Learning Outcomes
By the end of this section, you should be able to:
- 6.4.1 Describe the pathophysiology of inflammation.
- 6.4.2 Discuss the five cardinal signs of inflammation.
- 6.4.3 Identify the etiology and diagnostic studies related to inflammation.
- 6.4.4 Identify the characteristics of drugs used to treat inflammation.
- 6.4.5 Explain the indications, actions, adverse reactions, and interactions of drugs used to treat inflammation.
- 6.4.6 Describe the nursing implications of drugs used to treat inflammation.
- 6.4.7 Explain the client education related to drugs used to treat inflammation.
Inflammation, the body’s complex response to harmful stimuli, plays an important role in the immune system’s defense against injury and infection. This section of the chapter explores mechanisms for inflammation and drugs used to treat inflammation.
Inflammation
Inflammation is a fundamental biological response that the body activates in response to harmful stimuli, such as pathogens, tissue injury, or irritants. It is a crucial part of the immune system's defense mechanism, designed to protect the body and initiate the healing process. Inflammation involves a series of intricate events and interactions among cells, chemicals, and blood vessels. When tissues are damaged or infected, various immune cells are recruited to the site of injury or infection (Chen et al., 2018; Hannoodee & Nasuruddin, 2022). The key players in the inflammatory response include:
- Mast cells: These cells are present in connective tissues and release substances such as histamine, which trigger blood vessels to dilate and become more permeable, leading to increased blood flow and leakage of fluid into the affected area.
- White blood cells (leukocytes): Neutrophils and macrophages are the primary types of leukocytes involved in the inflammatory response. They migrate to the site of injury or infection to engulf and destroy invading pathogens and damaged cells.
- Cytokines: These are signaling molecules that help regulate the immune response and mediate communication between different cells. Pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), play a central role in initiating and amplifying the inflammatory process.
- Chemokines: These are a subgroup of cytokines that attract immune cells to the site of inflammation, promoting their migration and recruitment (Chen et al., 2018; Hannoodee & Nasuruddin, 2022; Patel & Mohiuddin, 2023).
There are five cardinal signs of inflammation that were first described by the Roman encyclopedist Celsus in the 1st century AD and are still widely recognized as classic indicators of an inflammatory response in the body (Cavaillon, 2021). These are (Chen et al., 2018; Hannoodee & Nasuruddin, 2022):
- Redness (rubor): The affected area becomes red due to increased blood flow and dilation of blood vessels in response to inflammation.
- Swelling (tumor): Swelling occurs as fluid and immune cells accumulate at the site of inflammation.
- Heat (calor): Inflammation leads to increased blood flow and metabolic activity in the affected area, resulting in elevated temperature and warmth.
- Pain (dolor): Inflammatory mediators sensitize nerve endings in the affected region, leading to pain.
- Loss of function (functio laesa): In more severe cases of inflammation, the affected area may lose some or all of its normal function. This can occur due to the damage caused by the inflammation or the body's protective response to limit further harm.
Pathophysiology
The body's inflammatory response is a complex and coordinated reaction aimed at defending against harmful stimuli and promoting tissue repair (Hannoodee & Nasuruddin, 2022). When tissues are damaged, injured, or infected, various immune cells and chemical mediators work together to initiate and regulate the inflammatory process. The response can be triggered by various factors, including pathogens (e.g., bacteria, viruses), physical injury, toxins, or autoimmune reactions. The inflammatory response (see Figure 6.4) presents as follows:
- Recognition of harmful stimuli: The process begins when the body detects a threat, such as a pathogen or tissue injury. Immune cells, particularly macrophages, recognize these harmful stimuli through pattern recognition receptors.
- Release of chemical mediators: Upon recognition of the threat, immune cells release signaling molecules called cytokines, such as interleukins and TNF-α, which trigger the cascade of events that lead to inflammation.
- Vasodilation: Cytokines and other chemical mediators cause blood vessels in the affected area to dilate, leading to increased blood flow and allowing more immune cells, antibodies, and nutrients to reach the site of injury or infection.
- Increased vascular permeability: The cytokines increase the permeability of blood vessel walls, leading to the leakage of fluid and proteins into the surrounding tissues, which contributes to the swelling, redness, and warmth.
- Migration of immune cells: Chemokines attract immune cells, particularly neutrophils and monocytes.
- Phagocytosis and immune response: Neutrophils and macrophages engulf and destroy invading pathogens, dead cells, and debris through a process called phagocytosis. This helps contain the infection and clear away damaged tissues.
- Activation of the adaptive immune system: As the inflammatory response progresses, dendritic cells, another type of immune cell, process and present antigens from the pathogens to T and B lymphocytes. This leads to the activation of the adaptive immune system, which provides a more specific and targeted response to infection.
- Resolution and tissue repair: As the threat is neutralized and the tissue damage begins to heal, the body releases anti-inflammatory cytokines, such as interleukin-10 (IL-10), which promote the resolution of inflammation. Immune cells shift their focus to tissue repair and regeneration.
The inflammatory response is a highly regulated process that aims to eliminate the threat, initiate healing, and restore tissue function. However, an exaggerated or dysregulated inflammatory response can lead to chronic inflammation and contribute to various diseases. Anti-inflammatory drugs are used to control and modulate this response, providing relief and preventing further tissue damage in certain conditions.
Etiology and Diagnostic Testing
Factors that trigger the inflammatory response in the body can arise from various sources, including infections (bacterial, viral, fungal, and parasitic), physical injury to tissue (trauma, burns), autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus), allergic reactions, irritants, and chronic conditions such as chronic obstructive pulmonary disorders (COPD) and peripheral vascular disorders (PVD).
Diagnostic and lab studies are essential for diagnosing and assessing inflammation. Some common tests and investigations include:
- Complete blood count (CBC) with differential: This test provides information about the number and types of blood cells, including white blood cells (WBCs). An increased WBC count, particularly neutrophils, can indicate an inflammatory response.
- C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR): These blood tests measure markers of inflammation. Elevated levels of CRP or an accelerated ESR suggest the presence of inflammation in the body.
- Blood cultures: If an infection is suspected as the cause of inflammation, blood cultures may be performed to identify the specific microorganism responsible.
- Imaging studies: X-rays, ultrasounds, CT scans, or MRIs can help visualize inflamed tissues and identify the extent of inflammation or structural damage.
- Biopsy: In some cases, a tissue sample may be obtained through a biopsy to determine the cause and severity of inflammation.
- Autoantibody testing: For suspected autoimmune disorders, specific autoantibody tests can be conducted to identify abnormal immune responses against the body's own tissues.
- Allergy testing: In cases of allergic inflammation, skin tests or blood tests can help identify specific allergens responsible for the allergic response.
The combination of clinical evaluation, medical history, and appropriate diagnostic tests helps health care providers diagnose the presence of inflammation, identify its underlying cause, and develop an effective treatment plan to address the condition.
Inflammation versus Infection
Inflammation and infection are related but distinct concepts in the context of the body's response to harmful stimuli. Inflammation is a general physiological response of the body to tissue injury, irritation, or foreign substances. It is a part of the body's immune defense mechanism and plays a vital role in protecting and healing tissues. Inflammation can be triggered by various factors, such as physical injury, exposure to irritants, autoimmune reactions, or the presence of pathogens like bacteria or viruses. When tissues are damaged or perceived to be under threat, immune cells and chemical mediators are recruited to the affected site, leading to the characteristic symptoms of inflammation, including redness, swelling, heat, and pain. The inflammatory response aims to eliminate the source of injury or infection, clear away damaged cells and debris, and initiate tissue repair (Chen et al., 2018; Hannoodee & Nasuruddin, 2022).
Infection, on the other hand, specifically refers to the invasion and colonization of the body by harmful microorganisms such as bacteria, viruses, or other microbes (CDC, 2016). When pathogens enter the body, they can multiply and cause damage to tissues, leading to illness. Infections can occur in various parts of the body, such as the respiratory tract, urinary tract, gastrointestinal system, or bloodstream. The body responds to infections by initiating an inflammatory response as part of its immune defense mechanism. Infections may or may not cause obvious symptoms of inflammation, depending on the type and location of the infection and the client’s immune response. While not all inflammation is caused by infections, infections frequently lead to an inflammatory response.
Anti-inflammatory Drugs
Anti-inflammatory drugs are a classification of drugs used to reduce inflammation, relieve pain, and alleviate fever (Ghlichloo & Gerriets, 2023). These drugs work by inhibiting the production of certain enzymes called cyclooxygenase (COX), which are involved in the synthesis of prostaglandins, hormone like-substances that play a role in the inflammatory response.
Nonsteroidal Anti-inflammatory Drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2 enzymes. COX-1 and COX-2 are enzymes involved in the production of prostaglandins, which are signaling molecules that regulate inflammation and various physiological processes. COX-1 is constitutively present in many tissues and plays a role in maintaining normal bodily functions, such as protecting the stomach lining and regulating blood clotting. COX-2 is induced during inflammation and is primarily responsible for generating prostaglandins that contribute to pain, inflammation, and other responses associated with injury and inflammation. The inhibition of these enzymes helps to decrease inflammation, pain, and fever. These drugs are for short-term use, and many can be found over the counter (OTC). Several subclassifications of NSAIDs are explored in the subsequent sections.
Salicylates
Salicylates are a group of chemical compounds that contain a salicylate acid backbone. The most common and well-known salicylate is acetylsalicylic acid, also known as aspirin. Salicylates can be found in various plants, including fruits (such as berries), vegetables (such as spinach), and herbs (such as peppermint). Salicylates are commonly used to alleviate pain, reduce inflammation, and lower fever, making them effective for various conditions, including headaches, arthritis, and minor injuries. See Table 6.8 for dosing information and Pain Response Drugs for additional information on salicylates.
Aspirin also has anti-platelet properties that are unrelated to its anti-inflammatory properties. At low doses, aspirin irreversibly inhibits the enzyme cyclooxygenase-1 (COX-1) in platelets, which are specialized blood cells involved in blood clotting, thereby inhibiting platelet aggregation and blood clot formation (see Anticoagulant, Antiplatelet, and Thrombolytic Drugs for additional information on aspirin as an antiplatelet).
Phenylacetic Acid Derivatives
Phenylacetic acid derivatives are a class of chemical compounds that have a phenylacetic acid structure. These derivatives are often found in medications and are used for various therapeutic purposes. Like salicylates, phenylacetic acid derivatives inhibit the enzyme cyclooxygenase, thereby decreasing inflammation. They also act as an antipyretic and analgesic to alleviate pain. Common phenylacetic acid derivatives include diclofenac and indomethacin. See Table 6.8 for dosing information.
Propionic Acid Derivatives
Propionic acid derivatives have a propionic acid base in their chemical structure. They also inhibit the enzyme COX, thereby decreasing inflammation, relieving pain, and reducing fever. Common propionic acid derivatives include ibuprofen and naproxen sodium. See Table 6.8 for dosing information and Pain Response Drugs for additional information on these drugs.
Oxicams
Oxicams are a class of NSAIDs that share a common chemical structure called “oxicam.” These drugs work by inhibiting the enzyme COX, thus decreasing the inflammatory response. Oxicams are used for their anti-inflammatory, analgesic (pain-relieving), and antipyretic (fever-reducing) properties, like other NSAIDs. Common oxicams include meloxicam and piroxicam. See Table 6.8 for dosing information.
COX-2 Inhibitors
COX-2 inhibitors are a specific class of NSAIDs that selectively target and inhibit the cyclooxygenase-2 (COX-2) enzyme. This class of drugs was developed to provide pain relief and anti-inflammatory effects while minimizing some of the gastrointestinal side effects associated with traditional non-selective NSAIDs, which inhibit both COX-1 and COX-2 enzymes. Celecoxib is the only COX-2 inhibitor on the market in the United States. See Table 6.9 for additional information.
Table 6.8 lists common nonsteroidal anti-inflammatory drugs and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Salicylates | |
| Salicylic acid (aspirin) |
Tablet or enteric coated tablet, 1 or 2 325 mg tablets orally every 4 hours while symptoms last. |
| Phenylacetic Acid Derivatives | |
|
Diclofenac (Voltaren) |
For the relief of osteoarthritis: 100–150 mg/day orally in divided doses, 50 mg 2 or 3 times a day. For the relief of rheumatoid arthritis: 150–200 mg/day orally in divided doses, 50 mg 3 or 4 times a day. |
| Indomethacin (Indocin, Tivorbex) |
Immediate release: 25 mg orally 2 or 3 times daily. Increase the daily dosage by 25–50 mg, if required by continuing symptoms, at weekly intervals until a satisfactory response is obtained or until a total daily dose of 150–200 mg is reached. Extended release: 75 mg orally once daily. |
| Propionic Acid Derivatives | |
|
Ibuprofen (Advil) |
200 mg orally every 4–6 hours while symptoms persist. |
| Naproxen sodium (Aleve) |
220 mg orally every 8–12 hours while symptoms last. Do not exceed 440 mg in any 8- to 12-hour period; do not exceed 660 mg in a 24-hour period. |
| Oxicams | |
|
Meloxicam (Mobic) |
5 mg orally once daily. May be increased to 10 mg orally in clients who require additional analgesia. Maximum daily dose: 10 mg. |
|
Piroxicam (Feldene) |
20 mg orally once daily. |
| COX-2 Inhibitor | |
| Celecoxib (Celebrex) |
100–200 mg orally twice daily. |
Adverse Effects and Contraindications
Although NSAIDs are generally well-tolerated, they can have adverse effects and contraindications that clients should be aware of. It is important to note that the severity and occurrence of adverse effects can vary from person to person, and not everyone will experience all of the listed adverse effects. Common adverse effects of NSAIDs include gastrointestinal issues (stomach pain, heartburn, indigestion, nausea, GI bleeding), headache, dizziness, fluid retention, high blood pressure, renal and liver impairment, and an increased risk of cardiovascular events such as heart attack and stroke.
Contraindications include hypersensitivity to the drug or any of its components; having a history of allergies, asthma, or urticaria (hives) after taking aspirin or other NSAIDs; coronary artery bypass graft (CABG) surgery; and with celecoxib sulfonamide allergy.
Table 6.9 is a drug prototype table for NSAIDs featuring celecoxib. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class NSAID, COX-2 inhibitor Mechanism of Action Inhibits prostaglandin synthesis, primarily via inhibition of COX-2 |
Drug Dosage 100–200 mg orally twice daily. |
|
Indications Osteoarthritis Rheumatoid arthritis Ankylosing spondylitis Acute pain Primary dysmenorrhea Therapeutic Effects Decreases inflammation and pain |
Drug Interactions No significant interactions Food Interactions No significant interactions |
|
Adverse Effects Abdominal pain Dyspepsia Peripheral edema Dizziness Rash Hepatotoxicity Renal toxicity GI bleeding Thrombocythemia Bronchospasm Photosensitivity |
Contraindications Hypersensitivity History of allergies, asthma, or urticaria after taking aspirin or other NSAIDs CABG surgery Sulfonamide allergy Caution: May increase risk of cardiovascular thrombotic events and GI bleeding |
FDA Black Box Warning
NSAIDs
NSAIDs increase the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
NSAIDs also increased the risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Older clients and clients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.
Glucocorticoid Drugs
Glucocorticoids, also known as corticosteroids or simply steroids, are a class of anti-inflammatory drugs that mimic the action of naturally occurring hormones produced by the adrenal glands. These hormones, specifically cortisol, play a crucial role in regulating the body's response to stress and inflammation. When used as medication, synthetic glucocorticoids have potent anti-inflammatory effects due to their ability to modify the immune response. See Immunosuppressants, Biologics, Monoclonal Antibodies, and Biosimilar Drugs and Hypothalamus, Pituitary, and Adrenal Disorder Drugs for drug information on glucocorticoids.
Disease-Modifying Antirheumatic Drugs (DMARDs)
Disease-modifying antirheumatic drugs (DMARDs) are a class of medications used primarily to treat autoimmune and inflammatory conditions such as rheumatoid arthritis (Benjamin et al., 2022; Mysler et al., 2021). These drugs work by targeting specific components of the immune system to suppress the abnormal immune reaction responsible for causing inflammation and tissue damage.
DMARDs have immunomodulatory effects, meaning they modify the immune response rather than just providing symptomatic relief. The main goal of DMARDs is to slow down or modify the underlying disease process, reduce joint damage, and improve long-term outcomes for clients with autoimmune diseases. They may take weeks to months to achieve the disease-modifying effects. DMARDs are usually prescribed for long-term use and are considered the ongoing management of autoimmune conditions.
Conversely, non-DMARDs, such as NSAIDs and glucocorticoids, primarily provide symptomatic relief by reducing pain and inflammation. They do not alter the underlying disease process or the progression of the autoimmune condition. Non-DMARDs are often used for short-term and intermittent relief of acute symptoms, especially pain and inflammation. Non-DMARDs are often used in combination with DMARDs for comprehensive autoimmune disease management.
DMARDs can include both biologics and non-biologic drugs (Mysler et al., 2021). The choice of DMARD depends on the specific condition being treated, disease severity, individual response, and potential side effects. Treatment decisions are made in consultation with a health care provider who will tailor the therapy to each client’s unique needs and health status.
Biologic DMARDs
Biologic DMARDs are drugs derived from living cells or organisms. They are typically large, complex molecules produced through biotechnology processes. They target specific components of the immune system to suppress the abnormal immune response seen in autoimmune diseases. Biologic drugs such as adalimumab, etanercept, infliximab, and rituximab are discussed in Immunosuppressants, Biologics, Monoclonal Antibodies, and Biosimilar Drugs.
Non-biologic DMARDs
Non-biologic DMARDs, also known as conventional or synthetic DMARDs, are small-molecule drugs synthesized chemically. They are not derived from living sources and typically have a more general or broader mode of action. They may act on multiple targets within the immune system or inhibit enzymes that play a role in the inflammatory process. For example, methotrexate inhibits an enzyme involved in the synthesis of DNA and RNA, which affects rapidly dividing cells, including immune cells. Common non-biologic DMARDs include methotrexate, sulfasalazine, and gold salts. See Table 6.10 for dosing information and Table 6.11 for additional information on methotrexate.
Table 6.10 lists common non-biologic DMARDs and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Methotrexate (Trexall) |
7.5 mg orally once weekly with escalation to achieve optimal response. Dosages of more than 20 mg once weekly result in an increased risk of serious adverse reactions, including myelosuppression. |
| Sulfasalazine (Azulfidine) |
Initial therapy: 3000–4000 mg orally daily in evenly divided doses with dosage intervals not exceeding 8 hours. Maintenance therapy: 2000 mg orally daily. |
Adverse Effects and Contraindications
Common adverse effects for non-biologic DMARDs include nausea/vomiting, diarrhea, abdominal pain, hepatotoxicity, rash, anemia, thrombocytopenia, neutropenia, photosensitivity, elevated blood pressure, hair loss, hypotension, pancreatitis, and with methotrexate, optic neuritis. Contraindications include hypersensitivity to the drug or any of its constituents, pregnancy and/or breastfeeding, myelosuppression, live vaccines, alcohol use, pre-existing bleeding disorders, and in clients who have an active infection. For adverse effects and contraindications for biologic DMARDs, see Immunosuppressants, Biologics, Monoclonal Antibodies, and Biosimilar Drugs in this chapter.
Table 6.11 is a drug prototype table for DMARDs featuring methotrexate. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class Anti-inflammatory, DMARDs, antineoplastic Mechanism of Action Inhibits enzyme AICAR transformylase, leading to hindrance in adenosine and guanine metabolism, thereby decreasing inflammation |
Drug Dosage 7.5 mg orally once weekly with escalation to achieve optimal response. Dosages of more than 20 mg once weekly result in an increased risk of serious adverse reactions, including myelosuppression. |
| Indications Rheumatoid arthritis Psoriasis Acute lymphoblastic leukemia and non-Hodgkin lymphomas Therapeutic Effects Decreases inflammation Suppresses the immune response |
Drug Interactions Neomycin Antifolate drugs NSAIDs Phenytoin Probenecid Folic acid Food Interactions No significant interactions |
|
Adverse Effects Deep vein thrombosis/pulmonary emboli Hypotension Hyperglycemia Optic neuropathy Pancreatitis Anemia Hepatoxicity Osteoporosis Alopecia Hematuria Pulmonary fibrosis Skin necrosis |
Contraindications Hypersensitivity Pregnancy and/or breastfeeding Myelosuppression Live vaccines Alcohol use Preexisting bleeding disorders Active infection Caution: May cause myelosuppression |
FDA Black Box Warning
Methotrexate and Gold Salts
Methotrexate can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, methotrexate tablets are contraindicated in pregnancy. For neoplastic diseases, advise clients of childbearing age of the potential risk to a fetus and to use effective contraception.
Serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys. Withhold or discontinue methotrexate tablets as appropriate.
Antimalarial Drugs
Antimalarial drugs are a group of medications primarily used to treat and prevent malaria, a parasitic infection transmitted by mosquito bites. However, some antimalarial drugs have been found to have beneficial effects in the treatment of certain autoimmune diseases due to their immunomodulatory properties.
The exact mechanisms of action of these drugs in autoimmune diseases are not fully understood, but they are believed to modulate the immune response by influencing the function of immune cells and cytokines involved in the inflammatory process (Haładyj et al., 2018). Therefore, they help to control disease activity by decreasing inflammation, slowing joint damage, and preserving joint function, reducing the frequency of flares and improving overall disease management.
The two main antimalarial drugs used in autoimmune disease treatment are hydroxychloroquine and chloroquine. These drugs are known to have anti-inflammatory and immunomodulatory effects, which can help in managing autoimmune conditions.
It is important to note that while antimalarial drugs can be beneficial for some clients with autoimmune diseases, not everyone responds the same way to these medications. The decision to suggest antimalarial drugs as part of the treatment plan is made by a health care professional, who considers the specific autoimmune condition, disease severity, individual response, and potential side effects.
Hydroxychloroquine
Hydroxychloroquine is the more commonly prescribed antimalarial drug for autoimmune disease treatment. It is used to manage conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Hydroxychloroquine works by interfering with the immune response and dampening the activity of certain immune cells. It can help reduce inflammation, slow disease progression, preserve joint function, and improve disease control in some clients with autoimmune disorders. See Table 6.13 for additional information on hydroxychloroquine.
Chloroquine
Chloroquine shares similar properties with hydroxychloroquine. It has been used to treat autoimmune diseases, but its use has decreased due to the availability of hydroxychloroquine, which is considered to have a better safety profile.
Table 6.12 lists common antimalarial drugs with typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Hydroxychloroquine (Plaquenil) |
Initial dosage: 400–600 mg orally daily. Chronic dosage: 200–400 mg orally daily. |
| Chloroquine (Chloroquine FNA) |
500 mg orally once per week on exactly the same day of each week. |
Adverse Effects and Contraindications
Common adverse effects of antimalarials used as anti-inflammatories include gastrointestinal issues (nausea, vomiting, diarrhea, abdominal pain), prolonged QT interval, tachycardia, rash, itching, hepatotoxicity, renal impairment, photosensitivity, visual field disturbances, retinopathy, alopecia, myopathy and muscle weakness, agranulocytosis, and aplastic anemia.
Contraindications include hypersensitivity to the drug or any of its components, preexisting eye conditions such as macular degeneration, preexisting heart conditions such as arrythmias, pregnancy and/or breastfeeding, and liver or renal impairment.
Table 6.13 is a drug prototype table for antimalarial drugs featuring hydroxychloroquine. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class Antimalarial Mechanism of Action Inhibits antigen presentation, B- and T-cell activation, and NOX signaling |
Drug Dosage Initial dosage: 400–600 mg orally daily. Chronic dosage: 200–400 mg orally daily. |
|
Indications Rheumatoid arthritis Systemic lupus erythematosus Chronic discoid lupus erythematosus Malaria Therapeutic Effects Decreases inflammation Suppresses the immune response |
Drug Interactions Antiarrhythmics Antiepileptics Methotrexate Digoxin Cimetidine Rifampin Praziquantel Antacids Ampicillin Food Interactions No significant interactions |
|
Adverse Effects Bone marrow suppression Anemia/thrombocytopenia Prolonged QT interval Tachycardia Pulmonary hypertension Retinopathy/visual field disturbances Nausea/vomiting Fatigue Urticaria Myopathy Headache Seizure Alopecia Hepatotoxicity Renal impairment |
Contraindications Hypersensitivity Pregnancy and/or breastfeeding Preexisting eye conditions Preexisting heart conditions Liver or renal impairment Caution: May worsen eye conditions such as macular degeneration |
Antigout Drugs
Antigout drugs are a class of medications used to treat gout, a condition caused by the buildup of uric acid crystals in the joints. These drugs work to manage acute gout attacks and prevent future gout flares by reducing the level of uric acid in the body or by alleviating inflammation and pain associated with gout attacks (National Institute for Health and Care Excellence (NICE), 2022).
Although various drugs can be used to treat gout, including glucocorticoids and NSAIDs, this section of the chapter will only discuss the more common drugs used to treat gout (and its inflammatory response): colchicine, allopurinol, and probenecid.
Colchicine
Colchicine is an alkaloid drug derived from the autumn crocus plant. It is used to treat acute gout attacks and can help reduce inflammation and pain in the affected joints. Colchicine works by interfering with the movement of white blood cells to the inflamed area, thereby reducing the inflammatory response. Despite its effectiveness, colchicine has side effects that may impact compliance with the medication regimen. These include gastrointestinal disturbances such as severe diarrhea, abdominal pain, nausea, and vomiting. Health care providers should discuss this drug thoroughly with the client so that gout can be adequately managed. See Table 6.15 for additional information on colchicine.
Allopurinol
Allopurinol is a medication used primarily to manage gout and certain other conditions associated with elevated levels of uric acid in the body. It is classified as a xanthine oxidase inhibitor and primarily works to lower uric acid levels in the body by inhibiting the enzyme xanthine oxidase.
When uric acid crystals accumulate in the joints, they can provoke an inflammatory response by activating the immune system. This leads to the release of inflammatory cytokines and other mediators that cause the characteristic swelling, redness, and pain associated with gout attacks. By lowering uric acid levels, allopurinol helps to reduce the frequency and severity of gout attacks, thereby indirectly contributing to the reduction of inflammation.
While allopurinol is effective in managing gout and preventing gout attacks, it may take several weeks or months of continuous use to achieve full benefits. See Table 6.14 for dosing information.
Probenecid
Probenecid is classified as a uricosuric agent, which means it works by increasing the excretion of uric acid in the urine. It does this by inhibiting the reabsorption of uric acid in the kidneys, which leads to more uric acid being eliminated from the body through urine. By increasing the excretion of uric acid, probenecid helps lower the levels of uric acid in the blood, reducing the risk of uric acid crystal formation and gout attacks. Probenecid indirectly helps to manage the inflammatory response associated with gout.
Table 6.14 lists common antigout drugs with typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Colchicine (Colcrys) |
0.6 mg orally once or twice daily; maximum dose 1.2 mg per day. |
| Allopurinol (Zyloprim) |
For mild gout: 200–300 mg/day orally. For moderately severe tophaceous gout: 400–600 mg/day orally. |
| Probenecid (Probalan) |
250 mg orally twice daily for 2 weeks, followed by 500 mg orally twice daily thereafter. |
Adverse Effects and Contraindications
Common adverse effects of antigout drugs include abdominal pain and cramping, nausea, vomiting, diarrhea, myopathy, abnormal liver and renal function, rash, and neuropathy. Common contraindications include hypersensitivity to the drug or any of its components, and renal or hepatic impairment.
Table 6.15 is a drug prototype table for antigout drugs featuring colchicine. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class Antigout, alkaloid Mechanism of Action Inhibits expression of E-selectin on endothelial cells and prevents neutrophil adhesion |
Drug Dosage 0.6 mg orally once or twice daily; maximum dose: 1.2 mg daily. |
|
Indications Prophylaxis of gout flare-ups Therapeutic Effects Decreases inflammation and pain |
Drug Interactions CYP3A4 inhibitors P-glycoprotein inhibitors HMG-CoA reductase inhibitors Fibrates Voriconazole Fluconazole Cimetidine Propafenone Food Interactions Grapefruit and grapefruit juice |
|
Adverse Effects Gastrointestinal (abdominal cramps/pain, diarrhea, nausea/vomiting) Sensory motor neuropathy Rash Alopecia Leukopenia/thrombocytopenia/pancytopenia Elevated AST and/or ALT Myopathy and muscle weakness/pain Elevated CPK Azoospermia/oligospermia (conditions affecting sperm motility or sperm count) |
Contraindications Hypersensitivity Renal impairment Hepatic impairment Caution: May cause colchicine toxicity when used concomitantly with CYP3A4 inhibitors and P-glycoprotein inhibitors |
Nursing Implications
The nurse should do the following for clients who are taking antigout drugs:
- Before administering antigout drugs, conduct a thorough assessment of the client's medical history, current medications, allergies, and kidney and liver function.
- Monitor the following laboratory studies: serum uric acid levels to assess effectiveness of medications in reducing uric acid levels, liver function for hepatotoxicity, renal function for nephrotoxicity, and electrolyte levels, which may be impacted by the use of these drugs.
- Educate the client about the drug’s purpose, potential side effects, and benefits to help the client make an informed decision about the treatment plan.
- Some antigout drugs may have potential side effects or interactions with other medications. The nurse should be vigilant for signs of adverse effects and monitor for drug interactions that could affect the client's health.
- Antigout drugs, especially during initial treatment, may not provide immediate relief of symptoms during an acute gout attack. The nurse should offer emotional support and symptom management strategies to help alleviate pain and discomfort.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking an antigout drug should:
- Take the medication at the scheduled times and follow the prescribed dosage. Consistent adherence to the medication regimen helps control uric acid levels and prevent gout attacks.
- Maintain adequate hydration by drinking plenty of water throughout the day to help the kidneys flush out excess uric acid from the body.
- Report adverse effects such as rash, diarrhea, muscle pain, and weakness to the health care provider, as these may be adverse effects of the medication.
- Avoid purine-rich foods, such as red meats, organ meats, and seafood, as these can lead to increased uric acid levels in the body and exacerbate gout flare-ups.
- Keep follow-up appointments to have uric acid levels assessed and to ensure that medication management is effective.
The client taking an antigout drug should not:
- Become dehydrated when using probenecid, as this may increase the risk of kidney stone formation.
- Eat grapefruit or drink grapefruit juice when taking colchicine, as this may impact the efficacy of the drug.