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Long-term Effects of Opioid Pain Relievers

Posted Aug 14 2009 6:45pm 1 Comment

As someone who suffers from chronic pain, I was wondering what are the long term effects of my pain medication? At this point in time Lyrica is not available to me and SSRIs, like Cymbalta, have horrible side-effects with me. So, my doctor in all his wisdom prescribes me Vicodin to control my pain. So, what are the long-term effects of it’s usage?

During my research I found very little on the long term effects. Most of what I found dealt with addiction to opioids and opioid-mix drugs. Currently, very few people become addicted to drugs like Vicodin and Percocet, though they do become physically dependent– which is not the same as addicted (explained further below). Some of what I found also dealt with the effects of overdose on opiods mixed with acetaminophen, such as liver and kidney damage that could ultimately lead to death (which is the case with any drug that contains acetaminophen).

Here are some of the facts regarding addiction and physical dependency to opioid/opioid-mix drugs from WebMD:

Addiction Myths1:
Addiction: Hospice patients worry about becoming addicted to opioids. With hospice, however, it is rarely an issue. People with chronic pain also worry about addiction, but it turns out that for most adults, if they do not already have a substance (alcohol or drug) abuse problem, addiction is not much of an issue even when opioids are used on a long-term basis.

  • A study was done in which 12,000 nonaddicted people who needed opioids were followed up to see if they had become addicted. Four out of 12,000 showed addictive behavior (less than one tenth of 1%).
  • Generally, the only people who develop addictive behavior after being given opioids had an addiction problem before the opioids were given for pain. Most people take opioids until the pain goes away. Then they stop taking them because they do not want to feel dizzy or drowsy. Once the pain goes away, the toxic side effects of dizziness and drowsiness come back.
  • Anyone who takes any medication just to “get high” is already showing addictive behavior and needs to stop taking addictive substances, including opioids, other addictive drugs, and alcohol, immediately.
  • Some people with actual painful illnesses are addicted to mind-altering substances. They get prescriptions because of their actual illnesses. Here’s how the patient or the family can tell the difference between someone who needs opioids for pain and someone who is abusing opioids. Normally, the dose of opioids is arrived at by the patient telling the doctor how they are doing with the pain and by participating in their activities of daily living. A chronic pain patient who is not addicted to medication will tell the doctor the truth about his or her ability to function and do what needs to be done in daily life.
  • Addicts will lie about performing activities of daily living. The addict will claim that the pain is so severe that they need a higher dose until they get to a dose that causes them to be asleep most of the time. Then, they will tell the doctor that they are doing fine and are able to do all the activities that they need to do.
  • Selling the medicine to others is a federal crime that could get the seller a very long jail sentence and could lead to government seizure of your car or your house.
  • Family members must let the doctor know what is actually happening in this sort of situation. When an addicted person actually has a painful syndrome, the doctor, with the help of the family, may have to decide what the dose of medication should be, without reference to the dose the pain patient thinks would be best. Sometimes, in severely addicted people, the opioids should not be used at all. Some addicted people can be treated with opioids if necessary as long as they cooperate carefully with the treatment plan.

The physical dependency of my Vicodin is well documented, but I’m glad to know that the kind of addiction exhibited in such shows as “House” is so rare. Still, I worry about the damage my body will have due to long-term use. The WebMD article tells me that opiod/acetaminophen and opioid/NSAID (ibuprophen, naproxen) aren’t recommended for long-term use by chronic pain sufferers simply because over time they can damage the liver, kidneys and stomach (NSAIDs). However, an article from the Mayo Clinic states2:

No evidence indicates that long-term use of single-agent opioid analgesic preparations results in end-organ failure, as may be seen with other analgesics (eg, NSAIDs), or with certain combination opioid analgesics

And the WebMD states:

Strong opioid medications are slightly different in this regard, and this is fortunate for people who suffer from severe pain. With strong opioids, the dose depends on the amount of pain. These medications should not mixed with acetaminophen or other non-opioid drugs when used to treat chronic pain. People with intense pain can take very high doses of opioids without getting side effects. Some people with intense pain get such high doses that the same dose would be fatal if taken by someone who was not suffering from pain. In the pain patient, that same high dose can control the pain and still allow the person to be wide awake enough to do his or her activities of daily living.

  • Long-acting opioid: The best way to treat chronic, severe pain is by keeping it under control all the time. Your doctor can do this by using a long-acting opioid to keep the pain under control and a short-acting opioid to deal with those few times during the day when the pain breaks through. So, if you are on morphine, you would get a slow-release tablet that would keep your pain under control most of the time, and a short-acting tablet or liquid for those times when your pain breaks through.
  • Bad opioids: Some opioids are not recommended for chronic pain.
    • Demerol (meperidine), which is used often for acute pain after surgery, is a poor drug for chronic pain. It is not absorbed well when taken by mouth, and it causes dysphoria (feeling truly lousy) and seizures if used for more than a few days.
    • Talwin (pentazocine) is also bad for chronic pain. It has a ceiling effect. There is a maximum dose after which raising the dose gives no further pain relief. It also causes withdrawal symptoms when given to someone who is also taking another opioid.
    • The opioid/acetaminophen or opioid/NSAID combination drugs are fine for short-term use, but acetaminophen is poisonous to the kidneys and liver when used for a long time or in high doses. Many NSAIDs are toxic to the kidneys and stomach when taken for a long time or in high doses.

Doctor’s Argoff and Silverstein, writing the article located on the Mayo Clinic Proceedings, clearly states that “single agent” opioids show no long-term effect leading to organ failure, but combined with acetaminophen or NSAIDs can have dire results as shown by WebMD. So, am I to take from this that I should find another way to manage my chronic pain? I’m thinking that over the long haul I will be forced to go back to Amitriptyline and possibly try Lyrica– after I talk to my doc about this new drug.

Yesterday, while I was doing my research for this post, the FDA was busy approving a new, long-acting opioid for moderate to severe chronic pain.

The US Food and Drug Administration (FDA) has approved morphine sulfate/naltrexone hydrochloride ( Embeda ), an extended-release oral opioid analgesic for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. This Schedule II agent is the first FDA-approved long-acting opioid that is designed to reduce drug liking and euphoria when tampered with by crushing or chewing.

Does this drug count as a “single agent opioid” and will it be safer to use than Vicodin (mixed with acetamenophin) or Percocet (mixed with NSAIDs)? Can this be something that will have fewer adverse long-term effects for chronic pain sufferers? As I’m not a doctor, I can’t really answer those questions– but they will be posed by me to my own doctor. It’s something I’m genuinely interested in. I have chronic noncancer pain and want relief from that without having to wonder if I know anyone close who would be willing to donate part of their liver later on in my life 3. This is something that I’ve been thinking about for quite some time and I believe it’s time to review my options and sit down with my doctors again.

A note on physical dependency:
Physical dependency is different than addiction in that addiction causes people to seek the drugs anyway that they can get them, including lying to their doctors about their pain and daily activities. Physical dependency cause the withdrawal symptoms when people stop taking the drugs as well as heightened tolerance over time. That means that people suffering from chronic pain are likely to take more of the medication to get relief– which is what can lead to the most damage. This is why it’s so important to talk to your doctor honestly about the need to increase your dose of medications if and/or when that happens.

One more note: One of the side-effects of Vicodin is intense itching all over. I’ve recently discovered this in my research (having developed this recently and wondering what is going on). It’s normal and you should make sure to tell your doctor if you experience. I was under the impression that this was an effect of long-term use of the medication, but I’m wrong. It’s normal and can occur in people that have just started taking it.

  1. WebMD: Chronic Pain Guide:
  2. Contemporary Clinical Opioid Use: Opportunities and Challenges * W. L. Lanier and E. D. Kharasch
    Mayo Clin Proc. July 1, 2009 84(7):572-575
  3. That statement is only half tongue-in-cheek, by the way.
Comments (1)
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Hello lizzie,

I hear you! You sound very intelligent and are doing the best thing possible to manage your CP (chronic pain) -- you are seeking knowledge. As a long term sufferer of CP (over 30 years from spinal conditions), I have been there and done that. Here's the good news.

Attitudes are changing about CP. Many states (over 30 at last count) have palliative care legislation on the books, which include language defining pain as the 6th vital sign, and giving non-terminal CP sufferers a right to treatment. In some states, doctors can be sued for not treating your chronic pain. At the same time, baby docs are being educated that there are many differences between the appopriate treatments for acute vs chronic pain. There is less fear among the medical community about goverment interference in writing sched. II scripts for palliative care.

 You have already discovered the #1 strategy in receiving adequate pain control medication -- education. The internet is full of medical articles on chronic pain issues. A good place to begin is the website for the American Pain Society, which is one of the most respected organizations in the field. A newer organization is the American Chronic Pain Association, which is another interdisciplinary society of providers and paitents. There are others, as I'm certain your googling has revealed.

OK, next on the list, let me suggest a slight change of vocabulary. You already have one down pat -- addiction vs. dependence or reliance. Addicition is a psychological syndrome that I've heard described as the compulsive need to return to familiar habits that have proven to have stopped having a beneficial effect, or to have an outright negative effect on one's life, family, and living situation.


Physical dependence is simply the human body's need for a particular medication. Some medications cause physically dependence, some don't. If a patient is experiencing a positive outcome from a medication that may have the potential of causing physical dependence, then that patient has a decision to make, with the help of their medical provider, whether or not to choose that route. This is as different from the addiction process as apples and oranges.

Notice also that I use the word medication -- these are the chemical substances we obtain, by prescription of a licensed provider, from a licensed pharmacy or dispensary. 

Drugs are substances that are bought outside of this system. In the minds of most Americans, drugs are illegal substances, which is why it is most beneficial to get into the habit right away to call your pain drugs, medications.

We all know that anything from ampicillin to Zyban is called a "drug". A person who suffers from type II diabetes can call their insulin dose a drug if they so choose. Because of the media, politicians, and the American mind, it is not in the best interest of a CPer (a CP is my abbreviation for a person who suffers from Chronic Pain), to call their legal pain medication, a drug.

Think about it. 

OK, let me make one suggestion, answer one question, and I'm outta here, for now.

 Your Vicodan contains acetaminophen, the main ingredient in the OTC (Over The Counter) med Tylenol. Acetaminophenis a great medication for reducing fever, and an adequate med for mild, acute pain, but should never be taken by a CPer. 

Why? Unfortunately, acetaminophen, when taken in large doses on a regular basis causes liver toxicity. No one should take more than 4000 mg of acetaminophenper day, and for my family, I've always halved that limit to 2000mg. Also, you'll read on most boxes of either Tylenol or generic acetaminophen that you should not take this medication for any longer than 3 weeks, especially at the maximum dose, which in simple terms, is 4 doses of "Maximum Strength" Tylenol, or 8 pills per day. 

Incidently, forget branding names like "Maximum Strength". That's a marketing term, not a medical term. Learn to read boxes and understand dosages in milligrams or whatever is an appropriate unit of measurement. For instance, liquid medications aren't usually measured in milligrams alone. A so-called Maximum Strength Tylenol pill contains 500mg of acetaminophen. A normal Tylenol capsule contains 325mg.

I don't have a PDR here, but it is easy to see how much acetaminophen is in your Vicodan pill. Usually, with the generics, they will be labeled something like 5/500 or 5/325 or 7.5/500. These are not fractions, but signify first, the amount of hydrocodone in each pill, and after the slash, the amount of acetaminophen in each pill. Hydrocodone in the codeine-based opiate medication in your Vicodan pill, which is the so-called "Controlled substance" part of your pill. 

 OK, finally, Percocet contains acetaminophen, not an NSAID. Percodan, contains an NSAID, probably aspirin. The formula for Percodan has changed over the years. In the old days (when the world was young), Percodan had a very nasty substance called phenacetin. If anyone was in the military 40 years ago, they are probably familiar with an "APC" tablet. APC stands for Aspirin, Phenacetin, and Caffeine. Certain OTC NSAIDs (by the way, NSAID is short for Non-Steriodal Anti-Inflamatory Drug), and contains many members from aspirin to ibuprofen (Advil) to naproxen (Naprosyn), to more exotic creatures like diclofenac (Voltaren). They are great for reducing soft tissue inflamation, but they can be very hard on the lining of the digestive system (esophagus, stomach, duodenum), causing ulcerative problems, and on the kidneys. By the way, I never did say way phenacetin was so nasty -- long term use was shown to case renal (kidney) failure, and people who took Percodan tablets popped a half-dozen APC tablets daily, for 20 or more years, ended up on dialysis machines three times a week.

Taking medication is always a trade-off between risk and benefit. There are, however, very safe meds to take for CP.

You spoke of single-substance opiates earlier, I believe. I'm not certain if hydrocodone is available as a single substance med in the US, yet. However, oxycodone, the opiate in Percocet, is available as a single substance med. It is generally called Roxicodone, named after the manufacturer, however, it is a generic substance now, and generic oxycodone tablets are available.

One of your problems is to calculate the amount of Tylenol you are taking daily. Remember I spoke of trade-offs.

Here's another one, and it is an artificial trade-off, but we have to deal with it none-the-less. Perhaps it could be argued that there are real, public health issues involved here, but personally, I think that's a load of manure that justifies yet another police agency empire. Now I'll get off my soapbox and talk about the issue.

Controlled substances are classified in 5 levels, so-called schedules, named 1 through 5. Often you'll see the large letter C surrounding a roman numeral I - V, on the large bottles of controlled substances behind the counter at the pharmacy. The C stands for Controlled, and the roman numeral is the level.

The lower the number, the more controlled it is. Oxycodone is a schedule 2 or C-II med. Hydrocodone, which is a very similar substance, is a schedule 3 or C-III med. By federal law, you need a written prescription for a C-II med, while you can obtain a C-III med with a fax or a phone call fom your doctor to the pharmacy. There are also other restrictions that I won't go into here. 

If you and your doctor decide to move from a C-III med to a C-II med, then you will no longer be able to 1.) Obtain an Rx for your meds without a doctor's visit, and 2.) Obtain refills with having a fresh, new written prescription. Some states, not the federal government, but state laws, require special prescription forms for CII meds. In California, for example, these are called "Triplicate" prescriptions, and the pads are issued by the state to practitioners who have a proper DEA license to prescribe Sched. 2 meds. (By the way, Sched. 1 meds include substances like LSD, and used to include Cannibis, however I believe that is now off the list. C-I meds are considered to have no medical use, but may have research value. One obtains C-I meds only through a special issued license from the DEA in Washington.)

Because of the state's interference with the Rx process by demanding the use of triplicate prescriptions, many California MDs were reluctant to write C-II scripts for CP, which is exactly what C-II meds should be used for, especially the long-acting meds like time-release MS (morphine), and methadone, probably the best "synthetic" pain reliever invented by man.

One of the problems with most opiates is the body develops a tolerance to the medication, requiring more medication for the same effect. Research has shown that tolerance is accelerated by quickly increasing, and quickly decreasing blood levels of that medication.

Most oral opiates  reach their full effective dosage about 2 hours after they are taken. This is a peak, and with any peak, comes valleys. Once the opiate blood level has peaked, that level will begin to fall, and in the case of oxycodone, the level will half within 4 hours. The time between swallowing a pill, having that pill reach peak blood level (and therefore maximum effectiveness), to the time that level has been halved is called the "half-life" of that medication. The half-life of oxy is about 4 hours, give or take, depending on the individual, their activity, and the amount of pain they are in. The same is true for other codeine-based products. (There is a time-release concotion of oxycodone called oxy-contin (oxycontin, really. I hyphenate for emphasis). -Contin meds (contin from the word continuous) are supposed to deal with the half-life problem. 

It is a proven fact that the up and down swing of opiate blood levels will bring on opiate tolerance within a few weeks, again, depending on the person, their pain level, their activity, etc.

So, the ideal opiate med for a CPer is an opiate with the longest half-life. Methadone has a half-life of over 48 hours, and has been measured to something close to 96 hours in certain people. This means that once an effective dose of methadone is reached, tolerance rarely becomes a problem.

There's another factor at work here, also. Methadone has a property of being an NMDA antagonist. Describing N-methyl-D-aspartate receptors is a little beyond the scope of my message, but as a CPer, all you need to know is that this is a good thing when it comes to holding down opiate tolerance. 

So, methadone is a great drug for 3 reasons. 1) for certain kinds of pain, there's nothing more effective. 2) it has a very long half-life and therefore, once your dose is properly regulated, your body never has to go through the see-saw effect or increasing and decreasing blood chemistry. 3) Finally, Methadone is a pain reliever with built-in anti-tolerance qualities.

Now, I'm not selling methadone. It is a very, very powerful med, and withdrawal from methadone is very difficult to manage. I was a CPer for over 20 years before we took that final step, and in my mind, methadone is a final step in opiate-based mediacation of CP.

I was blessed with a terrible cervical spine, a fact that required maybe 10 years for me to get my mind around -- I have a chronic disease. That's another subject for another message. 

I'm trying to make the point that methadone is not for everyone, that there are other alternatives, and a person like you, who's pain is handled with hydrocodone should not be taking methadone.

And allow me one more point, because my case, and your case illustrate what I'm about to say.

Only a qualified, chronic pain physician, preferably one who has completed a fellowship program at an accredited pain center, can make these kinds of judgements. Your family doctor does not understand chronic pain. He or she may not understand, for instance, how opiate tolerance works, or why opiate half life is so important. The research on NMDA antagonists is relatively recent, and unless one is in the field (as you are), they may no be aware of the effect of these proteins on opiate tolerance. There are many other factors that a trained pain physician would consider in finding effective treatments for you that your friendly family practioner would not be aware of.

I'm speaking in general -- your FP may be an excellent pain physician out of personal interest, but it is a rare doctor that knows the differences in treating acute and chronic pain.

A moment ago I said YOU were in the field of CP. It is my opinion that we are all responsible for our own health care, and that we should find the best consultants around to help us manage our health, but where the rubber meets the road, the final decisions lie with you. It's your body, and it's you who are feeling the pain. 

Once again, educate yourself to the highest level possible. Read, read, read. Ask questions.  Ask Why and Why Not, especially when dealing with medical pros who are reluctant to treat your pain effectively, when dealing with pharmacists who look at you like you are a criminal when you present a legal Rx for a controlled substance, who may refuse to fill your script, or try to convince you to take less than prescribed. That's called practicing medicine without a license and is illegal in every state I'm familiar with. Yet, it is done every day. 

It is still a hard road for many people to obtain adequate pain relief in this country, and that's a damn shame, but an educated patient is better equipped to develop this type of patient/doctor relationship which I describe. I've been working with my pain docs in this manner for many years, and when you get there, you will realize that it is the only way to. You do not have to suffer, but you do have to prepare yourself. 

Hang in the Lizzie. If I didn't get to all your questions, I apologize. Maybe I'l catch you next time I'm in town.

Keep learning.



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