The healthcare industry is putting new emphasis on pain management; some clinicians have called for pain to be regarded as "the fifth vital sign," and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has begun to consider a facility's pain-management practices as one of the standards for accreditation. Smaller surgical incisions and regional anesthesia have gone a long way toward helping clinicians decrease or eliminate their patients' pain, but pre-emptive and intra-operative measures often aren't enough. That's when oral pain medications can make a huge difference in making the post-operative period much less traumatic. Over the past five years, drug companies have developed a variety of oral pain medications that relieve pain faster and more completely, with fewer side effects. In this article, we'll tell you what you need to know about five of the most common oral pain meds your surgeons and/or anesthesiologists may be prescribing.

OxyContin
Pharmacology: OxyContin is a sustained-release version of oxycodone, an opioid that is a morphine-derivative. It works by altering and dulling pain signals in the brain and spinal cord and provides analgesic effects similar to those of codeine or methadone. OxyContin delivers the same level of pain relief as oxycodone, but the pill has a time-release mechanism to deliver pain-relief over a longer period of time. In the US, OxyContin is only approved for oral intake. In Europe, oxycodone is approved for IV use.

Intended Use: OxyContin is generally used as a baseline drug for chronic pain, such as cancer-related pain. However, according to Armen Ketchedjian, MD, an anesthesiologist in New Rochelle, NY, OxyContin is being used "more and more for treating post-operative pain."

In terms of treating acute pain, OxyContin is primarily prescribed for treating moderate to severe post-operative pain, particularly after certain orthopedic procedures, such as total joint replacements. Says Jeffrey Katz, MD, assistant professor and director, VA Pain Center, Northwest University Medical School, "We're in a center where patients experience massive amounts of pain following a total knee replacement," he says. "Their pain lasts for many days after surgery, including when the patient is involved in aggressive post-op physical therapy. That's why OxyContin is useful-it provides the sustained, powerful pain management that these patients need."

In general, a physician may prescribe OxyContin for post-operative pain over several days or weeks. Although OxyContin is not the preferred method for treating post-operative pain in most outpatient orthopedic procedures, such as ACL or shoulder surgery, short-term release oxycodone (in the form of Percocet or Percodan) is very common. OxyContin may in some instances be given to patients in extreme post-op pain following an outpatient procedure, with the intention of having him or her re-evaluated and put on a more regular analgesic regimen.

Dr. Ketchedjian reports that oxycodone is suitable for treating so-called "breakthrough pain" (or short-term elevations of pain) because of its rapid onset (about 20 to 30 minutes) and short duration (two to four hours). The rapid-release version of oxycodone is available under the brand name Oxy IR.

Benefits: In addition to its potent pain-killing properties, experts agree that the sustained-release mechanism of OxyContin makes it potentially more effective than other opioids. Says Dr. Katz, "It makes a lot more sense to give a patient OxyContin twice a day, instead of other pain-killing pills every few hours."

A study of 106 patients published in the March 27, 2000 edition of Archives of Internal Medicine concluded that "around-the-clock controlled ?release oxycodone therapy seemed to be effective and safe," adding that analgesia was maintained during long-term therapy.

Risks and Side-Effects: OxyContin has become a rather controversial drug because of media reports of its widespread abuse and the diversion of the medication as a street drug [see sidebar]. Experts agree, however, that as long as the drug is prescribed and taken responsibly, the chance of addiction is low.

The medication produces typical opioid side-effects during short-term and long-term usage. The most common side-effect of OxyContin is constipation, according to Alan Marco, MD, an anesthesiologist at the Medical College of Ohio, in Toledo. It can also cause respiratory depression, excessive drowsiness, light-headedness, nausea, and itching, he says. "Oxycodone and its variations affect the part of the brain that control respiration-that's why labored or slow breathing is a side-effect of the drug. These side-effects primarily occur when the drug is administered in large doses, but their significance should not be minimized." In unusual cases, opiates such as oxycodone can also slow the heartbeat because decreased breathing can easily lead to low blood oxygen and low blood oxygen can slow the heart rate. This is much more likely to occur in pediatric cases, because of kids' higher metabolic rate.

In addition to the potential special considerations with using oxycodone for children, there may also be issues concerning the elderly. Says Robert Catania, MD, an assistant professor at Brown University Medical School, "This is anecdotal evidence-I don't know of clinical data that supports this- but I have observed a difference with elderly patients. I have actually had to admit several patients in their 70s and up for confusion which resolved after stopping the OxyContin."

Percocet
Pharmacology: Percocet is a combination medication used to relieve moderate to severe post-operative pain. It contains oxycodone and acetaminophen. Percocet is similar to Percodan, which contains oxycodone and aspirin. The two drugs are detoxified by the liver and excreted via the kidneys. Other brand names for the same combination of drugs are Tylox and Roxicet.

Intended Uses: Percocet is widely prescribed to treat post-operative pain after a host of outpatient procedures, especially minimally-invasive procedures. It takes effect in about 15 minutes and lasts an average of four to six hours, depending upon the patient and the dosage (Dr. Ketchedjian notes that the usual dose is one to two tablets every three to four hours).

Says Dr. Marco, "This is one of the most common pain relief medications, along with Vicodin, Vicoprofen, and drugs that contain codeine. The decision of whether to prescribe a Percocet-type drug or something like Vicoprofen often has to do with the patient's reaction toward acetaminophen versus ibuprofen. " For reasons that we will discuss shortly, several of the experts we consulted prefer ibuprofen-based medications to acetaminophen or aspirin, as long as the patient does not have contraindications to ibuprofen.

Benefits: Percocet provides fast-acting pain relief and sedation; its two active agents used in tandem provide a more dramatic effect than when they are administered separately, according to Dr. Marco."The benefit of the combination of the two is that they act together to modulate or inhibit what I call ?evil humors,' which are the body's natural responses to painful stimuli," he says. "The drug inhibits the pathway of prostaglandins through the central nervous system and, at the same time, alters the perception of pain." He adds that Percocet may be a good option for patients who are intolerant of ibuprofen.

With Percocet, it is possible to achieve the same basic clinical effect produced by administering oxycodone and acetaminophan or an non-steroidal anti-inflammatory drug (NSAID) separately. Dr. Martin notes, for example, that this strategy is often used when treating cancer patients, so as not to cause kidney distress.

Another benefit of Percocet is its convenience in terms of documentation requirements when administered on-site (this may vary by state). Says John Abenstein, MD, anesthesiologist at the Mayo Clinic, "It's just easier to give a patient Percocet than fill out documentation in triplicate."

Risks and Side-Effects: According to the experts with whom we spoke, Percocet's biggest disadvantage is the fact that it contains acetaminophen. Says Dr. Katz, "We've got patients on large doses of OxyContin, with no problems whatsoever. But large doses of your basic Tylenol-type of medication can cause all sorts of problems. Acetaminophen is very hard on the liver. It's only safe to take four grams of acetaminophen in a day. Beyond that, there's a risk of liver toxicity."

Dr. Ketchedjian agrees, adding that due to liver-related concerns, a large segment of the medical community has withdrawn from using Percocet to treat chronic pain.

Experts report that Percocet mostly commonly produces the following side-effects: constipation, drowsiness, lightheadedness, shortness of breath, stomach distress, and nauseau and/or vomiting. Central nervous system depression can occur with high doses and/or if the patient has also taken antihistamines and/or drunk alcohol. Certain drugs, such Pentazocine and Nalbuphine may decrease Percocet's analgesic effects.

David Martin, MD, PhD, Mayo Clinic, identifies the following contraindications for Percocet:

• Patients who cannot take oxycodone, acetaminophen, and/or aspirin.
• Patients with a history of substance abuse. Due to the presence of oxycodone, Percocet has higher abuse potential than non-opiate pain relievers.
• Patients with asthma, urticaria, or certain types of allergies (the drug contains sodium metabisulfate, which can cause allergic reactions).

Vicoprofen
Pharmacology: Vicoprofen is an opiate/NSAID combination drug. In this case, the opiate is hydrocodone and the anti-inflammatory agent is ibuprofen. Like oxycodone, hydrocodone has similar effects on the body to codeine. Hydrocodone is also found in the well-known oral painkiller, Vicodin (hydrocodone and aspirin).

Experts disagree about whether there is a significant difference between hydrocodone and oxycodone. Dr. Abenstein thinks not. "In spite of what manufacturers will tell you, opiates differ only in two ways from one another-potency and speed of interaction. In the case of hydrocodone and oxycodone, I don't see much difference." Dr. Ketchedjian, however, believes that hydrocodone is a milder opiate than the oxycodone found in Percocet.

Intended Uses: Like Percocet, Vicoprofen is geared to relieve moderate pain and, when used post-operatively, is primarily intended for short-term use. Dr. Katz says it's generally taken for about five to ten days post-op. Dr. Ketchedjian prescribes it primarily for tackling moderate post-op pain, finding it most effective after orthopedic procedures. He recommends that patients be instructed to take the medication on a full stomach, to reduce the chances of irritation of the stomach lining. Vicroprofen starts to work within 30 minutes and lasts about four to six hours. The typical adult dosage is one tablet every four to six hours. Patients should not take more than four tablets in a 24-hour period.

Benefits: Because it does not contain acetaminophen or aspirin, experts such as Dr. Marco feel that Vicoprofen is safer on the liver than Percocet-like drugs, especially when high-dose pain relief is required.

A study of patients with moderate to severe post-operative obstetric or gynecological pain published in the May 22, 2000 issue of Clinical Therapy compared the combination hydrocone and ibuprofen with an oxycodone/acetaminophen combination and placebo. The study concluded that the combination of drugs in Vicoprofen offered an effective "additional option in combination pain therapy." Meanwhile, a study of 125 patients published in the June 2000 edition of the Journal of Oral and Maxillofacial Surgery, comparing Vicoprofen with a codeine/acetaminophen combination and placebo in patients with acute post-operative pain after dental surgery (specifically, molar extraction), concluded that its total analgesic effect, including duration of pain-relief, was superior to both acetaminophen with codeine and placebo.

Risks and Side-Effects: Dr. Martin cautions, "Vicoprofen is not a wonder drug." The medication has most of the same side effects and contraindications of other opiate/NSAID drugs. All NSAIDs have varying degrees of potential renal complications. Dr. Marco reports that patients with kidney problems should use caution in taking Vicoprofen, "although I'm reluctant to say that it's never appropriate." Ibuprofen may also affect blood clotting, causing complications with blood counts. Taken in combination with other NSAIDs or blood thinners, Vicoprofen may increase the possibility of gastrointestinal bleeding.

Various studies suggest that clinicians should use opiates and/or NSAIDs sparingly-or avoid them altogether- with pregnant or nursing women, because the medication can penetrate the placenta. NSAIDs may contribute to premature closure of the baby's ductus arteriosus. Some studies have indicated that the drug can also be passed to the baby in breast milk. Says Dr. Marco, "Avoid ibuprofen-containing compounds like Vicoprofen with pregnant or nursing women. Tylenol is used routinely, but Percocet may be more risky because of the opiates. It should also be said, though, that while opiates can be passed in breast milk, that is not sufficient reason to withhold them in certain pain-treatment cases, such as after a C-section."

Vioxx
Pharmacology: Vioxx, along with Celebrex, is one of the newer oral pain medications; it was first introduced three years ago. Vioxx is an NSAID (the active ingredient is rofecoxib) that works by indirectly inhibiting the formation of prostaglandins (PGs), which are chemicals that sensitize the nerve endings that detect pain. PGs make the area sensitive not only to the pain itself but also to touch; for example, PGs cause the pain and sensitivity that occurs when sunburned skin is touched. Inhibiting the formulation of PGs decreases pain, particularly pain after tissue injury.

Says Dr. Katz: "For many years, it was thought that there was a single enzyme (called a cyclooxygenase or COX enzyme) that produced PGs. In the 1980s, however, researchers discovered that there are actually two COX enzymes that produce prostaglandins. The COX-1 performs many of the housekeeping functions of the body, such as blood clotting and secreting mucous in the stomach to protect the stomach lining. COX-2, however, only appears to be related to pain sensitivity. Targeting just the COX-2 enzyme allows the COX-1 enzyme to keep producing the helpful PGs without compromising on the painkilling effects."

Intended Uses: Besides being used to treat post-op pain that would be considered to be in the mild to moderate range, Vioxx is also being prescribed for chronic osteoarthritis and menstrual pain. The recommended starting dose is 12.5 mg once daily; it can be taken with or without food.

Benefits: A study of 218 patients published in the January 30, 2001 edition of the American Journal of Orthopsychiatry concluded that 50 mg of rofecoxib once daily "effectively treated post-orthopedic surgery pain." Clinically, Vioxx has roughly the same analgesic effect as aspirin, acetaminophen, or ibuprofen.

Experts point to the increased safety profile of Vioxx as its primary benefit over similar pain-killers. Says Dr. Martin, "Because Vioxx and Celebrex only target the COX-2 enzyme, they are gentler on the stomach than NSAIDs that target both COX-1 and COX-2. It's not as clear how these drugs affect the kidneys, however."

Risks and Side-Effects: The side-effects of Vioxx fall in line with other NSAIDs. Says Dr. Martin, "Vioxx is no magic bullet. It may be safer on the stomach than aspirin or acetaminophen, but it can still cause stomach bleeding. It's a relatively rare side-effect but not negligible, either." Other uncommon, but serious reported side effects have included severe allergic reactions and severe liver problems, including hepatitis and jaundice. More common, but less serious, side-effects of Vioxx include upper and/or lower respiratory infection or inflammation, headaches, nausea and/or vomiting, swelling of the hands and feet, diarrhea, and dizziness.

Vioxx is contraindicated for patients with allergies to other NSAIDs, as well as patients with kidney disease, liver problems, high blood pressure, aspirin-sensitive asthma and chronic stomach problems. Like other NSAIDs, it should also be used cautiously, if at all, with pregnant and lactating women.

An article published in the March 15, 2001 issue of Biochemical Pharmacology raised questions as to whether COX-1 enzyme inhibition is actually the primary cause of NSAID-induced GI injury. The study offered the possibility that NSAID-induced side-effects on the gastrointestinal system are mostly due to direct injury to the GI-mucosa and have nothing to do to with the COX-1 enzyme. If so, the GI benefits of Vioxx and Celebrex would be no better or worse than traditional NSAIDs.

Celebrex
Pharmacology: Celebrex, the brand name for celecoxib capsules, is a COX-2 inhibiting NSAID.

Intended Uses: Celebrex is specifically indicated for the treatment of osteoarthritis, rheumatoid arthritis, and polyposis. It is not yet officially approved for treating post-operative pain. However, Dr. Marco opines, "Immediate post-operative pain therapy is definitely a potential additional use of Celebrex. It has the same basic effect as Vioxx, plus they both have a higher safety factor relative to acetaminophen." It can be taken once or twice a day (with or without food), depending on the severity of pain. The general maximum dose is 200 mg, twice a day (although 400 mg, twice a day, may be appropriate if being used for polyposis in the colon).

Benefits: The patient benefits of Celebrex are said to be virtually the same as with Vioxx. However, Dr. Katz says, "recent data has demonstrated that Celebrex may have potential safety advantages over Vioxx in patients with hypertension or compromised renal function."

Risks and Side-Effects: The most common side-effects of Celebrex are indigestion, diarrhea and abdominal pain. According to Dr. Martin, contraindications for Celebrex fall in line with Vioxx and other NSAIDs. Celebrex is specifically contraindicated in patients with allergies to aspirin and sulfoamide medications.

One note about Vioxx and Celebrex: Although the experts we consulted agree that the drugs are effective in combating pain, they disagree about whether they are cost effective. Says Dr. Marco, "Both of these drugs are sort of a mixed blessing. They do have a higher safety profile than some of the drugs with less well-understood actions-we know the pathways they take through the body. However, they tend to be expensive. For relatively healthy patients, I believe that aspirin, acetaminophen or ibuprofen are just as effective. By targeting specific patient populations where the risk is higher, we can better utilize the healthcare dollars that are available."

Dr. Katz, however, believes that the medications are worth their higher price tags. "COX-2 inhibitors justify their costs because of the reduced incidence of side-effects as compared with other NSAIDs. They do cost considerably more than over-the-counter meds like ibuprofen or acetaminophen, but if they keep the patient from being hospitalized, it ends up in the long run to be an economically, as well as medically, smart choice to use them."

Physicians have a plethora of choices for pain relief; the medications they choose for their patients will depend on several factors. Says Dr. Marco, "Some medications are better suited to certain patients after you look at their medical history, especially conditions that would cause contraindications to a medication, and assess their specific pain-management needs."

In the end, however, the choice often depends very little on manufacturers' claims and indications and more on the physician's judgement and experience. As Dr. Abenstein points out, "Most of us in the medical community don't pay close attention to the indication on the label. We look at what the drug does, take our own subjective observations of side effects and prescribe according to our own judgment. Once the drug is available, it's the doctor's call. That's the way medicine actually works." n

Special thanks to Nitin Shah, MD,Associate Clinical Professor, University of California at Irvine.