P.04 NSAIDS, DMARDS, AND ANALGESICS DRUGS USED IN GOUT
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Questions and Answers

What is the primary goal of treating patients with inflammation?

  • Prevention of autoimmune diseases
  • Elimination of all cytokines and chemokines
  • Relief of symptoms and maintenance of function (correct)
  • Inducing acute inflammatory response

    • What is the main source of continuous symptoms in patients if not addressed?

  • Release of multiple cytokines and chemokines
  • Tissue damaging process (correct)
  • Immunoactive cells interplay
  • Inflammatory responses

    • What is the consequence of not controlling the main source of inflammation or reactions?

  • Continuous relief of pain
  • Immediate reduction of inflammation
  • Continuous symptoms and tissue damage (correct)
  • Slowing down the damage to the tissues

    • Which indices are used to define response in rheumatoid arthritis (RA)?

    <p>Disease Activity Score28 (DAS28), American College of Rheumatology Response Index (ACR Response), Clinical Disease Activity Score (CDAI), Simplified Disease Activity Index (SDAI)</p> Signup and view all the answers

    Which conditions derive from abnormalities in the cascade involving autoimmune diseases and inflammatory conditions?

    <p>Rheumatoid arthritis and Systemic Lupus Erythematosus</p> Signup and view all the answers

    What occurs when immunologically competent cells are activated in response to foreign organisms or antigenic substances?

    <p>Immune response</p> Signup and view all the answers

    What does reduction of inflammation with NSAIDs often result in?

    <p>Relief of pain for significant periods</p> Signup and view all the answers

    Which phase involves the release of multiple cytokines and chemokines in the inflammatory responses?

    <p>Late phase</p> Signup and view all the answers

    What are the two primary goals in treating patients with inflammation?

    <p>Relief of symptoms and maintenance of function</p> Signup and view all the answers

    What is the purpose of slowing or arresting the tissue damaging process in treating inflammation?

    <p>To prevent continuous symptoms and tissue damage</p> Signup and view all the answers

    What is the consequence if the main source of inflammation or reactions is not controlled?

    <p>Continuous symptoms and tissue damage</p> Signup and view all the answers

    What do autoimmune diseases and inflammatory conditions derive from?

    <p>Abnormalities in the cascade involving immunologically competent cells</p> Signup and view all the answers

    Which NSAID is associated with a lower risk of serious bleeding and cardiovascular events after myocardial infarction?

    <p>Naproxen</p> Signup and view all the answers

    What is the main cause of nephrotoxicity associated with NSAID use?

    <p>Interference with prostaglandins</p> Signup and view all the answers

    Which adverse effect is NOT commonly associated with NSAID use?

    <p>Hepatic failure</p> Signup and view all the answers

    What effect do several NSAIDs, including aspirin, have on colon cancer incidence when taken chronically?

    <p>Reduce the incidence of colon cancer</p> Signup and view all the answers

    Which NSAID is mentioned as a gastric irritant but tends to cause less GI irritation than aspirin?

    <p>Naproxen</p> Signup and view all the answers

    What is the primary function of all newer NSAIDs except the COX-2–selective agents and the nonacetylated salicylates?

    <p>Inhibit platelet aggregation</p> Signup and view all the answers

    Which adverse effect is associated with central nervous system disturbances, such as headaches and tinnitus?

    <p>Dizziness</p> Signup and view all the answers

    As a group, which type of NSAIDs tend to cause less gastrointestinal irritation than aspirin?

    <p><strong>Newer agents</strong></p> Signup and view all the answers

    Headaches, tinnitus, and dizziness are adverse effects associated with which system when caused by NSAID use?

    <p><strong>Central nervous system</strong></p> Signup and view all the answers

    Abdominal pain, dyspepsia, nausea, and vomiting are commonly associated with which system disturbance caused by NSAID use?

    <p><strong>Gastrointestinal system</strong></p> Signup and view all the answers

    Fluid retention, hypertension, and edema are adverse effects associated with which system when caused by NSAID use?

    <p><strong>Cardiovascular system</strong></p> Signup and view all the answers

    What is the primary function of disease-modifying anti-rheumatic drugs (DMARDs) including biologics?

    <p>To improve the symptoms and slow the bone damage associated with rheumatoid arthritis</p> Signup and view all the answers

    Which mechanism chiefly mediates the anti-inflammatory activity of NSAIDs?

    <p>Inhibition of prostaglandin biosynthesis</p> Signup and view all the answers

    What is the main reason for taking NSAIDs after eating?

    <p>To prevent gastrointestinal irritation</p> Signup and view all the answers

    What is the primary characteristic of most NSAIDs in terms of protein binding?

    <p>Highly protein-bound (~98%)</p> Signup and view all the answers

    What is the primary reason for developing many NSAIDs as alternatives to aspirin?

    <p>To decrease their toxicity</p> Signup and view all the answers

    Which type of NSAID is naproxen?

    <p>Single enantiomer</p> Signup and view all the answers

    What is the main difference in platelet function between aspirin and selective COX-2 inhibitors?

    <p>Selective COX-2 inhibitors are reversible inhibitors while aspirin irreversibly acetylates and blocks platelet COX.</p> Signup and view all the answers

    What has been recommended concerning the cardiovascular risks associated with NSAIDs?

    <p>&quot;Black box&quot; warning concerning cardiovascular risks be added to all NSAID product labels.</p> Signup and view all the answers

    What is the main concern with selective COX-2 inhibitors in terms of side effects?

    <p>&quot;Black box&quot; warning concerning cardiovascular risks</p> Signup and view all the answers

    "Nabumetone" differs from other NSAIDs as it is:

    <p>&quot;Nabumetone&quot; is a ketone prodrug that is metabolized to the acidic active drug.</p> Signup and view all the answers

    What is one common characteristic of most NSAIDs in terms of pharmacokinetics?

    <p>Highly metabolized, some by phase I followed by phase II mechanisms and others by direct glucuronidation alone.</p> Signup and view all the answers

    Match the following adverse effects with the corresponding system disturbance caused by NSAID use:

    <p>Gastric upset and ulcers = Gastrointestinal system Hepatotoxicity and rashes = Integumentary system Asthma and triggered by aspirin = Respiratory system Renal toxicity = Urinary system</p> Signup and view all the answers

    Match the following pharmacokinetic terms with their definitions:

    <p>pKa = Acidity constant Half-life = Time for concentration to reduce by half Absorption = Uptake into the bloodstream Hydrolyzed to acetic acid and salicylate = Chemical breakdown in the body</p> Signup and view all the answers

    Match the following NSAIDs with their associated adverse effects:

    <p>Aspirin = Gastric upset and ulcers Naproxen = Lower risk of serious bleeding and cardiovascular events after myocardial infarction Selective COX-2 inhibitors = Concern over cardiovascular risks Nabumetone = Less gastrointestinal irritation than aspirin</p> Signup and view all the answers

    Match the following terms related to NSAID action with their descriptions:

    <p>COX inhibition lasting 8–10 days = Antiplatelet effect Synthesis of new COX replaces inactivated enzyme = Duration of action of 6–12 hours Inhibition of platelet COX = Mechanism of action Replacement by inactivated enzyme in other tissues = Mechanism of action</p> Signup and view all the answers

    Match the following NSAIDs with their primary mechanism of action:

    <p>Etodolac = Unknown mechanism of action Flurbiprofen = Inhibition of intraoperative miosis Ibuprofen = Inhibition of platelet aggregation Indomethacin = Inhibition of COX and lipoxygenase</p> Signup and view all the answers

    Match the following NSAIDs with their adverse effects:

    <p>Ketoprofen = Adverse effects on GI tract and central nervous system Nabumetone = Renal impairment leading to increased half-life Naproxen = Low incidence of upper GI bleeding Etodolac = Rarely associated with cogwheel rigidity, ataxia, tremor, and myoclonus</p> Signup and view all the answers

    Match the following NSAIDs with their primary usage:

    <p>Flurbiprofen = Perioperative analgesia in minor ear, neck, and nose surgery Ibuprofen = Closing patent ductus arteriosus in preterm infants Indomethacin = Reduction of pain after traumatic corneal abrasion Ketoprofen = Equivalent effectiveness to other NSAIDs at dosages of 100–300 mg/d</p> Signup and view all the answers

    Match the following NSAIDs with their unique characteristics:

    <p>Nabumetone = Nonacid NSAID with a half-life of more than 24 hours Naproxen = Marketed as a single enantiomer Etodolac = Racemic acetic acid derivative with an intermediate half-life Indomethacin = Potent nonselective COX inhibitor and may inhibit phospholipase A and C</p> Signup and view all the answers

    Match the following NSAIDs with their primary mechanism of action:

    <p>Celecoxib = Selective COX-2 inhibition Diclofenac = Nonselective COX inhibition Meloxicam = Preferential COX-2 inhibition Naproxen = Nonselective COX inhibition</p> Signup and view all the answers

    Match the following NSAIDs with their associated adverse effects:

    <p>Sodium Salicylate = Renal dysfunction Celecoxib = Cardiovascular thrombotic events Diclofenac = Elevation of serum aminotransferases Meloxicam = Clinical GI symptoms and complications</p> Signup and view all the answers

    Match the following NSAIDs with their primary usage:

    <p>Ibuprofen = Gastric irritant with less GI irritation than aspirin Piroxicam = Effective for solar keratoses Nabumetone = Lower risk of serious bleeding and cardiovascular events after myocardial infarction Sodium Salicylate = Preventative analgesia and postoperative nausea</p> Signup and view all the answers

    Match the following NSAIDs with their impact on platelet function:

    <p>Sodium Salicylate = Does not inhibit platelet aggregation Celecoxib = Does not affect platelet aggregation at usual doses Meloxicam = Inhibits synthesis of thromboxane A2 without decreasing in vivo platelet function Diclofenac = Impairs renal blood flow and glomerular filtration rate</p> Signup and view all the answers

    Match the following COX inhibitors with their selectivity:

    <p>Celecoxib = About 10–20 times more selective for COX-2 than for COX-1 Meloxicam = Preferentially inhibits COX-2 over COX-1, particularly at its lowest therapeutic dose of 7.5 mg/d Naproxen = Nonselective COX inhibition Sodium Salicylate = Nonacetylated salicylate with no selectivity for COX enzymes</p> Signup and view all the answers

    Match the NSAID with its major difference or unique characteristic:

    <p>Oxaprozin = Very long half-life (50-60 hours) Piroxicam = Increased risk of peptic ulcer and bleeding at high dosages Sulindac = Enterohepatic cycling and duration of action to 12-16 hours Tolmetin = Short half-life (1-2 hours)</p> Signup and view all the answers

    Match the NSAID with its associated adverse reactions:

    <p>Oxaprozin = Mildly uricosuric Piroxicam = Stevens-Johnson syndrome, thrombocytopenia, agranulocytosis Sulindac = Suppresses familial intestinal polyposis and may inhibit cancer development Tolmetin = Not often used due to severe adverse reactions</p> Signup and view all the answers

    Match the NSAID with its specific medical use or indication:

    <p>Oxaprozin = Mildly uricosuric Piroxicam = Usual rheumatic indications Sulindac = Suppresses familial intestinal polyposis and inhibits cancer development Tolmetin = Not effective for gout</p> Signup and view all the answers

    Match the NSAID with a relevant safety consideration or limitation:

    <p>Oxaprozin = Does not undergo enterohepatic circulation Piroxicam = Increased risk of peptic ulcer and bleeding at high dosages Sulindac = Associated with severe adverse reactions such as Stevens-Johnson syndrome Tolmetin = Not often used due to severe adverse reactions</p> Signup and view all the answers

    Match the NSAID with a relevant consideration for patients with specific conditions:

    <p>Oxaprozin = May be beneficial in patients with coronary artery disease or acute coronary syndrome Piroxicam = Associated with increased incidence of peptic ulcer and bleeding at high dosages Sulindac = May inhibit the development of colon, breast, and prostate cancer in humans Tolmetin = Not effective for gout</p> Signup and view all the answers

    What is the recommended dose of abatacept for the treatment of adult patients with RA?

    <p>750 mg intravenous infusion at day 0, week 2, and week 4</p> Signup and view all the answers

    Which patients should receive 125 mg of abatacept subcutaneously once weekly?

    <p>Patients aged 6–17 years</p> Signup and view all the answers

    What is the terminal serum half-life of abatacept?

    <p>13–16 days</p> Signup and view all the answers

    What coadministration does not influence abatacept clearance?

    <p>Methotrexate, NSAIDs, and corticosteroids</p> Signup and view all the answers

    When do most patients respond to abatacept after the initiation of the treatment?

    <p>Within 12–16 weeks</p> Signup and view all the answers

    What is the primary indication for using abatacept?

    <p>Moderate to severe RA or severe PJIA</p> Signup and view all the answers

    What is the slightly increased risk of infection associated with abatacept?

    <p>Urinary tract infections</p> Signup and view all the answers

    Why should live vaccines be avoided in patients while taking abatacept and up to 3 months after discontinuation?

    <p>To prevent serious infection</p> Signup and view all the answers

    What has been reported but is rare in relation to abatacept use?

    <p>Infusion-related reactions and hypersensitivity reaction</p> Signup and view all the answers

    "Anti-abatacept antibody formation" is infrequent. What does this mean?

    <p>The formation of these antibodies occurs rarely or in few cases.</p> Signup and view all the answers

    What are the adverse effects predominantly related to when coadministering abatacept with TNF-α antagonists or other biologics?

    <p>Infections</p> Signup and view all the answers

    What is the main difference between conventional synthetic (cs) and biologic (b) disease modifying antirheumatic drugs (DMARDs)?

    <p>Time to become clinically evident</p> Signup and view all the answers

    Which of the following is a T-cell–modulating biologic approved for rheumatoid arthritis?

    <p>Abatacept</p> Signup and view all the answers

    Which of the following is an example of a small molecule conventional synthetic DMARD?

    <p>Methotrexate</p> Signup and view all the answers

    Which of the following is a biosimilar DMARD type for rheumatoid arthritis?

    <p>BsDMARDs</p> Signup and view all the answers

    What is the main characteristic that differentiates Tofacitinib from other marketed drugs?

    <p>Targeted synthetic classification</p> Signup and view all the answers

    What type of large-molecule therapeutic agents are biologics often produced by?

    <p>Recombinant DNA technology</p> Signup and view all the answers

    Which agent belongs to the class of IL 1–inhibiting agents approved for rheumatoid arthritis?

    <p>All of the above</p> Signup and view all the answers

    Which of the following is NOT a TNF-α blocking agent approved for rheumatoid arthritis?

    <p>Rituximab</p> Signup and view all the answers

    Which of the following is a targeted synthetic DMARD for rheumatoid arthritis?

    <p>Tofacitinib</p> Signup and view all the answers

    Which of the following is NOT a conventional synthetic agent for treating rheumatoid arthritis?

    <p>Tocilizumab</p> Signup and view all the answers

    Which of the following biologics for rheumatoid arthritis is produced by recombinant DNA technology?

    <p>Rituximab</p> Signup and view all the answers

    Which of the following is a biosimilar DMARD type for rheumatoid arthritis?

    <p>bsDMARDs</p> Signup and view all the answers

    Which type of bDMARD is abatacept used for treating rheumatoid arthritis?

    <p>T-cell–modulating biologic</p> Signup and view all the answers

    Which of the following is a B-cell cytotoxic agent approved for rheumatoid arthritis?

    <p>Rituximab</p> Signup and view all the answers

    What is the primary goal of using abatacept in patients with moderate to severe RA or severe PJIA?

    <p>Modulating the activation of T cells</p> Signup and view all the answers

    What is the mechanism of action of mycophenolate mofetil (MMF)?

    <p>Interference with leukocyte adhesion to endothelial cells</p> Signup and view all the answers

    What is a potential adverse effect associated with mycophenolate mofetil (MMF) use?

    <p>All of the above</p> Signup and view all the answers

    What is the primary mechanism of action of rituximab?

    <p>Depletion of CD20 B lymphocytes</p> Signup and view all the answers

    Which disease is mycophenolate mofetil (MMF) effective for treating?

    <p>Systemic lupus erythematosus (SLE)</p> Signup and view all the answers

    What is a common adverse effect associated with rituximab use?

    <p>Increased incidence of infections</p> Signup and view all the answers

    What is the recommended interval for repeating rituximab treatment?

    <p>9 months</p> Signup and view all the answers

    What is the main purpose of pretreatment with acetaminophen, antihistamine, and intravenous glucocorticoids before rituximab infusion?

    <p>To decrease the incidence and severity of infusion reactions</p> Signup and view all the answers

    What adverse effect is associated with repeated courses of rituximab therapy?

    <p>Reduced immunoglobulin levels</p> Signup and view all the answers

    What is the active moiety when treating rheumatoid arthritis with sulfasalazine?

    <p>Sulfapyridine</p> Signup and view all the answers

    What is the main reason that approximately 30% of patients discontinue sulfasalazine due to toxicity?

    <p>Common adverse effects like nausea, vomiting, headache, and rash</p> Signup and view all the answers

    What is the mechanism of action of tocilizumab?

    <p>Binds to soluble and membrane-bound IL-6 receptors</p> Signup and view all the answers

    What is the half-life of tocilizumab dependent on?

    <p>Dose of tocilizumab</p> Signup and view all the answers

    In which type of patients is tocilizumab indicated?

    <p>Adult patients with moderately to severely active RA</p> Signup and view all the answers

    What adverse effect is commonly associated with tocilizumab use?

    <p>Increased risk of fungal infections</p> Signup and view all the answers

    What is the primary role of tocilizumab in the management of severe COVID-19 pneumonia?

    <p>To modulate IL-6-mediated signaling</p> Signup and view all the answers

    Study Notes

    Treatment Goals and Inflammation Management

    • Primary goal of treating inflammation is to alleviate symptoms and prevent tissue damage.
    • Continuous symptoms in patients can arise from uncontrolled inflammation.
    • Failure to manage inflammation can lead to chronic pain, functional impairments, and increased morbidity.
    • Indices such as DAS28 or ACR criteria are used to define response in rheumatoid arthritis (RA).
    • Autoimmune diseases and inflammatory conditions stem from abnormalities in immune regulation, leading to excessive inflammation.

    Immune Response Dynamics

    • Activation of immunologically competent cells occurs in response to foreign organisms or antigens, triggering inflammation.
    • Reduction of inflammation through NSAIDs typically results in decreased pain and improved function.

    NSAIDs and Their Effects

    • Multiple cytokines and chemokines are released during the acute phase of the inflammatory response.
    • Major goals in treating inflammation include controlling symptoms and halting tissue damage.
    • If inflammation sources are not regulated, patients may experience further tissue damage and deterioration in health.

    Specific NSAIDs and Their Properties

    • Nabumetone is less irritating to the gastrointestinal tract compared to traditional NSAIDs like aspirin.
    • Naproxen is categorized as a propionic acid derivative NSAID.
    • Selective COX-2 inhibitors generally pose cardiovascular risks, alongside concerns for renal side effects.
    • Chronic use of NSAIDs, including aspirin, may reduce colon cancer incidence.

    Safety and Adverse Effects

    • Increased fluid retention, hypertension, and edema are notable side effects attributed to NSAID use on the renal system.
    • Common adverse effects of NSAIDs include headaches, dizziness, dyspepsia, nausea, and abdominal pain.
    • Patients should take NSAIDs with food to minimize gastrointestinal irritation.

    Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

    • DMARDs and biologics primarily aim to alter disease progression and reduce joint damage in RA.
    • Abatacept is dosed at 125 mg subcutaneously once weekly for RA management.

    Biologics and Their Mechanisms

    • Mycophenolate mofetil (MMF) works by inhibiting nucleotide synthesis, affecting lymphocyte proliferation.
    • Rituximab, a B-cell depleting agent, targets CD20 and is effective in RA and other autoimmune diseases.
    • Tocilizumab blocks the IL-6 receptor, implicated in inflammation.

    Patient Management and Considerations

    • Coadministration of abatacept with TNF-α antagonists can heighten infection risk.
    • Administering acetaminophen, antihistamines, and glucocorticoids before rituximab minimizes infusion reactions.
    • Regular monitoring is essential due to the risk of serious infections and other adverse effects with such therapies.

    Treatment Intervals and Efficacy

    • Rituximab treatment intervals are recommended based on clinical need, typically repeated every 6 months after initial infusions.
    • Tofacitinib is distinguished from other DMARDs due to its oral administration as a smaller molecule.

    Final Notes

    • It is essential to avoid live vaccines during abatacept treatment and for 3 months post-discontinuation due to immunosuppression risks.
    • Individualized treatment plans are crucial for managing RA and other inflammatory conditions effectively.

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    Description

    Test your knowledge on the immune response and inflammatory conditions such as rheumatoid arthritis, vasculitis, SLE, and gout. Explore the activation of immunologically competent cells and the release of cytokines and chemokines during chronic inflammation.

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