Experience From - Suzi, Karl King #1, Jay Hodde#1, Jay Hodde#2, Shawn McDonald, Karl King#2, Karl King#3, Dan Brannen, Paul Comet #1, Matt Mahoney #1, Jay Hodde#3 , Larry Miller #1, Blake Wood , Kevin O'Neall , Kevin Dickerson , Jay Hodde#4 , Rich Schick #1, Don Davis #1, Rich Schick#2 , Paul Comet #2, Matt Mahoney #2, Jay Hodde#5 , Larry Miller #2 , Blake Wood#2, Kevin O'Neall , Don Davis #2, Scott Parker , Matt Mahoney #3, Jay Hodde #6 , Damon Lease , Terri , Ray Zirblis , Rich Schick #3,
As a vet tech I have always been a firm believer in drugs, for medicinal purposes only of course. Which means I used anti inflammatory drugs to relieve inflammation during every ultra. Prophylactic use was always indicated as I know something would get painful for sure!
During Western States '86 I participated in a study Dr. Lind conducted about the subject which revealed among other trivia, half the 60 runners in the study finished the race and about half of them used drugs. The result I thought was really fun was the CPK contest, ie who had the lowest at the finish. I was the slowest finish time in the group of finishers, but had the second lowest CPK. The lowest CPK was race winner Chuck Jones! I figure I was conservative enough to keep from destroying muscle tissue, and Chuck was probably trained. Anyway, I continued to use Advil as my drug of choice during another 12 - 15 100 milers and all the 50s, until one week end in Arkansas. My friend, MD, Minister, stand up comedian, and Ultra runner Dr. Ted Kendall told me Ibuprophen could be a renal problem risk. Well, I think Ted (and several other sources) is correct. As we say, all things in moderation. Early in the Arkansas Traveller '92 I tweaked the arch of one foot painfully enough that I began taking two Advil for survival about every 1-1 « hours. By mile 85 my foot still hurt, but now I was vomiting and could not keep down food or water. Of course I continued and at the finish was still unable to hold down water two hours later. For the first and only time in my ultra running life, I required IV fluids post event. Renal shut down is not my idea of a successful outcome to an ultra. Three liters later I was able to urinate, and spent the night napping, drinking water, and eating pizza hourly.
Bottom line here.... I do believe that I abused the drug. I do believe I will not be so foolish again. I still take Advil during an ultra, for the same reasons I did before, but now if a problem calls for high levels of Advil use, I'm "Out-O-There". I have found a certain pride in my 100 mile DNF's for GOOD CAUSE. It took 16 100 mile races before I hit one with good enough cause, and that was HARDROCK at 92 miles. Now after 26 100s I am getting better at recognizing GOOD CAUSE, and am up to 5 DNFs! I consider it "DID NOTHING FATAL".
In late January, Jason Hodde posted information here on the mechanisms of NSAIDs ( non-steroidal anti-inflammatory drugs ).
What got my attention was the fact that while reducing pain and inflammation, they also tend to inhibit the formation of leukotrienes which are important in the processes of healing the injured site.
For over two years I had been bothered by chronic tendinitis where the Gracilis muscle originates at the pelvic bone. Aleve was effective at reducing the soreness and inflammation, so I'd take one before any hard or long run, generally 2 or 3 per week.
The injury didn't keep me from running, but it did hamper the quality and quantity of the workouts. Massage of the adductor muscles and stretching of the associated hip rotator muscles helped, and the situation was steadily improving, but Jay's post made me wonder if the Aleve was slowing recovery. Based on that, I stopped taking the Aleve. The first week brought increased pain and inflammation, but then the situation improved a lot and the next week was nearly pain-free. There's still an achy day here and there, but the bottom line is that the healing rate has accelerated a lot since cessation of the NSAID. It feels good to get some quality back into the training.
Many thanks to Jay Hodde who helped by sharing his impressive knowledge on the subject.
If you have a chronic connective tissue injury, figure out the root cause and treat that, not just the symptoms. In the case above, the root cause was tightness in the hip and butt. The adductor was the one that ended up with the injury, but treating only it did not address the root cause. Finding the root cause may require professional help.
Finally, chronic use of NSAIDs may delay healing; think twice about that if you find yourself taking them on a regular basis.
Karl King writes,
In late January, Jason Hodde posted information here on the mechanisms of NSAIDs ( non-steroidal anti-inflammatory drugs ).I'd like to offer a few clarifying (?) comments about what Karl has written, and acknowledge with humility his kind words. This is *very* technical, so I've tried to make it "easy". I didn't do a very good job :)What got my attention was the fact that while reducing pain and inflammation, they also tend to inhibit the formation of leukotrienes which are important in the processes of healing the injured site. SNIP...
Finally, chronic use of NSAIDs may delay healing; think twice about that if you find yourself taking them on a regular basis.
NSAIDs generally all act in the same way: they inhibit the conversion of arachidonic acid to products known as eicosanoids. The eicosanoids include the compounds known as epoxides, leukotrienes, prostaglandins, prostacyclins and thromboxanes.
Arachidonic acid is broken down into its metabolites by one of three different enzymes. Monooxygenase converts it to the epoxides; lipoxygenase converts it to the leukotrienes; cyclooxygenase converts it to endoperoxide, a precursor to prostaglandins, thromboxanes, and prostacyclins.
The common feture among NSAIDs is that they *all* inhibit cyclooxygenase. This means that prostaglandin, thromboxane, and prostacyclin synthesis are stopped. In terms of inflammation and healing, this is good. Generally, the "good" is explained in terms of prostaglandin inhibition. Normally, PGs decrease the immune response and decrease lymphocyte function and proliferation. The immune system is important in inflammation and healing. When PG synthesis is blocked, healing occurs better.
The delayed healing that I was talking about is actually due to the effect of some NSAIDs on the lipoxygenase, the enzyme critical for the conversion of arachidonic acid to leukotrienes. Leukotrienes are important for healing in two different respects. They cause exudation of plasma from postcapillary venules and also act as powerful chemotactic agents for PMN leukocytes (white blood cells), eosinophils, and monocytes. These, too, are players in normal immune system function which are critical for healing and repair. When leukotriene synthesis is stopped (as a side effect to NSAID administration), healing is prolonged.
The NSAIDs don't *all* have this side effect. The most potent inhibitors of leukotriene synthesis are indomethacin (Indocin), tolmetin (Toradol), sulindac, and diclofenac. They are usually used as a last resort in the treatment of inflammatory diseases.
In addition to those above, ketoprofen (Orudis) also has this effect. Orudis is one to note because it is now available over the counter. In addition, since it is a close relative of ibuprofen and naproxen (Aleve), these drugs may also exhibit some of the same effects.
How does this effect the ultrarunner? NSAIDs are great analgesics, mainly because their primary action is to relieve inflammation that can lead to pain ("pressure"). That is why they are used. However, when you choose to use an NSAID, you pay for the decreased pain by slowing healing of injured tissue. As Karl mentioned, cycling off the drug for awhile may be beneficial.
In another arena, I was asked to comment on fat ingestion during exercise. I'll do this later, but keep this post around -- the topic of eicosanoids is going to come up again, and the information above could make good reference material when I start talking about Barry Sears and the 40-30-30 diet plan.
Hope I haven't confused everyone! (I probably have -- I'm sure you'll let me know!)
John M. writes:
I just read with interest your posting on the ultrarunning listserv about NSAIDS. As you may have seen in several issues of Ultrarunning last fall, there is anecdotal evidence going around that ibuprofen (and presumably other NSAIDS) may also cause kidney malfunction. I had a relatively mild effect of this sort last year when my kidneys appeared to shut down about 25 miles into a race. This seems a potentially more serious concern than the healing problem you have dealt with. Any hard information?Good question, John.
Generally, the NSAIDs are safer to use (at least in terms of frequency of side effects) than is average aspirin. However, they *have* gotten a bad reputation because kidney function can be adversely affected by them. The kidney toxicity is rare, but can occur in events such as ultras where the kidney is already trying to work as hard as it can in order to rid the blood of the toxic by-products of metabolism/.
The problem is actually related to one of the prostaglandins, PGE2. PGE2 has many different effects on the body. It enhances the pain-producing properties of bradykinin (a chemical mediator released in response to tissue injury -- one of the major "pain causers" injury.). Blocking prostaglandin synthesis decreases pain (at least in part) by inhibiting the synthesis of PGE2.
PGE release is also responsible for the production of fever, so that is why NSAIDs can be used to control an elevated internal body temperature.
Unfortunately, PGE2 is also responsible (in part) for proper kidney function. When levels of PGE2 are decreased, as they are when NSAIDs are administered, there is a propensity for fluid retention and edema (swelling) in the hands and limbs.
By far the most common side effect of NSAID use is gastric (stomach) irritation and ulcer formation. This is also a direct effect of blocking prostaglandin synthesis (stomach acid production is increased), and is the reason why NSAIDs should *always* be taken with food or milk.
There are many other factors that may play into kidney shut-down during an ultra. In my opinion, it is unlikely that NSAID use alone would cause problems, but taken in combination with the level of stress, dehydration, electrolyte balance, etc, that we may experience, it should be something to consider.
I can concur with what Karl said about cutting out NSAIDS as much as possible and treating the root causes of an injury. I have suffered from PF (plantar faciatis) for about two years. Last summer I got fed up with it and decided to get help. What I did was go to a chiropractor, to get my "alignment" checked. What the doc discovered is that my ankles were not working correctly (ie. the were not as loose as they should have been and were not absorbing much shock) so the bottoms of my feet and my Achilles were taking a beating. Also, my calves were real tight. So, I went to the doc regularly, had several one hour massage sessions, stretched the calves out more, and ran a lot less on pavement. Then once things were aligned and more supple, I cut out using NSAIDS this past Oct. after the 100 miler I ran. The healing is going well. The left ankle/heel is pain free, the right one bothers me after 3 or 4 hours on a trail, it is now though only a slight, background pain, that subsides within a few hours. I used to walk around the day after a long run with a noticeable limp. Once you learn how to treat injuries you can minimize the time they effect you and how long it takes to completely heal back to normal.
PS I was not taking that much ibuprofen, just a tablet each day (200 mg) after my daily run, and then another tablet in the evening. At the 100 I took 200mg at 50 mi and 200 mg more at 75 mi.
Below is my post to Jay Hodde, with his responses. Though it is fairly technical, it answers some pertinent questions on the use of NSAIDS.
Jay,
Thanks for the info on the NSAIDs. I was going to ask about that, so you answered my question before it got posted. A couple other things - You hinted in a previous post that using an NSAID ( I use Aleve once in a while ) would increase comfort at the expense of delaying healing. I thought they would aid healing by increasing blood flow to the area. Is that not the case?In general, the NSAIDS all act to inhibit the action of the enzyme called cyclooxygenase (COX), the critical enzyme for the formation of prostaglandins and thromboxane from arachidonic acid. Several may also block the action of lipoxygenase, the enzyme needed for the formation of leukotrienes.
What does this mean? First, leukotrienes (LT) and prostaglandins (PG) play important roles in the inflammatory response. The LT are responsible for phagocyte mobilization and also increase vascular permeability. These actions are critical to healing -- the phagocytes help clear the wounded area of debris and the vascular permeability is important for supply of nutrients and the removal of waste. When LT activity is blocked, healing is slowed. Not all the NSAIDs act to block LT synthesis, but it seems as all of them do so to at least a minor extent. Significant inhibition occurs with Indocin (indomethacin) and Voltaren (diclofenac), and is the major reason that these drugs are not the first choice of NSAID in normal cases.
The PGs are the other side of the equation. PGs normally promote edema and leukoctye (white blood cell) infiltration and enhance the pain-producing properties of bradykinin. When COX is blocked, PG formation is stopped and the pain and inflammation subsides. This is the action that we use the NSAIDs for. The LT interaction is the negative interaction that slows the healing -- that's what I was referring to in my earlier post.
In terms of blood flow, the NSAIDs act to increase blood flow to the area *only* by decreasing the amount of inflammation in the area. There is no direct action on blood flow -- it is only secondary to the anti-inflammatory process.
Shouldn't it be pointed out to the list that the body produces, during > a long run, Steroidal anti-inflammatories which are quite effective until they wear off? In an ultra, I'll take an Aleve an hour before the run starts, but not thereafter, figuring that by the time it wears off, I'll have my endogenous analgesics and anti-inflammatories in place.This is one of the major reasons that I don't take NSAIDs during an event. If I need to take a drug to get me through it, I know that I may suffer later. I will only use NSAIDs during an event if I know what my problem is (I can usually guess quite accurately if something major is wrong) -- and even then I don't always do it. I'll let you address the endogenous steroids -- you've done a great job in the past with it. [ KK will do that in a few days, after attending to some urgent Ice Age work. ]
In general, ultras have not been very painful for me ( and I don't want them to be! ) so I don't see the need to take drugs to finish. The very few times when natural analgesics were not enough to dull the pain, I had really serious muscle damage. Stopping at my earliest convenience was clearly the right thing to do. Accordingly, I don't see the point in defeating a natural mechanism that is reasonably protective.During a major 100K, a local runner was given ibuprofen like candy simply because of an upset stomach in the first 8K. The runner recovered later in the race to finish with a good result, but was sick for days afterward. At the dosage given, there was probably kidney and/or liver damage. I suggested that a runner should never accept drugs handed to him/her by a crew person who does not have the medical training necessary for safe application of them.
Having seen runners in ultras popping Ibuprofen like candy, the question arises, "Why do that?" You don't have to be around this sport long to hear of people who did serious damage to themselves with Ibufprofen, and in one case I know of, Aleve.
Dr. Noakes raised the point about benefits: what benefits do runners think they gain? Heavy use of NSAIDS is probably not justified by results, but is done as a ritual, handed down from one runner to another. If Tom Johnson and Ann Trason told the world that their secret was a jar of strawberry preserves one hour before race time, it would become a tradition for years to find runners downing strawberry preserves an hour before the run. Those who ran well would say, "Yes! It was the preserves.", and the tradition would continue.
The various NSAIDS and their mode of action was well covered by Jay Hodde in a previous post. Adding to that, we should note that the human body makes its own potent anti-inflammatory: cortisol. This is a steroidal hormone produced from cholesterol whenever the body is subjected to major stress, such as running more than 18 miles or so. It has many profound affects on the body, one of which is to block inflammation. It is so effective that drugs related to cortisol are prescribed for arthritis and other afflictions that need reduction of inflammatory response. So, virtually every runner in an ultra or long training run will make their own, effective internal anti-inflammatory.
Aiding the process of dealing with stress is another chemical, beta endorphin ( a protein ), which is a powerful analgesic. Being an opiate, it both dulls pain and elevates mood.
Individuals vary in their ability to tolerate pain, but in general, if you have pain and inflammation in a run which are strong enough to overwhelm your own cortisol and beta endorphin, it is probably a serious problem. You can get treatment, drop out, or you may elect to take a drug and risk damage if the circumstances warrant. Consider that if you've taken a lot of NSAIDs early in the run, more later may be an overdose. It is probably better to take one or none early in the run so that if you need to take some later it does not constitute an overdose.
It could be argued that to mask some minor pain it is reasonable to take one dose of NSAID at the start of a long run because it will take a few hours for cortisol and beta endorphin to reach effective levels. As long as you stay below the dosages given on product labels, you are not likely to haveproblems with NSAIDS. It is seldom justified to take more than recommended dosages when your body is combating stress with its own internal chemicals.
For the ongoing NSAID (aspirin, ibuprofen, etc.) discussion:
Last night I ran 20 miles on an injured hamstring (the NY Marathon is three weeks away, and desperate times call for desperate measures). As I was running, I had to constantly monitor my speed, as the injury appears to be sensitive to leg turnover.
Now consider this idea. As I run, fluid builds up in the damaged area (inflammation). This has got to be damaging the tissue. As I was running, the thought occurred to me that maybe I should have taken 800mg of Ibuprofen before the run started. My natural speed is not so great that I would risk severely tearing up the injured area, and I would have prevented additional damage due to inflammation. The downside is that the NSAID is also a pain killer, and pain is an important warning sign. I've always subscribed to the thesis that runners should not chemically mask pain, but now I'm rethinking that attitude, since it's depriving me of a therapeutic benefit. The point is: why wait till AFTER the run to take an NSAID, when the the damage has already been done? The ideal drug would be an NSAID that is not also an analgesic, but wishing don't make it so.
Has anybody had any bad experiences with taking 800 mg of Ibuprofen during a long run? Am I fooling myself?
Paul Comet wrote:
"Has anybody had any bad experiences with taking 800 mg of Ibuprofen during a long run? Am I fooling myself?"If you have an injury, the worst thing you can do is continue to run and injure it more. We had a regular runner around here in Florida that we nicknamed "Dr. Advil". He was in his late 40's, trained hard, and was fast as a result (10K in about 36 minutes). He claimed ibuprofin helped him train harder, but he was only fooling himself into ignoring the obvious signs of overtraining. One day several years ago I finally passed him at a local race, an 8K. He had pulled a hamstring and was walking in obvious pain. I have not seen him since.
Kevin asks:
"Wanted to ask a question about the best anti-inflamatory (over the counter) that you've had experience with. Here are some questions in particular: #1. Which one works best?"Each one needs to be evaluated individually because of differences in normal human physiology. What works best for one person could be useless for another. I personally have best luck with Aleve, and find it just as effective as *most* of the prescription preparations available. My NSAID "choice" is not available OTC.
"#2. Is it just masking pain or actually "good" for me to make my body heal quicker?"Well, good question. It masks pain. That can be good but it can be bad, too. If you mask pain, it is easier to harm yourself because your normal pain response is blocked. Pain limits most people, so if you take away the pain, you also take away the self-imposed limits. That *could* lead to injury, or more severe injury, if you use the NSAID inappropriately, excessively, or even at all. Pain blocking can be bineficial to the healing process, though, too. Think of PAIN-SPASM-INFLAMMATION as a cycle: pain leads to spasm, which leads to inflammation, which leads to pain, etc. Breaking the cycle is the goal of treatment -- and what will lead you to begin healing.
Healing quicker? The benefit of an NSAID is to decrease inflammation. This is generally a good idea, as inflammation can be a deterrent to healing (if it is excessive). Some inflammation is necessary for healing, and serves a useful purpose: increased blood flow to the area is important to bring nutrients to the injured site and to rid waste. PROLONGED inflammation and EXCESSIVE inflammation are what NSAID therapy is meant to address.
There is a down-side to NSAID treatment that is debated in the literature. While severe side-effects are uncommon, most people will have some sort of stomach discomfort as a result of taking high doses. That's the ulcer problem everybody talks about; there is no debate there.
The debate is prolonged effects on the liver and kidneys; while considered safe for shortterm treatment, long-term, low-doses are likely to have some effect (even minor) on organ systems. Most drugs do.
I also believe that (and this is an opinion here) NSAIDS, while they are useful in breaking the pain-spasm cycle, can slow the healing response dramatically. That is because the inhibit the enzyme cyclooxygenase (COX), an enzyme that effects leukotriene production in addition to prostaglandin production. Prostagladins are substances that lead to pain and inflammation; blocking their production deadens pain and reduces inflammation. I think of leukotrienes as an "interal check" for the prostaglandins. Some research suggests that leukotrienes may aid in the mechansims of wound repair. Mostly speculation, I know, but remember the saying, "You can't get something for nothing?" If something seems too good to be true, it probably is...
I know that Karl King and others have followed an NSAID dosing program that I use based on the above hypothesis with great success.
"#3. How much should I take?"To avoid legal battles, "Take as directed on the bottle." It's safe and usually effective for most people. If that doesn't work, follow the advice of your physician. I don't do either of the above things, but since my personal dosing schedule and philosophy about the drugs is not medically approved, I don't care to share things publically.
Note, however, that "amount" of drug to take is dependent on the drug and the person taking it. A 300-pound male wouldn't be expected to get the same effect out of a given dose as a 110-pound female. Likewise, a 70-year-old will probably need different amounts than a 20-year-old to get the same effect.
"#4. When should I take it? Some before exercies, some during, after, all at once, one every 2 hours, etc."See the caveats above. NSAIDS during an event are not advisable for most people because of the pain-deadening effect and the possibility of injury. Personally, I take a single Aleve before an event, then a single dose 6-8 hours later, then another 6-8 hours later, assuming I'm still running.
I take some right after finishing, too. (Sometimes, I'll take it when I know I have about an hour left to run.)
Specific dosing protocols depend on the drug you are taking, as well as your tolerance and personal physiologic response to the drug. There is no one-size-fits-all answer.
"#5. Does taking an anti-inflam drug every day make my body become more and more resistant to the drug, meaning will it eventually not give me the same benefits as if I were to only use it when i'm at the higher levels on the pain scale? Kind of like Caffeine. (I understand that the benefits that caffeine gives doesn't happen if you're a caffeine "user") I would appreciate some education on this. I now use Ibuprophren and it works well for me but I just had the above questions for long term use and wondering if anything was working better for others.If you are using it for a medical condition, it will be prescribed by your doctor. If you are taking it without the advisement of a doctor, ibuprofen is quite safe. If its effective, why change to other, possibly more expensive drugs?
My question to you, however, is this: Why do you want to take it on a prolonged basis? If you are using it to reduce the symptoms of rheumatoid arthritis (or other specific medical conditions that indicate prolonged NSAID therapy), that's one thing. If you think it's necessary to deaden the pain of running or to block the pain of a running injury, an NSAID won't help fix the problem, and can make things worse.
On tolerance: I don't know what the medical research says on this, but personal experience tells me that chronic use DOES lead to tolerance.
I will be attempting my 1st ultra this January in the Mountain Mist 50k Trail Run in Huntsville, AL. I also know that racing an ultra trail will be much different than a shorter distance road race. I have read in various articles about the possibilities of kidney failure in conjunction with NSAIDS use during an ultra. Here is how I understand it to work:
During an ultra, because of the pounding endured, RBC's are destroyed and myoglobin is released. In an attempt to clear the myoglobin, it is filtered through the kidneys. Since myoglobin is such a large molecule, prostaglandins must be released which dilate the kidney tubules and allow the myoglobin to be passed in the urine. But, with NSAID use, this inhibits prostaglandin formation, thereby not allowing the tubules to dilate. This ultimately leads to the myoglobin being trapped in the kidney and causing kidney failure.
I have also read that this condition is more common when: (a) the race distance exceeds 50m, (b) the temperature is high, (c) the runner is not well-trained for the event, and/or (d) NSAIDS are used excessively during the race.
Can anyone tell me if any of what I just said is actually true? Also, are there any recommendations as to how much (if any) and what kind of NSAIDS should be taken during a race? Is generic ibufrofen OK? (I'm a poor grad student!) Thanx.
I had an interesting experience recently with ibuprofen that is germane to this discussion. I've taken "vitamin I" during ultras over the years, typically every 6 hours or so. The effect during an ultra is subtle enough that I've never been able to gain any insight into whether 6 hours was an optimum spacing. Over the Columbus Day holiday a couple weeks ago, I developed a tooth abscess that was excruciatingly painful. Since it was a Holiday weekend, and my dentist was out of town anyway, I kept it under control with ibuprofen. Because it was so painful, I knew exactly when the ibuprofen kicked in and when it wore off. I was surprised to find that it took between 30-45 minutes for 600 mg of ibuprofen to dull the pain, and it was completely worn off after about 3 hours. Whether the anti-inflammatory benefits follow this same timescale I don't know, but it suggests that every 6 hours might be too great a spacing if you're trying for some consistent effect.
Alleve is OTC Naproxin. The label dose for alleve is one pill (220mg) twice daily. The 1998 PDR (physicians desk reference) lists dose ranges from 275mg up to 1000mg daily. That is followed by two pages of really tiny print listing all the side effects: Gastointestinal problems, neurologic problems, dermatologic problems, cardiovascular problems, hearing and vision disturbances.
Other OTC pain relievers are similar: An OTC dosage but much higher doses possible if one is willing to risk the side effects.
The problem with deciding whether you need medication is that the degree of pain does not always equal the degree of injury. Post-traumatic pain syndrome is common: The pain remains even after the injury is healed. Memory pain is another term for it. 4 months ago I fractured a rib. The latest radiographs show the bone to be fully healed, yet it still hurts like crazy. Someone who loses a limb can feel phantom pain.
These syndromes are thought to be generated by the brain and spinal cord, rather than the injured site. At least that's the theory that makes the most sense to me.
My point is if I've rested through an injury and feel ready to resume training, I use OTC doses of alleve and tylenol and try to ignore the pain that the meds don't cover. I assume that I'm experiencing that memory-pain stuff. If I needed higher doses, that would tell me I'm not yet healed.
The other side of the coin is the theory that nsaids slow down the healing process. So I try to avoid them if I'm injured. Tylenol (acetominophen) is not an nsaid. It works inside the brain so taking it won't slow down healing rates.
Acupuncture works very well on post-traumatic pain syndromes. The idea is there is this reverberating circuit and the needle acts like a ground, short-circuiting the circuit.
I'm not an MD, just a country vet.
Thanks for the comments i've heard so far but I still have a couple more questions.
Kevin asked:
"#1. What is a NSAID? I'm guessing that the AID stands for anti-inflam drug but not sure about the NS."NSAID stands for "Non-Steroidal Anti-Inflammatory Drug". It is a class of compounds that act to inhibit the enzyme, cyclooxygenase (COX). As the name states, it is a non-steroid compound. Steroid derivatives can also be used as anti-inflammatory agents, thus the distinction. NSAIDS are generally safer than steroid compounds, so that is why they are used. All available steroids are presecription-only drugs.
"#2. Another important point was brought out concerning dosage for different sized people. Assuming an averaged sized person, I understand that it takes at least 600mg of Ibuprophen to start an antiinflam response. Anyone heard that one before. That comes from my brother a Dentist."General dosing schedules are designed to place individuals in a therapeutic window quite quickly. 600 mg IBU is equal to 3 OTC tablets. Many people require that amount, but others get relief with as little as 200 mg. If you read the bottle, you will see a statement to the effect of: "The least effective dosage should be taken". That amount varies from person to person.
Thought I would help clarify this issue a bit. One of the first things to understand is that there are two distinct mechanism of pain relief invovled. One is analgesia and occurs at the lower dosages ie 200mg for motrin(ibuprofen) and the 220mg dosage of aleve(naprosyn). The second and often more important mechanism is the anti-inflammatory effect. This takes several several days at higher dosages ie 2400mg/day to achieve. The anti- inflammatory effect is of importance in injuries, but of less significance in headaches. Of course with the higher dosages, side effects increase also.
The most common side effect is gastritis which can and does lead to ulcers. It happens by two mechanisms. The first and strongest effect is by the caustic effect of the drug when it comes in contact with the stomach lining. A second mechanism though less potent is a thining of the lining of the stomach that occurs through an indirect effect of the drug.
The effect on the kidneys is real, however I am not aware of any good studies showing any increased incidence of renal problems in athletes that use NSAIDS, but I will do a current literature search when I get a chance.
I consider the use of NSAIDS during an ultra to be risky business because of the potential for bleeding from the stomach in the worst case, and much more commonly for the nausea and stomach problems many runners have during and after runs. I favor the use of long acting NSAIDS taken before and after, but not while running. There are a number of 24 hour preparations on the market that make this feasible for most races. They are all available by prescription only, but if used for races only the cost would not be that bad. If that is not an option than Aleve would be my choice. Simply because it has the longest duration of action.
Did a medline search, 90 - 98 and searched the online version archives of The Physician and Sportsmedicine as well as the Medscape archives - no articles about increased risk of myoglobinuria with NSAIDS. There was one article that showed some minor decrease in the function of the kidneys in triathletes, but not enough to be clinically significant(do any harm).
Piroxicam is the only generic available and as safe as any most bang for your buck. My fovorite is naprelan which is the 24 hour version of naprosyn, but it would be pricey without insurance, and even with insurance is not on many plan's formulary. Both are not too bad on the stomach.
Whenever the discussion comes around to NSAIDs and kidney failure, I feel compelled to chime in. Read my article in March 1995 UR (Kidney Failure and Ultramarathoning) or refer to my web site . My feeling is that the myoglobin release is pretty much independent of the NSAIDs use, except to the extent that the NSAIDs allow you to run harder and longer, thereby increasing the possibility of rhabdomyolysis. The role of the NSAIDs in kidney failure comes later. The NSAIDs inhibit the ability of the prostaglandins to help the kidneys defend themselves against the myoglobin.
In a 1993 Clinical Nephrology paper entitled "Ibuprofen as an over-the-counter drug: is ther a risk for renal injury?" the authors write "It is unquestionable that ibuprofen can cause renal damage." In a 1993 Annu Rev Pharmacol Toxicol paper entitled "Renal toxicity of the nonsteroidal anti-inflammatory drugs," the authors write "NSAIDs produce most of their therapeutic and adverse effects through inhibition of the prostaglandin synthesis."
"Does anyone have anyexperence with this product?"The problem is that no one has adequate experience with most herbals/natural products. They do not go through the testing and approval process of the FDA so little is known and much is claimed. They represent a pandora's box of side effects. When someone gets sick or for that matter dies when using the product there has never been any organized effort to see if the product might be responsible. As the old adage goes, buyer beware.
Even those products which have been used for centuries are not always safe. Two example are Ginko which can cause abnormal bleeding in some people and Ginseng which can cause increased problems in asthmatics. In both cases there is no requirement for label warnings unlike conventional medications.
Last night I ran 20 miles on an injured hamstring (the NY Marathon is three weeks away, and desperate times call for desperate measures). As I was running, I had to constantly monitor my speed, as the injury appears to be sensitive to leg turnover.
Now consider this idea. As I run, fluid builds up in the damaged area (inflammation). This has got to be damaging the tissue. As I was running, the thought occurred to me that maybe I should have taken 800mg of Ibuprofen before the run started. My natural speed is not so great that I would risk severely tearing up the injured area, and I would have prevented additional damage due to inflammation. The downside is that the NSAID is also a pain killer, and pain is an important warning sign. I've always subscribed to the thesis that runners should not chemically mask pain, but now I'm rethinking that attitude, since it's depriving me of a therapeutic benefit. The point is: why wait till AFTER the run to take an NSAID, when the the damage has already been done? The ideal drug would be an NSAID that is not also an analgesic, but wishing don't make it so.
Has anybody had any bad experiences with taking 800 mg of Ibuprofen during a long run? Am I fooling myself?
Paul wrote:
"Has anybody had any bad experiences with taking 800 mg of Ibuprofen during a long run? Am I fooling myself?"If you have an injury, the worst thing you can do is continue to run and injure it more. We had a regular runner around here in Florida that we nicknamed "Dr. Advil". He was in his late 40's, trained hard, and was fast as a result (10K in about 36 minutes). He claimed ibuprofin helped him train harder, but he was only fooling himself into ignoring the obvious signs of overtraining. One day several years ago I finally passed him at a local race, an 8K. He had pulled a hamstring and was walking in obvious pain. I have not seen him since.
Kevin asks:
"Wanted to ask a question about the best anti-inflamatory (over the counter) that you've had experience with. Here are some questions in particular: #1. Which one works best?"Each one needs to be evaluated individually because of differences in normal human physiology. What works best for one person could be useless for another. I personally have best luck with Aleve, and find it just as effective as *most* of the prescription preparations available. My NSAID "choice" is not available OTC.
"Is it just masking pain or actually "good" for me to make my body heal quicker?"Well, good question. It masks pain. That can be good but it can be bad, too. If you mask pain, it is easier to harm yourself because your normal pain response is blocked. Pain limits most people, so if you take away the pain, you also take away the self-imposed limits. That *could* lead to injury, or more severe injury, if you use the NSAID inappropriately, excessively, or even at all. Pain blocking can be bineficial to the healing process, though, too. Think of PAIN-SPASM-INFLAMMATION as a cycle: pain leads to spasm, which leads to inflammation, which leads to pain, etc. Breaking the cycle is the goal of treatment -- and what will lead you to begin healing.
Healing quicker? The benefit of an NSAID is to decrease inflammation. This is generally a good idea, as inflammation can be a deterrent to healing (if it is excessive). Some inflammation is necessary for healing, and serves a useful purpose: increased blood flow to the area is important to bring nutrients to the injured site and to rid waste. PROLONGED inflammation and EXCESSIVE inflammation are what NSAID therapy is meant to address.
There is a down-side to NSAID treatment that is debated in the literature. While severe side-effects are uncommon, most people will have some sort of stomach discomfort as a result of taking high doses. That's the ulcer problem everybody talks about; there is no debate there.
The debate is prolonged effects on the liver and kidneys; while considered safe for shortterm treatment, long-term, low-doses are likely to have some effect (even minor) on organ systems. Most drugs do.
I also believe that (and this is an opinion here) NSAIDS, while they are useful in breaking the pain-spasm cycle, can slow the healing response dramatically. That is because the inhibit the enzyme cyclooxygenase (COX), an enzyme that effects leukotriene production in addition to prostaglandin production. Prostagladins are substances that lead to pain and inflammation; blocking their production deadens pain and reduces inflammation. I think of leukotrienes as an "interal check" for the prostaglandins. Some research suggests that leukotrienes may aid in the mechansims of wound repair. Mostly speculation, I know, but remember the saying, "You can't get something for nothing?" If something seems too good to be true, it probably is...
I know that Karl King and others have followed an NSAID dosing program that I use based on the above hypothesis with great success.
"How much should I take?"To avoid legal battles, "Take as directed on the bottle." It's safe and usually effective for most people.
If that doesn't work, follow the advice of your physician.
I don't do either of the above things, but since my personal dosing schedule and philosophy about the drugs is not medically approved, I don't care to share things publically.
Note, however, that "amount" of drug to take is dependent on the drug and the person taking it. A 300-pound male wouldn't be expected to get the same effect out of a given dose as a 110-pound female. Likewise, a 70-year-old will probably need different amounts than a 20-year-old to get the same effect.
"When should I take it? Some before exercies, some during, after, all at once, one every 2 hours, etc. "See the caveats above. NSAIDS during an event are not advisable for most people because of the pain-deadening effect and the possibility of injury. Personally, I take a single Aleve before an event, then a single dose 6-8 hours later, then another 6-8 hours later, assuming I'm still running.
I take some right after finishing, too. (Sometimes, I'll take it when I know I have about an hour left to run.)
Specific dosing protocols depend on the drug you are taking, as well as your tolerance and personal physiologic response to the drug. There is no one-size-fits-all answer.
"Does taking an anti-inflam drug every day make my body become more and more resistant to the drug, meaning will it eventually not give me the same benefits as if I were to only use it when i'm at the higher levels on the pain scale? Kind of like Caffeine. (I understand that the benefits that caffeine gives doesn't happen if you're a caffeine "user") I would appreciate some education on this. I now use Ibuprophren and it works well for me but I just had the above questions for long term use and wondering if anything was working better for others."If you are using it for a medical condition, it will be prescribed by your doctor. If you are taking it without the advisement of a doctor, ibuprofen is quite safe. If its effective, why change to other, possibly more expensive drugs?
My question to you, however, is this: Why do you want to take it on a prolonged basis? If you are using it to reduce the symptoms of rheumatoid arthritis (or other specific medical conditions that indicate prolonged NSAID therapy), that's one thing. If you think it's necessary to deaden the pain of running or to block the pain of a running injury, an NSAID won't help fix the problem, and can make things worse.
On tolerance: I don't know what the medical research says on this, but personal experience tells me that chronic use DOES lead to tolerance.
I will be attempting my 1st ultra this January in the Mountain Mist 50k Trail Run in Huntsville, AL. I also know that racing an ultra trail will be much different than a shorter distance road race. I have read in various articles about the possibilities of kidney failure in conjunction with NSAIDS use during an ultra. Here is how I understand it to work:
During an ultra, because of the pounding endured, RBC's are destroyed and myoglobin is released. In an attempt to clear the myoglobin, it is filtered through the kidneys. Since myoglobin is such a large molecule, prostaglandins must be released which dilate the kidney tubules and allow the myoglobin to be passed in the urine. But, with NSAID use, this inhibits prostaglandin formation, thereby not allowing the tubules to dilate. This ultimately leads to the myoglobin being trapped in the kidney and causing kidney failure.
I have also read that this condition is more common when: (a) the race distance exceeds 50m, (b) the temperature is high, (c) the runner is not well-trained for the event, and/or (d) NSAIDS are used excessively during the race.
Can anyone tell me if any of what I just said is actually true? Also, are there any recommendations as to how much (if any) and what kind of NSAIDS should be taken during a race? Is generic ibufrofen OK? (I'm a poor grad student!)
I had an interesting experience recently with ibuprofen that is germane to this discussion. I've taken "vitamin I" during ultras over the years, typically every 6 hours or so. The effect during an ultra is subtle enough that I've never been able to gain any insight into whether 6 hours was an optimum spacing. Over the Columbus Day holiday a couple weeks ago, I developed a tooth abscess that was excruciatingly painful. Since it was a Holiday weekend, and my dentist was out of town anyway, I kept it under control with ibuprofen. Because it was so painful, I knew exactly when the ibuprofen kicked in and when it wore off. I was surprised to find that it took between 30-45 minutes for 600 mg of ibuprofen to dull the pain, and it was completely worn off after about 3 hours. Whether the anti-inflammatory benefits follow this same timescale I don't know, but it suggests that every 6 hours might be too great a spacing if you're trying for some consistent effect.
Alleve is OTC Naproxin. The label dose for alleve is one pill (220mg) twice daily. The 1998 PDR (physicians desk reference) lists dose ranges from 275mg up to 1000mg daily. That is followed by two pages of really tiny print listing all the side effects: Gastointestinal problems, neurologic problems, dermatologic problems, cardiovascular problems, hearing and vision disturbances.
Other OTC pain relievers are similar: An OTC dosage but much higher doses possible if one is willing to risk the side effects.
The problem with deciding whether you need medication is that the degree of pain does not always equal the degree of injury. Post-traumatic pain syndrome is common: The pain remains even after the injury is healed. Memory pain is another term for it. 4 months ago I fractured a rib. The latest radiographs show the bone to be fully healed, yet it still hurts like crazy. Someone who loses a limb can feel phantom pain.
These syndromes are thought to be generated by the brain and spinal cord, rather than the injured site. At least that's the theory that makes the most sense to me.
My point is if I've rested through an injury and feel ready to resume training, I use OTC doses of alleve and tylenol and try to ignore the pain that the meds don't cover. I assume that I'm experiencing that memory-pain stuff. If I needed higher doses, that would tell me I'm not yet healed.
The other side of the coin is the theory that nsaids slow down the healing process. So I try to avoid them if I'm injured. Tylenol (acetominophen) is not an nsaid. It works inside the brain so taking it won't slow down healing rates.
Acupuncture works very well on post-traumatic pain syndromes. The idea is there is this reverberating circuit and the needle acts like a ground, short-circuiting the circuit.
I'm not an MD, just a country vet.
Whenever the discussion comes around to NSAIDs and kidney failure, I feel compelled to chime in. Read my article in March 1995 UR or at http://www.lehigh.edu/~dmd1/dmd1.html. My feeling is that the myoglobin release is pretty much independent of the NSAIDs use, except to the extent that the NSAIDs allow you to run harder and longer, thereby increasing the possibility of rhabdomyolysis. The role of the NSAIDs in kidney failure comes later. The NSAIDs inhibit the ability of the prostaglandins to help the kidneys defend themselves against the myoglobin.
In a 1993 Clinical Nephrology paper entitled "Ibuprofen as an over-the-counter drug: is ther a risk for renal injury?" the authors write "It is unquestionable that ibuprofen can cause renal damage." In a 1993 Annu Rev Pharmacol Toxicol paper entitled "Renal toxicity of the nonsteroidal anti-inflammatory drugs," the authors write "NSAIDs produce most of their therapeutic and adverse effects through inhibition of the prostaglandin synthesis."
Peter wrote:
"I was wondering if anyone could explain in simple layman's language the difference between aspirin, advil and aleve, in terms of:As a licensed physician I offer the following as a response to your questions: All of the "non-steroidal anti-inflammatory drugs" (NSAIDS) inhibit the enzyme cyclooxygenase, which generates prostaglandins (D, E, F, G, H, and I) and thromboxane from arachidonic acid found in cell membranes. Aspirin, Ibuprofen, and Alieve are all NSAIDS with similar side effects that arise as a consequence of an alteration in prostaglandin metabolism: decreased blood flow and/or inflammation in the kidney that may result in renal failure; interference in the normal mechanisms that protect the lining of the stomach from stomach acid, resulting in gastritis and/or ulcers; and interference with platelet aggregation that may cause excessive bleeding from open wounds. The only NSAID that is different is the newly released, and very expensive, Celecoxib (Celebrex) which does not cause stomach irritation. They are all similar in their anti-inflammatory effects, but some last longer (Alieve) and can be taken less frequently. Despite the potential side effects, these drugs are enormously successful and generally safe if used within reason. In fact, it is an under-appreciated fact that daily aspirin in low doses significantly reduces risk of death (from any cause), particularly in older populations.
- how well each works as an anti-inflammatory agent
- how do they compare in the danger they pose to kidney function; i.e., is one of these much more effective or more dangerous than the others?"
Is there any reason that you HAVE to take painkillers during an ultra, or before, or after, or in training? It seems to me that if you are taking NSAIDS (aspirin, iboprofin, COX-2 or whatever) on a regular basis, then you aren't addressing the problem. There is a reason for pain. I have seen too many people take drugs for overuse injuries so they could continue to run. Where is the evidence that NSAIDs will speed up healing? Usually the effect is the opposite. People use NSAIDs to mask the pain so they can continue to run and make the injury worse. Ultimately the problem becomes severe and they have to stop running completely, sometimes for years. Usually they drop out of the running community and I don't hear about them again.
I carry aspirin and/or ibuprofin during ultras, but I only take it if the pain becomes bad enough that it is slowing me down severely, and then I only take the smallest dose I can get away with. Most of the time, I don't need any. I never use it afterwards, even though I will probably be sore. The soreness is my body telling me not to run. A better way to deal with soreness is to massage my legs frequently, take 1-2 mile walks a couple of times a day, and eating plenty of food, especially protein. Taking drugs isn't going to reduce your need for recovery, so what's the point? Wouldn't this be sending a false message that it's OK to run when it really isn't?
I looked at the abstracts of some of these and found some interesting things:
"After Rich Schick's email, I requested references from the UCSF instructor who claimed that long-term use of NSAID's could decrease cartlidge metabolism, which could damage joints. The instructor has provided the following references (please check them out - I won't):""Vidal y Plana RR et al. Articular cartilage pharmacology: I. In vitro studies on glucosamine and non steroidal antiinflammatory drugs. Pharmacol Res Commun 1978;10:557-69."
Abstract not available to me.
"Palmoski MJ et al. Marked suppression by salicylate of the augmented proteoglycan synthesis in osteoarthritis cartilage. Arthitis Rheum 1980;23:83-91."This study talks about decreased rate of glycosaminoglycan degradation with fenoprofen, and mentions no change from controlsin ibuprofen or sulindac sulfide treated groups. While the authors claim proteoglycan synthesis is decreased in some of the treated groups, I sense that *turnover* of cartilage components in treated animals is decreased overall. It makes physiologic sense that if less is broken down, less must be made in order to maintain a given level of a substance.
I don't find this troublesome or problematic and I fail to be pursuaded that this study proves the assertion that was made.
"Gray RG et al. Local corticosteroid injection treatment in rheumatic disorders. Semin Arthrit Rheum 1981;10:231-54."No abstract available here, either. But we're discussing *nonsteroidal* medication, anyway, so I'd doubt this applies directly.
"Rashad S et al. Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. Lancet 1989;2:519-22."This one is interesting because the authors conclude only that prostaglandin synthesis inhibitors may be inappropriate to the management of hip osteoarthritis. It doesn't show or prove that NSAIDS are damaging to normal (i.e., non-arthritic) tissue.
Of further interest here is that only a strong PG-synthesis inhibitor (indomethacin, one of the strongest available, to my knowledge) had a negative effect on their measurements. A weaker drug showed no difference from controls.
"Howell DS et al. Biochemical changes in cartilage relevant to the cause and management of osteoarthritis. Rheumatol 1982;7:29-45."I was not able to pull up this reference from a Medline search.
Take my comments for what they are worth, but I don't think these articles (at least the abstracts of them that I was able to access) support the assertion that NSAIDS lead to joint damage as a result of decreased cartilage metabolism.
Matt Mahoney wrote:
"Is there any reason that you HAVE to take painkillers during an ultra, or before, or after, or in training?"I rarely use NSAIDs - first of all, they cause me severe stomach problems at times. I also suffer from occasional ITBS problems.
When I am training regularly, and not tapering for an event, I stretch every day that I run, and the stretching keeps the ITBS at bay. Sometimes though, when I'm tapering, I neglect the stretches - just forgetting. When this happens, the problem can flare up in a race. It happened this year at AR50 at mile 18.
I took ibuprofen three times during the race. Without it, I might not have finished. My knee was sore for a week after the race, but I used no more NSAIDs - just ice and stretching. I made a rapid and complete recovery, and got another reminder that I need to stretch every day, whether I run or not.
Without the ibuprofen, I doubt that I would have finished AR50. There was a point around mile 35-36, where I could no longer walk down hills comfortably. I had taken one dose before, at mile 18, and it was no longer effective - it had worn off or the problem had progressed or both..
So, to answer your question, I reached a point where I felt I HAD to take the ibuprofen to finish the race. People can judge that however they like, but I had trained for the race, I wanted to finish, I was in pain that was pretty bad at the time, but I was not afraid of true long term damage. I weighed my options, and decided to continue with the ibuprofen..
Anyone offended by that decision is welcome to place a star beside my name in your own personal copy of the finishers. Or cross my name off the list completely..
You'll find me near the back, but you will find me. Walking half of the last 32 miles makes for a long day..
I don't think that this contradicts Matt's point, since he went on to write:.
"I carry aspirin and/or ibuprofin during ultras, but I only take it if the pain becomes bad enough that it is slowing me down severely, and then I only take the smallest dose I can get away with."That is exactly what I feel that I did, yet at the same time, to answer your question above, I did feel that I had to take it to finish..
Matt wrote:
"Is there any reason that you HAVE to take painkillers during an ultra, or before, or after, or in training? It seems to me that if you are taking NSAIDS (aspirin, iboprofin, COX-2 or whatever) on a regular basis, then you aren't addressing the problem."I agree whole heartedly. As a medical professional (physical therapist and athletic trainer) I am frequently call upon to try to put some of you guys back together. Trust me if you have been medicating something for long enough just to continue working out It ain't going away all that quicly if at all. Pain is your bodies way of saying back off buddy. List to it, don't cover it up. Figure out what is causing it or visit someone who can figure it out for you and take their advise. You are only given one set of knees, ankles, shoulders etc., you will miss them when they are gone..
Personally I suffer from a funny heel disorder called Hagland's Deformity. In plain language -- my heels (more so the right) become 2-3x normal size and very painful if I don't stretch, run too much especially speed and hills and if my shoes/orthotics are too stiff. It has take me almost 1 year to figure out how to prevent/minimize soreness in the heels which had once had me eating Naprosyn, Daypro and Vicoprofen (ibuprofen plus coedine) like M+M's. Stretching, rest days, more cross training in addition to my running miles, more flexible orthotics and sleeping in a dynasplint several times a week especially after long runs and ultras-- and I have only had one day of soreness where I felt compelled to take meds-- that on 10-12 marathon or longer runs in the past 4 months. The effort is definately worth it..
Matt raises a worthwhile point, about which there was back and forth on the list sometime ago. I've gone from taking NSAIDs or asperin proactively and often, to not using the stuff at all except for what I consider emergencies.
I am not here to say which is better, but my own experience is that in not taking NSAIDS, when I do use them, say, in a 100 mile or 24 hour race, they really, really kick in. Back when I took them with some regularity, I found myself taking a capsule, then feeling like I had to take another, and another. I also found that the chronic 'low grade' pains and injuries I was dosing myself for, stayed about the same, with or without drugs.
Perhaps it was Matt who suggested this procedure with cafiene, too. After being something of a pill popper, I have very much enjoyed the strong benefits of only taking NSAIDS (and asperin & cafiene) in long races and training runs of over 40 miles.
Subject: Kidney Shutdown During Ultras
The use of NSAIDS, ibuprofen as well as any of the related drugs during ultras is playing with fire. The kidneys as well as the stomach are at risk. The abstract below is a bit technical but what it says in a nutshell is that any time you are likely to be dehydrated or have even a temporary imbalance of electrolytes, the risk of kidney problems becomes much more likely. You may have gotten away with it in the past, you may in the future, then again you might just permanently damage your kidneys. Neither dialysis nor renal transplants are fun or cheap.
Title: Nephrotoxicities of nonsteroidal anti-inflammatory drugs.
Author: Wen SF
Address: Department of Medicine, University of Wisconsin Center for Health Sciences,
Madison, USA.
Source: J Formos Med Assoc, 96(3):157-71 1997 Mar
Abstract:
While the relative incidence of serious nephrotoxicities in the population consuming nonsteroidal anti-inflammatory drugs (NSAIDs) is very low, the frequency of adverse events in patients at risk has considerably increased due to the rising popularity of the use of the drugs in recent years. Under normal conditions, NSAIDs have relatively little effect on the kidney because of low renal production of prostaglandins. However, in the presence of renal hypoperfusion in which local synthesis of vasodilator prostaglandins is increased to protect the glomerular hemodynamics and to maintain appropriate renal tubular transport of fluid and electrolytes, inhibition of prostaglandin synthesis by NSAIDs can lead to vasoconstrictive acute renal failure as well as fluid and electrolyte disorders such as sodium retention and resistance to diuretics, hyponatremia and hyperkalemia. Conditions that increase the risk for NSAID-induced nephrotoxicities include volume depletion from diuretics and other causes, edematous states such as congestive heart failure and cirrhosis of the liver, old age and underlying renal disease, especially in the presence of renal functional impairment. In addition, renal parenchymal diseases may develop in susceptible patients taking NSAIDs. These include acute tubulointerstitial nephritis, frequently associated with nephrotic syndrome, and chronic progressive renal disease, with or without renal papillary necrosis. Rare cases of vasculitis and glomerulonephritis have also been reported. Finally, NSAIDs may aggravate hypertension by interacting with antihypertensive drugs, especially with diuretics and beta-blockers. Withdrawal of NSAIDs in patients at risk can frequently reverse or improve the nephrotoxicities. It is recommended that physicians be aware of the clinical settings that increase the risk for NSAID-induced nephrotoxicities and take preventive or therapeutic measures accordingly.