|
Although researchers are working hard to determine the exact neurologic and chemical pathways for pain, much remains to be discovered about its physiology and the chemicals that can facilitate or block it. This article provides an update on new medications and new delivery systems that have resulted from the ongoing study of pain.
Proven Options
The standard opioids, morphine, hydromorphone and fentanyl, are considered first-line therapies for severe pain. For moderate pain, combination medications such as acetaminophen with codeine (Tylenol #3), acetaminophen with hydrocodone (Vicodin, Lortab, Norco), acetaminophen with oxycodone (Percocet) and other oxycodone-containing medications (Oxycontin) are among the first choices.
The World Health Organization (WHO) stepwise approach to choosing an analgesic medication provides some direction about which type of medication to choose for pain complaints.
Level 1 pain medications for mild pain include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) - including the nonselective NSAID ibuprofen and the COX-2 selective celecoxib (Celebrex) - and adjuvant medications such as antidepressants and antiseizure medications (gabapentin or duloxetine).
Level 2 medications for moderate pain are the short-acting combination medications, such as hydrocodone-oxycodone combinations (Lortab, Vicodin, etc.), oxycodone (Oxycontin), oxymorphone-containing medications (Opana) and tramadol (Ultram). Level 3 medications for severe pain include opioids such as morphine, hydromorphone (Dilaudid), methadone (Dolophine) and fentanyl (Duragesic).
When using this ladder, two important steps are determining which level of pain medication to use and deciding whether to continue adjuvant pain medications once opioid medications are increased.1 Selecting a medication that reflects the level of pain the patient reports is a way to meet the need with the best choice.
New Medications
Research by IMS Health Inc. shows that short-acting combination pain medications such as Tylenol #3 and hydrocodone with acetaminophen are among the most commonly prescribed medications in this country. Most patients have at some time used a short-acting opioid to relieve pain associated with surgery or injury. New extended-release opioid medications are becoming available to enhance medication choices when long-term therapy is needed for chronic, persistent pain. As with any new medication for pain, patient selection is critical.
Combunox
One of the most recent combination medications to pair an opioid with a nonopioid is Combunox. This medication combines 5 milligrams of oxycodone with 400 milligrams of ibuprofen and is intended for acute moderate to severe pain.2 The maximum time for use is 7 days.2
This medication contains the highest amount of ibuprofen of any combination medication. The combination of the two medications creates a synergistic effect that provides a greater level of pain relief than if the two drugs were taken independently for pain relief. This is the greatest advantage of short-acting combination medications.
The biggest concern with Combunox is its NSAID component. Research shows that gastrointestinal (GI) bleeding is a common side effect of NSAID use.3 Adding a proton pump inhibitor such as omeprazole (Prilosec) will only provide protection for the upper GI system, leaving the lower GI system vulnerable to asymptomatic ulceration.4
When prescribing this medication, caution patients to report any signs or symptoms of GI bleeding: bright red blood in the stools, hematemesis or black, tarry stools.
Patients with cardiovascular disease are not good candidates for Combunox because of potential increased risk for myocardial infarction or stroke as a result of its ibuprofen component.5
Frova
Migraines are caused by triggers such as estrogen fluctuation, alcohol, caffeine, stress, aged foods or food additives. During a migraine, the blood vessels in the head dilate, causing pain. Symptoms include throbbing on one side of the head, changes in vision and flickering lights, spots or lines, often called an aura. For some women, migraine is linked with menstruation and therefore occurs monthly. Approximately 21 million U.S. women report experiencing migraine regularly. Of these, 12.3 million report menstrual migraines.6
For many migraine patients, triptan medications such as sumatriptan (Imitrex) may control the effects of migraine. Frovatriptan succinate (Frova) is a new triptan medication for menstrual migraine. It is not an appropriate treatment for tension or cluster headaches. Each tablet contains 2.5 milligrams of drug; the maximum daily dose is three tablets in a 24-hour period. Women should take the first tablet at the onset of headache.
Frova is not recommended for all women affected by menstrual migraine. Patients who experience basilar migraines and patients who have uncontrolled hypertension, a history of stroke or circulation problems are not good candidates. Frova should not be taken in combination with other serotonin receptor agonist medications or medications that are ergot derivatives, such as Bellergal (a combination of ergotamine, belladonna alkaloids and phenobarbital).
New Extended-Release Formulations
In other developments in pharmacologic pain management, old medications have taken on a new look and current medications have been formulated into extended-release versions.
Consider prescribing an extended-release formulation for a patient who has daily consistent pain and has reached the total daily maximum dose of acetaminophen (4,000 milligrams per day) or is taking six tablets of a short-acting combination medication such as acetaminophen and hydrocodone. An extended-release medication provides a more consistent level of pain relief without the frequent dosing of short-acting medications, which can provide a cyclic peak-and-trough effect rather than a steady level of pain relief. When converting to an extended-release opioid medication, prescribe short-acting medication for breakthrough pain coverage.
Medications that have taken on a new look are tramadol (Ultram) and acetaminophen with hydrocodone (Vicodin). Ultram ER is now available in a 100-milligram tablet that is dosed once per day; the maximum dose is 300 milligrams per day. Ultram has the properties of an opioid (it is a mu agonist drug) and a selective serotonin reuptake inhibitor (SSRI).3 Tramadol is recommended to treat pain on level 2 of the WHO analgesic ladder (moderate pain). It is not a scheduled drug.
Adjusted dosing of tramadol may be necessary for some patients. Because it is metabolized through the kidneys, patients with kidney disease or liver disease should be dosed at a lower level. Elderly patients should receive lower doses because of their slower metabolism.3
An extended-release formulation of acetaminophen and hydrocodone is awaiting FDA clearance. This form of one of the most popular pain medications would have a great impact on patients who have consistent daily pain and require an extended-release medication.
The newest addition to the extended-release medication group is oxymorphone HCL (Opana). Opana is available in immediate-release and extended-release formulations (Opana ER), and an intravenous form is also available for the management of acute pain.
Opana ER is designed for patients who require pain control over the course of the day and night. It is dosed on a 12-hour schedule or twice per day. Opana and Opana ER have been studied in patients with cancer, chronic pain and postoperative pain.7-9
The ability to prescribe both long-acting and short-acting formulations of the same drug, oxymorphone, is an attractive option based on preliminary experience in clinical settings. Opana ER and Opana contain the oxymorphone molecule, just as oxycodone and oxycontin do. Many polymorphisms exist in the mu binding sites for opioids. When one type of opioid works well for a patient, it is useful to have two types of the same formulation available - one that can provide shorter action for breakthrough pain and one that can provide extended pain relief if needed.
New Transdermal Options
Transdermal patches have been in the news recently due to concerns about the safety aspects of this delivery system. At least 100 patients have died while using patches of all types (fentanyl, estrogen, etc.). Some of these deaths occurred in people who did not heed warnings about temperature; heat increases the absorption rate of the medication.10 Other deaths occurred as a result of exposure to used patches, which contain enough leftover medication to harm a child or small pet.10 For all patients who use transdermal therapies, patient education about how to use and dispose of the patches is essential.
Two very different patches for pain relief are in development, an opioid and an NSAID. A sufentanil (Sufenta) patch is being developed for use in patients who have chronic moderate to severe pain and are opioid dependent and opioid responsive.11 The sufentanil patch is similar to the fentanyl patch in concept and uses a transdermal delivery system, but the medication in the sufentanil patch lasts up to 7 days. This will allow a patient who needs continuous pain relief over extended periods to experience more consistent relief for a longer time.
The pending NSAID patch, consisting of ketoprofen (Orudis), is placed directly over the site of pain. The ketoprofen patch is designed to treat minor injuries such as sprains and soft tissue injuries. Ketoprofen is a nonselective NSAID currently available in oral form only. The advantage to a transdermal delivery system for an NSAID is the avoidance of systemic uptake and side effects such as GI bleeds.12 As this article went to press, the ketoprofen patch was in phase III clinical trials.
New Classes and Medications
Cannabinoids have long been considered drugs of abuse rather than medications that could be used to treat pain. That perception is changing.
Dronabinol (Marinol), a marijuana extract, is a prescription medication designed to control chemotherapy-related nausea in oncology patients. It has been available in the United States for several years. Sativex, a cannabinoid medication used to treat chronic neuropathic pain in multiple sclerosis patients, was recently introduced in Canada.13 Its application for FDA clearance in the United States is pending. This drug uses pain relief pathways in a manner similar to opioids. Sativex targets receptor sites in the brain, spinal cord and peripheral afferents. It also has a significant anti-inflammatory effect. The drug has been compounded so that it produces no psychoactive effect.
Sativex is supplied as an oromucosal spray. Current indications for use include neuropathic pain resulting from multiple sclerosis and other neuropathic pain syndromes. Side effects noted with the use of this drug are bad taste, dry mouth, dizziness, nausea and fatigue.
Another unique medication is administered intrathecally using implanted pumps. Ziconotide (Prialt) is derived from the venom of the conus magnus sea snail found in the waters surrounding the Philippine Islands. Prialt is a nonopioid that halts pain by blocking the presynaptic calcium channel neurotransmitters from the primary afferent nerve endings. Prialt has been studied in patients with chronic pain, and they have reported good to excellent pain control compared with placebo.
Prialt is started at low doses (<2.4 micrograms per day) and should not be titrated more than 2.4 micrograms per day. The maximum recommended daily dose is 19.2 micrograms per day. Reported side effects include headache, somnolence, nystagmus, asthenia and pain. The package insert contains a warning about the potential for severe psychiatric symptoms and neurologic impairment, so patients with a preexisting history of psychosis are not candidates for treatment with Prialt.14
New Delivery Methods
Fentanyl is a unique pain medication in that it degrades in the acidic fluids of the stomach. An oral route is not possible for this drug. Fentanyl is available for transdermal use as Duragesic and for buccal and sublingual absorption as fentanyl oralets (Actiq). It is also available in effervescent tablets as Fentora. A second sublingual form, Rapinyl, is in phase III clinical trials.
Fentanyl oralets were developed for breakthrough pain in opioid-dependent patients with cancer. The patient rubs an oralet on the buccal membrane, where the medication is rapidly absorbed. These oralets are available in several strengths, starting with 400 micrograms.
The newest form of fentanyl for breakthrough pain is the effervescent tablet. OraVescent is a new delivery system for fentanyl. The patient places the tablet along the buccal membrane, where an effervescent reaction speeds absorption of the medication.15 Studies presented to the FDA show that the onset of pain relief can occur within 15 minutes. The tablets are well tolerated, and clinical trial patients were observed carefully for any signs of respiratory depression.
Another form of fentanyl, Rapinyl, is a sublingual tablet that is also indicated for opioid-tolerant patients with cancer.16
New Delivery Systems
On-Q C-bloc. Regional anesthesia techniques such as continuous peripheral nerve blocks are recommended for adjunct pain relief by the American Society of Anesthesiologists.17 The On-Q C-bloc system from I-Flow allows a patient with a peripheral nerve catheter to administer additional doses of a local anesthetic as needed. The concept is similar to patient-controlled analgesia, but instead of delivering opioid medication, the On-Q delivers local anesthetic, most commonly bupivacaine. (The original On-Q delivered anesthetic at a preset rate.)
The original On-Q pump has a small, ball-shaped reservoir attached to a nerve catheter. This catheter is located along the femoral nerve for patients who have had total knee replacements and intra-articularly for patients who have undergone shoulder surgery. For patients who have had major abdominal surgery, it is threaded along a surgical incision. Research involving orthopedic patients determined that the On-Q system provides adequate pain relief.18,19
The aspect of this treatment that some patients particularly appreciate is the decreased need for opioids. Patients who are using the On-Q system find it helpful as an adjunct to standard pain medications. The addition of the C-bloc feature allows the patient to have additional control over the amount of local anesthetic being delivered by the system.
Ionsys. Another novel patient-controlled medication delivery system is the Ionsys. This transdermal administration system uses fentanyl. Ionsys is about the size of a credit card, requires no pump, and uses a small battery for power.20-22 The patient wears it on the arm or chest, providing easy access to activate it and deliver a dose of medication. The device contains 40-microgram doses of fentanyl that can be self-delivered every 10 minutes up to six times per hour.22 Surgical patients are good candidates for Ionsys, but only after pain management is achieved in the immediate postoperative period.
The device has a digital display that indicates how many doses of medication a patient has taken. After the medication is depleted, the device automatically shuts off. The biggest advantage to this system is the freedom it gives the patient. He or she is not tied to a pump, and there are no additional lines to become tangled in. The adverse event profile is similar to that associated with all opioids. Nausea, headache, pruritis, vomiting, constipation and dizziness are the most common complaints.22
Putting It Into Practice
The need for more and better pain medications, along with ways to deliver them, will probably always exist. Each year, many medications enter clinical trials and do not succeed in getting to market. For chronic pain patients who use pain medications regularly, the approval of new choices is good news. Neuropathic pain patients in particular welcome the addition of new medications such as Sativex, since this form of pain is so difficult to treat. In addition, new delivery systems are improving the quality of pain relief and can contribute to patient satisfaction with pain management in acute care settings.
As medications evolve and new techniques are developed, pain management may become easier for those who experience pain as well as those who treat patients with pain.
Yvonne D'Arcy is an adult nurse practitioner who specializes in pain management and palliative care at Suburban Hospital in Bethesda, Md. She is the author of Pain Management: Evidence-based Tools and Techniques for Nursing Professionals (HC Pro Publishing; 2007).
The author has completed a disclosure statement and reports the following: advisory and speaker bureau roles with Endo Pharmaceuticals, Pricara (unit of Ortho-McNeil), Abbott Laboratories and Pfizer Inc.
|