Medical Management PDF

11/21/23, 3:15 PM Realizeit for Student Medical Management The goal of treatment at all phases of the RA disease process is to decrease joint pain and swelling, achieve clinical remission, decrease the likelihood of joint deformity, and minimize disability. Initial treatment delays have been impli...

11/21/23, 3:15 PM Realizeit for Student Medical Management The goal of treatment at all phases of the RA disease process is to decrease joint pain and swelling, achieve clinical remission, decrease the likelihood of joint deformity, and minimize disability. Initial treatment delays have been implicated in greater long-term joint deformity. Aggressive and early treatment regimens are warranted. The use of a targeted pharmacologic treatment strategy is recommended to decrease RA disease activity (Singh et al., 2016). Early Rheumatoid Arthritis Once the diagnosis of RA is made, treatment should begin with either a nonbiologic or biologic DMARD. The goal of using DMARD therapy is preventing inflammation and joint damage. Recommended treatment guidelines include beginning with the nonbiologic DMARDs (methotrexate is the preferred agent but leflunomide, sulfasalazine, or hydroxychloroquine are also used) biologics, or tofacitinibic within 3 months of disease onset. Care should be used with each of these medications by performing routine blood testing for liver and kidney function, along with monitoring the CBC for anemia. Dosage may need to be modified for patients with renal impairment (Comerford & Durkin, 2020). Another treatment approach for RA is the use of biologic DMARDs. These agents have been specifically engineered to target the most prominent proinflammatory mediators in RA—TNF-α, B cells, T cells, IL-1, and IL-6 (see Table 34-2). Biologic DMARDs are the first targeted therapy for RA. Clinical evidence suggests that biologic DMARDs work more quickly and show a greater delay in radiologic disease progression when compared to nonbiologic DMARDs. The biologic DMARDs are more expensive and have fewer years of usage with the RA population. Therefore, they tend to be reserved for patients with persistent moderate to severe RA who have not responded adequately to synthetic DMARDs (Singh et al., 2016). After initiating treatment with a DMARD, patients generally report a beneficial effect within 6 weeks and tolerate the medication relatively well. However, some patients may take longer to see improvement. Corticosteroids are recommended as a “bridge” in the early treatment but are not recommended for long-term therapy due to side effects (Singh et al., 2016). A newer class of drugs, the Janus Kinase (JAK) inhibitors, bind to the active JAK enzyme sites, inhibiting autophosphorylation and thus inhibiting cytokine production and decreasing the immune response (Mogul et al., 2019). JAK inhibitors are used in combination with methotrexate or other nonbiologic DMARDs. They may also be used as monotherapy (Mogul et al., 2019; Singh et al., 2016). NSAIDs and specifically the cyclo-oxygenase 2 (COX-2) enzyme blockers are used for pain and inflammation relief. NSAIDs, such as ibuprofen and naproxen, are commonly prescribed because of their low cost and analgesic properties. They must be used with caution, however, in long-term chronic diseases because of the possibility of gastric ulcers. Several COX-2 enzyme blockers have been approved for treatment of RA. Cyclo-oxygenase is an enzyme that is involved in the inflammatory process. COX-2 medications block the enzyme involved in inflammation (COX-2) while leaving intact the enzyme involved in protecting the stomach lining (COX-1). As a result, COX-2 enzyme blockers are less likely to cause gastric irritation and ulceration than other NSAIDs; however, they are associated with increased risk of cardiovascular disease and must be used with caution (Comerford & Durkin, 2020). The nurse should be aware that NSAIDs do not prevent erosions or alter disease progression and, consequently, are medications useful only for symptom relief (Singh et al., 2016). Additional analgesia may be prescribed for periods of extreme pain. Opioid analgesic agents are avoided because of the potential for continuing need for pain relief. Nonpharmacologic pain management techniques (e.g., relaxation techniques, heat and cold applications) are taught. Additional analgesia may be prescribed for periods of extreme pain. Opioid analgesic agents are avoided because of the potential for continuing need for pain relief. Nonpharmacologic pain management techniques (e.g., relaxation techniques, heat and cold applications) are taught (Carter et al., 2015). Arthritis https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX01cMmy1tXd%2bA0lN30h55hoLMwB%2fCluMLMNM… 1/10 11/21/23, 3:15 PM Realizeit for Student Corticosteroids are the most effective drugs for rapid relief of the pain, edema, and restricted mobility associated with acute episodes of joint inflammation. They are usually given on a short-term basis. When inflammation is limited to three or fewer joints, the preferred route of drug administration is by injection directly into the joint. Intra-articular injections relieve symptoms in approximately 2 to 8 weeks, and several formulations are available for this route. However, corticosteroids do not prevent disease progression and joint destruction. As a general rule, a joint should not be injected more often than three times yearly because of risks of infection and damage to intra-articular structures from the injections and from overuse when pain is relieved. Other Drugs in the Class Health care providers have long used methotrexate (Otrexup, Rasuvo, Trexall, Xatmep) for the treatment of cancer (higher doses), as well as for the treatment of autoimmune disorders, such as severe rheumatoid arthritis, juvenile rheumatoid arthritis, and severe psoriasis (lower doses). The use of methotrexate in combination with cyclosporine is the most widely used regimen in the prevention of GVHD after bone marrow transplantation. Excretion of methotrexate is mainly in the urine, so the drug’s half-life is prolonged in patients with renal impairment, with risks of accumulation to toxic levels and additional renal damage. However, the risks are less with the small doses used for treatment of rheumatoid arthritis than for the high doses used in cancer chemotherapy. To decrease these risks, it is important to document adequate renal function using the drug. Patients should be well hydrated. The lower doses of methotrexate used for autoimmune disorders and transplant therapy reduce the incidence and severity of adverse effects. Oral mucositis can occur with methotrexate therapy, interfering with nutritional intake and contributing to the risk of infection. However, even in the low doses used in rheumatoid arthritis and psoriasis, methotrexate may cause hepatotoxicity. Prior to and during therapy, monitoring the CBC, renal function, and liver function is essential. Liver function tests help guide methotrexate dosage. In general, dosage reduction is warranted if bilirubin is between 3 and 5 mg/dL, or aspartate aminotransferase (AST) is above 180 International Units per liter, and the drug should be omitted if bilirubin is above 5 mg/dL. Many clinicians recommend serial liver biopsies for patients on longterm, low-dose methotrexate. Administration of methotrexate is weekly for rheumatoid arthritis or psoriasis, and patients should keep an accurate record of the date and time of each dose. To reduce gastric upset, they may take the drug with food. However, daily dosing for cytotoxic immunosuppressants should be consistent with regard to time and food (i.e., at the same time of day, with the same meal). QSEN Alert: Safety It is necessary to follow individual manufacturer's instructions for reconstituting and administering IV preparations of methotrexate—in consultation Leflunomide (Arava), an anti-inflammatory immunosuppressant, is useful only in the treatment of adults with rheumatoid arthritis. Authorities do not recommend the drug for children younger than 18 years of age. Contraindications include the presence of active hepatitis B or C infection or if the alanine aminotransferase (ALT) level is greater than two times normal. With leflunomide, hepatotoxicity is a concern; hence, it is essential to obtain liver function tests before starting therapy. Also, patients should have renal function tests, as well as liver function tests, every month for the first 6 months then every 6 to 8 weeks thereafter. The FDA has issued a BLACK BOX WARNING for leflunomide regarding the risk of fetal loss and malformations. Women of childbearing age must use contraception. A negative pregnancy test for such women of childbearing age is necessary prior to starting therapy. Contraceptive counseling for both genders is recommended prior to treatment and for several months after stopping treatment. Tumor Necrosis Factor-Alpha–Blocking Agents The TNF-alpha–blocking agents act more rapidly than cytotoxic immunosuppressants (e.g., methotrexate) for autoimmune disorders and greatly improve the quality of life for patients with rheumatoid arthritis and Crohn’s disease. However, their use is also associated with significant risks of serious infections, especially with opportunistic organisms. Tuberculosis characterized by increased extrapulmonary and/or disseminated disease may occur. Other serious infections include pneumococcal infections, necrotizing fasciitis, Pneumocystis pneumonia, and systemic fungal infections such as aspergillosis and cryptococcosis. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX01cMmy1tXd%2bA0lN30h55hoLMwB%2fCluMLMNM… 2/10 11/21/23, 3:15 PM Realizeit for Student Infliximab (Remicade) is a humanized IgG monoclonal antibody used to treat rheumatoid arthritis and Crohn’s disease. The drug inhibits TNF-alpha from binding to its receptors and thus neutralizes its actions. Its ability to neutralize TNF-alpha accounts for its anti-inflammatory effects. Adverse effects of infliximab include formation of autoimmune antibodies and hypersensitivity reactions. Infections reportedly developed in approximately 21% of patients in clinical trials. In addition, dyspnea, hypotension, and urticaria have occurred. It is important (1) to administer infliximab in settings in which personnel and supplies (e.g., epinephrine, antihistamines, corticosteroids) are available for treatment of hypersensitivity reactions and (2) to discontinue the drug if severe reactions occur. The drug may aggravate heart failure. Adalimumab (Humira) is a recombinant monoclonal antibody that binds to TNF-alpha receptor sites and prevents endogenous TNF-alpha from binding to the sites and exerting its injurious effects. Used to treat moderate to severe rheumatoid arthritis, the drug reduces the elevated levels of TNF-alpha in synovial fluid that are thought responsible for pain and joint destruction. Common adverse effects include injection site reactions, upper respiratory tract infections, headache, nausea, and skin rash. Certolizumab (Cimzia), a TNF-alpha monoclonal antibody, has recently received approval for treating refractory Crohn’s disease. As with the other TNF-alpha blockers, risk of infection and allergic reactions are the major adverse effects of this drug. In addition, caution is advised when using certolizumab in patients with heart failure. Other common adverse effects include upper respiratory or bladder infection, rash, GI upset, headache, and injection site reactions. Etanercept (Enbrel) is a synthetic TNF receptor that binds with TNF and prevents it from binding with its “normal” receptors on cell surfaces. This action inhibits TNF activity in inflammatory and immune responses. The drug is indicated for the treatment of moderate to severe rheumatoid arthritis in adults and children. In this condition, the TNF increases in joint synovial fluid are considered important in joint inflammation and destruction. Etanercept may be effective in combination with methotrexate in patients who do not respond adequately to methotrexate alone. Common adverse effects include headache, injection site reactions, and infections. Limited information is available about the use of many of the newer immunosuppressants in children. The FDA has approved three TNFalpha blockers—etanercept, infliximab, and adalimumab—for use in children 4 to 17 years of age who have severe juvenile rheumatoid arthritis that has not responded to conventional therapy. Interleukin-Blocking Agents Anakinra (Kineret) is a recombinant IL-receptor antagonist. The drug binds to the IL-1 receptor and thereby blocks the inflammatory effects of IL-1. Indications for use include moderate to severe rheumatoid arthritis in adults. It may be used alone or in combination with cytotoxic immunomodulators but not with TNF-alpha–blocking agents or the fusion protein inhibitor abatacept because of increased risk of infection when these biologic agents are combined. Common adverse effects include headache, injection site reactions (redness, bruising, inflammation, pain), infection, nausea, diarrhea, decreased white blood cells, sinusitis, and flulike symptoms. Alefacept (Amevive) is a monoclonal antibody used to treat moderate to severe psoriasis. This drug binds to receptors on the surface of T lymphocytes, preventing the receptors from interacting with particular antigens, and thereby inhibiting activation of T lymphocytes. Common adverse effects include lymphopenia and injection site reactions (e.g., edema, inflammation, pain). Tocilizumab (Actemra), a humanized monoclonal antibody that blocks IL-6 receptors, recently received approval for use in adults and children with severe rheumatoid arthritis that has not responded to conventional immunosuppressants. IL-6, an inflammatory cytokine, is found in higher than normal concentrations in joints of patients with rheumatoid arthritis and contributes to chronic inflammation and joint destruction in the disorder. Tocilizumab may be combined with methotrexate. Common adverse effects include upper respiratory infection, hyperlipidemia, hypertension, leukopenia, and elevated liver enzymes. Screening for tuberculosis prior to treatment and monitoring of lipid levels and liver enzymes every 3 months during therapy is recommended. Ustekinumab (Stelara) is a monoclonal antibody used to treat psoriasis. It blocks IL-12 and IL-23, reducing the inflammatory response and overactivity of T cells. Common adverse effects include headache, infection, lymphocytosis, and a first-dose reaction characterized by chills, fever, muscle aches, and nausea. Ixekizumab (Taltz) is another monoclonal antibody used to treat adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This humanized IgG4 monoclonal antibody selectively binds with the IL-17A cytokine and inhibits its interaction with the IL-17 receptor. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines. Fusion Protein Inhibitors Abatacept (Orencia) is a fusion protein inhibitor synthesized from an IgG antibody fused to a cell protein that binds to antigen-presenting molecules. This action prevents the activation of T lymphocytes and the production of inflammatory cytokines. It inhibits activation of T https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX01cMmy1tXd%2bA0lN30h55hoLMwB%2fCluMLMNM… 3/10 11/21/23, 3:15 PM Realizeit for Student lymphocytes in synovial membranes of joints affected by rheumatoid arthritis and decreases inflammation and structural joint destruction. Abatacept may be used alone or with other antirheumatoid arthritis drugs except anakinra and TNF-alpha–blocking agents. Common adverse effects include dizziness, headache, infections, and nausea. Evidence does not suggest the need for dose adjustment in the presence of liver or renal disease. Belatacept (Nulojix), a fusion protein inhibitor, is approved for use in the prevention of acute organ rejection after kidney transplantation. The drug binds to a receptor protein on antigen-presenting cells and inhibits the costimulatory signal required for T-cell activation. This prevents T-cell activation and cytokine production, thus reducing the risk of transplant organ rejection. There is an increased risk of lymphoma in people who develop Epstein-Barr virus infection during belatacept therapy. Because of that risk, the FDA has issued a BLACK BOX WARNING that limits belatacept use to people who test positive for Epstein-Barr virus prior to transplant. Authorities do not recommend the drug for use after liver transplant because of increased risk of graft loss and associated mortality. Adverse effects include anemia, peripheral edema, hypertension, vomiting, diarrhea, constipation, fever, bladder and kidney infection, and leukopenia. Conventional Antirejection Agents Cyclosporine (Neoral, Gengraf, Sandimmune), the first antirejection drug used to prevent transplant rejection reactions, is the prototype antirejection agent. Cyclosporine and related drugs are fungal metabolites with strong immunosuppressive effects. By selectively inhibiting proliferation of helper T cells and expression of cytokines, these antirejection drugs reduce the activity of other immune cells involved in graft rejection. Consequently, they are widely used in transplant therapy to prevent or reduce the graft rejection response. Pharmacokinetics Absorption of cyclosporine is highly variable. After oral administration, absorption is rather poor. The drug is highly bound to plasma proteins, and approximately 50% is distributed in erythrocytes, so drug levels in whole blood are higher than those in plasma. Peak plasma levels occur 4 to 5 hours after a dose. Metabolism of cyclosporine involves the CYP3A4 liver enzyme system, and elimination occurs mainly in the bile. Action Cyclosporine inhibits calcineurin, a protein needed for the synthesis of IL-2 and the subsequent proliferation of T cells and B cells. The drug binds with calcineurin on T lymphocytes and interferes with the production of IL-2. As previously described, activated T cells produce a cytokine, IL-2, which, in turn, inhibits signaling through the T-cell receptor. This action activates other lymphocytes, amplifying the immune response and producing the damaging inflammatory changes in tissue that occur with organ rejection and autoimmune disease. Use Health care providers use cyclosporine to prevent rejection reactions and prolong graft survival after solid organ transplantation (e.g., kidney, liver, heart, lung) or to treat chronic rejection in patients previously treated with other immunosuppressive agents. The drug inhibits both cellular and humoral immunity but affects T lymphocytes significantly more than B lymphocytes. With cyclosporine-induced deprivation of IL-2, T cells stimulated by the graft antigen are unable to multiple and differentiate, and graft organ destruction is inhibited. In addition to its use in solid organ transplantation, cyclosporine is useful in the prevention and treatment of GVHD, a complication of bone marrow transplantation. In GVHD, T lymphocytes from the transplanted marrow of the donor mount an immune response against the tissues of the recipient. Cyclosporine may inhibit donor T-cell activity, reducing the risk of GVHD. Other indications for use include treatment of psoriasis and rheumatoid arthritis. Cyclosporine dosing is weight based in both adults and children, with higher doses given immediately before and after the transplant and then tapered over several months to minimize adverse effects and avoid excessive immunosuppression. Use in Older Adults Due to an increased incidence of infection and a greater risk of malignancy, it is necessary to monitor older adults carefully during antirejection drug therapy. Doses are individualized, considering age, function, and concurrent conditions. More frequent assessment and therapeutic blood level monitoring are essential in older adults after organ transplantation because of the increased risk of organ toxicity. Use in Patients With Renal Impairment Patients with solid organ transplants commonly use cyclosporine, but the risk of nephrotoxicity increases as a result. Clinical studies have demonstrated that this nephrotoxicity is dose related. To reduce toxicity and increase efficacy, attention must be given to dosage, other https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX01cMmy1tXd%2bA0lN30h55hoLMwB%2fCluMLMNM… 4/10 11/21/23, 3:15 PM Realizeit for Student adverse effects, and potential drug interactions. Monitoring serum blood levels can help reduce this risk, and nephrotoxicity usually subsides after decreasing the dosage or stopping the drug. In kidney transplant recipients, when serum creatinine and blood urea nitrogen (BUN) levels remain elevated, an evaluation of the patient and tissue biopsy is often necessary to differentiate cyclosporine-induced nephrotoxicity from a transplant rejection reaction. Use in Patients With Hepatic Impairment With cyclosporine, it is important to check serum bilirubin and liver enzymes prior to and during treatment. Clinical trials have shown that cyclosporine is associated with mild elevations of serum bilirubin, often without elevated ALT or alkaline phosphatase. These complications are now less frequent possibly because dosing and monitoring of cyclosporine levels have become more precise. Use in Patients With Critical Illness Use of immunosuppressants during critical illness requires individualized risk versus benefit decision making. It is necessary to balance the need to prevent transplant organ rejection against the risk of infection and associated drug toxicities, which may lead to loss of the engrafted organ. Use in Patients Receiving Home Care Survival rates are now longer in transplant recipients, and multiple organ transplants and retransplants occur. Thus, there are challenges in managing chronic rejection and minimizing drug toxicities in the home setting. Promoting correct medication use is critical to maintaining therapeutic blood levels after transplantation and preventing organ rejection. Due to the variable bioavailability of cyclosporine when taken orally, patients should consistently take the drug at the same time each day. In addition to monitoring medication use, the home care nurse provides self-care teaching, monitors for sources of infection, obtains and monitors blood work, and implements health maintenance measures. Adverse Effects Nephrotoxicity, hirsutism, gingival hypertrophy, hypertension, and hyperlipidemia are significant adverse effects of cyclosporine. The FDA has issued a BLACK BOX WARNING for cyclosporine regarding risks of hypertension and nephrotoxicity. After solid organ transplantation, with the need to continue lifelong immunosuppression to avoid graft rejection, serious infection is an ongoing concern. As previously stated, transplant recipients are living longer, and this has led to the recognition that there are long-term adverse effects associated with immunosuppressant drug therapy. As a consequence of long-term survival and chronic immunosuppression, patients have an increased risk of developing a malignancy. The incidence of malignancy is unknown, but after 10 years of immunosuppression, authorities often estimate it to be 20% or more. The most common malignancies in transplant recipients are skin cancers and lymphomas, and solid organ tumors may also occur. Regular screening tests for breast, cervical, colon, and prostate cancer, along with annual skin examinations, are recommended. The FDA has issued a BLACK BOX WARNING limiting all long-term use of antirejection drugs to prescribers experienced in transplant therapy because of the increased risk of infections and certain malignancies such as lymphoma and skin cancer. Contraindications Contraindications to cyclosporine include the combined use of antirejection drugs that have the same mechanism of action and toxicities (e.g., tacrolimus and cyclosporine). Prescribers usually avoid such use after organ transplant. Nursing Implications Preventing Interactions Numerous potential drug interactions affect the blood levels of cyclosporine, increasing or decreasing its effects. Because these drugs are metabolized mainly by CYP3A4 enzymes and have a low therapeutic index, any drugs that increase or decrease levels of these enzymes have the potential to alter blood levels of cyclosporine. The herb St. John's wort may reduce this drug's therapeutic effects. Administering the Medication It is necessary to initiate antirejection drugs several hours prior to the transplant procedure. Administration is by IV infusion only until the patient can take the drug by the oral route. The risk of a severe allergic reaction is significantly higher following IV administration. Dilution of an oral cyclosporine solution should follow package instructions. To improve bioavailability, cyclosporine preparations were once prepared in alcohol and olive oil for oral administration and in alcohol and castor oil for IV administration. Anaphylactic reactions, attributed to the castor oil, have occurred with the IV formulation. Neoral and ption and cannot be used interchangeably.Sandimmune. These different drug formulations are not equivalent in their absorGengraf are oral microemulsion formulations that are better absorbed than oral. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX01cMmy1tXd%2bA0lN30h55hoLMwB%2fCluMLMNM… 5/10 11/21/23, 3:15 PM Realizeit for Student Assessing for Therapeutic Effects The nurse assesses therapeutic effects by monitoring for organ function and signs of rejection with solid organ transplants, assessing serum blood levels, and monitoring and managing adverse drug effects. Cyclosporine has a very narrow therapeutic index; therefore, prescribers use serum drug levels to regulate cyclosporine dosing, and close monitoring is necessary. They use blood levels measured 2 hours after a dose for dosage adjustments. Subtherapeutic levels may lead to organ transplant rejection, whereas high levels increase adverse effects. Assessing for Adverse Effects Acute nephrotoxicity can occur, progressing to chronic nephrotoxicity and kidney failure. It is essential to monitor renal function tests (serum creatinine and BUN) and urine protein throughout cyclosporine therapy. To check for hepatotoxicity, it is necessary to conduct liver function tests (bilirubin, ALT, and AST) regularly. Periodic monitoring of fasting lipid levels (cholesterol, high- and low-density lipoproteins, and triglycerides) should also occur. Nonsteroidal Anti-Inflammatory Drugs These drugs are classified into two types, or “generations.” First-generation NSAIDs block both COX-1 and COX-2, and second-generation NSAIDs block only COX-2. Both first- and second-generation NSAIDs have the potential to cause serious cardiovascular thrombotic events. All NSAIDs are contraindicated in the setting of coronary artery bypass graft surgery. The nonsteroidal anti-inflammatory agents ibuprofen and indomethacin are used initially in treating patent ductus arteriosus. Propionic Acid Derivatives The propionic acid derivatives are NSAIDs that inhibit prostaglandin synthesis in both the central and peripheral nervous systems. The prototype is ibuprofen (Motrin, Advil). Pharmacokinetics Ibuprofen is 80% absorbed in the GI tract. Its onset of action is 1 hour, producing antipyretic effects, reaching a peak in 1 to 2 hours. The duration of action is 6 to 8 hours. Ibuprofen is metabolized in the liver and eliminated in the urine. A small amount of the medication is eliminated in biliary excretion. Action Ibuprofen blocks prostaglandin synthesis and modulates T-cell production. It inhibits the inflammatory cells by the process of chemotaxis to destroy the cells of inflammation. A first-generation NSAID, it blocks COX-1 and COX-2 but is more selective with COX-1. Use Ibuprofen is used to relieve mild to moderate pain, including dysmenorrhea (painful menstruation). It is also used to treat inflammation related to rheumatoid arthritis and osteoarthritis. Use in Older Adults Ibuprofen is relatively safe in therapeutic doses for occasional use as an analgesic or antipyretic in older people. The incidence of musculoskeletal disorders such as osteoarthritis is higher in older adults. However, the nurse should ensure that older adults taking ibuprofen on a long-term basis are evaluated for GI blood loss, renal dysfunction, edema, hypertension, and drug–drug or drug–drug disease interactions. A gastroprotective agent is recommended for patients at risk for upper GI bleeding. Use in Patients With Renal Impairment Ibuprofen can cause or aggravate renal impairment even though it is eliminated mainly by hepatic metabolism. By inhibiting prostaglandins that dilate renal blood vessels, it can decrease the blood flow in the kidneys. When renal blood flow is normal, the activity of these prostaglandins is limited. However, when renal blood flow is decreased, synthesis of these prostaglandins is increased, and they protect the kidneys from ischemia and hypoxia by antagonizing the vasoconstrictive effects of angiotensin II, norepinephrine, and other substances. Thus, in patients who depend on prostaglandins to maintain an adequate renal blood flow, the prostaglandin-blocking effects of ibuprofen result in constriction of renal arteries and arterioles, decreased renal blood flow, decreased glomerular filtration rate, and retention of salt and water. Ibuprofen can also cause kidney damage by other mechanisms, including a hypersensitivity reaction that leads to acute renal https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX01cMmy1tXd%2bA0lN30h55hoLMwB%2fCluMLMNM… 6/10 11/21/23, 3:15 PM Realizeit for Student failure, manifested by proteinuria, hematuria, and pyuria. Biopsy reports usually indicate inflammatory reactions such as glomerulonephritis or interstitial nephritis. People at highest risk from the use of ibuprofen and related drugs are those with preexisting renal impairment, those older than 50 years of age, those taking diuretics, and those with hypertension, diabetes, or heart failure. Measures to prevent or minimize renal damage include avoiding nephrotoxic drugs when possible, treating the disorders that increase risk of renal damage, stopping the ibuprofen if renal impairment occurs, monitoring renal function, reducing dosage, and maintaining hydration. Use in Patients With Hepatic Impairment Ibuprofen is metabolized in the liver, requiring that the dosage of the medication be decreased in patients with hepatic problems. The maximum daily dosage of ibuprofen in patients with hepatitis is 2 g. Use in Patients With Critical Illness The FDA has issued a BLACK BOX WARNING ♦ stating that ibuprofen is contraindicated for the treatment of perioperative pain after coronary artery bypass graft. Use in Patients Receiving Home Care It is important for the home care nurse to instruct the patient about all aspects of administration of ibuprofen. Because the medication is available in OTC preparations with many trade names, patients may not realize that they are taking an ibuprofen-containing drug. Overdosing may occur. Adverse Effects The GI adverse effects of ibuprofen are many: dry mouth, gingival hyperplasia, dyspepsia, heartburn, nausea, epigastric pain, constipation, and GI ulceration with occult blood loss. The genitourinary effects include nephrotoxicity, elevated blood urea nitrogen and creatinine, and edema. The respiratory adverse effects include dyspnea, bronchospasm, hemoptysis, and pharyngitis. In addition, anaphylactic reactions may also occur. The FDA has issued a BLACK BOX WARNING stating that NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including stroke or myocardial infarction. Contraindications Ibuprofen is contraindicated in patients with a known allergy to NSAIDs and salicylates. Allergic reactions are more common in patients with rhinitis, asthma, chronic urticaria, and nasal polyps (Nursing, 2019). Nursing Implications Preventing Interactions Medications and herbs interact with ibuprofen, increasing or decreasing its effects. Administering the Medication Ibuprofen is administered orally, and the total daily dose should not exceed 3200 mg. When administered intravenously, it should be diluted in a concentration of 4 mg/mL or less using 0.9% sodium chloride, 5% dextrose, or lactated Ringer’s. The dilution remains stable for 24 hours. Prior to the administration of the IV preparation, the patient should be well hydrated. Researchers have reported that the rapid infusion of ibuprofen intravenously was safe and effective in treating pain. The maximum total serum amount of IV ibuprofen was twice that of oral ibuprofen. Assessing for Therapeutic Effects When ibuprofen is administered for pain, the nurse assesses for pain. The patient should report diminished pain on a pain scale. When the drug is administered for fever, the nurse records the patient's temperature every 2 to 4 hours. Reduced fever should occur. When the drug is administered for inflammation, the nurse notes anti-inflammatory effects, particularly in the joints related to arthritis. Decreased inflammation should occur. Assessing Adverse Effects The nurse assesses the patient for dyspepsia or GI bleeding, including hemoptysis or melena. He or she also assesses complete blood count and clotting times for signs of anticoagulation. In addition, the nurse assesses for signs and symptoms of hypersensitivity to ibuprofen, including rash and bronchospasm. Patient Teaching Box 16.10 presents patient teaching guidelines for ibuprofen. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX01cMmy1tXd%2bA0lN30h55hoLMwB%2fCluMLMNM… 7/10 11/21/23, 3:15 PM Realizeit for Student BOX 16.10 Patient Teaching Guidelines for Ibuprofen Take this drug with food or liquid to decrease gastric irritation. Drink 2 to 3 quarts of fluid daily when taking this drug regularly. Report any signs of bleeding (e.g., nosebleed, vomiting blood, bruising, blood in the urine or stool), difficulty breathing, severe stomach upset, sw provider. Selective COX-2 Inhibitor: Celecoxib Celecoxib (CeleBREX) is the only selective COX-2 inhibitor on the market in the United States. The selective COX-2 inhibitors etoricoxib and parecoxib, which are available in the United Kingdom and other countries, are currently under review by the FDA. COX-2 inhibitors were designed to selectively block production of prostaglandins associated with pain and inflammation without blocking those associated with protective effects on gastric mucosa, renal function, and platelet aggregation. Thus, they produce less gastric irritation and renal impairment than aspirin and other NSAIDs. Pharmacokinetics Celecoxib, which is administered orally, has a slow onset of action. The drug reaches its peak in 3 hours. It is highly protein bound (97%), and the serum half-life is 11 hours. It is metabolized by the cytochrome P450 enzymes in the liver to inactive metabolites that are then excreted in the urine. A small amount is excreted unchanged in the urine. Celecoxib crosses the placenta and enters the breast milk. Action COX-2 is activated with inflammation. Celecoxib inhibits the COX-2 enzyme to decrease inflammation. It does not affect the COX-1 enzyme, thus protecting the lining of the GI tract and not inhibiting clotting factors. Use Celecoxib is administered for acute and long-term treatment of juvenile rheumatoid arthritis, rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. It is used to treat acute pain and primary dysmenorrhea. Use in Patients With Renal Impairment In patients with significant renal impairment, celecoxib should not be administered. Use in Patients With Hepatic Impairment In patients with hepatic impairment, the dosage of celecoxib should be reduced by 50%. Adverse Effects The CNS adverse reactions of celecoxib include headache, dizziness, somnolence, and insomnia. Some patients have noted ophthalmic changes with administration of the drug. Patients taking celecoxib are at increased risk for myocardial infarction and cerebrovascular accident. The FDA has issued a BLACK BOX WARNING for celecoxib concerning its cardiac and vascular risks. Dermatologic adverse effects include rash, pruritus, sweating, dry mucous membranes, and stomatitis. Dyspepsia and GI bleeding can occur with the administration of prolonged high doses of celecoxib, but the risk is not as profound as the COX-1 and COX-2 inhibitors. Anaphylactic reactions can also occur if the patient is allergic to celecoxib or has an aspirin or NSAID-related allergy. Contraindications Celecoxib is contraindicated in patients who have a known allergy to sulfonamides, NSAIDs, and aspirin. It is also contraindicated in patients with renal impairment. It should not be administered to patients with perioperative pain or to those who have just undergone coronary artery bypass graft surgery. Nursing Implications Preventing Interactions https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX01cMmy1tXd%2bA0lN30h55hoLMwB%2fCluMLMNM… 8/10 11/21/23, 3:15 PM Realizeit for Student The administration of anticoagulants or aspirin with celecoxib increases the risk of bleeding. Patients taking lithium and celecoxib are at risk for lithium toxicity. Celecoxib combined with alcohol or smoking increases the patient's risk of GI bleeding. Administering the Medication When administering celecoxib, the nurse should be certain to administer it 2 hours before or after an antacid to ensure absorption. Prior to administering celecoxib, assess the patient for allergic reactions to NSAIDs. It is necessary to store the medication in a light-protected container. Assessing for Therapeutic Effects The nurse assesses for diminished pain and swelling associated with inflammation. The nurse assesses joints for redness, heat, and stiffness. Mobility should increase with the administration of celecoxib. Assess for Adverse Effects The nurse assesses the patient for signs and symptoms of chest pain, shortness of breath, confusion, or numbness of the extremities. These symptoms are indicative of cardiac event such as myocardial infarction or cerebrovascular accident. Also, it is necessary to assess for dyspepsia, GI irritation, and GI bleeding. In addition, the nurse assesses for CNS depression and ophthalmic changes. Finally, he or she assesses for anaphylactic reactions, including sore throat, itching, weight gain, and edema. Drug Therapy Antidepressant therapy may be indicated if depressive symptoms persist at least 2 weeks, impair social relationships or work performance, and occur independently of life events. Antidepressants are used to regulate mood specifically affecting serotonin, norepinephrine, and dopamine. Antidepressant effects are attributed to changes in receptors rather than changes in neurotransmitters. Although some of the drugs act more selectively on one neurotransmission system than another initially, this selectivity seems to be lost with chronic administration. Drugs used in the pharmacologic management of depressive disorders are derived from several chemical groups. Older antidepressants include the tricyclic antidepressants (TCAs) and the monoamine oxidase (MAO) inhibitors. Newer drugs include the selective serotonin reuptake inhibitors (SSRIs), the serotonin–norepinephrine reuptake inhibitors (SNRIs), and several adjuvant atypical antidepressant drugs that differ from TCAs and MAO inhibitors. As the name implies, reuptake inhibitors block the reuptake of certain neurotransmitters (serotonin with the SSRIs and serotonin and norepinephrine with the SNRIs). BOX 17.4 Patient Teaching Guidelines for Long-Term Corticosteroid Therapy General Considerations Realize that in most instances, corticosteroids are used to relieve symptoms; they do not cure the underlying disease process. However, they can When taking an oral corticosteroid (e.g., prednisone) for longer than 2 weeks, take the drug as directed. This is extremely important. Missing a do the amount or time of administration, taking extra drug (except as specifically directed during stress situations), or any other alterations may resu are relatively minor; several are serious, even life threatening. When these drugs are being discontinued, the dosage is gradually reduced over se abruptly. Wear a special medical alert bracelet or tag or carry an identification card stating the drug being taken; the dosage; the prescriber’s name, addre instructions for emergency treatment. If an accident or emergency situation occurs, health care providers must know about corticosteroid drug th the stress of the emergency. Report to all health care providers consulted that corticosteroid drugs are being taken or have been taken within the past year. Current or previou treatment measures, and such knowledge increases the ability to provide appropriate treatment. Maintain regular medical supervision. This is extremely important so that the prescriber can detect adverse reactions, evaluate disease status, an for dosage change, as well as other responsibilities that can be carried out only with personal contact between the prescriber and the patient. Pe other tests may be performed during long-term corticosteroid therapy. Take no other drugs, prescription or nonprescription, without notifying the prescriber who is supervising corticosteroid therapy. Corticosteroid dr some other drugs interact with corticosteroids to either increase or decrease their effects. Thus, taking other drugs can decrease the expected th incidence or severity of adverse effects. Avoid exposure to infection when possible. Avoid crowds and people known to have an infection. Also, wash hands frequently and thoroughly. T infection, so preventive measures are necessary. Also, if infection does occur, healing is likely to be slow. Practice safety measures to avoid accidents (e.g., falls and possible fractures due to osteoporosis, cuts or other injuries because of delayed wou increased tendency to bruise easily). Weigh frequently when starting corticosteroid therapy and at least weekly during long-term maintenance. An initial weight gain is likely to occur a appetite. Later weight gains may be caused by fluid retention. Ask the prescriber about the amount and kind of activity or exercise needed. As a general rule, being as active as possible helps prevent or delay However, increased activity may not be desirable for everyone. A patient with rheumatoid arthritis, for example, may become too active when dru mobility. Follow instructions for other measures used in treatment of the particular condition (e.g., other drugs and physical therapy for rheumatoid arthriti doses of corticosteroids and decrease adverse effects. Understand that the dosage may need to be temporarily increased with illness, surgery, or other stressful situations because corticosteroids impa with the prescriber predictable sources of stress and the amount of drug to be taken if the stress cannot be avoided. In addition to stressful situations, report sore throat, fever, or other signs of infection; weight gain of 5 lb or more in a week; or swelling in the ank indicate adverse drug effects, and changes in corticosteroid therapy may be indicated. Realize that muscle weakness and fatigue or disease symptoms may occur when drug dosage is reduced, withdrawn, or omitted (e.g., the nondr these symptoms may cause some discomfort, they should be tolerated if possible rather than increasing the corticosteroid dose. If severe, of co have to be changed. Understand that dietary changes may be helpful in reducing some adverse effects of corticosteroid therapy. Decreasing salt intake (e.g., by not a obviously salty foods, such as many snack foods and prepared sandwich meats) may help decrease swelling. Eating high-potassium foods, such https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX01cMmy1tXd%2bA0lN30h55hoLMwB%2fCluMLMNM… 9/10 11/21/23, 3:15 PM Realizeit for Student may help prevent potassium loss. An adequate intake of calcium, protein, and vitamin D (meat and dairy products are good sources) may help to (e.g., from citrus fruits) may help to prevent excessive bruising. Do not object when your prescriber reduces your dose of oral corticosteroid, with the goal of stopping the drug entirely or continuing with a sma used only when necessary because of the potential for serious adverse effects, and the lowest effective dose should be given. Understand that with local applications of corticosteroids, there is usually little systemic absorption and few adverse effects, compared with oral relieving symptoms, it is better to use a local than a systemic corticosteroid. In some instances, combined systemic and local application allows systemic drug. Commonly used local applications are applied topically for skin disorders, by oral inhalation for asthma, and by nasal inhalation for allergic rhiniti tolerated, systemic toxicity can occur if excess corticosteroid is inhaled or if occlusive dressings are used over skin lesions. Thus, a corticosteroi correctly and not overused. Know that corticosteroids are not the same as the steroids often abused by athletes and body builders. Those are anabolic steroids derived from Self or Caregiver Administration Take an oral corticosteroid with a meal or snack to decrease GI upset. If taking the medication once a day or every other day, take before 9:00 am; if taking multiple doses, take at evenly spaced intervals throughout t Report to the prescriber if unable to take a dose orally because of vomiting or some other problem. In some circumstances, the dose may need t If taking an oral corticosteroid in tapering doses, be sure to follow instructions exactly to avoid adverse effects. When applying a corticosteroid to skin lesions, do not apply more often than ordered and do not cover with an occlusive dressing unless specific With an intranasal corticosteroid, use on a regular basis (usually once or twice daily) for the best anti-inflammatory effects. With an oral inhalation corticosteroid, use on a regular schedule for anti-inflammatory effects. The drugs are not effective in relieving acute asthm should not be used “as needed” for that purpose. Use metered-dose inhalers as follows (unless instructed otherwise by a health care provider): 1. Shake canister thoroughly.2. Place canister between lips (both open and pursed lips have been recommended) or outside lips.3. Exhale comp slow, deep breath.5. Hold breath for 10 seconds or as long as possible.6. Wait at least 1 minute before taking additional inhalations.7. Rinse mou incidence of oral thrush (a fungal infection).8. Rinse mouthpiece at least once per day. TCAs, second-line medications in the treatment of depression, produce a high incidence of adverse effects (e.g., sedation, orthostatic hypotension, cardiac dysrhythmias, anticholinergic effects, and weight gain). SSRIs are considered to be first-line medications in the treatment of depression because they have a more favorable side effect profile (e.g., GI symptoms, sexual dysfunction, CNS stimulation, and increased risk of GI bleeding). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX01cMmy1tXd%2bA0lN30h55hoLMwB%2fCluMLMN… 10/10