Gout and NSAIDS

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Questions and Answers

What is a cardiovascular risk associated with the use of COX-2 selective NSAIDs?

Decreased risk of thrombotic events

Improved renal blood flow

Reduced hypertension

Increased risk of thrombotic events (correct)

What is a common gastrointestinal adverse effect of NSAIDs?

Constipation

Hyperkalemia

Abdominal pain (correct)

Hyperventilation

What is a therapeutic use of NSAIDs?

Treatment of cancer

Treatment of arthritis (correct)

Treatment of diabetes

Treatment of hypertension

What is the mechanism of action of coxibs?

Selective inhibition of COX-2 Signup and view all the answers

What is an anti-inflammatory mechanism of NSAIDs?

Reduction of vessel sensitivity to bradykinin and histamine Signup and view all the answers

What is a renal adverse effect of NSAIDs?

Salt and water retention Signup and view all the answers

What is a unique effect of aspirin compared to other NSAIDs?

Antiplatelet effect Signup and view all the answers

What is the main concern associated with COX-2 selective inhibitors like celecoxib?

Increased risk of cardiovascular events Signup and view all the answers

Which of the following NSAIDs is known for its short half-life and is often used post-operatively?

Ketorolac Signup and view all the answers

What is the main advantage of using COX-2 selective inhibitors over non-selective NSAIDs?

Fewer gastrointestinal side effects Signup and view all the answers

What is the mechanism of action of acetaminophen?

Unclear mechanism Signup and view all the answers

Which of the following NSAIDs is commonly used in children and has a flavoured chewable tablet formulation?

Ibuprofen Signup and view all the answers

What is the contraindication for using aspirin in children?

Viral infection Signup and view all the answers

What is the main reason for avoiding NSAIDs in patients with hypertension?

Reduced efficacy of antihypertensive medications Signup and view all the answers

What is the main purpose of inflammation?

To remove injurious agents and restore tissue to normal Signup and view all the answers

What is the primary cause of redness in inflammation?

Increased blood flow Signup and view all the answers

Which of the following is NOT a characteristic of inflammation?

Increased appetite Signup and view all the answers

What is the role of prostaglandins in inflammation?

They cause peripheral vasodilation and increase edema Signup and view all the answers

What is the mechanism of fever in inflammation?

Release of prostaglandin E2, which raises the set point of the temperature regulating centre Signup and view all the answers

What is the main goal of anti-inflammatory therapy?

To reduce inflammation and its consequences Signup and view all the answers

Which of the following is a mediator of inflammation?

Histamine Signup and view all the answers

What is a therapeutic use of NSAIDs in osteoarthritis?

Anti-inflammatory Signup and view all the answers

Which of the following NSAIDs is known for its antiplatelet effect?

Aspirin Signup and view all the answers

What is a common gastrointestinal adverse effect of NSAIDs?

Nausea Signup and view all the answers

Which of the following is an anti-inflammatory mechanism of NSAIDs?

Inhibition of prostaglandin production Signup and view all the answers

What is the mechanism of action of coxibs?

Inhibition of COX-2 enzyme Signup and view all the answers

Which of the following NSAIDs is commonly used to treat headache?

Ibuprofen Signup and view all the answers

What is a cardiovascular risk associated with the use of NSAIDs?

Hypertension Signup and view all the answers

Which of the following NSAIDs is known for its short half-life and is often used post-operatively?

Ketorolac Signup and view all the answers

What is the main advantage of using COX-2 selective inhibitors over non-selective NSAIDs?

Reduced gastrointestinal adverse effects Signup and view all the answers

What is a characteristic of an acute classic attack of gout?

Rapid, localized onset of excruciating pain and swelling Signup and view all the answers

What is a consequence of not treating gout?

Increased risk of cardiovascular mortality Signup and view all the answers

What is a common complication of gout?

Metabolic syndrome Signup and view all the answers

What is a characteristic of intercritical gout?

Most patients experience a second episode within 2 years Signup and view all the answers

What is a lab test used to diagnose gout?

High UA level Signup and view all the answers

What is a goal of uric acid lowering treatment in gout?

To preserve renal function Signup and view all the answers

How often do untreated patients experience a second episode of gout?

All of the above Signup and view all the answers

What is the primary reason for assessing patients who present with gout before the age of 25 or those with renal stones?

To identify potential underlying causes of gout Signup and view all the answers

What is the characteristic of the majority of patients with gout?

They have a relative decrease in renal excretion of uric acid for an unknown reason Signup and view all the answers

What is the typical duration of an acute inflammatory monoarthritis episode in gout?

3-14 days Signup and view all the answers

What is the most common joint involved in the initial attack of gout?

First metatarsophalangeal joint (great toe) Signup and view all the answers

What is the definitive method of diagnosing gout?

Visualizing uric acid crystals in joint fluid by aspiration Signup and view all the answers

Which of the following conditions can lead to overproduction of uric acid?

Myeloproliferative disorders Signup and view all the answers

What is the typical serum uric acid level for diagnosing hyperuricemia in females?

>357 umol/L Signup and view all the answers

What is the primary cause of Gout?

Deposition of monosodium urate crystals in joints and soft tissues Signup and view all the answers

Which of the following individuals is at a higher risk of developing Gout?

A 45-year-old male with hypertension and obesity Signup and view all the answers

What is the primary goal of therapy in the intercritical stage of Gout?

To manage hyperuricemia and prevent further complications Signup and view all the answers

What is a characteristic symptom of Gout?

Pain and inflammation in a single joint, typically in the big toe Signup and view all the answers

What is the term used to describe the stage of Gout characterized by asymptomatic hyperuricemia?

Asymptomatic hyperuricemia Signup and view all the answers

Why is Gout no longer restricted to populations with a high standard of living?

Due to an increase in obesity and hypertension in Western industrialized countries Signup and view all the answers

What is the term used to describe the stage of Gout characterized by repeated gouty flares and joint damage?

Chronic gouty arthritis Signup and view all the answers

What is the term used to describe the stage of Gout characterized by the period between gouty flares?

Intercritical gout Signup and view all the answers

What is the historical term used to describe Gout?

The Disease of Kings Signup and view all the answers

What is a characteristic of acute gout attacks if left untreated?

They occur in progressively shorter asymptomatic periods. Signup and view all the answers

What is a common site for tophaceous deposits in gout?

Base of fingers Signup and view all the answers

What is a goal of pharmacologic treatment in chronic gout?

To lower uric acid levels to prevent precipitation and tophi formation Signup and view all the answers

What is a type of medication used to treat acute gout attacks?

Oral colchicine Signup and view all the answers

What is a complication of chronic gout?

Bony erosions and deformities Signup and view all the answers

What is a non-pharmacologic approach to managing gout?

Educating patients on lifestyle modifications Signup and view all the answers

What is a goal of treating an acute gout attack?

To control inflammation and pain Signup and view all the answers

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.