Gout Therapy Flashcards
Recurrent episodes of pain and joint inflammation due to formation os crystals and deposition of those crystals in soft tissues is…
Gout
What is deposited in gout?
Monosodium urate monohydrate (MSU( crystals
What is the cause of gout?
Hyperuricemia
Deposition of calcium pyrophosphate (CPP) crystals is associated with…
Pseudogout
What disorder is also referred to as Calcium Pyrophosphate Disease (CPPD)
Pseudogout
T or F: Humans lack the enzyme uricase.
True
Uricase function:
turns uric acid to allantoin (soluble form)
What enzyme is responsible for conversion of Hypoxanthine –> Xanthine –> Uric Acid?
Xanthine oxidase
What is the drug that acts on xanthine oxidase function?
Allopurinol
Intermittent acute attacks that spontaneously resolve typically over a period of 7-10 days with asymptomatic periods between attacks is ______ gout
Phase 1
Inadequately treated hyperuricemia can cause a transition to _____ gout
Second Phase
Which gout phase is manifested as chronic tophaceous gout which often involves polyarticular attacks, symptoms between attacks, and crystal deposition (tophi) in soft tissues or joints?
Second phase
Severe degenerative arthritis, secondary infections, urate or uric acid nephropathy, nerve or spinal chord impingement, increased infection risk, renal stones, and fractures are…
Complications associated with gout
In acute gout, the aim is to…
relieve pain, prevent disease progression, and prevent tissue deposition of uric acid
Top four options for managing acute gout attacks are:
NSAIDs
Colchicine
Glucocorticoids
(possibly) corticotropin
What are the first line treatments of acute gout attacks?
NSAIDs and colchicine
When NSAIDs or colchicine are poorly tolerated, you can use…
glucocorticoids or coticotropin
You should not use ____ _____ drugs for treatment of acute gout
Urate lowering drugs
No benefit
Is Aspirin indicated for treating acute gout?
NO
low doses –> uric acid retention (bad)
high doses –> uricosuric effect (excretion of uric acid) which seems good but you need HIGH doses which is dangerous
Patients with hyperuricemia that have at least two gout attacks per year or presence of tophi (clinically or radiographically) have…
Chronic gout
What is the aim for treatment of chronic gout?
lowering the serum urate levels
What drugs are used for chronic gout?
Urate lowering therapy (ULT) continued indefinitely
What urate level are you trying to maintain?
less than 6mg/dL
What are the three classes of agents used for ULT?
Xanthine oxidase inhibitors
Uricosuric agents
Uricase agents
Drugs that block production of uric acid?
Xanthine oxidase inhibitors
Drugs that increase secretion of uric acid by increasing its concentration in urine?
Uricosuric agents
Drugs that promote conversion to soluble form allantoin?
Uricase agents
What ULT drug is first-line therapy?
xanthine oxidase inhibitors
Allopurinol
Xanthine oxidase inhibitor
Febuxostat
Xanthine oxidase inhibitor
Probenecid and Lesinurad
Uricosuric Drugs
What drugs are used less frequently than xanthine oxidase inhibitors and are contraindicated in patients with nephrolithiasis?
Uricosuric Drugs
What drug is a combination of Uricosuric drug, Lesinurad, and a xanthine oxidase inhibitor, Allopurinol?
Duzallo
Fixed-dose oral combination for treatment of hyperuricemia
Used when patients don’t respond to only allopurinol
Pegloticase
Uricase Agent
Polyethylene glycolated modified porcine recombinant uricase
How is pegloticase administered?
Intravenously
Uricase agent
Infusion reactions are common for…
Uricase agent, Pegloticase, which is given IV
What are some non-pharmacologic therapies for gout treatment?
To decrease serum urate levels, you can avoid alcohol or modify diet by eating less meat (high purine –> uric acid)
What diet is associated with less consumption of red meat and more consumption of fruits and vegetables?
DASH diet
fruits and veggies –> increase vit C
In pseudogout, do you see elevated serum urate levels?
No! It’s different from gout. You have CPP depositions that are rhomboid shaped
Colchicine MOA is…
inhibition of microtubule assembly
Colchicine should NOT be used in patients with…
Advanced renal or hepatic impairment
If a patient has active peptic ulcer disease or history of NSAID intolerance, what drug should you use to treat acute gout flares?
Colchicine
What drug has a symptom of mild rash, can cause leukopenia or thrombocytopenia, diarrhea, acute gouty arthritis?
Allopurinol
Allopurinol is used more than febuxostat because…
it is less expensive
Probenecid MOA is…
Promotes renal clearance of uric acid by inhibiting urate anion exchanges (including URAT1) in the proximal tubule that mediates urate reabsorption
Increases urate excretion
Uricosuric agent
Nephrolithiasis or uric acid nephropathy are contraindications for…
Probenecid
Uricosuric agent
MOA of Lesinurad is…
Inhibits activity of URAT1 and OAT4 in vitro, does not inhibit GLUT9 or ABCG2
Unlike probenecid, it doesn’t inhibit OAT1 or OAT3 in clinical setting
What drug is often administered with allopurinol?
Lesinurad
Pegloticase
Recombinant uricase agent which converts uric acid to allantoin
