Opiods for Pain Control

* (generic) next to the brand name means that it is available in generic form.

Opioid Treatment for Chronic Pain

The benefits of opioid maintenance therapy are substantial. The overwhelming majority of patients appear not only to obtain significant pain relief, but to take advantage of their freedom from disabling pain to become more physically active, more socially productive, and to live a generally more fulfilling life. Unfortunately, this treatment also entails a number of risks. The medications have a variety of dangerous side effects: 
sedation, respiratory depression, and death from overdose. These side effects pose a risk not only to the patient, but to others who may be injured if a patient is impaired by the medication or behaves irresponsibly. In addition, such side effects as constipation, nausea, itching, and urinary retention may make opioid medications difficult to tolerate. 

 Finally, the risk of illegitimate use or diversion by patients is a medical, as well as a regulatory, concern. We provide this brochure in the hope of making this treatment as safe as possible. But providing information is not enough. More than in most clinical circumstances, the failure of patients to act intelligently, responsibly, and honestly can lead to disaster. For all of these reasons, patients who undertake opioid maintenance therapy should behave in a way that is beyond reproach or suspicion in all matters relating to their use of medications. Patients who are unwilling or unable to do so jeopardize not only their own health and safety, but the health and safety of other patients with chronic pain.

Approach to Pain Treatment with Opioid Analgesics

Treatment is guided by two factual premises: 1) each patient is unique in his perception of pain and in his response to medications; and 2) there is no limit to tolerance, and therefore, no arbitrary limit to the dose that may be required to achieve pain relief. Accordingly, a patient's response is the ultimate guide to treatment.

To learn from patient response, medication trials must be conducted in a systematic and disciplined way. We try to help patients to become sophisticated and disciplined observers and reporters of their physical symptoms and of their responses to medications. These reports allow us to adjust medication and dose to achieve optimal pain control with minimal side effects at the least expense.

This brochure provides an overview of opioid maintenance therapy. We begin with the medications and a description of some of their clinically important characteristics.
We proceed with a description of the three stages of opioid maintenance therapy:   initiation, titration, and maintenance. We conclude with a discussion of the management of common opioid side effects and the management of the withdrawal syndrome.

The Opioid Medications

The mainstay of pain management of intractable pain is provided by opioid medications. These medications are also referred to as narcotics. Although they are marketed under a number of brand names, the list is relatively short. The ones used most frequently in our practice include the following:
Generic  listed first
Morphine Sulfate
                                MSIR, MS Contin, Oramorph Methadone
                                        Dolophine Oxycodone
                                        Roxicodone, Percolone, OxyContin
Hydromorphone
                                  Dilaudid, Levorphanol   

Other opioids are commonly prescribed for the management of pain. However, our belief is that these medications should be used less frequently and in restricted dose, or should be avoided altogether. Demerol (Meperidine), for example, is unsuitable for chronic administration, as it can lead to the accumulation of a toxic metabolite which predisposes to seizures. Medicines containing Acetaminophen (Percocet, Lorcet, Vicodin, Tylenol #3 or #4) are toxic to the liver in high doses, and my lead to kidney damage, if taken chronically.

These medications all work to relieve pain in the same way--by attaching to opioid receptors on nerve cells, which causes a decrease in the transmission of pain impulses to the brain. These medications differ in strength, in duration of action, and in their side effects. And, as noted above, individuals differ in their reactions to the same medication. One important characteristic of opioid medications is that they are capable of inducing tolerance. Tolerance refers to a decrease in the effect of a drug in response to repeat exposure. As applied to opioids, this means that after a few days to a few weeks of exposure to a particular dose of medication, that dose becomes less effective in relieving pain. It also becomes less likely to cause nausea, fatigue, euphoria, or respiratory depression.
The flip side of this is that it takes more medication to achieve the same level of pain relief.

Fortunately, tolerance to most side effects develops before tolerance to the pain relieving properties of these medications.
Most patients become tolerant to the depressing effect of these medications on respiratory drive early in the course of treatment. Early tolerance to respiratory depression makes these medications safer than is commonly believed and provides for a considerable range of safe dosing. Tolerance to one medication may lead to partial tolerance to one of the others. This is often referred to as cross-tolerance.

The clinical implications of tolerance and cross-tolerance are:
1. Once a medication has been found that provides pain relief, it is likely to continue to provide pain relief if the dose is increased to compensate for tolerance.
2. Side effects noted during the initial period of exposure to a medication are likely to disappear with continued use.
Individuals vary in the extent to which they become tolerant to these medications. Some maintain adequate pain relief at modest doses for very long periods of time. Others require doses to be raised frequently to maintain effect.

It is our experience, however, that most patients reach a plateau within the first few months of treatment, after which only small adjustments in dose are necessary. Even at high doses, these medications do not appear to cause organ damage. Their side effects are reversed after the medication is discontinued.

Supplemental Medications

A variety of non-opioid medications are used in chronic pain treatment. Some are used to treat related symptoms, like muscle spasm. Others are used to enhance the effectiveness of the opioids or to counteract their side effects.

Below is a list of the symptoms most commonly associated with chronic pain or with opioid medications.
Constipation
Insomnia
Decreased Libido                                                   
  Itching
Depression                                                           
  Loss of Menstrual Period
Difficulty Urinating                                                   
Muscle Spasm or Jerking
Fatigue
Nausea and Vomiting
Fluid Retention
Weight Gain or Loss
Headache
Withdrawal Syndrome

This list is not exhaustive, but its very length should give an idea of the complexity of managing chronic pain patients. Each of the medications used to treat opioid side effects may cause new side effects or interact with other medications. In the "Treatment of Common Side Effects"section, we review in detail most of these side effects and the medications used to treat them. It should be clear that managing pain with opioids can become a complex matter and that a cautious and systematic approach is needed to find the optimal therapeutic regimen.

Finding the Right Dose

To find the medication or combination of medications which provides the best pain relief with the fewest side effects at the lowest cost requires a careful process of medication trials and dosage adjustments--aided by precise record- keeping of the time and dose of medication, the degree of pain relief, and the occurrence of side effects. To prepare for this process please review the Medication Log Instructions and the sample Medication Log.

The general strategy is to begin treatment with short-acting opioids (Morphine, Roxicodone, or Dilaudid) trying one medication at a time. Begin with a low test dose to make sure that the medication has no serious or intolerable side effects. If it does have a bad effect, put the medicine aside and try the next one.
If the initial dose is well tolerated, but fails to produce significant pain relief, try a dose 50-100% higher 3-4 hours later.
If the second dose is well tolerated but ineffective, 3-4 hours later try a third 50 % higher than the second dose.
With each dose, reevaluate the degree of pain relief and the presence of side effects and keep a record of your response.

Once a pain relief response has been achieved at a particular dose, repeat that dose as you notice the level of pain begin to rise. This usually occurs within 4 to 6 hours. Again, record the time you take the medication, the degree and duration of pain relief, and any side effects. Adjust the dose up or down, depending on the degree of pain relief and the presence of side effects. If a medication causes noticeable sedation, discontinue the medication or decrease the dose. If your companion observes that you are very sedated and not easy to arouse, this is an emergency requiring medical supervision. As a general matter, if a given dose has been well- tolerated for a period of days, but becomes progressively less effective, it is safe to increase the dose by 50%. If a medicine provides less than satisfactory pain relief or unpleasant side effects, put it aside and repeat the process with a different medication.

After your tolerance to short acting medications has been demonstrated, it may be possible to achieve equivalent pain relief with fewer doses of medication by substituting an equivalent long- acting opioid medication (methadone, MS Contin, OxyContin, Kadian, or Duragesic). These long- acting medications may be supplemented with rescue doses of short-acting medicines to control break- through pain.
If methadone is used, wait three days before making each upward dose adjustment. This is because methadone's slow excretion may lead to increasing serum levels over two or three days on constant dosing. The rising serum level may sneak up on patient, leading to increasing sedation and respiratory depression.

Many patients have had prior experience with opioid medications for pain relief. For patients who know which medication has worked well in the past, we begin with that medication at the dose to which you have become accustomed. However, if the prior medication contained Acetaminophen (Percocet, Vicodin, Lorcet, or Tylenol #3 or #4), we reduce the dose to allow no more than 4 grams per day of Acetaminophen. If the reduced dose is ineffective, supplement the prior medication with an opioid that does not contain Acetaminophen. Again, begin with 1 tablet, assess the response, and make adjustments as described above. This process is not so complicated in practice as it may seem in this description.
During the first weeks of treatment, you will become familiar with the medications and the record-keeping system. If you have any questions or problems, we are always available to help you.

The Management of Opioid Maintenance

After an effective dose of medication is determined, patients generally obtain reliable pain control by repeating the customary dose in a routine pattern, varying the timing or dose only to accommodate changes in activity level or exacerbations of pain. Although the choice of medicine and dose are relatively routine during this phase, circumstances arise which require adjustments in the regimen or more aggressive clinical support.
First, new side effects may emerge or become clinically more significant with prolonged opioid administration and their treatment may require dosage adjustment or the addition of adjunctive medications. Second, the underlying condition causing pain may worsen, requiring new evaluation and therapeutic intervention. And third, a patient may experience new medical or psychological symptoms the evaluation and treatment of which is complicated by the medications to treat pain.

To ensure patient safety, continued routine patient reporting and monitoring is required during this phase. Patients are asked to report not only on their medical conditions and medication requirements, but on any changes in their activity, employment, or social situation. By systematic monitoring, we hope to increase our understanding of the clinical, social, and economic consequences of opioid maintenance therapy. To facilitate reporting and monitoring, we have designed Interval Report Forms that patients and physicians are asked to fill out and submit on a monthly basis.

Possible Side Effects of Opioids

Opioid medications are associated with a number of side effects.
This section will review the most common problems that patients encounter and how to respond to them.

Constipation
Patients with chronic pain often have constipation as a side effect of their medications. Constipation may produce nausea, vomiting, and abdominal cramping pain. The strategy for managing constipation from chronic opioid maintenance is to follow a regimen on a routine basis to counteract the constipating effect of the opioid medication. For many patients, a diet high in certain fruits or cereals is sufficient. Many patients find that laxatives are necessary, however.
The following laxatives have been found to be effective: Senekot, PeriColace (Docusate Plus Casanthrol), Milk of Magnesia, Maalox (or generic equivalent), and Dulcolax tablets or suppositories. The laxatives should be taken in whatever dose is necessary to provide regular BMs. Do not wait for a crisis. For patients who do not respond to conventional measures of diet and over-the- counter laxatives, Mestinon 60 mg, ½ -1 tab 3-4 times daily may be effective. This medicine, normally used to treat Myasthenia Gravis, has a direct effect on the muscles of the bowel to counteract the constipating effect of the opioids. It also relieves the dry mouth often associated with opioid therapy.
If your bowels have not moved for a number of days, you may try a higher dose than usual of your customary laxative. If constipation is associated with severe nausea or vomiting, use an enema (tap water, soap suds, or commercial Fleet's enema) to relieve the obstruction from below. If these measures are ineffective, seek medical attention.

Decreased Libido
Men may lose interest in sex or suffer from decreased potency with chronic opioid use.   In most cases, this is due to suppression of testosterone production and can be reversed by administering supplemental testosterone as an oral tablet or as an injection.

Depression
Just as chronic pain may lead to depression and a sense of hopelessness, pain relief may bring a renewed sense of vitality and enjoyment of life.  If pain relief and increased activity do not by themselves relieve depression, antidepressant medications may be useful.  The selection of the right medication is a trial and error process made more complicated by interactions between pain medications and the antidepressant medicines.  Occasionally, depression may be caused or worsened by tranquilizing medications like Valium or Klonopin.  Discontinuing such medication is the first step in evaluating and treating depression.

Edema (fluid retention)
Many patients on opioids develop swelling in their feet and lower legs. This may be a response to increased fluid intake to relieve a chronically dry mouth, or it may be due to fluid retention or vascular dilatation caused by opioids. In either case, the treatment is a low salt diet and the restriction of fluid intake. The patient should also lie down in bed with legs raised on pillows until the edema disappears. If these measures are ineffective, a diuretic, such as Demadex , Maxzide, Aldactone, or Lasix, may be added. Headache
Opioids may trigger vascular headaches, characterized by a sense of heaviness or throbbing in the back of the skull or in the forehead and temples. Often these headaches will respond to Acetaminophen (Tylenol), Aspirin, or Ibuprofen (Advil or Motrin). In susceptible patients, opioids can trigger Migraines. Ritalin may prevent or abort these headaches.

Insomnia
Paradoxically, insomnia is often a side effect of opioid medication. If it is found that one of the opioids causes sedation (usually Methadone or Morphine), this medication may be reserved for use at bed time. If a patient awakens in pain, a long acting form of Morphine may be used at bedtime (MS Contin). Increasing the level of physical activity and exercise helps to promote sleep, as does keeping to a consistent schedule. Some patients have benefited from Melatonin, the hormone the body produces to induce sleep, which is available without a prescription.
If these strategies are not successful, insomnia may be treated with medication which do not have a significant risk of respiratory depression. The anti-depressant medications, such as Desyrel (Trazadone) 50-100 mg or Pamelor(Nortriptyline) 25-50 mg at bed time are safe for this purpose. In many patients the use of stimulants, such as Ritalin or caffeine, early in the day may improve sleep at night by promoting daytime physical activity and, perhaps, as a rebound effect from the stimulant. Occasionally, such sedating medicines as Valium or Serax (Oxazepam) may be necessary, although these medications pose a higher risk of respiratory depression and are often associated with worse pain control and psychological depression.

Itching and Skin Rash
Itching without a rash is a pharmacological side effect of opioid medication rather than a true allergic reaction. It will respond to treatment with Vistaril 25 mg or Benadryl 25 mg every 4-6 hours. As tolerance to the medication develops, the itching will usually become less or cease altogether. Itching associated with a rash is an allergic symptom. When this occurs, the offending medication should be discontinued and an alternative substituted.

Nausea and Vomiting
Nausea and vomiting are among the most frequent early side effects of opioid treatment. Nausea and vomiting can arise from a direct effect of opioids on the brain, or from constipation. If the nausea is mild it may be controlled by decreasing the dose or frequency of opioid medication and by taking Vistaril 25 mg 1 tab every 4-6 hours as needed. An alternative medication is: Phenergan 25 mg 1 tab every 4-6 hours. Nausea usually disappears as patients become tolerant to the medication that causes it, but some patients are unable ever to tolerate certain of the opioid medications. During the initial medication trial, if a medication causes significant nausea, that medication should be stopped and an alternative tried instead.
Although all of the opioids can cause nausea and vomiting, Hydromorphone (Dilaudid) and Levorphanol (LevoDromoran) seem to do so less frequently. Severe nausea and vomiting to the point that a patient is unable to keep any liquids down is a serious medical situation that requires evaluation by a physician. Some patients may require IV fluids to maintain hydration. These symptoms may indicate serious conditions other than opioid toxicity, such as bowel obstruction, stomach ulcers, Acetaminophen toxicity, or gastroenteritis.

Sedation
Although sedation is a common side effect during the initiation of opioid treatment, particularly with Methadone and Morphine, this symptom often becomes less troubling as tolerance to the medication develops. However even for opioid-tolerant patients, the addition of Muscle Relaxants, such as Soma, (Carisoprodol) and Tranquilizers, such as Valium, Klonopin, Ativan (Lorazepam) may have an exaggerated sedative effect. Patients on opioids should also abstain from alcohol. Excess sedation may be manifest by slurred speech, poor balance and coordination, and excessive sleepiness. These symptoms may indicate significant danger, as in some cases, excess sedation may proceed to respiratory depression and death. Such medication may also impair memory and judgment and the ability to recognize the above symptoms in one's self.

Anyone with a history of sleep apnea (pauses in respiration for 15-20 seconds during sleep) should not take these medications. Spouses, room-mates, or close friends should be advised to seek medical assistance if they observe any of the above signs of excess sedation. These medications should be used sparingly, in the minimum dose and frequency to relieve symptoms.

Withdrawal Syndrome
Anyone who has been taking opioid medication routinely is likely to suffer withdrawal symptoms if the medication is abruptly discontinued. Occasionally, the withdrawal syndrome occurs as a side effect of taking Talwin (Pentazocine) a pain medication that has opioid antagonist activity. The intensity and duration of the syndrome varies from person to person, depending on the dose of medication they routinely take. The acute symptoms may last from a few days to more than a week.
The most common symptoms of withdrawal are: increased pain, generalized aching, cold sweats, restlessness, tremors, involuntary movements, dizziness, nausea, vomiting, diarrhea, sneezing and yawning. The syndrome can be stopped by resuming opioid medications. If you anticipate discontinuation of opioids, the withdrawal syndrome can be made more tolerable by gradually tapering the dose. A reduction of 10-20 % of the initial dose every 3-6 days will reduce the severity of the withdrawal syndrome. The addition of Clonidine 0.1-0.3 mg 1-2 tabs every 6-8 hours will further mitigate symptoms. Clonidine is also available as a transdermal administration in the Catapress TTS patch. Restlessness and tremors respond to tranquilizers, such as Valium 5-10 mg every 6 hours.

To avoid running out of medications and suffering unplanned withdrawal symptoms, take precautions to avoid loss, keep track of your rate of utilization of medication, order refills in a timely manner, and maintain a reserve supply for emergencies. The development of severe nausea and vomiting may make it impossible for a patient to take his or her customary medications. As noted above, inability to take food or fluids that doesn't resolve in a few hours requires medical attention to maintain hydration and to administer opioids by means of injection. For patients who suffer frequently recurrent nausea and vomiting, the Duragesic Patch may provide an alternative route of opioid administration. MS Contin, OxyContin, and Methadone may be administered rectally, if oral administration is not tolerated.

  This article was written by Dr. William Hurwitz
http://www.drhurwitz.com/Opioid_Therapy_FAQ_F rame.htm

PAIN RELIEF PUMP #1449
Television News Service/Medical Breakthroughs
©Ivanhoe Broadcast News, Inc. July 1999

When fighting a painful, terminal condition, prolonging life is just one
battle. The other is maintaining a decent quality of life. According to
a Wake Forest University pain specialist, about 20 to 30 percent of
terminal patients don't get adequate pain relief. Others can't tolerate
their side effects. Now there's a new method of pain relief for these
patients.

With painful cancer inside his bones, Bill Webster can't get around like
he used to. That doesn't stop him from going places. "A lot of times I
imagine I'm on a trip, going to Tennessee or somewhere," says Bill.

 Bill's got something inside that helps him control the pain that not
many other Americans have -- a morphine pump beneath his skin. He says,
"I don't know it's there until I use it. It's just part of my body."

Richard Rauck, M.D., a pain specialist at Wake Forest University's
Baptist Medical Center in Winston-Salem, N.C., headed a clinical trial
at the university to test the new device. He expects FDA approval by
January 2000.

"I can give somebody like Bill about one one-hundredth of the amount of
morphine he would take by mouth or even through an intravenous line.
It's a much more powerful way to deliver the morphine," say Dr. Rauck.

Bill pushes buttons through his skin. One dose of morphine travels from
the implanted pouch straight into his spinal cord. The pouch holds 50
doses and is refilled by syringe once a month.
Dr. Rauck says, "Before now, patients either stayed in very bad pain, or
they were almost anesthetized or asleep all the time." That's not the
life Bill wants. He's ready to roll.

The pump has a built-in safety mechanism that keeps the patient from
being able to overdose on the medication. It only allows a dose to be
given every 60 to 90 minutes. The manufacturer of the device expect it
to be available this winter.

If you would like more information, please contact:

Wake Forest University/Baptist Medical Center

Health on Call
Medical Center Blvd.
Winston-Salem, NC 27157
(800) 446-2255

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