If you have ever taken a medicine that didn't work, you may have wondered why that happens sometimes. There are several possibilities:
- It's the wrong medication for your condition.
- Your condition will not respond to any medication — that is, there is no known effective medication therapy for your particular medical problem.
- Your problem needs a different dose of the medication or a longer duration of treatment.
- The condition has changed in a way that makes the medication less effective. For example, an infectious organism could mutate so that it is now resistant to the antibiotic you are taking.
One other reason I've often heard from patients is that a medication does not work well because they have become "used to it" or "immune to it." Can you really become immune to a medication or is that a medical myth? The answer depends in part on how you define "immune," but, for the most part, it is a myth. Then again, as with most myths, there is some element of truth to it.
Rare, but True
Though rare, there are clearly times when a person takes a medication and his or her immune system responds to it by making antibodies. These antibodies can then cancel the effects of the medication. The person has truly become "immune" to the medicine, and continued treatment is unlikely to accomplish much (and may even be harmful). Such is the case for the occasional patient taking infliximab (brand-name Remicade). This intravenous medication is injected every one to two months for rheumatoid arthritis that has not responded well to other medicines.
Because infliximab itself is a protein that is created in part from a mouse, there was concern during its development that the immune system would see it as a "foreign" invader and create antibodies that would attack it (so-called "neutralizing" antibodies). This process could eliminate its benefit. In fact, for this reason an additional immune-suppressing medication, methotrexate, is routinely given along with infliximab to people with rheumatoid arthritis. There are other, though relatively few, examples of this phenomenon, especially with agents that are derived from animal sources.
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The Myth Revealed
Considering all of the pills, liquids, injections and suppositories out there for hundreds of ailments, "becoming immune" to a medication is exceedingly rare. More often, a medicine does not work for other reasons having nothing to do with the immune system. For example, many people with high blood pressure take a water pill, hydrochlorothiazide (HCTZ). In a single daily dose, it often returns the elevated blood pressure to normal. However, even when it does, the blood pressure may rise again over time, not because of the immune system, but because the person increases their salt intake, gains weight, forgets to take a dose here and there, or takes an additional medication for unrelated problems that interacts with or counteracts the HCTZ.
In many cases, there may be no clear explanation for the rising blood pressure, but because the cause of most hypertension is unknown, the reason it worsens over time is usually unknown as well. But the requirement for an increased dose of a blood pressure medicine or needing an additional medication does not mean that the immune system is the culprit.
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The human body can become "tolerant" of certain medications because of their chemical properties. When this happens, more and more of that medicine is necessary to have the same beneficial effect. The most notorious examples are narcotic medications. A person with chronic headaches who takes a codeine pill each day might need two pills for the same benefit in a month or two. Over time, the dose requirement may continue to rise even if the pain severity is unchanged.
The reasons are not entirely clear, but it is thought that narcotics somehow provoke an increased number of "binding sites" — the proteins on the surface of nerve cells to which narcotics attach and reduce pain signals — and more binding sites means more medication is needed to attach to them. This is one reason that many physicians are hesitant to prescribe narcotic medications for chronic pain.
Another aspect of tolerance is the reduction in what we might consider to be side effects of the drug. For example, many people who begin to take a diuretic for their high blood pressure will have increased urination for several days to a week. After that initial period, increased urination disappears but their blood pressure will still be lowered. That is because the diuretic effect on the kidney is limited. At a given dose, the diuretic can only cause a certain amount of urination. As long as fluid intake stays about the same, a new balance develops between amount of fluid taken in and amount of urine made.
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Recruiting the Immune System
There are also times when a medication stimulates the immune system without reducing the drug's intended effects. Rather dramatic examples include drug-induced lupus and drug-induced vasculitis. Drug-induced lupus and drug-induced vasculitis are worse than a drug not working for you — these are examples of a drug actually causing disease.
In these conditions, drugs such as hydralazine, procainamide or certain antibiotics are thought to prod the immune system into attacking several parts of the body. The attack continues until the drug is stopped. The immune system seems clearly involved, but rather than just attacking the medication and preventing it from doing its job, the attack is directed at the skin, the joints or other tissues. Fortunately, the medications associated with drug-induced lupus are rarely used anymore.
Although there are many allergic and non-allergic reactions to drugs, a sampling of some of the more severe reactions that might include components of the immune system include:
- Stevens-Johnson syndrome — This reaction includes fever, sores in the mouth, eye inflammation and severe skin inflammation. It may be called "toxic epidermal necrolysis" if more than 30% of the skin becomes detached (with the appearance of burned skin).
- Anaphylaxis — This refers to a severe and sudden reaction minutes to hours after exposure to a drug or other trigger. Symptoms may include hives, itching, skin swelling, shortness of breath with wheezing, nausea, abdominal cramping and loss of consciousness.
- Drug-induced kidney disease — Termed "acute interstitial nephritis." this rare condition may develop days to weeks after exposure to a medication, especially nonsteroidal anti-inflammatory drugs, antibiotics, cimetidine, allopurinol and ciprofloxacin. Symptoms include fever, rash and kidney damage.
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The Bottom Line
In some ways, it may be just a matter of semantics to suggest that one rarely becomes immune to a medication. After all, when a medicine causes a significant side effect, it usually will have to be stopped whether the immune system is involved or not. And the fact is, much of the time, we don't know for sure why a medicine stops working.
When a medicine is not effective, you and your health care professional will have to decide whether to adjust the dosage, try something new or discontinue medicines altogether, because one is rarely immune to a medication. Mistakenly assuming it won't work due to "immunity" may deprive you of that medicine's benefits. Instead of switching, some adjustment in that medication's dosage or schedule of use may be all that is needed.
It is often the case that doctors choose medications without being able to predict exactly what response you will have. Researchers are working hard to improve our understanding of how drugs work, and this may lead to better choices of drug therapy. For example, the field of "pharmacogenomics" in which an individual's genes are analyzed to predict response to a particular medicine, could be used not only to pick the most effective drug but to minimize the risk of a side effect.
Until that happens, don't blame your immune system if a medication does not work — most of the time, your blame will be misplaced. Instead, work with your health care professional to figure out why a medicine is not effective so that a different dose or duration of therapy, or an entirely different medication can be chosen. It could even turn out that your medical problem does not need a medication at all.
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Robert H. Shmerling, M.D. is associate physician at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School. He has been a practicing rheumatologist for over 20 years at Beth Israel Deaconess Medical Center. He is an active teacher in the Internal Medicine Residency Program, serving as the Robinson Firm Chief. He is also a teacher in the Rheumatology Fellowship Program.