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The use of pharmacologic agents for the control of pain is not limited to the use of narcotics or opioids. Many non-opioid medications are effective against moderate to severe pain. Since many of these medications are available over the counter (OTC), we tend to perceive them as less effective. In fact, the salicylates (such as aspirin), acetaminophen and ibuprofen are very important tools for the control of pain. They can be given alone, or given in conjunction with opioids to provide better pain relief with fewer side effects.
Salicylates, acetaminophen and other NSAIDs act peripherally by inhibiting prostaglandins. This prevents the transmission of noxious stimuli. Since they act peripherally, they have few central nervous system (CNS) side effects. They do not cause drug tolerance or respiratory depression. However, most cause irritation of the gastric mucosa and increased bleeding times. Certain NSAIDs are more effective for some types of pain than others. Individuals may respond to one NSAID and not another. For this reason, it is important to try several before giving up on them.1
In general, all of the drugs in this group have three separate actions: anti-inflammatory, antipyretic and analgesia. They are especially useful for pain that is secondary to inflammation, such as arthritis and muscle-skeletal injuries. Since each of the drugs in this category have slightly different uses, doses and side effects, it is important to review them all. As nurses, we tend to look up the drugs we do not know. When was the last time you looked up aspirin or acetaminophen? Since we use these medications frequently, we probably have not reviewed them in quite a while.
Salicylates (aspirin). The analgesic action of aspirin is due to inhibition of prostaglandins. It decreases pain perception by decreasing the sensitivity of peripheral pain receptors. It reduces fever by promoting vasodilation and sweating, which increases heat loss. Aspirin decreases capillary permeability, which prevents leakage of fluid into surrounding tissue. In this way, it controls inflammation. Aspirin is indicated for the treatment of mild to moderate pain, especially the pain due to inflammation. Aspirin is used to treat headaches, arthralgia, dental pain, dysmenorrhea, rheumatoid arthritis and osteoarthritis. In patients with rheumatoid arthritis, aspirin decreases pain, swelling, fever, tenderness and morning stiffness. It also has been shown to increase mobility and grip strength.
Aspirin is well absorbed via the GI tract. The small intestine is the primary site of absorption. Aspirin is available as tablet, liquid and suppository. The oral forms are available in chewable, extended-release and enteric-coated tablets. The usual dose for an adult is 325-650 mg every 4-6 hours. Aspirin is also found in several creams and ointments used for muscle and arthritis pain. Dosages in children are weight-dependent. When taken orally the analgesic action begins in about 30 minutes, peaks in 1-3 hours and lasts about 3-6 hours. When given rectally the effect begins in 1-2 hours, peaks in 4-5 hours, and lasts about 7 hours.
Side effects of aspirin include tinnitus and hearing loss (dosage-related), gastric irritation, GI bleeding, dyspepsia and nausea. Since aspirin also prevents platelet aggregation, it prolongs bleeding times. Persons at risk for bleeding, or those taking anticoagulants, should avoid aspirin and aspirin products. Other drug interactions include corticosteroids, methotrexate and other NSAIDs.2
Acetaminophen. Unlike aspirin and the other NSAIDs, acetaminophen has no anti- inflammatory properties. It is useful as an analgesic and antipyretic. It is rapidly absorbed from the GI tract. Acetaminophen is useful for the treatment of mild to moderate pain. It is often used when patients are unable to tolerate salicylates or other NSAIDs. Like aspirin, it is useful as a concomitant treatment for patients who are on opioids. It increases the analgesic action of opioids without the need to increase the opioid dose. Like aspirin, it acts peripherally while the opioids act centrally. This combination allows for more analgesic effect without increasing the incidence of side effects such as drowsiness and respiratory depression.
Acetaminophen is indicated for the relief of mild to moderate pain of low intensity. Since it has little anti-inflammatory effect, it is not as useful for pain caused by inflammation as the other NSAIDs. However, acetaminophen does not increase bleeding times and rarely causes GI distress. One precaution that the nurse must consider is the use of acetaminophen, or products which contain acetaminophen, for patients with liver disease.
Acetaminophen is toxic to the liver in large doses. Since it is metabolized in the liver, persons with liver disease build up toxic levels quickly. Acetaminophen at normal doses does not interact with other medications. For these reasons, it is often preferred over aspirin and NSAIDs.
Acetaminophen is available in liquid, tablet and suppository form. The normal adult dose is 325-650 mg every 4-6 hours. Dosages for children are based on weight.
Acetaminophen is also used in many combination drugs such as Darvocet-N 100, Vicodin, Fioricet, and Percogesic.3 When using these combination drugs, care must be taken when increasing dosages not to exceed toxic levels of acetaminophen. For example, if Darvocet-N 100 is not effective at one tablet every 4-6 hours, increasing it to two tablets would increase the acetaminophen dose from 2600-3900 mg to 5200-7800 mg. For this reason, it is especially important that nurses be aware of the individual ingredients in each combination drug which they administer.4
Diclofenac sodium (Voltaren). Like aspirin, Voltaren has analgesic, antipyretic, and anti-inflammatory actions. Its mechanism of analgesic action is the inhibition of prostaglandins which inhibits pain impulses at the peripheral site. Voltaren is useful for the treatment of dysmenorrheal, pain from dental surgery, muscle-skeletal pain associated with strains and sprains, rheumatoid arthritis and osteoarthritis. It has been shown to decrease pain and stiffness associated with arthritis. Voltaren dosage is 100-200 mg per day in divided doses of 50-75 mg b.i.d. or t.i.d. Like aspirin, Voltaren causes gastric distress, may increase bleeding times and can result in GI bleeding.5
Diflunisal (Dolobid). Dolobid has analgesic and anti-inflammatory properties. It is not as useful as aspirin for the control of fever. As an analgesic, its onset of action takes longer than aspirin, but it has a longer duration. Dolobid is useful for the treatment of mild to moderate pain. The side effects are similar to those of aspirin. It interacts with anticoagulants, antidiabetic agents (especially tolbutamide), acetaminophen and other NSAIDs. An initial loading dose of 1 gm is given, followed by 500 mg every 8 hours.6
Indomethacin (Indocin). Indocin has been found to be very useful for the treatment of moderate to severe pain. Indocin is also useful as an anti-inflammatory and antipyretic agent. It is available in tablet, extended release and suppository. It is rapidly absorbed via the GI tract. Indocin is used for management of pain from rheumatoid arthritis, osteoarthritis, bursitis, tendinitis and gouty arthritis. Indocin is a very effective analgesic, however, it has a high incidence of side effects. It causes GI distress, nausea, diarrhea and GI bleeding. It also has CNS side effects such as morning headaches, insomnia and vertigo. Indocin may increase serum potassium and should be monitored closely. It interacts with anticoagulants, alcohol, NSAIDs, lithium, and methotrexate and should be used with caution in these patients.
The usual dose of Indocin is 25-50 mg b.i.d. or t.i.d. As with other NSAIDs, Indocin should be taken with food to decrease gastric upset. The extended release form should not be used for the treatment of gouty arthritis.7
Ketoprofen (Orudis). Orudis is another NSAID with properties similar to aspirin. It has anti-inflammatory, antipyretic and analgesic properties. It is useful for the treatment of mild to moderate pain associated with dental surgery, post-partum pain, muscle-skeletal pain of sprains and strains, rheumatoid arthritis and osteoarthritis.
The analgesic effect of Orudis lasts longer than either aspirin or codeine. It has less side effects than other NSAIDs. The side effects seem to be dose-related and include dyspepsia and GI upset. It has also been associated with insomnia, nervousness and headaches. Drug interactions are similar to other NSAIDs. The normal dose of Orudis is 50-75 mg every 6-8 hours.8
Naproxen (Naprosyn, Anaprox). Naproxen has the same action of the other NSAIDs. It is useful for the treatment of mild to moderate pain, especially muscle-skeletal pain, pain associated with soft tissue inflammation, gouty arthritis, rheumatoid arthritis and osteoarthritis. It is also helpful for the treatment of headaches, pain from dental surgery and visceral pain from cancer.
Side effects of naproxen include headache, drowsiness, constipation, heartburn and nausea. It may reactivate ulcers and result in GI bleeding. Dose for treatment of mild to moderate pain is 250-500 mg b.i.d. of naproxen or 275-550 mg b.i.d. of naproxen sodium. When used for the treatment of gouty arthritis a 750 mg loading dose is given, followed by 250 mg every 8 hours.9
Ketorolac tromethamine (Toradol). Toradol has properties similar to other NSAIDs. It is available in oral and parenteral forms. The anti-inflammatory effect is greater than that of naproxen and Indocin. Toradol is rapidly absorbed. When given I.M. it has an onset of action of 10 minutes, a peak of 75-150 minutes, and a duration of 6-8 hours. Oral Toradol has an onset of 30-60 minutes, a peak of 1.5-4 hours and a duration of 6-8 hours. Toradol I.M. is only indicated for short-term treatment of pain. A loading dose of 30-60 mg I.M. is followed by 5-10 mg p.o. every 6-8 hours.
Toradol is useful for the treatment of moderate to severe pain. It may be as effective as Morphine or Demerol and does not cause respiratory depression or sedation. Toradol can be used in conjunction with opioids for the treatment of severe pain. Toradol is helpful for the management of orthopedic pain and visceral pain associated with cancer. It has less incidence of side effects than other NSAIDs. 10 Recently Toradol has been approved for intravenous (I.V) use. When given intravenously, 15-30 mg can be given I.V push over at least 15 seconds. Patients over 65 should be given 15 mg. Dosage should not exceed 60-120 mg per day.11
Meclofenamate sodium (Meclomen). Meclomen acts peripherally by inhibiting the synthesis of prostaglandins. It has excellent anti-inflammatory properties. As with other NSAIDs, it also has antipyretic and analgesic properties. It is used for the treatment of mild to moderate pain associated with rheumatoid and osteoarthritis. Side effects include diarrhea (usually dose-related), reoccurrence of ulcer disease, dizziness and headache. Adverse effects can be minimized by taking this drug with food. The usual dose is 200-300 mg per day in divided doses.12
Piroxicam (Feldene).Feldene has properties and actions similar to the other NSAIDs discussed. It acts peripherally to close the pain gates. Feldene is useful for the treatment of rheumatoid arthritis, osteoarthritis and gouty arthritis. This drug has a long half-life, and often the effectiveness improves over time. The normal dose is 10-20 mg once a day. Side effects and interactions appear to be the same as for most other NSAIDs.13
Sulindac (Clinoril). Sulindac is similar to Indocin. It is useful for the treatment of arthritis, bursitis, tendinitis and the pain of gouty arthritis. GI side effects are most common with sulindac, however they are less severe than the side effects associated with aspirin. The dose ranges from 300-400 mg in divided doses (150-200 mg b.i.d.).
There are new NSAIDs coming on the market all of the time. One problem for the practitioner is availability of NSAIDs due to cost containment. Many hospital pharmacies carry only two or three NSAIDs for use. In many cases, Toradol is either not available or is available only parenterally.14
Acetaminophen and the NSAIDs are useful in mild to severe pain management alone and in conjunction with opioid analgesics. They are an essential part of the three-step analgesic ladder recommended by the World Health Organization for the treatment of cancer pain. (AHCPRNo. 94-0593:6) A dosing chart for the use of these drugs is included. It is available from the US Department of Health and Human Services, Agency for Health Care Policy and Research.15'16 According to the American Pain Society, all analgesic regimens should include a NSAID. The public and nurses often underestimate the effectiveness of NSAIDs in providing pain relief. We are especially skeptical of medications that can be purchased OTC. However, research has demonstrated their usefulness (See Acute Pain Management, Bl. Pharmacologic Interventions chart from The US Department of Health and Human Services). NSAIDs are recommended for use in patients with post-operative pain, cancer pain, dysmenorrhea, migraines, arthritis pain and low back pain.
NSAIDs are not without side effects. The most common problems are GI upset, increased bleeding and renal toxicity. Aspirin is a very effective analgesic and anti-inflammatory drug However, since it inhibits platelet aggregation and can increase bleeding times, it should be used with caution in persons who are taking anticoagulants or those with a history of ulcer disease. A good history is essential prior to establishing any pain relief plan. Acetaminophen is probably the least likely OTC medication to cause GI upset. It has no effect on bleeding times. However, it has no anti-inflammatory properties. This makes it less effective against pain that is due to inflammation. Ibuprofen has both analgesic and anti-inflammatory properties and causes fewer side effects than aspirin, however it may still affect bleeding times and should be used with caution in persons with a history of ulcer disease or persons using anticoagulants.
Some NSAIDs are less likely to cause bleeding or renal dysfunction. Drugs such as Trilisate, Disalcid and Relafen are effective analgesics with fewer side effects and are often the drug of choice in patients with bleeding, renal or ulcer problems. Indocin is one of the most effective NSAIDs, but because of its high incidence of side effects must be used with caution. It is probably not advisable to use it more than a few days. Toradol is also a very effective analgesic. It has advantages over other NSAIDs because it is available in parenteral and oral forms. When given parenterally, for short-term pain relief it has few side effects. We have found Toradol to be very effective in treating pain symptoms in the emergency room. In many cases it is as effective as opioids, and it does not produce CNS side effects.
Table 4. Dosing Data for NSAIDs
| Drug | Usual adult dose | Usual pediatric dose1 | Comments |
| Oral NSAIDs | |||
| Acetaminophen | 650-975 mg q 4 hr | 10-15 mg/kg q 4 hr | Acetaminophen lacks the peripheral anti-inflammatory activity of other NSAIDs |
| Aspirin | 650-975 mg q 4 hr | 10-15 mg/kg q 4hr2 | The standard against which other NSAIDs are compared. Inhibits platelet aggregation; may cause postoperative bleeding |
| Choline magnesium trisalicylate (Trilisate) | 1000-1500 mg bid | 25 mg/kg bid | May have minimal anti-platelet activity; also available as oral liquid |
| Diflunisal (Dolobid) | 1000 mg initial dose followed by 500 mg q 12 hr | ||
| Etolodac (Lodine) | 200-400 mg q 6-8 hr | ||
| Fenoprofen calcium (Nalfoa) | 200 mg q 4-6 hr | ||
| Ibuprofen (Motrin, others) | 400 mg q 4-6 hr | 10 mg/kg q 6-8 hr | Available as several brand names and as generic; also available as oral suspension |
| Ketoprofen (Omdis) | 25-75 mg q 6-8 hr | ||
| Magnesium salicylate | 650 mg q 4 hr | Many brands and generic forms available | |
| Meclofenamate sodium (Meclomen) | 50 mg q 4-6 hr | ||
| Mefenamic acid (Ponstel) | 250 mg q 6 hr | ||
| Naproxen (Naprosyn) | 500 mg initial dose followed by 250 mg q 6-8hr | 5mg/kg q 12 hr | Also available as oral liquid |
| Naproxen sodium (Anaprox) | 550 mg initial dose followed by 275 mg q 6-8 hr | ||
| Salsalate (Disalcid, others) | 500 mg q 4 hr | May have minimal antiplatelet activity | |
| Sodium salicylate | 325-650 mg q 3-4hr | Available in generic form from several distributors | |
| Parenteral NSAID | |||
| Ketolorac tromethamine (Toradol) |
30 or 60 mg IM initial dose followed by 15 or 30 mg q 6 h. Oral dose following IM dosage: 10 mg q 6-8 hr | Intramuscular dose not to exceed 5 days | |
| Note: Only the above NSAIDs have PDA approval for use as
simple analgesics, but clinical experience has been gained with other drugs
as well. 1 Drug recommendations are limited to NSAIDs where pediatric dosing experience is available. 2 Contraindicated in presence of fever or other evidence of viral illness. |
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1 Selected references are included in this Clinical Practice Guideline. More
complete references are available; see Acute Pain Management Guideline Panel.
Acute Pain Management: Operative or Medical Procedures and Trauma. Guideline
Report. AHCPR Pub. No. 92-0022. Rockville, MD: Agency for Health Care
Policy and Research, Public Health Service, U.S. Department of Health and
Human Services. In press.
2 See type of evidence key following the page after B2.
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1 Selected references are included in this Clinical Practice Guideline. For more complete references, see: Acute Pain Management Guideline Panel. Acute Pain Management: Operative or Medical Procedures and Trauma. Guideline Report. AHCPR Pub. No. 92-0022. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services. In press.
2 Insufficient scientific evidence is available to provide specific recommendations regarding the use of hypnosis, acupuncture, and other physical modalities for relief of postoperative pain.
Type of Evidence — Key
| la | Evidence obtained from meta-analysis of randomized controlled materials. b Evidence obtained from at least one randomized controlled trial. |
| IIa | Evidence obtained from at least one well-designed controlled study without randomization. |
| b | Evidence obtained from at least one other type of well-designed quasi-experimental study. |
| Ill | Evidence obtained from well-designed nonexperimental studies, such as comparative studies, correlational studies, and case studies. |
| IV | Evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities. |
In addition to acetaminophen and NSAIDs, several other drugs have been found to be useful for the treatment of pain. These are referred to as adjuvant drugs. These drugs are given to enhance opioid action for the relief of pain. They treat associated symptoms and side effects. Many also have pain relief properties of their own. See Management of Cancer Pain.
Corticosteroids decrease inflammation, stimulate appetite, decrease nausea and elevate mood. These effects are especially useful when treating persons with pain related to terminal cancer. It is especially useful for the pain associated with brain metastasis as well as spinal cord compression. Side effects of steroids must be monitored closely. Steroids may cause fluid retention and hyperglycemia. Side effects are associated with length of therapy.17
Anticonvulsants. Neuropathic pain is often successfully managed with the addition of anticonvulsants. Patients receiving carbamazepine or phenytoin need to be monitored closely for signs of toxicity. It may be contraindicated in patients who have undergone bone marrow transplants.18 Tegretol and Klonopin have been used to treat pain associated with peripheral nerve syndromes. (See Table 2. Common cancer pain syndromes due to peripheral nerve injury.)
Antidepressants. Tricyclic antidepressants such as amitriptyline, doxepin, imipramine, and trazodone are useful for the treatment of cancer pain. These drugs have analgesic properties of their own and they potentiate the effects of opioids. They also enhance mood, which can result in increased appetite, decreased depression and improved quality of life. The antidepressant of choice is amitriptyline. It has several side effects that nurses need to assess for and manage. They can cause dry mouth, constipation and urinary retention. The analgesic effect of these medications is usually not seen for several weeks after they are added to the regimen.19 Tricyclics are used for the treatment of dull, aching or burning neuropathic pain.
Neuroleptic Agents. These medications include the major tranquilizers. The drug of choice is methotrimeprazine. This drug has analgesic and antiemetic properties that make it useful for the treatment of cancer pain. Disadvantages are that currently this drug must be given I.M. It also causes sedation and hypotension.20
Benzodiazepines. Medications such as Valium, Librium, Ativan and Halcion have been found to be useful in the management of pain by decreasing anxiety that may actually be increasing pain perception. Side effects include weakness, vertigo, nausea and vomiting. Since these medications cause sedation, they must be used cautiously in patients receiving opioids. For this reason, benzodiazepines are not recommended for use in the treatment of cancer pain.21 They are effective for the treatment of pain related to muscle spasm.
| Drug | Approximate adult daily dose range | Route of administration1 | Type of Pain |
| Corticosteroids | |||
| Dexamethasone | 16-96 mg | PO, IV | Pain associated with brain metastases and epidural spinal cord compression |
| Prednisone | 40-100 mg | PO | |
| Anticonvulsants | |||
| Carbamazepine3 | 200-1,600 mg | PO | Neuropathic pain |
| Phenytoin4 | 300-500 mg | PO | |
| Antidepressants | |||
| Amitriptyline5 | 25-150 mg | PO | Neuropathic pain |
| Doxepin6 | 25-150 mg | PO | |
| Imapramine7 | 20-100 mg | PO | |
| Trazodone8 | 75-225 mg | PO | |
| Neuroleptics | |||
| Methotrimeprazine9 | 40-80 mg | IM | Analgesia; sedation; antiemetic |
| Antihistamincs | |||
| Hydroxine10 | 300-450 mg | IM | Adjuvant to opioids in post-operative and other types of pain; relief of complicating symptoms including anxiety, insomnia, nausea |
| Local anesthetics / antiarrythmics | |||
| Lidocaine11 | 5 mg/kg | IV/SC | Neuropathic pain |
| Mexiletine12 | 450-600 mg | PO | |
| Tocainide13 | 20 mg/kg | PO | |
| Psychostimulants | |||
| Dextroamphetamine14 | 5-10 mg | PO | Improve opioid analgesia, decrease sedation |
| Methylphenidate15 | 10-15 mg | PO | |
| Source: AHPCR No. 94-0592 1 PO=orally. IV=intravenously.
IM=intramuscularly. SC=subcutaneously. |
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Coanalgesics are called adjuvants. These are medications that were not intended for analgesic relief, but have been found useful for some types of pain. They are typically used to treat chronic pain syndromes. Their effectiveness varies depending on the origin of the pain. The onset of analgesia is delayed and may not occur for several weeks.
Another classification of drug used for the treatment of pain is potentiator. These drugs are thought to increase the analgesic effect of other medications. For many years it was thought that Phenergan potentiated opioid analgesia. However, recent studies have found that it is not an effective potentiator and it increases the CNS side effects of the opioid. Phenergan is probably not effective unless it is being used to control nausea. It is not recommended by the American Pain Society.22
Vistaril and Atarax have demonstrated analgesic properties. They are effective as potentiators. However, Vistaril and Atarax are usually given I.M. and are very irritating to the tissue. If you have ever had an injection of Vistaril, you know how painful it can be. If the patient can take fluids by mouth, the preferred route of administration is oral. When giving it I.M., change the needle after drawing it up and use the Z-tract method of administration. Problems associated with the use of Vistaril and Atarax are the increased sedation the drugs cause. Patients need to be monitored closely.23
Other drugs which may be effective potentiators include dextroamphetamine and Ritalin. Caffeine has also been suggested as a potentiator. It is especially effective when combined with aspirin or acetaminophen. Studies suggest that caffeine potentiates not only the analgesia effect but also the anti-inflammatory effect of NSAIDs.24
Review of Non-Opioid Pharmacology
Answer each of the following questions:
Answers
1. e
2. c
3. c
4. c
5. b
6. d
7. b
8. b
9. a
10. c
11.a
12. d
13. d
14. c