are, neither does your doctor, at least, not for certain. Are the risks of taking this antibiotic going to outweigh the benefits? Probably, unless you're taking telithromycin for acute bacterial sinusitis (which is not an acceptable use of the drug).
That bit about telithromycin was a bit of pharmacy dark humor. If you didn't get the joke, forget I mentioned it and move on with your life.
The only way to know if a given antibiotic will be effective in treating a particular infection is to culture the microorganism causing the disease. This means taking a sample from the patient, growing the sample on a petri dish, and then trying to grow the sample in the presence of various antibiotics that are released by little discs inserted into the growth medium. The bacterial growth results are then compared to a table for each antibiotic to determine whether or not the antibiotic sufficiently inhibited bacterial proliferation to say that the antibiotic will be effective against an infection in a living person.
This process takes anywhere from three days to a week to get right. Most patients are not willing to wait that long, and the lab tests are both costly and time-intensive. Most doctor's offices are not equipped to do a lot of lab testing. As a result, most doctor's visits where patients complain of what sounds like an infection result in the patient being sent out the door with a prescription for some antibiotic that the doctor thinks will be appropriate.
You can't blame physicians for not taking the time to culture everything, though I imagine most infectious disease specialists would bite your head off for suggesting that it's acceptable to start throwing around prescriptions without doing a culture. My microbiology professor would have a heart attack if I showed him the script I transcribed from a phone conversation on Saturday; Tamiflu and an antibiotic. Tamiflu kills influenza A viruses, but not bacteria. Antibiotics kill bacteria, but not viruses. You could argue that the physician is just covering his bases and trying to help the patient.
You could also argue that this is a little bit like using a blunderbuss to kill a mosquito.
The point of culturing bacteria is that antibiotics are not like a set of progressively bigger guns. They're specific tools in a toolbox. Using the wrong antibiotic is like using a hammer instead of a screwdriver. The problem is not that the tool isn't "strong" enough, it's that it isn't specific enough. Even healthcare professionals throw around terminology that makes it sound like some antibiotics are explicitly more "powerful" than others, but what they're really talking about is antibiotics that are used as last resorts. There are certain antibiotics that are used after everything else has failed--not because they're better and the others are "weaker," but because bacteria are less likely to resist them.
Which brings me to my second point. Bacterial resistance.
Bacterial resistance is a matter of evolution, i.e., natural selection. Suppose that 99% of all bacteria exposed to genericillin die. The 1% of the population that survives does so because it has randomly developed a means to protect itself from genericillin; perhaps it breaks down genericillin by secreting enzymes before the drug can affect the bacteria. That 1% of the population goes about its life and continues to reproduce, so that 1% of the old population is now billions of bacteria. The population rebuilds itself rapidly (due to lack of competition for resources), so we expose the bacteria to genericillin again. But this time, it doesn't work, because these bacteria are immune to genericillin. They were never susceptible to genericillin. What we have done is selectively bred the organisms most fit to survive in a genericillin-laden environment and killed off all of their competition, permitting their population to explode.
You do not become "immune" to an antibiotic because antibiotics don't do anything to "you" (at least, not ideally). This is probably the biggest misunderstanding of antibiotic resistance that I encounter--patients who think that they have become "immune" to genericillin because they took too much of it.
This is a little like expecting to be immune to bullets because you've shot too many people.
Unfortunately, the situation is much worse than that. You aren't the only one who has to deal with the consequences of resistant bacteria. We all do. And we have no one to blame but ourselves. Every unnecessary antibiotic prescription, every antibiotic that someone stops taking halfway through their therapy or that they "save for later," every "borrowed" medication--all of these contribute to resistant bacteria. The resistant bacteria already exist, for the most part, results of genetic mutations. But we're selectively breeding them by killing off their competition. Curing syphilis today requires eight times the dose that was required in 1960.
I've said it before, and I'll say it again. I would rather see physicians overprescribe narcotics than antibiotics. Drug addiction and substance abuse are bad, from a public health perspective, but breeding "superbugs" is a great deal worse. Addicts are, as a rule, only hurting themselves; overuse of antibiotics hurts everyone.
Tuesday, February 12, 2008
Diabetes Discussed: Part 3
Thus PalMD and I continue our cross-blogging endeavor to explain what researchers have figured out about diabetes in light of recent proclamations from the mouthpiece of science that type II diabetics may not benefit from dropping blood glucose levels to their minimum levels as much as previously thought.
Treatment of diabetes is multifaceted. As Pal pointed out, insulin is the mainstay of therapy, especially for type I diabetes. In type I, insulin is the only reasonable therapy; right now, nothing else works. They don't make insulin. They need insulin. Simple enough.
Insulin was the first protein drug product developed and widely used--it was originally derived from pigs or cows. Nowadays, we get our insulin from E. coli that have been genetically "reprogrammed" to produce human insulin through bioengineering. And we also have a huge variety of insulin products that are essentially just modifications made to the basic insulin design. Some insulins act more rapidly (like Humalog or Novolog) whereas others are intended to last up to 24 hours to provide an insulin "baseline" (like Lantus or Levemir). Insulin dosing may initially be based on weight, but after that, dosages are recalculated based on trial and error. It is difficult to predict precisely what quantity of insulin will produce the desired result, and there are several different rules and protocols for optimizing insulin dose. In short, insulin doses must be individualized to the patient, requiring a lot of careful monitoring by both the health care provider and the patient (with a home blood glucose monitor).
Treatment of type II diabetes is way, way more complicated.
Because type II diabetics can create insulin, but their cells are less responsive to its effects, the initial treatment of choice is usually metformin. Metformin is amazing. It's the only drug in its pharmaceutical "family" on the market, and nearly every type II diabetic is on it. It works by increasing the sensitivity of cells to insulin and by decreasing the amount of glucose the liver makes--it's that gluconeogenesis process again--which results in an overall decrease in blood sugar. It even causes some patients to lose weight, which is excellent; losing weight generally decreases the severity of type II diabetes.
Pal covered metformin and the other "oral hypoglycemics" already--sulfonylureas, like glipizide, force the pancreas to spit out more insulin. And thiazolidinediones (TZDs for short; that word is quite a mouthful) have multiple body effects, including increasing insulin sensitivity, but by a different mechanism than metformin--which means that they can be combined, and sometimes this produces better results.
I would like to stress at this point that if you or a loved one have diabetes, while this series may be thought-provoking and raise interesting questions, that you should discuss the matter with your primary care physician when it comes to individual treatment recommendations--not here. I'm not a licensed medical practitioner*, just a student of pharmacy with a flair for words and a desire to share his knowledge with the world. And even if I were licensed, reading some article written by an anonymous blogger is not an appropriate substitute for face-to-face medical advice.
With that out of the way. What does recent research tell us? Past research tells us that blood glucose is important. But new research says other things might be just as important--maybe more.
Heart disease is a number one killer of patients with type II diabetes. Kidney failure is more common in type I. They're both considered to be manifestations of the same disease. But they're clearly different in several ways. Pal mentioned ketoacidosis--that's common in type I, but incredibly rare in type II. What explains these differences?
If I wanted to indulge my inner conspiracy theorist I'd blame the drugs used to treat type II diabetes, which is kind of like the absurd claims made by tinfoil-hatwearing HIV denialists that AZT causes AIDS.
Much more likely is the difference in co-morbidities ("other diseases/conditions the same patient has") for both type I and type II patients. Type II patients are typically obese, or at least overweight. The Framingham heart study has demonstrated that being overweight (as defined by medical science, not People magazine) is a risk factor for cardiovascular disease. So is having wonky cholesterol levels--and those are pretty common for type II diabetics, too.
This study is kind of interesting. Essentially, cholesterol deposited on beta-cells--the part of the pancreas that secretes insulin--can induce beta-cell failure. Cholesterol essentially "clogs the pipes." Even more interesting is the fact that this whole problem may be tied to a gene that codes for a protein called ABCA1. ABCA1 is essentially the "conductor" responsible for regulating lipid transport in and out of beta-cells. People whose genes incorrectly code for the ABCA1 transmembrane protein may be more susceptible to lipid-based damage to the pancreas. It is entirely possible that controlling lipids is at least as important as controlling blood sugar in type II diabetes, which means that dietary modifications, exercise, and cholesterol-lowering drug therapy may all play an even greater role in achieving good treatment outcomes than previously thought. This is exciting research!
That study's too neat to just be a throwaway link. I might come back to it later.
I think the point of recent research basically demonstrates that we can't just treat blood sugar. It doesn't mean we're completely mean about how we're treating diabetes. It just gives us a new direction to focus our research. Diabetes may be conceptualized as a problem with glucose metabolism, but that isn't the end of the story. Physicians, pharmacists, and patients have to work together to design treatment regimens that address cholesterol and sugar, among other factors.
*Well, I have a pharmacy intern's license. Which permits me to practice pharmacy, compound medications, and counsel patients under the guidance of a licensed pharmacist. But it's essentially a learner's permit. And you shouldn't be using the internet as your sole source of health advice anyway. It's not a good resource. In pharmacy, we call using a drug by itself that shouldn't be used alone "inappropriate monotherapy." Getting all your medical information online is the same. Go talk to your doctor!
Treatment of diabetes is multifaceted. As Pal pointed out, insulin is the mainstay of therapy, especially for type I diabetes. In type I, insulin is the only reasonable therapy; right now, nothing else works. They don't make insulin. They need insulin. Simple enough.
Insulin was the first protein drug product developed and widely used--it was originally derived from pigs or cows. Nowadays, we get our insulin from E. coli that have been genetically "reprogrammed" to produce human insulin through bioengineering. And we also have a huge variety of insulin products that are essentially just modifications made to the basic insulin design. Some insulins act more rapidly (like Humalog or Novolog) whereas others are intended to last up to 24 hours to provide an insulin "baseline" (like Lantus or Levemir). Insulin dosing may initially be based on weight, but after that, dosages are recalculated based on trial and error. It is difficult to predict precisely what quantity of insulin will produce the desired result, and there are several different rules and protocols for optimizing insulin dose. In short, insulin doses must be individualized to the patient, requiring a lot of careful monitoring by both the health care provider and the patient (with a home blood glucose monitor).
Treatment of type II diabetes is way, way more complicated.
Because type II diabetics can create insulin, but their cells are less responsive to its effects, the initial treatment of choice is usually metformin. Metformin is amazing. It's the only drug in its pharmaceutical "family" on the market, and nearly every type II diabetic is on it. It works by increasing the sensitivity of cells to insulin and by decreasing the amount of glucose the liver makes--it's that gluconeogenesis process again--which results in an overall decrease in blood sugar. It even causes some patients to lose weight, which is excellent; losing weight generally decreases the severity of type II diabetes.
Pal covered metformin and the other "oral hypoglycemics" already--sulfonylureas, like glipizide, force the pancreas to spit out more insulin. And thiazolidinediones (TZDs for short; that word is quite a mouthful) have multiple body effects, including increasing insulin sensitivity, but by a different mechanism than metformin--which means that they can be combined, and sometimes this produces better results.
I would like to stress at this point that if you or a loved one have diabetes, while this series may be thought-provoking and raise interesting questions, that you should discuss the matter with your primary care physician when it comes to individual treatment recommendations--not here. I'm not a licensed medical practitioner*, just a student of pharmacy with a flair for words and a desire to share his knowledge with the world. And even if I were licensed, reading some article written by an anonymous blogger is not an appropriate substitute for face-to-face medical advice.
With that out of the way. What does recent research tell us? Past research tells us that blood glucose is important. But new research says other things might be just as important--maybe more.
Heart disease is a number one killer of patients with type II diabetes. Kidney failure is more common in type I. They're both considered to be manifestations of the same disease. But they're clearly different in several ways. Pal mentioned ketoacidosis--that's common in type I, but incredibly rare in type II. What explains these differences?
If I wanted to indulge my inner conspiracy theorist I'd blame the drugs used to treat type II diabetes, which is kind of like the absurd claims made by tinfoil-hatwearing HIV denialists that AZT causes AIDS.
Much more likely is the difference in co-morbidities ("other diseases/conditions the same patient has") for both type I and type II patients. Type II patients are typically obese, or at least overweight. The Framingham heart study has demonstrated that being overweight (as defined by medical science, not People magazine) is a risk factor for cardiovascular disease. So is having wonky cholesterol levels--and those are pretty common for type II diabetics, too.
This study is kind of interesting. Essentially, cholesterol deposited on beta-cells--the part of the pancreas that secretes insulin--can induce beta-cell failure. Cholesterol essentially "clogs the pipes." Even more interesting is the fact that this whole problem may be tied to a gene that codes for a protein called ABCA1. ABCA1 is essentially the "conductor" responsible for regulating lipid transport in and out of beta-cells. People whose genes incorrectly code for the ABCA1 transmembrane protein may be more susceptible to lipid-based damage to the pancreas. It is entirely possible that controlling lipids is at least as important as controlling blood sugar in type II diabetes, which means that dietary modifications, exercise, and cholesterol-lowering drug therapy may all play an even greater role in achieving good treatment outcomes than previously thought. This is exciting research!
That study's too neat to just be a throwaway link. I might come back to it later.
I think the point of recent research basically demonstrates that we can't just treat blood sugar. It doesn't mean we're completely mean about how we're treating diabetes. It just gives us a new direction to focus our research. Diabetes may be conceptualized as a problem with glucose metabolism, but that isn't the end of the story. Physicians, pharmacists, and patients have to work together to design treatment regimens that address cholesterol and sugar, among other factors.
*Well, I have a pharmacy intern's license. Which permits me to practice pharmacy, compound medications, and counsel patients under the guidance of a licensed pharmacist. But it's essentially a learner's permit. And you shouldn't be using the internet as your sole source of health advice anyway. It's not a good resource. In pharmacy, we call using a drug by itself that shouldn't be used alone "inappropriate monotherapy." Getting all your medical information online is the same. Go talk to your doctor!
Monday, February 11, 2008
Diabetes Explained: Part 1
The medical world is abuzz regarding the recent revelation that driving blood sugar to its lowest theoretical level may not be the optimal treatment regimen. PalMD of WhiteCoat Underground has already addressed the issue in a short post, noting wisely that this whole issue just raises more questions about the nature of diabetes and how it should be treated.
But what is diabetes, anyway? There are a lot of misconceptions, perhaps the most popular being that diabetes is a disease you contract as a result of eating too much sugar. My own mother was convinced that a diet proportionally high in carbohydrates was likely to cause diabetes until I made an attempt to explain otherwise. It also gets likened to a sort of food intolerance--the idea that diabetics can't eat sugar because it will cause acute damage. Naturally, the truth is far more complicated; patients with diabetes won't keel over and die in minutes if they eat cake.
Diabetes is often conceptualized as a problem with glucose metabolism. When you or I eat, the body breaks down complex carbohydrates into simple glucose units. Certain amino acids, the building blocks of proteins, are converted into glucose by complex pathways in the liver (the big, scientific word for this is "gluconeogenesis"). Glucose then circulates through the blood and is delivered to various sites; it is the preferred fuel for every cell type in the body, especially neurons. Something like 80% of the glucose in your body is utilized by the brain and nerve tissue.
The issue is that glucose is unable to enter cells unless the drawbridge is down, because glucose molecules are too big to freely pass through cell membranes. In order for glucose to enter cells, special pores on the cell surface need to open. And the trigger that opens those pores is insulin. Without insulin, most of the body's cells have no way to utilize glucose--and therefore, they are unable to fuel themselves efficiently.
It isn't that sugar is somehow toxic to patients with diabetes--the problem is more like having a blocked fuel line in your car. No matter how much gas you put in, your car can't get the gas because of the obstruction. And if you keep filling the tank anyway, you're going to cause it to overflow and spill gas onto the street, harming the environment with damaging emissions.
There are two types of diabetes. Type I diabetics are unable to make insulin; this could be because of a genetic defect, damage to the pancreas by infection or trauma, etc. The net effect is that no matter how much the type I diabetic eats, he is essentially starving, because his body's cells have no way to use glucose. Instead, they rely on far less efficient fuel sources like ketone bodies, which is sort of like putting the lighter fluid-soaked charcoal remnants from last night's bonfire into your car's gas tank and expecting it to operate well. The typical untreated type I diabetic is thin and malnourished. There is tons of glucose floating around in the bloodstream and none of it is accessible, so it gets excreted in the urine.
Type II diabetics make insulin--in fact, they frequently make tons of insulin, especially in the early stages of the disease. The problem is that their cells are less responsive to the effect of insulin, so they use glucose very inefficiently. If type I diabetes is an obstructed fuel line, type II diabetes is a leaky gas tank. Type II diabetics are commonly overweight--having large amounts of fat cells decreases the body's response to insulin. Fat doesn't just sit there; it secretes hormones that regulate glucose usage and appetite, among other things. The bizarre thing is that from a metabolic standpoint, your type II diabetic, despite being overweight, is functionally starving.
If I were stranded on a desert island with nothing to eat, my body's metabolic machinery would switch gears in less than 24 hours. We're starving, it would say, and the pancreas would release a hormone called glucagon to remedy the situation. Glucagon would tell my body to break down my fat stores (the few that I have), cannibalize muscle tissue, and instruct the liver to release its glucose hoard to feed the brain. Eventually, the stores would run out and my brain, cut off from its supply of necessary glucose, would shut down, taking the rest of the body with it. My heart, ever a trooper, would keep on truckin' until the autonomic nervous system crashed, because it is perfectly happy to feed on metabolic scraps.
An untreated diabetic's body is doing this all the time, and the only reason it doesn't kill them is that the brain, kidneys, and nerves don't need insulin to take in glucose. They're the exception to the rule, and if they weren't, diabetes would be fatal a lot more quickly than it actually is.
The reason sugar is harmful to diabetics has less to do with the essential properties of sugar itself and more to do with the effects of wildly fluctuating glucose levels on those three tissues. When glucose levels are high, glucose rushes into the big three--the nerves, the nephrons (the functional units of the kidney), and the retina of the eye. When blood glucose finds its way back down, frequently by being excreted in the urine, there is a huge disparity between the amount of glucose in the nerves and in the blood.
Those of you who remember basic chemistry will recall that such concentration differences are considered unfavorable in accordance with physical law. If we put a tablespoon of sugar in a glass of water, the sugar molecules would slowly spread out throughout the glass (though more slowly than we might like, which is why most people opt to stir the glass). Given enough time, the concentration of the sugar will be uniform throughout the water, and we will have a solution.
But what if we put a barrier in the glass dividing it in half from top to bottom, and the barrier permitted the passage of water, but not sugar? If we put sugar in one partition, the sugar-water on that side will be much more concentrated. Physics doesn't especially like this scenario; equal concentrations on both sides would be preferable. Sugar can't move through the barrier, but water can. As a result, water is going to pass through the no-sugar side to the sugar side in an attempt to equalize the concentrations.
This is the precise scenario that takes place in the human body. Once sugar concentrations in the bloodstream go down, the sugar concentration inside cells (retina, nephron, and neuron) is higher than the sugar concentration outside the cells. Since the sugar can't come out, water goes in. But the cells are limited in size by the boundaries of their membranes. When enough water rushes into the cells, they burst and are destroyed like overfilled water balloons.
So the big problem with sugar and diabetes has less to do with sugar itself being harmful and more to do with osmotic pressure, the situation described above with the barrier that will permit water to cross but not glucose. This is why diabetics with poorly-controlled blood sugar--blood glucose that fluctuates from low to high with great frequency--are more likely to suffer nerve damage, blindness, or kidney failure.
The recent study suggests that type II diabetics (NOT type I diabetics) were just as likely to die from their condition if they maintained low blood glucose levels than if they didn't (this isn't the whole story, so nobody panic). This is a surprise mostly because prior research has fairly conclusively confirmed that controlling blood sugar reduces the risk of those three problems I mentioned earlier in addition to reducing the likelihood of heart attacks, strokes, and other cardiovascular complications.
Why might this be? To understand this issue, we'll need to look at the way diabetes is treated, which will make absolutely no sense without an understanding of what diabetes is. Next post, we'll explore the issue of treatments for diabetes, how they work, and what this new research might mean.
But what is diabetes, anyway? There are a lot of misconceptions, perhaps the most popular being that diabetes is a disease you contract as a result of eating too much sugar. My own mother was convinced that a diet proportionally high in carbohydrates was likely to cause diabetes until I made an attempt to explain otherwise. It also gets likened to a sort of food intolerance--the idea that diabetics can't eat sugar because it will cause acute damage. Naturally, the truth is far more complicated; patients with diabetes won't keel over and die in minutes if they eat cake.
Diabetes is often conceptualized as a problem with glucose metabolism. When you or I eat, the body breaks down complex carbohydrates into simple glucose units. Certain amino acids, the building blocks of proteins, are converted into glucose by complex pathways in the liver (the big, scientific word for this is "gluconeogenesis"). Glucose then circulates through the blood and is delivered to various sites; it is the preferred fuel for every cell type in the body, especially neurons. Something like 80% of the glucose in your body is utilized by the brain and nerve tissue.
The issue is that glucose is unable to enter cells unless the drawbridge is down, because glucose molecules are too big to freely pass through cell membranes. In order for glucose to enter cells, special pores on the cell surface need to open. And the trigger that opens those pores is insulin. Without insulin, most of the body's cells have no way to utilize glucose--and therefore, they are unable to fuel themselves efficiently.
It isn't that sugar is somehow toxic to patients with diabetes--the problem is more like having a blocked fuel line in your car. No matter how much gas you put in, your car can't get the gas because of the obstruction. And if you keep filling the tank anyway, you're going to cause it to overflow and spill gas onto the street, harming the environment with damaging emissions.
There are two types of diabetes. Type I diabetics are unable to make insulin; this could be because of a genetic defect, damage to the pancreas by infection or trauma, etc. The net effect is that no matter how much the type I diabetic eats, he is essentially starving, because his body's cells have no way to use glucose. Instead, they rely on far less efficient fuel sources like ketone bodies, which is sort of like putting the lighter fluid-soaked charcoal remnants from last night's bonfire into your car's gas tank and expecting it to operate well. The typical untreated type I diabetic is thin and malnourished. There is tons of glucose floating around in the bloodstream and none of it is accessible, so it gets excreted in the urine.
Type II diabetics make insulin--in fact, they frequently make tons of insulin, especially in the early stages of the disease. The problem is that their cells are less responsive to the effect of insulin, so they use glucose very inefficiently. If type I diabetes is an obstructed fuel line, type II diabetes is a leaky gas tank. Type II diabetics are commonly overweight--having large amounts of fat cells decreases the body's response to insulin. Fat doesn't just sit there; it secretes hormones that regulate glucose usage and appetite, among other things. The bizarre thing is that from a metabolic standpoint, your type II diabetic, despite being overweight, is functionally starving.
If I were stranded on a desert island with nothing to eat, my body's metabolic machinery would switch gears in less than 24 hours. We're starving, it would say, and the pancreas would release a hormone called glucagon to remedy the situation. Glucagon would tell my body to break down my fat stores (the few that I have), cannibalize muscle tissue, and instruct the liver to release its glucose hoard to feed the brain. Eventually, the stores would run out and my brain, cut off from its supply of necessary glucose, would shut down, taking the rest of the body with it. My heart, ever a trooper, would keep on truckin' until the autonomic nervous system crashed, because it is perfectly happy to feed on metabolic scraps.
An untreated diabetic's body is doing this all the time, and the only reason it doesn't kill them is that the brain, kidneys, and nerves don't need insulin to take in glucose. They're the exception to the rule, and if they weren't, diabetes would be fatal a lot more quickly than it actually is.
The reason sugar is harmful to diabetics has less to do with the essential properties of sugar itself and more to do with the effects of wildly fluctuating glucose levels on those three tissues. When glucose levels are high, glucose rushes into the big three--the nerves, the nephrons (the functional units of the kidney), and the retina of the eye. When blood glucose finds its way back down, frequently by being excreted in the urine, there is a huge disparity between the amount of glucose in the nerves and in the blood.
Those of you who remember basic chemistry will recall that such concentration differences are considered unfavorable in accordance with physical law. If we put a tablespoon of sugar in a glass of water, the sugar molecules would slowly spread out throughout the glass (though more slowly than we might like, which is why most people opt to stir the glass). Given enough time, the concentration of the sugar will be uniform throughout the water, and we will have a solution.
But what if we put a barrier in the glass dividing it in half from top to bottom, and the barrier permitted the passage of water, but not sugar? If we put sugar in one partition, the sugar-water on that side will be much more concentrated. Physics doesn't especially like this scenario; equal concentrations on both sides would be preferable. Sugar can't move through the barrier, but water can. As a result, water is going to pass through the no-sugar side to the sugar side in an attempt to equalize the concentrations.
This is the precise scenario that takes place in the human body. Once sugar concentrations in the bloodstream go down, the sugar concentration inside cells (retina, nephron, and neuron) is higher than the sugar concentration outside the cells. Since the sugar can't come out, water goes in. But the cells are limited in size by the boundaries of their membranes. When enough water rushes into the cells, they burst and are destroyed like overfilled water balloons.
So the big problem with sugar and diabetes has less to do with sugar itself being harmful and more to do with osmotic pressure, the situation described above with the barrier that will permit water to cross but not glucose. This is why diabetics with poorly-controlled blood sugar--blood glucose that fluctuates from low to high with great frequency--are more likely to suffer nerve damage, blindness, or kidney failure.
The recent study suggests that type II diabetics (NOT type I diabetics) were just as likely to die from their condition if they maintained low blood glucose levels than if they didn't (this isn't the whole story, so nobody panic). This is a surprise mostly because prior research has fairly conclusively confirmed that controlling blood sugar reduces the risk of those three problems I mentioned earlier in addition to reducing the likelihood of heart attacks, strokes, and other cardiovascular complications.
Why might this be? To understand this issue, we'll need to look at the way diabetes is treated, which will make absolutely no sense without an understanding of what diabetes is. Next post, we'll explore the issue of treatments for diabetes, how they work, and what this new research might mean.
Wednesday, February 6, 2008
Rx Essentials: Are They Really?
You may have seen a product line on the shelves recently called RxEssentials. The marketing for these new vitamin supplements is actually pretty slick; Nature Made is a big company, and they do produce some quality products. A lot of their supplements are USP Verified, which means that the United States Pharmacopoeia has verified that what's on the label is what's in the bottle. Always a good thing. I have to commend them for going the extra mile to meet those standards.
RxEssentials, on the other hand, is a clever way to get you to pay more for your vitamins than you would otherwise.
The basic claim behind RxEssentials is that each formulation supplies key nutrients for people taking specific medications. Sometimes this is the case because the drug blocks or reduces nutrient absorption; in other cases, the manufacturers seem to be taking a page out of Pauling's orthomolecular medicine, which posits that nutritional deficiencies (or, for extra woo flavoring, "imbalances") are the root cause of basically every disease ever. There's a little bit of truth to some of this reasoning. Some drugs do reduce absorption of specific vitamins or minerals. Isoniazid, which is used to treat tuberculosis, can reduce vitamin B6 levels to the point where patients may actually suffer neurological problems if they fail to supplement. And methotrexate, an immune system modifying drug, is usually given with folic acid to prevent deficiency--methotrexate actually works by inhibiting the conversion of folic acid to its active form, tetrahydrofolate.
So let's look closely at RxEssentials. What do they offer that your basic multivitamin might not? They cost, on average, about $10 a bottle for 60 tablets, a two-month supply.
The arthritis formula is recommended for anyone taking ibuprofen, naproxen, or aspirin to relieve arthritis pain. It contains vitamin C, vitamin D, and folic acid. Fail. None of these drugs are going to significantly impair absorption of these nutrients, and most of that 500 mg of vitamin C is going to end up excreted in the urine. Vitamin C is abundant in the diet, and vitamin C tablets are dirt cheap ($6 for 250 tablets is pretty common). The most valuable component of the formula might be the vitamin D; most people with arthritis are older, and most older people get insufficient vitamin D. But vitamin D isn't expensive, either. An inexpensive multivitamin a day is going to cover everything.
The cholesterol formula is designed for patients on statin drugs--Lipitor, Zocor, or their close cousins. As expected, it contains CoQ10. Oh, and B-vitamins, but those are in everything, including bread. CoQ10, or coenzyme Q10, is commenly touted as a means of preventing muscle damage due to statin use. Unfortunately, the evidence doesn't hold up. Some studies show benefit; others don't. One study using 200 mg of CoQ10 daily showed no benefit but noted that patients might respond due to the placebo effect. Another showed some benefit with a 100 mg dose. The evidence is inconclusive. CoQ10 is also kind of expensive, as much as $20 for a bottle of 30 softgels containing 100 mg each. RxEssentials might actually be the better buy if you're dying to try CoQ10, but that's not saying much.
I have to admit that I find the depression formula particularly lacking. B-vitamins, folic acid (maybe for pregnant, depressed women?) and vitamin D. Yes, it's the old "depression is caused by vitamin deficiencies" gambit, except that they're telling you to stay on your Zoloft or Prozac and "supplement." More orthomolecular medicine at work. B-vitamins are important cofactors in energy production; the idea is that a lack of B-vitamins results in "decreased energy," which somehow translates into "depressed mood," "sleep disturbances," "loss of pleasure in daily activities," and, my personal favorite, "suicidal ideations." There is no evidence whatsoever that nutrient deficiency is a primary cause of depression; B-vitamin deficiencies can cause neurological problems, but B-vitamins are so prevalent in the diet that hardly anyone has a problem meeting their needs. You're going to get all this stuff in your (much cheaper) multivitamin. Vitamin D is great for bone health, but store brands are generally cheaper. The manufacturers are clearly assuming depressed people don't get enough sun.
I was really hoping that they'd get their heartburn formula right. An acidic environment is important for the absorption of iron, and chronic acid-suppression therapy coupled with low iron intake creates a situation where deficiency is a very real possibility. Except that there's no iron in the supplement! None! Instead, they're pushing B-vitamins again. B-vitamins are a very necessary component of nutrition. They aren't worth paying a lot of money for; they're in everything, including enriched flour, grains, vegetables, bananas, and even beer (although alcoholic beverages are not a good source of nutrients and chronic alcohol consumption, in excess, can cause other problems). Oh, and they throw in some calcium, but only 120 mg per dose. For reference, most people need 1200 to 1500 mg of calcium per day in divided doses (you can only absorb 500 mg "at a time"). It would've been easy to formulate an iron-replacement regimen for patients with acid reflux; I can't believe they blew this one.
Finally, we have the diabetes formula. In case you hadn't guessed by now, their supplement for diabetics includes--yeah, it really should've been obvious--B-vitamins! Oh, and folic acid. We wouldn't want anyone giving birth to babies with neural tube defects. Except that, of course, that's not why the manufacturers chose to include folic acid in the supplement; it's to "maintain energy." Argh! Yes, patients with diabetes have problems with "energy" metabolism; they can't properly utilize glucose to fuel cells because they produce insufficient insulin. But taking extra B-vitamins doesn't help the body utilize glucose any better, unlike oral diabetes medications or insulin injections.
To summarize, RxEssentials gets the big thumbs-down. The manufacturers claim that RxEssentials "provide specially selected nutrients." But as you can see, most of the products contain the same ingredients: B-vitamins and folic acid. At least they're being responsible and telling people that RxEssentials are not a replacement for their prescription drugs.
There are therapeutic precedents for taking specific nutrient supplements for various conditions or with particular medications. I already mentioned a few. But any responsible physician is going to prescribe those nutrients alongside the medication--especially if serious harm will result from not having them. Note that none of these products are for people on methotrexate! Arbitrarily deciding you need to supplement is a waste of time and money.
So what should you do if you think you have a nutritional deficiency? Talk to your doctor. Evaluate your diet with information from appropriate food guides. Nutritional deficiencies have a set of clear diagnostic criteria; less-specific concerns like "I feel tired sometimes" or "I get a lot of colds" are generally not indicative of a problem. Everyone feels tired sometimes. B-vitamins are not effective in reducing the effects of "stress" or a replacement for a good night's sleep. You probably don't need RxEssentials. And even if you did, a cheaper multivitamin would offer the same benefits.
Like most dietary supplements, RxEssentials relies on good marketing to make sales. It's too bad that marketing is all they have.
RxEssentials, on the other hand, is a clever way to get you to pay more for your vitamins than you would otherwise.
The basic claim behind RxEssentials is that each formulation supplies key nutrients for people taking specific medications. Sometimes this is the case because the drug blocks or reduces nutrient absorption; in other cases, the manufacturers seem to be taking a page out of Pauling's orthomolecular medicine, which posits that nutritional deficiencies (or, for extra woo flavoring, "imbalances") are the root cause of basically every disease ever. There's a little bit of truth to some of this reasoning. Some drugs do reduce absorption of specific vitamins or minerals. Isoniazid, which is used to treat tuberculosis, can reduce vitamin B6 levels to the point where patients may actually suffer neurological problems if they fail to supplement. And methotrexate, an immune system modifying drug, is usually given with folic acid to prevent deficiency--methotrexate actually works by inhibiting the conversion of folic acid to its active form, tetrahydrofolate.
So let's look closely at RxEssentials. What do they offer that your basic multivitamin might not? They cost, on average, about $10 a bottle for 60 tablets, a two-month supply.
The arthritis formula is recommended for anyone taking ibuprofen, naproxen, or aspirin to relieve arthritis pain. It contains vitamin C, vitamin D, and folic acid. Fail. None of these drugs are going to significantly impair absorption of these nutrients, and most of that 500 mg of vitamin C is going to end up excreted in the urine. Vitamin C is abundant in the diet, and vitamin C tablets are dirt cheap ($6 for 250 tablets is pretty common). The most valuable component of the formula might be the vitamin D; most people with arthritis are older, and most older people get insufficient vitamin D. But vitamin D isn't expensive, either. An inexpensive multivitamin a day is going to cover everything.
The cholesterol formula is designed for patients on statin drugs--Lipitor, Zocor, or their close cousins. As expected, it contains CoQ10. Oh, and B-vitamins, but those are in everything, including bread. CoQ10, or coenzyme Q10, is commenly touted as a means of preventing muscle damage due to statin use. Unfortunately, the evidence doesn't hold up. Some studies show benefit; others don't. One study using 200 mg of CoQ10 daily showed no benefit but noted that patients might respond due to the placebo effect. Another showed some benefit with a 100 mg dose. The evidence is inconclusive. CoQ10 is also kind of expensive, as much as $20 for a bottle of 30 softgels containing 100 mg each. RxEssentials might actually be the better buy if you're dying to try CoQ10, but that's not saying much.
I have to admit that I find the depression formula particularly lacking. B-vitamins, folic acid (maybe for pregnant, depressed women?) and vitamin D. Yes, it's the old "depression is caused by vitamin deficiencies" gambit, except that they're telling you to stay on your Zoloft or Prozac and "supplement." More orthomolecular medicine at work. B-vitamins are important cofactors in energy production; the idea is that a lack of B-vitamins results in "decreased energy," which somehow translates into "depressed mood," "sleep disturbances," "loss of pleasure in daily activities," and, my personal favorite, "suicidal ideations." There is no evidence whatsoever that nutrient deficiency is a primary cause of depression; B-vitamin deficiencies can cause neurological problems, but B-vitamins are so prevalent in the diet that hardly anyone has a problem meeting their needs. You're going to get all this stuff in your (much cheaper) multivitamin. Vitamin D is great for bone health, but store brands are generally cheaper. The manufacturers are clearly assuming depressed people don't get enough sun.
I was really hoping that they'd get their heartburn formula right. An acidic environment is important for the absorption of iron, and chronic acid-suppression therapy coupled with low iron intake creates a situation where deficiency is a very real possibility. Except that there's no iron in the supplement! None! Instead, they're pushing B-vitamins again. B-vitamins are a very necessary component of nutrition. They aren't worth paying a lot of money for; they're in everything, including enriched flour, grains, vegetables, bananas, and even beer (although alcoholic beverages are not a good source of nutrients and chronic alcohol consumption, in excess, can cause other problems). Oh, and they throw in some calcium, but only 120 mg per dose. For reference, most people need 1200 to 1500 mg of calcium per day in divided doses (you can only absorb 500 mg "at a time"). It would've been easy to formulate an iron-replacement regimen for patients with acid reflux; I can't believe they blew this one.
Finally, we have the diabetes formula. In case you hadn't guessed by now, their supplement for diabetics includes--yeah, it really should've been obvious--B-vitamins! Oh, and folic acid. We wouldn't want anyone giving birth to babies with neural tube defects. Except that, of course, that's not why the manufacturers chose to include folic acid in the supplement; it's to "maintain energy." Argh! Yes, patients with diabetes have problems with "energy" metabolism; they can't properly utilize glucose to fuel cells because they produce insufficient insulin. But taking extra B-vitamins doesn't help the body utilize glucose any better, unlike oral diabetes medications or insulin injections.
To summarize, RxEssentials gets the big thumbs-down. The manufacturers claim that RxEssentials "provide specially selected nutrients." But as you can see, most of the products contain the same ingredients: B-vitamins and folic acid. At least they're being responsible and telling people that RxEssentials are not a replacement for their prescription drugs.
There are therapeutic precedents for taking specific nutrient supplements for various conditions or with particular medications. I already mentioned a few. But any responsible physician is going to prescribe those nutrients alongside the medication--especially if serious harm will result from not having them. Note that none of these products are for people on methotrexate! Arbitrarily deciding you need to supplement is a waste of time and money.
So what should you do if you think you have a nutritional deficiency? Talk to your doctor. Evaluate your diet with information from appropriate food guides. Nutritional deficiencies have a set of clear diagnostic criteria; less-specific concerns like "I feel tired sometimes" or "I get a lot of colds" are generally not indicative of a problem. Everyone feels tired sometimes. B-vitamins are not effective in reducing the effects of "stress" or a replacement for a good night's sleep. You probably don't need RxEssentials. And even if you did, a cheaper multivitamin would offer the same benefits.
Like most dietary supplements, RxEssentials relies on good marketing to make sales. It's too bad that marketing is all they have.
Friday, January 25, 2008
Introducing...RxWiki!
I'd like to point you all in the general direction of RxWiki.
RxWiki is a wiki that only licensed pharmacists are permitted to edit; it's being compiled as a resource for anyone, but it's generally being directed at patients. I've been browsing it a bit myself, and I'm very impressed so far. Apparently they have a panel of pharmacists who review everything and approve articles, and they're endorsed by the APhA.
I do take serious issue with their little blurb that's currently on the front page about placebos. The information presented in the articles seems solid, though.
Check it out. I think it might just become my new source for links whenever I cite a drug name.
RxWiki is a wiki that only licensed pharmacists are permitted to edit; it's being compiled as a resource for anyone, but it's generally being directed at patients. I've been browsing it a bit myself, and I'm very impressed so far. Apparently they have a panel of pharmacists who review everything and approve articles, and they're endorsed by the APhA.
I do take serious issue with their little blurb that's currently on the front page about placebos. The information presented in the articles seems solid, though.
Check it out. I think it might just become my new source for links whenever I cite a drug name.
Saturday, December 29, 2007
Extra, Extra: College Student Endorses Alcohol Use
The astute may have noticed that many medications warn that they should not be taken with alcohol. The "can I drink while I'm taking this medication?" question is one that I get a lot when I'm working. There are a lot of misconceptions about the effect of alcohol when combined with different drugs; this can be largely attributed to the fact that there are rarely degrees of severity described on "no alcohol" warning labels.
Let's put this another way. I'm an inquisitive youth and always have been, and I'm in my early 20's, the only decade where rebellion is anywhere near as likely as in the teens. I always thought warnings or prohibitions without explanations were patently stupid. You can't just tell me "don't do it." I have to know why I can't do it so that I can decide for myself whether the rule is worth following.
Let me also remind you that you should always follow any precautions listed on medications and consult your doctor or pharmacist instead of taking advice from an anonymous blogger. If I'm your only source of medical information, you should seriously reconsider your actions.
From a counseling perspective, there are two ways to handle the alcohol question. You can assume that all people are good little boys and girls and tell them that should a drop of whisky pass their lips while they're on amoxicillin that they will suffer terrible consequences (this is clearly an exaggeration). Or you can be realistic. Amusingly, most patients are very careful about how they phrase their "can I drink" question. Anecdotally, the most common phrasing is "is it okay if I have a glass of wine with dinner?" Nobody wants to sound like a booze hound who can't put down the liquor when they're sick. I think the lone exception I've seen so far in practice was the fellow who wanted to know if he could keep up his six-beer-a-day habit. That's ten-foot-pole category stuff, there. So many things are wrong that you have no idea where to start and you pray silently to the cosmos that someone else with more time on his hands will refer this man for a different flavor of counseling.
Alcohol is a drug. There are two different categories of drug interactions; pharmacodynamic and pharmacokinetic interactions. P-dyamics is essentially what the drug does to the body, whereas p-kinetics is what the body does to the drug. P-kinetics has four components, absorption, distribution, metabolism, and excretion, often abbreviated ADME. Here's a simplified look at both sides of the equation for alcohol:
P-Dynamics: Alcohol is central nervous system depressant.
P-Kinetics: Alcohol is absorbed through the small intestine, distributed into the blood and other fluid portions of the body, metabolized by liver enzymes into other compounds and excreted in sweat, urine, and saliva.
When we're talking about drug interactions, we have to know if the interactions are dynamic or kinetic. For example:
P-Dynamics: Some antihistamines cause drowsiness. Antidepressants can cause drowsiness. Combining the two produces more drowsiness.
P-Kinetics: Lipitor and other statins are broken down by liver enzymes. Grapefruit juice reduces the action of these enzymes. Combining the two prevents the breakdown of Lipitor, increasing Lipitor levels in the body.
A lot of common drug interactions with alcohol are p-dynamic in nature. Alcohol causes drowsiness, so combining it with other drugs that may cause drowsiness will result in the patient experiencing potentially unexpected levels of sedation. In the case of moderate drinking, most interactions with antihistamines, antidepressants, and anti-anxiety drugs and alcohol fall into this category. You're not going to die if you have a couple beers. But you're going to feel a lot sleepier than you would otherwise.
Painkillers are a slightly different story. Acetaminophen and alcohol are both toxic to the liver, and that toxicity is amplified when the two are used in conjunction. NSAIDs are more likely to cause stomach bleeding when taken with alcohol, which can also damage the lining of the gut. And combining opioids like Vicodin or Oxycontin with alcohol can lead to fatal respiratory depression. Don't do it! It's dangerous!
Most antibiotics do not significantly interact with alcohol, but you aren't doing yourself any favors by drinking while sick. The dehydration caused by alcohol does your body no good in fighting an infection and might also worsen some symptoms of illness. There are a few noteworthy exceptions, however; perhaps the most notorious of these is metronidazole, otherwise known as Flagyl. This is a classic p-kinetic interaction. Metronidazole inhibits aldehyde dehydrogenase, a key enzyme in alcohol metabolism. Without this enzyme, toxic levels of acetaldehyde, a by-product of ethanol breakdown, build up in the body and cause nausea and vomiting, among other potentially more serious symptoms of acetaldehyde toxicity. The reaction in question is often referred to as a disulfiram reaction. If your pharmacist tells you absolutely no drinking while taking an antibiotic, he or she is probably trying to warn you of a potential disulfiram reaction.
The disulfiram reaction can actually be used therapeutically. Ever heard of Antabuse? It's the drug for which the disulfiram reaction was named. When administered to alcoholics, it causes them to become violently ill after consuming alcohol--a form of aversion therapy. Cute, huh?
I don't like seeing patients who are afraid of their medications or who feel that being committed to a particular therapy is going to significantly affect their quality of life. Many people enjoy the occasional drink, and for the vast majority of them, being on medication is no reason to give up that pleasure. Other health complications might be a reason to avoid alcohol, but I've spoken to way too many otherwise healthy people on antidepressants or mood stabilizers that almost pathologically avoided drinking not because they feared it would interfere with their therapy from a mental health perspective but because they were certain that combining alcohol with their medications would be irreversibly harmful or even fatal. With a little time and explanation as to the "whys" behind drug and alcohol interactions, patients can be reassured that they don't have to change their lives to revolve around their medications. And if your doctor or pharmacist hasn't told you why there's a particular warning on your medication, don't hesitate to ask! The more informed you are, the better, especially if you're going to be putting these medications into your body for years to come.
Don't forget that all of this applies primarily to occasional, responsible alcohol use. If you're drinking four or five alcoholic beverages a day, some of your body's metabolic machinery operates under different rules. But don't feel like you have to give up your New Year's bubbly just because you've been prescribed a Z-Pak.
Let's put this another way. I'm an inquisitive youth and always have been, and I'm in my early 20's, the only decade where rebellion is anywhere near as likely as in the teens. I always thought warnings or prohibitions without explanations were patently stupid. You can't just tell me "don't do it." I have to know why I can't do it so that I can decide for myself whether the rule is worth following.
Let me also remind you that you should always follow any precautions listed on medications and consult your doctor or pharmacist instead of taking advice from an anonymous blogger. If I'm your only source of medical information, you should seriously reconsider your actions.
From a counseling perspective, there are two ways to handle the alcohol question. You can assume that all people are good little boys and girls and tell them that should a drop of whisky pass their lips while they're on amoxicillin that they will suffer terrible consequences (this is clearly an exaggeration). Or you can be realistic. Amusingly, most patients are very careful about how they phrase their "can I drink" question. Anecdotally, the most common phrasing is "is it okay if I have a glass of wine with dinner?" Nobody wants to sound like a booze hound who can't put down the liquor when they're sick. I think the lone exception I've seen so far in practice was the fellow who wanted to know if he could keep up his six-beer-a-day habit. That's ten-foot-pole category stuff, there. So many things are wrong that you have no idea where to start and you pray silently to the cosmos that someone else with more time on his hands will refer this man for a different flavor of counseling.
Alcohol is a drug. There are two different categories of drug interactions; pharmacodynamic and pharmacokinetic interactions. P-dyamics is essentially what the drug does to the body, whereas p-kinetics is what the body does to the drug. P-kinetics has four components, absorption, distribution, metabolism, and excretion, often abbreviated ADME. Here's a simplified look at both sides of the equation for alcohol:
P-Dynamics: Alcohol is central nervous system depressant.
P-Kinetics: Alcohol is absorbed through the small intestine, distributed into the blood and other fluid portions of the body, metabolized by liver enzymes into other compounds and excreted in sweat, urine, and saliva.
When we're talking about drug interactions, we have to know if the interactions are dynamic or kinetic. For example:
P-Dynamics: Some antihistamines cause drowsiness. Antidepressants can cause drowsiness. Combining the two produces more drowsiness.
P-Kinetics: Lipitor and other statins are broken down by liver enzymes. Grapefruit juice reduces the action of these enzymes. Combining the two prevents the breakdown of Lipitor, increasing Lipitor levels in the body.
A lot of common drug interactions with alcohol are p-dynamic in nature. Alcohol causes drowsiness, so combining it with other drugs that may cause drowsiness will result in the patient experiencing potentially unexpected levels of sedation. In the case of moderate drinking, most interactions with antihistamines, antidepressants, and anti-anxiety drugs and alcohol fall into this category. You're not going to die if you have a couple beers. But you're going to feel a lot sleepier than you would otherwise.
Painkillers are a slightly different story. Acetaminophen and alcohol are both toxic to the liver, and that toxicity is amplified when the two are used in conjunction. NSAIDs are more likely to cause stomach bleeding when taken with alcohol, which can also damage the lining of the gut. And combining opioids like Vicodin or Oxycontin with alcohol can lead to fatal respiratory depression. Don't do it! It's dangerous!
Most antibiotics do not significantly interact with alcohol, but you aren't doing yourself any favors by drinking while sick. The dehydration caused by alcohol does your body no good in fighting an infection and might also worsen some symptoms of illness. There are a few noteworthy exceptions, however; perhaps the most notorious of these is metronidazole, otherwise known as Flagyl. This is a classic p-kinetic interaction. Metronidazole inhibits aldehyde dehydrogenase, a key enzyme in alcohol metabolism. Without this enzyme, toxic levels of acetaldehyde, a by-product of ethanol breakdown, build up in the body and cause nausea and vomiting, among other potentially more serious symptoms of acetaldehyde toxicity. The reaction in question is often referred to as a disulfiram reaction. If your pharmacist tells you absolutely no drinking while taking an antibiotic, he or she is probably trying to warn you of a potential disulfiram reaction.
The disulfiram reaction can actually be used therapeutically. Ever heard of Antabuse? It's the drug for which the disulfiram reaction was named. When administered to alcoholics, it causes them to become violently ill after consuming alcohol--a form of aversion therapy. Cute, huh?
I don't like seeing patients who are afraid of their medications or who feel that being committed to a particular therapy is going to significantly affect their quality of life. Many people enjoy the occasional drink, and for the vast majority of them, being on medication is no reason to give up that pleasure. Other health complications might be a reason to avoid alcohol, but I've spoken to way too many otherwise healthy people on antidepressants or mood stabilizers that almost pathologically avoided drinking not because they feared it would interfere with their therapy from a mental health perspective but because they were certain that combining alcohol with their medications would be irreversibly harmful or even fatal. With a little time and explanation as to the "whys" behind drug and alcohol interactions, patients can be reassured that they don't have to change their lives to revolve around their medications. And if your doctor or pharmacist hasn't told you why there's a particular warning on your medication, don't hesitate to ask! The more informed you are, the better, especially if you're going to be putting these medications into your body for years to come.
Don't forget that all of this applies primarily to occasional, responsible alcohol use. If you're drinking four or five alcoholic beverages a day, some of your body's metabolic machinery operates under different rules. But don't feel like you have to give up your New Year's bubbly just because you've been prescribed a Z-Pak.
Sunday, December 23, 2007
Patchwork
This is the dumbest thing ever.
Fentanyl is an opioid analgesic, like morphine or codeine. Unlike everyone's favorite analgesics, Tylenol #3 and Vicodin, fentanyl is most commonly administered via a transdermal patch that is worn on the skin. Oral forms are available, but considerably less common (notably orally-disintegrating tablets and even a narcotic sucker). Fentanyl is very potent, and must be used in small doses--25 micrograms (or 0.025 mg) of fentanyl per hour over a 24-hour period is recommended for patients taking between 60 and 134 milligrams of oral morphine per day. Fentanyl should not even be initiated in patients taking less than this--for comparison's sake, 60 mg of morphine is equivalent to 30 mg of oxycodone. Your standard Percocet tablet has 5 mg of oxycodone per tablet.
I may be belaboring the point. In any case, fentanyl is potent stuff. It takes very little fentanyl to match an equivalent dose of some other opioid painkiller.
Prescribing fentanyl for patients with anything less than chronic pain due to cancer or long-term injuries is irresponsible. The package insert itself says that using fentanyl patches for short-term pain is a mistake. Physicians prescribing the patches for patients with headaches are only part of the problem; there are no statistics available, as far as I can tell, but I'm willing to bet that much of the problem not misprescribing of fentanyl. The problem is misuse. Not in the sense of drug abuse, but rather in the sense of improper administration of the patches. Heating pads are a popular means of relieving chronic pain. But putting a heating pad over a fentanyl patch will dramatically increase the rate of transfer from the patch into the patient's bloodstream, potentially resulting in death when the patient's central nervous system stops triggering the breathing reflex. Patients who slap on a patch and then get into a hot tub may not get out.
An interesting issue is that transdermal patches must contain much more active ingredient than is to be delivered to the patient because the rate of transfer from the patch to the bloodstream is dependent on the difference between drug in the skin and drug in the patch. In short, a patch that only delivers 0.025 mg per hour may have to contain 3 mg of total drug to keep the flow moving. This means that a "used" patch still contains a lot of drug, and improper disposal of the patch can result in children or animals getting ahold of a lot of "leftover" fentanyl--easily fatal, should the patch be chewed or torn.
These deaths are so preventable it's ridiculous. A little patient education about the proper use and disposal of fentanyl would have saved nearly everyone involved. This is the task set before pharmacists. This is the value of proper patient counseling. Like all drugs, fentanyl has risks. But the risks can be minimized if patients are properly informed. Counseling for such drugs should be legally mandated--and furthermore, drugstores should be required to give pharmacists the time and staffing to perform the task adequately. These deaths aren't the fault of pharma. They're due to ignorance and irresponsibility. Pharmacists need to educate their patients--and patients need to pay attention instead of quacking away on cellphones while they sign the pick-up log for their fentanyl patches.
If in two weeks I have to read another article about fentanyl patches for the fourth month in a row I'm going to go crazy.
Fentanyl is an opioid analgesic, like morphine or codeine. Unlike everyone's favorite analgesics, Tylenol #3 and Vicodin, fentanyl is most commonly administered via a transdermal patch that is worn on the skin. Oral forms are available, but considerably less common (notably orally-disintegrating tablets and even a narcotic sucker). Fentanyl is very potent, and must be used in small doses--25 micrograms (or 0.025 mg) of fentanyl per hour over a 24-hour period is recommended for patients taking between 60 and 134 milligrams of oral morphine per day. Fentanyl should not even be initiated in patients taking less than this--for comparison's sake, 60 mg of morphine is equivalent to 30 mg of oxycodone. Your standard Percocet tablet has 5 mg of oxycodone per tablet.
I may be belaboring the point. In any case, fentanyl is potent stuff. It takes very little fentanyl to match an equivalent dose of some other opioid painkiller.
Prescribing fentanyl for patients with anything less than chronic pain due to cancer or long-term injuries is irresponsible. The package insert itself says that using fentanyl patches for short-term pain is a mistake. Physicians prescribing the patches for patients with headaches are only part of the problem; there are no statistics available, as far as I can tell, but I'm willing to bet that much of the problem not misprescribing of fentanyl. The problem is misuse. Not in the sense of drug abuse, but rather in the sense of improper administration of the patches. Heating pads are a popular means of relieving chronic pain. But putting a heating pad over a fentanyl patch will dramatically increase the rate of transfer from the patch into the patient's bloodstream, potentially resulting in death when the patient's central nervous system stops triggering the breathing reflex. Patients who slap on a patch and then get into a hot tub may not get out.
An interesting issue is that transdermal patches must contain much more active ingredient than is to be delivered to the patient because the rate of transfer from the patch to the bloodstream is dependent on the difference between drug in the skin and drug in the patch. In short, a patch that only delivers 0.025 mg per hour may have to contain 3 mg of total drug to keep the flow moving. This means that a "used" patch still contains a lot of drug, and improper disposal of the patch can result in children or animals getting ahold of a lot of "leftover" fentanyl--easily fatal, should the patch be chewed or torn.
These deaths are so preventable it's ridiculous. A little patient education about the proper use and disposal of fentanyl would have saved nearly everyone involved. This is the task set before pharmacists. This is the value of proper patient counseling. Like all drugs, fentanyl has risks. But the risks can be minimized if patients are properly informed. Counseling for such drugs should be legally mandated--and furthermore, drugstores should be required to give pharmacists the time and staffing to perform the task adequately. These deaths aren't the fault of pharma. They're due to ignorance and irresponsibility. Pharmacists need to educate their patients--and patients need to pay attention instead of quacking away on cellphones while they sign the pick-up log for their fentanyl patches.
If in two weeks I have to read another article about fentanyl patches for the fourth month in a row I'm going to go crazy.
Tuesday, November 27, 2007
The Acetaminophen Blues
Nearly everyone I talk to has a favorite pain-reliever. It isn't always a branded product, and I'd love to conduct an informal survey or track customer buying habits in my store as I couldn't find any data I wanted online, but right now all I have are informal observations. Most of the people I talk to take either ibuprofen or acetaminophen for everyday aches and pains, with a few opting for Aleve or combination products like Excedrin. And they quickly become annoyed if they can't find their favorite product; Excedrin PM and Tylenol PM are identical except for the packaging, and one customer I spoke with yesterday was very certain that there was some other product called Excedrin Migraine PM that was nowhere to be found on our shelves.
Then there are the oddball homeopathy fans who spray diluted capsaicin into their noses when they have a headache. Apparently they even have a formula for prostate trouble. I am having an incredibly difficult time wrapping my brain around the idea of spraying hyperdiluted pepper oil and saw palmetto into your nose because it's stuffy and you're coincidentally having trouble urinating.
I could probably go on about what's wrong with the aforementioned products all day, but that would be silly when I can bring up something that's actually useful.
A lot of patients are a little confused on the whole anti-inflammatory issue. Most of them assume that NSAIDs, the most common OTC anti-inflammatory drugs for oral administration, are automatically better at relieving pain than acetaminophen (or paracetamol if you're on the other side of the pond). And that simply isn't true.
Acetaminophen, hereafter referred to as APAP, is a real miracle drug in a lot of ways. In fact, its mechanism of action is not perfectly understood. It provides pain relief via a slightly different mechanism than NSAIDs; like NSAIDs, it blocks the effect of substances called prostaglandins. Prostaglandins have various short-duration effects on tissues, one of which is to sensitive nerve endings to pain stimuli; in essence, prostaglandins lower the threshold required to make the neurons associated with pain fire. NSAIDs prevent prostaglandins from being formed entirely by blocking the effect of an enzyme called cyclooxygenase, or COX. APAP appears to block prostaglandin synthesis, but not in peripheral tissues; at least one theory suggests that APAP has an effect on the same receptors that the THC in marijuana. I say APAP is a miracle drug because it does this without the side-effects that NSAIDs have, asprin included, and it provides equal pain relief to aspirin milligram for milligram. APAP does not damage the stomach, thin the blood, or affect kidney function. It's very safe at appropriate doses, non-addictive, and it's even okay to use in pregnancy!
Because NSAIDs block the formation of prostaglandins by COX at the site of injury, they provide both relief of inflammation and pain. But for many minor causes of pain, an anti-inflammatory component is unnecessary. At least one study in the American Journal of Sports Medicine suggested that anti-inflammatory effects were not necessarily especially valuable in muscle injuries. In fact, the study compared simple APAP with Merck blockbuster Vioxx and found APAP to be just as effective without causing the poor atheletes to keel over from strokes! (Just kidding about the strokes. Sorta.) And for patients with mild-to-moderate pain due to osteoarthritis, the American College of Rheumatology, recommends APAP as first-line treatment unless significant inflammation is present.
NSAIDs are commonly cited by patients as being better for pain relief, and even a lot of pharmacists will immediately reach for the ibuprofen when it comes to recommending a painkiller, but the pain-relieving component is ultimately more important in many cases than the anti-inflammatory component. And for that, APAP is often just fine. APAP isn't necessarily the best drug for all pain relief; that's something to discuss with your personal healthcare provider. But it's often a good first choice for mild pain, especially since the inflammatory response is a part of wound healing. It's cheap, too, even compared to other pain-relievers, perhaps aside from uncoated aspirin tablets.
Then there are the oddball homeopathy fans who spray diluted capsaicin into their noses when they have a headache. Apparently they even have a formula for prostate trouble. I am having an incredibly difficult time wrapping my brain around the idea of spraying hyperdiluted pepper oil and saw palmetto into your nose because it's stuffy and you're coincidentally having trouble urinating.
I could probably go on about what's wrong with the aforementioned products all day, but that would be silly when I can bring up something that's actually useful.
A lot of patients are a little confused on the whole anti-inflammatory issue. Most of them assume that NSAIDs, the most common OTC anti-inflammatory drugs for oral administration, are automatically better at relieving pain than acetaminophen (or paracetamol if you're on the other side of the pond). And that simply isn't true.
Acetaminophen, hereafter referred to as APAP, is a real miracle drug in a lot of ways. In fact, its mechanism of action is not perfectly understood. It provides pain relief via a slightly different mechanism than NSAIDs; like NSAIDs, it blocks the effect of substances called prostaglandins. Prostaglandins have various short-duration effects on tissues, one of which is to sensitive nerve endings to pain stimuli; in essence, prostaglandins lower the threshold required to make the neurons associated with pain fire. NSAIDs prevent prostaglandins from being formed entirely by blocking the effect of an enzyme called cyclooxygenase, or COX. APAP appears to block prostaglandin synthesis, but not in peripheral tissues; at least one theory suggests that APAP has an effect on the same receptors that the THC in marijuana. I say APAP is a miracle drug because it does this without the side-effects that NSAIDs have, asprin included, and it provides equal pain relief to aspirin milligram for milligram. APAP does not damage the stomach, thin the blood, or affect kidney function. It's very safe at appropriate doses, non-addictive, and it's even okay to use in pregnancy!
Because NSAIDs block the formation of prostaglandins by COX at the site of injury, they provide both relief of inflammation and pain. But for many minor causes of pain, an anti-inflammatory component is unnecessary. At least one study in the American Journal of Sports Medicine suggested that anti-inflammatory effects were not necessarily especially valuable in muscle injuries. In fact, the study compared simple APAP with Merck blockbuster Vioxx and found APAP to be just as effective without causing the poor atheletes to keel over from strokes! (Just kidding about the strokes. Sorta.) And for patients with mild-to-moderate pain due to osteoarthritis, the American College of Rheumatology, recommends APAP as first-line treatment unless significant inflammation is present.
NSAIDs are commonly cited by patients as being better for pain relief, and even a lot of pharmacists will immediately reach for the ibuprofen when it comes to recommending a painkiller, but the pain-relieving component is ultimately more important in many cases than the anti-inflammatory component. And for that, APAP is often just fine. APAP isn't necessarily the best drug for all pain relief; that's something to discuss with your personal healthcare provider. But it's often a good first choice for mild pain, especially since the inflammatory response is a part of wound healing. It's cheap, too, even compared to other pain-relievers, perhaps aside from uncoated aspirin tablets.
Subscribe to:
Posts (Atom)
