Anti-Inflammatory, Antiarthritis, and Antigout Drugs PDF

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anti-inflammatory drugs arthritis pharmacology medicine

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This document is about anti-inflammatory drugs, including NSAIDs, corticosteroids, and disease-modifying antirheumatic drugs (DMARDs). It discusses the actions, potential adverse effects, and uses of these drugs. It also covers inflammation, its causes, management, and possible side effects.

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12 Anti-Inflammatory, Antiarthritis, and Antigout Drugs LEARNING OUTCOMES 1. List the names, actions, and possible adverse effects of NSAIDs. 2. Explain what to teach patients and families about anti-inflammatory drugs (NSAIDs). 3. List the names, actions, and possible adverse effects of corticoste...

12 Anti-Inflammatory, Antiarthritis, and Antigout Drugs LEARNING OUTCOMES 1. List the names, actions, and possible adverse effects of NSAIDs. 2. Explain what to teach patients and families about anti-inflammatory drugs (NSAIDs). 3. List the names, actions, and possible adverse effects of corticosteroid-based anti-inflammatory drugs. 4. Explain what to teach patients and families about corticosteroid-based anti-inflammatory drugs. 5. List the names, actions, and possible adverse effects of disease-modifying antirheumatic drugs for management of arthritis and other inflammatory disorders. 6. Explain what to teach patients and families about disease-modifying antirheumatic drugs for management of arthritis and other inflammatory disorders. 7. List the names, actions, and possible adverse effects of antigout drugs. 8. Explain what to teach patients and families about antigout drugs. KEY TERMS antigout drug (p. 237) These drugs are used to prevent gout and shorten gout attacks. For gout prevention, they must be taken daily. anti-inflammatory drug (N-tī-ĭn-FLĂ-mĕ-tōr-ē, p. 226) The primary purpose of these drugs is to reduce pain and prevent or limit the tissue and blood vessel responses to injury or invasion. corticosteroids (kōr-tĭ-kō-ˈSTĔR-oid, p. 230) These drugs, also known as glucocorticoids, prevent or limit inflammation by slowing or stopping all known pathways of inflammatory cytokine production. They are similar to the natural cortisol hormones secreted by the adrenal gland that are necessary for life. disease-modifying antirheumatic drug (DMARD) (p. 235) These drugs reduce the progression and tissue destruction of the inflammatory disease process, especially rheumatoid arthritis, by inhibiting TNF. nonsteroidal anti-inflammatory drug (NSAID) (nŏn-stĕ-RŌĪ-dĕl ĂN-tī-ĭn-FLĂmĕ-tōr-ē, p. 227) These drugs prevent or limit the tissue and blood vessel responses to injury by slowing the production of one or more inflammatory 416 mediators. They are divided into two categories: (1) nonselective NSAIDs that inhibit the actions of both COX-1 and COX-2, and (2) selective NSAIDs that have more inhibitory effects on the COX-2 enzyme and fewer effects on the COX-1 enzyme. Inflammation Causes and Action Inflammation is a predictable set of tissue and blood vessel actions caused by white blood cells (WBCs; leukocytes) and their products as a response to injury or infection. These tissue and blood vessel actions cause the five major symptoms of inflammation: pain, redness, warmth, swelling, and loss of function. For example, think about having a severely sprained ankle. With the sprain, you can have redness, warmth, and pain. In addition, you cannot walk well on the ankle (loss of function). Although inflammation can be uncomfortable, it is a normal reaction of the body to tissue injury and is generally protective. However, when inflammation lasts a long time or occurs without tissue injury (or invasion by bacteria and other organisms), it is an overreaction that can damage and even destroy tissues over time. Memory Jogger The five main symptoms of inflammation are pain, redness, warmth, swelling, and loss of function. When an injury occurs (continuing with the sprained ankle example), the damaged tissues and WBCs in the ankle release inflammatory chemical mediators that cause certain actions to occur. These mediators, which are important in starting and continuing inflammation, include kinins, prostaglandins (PGs), histamine, and tumor necrosis factor (TNF). Some mediators, especially histamine, act on blood vessels in the injured area, causing them to dilate and leak fluid from the capillaries. This results in redness and warmth of the tissues. Increased blood flow brings more WBCs to injured tissues, and the leaking capillaries cause swelling. Released kinins trigger pain receptors in nerve endings, which makes the area painful. This pain lets you know an injury has occurred so that you will take steps to protect your ankle from more harm. As more WBCs come to the injured area, the arachidonic acid (AA) cascade increases the inflammatory response (Fig. 12.1). This begins by converting fat from injured cell membranes into AA. Then the enzyme cyclooxygenase (COX) converts AA into many mediators, especially different types of PGs. There are two forms of the COX enzyme: COX-1 and COX-2. COX-1 is present in all cells and makes PGs that are helpful and protective (think of COX-1 as “good COX”). For example, COX-1 in stomach lining cells makes PGs that produce thick mucus. The mucus protects the stomach lining from being harmed by the gastric acids needed for food digestion. In contrast, COX-2 is present mainly in areas of inflammation. COX-2 is responsible for the types of PGs and other mediators that start and continue the inflammation response (think of COX-2 as “bad COX”). 417 FIG. 12.1 Arachidonic acid (AA) cascade resulting from injured cells. You can see the influence of the cyclooxygenase enzymes. (From Workman ML, LaCharity LA: Understanding pharmacology, ed 2, St. Louis, 2016, Elsevier.) Although uncomfortable, inflammation responses also help injured tissue to regain function. WBCs release growth factors that trigger repair of damaged tissues and cells by stimulating healthy cells in the injured area to divide and replace dead or damaged cells, and by promoting scar tissue formation in tissues that can no longer divide. It is important to remember that scar tissue does not act or function like normal tissue. Although inflammation is mostly a protective process that helps prevent infection and promote healing, it can cause serious and sometimes painful tissue damage if it goes on for too long or occurs when it is not needed. For example, some people experience development of autoimmune diseases in which the immune system fails to recognize normal body cells and attacks some tissues continually with inflammation. One such disease is rheumatoid arthritis. The chronic inflammation in the joints with excessive and continual release of mediators (especially TNF) causes destruction of joint cartilage and other normal joint tissues, resulting in severe pain and greatly reduced joint function. Over time the person can lose all function in one or more joints and have very limited mobility along with chronic pain. Bookmark This! Here are some useful websites regarding inflammatory disorders and their treatment: National Institute of Arthritis and Musculoskeletal and Skin Disorders: https://www.niams.nih.gov Arthritis Foundation: http://www.arthritis.org Centers for Disease Control and Prevention Arthritis: https://www.cdc.gov/arthritis 418 Inflammation Management Many acute problems that cause inflammation, such as sprains, fractures, or tears, require short-term therapy with anti-inflammatory drugs. These drugs have as their primary purpose to reduce pain and prevent or limit the tissue and blood vessel responses to injury or invasion. On the other hand, a variety of chronic inflammatory disorders, such as arthritis, may require long-term therapy with anti-inflammatory drugs. The long-term therapy is prescribed to reduce symptoms of inflammation and prevent tissue-damaging complications. It is important to recognize that most of these drugs, whether used for short-term or long-term inflammation, can have serious adverse reactions, and patient response to therapy must be closely monitored. A variety of drug categories—nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and antigout drugs—are useful in managing acute and chronic inflammatory conditions. As mentioned in Chapter 11, one of the symptoms of inflammation is pain. Often when inflammation is managed, pain is also relieved to some degree. Thus antiinflammatory drugs are also prescribed for pain management. For inflammation caused by gout, management also includes drugs that reduce the production of uric acid, the cause of gout. Nsaids Actions NSAIDs are able to prevent or limit the tissue and blood vessel responses to injury by slowing the production of one or more inflammatory mediators. NSAIDs are divided into two categories: (1) nonselective NSAIDs that inhibit the actions of both COX-1 and COX-2, and (2) selective NSAIDs that have more inhibitory effects on the COX-2 enzyme and fewer effects on the COX-1 enzyme (Fig. 12.2). 419 FIG. 12.2 Basic actions of selective and nonselective NSAIDS. (A) Normally cells produce the enzymes cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The enzymes cause chemical reactions with specific functions You can consider COX-1 enzymes as “good COX” such that they have the positive effects, whereas COX-2 (or “bad COX”) enzymes have negative effects. (B) Aspirin and other nonselective NSAIDs block both the good COX (COX-1) and the bad COX (COX-2). While you reduce pain and suppress inflammation, you also can get the negative side effects. (C) Selective COX-2 inhibitors primarily block the COX-2 enzyme, so they have fewer side effects at normal doses. (From Kee JL, Hayes ER, McCuistion LE: Pharmacology, ed 8, St. Louis, 2015, Saunders.) Nonselective COX inhibitors (e.g., aspirin, ibuprofen, and other NSAIDs) disrupt both COX-1 and COX-2 enzymes (see Fig. 12.2). So the nonselective COX inhibitors can block the protective and helpful cellular COX-1 effects (in other words, they block the “good COX”), as well as reduce the inflammation associated with activation of COX-2 (the “bad COX”). As a result, nonselective NSAIDs have more side effects than selective COX-2 inhibitor NSAIDs (those that affect only COX-2). Regardless of whether an NSAID is selective or nonselective, they all have the same anti-inflammatory action: reducing the production of PGs, kinins, histamine, TNF, and other inflammation mediators from AA. These effects produce the analgesic, anti-inflammatory, and antipyretic (fever-reducing) effects associated with NSAIDs. The oldest NSAID still in use today is aspirin (acetylsalicylic acid [ASA]), which has a salicylate chemical structure. This chemical was first extracted from the bark and root of the white willow tree and has been used as an anti-inflammatory agent for centuries. More is known about aspirin from such longtime use, so it is considered the classic NSAID to which all other NSAIDs are compared. Aspirin is a salicylate, but different chemicals are used as the drug base in other NSAIDs. They work in the same way as aspirin but have different strengths and expected side effects and adverse effects. 420 Some other earlier nonselective NSAIDs were more potent than aspirin but also had some very harsh side effects that limited their use. For example, colchicine and indomethacin are rarely prescribed today. Newer NSAIDs and other types of targeted therapies have also reduced the need to use these drugs. Table 12.1 lists the most common NSAIDs in use today. Table 12.1 Common NSAIDs for Inflammatory Problems COX-1 inhibitors: These drugs decrease the activity of both COX-1 and COX-2 to reduce the formation of inflammatory mediators from arachidonic acid. These drugs disrupt the normal functions of other products from arachidonic acid that are helpful and protective. DRUGS/ADULT DOSAGE RANGE NURSING IMPLICATIONS aspirin (Bayer aspirin, Ecotrin, Aspirtab, many others) • All COX-1/COX-2 inhibitors have more side effects at lower doses than do selective COX-2 325–650 mg every 4–6 hours as needed; extra strength inhibitors. 1000 mg every 6 hours as needed • Warn patients that these drugs all increase the risk for bleeding because they all interfere ibuprofen (Advil, Motrin, Midol) 200–800 mg orally with the platelet function of the clotting process. three to four times daily or as needed • Remind patients to stop taking aspirin 1 week before dental or surgical procedures, and ketorolac (Toradol) oral: 10–20 mg every 4–6 hours; IM: other COX-1/COX-2 inhibitors at least 2–4 days before dental or surgical procedures because 15–30 mg every 6 hours. of the increased risk for bleeding from the procedure. nabumetone (Relafen) 500–1000 mg orally once or twice • Tell patients to report stomach/abdominal pain or any signs of blood in the stool to their daily prescriber because these drugs all increase the risk for GI ulcer formation. naproxen (Aleve, Anaprox, Naprosyn) 220-500 mg orally • Teach patients not to take NSAIDs while taking warfarin because the risk for bleeding is every 12 hours; controlled release tablets initial dose then so severe that hemorrhage and strokes are likely. 750 or 1000 mg orally once daily. • Teach patients who are taking any NSAID except aspirin to weigh themselves at least twice piroxicam (Feldene) 20 mg orally once daily weekly and keep a record because these drugs increase salt and water retention, which can worsen heart failure and raise blood pressure. • Instruct patients to take any NSAID with food to help prevent stomach irritation. • Teach patients to drink 2–3 L of fluid daily while on NSAIDs to ensure good blood flow to the kidneys because all of these drugs, except aspirin, can cause kidney damage. • Instruct patients who have diabetes to check blood sugar levels more often because these drugs increase the risk for hypoglycemia (low blood sugar) in patients who take oral antidiabetic drugs. • Teach patients to take the prescribed NSAIDs on a regular schedule because inflammation is better relieved when there is a stable blood level of the drug. COX-2 inhibitors: These drugs are more selective and mostly inhibit the COX-2 arachidonic acid production of inflammatory mediators. Although the same side effects are possible as with the COX-1/COX-2 inhibitors, they usually occur only at higher dosages or with prolonged use. DRUG/ADULT DOSAGE RANGE NURSING IMPLICATIONS celecoxib (Celebrex) 100–400 mg orally daily. May be in • Before the first dose of celecoxib, ask whether the patient has an allergy to sulfa-based one to two divided doses antibiotics because a patient allergic to sulfa is likely to also be allergic to celecoxib (it meloxicam (Mobic) 7.5–15 mg orally once daily; capsules contains a chemical similar to sulfa). 5–10 mg orally once daily • Suggest to the patient that they should take these drugs with a full glass of water or a small amount of food to reduce GI upset. • Teach patients to take a COX-2 inhibitor exactly as prescribed because higher doses will result in the same side effects and adverse reactions as the COX-1/COX-2 inhibitors. • Avoid giving these drugs to anyone who has angina, who smokes, or who has severe coronary artery disease because they increase clot formation and the risk for heart attacks. COX-1, Cyclooxygenase 1; COX-2, cyclooxygenase 2. Uses NSAIDs are used as first-line therapy to treat a variety of illnesses, often associated with pain and/or fever. Pain in the muscles, nerves, and joints (myalgias, neuralgias, and arthralgias, respectively), as well as headache and dysmenorrhea, are commonly treated with NSAIDs. Various forms of arthritis, such as rheumatoid arthritis, osteoarthritis, and psoriatic arthritis, may be responsive to NSAIDs for pain and other symptoms of inflammation. NSAIDs are also used short-term for pain management from dental extraction, minor surgery, and soft tissue athletic injuries. Although many NSAIDs are available over the counter, they are still potentially dangerous drugs, and great care should be taken to avoid overdose. Larger doses must be obtained from a licensed prescriber and monitored very carefully. As a side note, nonselective NSAIDs, particularly aspirin, inhibit platelet clumping or aggregation. This effect is very helpful when used in low doses for patients with coronary heart disease. Nevertheless, the effect on platelets can also lead to an increased risk for bleeding, particularly at higher doses. For NSAIDs other than 421 aspirin, platelet inhibition is dose related and reversible. Patients who take aspirin must be monitored for bleeding because of irreversible platelet inhibition for the lifespan of the platelet, for as long as 7 to 8 days. This is very important if a patient is scheduled for an invasive procedure or surgery, so make sure to notify the prescriber if the patient has an upcoming surgery. Memory Jogger Nonselective NSAIDs inhibit both the COX-1 and COX-2. Selective NSAIDs primarily inhibit the COX-2 and thus have fewer side and adverse effects. Expected Side Effects Common side effects of nonselective NSAIDs are heartburn, nausea, vomiting, dizziness, headache, and increased risk for bleeding and bruising. The GI effects may be minimized or avoided if the drug is taken with at least a full glass of water. If the drug does cause mild GI upset, the patient may take the drug with a small amount of food or milk. All NSAIDs except aspirin can cause some degree of fluid retention, edema formation, and even raise blood pressure. This is particularly important to note in that NSAIDs should be avoided in patients who have high blood pressure, heart failure, or renal failure. Selective NSAIDs (the COX-2 inhibitors) have fewer GI effects because they do not impact the protective effects associated with the COX-1 enzyme. Adverse Reactions Although expected side effects are often bothersome to the patient, they typically can be managed and the patient can continue taking the drug. Adverse reactions, however, must be recognized and reported to the prescriber immediately, and the drug will most likely be discontinued. Several adverse reactions may occur in patients who are taking NSAIDs. These reactions include allergy (from mild symptoms of rash and shortness of breath to anaphylaxis), renal failure, GI bleeding (upper or lower), and blood disorders. Patients who are taking COX-2 inhibitors may have an increased risk for myocardial infarction and stroke, so it is important to recognize symptoms associated with those disorders. It is important to note that patients allergic to one nonaspirin NSAID may be allergic to another because of cross-sensitivity. Although this is generally rare, it is very important to note all allergies in the medical record and report to the prescriber before giving the drug. Aspirin has been associated with the occurrence of Reye syndrome when given to children suffering from a viral infection such as varicella (chickenpox) or influenza. In Reye syndrome, symptoms may affect all organs of the body, but most seriously affected are the brain and liver. It can even lead to permanent brain damage and death. Thus the use of aspirin is avoided in children, especially those who have an acute illness. Lifespan Considerations 422 Pediatric Aspirin should not be given to infants or children who have an acute illness because of its association with the development of a very serious problem known as Reye syndrome. This disorder can lead to mental deficits, coma, or death. Too much aspirin can lead to toxicity and can even be life-threatening. Symptoms of aspirin toxicity may progress from mild to severe, beginning with tinnitus (ringing of the ears), hyperventilation, diaphoresis (sweating), thirst, headache, drowsiness, skin eruptions, and electrolyte imbalance. These progress to central nervous system (CNS), depression, stupor, convulsions and coma, tachycardia (rapid heartbeat), and respiratory insufficiency. If patients exhibit any of these symptoms, it is very important to notify the prescriber early. Lifespan Considerations Older Adults Older adults who are taking NSAIDs have a higher incidence of excessive bleeding and even perforated ulcer than younger adults. Those older adult patients who have some degree of renal impairment are at higher risk for damage to the liver and kidney caused by NSAIDs. These drugs should be avoided in older adults. If prescribed, they should be given with a proton-pump inhibitor, such as misoprostol (Cytotec), to reduce risks for GI effects. Drug Interactions Alcohol taken with any of the NSAIDs increases the risk for GI bleeding. There is an increased effect of anticoagulants, sulfonylureas, and sulfonamides if they are used at the same time as aspirin. NSAIDs interact with each other, which increases the risk for side effects, adverse effects, and toxicities. Thus the patient should not be taking more than one type of NSAID at any one time. Different NSAIDs interact differently with other drugs, and interactions are common. Consult a pharmacist or drug handbook for a complete discussion of the interactions associated with a particular NSAID. Examples of common interactions include: • Aspirin and other NSAIDs should not be given to treat vaccination-associated fever and pain because they can prevent the immune response and its protection. • NSAIDs (except for aspirin) decrease the effectiveness of many antihypertensive drugs, especially the angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, and most diuretics. 423 • All NSAIDs increase the risk for bleeding for patients who take any type of anticoagulant. • All NSAIDs increase the risk for hypoglycemia (low blood sugar) in patients with diabetes who take oral antidiabetic drugs. Nursing Implications and Patient Teaching Assessment. Do not be afraid to ask patients directly if they are using any other over-the-counter or prescribed NSAIDs because patients sometimes do not report or even forget occasional use of aspirin or other over-the-counter NSAIDs. So many different forms of NSAIDS are available over the counter, so it is important to assess whether patients are taking more than one kind. Make sure to check for the presence of allergy to aspirin or other NSAIDs, history of asthma, blood disorders, GI problems or ulcer disease, or other liver or kidney problems. These conditions are precautions or contraindications to the use of NSAIDs and thus should be reported to the prescriber before giving the drug. Assess which other prescribed and over-the-counter drugs the patient takes daily because NSAIDs interact with many other drugs. Check with the pharmacist to determine whether or how the NSAID is expected to interact with the patient's other drugs. Planning and implementation. The dosages for different NSAIDs vary widely, so make sure that you know the correct dosage range for the specific drug you are giving. There are many forms of NSAIDS, including tablets, capsules, eye drops, chewable preparations, suppositories, and injectable. Several NSAIDs may even be applied topically. This is very helpful when the prescriber considers the best form for the patient's individual needs. Give any NSAID with a full glass of water to reduce risk for GI disturbances. If the patient has any stomach upset, try giving with food or milk to reduce the symptoms. If the patient continues to have GI upset, notify the prescriber. If in suspension form, make sure to shake well so that the dosage is accurate. The patient should be well hydrated before taking the drug to reduce the risk for kidney damage. Evaluation. Monitor the patient to see that symptoms resolve (e.g., pain level decreased and temperature is reduced to 101°F or lower). Pain relief typically decreases after administration of the drug. Reduction of inflammation may take longer, even 1 to 2 weeks in some cases. The dosage should be reduced or the drug stopped if tinnitus (ringing in ears) develops. Observe for symptoms, such as pain or fever, that do not respond to the drug that suggest that the patient is getting worse, and notify the healthcare provider. The patient may need a larger dose, more potent drug, or alternative therapy. Assess the patient for any signs of increased bleeding, especially of the gums and 424 mucous membranes. Check skin for large bruises or those that flow together. Also assess for the presence of petechiae (pinpoint purple and reddish spots) on the torso or extremities. Examine stool, urine, and vomitus for the presence of obvious blood. When blood counts are performed, assess whether the number of red blood cells and platelets is normal or low. Report low counts to the healthcare provider immediately. Patient and family teaching. Tell the patient and family the following: • These drugs may cause stomach upset, so NSAIDs should be taken with a full glass of water. If symptoms do occur, try taking the drug with food or milk. • Contact your healthcare provider right away if ringing in the ears, abnormal bleeding or bruising, or bloody or black, tarry stools are noted. • For some chronic problems you may need to take your prescribed NSAID for more than a week or two before noticing a decrease in symptoms. • Make sure to drink at least 8 to 10 glasses of water a day to stay well hydrated while taking the NSAID. • For best effect to reduce inflammation, take the prescribed NSAIDs on a regular schedule to keep a stable blood level of the drug. • Do not take any other drugs, including over-thecounter drugs (especially aspirin or another NSAID), at the same time without informing your healthcare provider. • Contact your healthcare provider if your fever does not come down within 24 to 48 hours. • Keep aspirin and all other NSAIDs out of the reach of children because wrong doses may be toxic to a child. • If you are unable to take the drug in the form prescribed (such as difficulty swallowing), contact your healthcare provider so that another form of the drug may be prescribed. 425 Corticosteroids Corticosteroids, also known as glucocorticoids, are drugs built on the structure of cholesterol that are able to prevent or limit inflammation by slowing or stopping all known pathways of inflammatory cytokine production. The corticosteroids are similar to the natural cortisol hormones secreted by the adrenal gland that are necessary for life. As a matter of fact, these drugs may be given to replace missing or low hormone levels in cases of adrenal insufficiency (Addison disease). They are most commonly used, however, to reduce the inflammatory response. Common systemic corticosteroid drugs include prednisone, methylprednisolone, hydrocortisone, and dexamethasone (Table 12.2). Table 12.2 Common Corticosteroid Drugs Corticosteroids: These drugs inhibit enzymes and proteins that allow the COX-1 and COX-2 enzyme systems to start and continue the arachidonic acid production of inflammatory mediators. They are very powerful in decreasing the production of all known mediators that trigger inflammation. The systemic forms of these drugs disrupt the normal functions of other products from arachidonic acid that are helpful and protective. DRUG/ADULT DOSAGE RANGE NURSING IMPLICATIONS dexamethasone (Decadron, Maxidex) 0.75 to 9 mg daily orally, IM, • Check the order carefully because different types of corticosteroids come in or IV given in 2 to 4 divided doses. Doses are adjusted according different strengths and are not interchangeable. to patient response. • Doses must be tapered rather than stopped suddenly to avoid adrenal prednisolone (Millipred, Econopred, Pred-Forte) 5–60 mg daily by insufficiency mouth as a single dose or in divided doses • Oral drugs should be taken with food or milk to reduce the risk for gastric ulcers. prednisone (Deltasone, Predone, Sterapred) 5–60 mg orally daily in • Check the patient's blood pressure and weight when giving oral or parenteral single or divided doses corticosteroids because these drugs cause water retention and raise blood hydrocortisone sodium succinate (Solu-Cortef) 100–500 mg IM or pressure. IV. Repeat doses at 2-, 4-, or 6-hour intervals as ordered. • Assess for infection because these drugs reduce the immune response and methylprednisolone (Medrol, Solu-Medrol) 4–48 mg orally daily in increase the susceptibility to infection. divided doses according to patient condition and response; 10–120 • When patients are taking these drugs long term, be sure to handle the patient mg IM, frequency of doses determined by patient condition and carefully and not apply tape to the skin because these drugs increase bruising and response thin the skin. betamethasone (Beta Derm, Del-Beta) Topical: apply a thin film of a • Never apply a topical corticosteroid cream, ointment, or lotion to a skin area that 0.1% as directed has indications of infection because the infection can spread. hydrocortisone (Dermacort, Lanacort) Topical: 0.1%–1% apply as • Make sure to monitor blood sugar regularly for patients with diabetes or directed prediabetes because corticosteroids reduce the sensitivity of insulin receptors and triamcinolone (Kenalog, Triderm) Topical: 0.025% to 0.5% apply to increase blood glucose levels. They may need adjustments in oral antidiabetic affected area as directed drugs or insulin. • Patients may experience a change in mood while on corticosteroids; make sure to notify the prescriber if the patient has significant mood changes to reduce the risk for psychotic reactions. • For topical forms such as lotions, creams or ointments, make sure to apply a thin layer to the affected area as directed to avoid giving too large of a dose of corticosteroid. COX-1, Cyclooxygenase 1; COX-2, cyclooxygenase 2. Do Not Confuse Do not confuse prednisone with prednisolone. Although both drugs are corticosteroids, their strengths, dosages, and some routes of administration differ. Actions Corticosteroids are very useful in managing severe or chronic inflammation. They are very powerful in decreasing the production of all known mediators that trigger inflammation. Corticosteroids inhibit enzymes and proteins that allow the COX-1 and COX-2 enzyme systems to start and continue the AA production of inflammatory mediators. They also slow the production of WBCs in the bone marrow. This action also helps reduce inflammation because WBCs usually are the source of the mediators that trigger inflammation. The actions of corticosteroids 426 occur in all cells, not just those involved in inflammation. As a result, their therapeutic effects, side effects, and adverse effects are widespread. These problems limit how and when they can be used. Uses Corticosteroids are most commonly given to reduce inflammatory, allergic, or immunologic responses. Examples of when corticosteroids might be used are acute adrenal emergencies, allergic states, acute brain injury, severe asthma, and any condition in which chronic inflammation could lead to tissue damage, such as osteoarthritis, rheumatoid arthritis, inflammatory bowel diseases, and systemic lupus erythematosus, among a wide variety of inflammatory and autoimmune diseases. Local injection of corticosteroids can be used for intraarticular (into joints), soft tissue, or intrabursal (into bursae) problems, or for intralesional (into lesions) or subcutaneous dermatologic problems. Corticosteroids might also be used topically for acute and chronic dermatoses (see Table 12.2), rectal problems, and some eye (ophthalmic) or ear (otic) problems. Inhaled corticosteroids are commonly used to manage inflammation associated with asthma. Expected Side Effects The side effects of systemic corticosteroids in pharmacologic doses are predictable exaggerations of the actions of the corticosteroids that are normally produced by the adrenal glands, or the results of reduced function of the hypothalamic-pituitaryadrenal axis. Table 12.3 lists the short-term and long-term effects of corticosteroid use. Common side effects of corticosteroids that occur even when used for relatively short periods include sodium retention, increased blood pressure, weight gain, bruising, and reduced immunity. It is not unusual for patients, particularly patients with diabetes, to have an elevated blood sugar level, so doses of insulin or oral hypoglycemic agents may need to be adjusted while the patient is on steroid therapy. Patients may experience a change in mood while on corticosteroids; some patients may experience mild euphoria, whereas others may experience some depression. These drugs also increase the risk for bleeding in general and especially in the GI tract. Although many of these effects may be considered expected, if they become severe, it is very important to notify the prescriber. Fig. 12.3 shows physical changes associated with long-term corticosteroid use known as cushingoid syndrome. Changes may reverse after the patient stops taking the drug, but that may take several months to a year. Table 12.3 Common Side Effects of Systemic Corticosteroids Side Effects That Can Occur as Soon as 1 Week of Therapy • Acne • Sodium and fluid retention • Elevated blood pressure • Sensation of “nervousness” • Difficulty sleeping • Emotional changes, crying easily Side Effects That Can Occur Within a Month After Therapy • Weight gain • Fat redistribution (moon face and “buffalo hump” between the shoulders) • Increased risk for GI ulcers and bleeding 427 • Fragile skin that bruises easily • Loss of muscle mass and strength • Thinning scalp hair • Increased facial and body hair • Increased susceptibility to colds and other infections • Stretch marks FIG. 12.3 Physical changes from long-term corticosteroid therapy, known as a “cushingoid” appearance. (From Workman ML, LaCharity LA: Understanding pharmacology, ed 2, St. Louis, 2016, Elsevier.) Adverse Reactions Many effects of systemic corticosteroids can cause serious problems if not carefully 428 managed. The most important problems are associated with long-term use and include adrenal gland suppression and reduced immunity. Thus long-term use of corticosteroids is limited to more severe inflammation that cannot be managed any other way. Adrenal suppression occurs when circulating blood levels of corticosteroids are higher than the amount of cortisol normally made by the adrenal glands (Fig. 12.4). This causes the adrenal glands to quit making and secreting natural cortisol because the body appears not to need the natural cortisol. Therefore the adrenal glands cells shrink (atrophy) and cannot quickly start making cortisol again. This becomes a problem if the patient suddenly stops taking corticosteroids because it may take weeks or even months for the adrenal glands to produce normal levels of cortisol again. FIG. 12.4 Corticosteroid influence on adrenal production of cortisol. (From Workman ML, LaCharity LA: Understanding pharmacology, ed 2, St. Louis, 2016, Elsevier.) Cortisol is necessary to maintain life; therefore the patient who suddenly stops taking systemic corticosteroids has no circulating cortisol and could die of acute adrenal insufficiency. Symptoms include anorexia, nausea and vomiting, lethargy, headache, fever, joint pain, skin peeling, myalgia (widespread muscle pain), weight loss, and hypotension. Abruptly stopping the drug may also result in a rebound of symptoms of the condition being treated. So the patient who has been taking any 429 corticosteroid daily for a week or longer needs to slowly decrease the dose over time (tapering) instead of just stopping the drug suddenly. Tapering of the drug allows the atrophied adrenal gland cells to gradually begin producing cortisol again and prevents acute adrenal insufficiency. Fig. 12.5 provides an example of a “dose pack” to assist the patient with dosing days 1 to 6, with each day tapering the dose. FIG. 12.5 Oral corticosteroid dose pack. Patients begin day 1 taking six tablets. Then, as the patient goes through the week, the drug dosages taper down daily until the sixth day. (Courtesy Sandoz International GmbH.) Any use of corticosteroids also reduces the number of WBCs, which can decrease inflammation but also decrease immune response. The longer the patient has been taking a corticosteroid and the higher the dose, the more the immunity is reduced. This greatly increases the patient's risk for infection. Also, because inflammation is reduced, the usual symptoms of infection, especially fever and pus formation, may not be present. It is especially important to monitor the patient for other signs of infection such as cough, changes in color of any sputum or other drainage, and even symptoms such as headache or behavior changes. Other adverse effects associated with long-term corticosteroid use include osteoporosis, cataract, hypertension, and ocular hemorrhage. Delirium or extreme changes in behavior such as mania may warrant reduction of dose or even cessation of the corticosteroid in affected patients. Memory Jogger Doses of systemic corticosteroids must be tapered rather than stopped abruptly, to prevent adrenal insufficiency. Drug Interactions Corticosteroids increase the effects of barbiturates, sedatives, narcotics, and anticoagulants. They decrease the effects of insulin and oral hypoglycemics, isoniazid, and broad-spectrum antibiotics. Drugs that increase the effects of corticosteroids include other NSAIDs and oral contraceptives, especially estrogen. 430 Drugs that decrease the effects of corticosteroids include ephedrine, phenytoin, antihistamines, rifampin, and propranolol. The effect of corticosteroids on warfarin anticoagulants is variable; in some cases it may increase effect, whereas other cases decrease effect. Some drugs produce exaggerated side effects when given with corticosteroids. These include alcohol, NSAIDs, amphotericin B, thiazides and other potassium-wasting diuretics, anticholinergics, cardiac glycosides, and stimulants such as adrenaline, amphetamines, and ephedrine. The use of aspirin or any other NSAID should be avoided while taking corticosteroids because they also can cause GI distress. Nursing Implications and Patient Teaching Assessment. The use of corticosteroids has many contraindications and precautions, so it is very important to obtain a good drug history, including over-the-counter drugs, herbal agents, and any topical or inhaled drugs. The most important contraindication is infection that is not also being managed with anti-infective drug therapy. Assess the patient for any signs or symptoms of local or systemic infection before starting the drug. These include fever, drainage, foul-smelling urine, productive cough, or redness around a wound or other open skin area. Steroids tend to thin the skin and so their use increases the risk for skin tears. Steroids can also slow wound healing, so they must be carefully assessed in patients who are to have any kind of surgery. Report any symptoms of infection to the prescriber because corticosteroids reduce immunity and can make any existing untreated infection worse. Planning and implementation. Steroids come in many forms. Corticosteroids may be given by many different routes including oral, inhalation, intranasal, subcutaneous, IM, and IV. Topically, they can be given as creams or gels or as opthalmic or otic (ear) preparations. Only corticosteroid preparations with specific labels should be used for ophthalmologic or otic (ear) administration. Topical steroids should not be applied to open wounds. They should be avoided if there are any signs of infection because they may increase the risk of the infection spreading because of their effect on the immune/inflammatory response. It is vitally important to confirm the proper form of the drug and the proper route of administration of corticosteroids. State practice acts will guide which route of drug administration is appropriate for the LPN/VN. Even if you do not give the drug, it will be important to monitor for expected side effects, adverse effects, and effectiveness. Dosages vary a lot; the dose will be determined for each patient and each problem, based on the diagnosis, severity, prognosis, and estimated length of treatment. The general rule is that the patient will receive as high a dose as necessary initially to get a favorable response and then a decreasing amount until reaching the lowest level that will maintain the therapeutic effect but not produce complications. It is critical to check the dose, the route, and the specific drug name carefully because the strength of each drug may differ. Do not exchange one type of systemic corticosteroid for another because the dosages may not be equivalent. 431 It is recommended that doses of oral corticosteroids be taken with meals or a light snack to help reduce the chance of GI distress and peptic ulcer. Systemic corticosteroids are typically given orally, except in patients who are acutely ill or when the patient is unable to take them orally. The onset of action is typically 2 to 8 hours, and the effects are anywhere from 12 to 24 hours, depending on the drug. Oral corticosteroids are almost completely absorbed in the GI tract. For corticosteroids injected into a muscle or joint, effects may take several days to weeks for onset and duration of effects. When corticosteroids are given orally to patients with functioning adrenal glands, the total dose should be taken first thing in the morning. This is the time when the adrenal glands are normally secreting the most cortisol, so the corticosteroid dose more closely mimics the body's usual actions. Evaluation. All patients who are receiving systemic corticosteroids should be carefully monitored, and the dosage may be adjusted by the prescriber to reflect reduced or increased symptoms, the patient's response, and any periods of stress in the patient's life (e.g., injury, infection, surgery, and emotional crisis). Patients who require highdose or long-term treatment should be carefully monitored for symptoms of adrenal insufficiency for up to 1 year after stopping the drug. Top Tip for Safety Make sure to carefully protect the skin of patients who are taking corticosteroids while transferring or positioning to prevent skin tears. Corticosteroids can hide the usual symptoms of infection and also increase the patient's risk for infection. This makes it essential for you to monitor for any unusual symptoms that the patient may be having that might suggest infection. For example, corneal fungal infections are particularly likely to develop with extensive ophthalmologic corticosteroid use. Therefore if the patient has any new blurred vision, discoloration of the eye, or tearing, they should contact their healthcare provider. Corticosteroids are particularly dangerous in patients with a history of tuberculosis, because the disease can be reactivated, so it is important to monitor for cough or shortness of breath. Patient and family teaching. Tell the patient and family the following: • Keep all appointments to monitor therapy while taking this drug. • Heavy smoking may add to the expected action of a corticosteroid because nicotine raises the blood level of naturally secreted cortisol. 432 • Avoid alcohol during the course of therapy because it enhances the risk for GI ulcers. • Report any signs and symptoms of infection (e.g., fever, cough, pain or burning on urination, foul-smelling drainage, generally feeling unwell) to your healthcare provider immediately because corticosteroids reduce resistance to infection. • Inform other healthcare providers, including your dentist, that you are taking a corticosteroid. • Report any of the following signs and symptoms to the healthcare provider immediately because they indicate a life-threatening problem of the adrenal glands: malaise, weakness, hypotension, anorexia, nausea and vomiting, aching of bones and muscles, headache, increased temperature, and diarrhea. • Do not stop taking the steroids suddenly. • During and after corticosteroid treatment, wear a MedicAlert bracelet or necklace or carry a medical identification card with the name of the drug. • Do not receive any immunizations without consulting the nurse or other healthcare provider first. • Take oral corticosteroids with a meal or light snack to minimize stomach upset. • Eat a diet rich in potassium and low in sodium to replace lost potassium and prevent excessive water retention. • If you forget to take a prescribed dose, take a dose as soon as possible and then follow the prescribed schedule. • Call the healthcare provider if rapid weight gain, black or tarry stools, unusual bleeding or bruising, or signs of hypokalemia (decreased potassium in the blood), such as anorexia, lethargy, confusion, nausea, and/or muscle weakness, develop. Disease-Modifying Antirheumatic Drugs 433 Disease-modifying antirheumatic drugs (DMARDs) reduce the progression and tissue destruction of the inflammatory disease process, especially rheumatoid arthritis, by inhibiting TNF. They are prescribed primarily by specialists to prevent or limit bone destruction and are used only in diagnosed cases of rheumatoid arthritis or other chronic inflammatory disorders that have been getting worse despite other types of treatment. You need to know about these drugs because none of these agents is without significant risk and toxic effects. Patients who are taking these drugs need constant follow-up and regular evaluation, and may be admitted to the hospital or seen in offices for other problems. Actions DMARDs work through a variety of actions to decrease or suppress the inflammatory response and, in cases of rheumatoid arthritis, slow down the progression of disease and preserve joint function. The most commonly used DMARDs inhibit the inflammatory mediator TNF. They do this by binding to the TNF molecules produced by WBCs and prevent them from binding to TNF receptor sites on inflammatory cells and other cells. This prevents the cells with TNF receptors from continuing to produce even more TNF and other substances that enhance the inflammatory responses and cause direct tissue destruction. As a result, pain is relieved, physical function improves, and tissue damage is reduced or delayed. Most DMARDs are given by injection, although there are a few oral drugs as well. The two most common DMARDs are adalimumab and etanercept (Table 12.4). Table 12.4 Disease-Modifying Antirheumatic Drugs Disease-modifying antirheumatic drugs: These drugs reduce the progression and tissue destruction of the inflammatory disease process by inhibiting tumor necrosis factor. As a result, pain is relieved, physical function improves, and tissue damage is reduced or delayed. DRUG/ADULT DOSAGE NURSING IMPLICATIONS RANGE adalimumab (Humira) 40 mg • The first dose of an injectable DMARD should be given by the healthcare provider or the registered nurse because of subcutaneously every other the risk of severe allergy. Monitor the patient every 15 minutes for the first 2 hours to detect adverse reaction. week. • Tell patients that injection-site reactions including redness, pain, swelling, and itchiness may occur but typically etanercept (Enbrel) 50 mg subside in a few days. subcutaneously once to • Make sure to rotate injection sites on the front of the thighs and the abdomen to ensure best absorption and prevent twice weekly skin problems. Avoid giving within 2 inches of the umbilicus because this area has many blood vessels and absorption can be too rapid. • Read administration directions very carefully before giving to avoid improper dosing or damage to the drug. These drugs often must be refrigerated before giving. • Do not rub the site after giving the injection, to prevent bleeding and bruising of the site. • For patients with psoriasis, make sure not to inject in any lesions because drug absorption is delayed in these areas and the lesions may mask skin reactions to the drug. • Do not give these drugs to any patients with an active infection, including local infections, because the drug reduces the immune response and can make infections worse. • Teach patients to report any signs of infection to the healthcare provider immediately because the drug reduces the immune response and can make infections worse. • Patients who take these drugs before surgery may have greater risk for infections postoperatively because the drug reduces the immune response. • Instruct patients to avoid vaccination with live viruses while taking disease-modifying antirheumatic drugs because they may not be fully effective because of a reduced immune response. • Teach patients that it is not unusual to experience a mild headache while taking these drugs so that they will not be alarmed by this side effect. TB, Tuberculosis. Uses DMARDs are used to treat many different types of chronic inflammatory disorders that involve severe tissue destruction caused by excessive amounts of TNF. In 434 addition to rheumatoid arthritis, other autoimmune disorders that respond to DMARDs include ankylosing spondylitis, psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. Expected Side Effects The most common side effect from the injected drugs are injection-site reactions. These include pain, swelling, itching, and redness at the site for about 1 week. Many patients also have headache and nausea. Patients may develop anemia and have an increased risk for bleeding because these drugs reduce bone marrow production of red blood cells and platelets. Adverse Reactions Severe adverse reactions are possible and relatively common in patients who are taking DMARDs, so it is important to monitor patients very carefully and teach patients the symptoms to report. All DMARDs reduce the patient's immune response to some degree, increasing his or her risk for infections. In fact, if a patient has had tuberculosis or viral infections (such as shingles or hepatitis) in the past, he or she is at high risk for reactivating these old infections. Even though reduced immunity is an expected result of therapy with DMARDs, it is considered an adverse reaction that must be monitored for severity. If reduced immunity is severe enough or severe infection develops, the DMARD therapy must be stopped. Memory Jogger All DMARDs reduce immunity and increase the risk for infection. Heart failure can occur with these drugs. The heart failure may be new or, if the patient already has heart failure, it can become more severe while taking DMARDs. DMARDs should not be used in anyone who has severe heart failure. Patients who are taking injectable DMARDs may be at greater risk for allergic reaction, even anaphylaxis, because the solutions may contain some animal proteins. Fortunately these reactions are not common. Drug Interactions If the patient is taking any other type of drug that reduces immunity, the suppression will be more severe if taken with a DMARD, greatly increasing the risk for infections. It is not recommended to give two different DMARDs that interfere with TNF at the same time. Some immunizations contain live vaccines. For the patient who is receiving DMARDs, live vaccine immunizations are avoided because the patient may actually develop the disease the immunization is supposed to prevent. DMARDs reduce immunity, so the patient may not have an accurate response to tuberculosis testing with the PPD (purified protein derivative) test. The response could be negative even if the person has active tuberculosis. Nursing Implications and Patient Teaching 435 Assessment. Before giving the drug, ask the patient to list every drug he or she is currently taking. Ask about symptoms of infection such as fever, cough, foul-smelling drainage, pain or burning on urination, general malaise, and any recent exposure to people who are ill. Also ask whether the patient has received an immunization within the past month. All patients must be tested for tuberculosis before starting a DMARD. Top Tip for Safety Always ask patients whether they have a current infection or have had any of these infections in the past: tuberculosis, hepatitis, shingles, HIV infection, pneumocystis pneumonia, or any type of opportunistic infection. Planning and implementation. The first dose of an injectable DMARD must be given by either a healthcare provider or a registered nurse in a setting that can handle severe allergic reactions. It cannot be started in an extended care facility or in the home. Take the patient's vital signs, especially pulse, blood pressure, and oxygen saturation, before giving the first dose. Use this information as a baseline to assess for an adverse drug reaction. Keep an emergency cart close to the patient during and for 2 hours after the first injection. After the first dose is given, observe the patient every 15 minutes for any type of allergic or adverse reaction for at least 2 hours. These observations include respiratory rate, ease of respirations, blood pressure, pulse oximetry, and rash or hives at the injection sites. After the first therapeutic dose is given and no adverse reactions have occurred, LPN/VNs can give subsequent dosages. Some patients can be taught to self-inject subcutaneous doses. It is very important to carefully read specific directions for administration of the drugs before giving them. For example, adalimumab should not be shaken before giving because damage to the drug may occur. The drug can be left at room temperature for 15 to 30 minutes before injecting, but the cap or cover must be left on the drug bottle while allowing it to warm to room temperature. Evaluation. Closely monitor the injection site and the whole patient for signs of an adverse reaction. Document the patient's responses, even if no problems occur. Also document any symptoms or injection-site responses that do occur. Patient and family teaching. • Check for and report the signs and symptoms of infection (e.g., fever, cough, malaise, foul-smelling drainage, pain or burning on urination) to your prescriber immediately. 436 • If you have learned how to inject the drug, make sure to always use the proper technique and contact your healthcare provider if you have any questions. • Report any nausea, vomiting, loss of appetite, severe fatigue, or changes in color of the urine because they may be symptoms of problems with the liver. • Avoid any over-the-counter drugs without contacting the prescriber to avoid dangerous drug interactions. Gout Gout is a metabolic disorder that causes a person to either make too many uric acid crystals from the proteins he or she eats or to not eliminate the crystals in the urine. These crystals then deposit into the joints, causing arthritis symptoms of pain, redness, and swelling (gouty arthritis), and also causing progressive joint damage with function loss. Although the metabolic disorder is always present, the symptoms of gout come and go. Management of Inflammation and Gout Pain About 10% of people who have gout can control the problem with lifestyle changes that involve eating less of the foods that produce uric acid (e.g., shellfish and fish such as herring, sardines, salmon, haddock, and anchovies; red meat, organ meats, and pork; beer and wine). For the other 90% of people with gout, diet is not the cause. Rather, they are unable to eliminate uric acid well through the kidneys. Weight loss if obese, avoidance of alcohol, and including low-fat dairy products and complex carbohydrates in the diet may also reduce the risk for flare-ups. When symptoms of gout are present, general antiinflammatory drugs can help to reduce the pain and inflammation but do not address the uric acid problem. These drugs also do not prevent the progressive joint damage. Specific drugs for pain management may also be prescribed during acute attacks (see Chapter 11). Drugs that actually lower uric acid levels can prevent gout attacks as well as reduce the symptoms during an attack. Antigout Drugs The most common drugs used to reduce the uric acid levels associated with gout are uric acid synthesis inhibitors. The two drugs in this class are allopurinol and febuxostat (Table 12.5). Table 12.5 Common Antigout Drugs Uric acid synthesis inhibitors: prevent gout and reduce gout symptoms by lowering blood uric acid levels through inhibiting the enzyme that converts the purines of proteins into uric acid. DRUG/ADULT DOSAGE RANGE NURSING IMPLICATIONS 437 allopurinol (Aloprim, Zyloprim) 100–800 mg orally daily. Dosages higher than 300 mg must be given in divided doses. febuxostat (Uloric) 40–80 mg orally daily. Dose may increase if the patient's uric acid level remains high. • Take allopurinol after a meal to prevent GI side effects. • Wait at least 3 hours after taking an aluminum-based antacid before taking allopurinol because the antacid inhibits its absorption. • If patients also take warfarin, they will need more frequent monitoring of international normalized ratios (INRs) because allopurinol interferes with warfarin metabolism. • Do not give either drug to a breast-feeding woman because the drugs do enter breast milk and their effects on the baby are not known. • Febuxostat can be taken any time of day regardless of meals. • Teach patients to drink plenty of fluids to dilute uric acid and prevent kidney complications of the drug. • Teach patients to keep all appointments for laboratory tests to monitor for drug effectiveness and toxicities. Actions Allopurinol and febuxostat help prevent gout attacks by reducing the amount of an enzyme that converts the purines in protein into uric acid. So there is less uric acid available to form irritating and inflammatory deposits in joints. These drugs help patients to maintain a lower blood uric acid level. Uses The main use of antigout drugs is to prevent gout and shorten gout attacks. For gout prevention, they must be taken daily. Allopurinol (but not febuxostat) is also used to lower uric acid levels that occur when rapid cell destruction (such as with cancer chemotherapy) results in a huge release of the purines from proteins inside the cancer cells. Expected Side Effects The most common side effects of allopurinol and febuxostat are headache, rash, and minor nausea. Rare side effects include breast development in men and erectile dysfunction. There is a risk for gout flare with the start of therapy, so teach patients to report increased gout symptoms. Gout flare may be managed with NSAIDs or colchicine. Adverse Reactions Adverse reactions with allopurinol and febuxostat are rare and occur only with very long-term use. Examples of adverse effects include kidney stone formation, liver failure, heart failure, and stroke. Rarely, depression and cardiac dysrhythmias have been reported. Drug Interactions Aluminum-based antacids inhibit absorption of allopurinol. Antigout drugs also interfere with the metabolism and action of warfarin. Febuxostat interacts with many chemotherapy drugs to form other metabolic products that can damage kidneys. This is why it is not used for the hyperuricemia associated with cancer therapy. Nursing Implications and Patient Teaching Patients are rarely hospitalized for gout. The most important action is to teach patients how to take these drugs to prevent and control gout. Patient and family teaching. Tell the patient and family the following: 438 • Take allopurinol after a full meal to avoid an upset stomach. • Drink 8 to 16 glasses of liquids, especially water, throughout the 24-hour day. • Wait at least 3 hours to take allopurinol after using an aluminum-based antacid. • Febuxostat can be taken with or without meals and is not affected by antacids. • Avoid foods that are high in purines, such as beer or organ meats, because those foods may precipitate an acute attack. • Keep all appointments for laboratory tests of uric acid levels, as well as for liver and kidney function while taking these drugs. • Many drugs can trigger gouty flare-ups, so it is important to let your healthcare provider know if you have gout. Get Ready for the NCLEX® Examination! Key Points • Acute inflammatory reactions are uncomfortable but are often helpful or protective. • Chronic inflammatory re

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