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Questions and Answers
What is a cardiovascular risk associated with the use of COX-2 selective NSAIDs?
What is a cardiovascular risk associated with the use of COX-2 selective NSAIDs?
What is a common gastrointestinal adverse effect of NSAIDs?
What is a common gastrointestinal adverse effect of NSAIDs?
What is a therapeutic use of NSAIDs?
What is a therapeutic use of NSAIDs?
What is the mechanism of action of coxibs?
What is the mechanism of action of coxibs?
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What is an anti-inflammatory mechanism of NSAIDs?
What is an anti-inflammatory mechanism of NSAIDs?
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What is a renal adverse effect of NSAIDs?
What is a renal adverse effect of NSAIDs?
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What is a unique effect of aspirin compared to other NSAIDs?
What is a unique effect of aspirin compared to other NSAIDs?
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What is the main concern associated with COX-2 selective inhibitors like celecoxib?
What is the main concern associated with COX-2 selective inhibitors like celecoxib?
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Which of the following NSAIDs is known for its short half-life and is often used post-operatively?
Which of the following NSAIDs is known for its short half-life and is often used post-operatively?
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What is the main advantage of using COX-2 selective inhibitors over non-selective NSAIDs?
What is the main advantage of using COX-2 selective inhibitors over non-selective NSAIDs?
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What is the mechanism of action of acetaminophen?
What is the mechanism of action of acetaminophen?
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Which of the following NSAIDs is commonly used in children and has a flavoured chewable tablet formulation?
Which of the following NSAIDs is commonly used in children and has a flavoured chewable tablet formulation?
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What is the contraindication for using aspirin in children?
What is the contraindication for using aspirin in children?
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What is the main reason for avoiding NSAIDs in patients with hypertension?
What is the main reason for avoiding NSAIDs in patients with hypertension?
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What is the main purpose of inflammation?
What is the main purpose of inflammation?
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What is the primary cause of redness in inflammation?
What is the primary cause of redness in inflammation?
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Which of the following is NOT a characteristic of inflammation?
Which of the following is NOT a characteristic of inflammation?
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What is the role of prostaglandins in inflammation?
What is the role of prostaglandins in inflammation?
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What is the mechanism of fever in inflammation?
What is the mechanism of fever in inflammation?
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What is the main goal of anti-inflammatory therapy?
What is the main goal of anti-inflammatory therapy?
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Which of the following is a mediator of inflammation?
Which of the following is a mediator of inflammation?
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What is a therapeutic use of NSAIDs in osteoarthritis?
What is a therapeutic use of NSAIDs in osteoarthritis?
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Which of the following NSAIDs is known for its antiplatelet effect?
Which of the following NSAIDs is known for its antiplatelet effect?
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What is a common gastrointestinal adverse effect of NSAIDs?
What is a common gastrointestinal adverse effect of NSAIDs?
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Which of the following is an anti-inflammatory mechanism of NSAIDs?
Which of the following is an anti-inflammatory mechanism of NSAIDs?
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What is the mechanism of action of coxibs?
What is the mechanism of action of coxibs?
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Which of the following NSAIDs is commonly used to treat headache?
Which of the following NSAIDs is commonly used to treat headache?
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What is a cardiovascular risk associated with the use of NSAIDs?
What is a cardiovascular risk associated with the use of NSAIDs?
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Which of the following NSAIDs is known for its short half-life and is often used post-operatively?
Which of the following NSAIDs is known for its short half-life and is often used post-operatively?
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What is the main advantage of using COX-2 selective inhibitors over non-selective NSAIDs?
What is the main advantage of using COX-2 selective inhibitors over non-selective NSAIDs?
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What is a characteristic of an acute classic attack of gout?
What is a characteristic of an acute classic attack of gout?
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What is a consequence of not treating gout?
What is a consequence of not treating gout?
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What is a common complication of gout?
What is a common complication of gout?
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What is a characteristic of intercritical gout?
What is a characteristic of intercritical gout?
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What is a lab test used to diagnose gout?
What is a lab test used to diagnose gout?
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What is a goal of uric acid lowering treatment in gout?
What is a goal of uric acid lowering treatment in gout?
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How often do untreated patients experience a second episode of gout?
How often do untreated patients experience a second episode of gout?
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What is the primary reason for assessing patients who present with gout before the age of 25 or those with renal stones?
What is the primary reason for assessing patients who present with gout before the age of 25 or those with renal stones?
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What is the characteristic of the majority of patients with gout?
What is the characteristic of the majority of patients with gout?
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What is the typical duration of an acute inflammatory monoarthritis episode in gout?
What is the typical duration of an acute inflammatory monoarthritis episode in gout?
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What is the most common joint involved in the initial attack of gout?
What is the most common joint involved in the initial attack of gout?
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What is the definitive method of diagnosing gout?
What is the definitive method of diagnosing gout?
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Which of the following conditions can lead to overproduction of uric acid?
Which of the following conditions can lead to overproduction of uric acid?
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What is the typical serum uric acid level for diagnosing hyperuricemia in females?
What is the typical serum uric acid level for diagnosing hyperuricemia in females?
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What is the primary cause of Gout?
What is the primary cause of Gout?
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Which of the following individuals is at a higher risk of developing Gout?
Which of the following individuals is at a higher risk of developing Gout?
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What is the primary goal of therapy in the intercritical stage of Gout?
What is the primary goal of therapy in the intercritical stage of Gout?
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What is a characteristic symptom of Gout?
What is a characteristic symptom of Gout?
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What is the term used to describe the stage of Gout characterized by asymptomatic hyperuricemia?
What is the term used to describe the stage of Gout characterized by asymptomatic hyperuricemia?
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Why is Gout no longer restricted to populations with a high standard of living?
Why is Gout no longer restricted to populations with a high standard of living?
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What is the term used to describe the stage of Gout characterized by repeated gouty flares and joint damage?
What is the term used to describe the stage of Gout characterized by repeated gouty flares and joint damage?
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What is the term used to describe the stage of Gout characterized by the period between gouty flares?
What is the term used to describe the stage of Gout characterized by the period between gouty flares?
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What is the historical term used to describe Gout?
What is the historical term used to describe Gout?
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What is a characteristic of acute gout attacks if left untreated?
What is a characteristic of acute gout attacks if left untreated?
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What is a common site for tophaceous deposits in gout?
What is a common site for tophaceous deposits in gout?
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What is a goal of pharmacologic treatment in chronic gout?
What is a goal of pharmacologic treatment in chronic gout?
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What is a type of medication used to treat acute gout attacks?
What is a type of medication used to treat acute gout attacks?
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What is a complication of chronic gout?
What is a complication of chronic gout?
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What is a non-pharmacologic approach to managing gout?
What is a non-pharmacologic approach to managing gout?
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What is a goal of treating an acute gout attack?
What is a goal of treating an acute gout attack?
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Study Notes
Inflammation
- Inflammation is a response by living, vascularized tissue to remove an injurious agent, including mechanical, chemical, thermal, or radioactive agents.
- It is a mechanism to restore tissue to normal.
Characteristics of Inflammation
- Redness: caused by increased blood flow
- Swelling: caused by fluid retention/edema
- Heat: caused by increased blood flow
- Pain: caused by impingement/pressure on local nerves
- Loss of function: excess of all of the above
Mediators of Inflammation
- Histamine: released by mast cells in tissue and platelets in blood
- Prostaglandins: cause peripheral vasodilation with redness and edema (partly due to bradykinin activation)
- Bradykinin: contributes to edema and pain
- Serotonin: involved in pain modulation
Consequences of Inflammation
- Pain: often accompanied by fever
- Fever: caused by exogenous pyrogens, lymphokines, and TNFα
Pain Modulators
- Nociceptors (pain receptors) are activated mechanically or chemically
- Inflammatory mediators can directly induce pain or decrease pain threshold
Mechanism of Fever
- Exogenous pyrogens increase prostaglandin E2 in the hypothalamus, raising the set point of the temperature regulating center
- This leads to cutaneous vasoconstriction, decreased heat loss, increased heat generation, and increased body temperature
Treatment of Inflammation
- Two major goals: relieve pain and other symptoms, and slow or arrest the tissue-damaging process
- NSAIDs are commonly used to treat inflammation, with aspirin being the original drug; numerous modifications have been made to refine efficacy, safety, and efficiency
NSAIDs
- Classes of NSAIDs:
- Phenylacetic acid derivatives (e.g. diclofenac)
- Indols (e.g. indomethacin)
- Phenylpropionic acid derivatives (e.g. ibuprofen, naproxen)
- Acetic acid derivatives (e.g. ketorolac)
- Pharmacokinetics: highly protein-bound, well absorbed, and metabolized, with primarily renal elimination
- Mechanism of action: competitive inhibitors of cyclooxygenase, reducing prostaglandin production and resulting in anti-inflammatory, analgesic, and antipyretic effects
- Therapeutic uses: arthritis, gout, antipyretics, analgesics, and cardioprotection
Adverse Effects of NSAIDs
- GI: abdominal pain, nausea, diarrhea, anorexia, ulcers
- Platelets: inhibited platelet activation, increased bruising, and hemorrhage
- Renal: salt and water retention, edema, decreased effectiveness of antihypertensive drugs, and hyperkalemia
- CV: closure of ductus arteriosus, increased risk of thrombotic events (especially with COX2 selective drugs)
- CNS: headache, vertigo, dizziness, confusion, and hyperventilation
Specific NSAIDs
- Aspirin: antiplatelet effect, used in cardioprotection and closure of patent ductus arteriosus
- Diclofenac: very potent anti-inflammatory, used in acute gout, severe osteoarthritis, and rheumatoid arthritis
- Indomethacin: potent anti-inflammatory, used in rheumatoid arthritis, ankylosing spondylitis, and acute bouts of gout
- Ibuprofen: well-tolerated for long-term use, used in children, and available in flavored chewable tablets and suspensions
- Naproxen: generally safe, but can cause GI disturbances, and has a longer half-life than most other NSAIDs
- Ketorolac: potent analgesic with moderate anti-inflammatory effects, used post-operatively, but has a risk of serious GI irritation, renal complications, and bleeding
COX2 Selective Inhibitors
- Developed to inhibit prostaglandin synthesis by the COX2 isozyme at sites of inflammation without affecting COX1
- Example: celecoxib, which is 15-20 times more selective for COX2 than COX1
Acetaminophen
- Non-anti-inflammatory analgesic, primarily used as an antipyretic and analgesic
- Mechanism of action is unclear
- Not useful as anti-rheumatic therapy
- Ideal analgesic for individuals susceptible to gastric irritation of NSAIDs
- Pharmacokinetics: rapid oral absorption, peak plasma levels in 30-60 minutes, and hepatic metabolism
De Novo Synthesis of Purine Bases
- Purines enter a common metabolic pathway leading to production of either nucleic acid or uric acid
- Uric acid accumulates if production exceeds excretion (average production: 600-800mg UA/day)
- Enzyme systems regulate purine metabolism, which can result in overproduction of uric acid
Overproduction of Uric Acid
- Can occur due to increased breakdown of tissue nucleic acids and excessive rates of cell turnover
- Associated with conditions such as:
- Myeloproliferative and lymphoproliferative disorders
- Psoriasis
- Polycythemia vera
- Certain anemias
Underexcretion of Uric Acid
- Under normal conditions, 2/3 of uric acid is excreted in urine, and 1/3 is eliminated via GI tract after enzymatic degradation by colonic bacteria
- Primary idiopathic hyperuricemia: majority of patients with gout have a relative decrease in renal excretion of uric acid for an unknown reason
Hyperuricemia
- Defined as:
- Serum levels >416 μmol/L in males
- Serum levels >357 μmol/L in females
- Overproducers: individuals with hyperuricemia who excrete >1000mg of UA/24hrs
Signs and Symptoms of Gout
- Generally presents as acute inflammatory monoarthritis
- Onset: usually at night
- Duration: 3-14 days (untreated)
- Lower extremity involvement, with 85% of initial attacks involving a single joint
- Most commonly affects the first metatarsophalangeal joint (great toe) = "Podagra" (50%)
Diagnosis
- Definitive: visualization of uric acid crystals in joint fluid by aspiration
- Presumptive diagnosis:
- Inflammatory monoarthritis
- Elevated UA
- Response to colchicine
- Lab test: high UA level, leukocytosis
- Long-standing gout: x-ray – asymmetric swelling
Acute Classic Attack
- Rapid, localized onset of excruciating pain (night), swelling, redness, and inflammation
- Typically monoarticular at first, affecting the big toe, and may include other joints
- Debilitating, with unilateral attack lasting 3-14 days, maximal severity within 12-24 hours
- Complete resolution (untreated): days to weeks
Intercritical Gout
- Most untreated patients experience a second episode within 2 years
- Typically, uric acid-lowering treatments begin if >2 flares per year
Tophaceous Gout/Chronic Gouty Arthropathy
- Bony erosions/deformities may develop, typically associated with chronic tophaceous (crystal) deposits
- Most common sites: base of fingers, olecranon bursae, ulnar aspect of forearm, Achilles tendon, knees, wrists, and hands
Treatment Goals
- Terminate acute attack: goal is to control inflammation and pain
- Prevention of acute and chronic gout: goal is to lower uric acid level to prevent precipitation, acute attacks, and formation of tophi
Nonpharmacologic Therapies
- Awareness of nonpharmacologic therapies is essential for patient education and tailored therapy
- Role in management: acute attack, prevention/chronic management
Pharmacologic Treatment Options
- Acute: NSAIDs, oral colchicine, corticosteroids
- Chronic: xanthine oxidase inhibitors (allopurinol, febuxostat), uricosurics (probenecid)
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Description
This quiz covers the basics of inflammation, its characteristics, and the inflammatory response. Learn about the mechanisms of inflammation and how it helps to restore tissue to normal.