Conditions Effecting the Musculoskeletal System and PharmacotherapyPart Five: Inflammatory DX

Patho of Gout

Normal A&P
Purines: How are they found in the body?

Found naturally in body

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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

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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

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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

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Patho

Normal A&P:

What is UA formation dependent on?

UA formation is pH dependent

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Patho

What is Gout?

Type of inflammatory arthritis

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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)

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Patho

What two things must occur for gout to form?

Overproduction/Underexcretion of UA

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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

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Gout:

How does immune system react to uric acid crystals?

The immune system reacts to these crystals, causing intense inflammation and pain.

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Gout:

What do leukocytes do?

Infiltration of leukocytes inside synovial cavity phagocytize crystals

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Gout:

What does the breakdown of crystals lead to?

Crystals breakdown –> release of destructive enzymes

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Gout:

What forms in affected joints from crystal deposition?

Large, gritty deposits (tophi) form in affected joint from crystal deposition in subcu tissues

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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

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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

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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

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Prevalence:

What is the most common inflammatory arthritis in older adults?

Gout

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Prevalence:
Gout
How are women affected compared to men?

Men affected three times as often as women

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Prevalence:
Gout
What ethnicity are incidences higher in?

Incidences higher among African Americans

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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

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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

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Complex series of events in Gout:

What triggers an inflammatory response?

Crystals trigger inflammatory response

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Complex series of events in Gout:

When crystals trigger inflammatory response, what is activated?

Activation of cytokines, interleukins

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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

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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

1. Asymptomatic hyperuricemia 2. Acute gouty arthritis 3. 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

Conditions Effecting the Musculoskeletal System and PharmacotherapyPart Five: Inflammatory DX - Gout Flashcards

Exam 4 (Final) (108 cards)