Conditions Effecting the Musculoskeletal System and PharmacotherapyPart Five: Inflammatory DX - Gout Flashcards
Exam 4 (Final)
Patho of Gout
Normal A&P
Purines: How are they found in the body?
Found naturally in body
Patho of Gout
Normal A&P
Purines: When does the body produce uric acid?
Body produces uric acid (UA) when it breaks down purines
Purines –> UA
Patho of Gout
Normal A&P
Purines: What kind of foods are they in?
Foods: Organ meats, shellfish, anchovies,
herring, asparagus, mushrooms, salmon, beer, high fructose sugar-sweetened beverages
Patho of Gout
Normal A&P
Purines: What kind of products are formed from the breakdown of purines?
Waste product formed from the breakdown of purines
Patho
Normal A&P:
What is UA formation dependent on?
UA formation is pH dependent
Patho
What is Gout?
Type of inflammatory arthritis
Patho
When does gout occur?
Occurs from deposits of urate crystals formed from high levels of uric acid in the blood, body or synovial fluids (hyperuricemia)
Patho
What two things must occur for gout to form?
Overproduction/Underexcretion of UA
Gout:
Elevated level of Uric Acid leads to what kind of deposits and where?
Elevated level of UA –> needle-shaped deposits of monosodium urate crystals in/around joints
Gout:
How does immune system react to uric acid crystals?
The immune system reacts to these crystals, causing intense inflammation and pain.
Gout:
What do leukocytes do?
Infiltration of leukocytes inside synovial cavity phagocytize crystals
Gout:
What does the breakdown of crystals lead to?
Crystals breakdown –> release of destructive enzymes
Gout:
What forms in affected joints from crystal deposition?
Large, gritty deposits (tophi) form in affected joint from crystal deposition in subcu tissues
Gout:
Large, gritty deposits (tophi) form in affected joint from crystal deposition in subcu tissues:
What situations does this happen?
How does it appear?
Happens in chronic gout
Appears as lumps, nodules
Gout:
Large, gritty deposits (tophi) form in affected joint from crystal deposition in subcu tissues:
What does it develop with?
Develops with long-standing hyperuricemia, recurrent gout attacks
Gout:
Large, gritty deposits (tophi) form in affected joint from crystal deposition in subcu tissues:
What can it cause?
Can cause joint damage, ulceration if skin over tophi breaks down
Prevalence:
What is the most common inflammatory arthritis in older adults?
Gout
Prevalence:
Gout
How are women affected compared to men?
Men affected three times as often as women
Prevalence:
Gout
What ethnicity are incidences higher in?
Incidences higher among African Americans
Prevalence:
Gout
What is the peak age to develop gout in men? How are incidences with age (men and women)
Men (age 40-50 peak age)
Increased age
Gout: Predisposing Factors (other factors beside hyperuricemia)
Genetic predisposition (deficiency of enzyme –> increase UA), fam hx
Obesity, kidney disease, DM, HF
High alcohol consumption
Low urinary pH
Diuretics
Dietary intake of purine-rich food (e.g., red meat, shellfish), alcohol, and sugary beverages
Complex series of events in Gout:
What triggers an inflammatory response?
Crystals trigger inflammatory response
Complex series of events in Gout:
When crystals trigger inflammatory response, what is activated?
Activation of cytokines, interleukins
Complex series of events in Gout:
When crystals trigger inflammatory response, what occurs next (having to do with neutrophils)?
Draws out neutrophils from circulation attracted to site of crystal deposition, phagocytizes the crystals
Complex series of events in Gout:
When crystals trigger inflammatory response, what kind of damage occur??
Tissue damage
Complex series of events in Gout
What is an acute gouty attack?
Acute Gouty Attack: The inflammatory response leads to sudden and severe pain, swelling, redness, and warmth in the affected joint.
Clinical Manifestations of Gouty Arthritis
What are signs and symptoms?
Warm to touch, red, swollen, stiff, and extremely painful joint
Clinical Manifestations of Gouty Arthritis
What formation occurs? Where? When does this formation occur?
Tophi formation, usually on the affected joint, great toe, the extensor surfaces, or the forearm, or in the pinnae of the ear; occurs a few years after the first attack
Clinical Manifestations of Gouty Arthritis
What causes the acute inflammatory response seen in gout?
Uric acid crystals and urate crystals in the joint synovia fluid causing an acute inflammatory response
Clinical Manifestations of Gouty Arthritis
What causes a local inflammatory response seen in gout?
Hard nodule(s) painless from urate crystals in soft tissue or bone causing a local inflammatory response
Clinical Manifestations of Gouty Arthritis
What are deposits of crystals surrounded by?
Accumulation of urate crystals
Deposits of crystals surrounded by inflammatory cells, collagen fibers, and sometimes calcium deposits.
Gout
Clinical Manifestations: What can happen to joints (other than uric crystal build up)?
Tophi in/around joints
Abrupt attacks in joint
Gout
Clinical Manifestations: What will reoccur?
Recurrent arthritic attacks
Gout
Clinical Manifestations: Where are the sites where abrupt attacks on joints occur?
Joint of great toe
Hot, red, tender, swollen
Stiff, aching
Gout
Clinical Manifestations: What are other symptoms?
Severe pain
Lymphagitis & systemic sx
Gout
Clinical Manifestations: When does severe pain occur?
Mostly at night
Gout
Clinical Manifestations: Lymphagitis & systemic sx include what?
Fever, leukocytosis
Gout
Clinical Manifestations:
When do Untreated attacks subside?
mild v severe. How are symptom resolution?
Subside several hours –> 1-2 days
Severe – days/weeks
Sx resolve upon recovery
Clinical Manifestations:
Evaluation and Treatment
What would you evaluate?
High uric acid levels
Elevation sedimentation rate (ESR)
BUN & Creat
Clinical Manifestations:
Evaluation and Treatment:
What is non-pharmacological treatment?
Ice
Monitor diet
Fluids to dilute UA in blood, reducing saturation, support kidney function, prevent stones
Clinical Manifestations:
Evaluation and Treatment:
Non-pharmacological treatment: What should be avoided?
Avoid weight-bearing on joint
Avoid etoh
3 phases of Gout
- Asymptomatic hyperuricemia
- Acute gouty arthritis
- Tophaceous gout
3 phases of Gout
Asymptomatic hyperuricemia:
How do labs appear?
Elevated serum urate level
3 phases of Gout
Asymptomatic hyperuricemia: What is not present in this stage?
Arthritic sx, tophi, renal stones - not present
3 phases of Gout
Asymptomatic hyperuricemia: How long does this stage persist?
This stage may persist throughout life
3 phases of Gout
Acute gouty arthritis: How do attacks develop?
Attacks develop with increased serum urate concentrations
3 phases of Gout
Acute gouty arthritis: How do attacks tend to occur?
Tends to occur with sudden or sustained increases of hyperuricemia
3 phases of Gout
Acute gouty arthritis: What can trigger it?
Can be triggered by trauma, drugs, alcohol
3 phases of Gout
Tophaceous gout: What kind of stage is it?
Chronic stage
3 phases of Gout
Tophaceous gout: When does it begin?
Can begin anywhere from 3 to 40 years after initial attack of gouty arthritis
3 phases of Gout
Tophaceous gout: What appears and why?
Progressive inability to excrete UA –> crystal deposits (tophi) appear in cartilage, synovial membranes, tendons, soft tissue
Overview of Drug Therapy
What are the two groups of drugs?
Short-term to relieve symptoms of attack (Anti-inflammatory)
Long-term to lower blood levels of uric acid
Overview of Drug Therapy
Short-term to relieve symptoms of attack (Anti-inflammatory)
What kind of flareups are they used for?
Infrequent flare-ups (fewer than 3 times/year)
Overview of Drug Therapy
Short-term to relieve symptoms of attack (Anti-inflammatory)
What is the first line medication? What is it used for? When does relief occur?
NSAIDs: First-line agents to suppress inflammation – marked relief after 24h
Overview of Drug Therapy
Short-term to relieve symptoms of attack (Anti-inflammatory)
What are other medications used? What is it used for? When does relief occur?
Glucocorticoids also used
Colchicine
Overview of Drug Therapy
Short-term to relieve symptoms of attack (Anti-inflammatory)
How are meds tolerated?
When should meds be started?
Better tolerated
More predictable
Start ASAP after sx onset
Overview of Drug Therapy
Long-term to lower blood levels of uric acid
What kind of drugs does this include?
Uricosuric drugs
Allopurinol
Overview of Drug Therapy
Long-term to lower blood levels of uric acid
What does Uricosuric drugs do?
Uricosuric drugs to decrease UA production & increase UA excretion
Overview of Drug Therapy
Long-term to lower blood levels of uric acid- what are they used for specifically?
Used for chronic gout, tophaceous gout, frequent attacks (3+ per yr)
Overview of Drug Therapy
What is not recommended while taking Gout meds?
Breast-feeding is not recommended for other drugs taken for gout.
Colchicine (anti-inflammatory):
What is it used to treat? What does this increase and lead to?
Treats acute gouty attack/flares (high dose) – increases joint movement, inflammation gone 2-3d
Colchicine (anti-inflammatory):
What does this reduce?
Reduces incidences of attack
Decreases pain & inflammation
Colchicine (anti-inflammatory):
What does this do to an impending attack?
Aborts an impending attack
Colchicine (anti-inflammatory)
What is it used short term and long term for?
Short-term tx of gout flare & long-term to prevent (low dose) attacks from recurring
Colchicine (anti-inflammatory)
MOA
Anti-Inflammatory Effects:
What does it inhibit?
Inhibits the migration of neutrophils to the site of inflammation & leukocyte infiltration.
Colchicine (anti-inflammatory)
MOA
Anti-Inflammatory Effects:
What does it disrupt?
Disrupts microtubules
Colchicine (anti-inflammatory)
MOA
Anti-Inflammatory Effects:
What are Microscopic hollow tubes required for?
Microscopic hollow tubes required for cell movement, cell division
Colchicine (anti-inflammatory)
MOA
Anti-Inflammatory Effects: What plays a key role in inflammatory response in gout?
Neutrophils play a key role in the inflammatory response in gout.
Colchicine (anti-inflammatory)
MOA
Anti-Inflammatory Effects: What does neutrophils do exactly?
They are attracted to the urate crystals in joints and release inflammatory mediators, causing pain and swelling.
Colchicine (anti-inflammatory)
MOA
Anti-Inflammatory Effects: What does this drug do? What does this lead to?
By preventing the migration of neutrophils, colchicine reduces inflammation and the severity of gouty attacks.
Colchicine
Pharmacokinetics: How is it absorbed?Metabolized? Excreted?
PKs: readily absorbed, with or without meals, met by liver, renal excretion
Colchicine :
Adverse effects:
Severe GI ADE during tx of acute attacks ~ n/v/d, abdominal pain
Myelosuppression
Myopathy
Colchicine :
Adverse effects: Severe GI ADE during tx of acute attacks ~ n/v/d, abdominal pain
What should be done if this occurs?
D/C regardless of joint pain!!!
Colchicine :
Adverse effects: Severe GI ADE during tx of acute attacks ~ n/v/d, abdominal pain
Why does this occur?
Injury to rapidly proliferating cells of GI epithelium – toxic to any tissue with large % of proliferating cells
Colchicine :
Myelosuppression
Injury to rapidly dividing cells
Colchicine :
Myopathy: What occurs?
Rhabdomyolysis (muscle breakdown) with LT low dose tx
Colchicine :
Myopathy: What should be monitored?
Monitor for sx of muscle injury (tenderness, pain, weakness)
Colchicine :
Myopathy:
What should this medication be used cautiously with?
Caution with concurrent statins
Hyperuricemia drug: Urate-lowering tx (ULT):
What is this used for?
ULT is for frequent gouty attacks
Hyperuricemia drug: Urate-lowering tx (ULT):
What does it do?
Dissolves urate crystals
Hyperuricemia drug: Urate-lowering tx (ULT):
What does it prevent?
Prevent new crystals & disease progression
Hyperuricemia drug: Urate-lowering tx (ULT):
What does it prevent? What does it improve?
Reduce frequency of acute attacks
Improve quality of life
Hyperuricemia drug: Urate-lowering tx (ULT):
What kind of effect does it not have? So what should it NOT be used for?
No anti-inflammatory effects
so ⍉ use against acute gouty attack or pain directly
Hyperuricemia drug: Urate-lowering tx (ULT):
What is the prototype drug?
Prototype drug: Allopurinol
Xanthine Oxidase Inhibitors:
What is the prototype?
Allopurinol
Xanthine Oxidase Inhibitors:
Allopurinol: What is it used for specifically?
Use: chronic tophaceous gout
Xanthine Oxidase Inhibitors:
Use: chronic tophaceous gout
How does it stop chronic tophaceous gout?
Prevents new tophi from forming
Lessens tophi that have already formed
Xanthine Oxidase Inhibitors:
Use: chronic tophaceous gout
What does it do to joint function?
Better joint function
Xanthine Oxidase Inhibitors:
Use: chronic tophaceous gout
What does it do to serum uric acid levels?
Lowers serum uric acid levels
Xanthine Oxidase Inhibitors:
Use: chronic tophaceous gout
What does it prevent? What does it not do?
Prevents but does not relieve acute gout attack
Xanthine Oxidase Inhibitors
MOA
Inhibits xanthine oxidase (XO), the enzyme required for UA formation from breakdown of DNA products
Xanthine Oxidase Inhibitors
ADEs
Mild GI effects, drowsiness, metallic taste and exacerbation of gouty attacks
Paradox acute attack w/ initiation
Hypersensitivity syndrome
Xanthine Oxidase Inhibitors
ADEs: What ADE occurs with initiation?
Paradox acute attack w/ initiation
Xanthine Oxidase Inhibitors
Paradox acute attack w/ initiation: What may initial therapy elicit?
Initial therapy may elicit acute gouty attack from urate crystals being shed into the joint space
Xanthine Oxidase Inhibitors
Paradox acute attack w/ initiation:
How could this be avoided?
Prevented by co-administration with colchicine or low-dose NSAID
Xanthine Oxidase Inhibitors
Paradox acute attack w/ initiation: What should you tell patients?
Forewarn pts & educate not to stop med in an attack
Xanthine Oxidase Inhibitors
Paradox acute attack w/ initiation: When should you not start this medication (XIO)?
Don’t start in attack
Xanthine Oxidase Inhibitors
Who may it be given to?
May be given to children under 6 years old to treat hyperuricemia associated with cancer therapy
Allopurinol:
ADEs: Hypersensitivity syndrome
How common is it? How is it seen?
Rare, but potentially fatal
Allopurinol:
ADEs: Hypersensitivity syndrome
What kind of symptoms are seen?
Eosinophilia, hepatic & renal dysfunction, rash
Allopurinol:
ADEs:
What is a situation in which this med should be dc’d?
D/C if (+) fever, 1st sign of rash
Rash ALL Over – ALLopurinol – could be deadly, even a mild rash
Allopurinol:
ADEs:
What can a rash progress to?
Can progress to SJS, TENS
Allopurinol:
ADEs:
What may be required for treatment for ADEs?
Some may require hemodialysis or GCs if ⍉ spontaneous recovery
Allopurinol
Interactions
Can inhibit hepatic drug-metabolizing enzymes, delaying inactivation of other drugs
Allopurinol
Interactions: Can inhibit hepatic drug-metabolizing enzymes, delaying inactivation of other drugs
So what must be monitored?
Monitor LFTs
Allopurinol
Interactions: What drugs?
Warfarin
Ampicillin
Allopurinol
Interactions: If warfarin is used, what should be done?
decrease dose is warranted
Allopurinol
Interactions: If ampicillin is used, what could be occur? What should be done?
Combo TX ~ rash
D/c if occurs
