Pain Management: Nonsteroidal Anti-inflammatory Drugs (NSAIDs) PDF

A pain signal begins at the nociceptors in the periphery and proceeds throughout the CNS. Knowing how and where pharmacologic agents work is essential to controlling pain. The body produces neurohormones called endorphins (peptides) that naturally suppress pain conduction, although the method is not...

A pain signal begins at the nociceptors in the periphery and proceeds throughout the CNS. Knowing how and where pharmacologic agents work is essential to controlling pain. The body produces neurohormones called endorphins (peptides) that naturally suppress pain conduction, although the method is not completely understood. Opioids such as morphine activate the same receptors as endorphins to reduce pain. NSAIDs control pain at the peripheral level by blocking the action of cyclooxygenase, a pain-sensitizing chemical, and interfering with the production of prostaglandins. Cortisone decreases pain by blocking the action of phospholipase, reducing the production of both prostaglandins and leukotrienes. NONSTEROIDAL ANTIINFLAMMATORY DRUGS NSAIDs include aspirin and aspirin-like drugs that inhibit the enzyme COX, which is needed for the biosynthesis of prostaglandins. Chapters 25 and 40 present expanded discussions of NSAIDs in their roles as analgesics and anticoagulants, respectively. These drugs may be called prostaglandin inhibitors with varying degrees of analgesic and antipyretic effects, but they are used primarily as antiinflammatories to relieve inflammation and pain. Their antipyretic effect is less than their antiinflammatory effect. With several exceptions, NSAID preparations are not suggested for use in alleviating mild headaches and mildly elevated temperature. Preferred drugs for headaches and fever are aspirin (adults only for fever), acetaminophen, and ibuprofen. NSAIDs are more appropriate for reducing swelling, pain, and stiffness in joints. Most NSAIDs cost more than aspirin. Other than aspirin, the only NSAIDs that can be purchased over the counter (OTC) are ibuprofen and naproxen. All other NSAIDs require a prescription. Examples of prescription products on the market that contain NSAID contents alone or in combination include celecoxib, meloxicam, oxaprozin, nab-umetone, sulindac, and ketorolac. If a patient can take aspirin for the inflammatory process without gastrointestinal (GI) upset, salicylate products are usually recommended. There are six groups of NSAIDs: 1. Salicylates 2. Para-chlorobenzoic acid derivatives, or indoles 3. Propionic acid derivatives 4. Fenamates 5. Oxicams 6. Selective COX-2 inhibitors NONOPIOID ANALGESICS Nonopioid analgesics such as aspirin, acetaminophen, ibuprofen, and naproxen are less potent than opioid analgesics and are used to treat mild to moderate pain. Nonopioids are usually purchased over the counter, but cyclooxygenase 2 (COX-2) inhibitors require a prescrip-tion. Nonopioids are effective for the dull, throbbing pain of headaches; dysmenorrhea (menstrual pain); inflammation; minor abrasions; muscular aches and pain; and mild to moderate arthritis. Most analgesics also have an antipyretic effect and will lower an elevated body tem-perature. Some, such as aspirin, have antiinflammatory and antiplatelet effects as well. Nonsteroidal Antiinflammatory Drugs All NSAIDs have an analgesic effect as well as an antipyretic and antiin-flammatory action. NSAIDs such as aspirin, ibuprofen, and naproxen can be purchased as over-the-counter (OTC) drugs. Aspirin, a salicylate NSAID, is the oldest nonopioid analgesic drug still in use. Adolf Bayer marketed the original formulation in 1899, and currently aspirin can be purchased under many names and with added ingredients. The American Academy of Pediatrics, Centers for Disease Control and Prevention (CDC), US Food and Drug Administration (FDA), National Reyes Syndrome Foundation, US Surgeon General, and World Health Organization (WHO) recommend aspirin products not be given to children and adolescents younger than 19 years of age during episodes of fever or viral illnesses because of the danger of Reye syndrome. Reye syndrome is a rare but serious condition associated with viral infections treated with salicylates that causes swelling of the brain and liver. In these circumstances, acetaminophen is recommended instead of aspirin.In addition to its analgesic, antipyretic, and antiinflammatory properties, aspirin decreases platelet aggregation (clotting). Some health care providers may therefore prescribe one 81-mg, 162-mg, or 325-mg aspirin tablet every day or one 325-mg tablet every other day as a preventive measure against transient ischemic attacks (TIAs, or ministrokes), heart attacks, or any thromboembolic episode. Aspirin is discussed in depth in Chapter 24 along with other NSAIDs. Aspirin and other NSAIDs relieve pain by inhibiting biosynthesis of prostaglandin by different forms of the COX enzyme. As explained in Chapter 24, NSAIDs inhibit or block both COX-1 and COX-2 enzymes, whereas COX-2 inhibitors are selective and only inhibit COX-2 enzyme. Inhibition of COX-1 decreases protection of the stomach lining, whereas inhibition of COX-2 decreases inflammation and pain. As a result of an NSAID's inhibition of COX-1, gastric irritation and bleeding may occur. Aspirin is the drug of choice for alleviating pain and inflammation in arthritic conditions, but when given in high doses, severe gastrointestinal (GI) irritation and possible ulceration develop in approximately 20% of patients. Side Effects and Adverse Reactions A common side effect of NSAIDs is gastric distress, including anorexia, nausea, vomiting, and diarrhea. These drugs should be taken with food, at mealtime, or with a full glass of fluid to help reduce this problem. Excessive bleeding might occur as a side effect if an NSAID is taken for dysmenorrhea during the first 2 days of menstruation. Adverse effects of salicylate toxicity include tinnitus, vertigo, hyperventilation, and potential metabolic acidosis. Some patients are hypersensitive to aspirin. Dyspnea, broncho-spasm, and urticaria are some of the symptoms that indicate anaphylaxis to salicylate products. Certain foods also contain salicylates: prunes, raisins, paprika, and licorice. Those with a hypersensitivity to aspirin and salicylate products may be sensitive to other NSAIDs. This hypersensitivity may be related to inhibition of the COX enzyme by the salicylate. It is recommended that aspirin not be given to children or adolescents unless specifically directed by a health care provider because of the danger of Reye syndrome. Acetaminophen The analgesic acetaminophen, a para-aminophenol derivative, was first marketed in the mid-1950s as an analgesic and antipyretic drug used for muscular aches and pains, and for fever caused by viral infections in infants, children, adults, and older adults. It is a popular nonprescription drug; it constitutes 25% of all OTC drugs sold. Acetaminophen is a nonopioid drug, but it is not an NSAID. Because acetaminophen does not have the antiinflammatory properties of aspirin, it is not the drug of choice for any inflammatory process. Acetaminophen is a safe, effective drug when used at therapeutic doses, causes little to no gastric distress, and does not interfere with platelet aggregation. Complementary and Alternative Thera-pies: Capsaicin describes the use of these products in pain relief. An intravenous (IV) formulation of acetaminophen was approved by the FDA for treating pain and fever. It should be administered undiluted over 15 minutes. There is no link between acetaminophen and Reye syndrome, and unlike aspirin and NSAIDs, it does not increase the potential for excessive bleeding if taken for dysmenorrhea Pharmacokinetics. Acetaminophen is well absorbed from the GI tract. Rectal absorption may be erratic because of the presence of fecal material or a decrease in blood flow to the colon. Because of acetaminophen's short half-life, it can be administered every 4 hours as needed with a maximum dose of 4 g/day for adults. However, it is suggested that a patient who frequently takes acetaminophen limit the dose to 2000 mg/day (2 g/day) to avoid the possibility of hepatic or renal dysfunction. More than 85% of acetaminophen is metabolized to drug metabolites by the liver. Large doses or overdoses can be toxic to the hepatic cells, so when large doses are administered over a long period, the serum level of acetaminophen should be monitored. The therapeutic serum range is 10 to 20 mcg/mL. Hepatic enzyme levels (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP]) and serum bilirubin should also be monitored. Ingesting alcohol concurrently with acetaminophen may lead to hepatic injury, hepatic failure, and death. When acetaminophen toxicity occurs, acetylcysteine is the antidote, which reduces liver injury by converting toxic metabolites to a nontoxic form. Pharmacodynamics. Acetaminophen weakly inhibits prostaglandin synthesis, which decreases pain sensation. It is effective in eliminating mild to moderate pain and headaches and is useful for its antipyretic effect. Acetaminophen does not possess antiinflammatory action. Severe adverse reactions may occur with an overdose, so acetaminophen in liquid or chewable form should be kept out of children's reach. Side Effects and Adverse Reactions An overdose of acetaminophen can be extremely toxic to liver cells; death could occur in 1 to 4 days from hepatic necrosis. If a child or adult ingests excessive amounts of acetaminophen tablets or liquid, a poison control center should be contacted immediately, and the child or adult should be taken to the emergency department. Early symptoms of hepatic damage include nausea, vomiting, diarrhea, and abdominal pain. Acetylsalicylic acid( ASA)Pharmacokinetics. Aspirin is well absorbed from the GI tract (Prototype Drug Chart: Aspirin). It can cause GI distress, which includes anorexia, nausea, vomiting, diarrhea, and abdominal pain, so it should be taken with water, milk, or food. The EC or buffered form can decrease gastric distress. EC tablets should not be crushed or broken. Aspirin has a short half-life. It should not be taken during the last trimester of pregnancy because it could cause premature closure of the ductus arteriosus in the fetus. Children with flu symptoms should not take aspirin because it may cause the potentially fatal Reye syndrome. Hypersensitivity to Salicylate Products Patients may be hypersensitive to aspirin. Tinnitus (ringing in the ears), vertigo (dizziness), and bronchospasm-especially in asthmatic patients—are symptoms of aspirin overdose or hypersensitivity to aspirin. Salicylates are present in numerous foods such as prunes, raisins, and licorice, and in spices such as curry and paprika. Propionic Acid Derivatives The propionic acid group is a relatively new group of NSAIDs. These drugs are aspirin-like but have stronger effects and create less GI irrita-tion. Drugs in this group are highly protein bound, so drug interactions might occur, especially when given with another highly protein-bound drug. Propionic acid derivatives are better tolerated than other NSAIDs. Gastric upset occurs, but it is not as severe as with aspirin and indomethacin. Severe adverse reactions such as blood dyscrasias are not frequently seen. Ibuprofen is the most widely used propionic acid NSAID, and it may be purchased OTC in lower doses (200 mg). Prototype Drug Chart: Ibuprofen details the pharmacologic behavior of ibuprofen. Five other propionic acid agents are fenoprofen calcium, naproxen, ketoprofen, flurbiprofen, and oxaprozin. Pharmacokinetics. Ibuprofens are well absorbed from the GI tract. These drugs have a short half-life but are highly protein bound. If ibuprofen is taken with another highly protein-bound drug, severe side effects may occur. The drug is metabolized in the liver to inactivate metabolites and is excreted as inactive metabolites in the urine. Pharmacodynamics. Ibuprofen inhibits prostaglandin synthesis and is therefore effective in alleviating inflammation and pain. It has a short onset of action, peak concentration time, and duration of action. It may take several days for the antiinflammatory effect to be evident. Many drug interactions are associated with ibuprofen. Because ibuprofen can increase the effects of warfarin, sulfonamides, many of the cephalosporins, and phenytoin, it should be avoided with these drugs. However, when taken with aspirin, its effect can be decreased. Hypoglycemia may result when ibuprofen is taken with insulin or an oral hypoglycemic drug, and risk of toxicity is high when ibuprofen is taken concurrently with calcium channel blockers. Use of NSAIDs in Older Adults Older adults frequently use NSAIDs to treat pain associated with inflammation caused by osteoarthritis, RA, and neuromuscular-skeletal disorders. As older adults age, the number of drugs taken daily increases; therefore drug interactions are more common, especially when numerous drugs are taken with NSAIDs. With the use of NSAIDs, GI distress-including ulceration-is four times more common in older adults, and hospitalization is often necessary. The introduction of COX-2 inhibitors (second-generation NSAIDs) has decreased the incidence of GI problems associated with NSAID use; however, edema is likely to occur. Renal function should be eval-uated, and older adults should increase their fluid intake for adequate hydration. To decrease possible complications, the NSAID dose should be lowered. Nonsteroidal Antiinflammatory Drugs Dong quai, feverfew, garlic, ginger, and ginkgo may cause bleeding when taken with nonsteroidal antiinflammatory drugs (NSAIDs). OPIOID ANALGESICS Opioid analgesics, called opioid agonists, are prescribed for moderate and severe pain. In the United States the Harrison Opioid Act of 1914 required that all forms of opium be sold with a prescription and that it no longer be used as a nonprescription drug. The Controlled Substances Act of 1970 classified drugs with high abuse potential, opioids among them, in five schedule categories according to their potential for drug abuse (see Chapter 8). Addiction, or substance use disorder, is defined as a psychological and physical dependence upon a substance beyond normal voluntary control, usually after prolonged use of a substance. Morphine, a prototype opioid, is obtained from the sap of seedpods of the opium poppy plant. Codeine is another drug obtained from opium. In the past decades, many synthetic and semisynthetic opioids have been developed; for example, meperidine. Although nonopioid analgesics act on the PNS at the pain receptor sites, opioid analgesics act mostly on the CNS. Opioids act primarily by activating the j-receptors, but they also exert a weak activation of the kappa (K) receptors. Analgesia, respiratory depression, euphoria, and sedation are effects of -receptor activation. Activation of k-receptors leads to analgesia and sedation but has no effect on respiratory depression and euphoria. Opioids not only suppress pain impulses but also suppress respiration and coughing by acting on the respiratory and cough centers in the medulla of the brain stem. One example of such an opioid is morphine, a potent analgesic that can readily depress respira-tions. Codeine is not as potent as morphine (1/15 to 1/20 as potent), but it also relieves mild to moderate pain and suppresses cough, which allows it also to be classified as an antitussive. Most opioids, with the exception of meperidine, have an antitussive (cough sup-pression) effect. In addition to pain relief and antitussive effects, many opioids possess antidiarrheal effects. Common side effects with high doses of most opioids include nausea and vomiting, particularly in ambulatory patients; constipation; a moderate decrease in blood pressure; and orthostatic hypotension. High doses of opioids may also cause respiratory depression; urinary retention, usually in older adults; and antitussive effects. Side Effects and Adverse Reactions Many side effects are known to accompany the use of opioids. Of particular importance are signs of respiratory depression (respiration