GOUT Rx Flashcards
What is uric acid?
metabolite of purines
Uric acid is made from….
via which enzyme?
hypoxanthine -> xanthine -> uric acid
xanthine oxidase
What is the purpose of Uric acid?
contains a lot of nitrogens and is a mechanism by which the body excretes large amounts of nitrogen
When does uric acid tend to precipitate?
High concentrations & Low pH
T/F Solubility of uric acid remains the same at all concentrations
T/F Solubility of uric acid remains the same at all pHs
False
Solubility 200 mg/dL at pH 7.0
Solubility 15 mg/dL at pH 5.0
Where are the 3 final destinations of purines/uric acid?
joints
kidneys
soft tissue
What happens if there is excess deposition of uric acid into joints?
What are the risk factors?
How is this normally treated?
excess uric acid in joint fluid causes phagocytosis and subsequent release of inflammatory cytokines, resulting in inflammation + pain
risk factors: uric acid levels, obesity, OH
Acute attacks: naproxen, colchicine, steroids, otherwise it lasts 3-7d w/o treatment
What happens if there is excess deposition of uric acid into kidneys?
What are the symptoms if this happens?
What is the difference between using low-dose aspirin vs high dose aspirin for pain management in acute attacks?
- excess uric acid in the urine (can precede or follow a gout attack); precipitation favored by acidic urine
- wickedly painful
**low dose aspirin - **
- avoided in acute gout attacks due to paradoxical effects of aspirin on renal handling of uric acid
- increases risk of uric stones
high doses
- uricosuria at higher doses because aspirin actually acts as an anion in the lumen and competes for reabsorption with uric acid (therefore more is excreted)
What happens if there is excess deposition of uric acid into soft tissue?
What do they look like?
excess uric acid in plasma causes crystal deposits in cartilage, tendons, and soft tissues, causing acute and chronic inflammation
Unslightly, but is NOT very painful
Can break through skin and appear as white/yellowish chalky nodules
Acute attacks of gout (4)
1st line? 2nd line? 3rd line? 4th line?
in order of treatment prefrence
- Naproxen (or indomethacin)
- Colchicine PO
- Prednisone PO
- Methylprednisolone, IV or Triamcinolone acetonide, IA
How does naproxen work?
How fast does Naproxen work to alleviate symptoms of Gout?
What are some side effects of naproxen?
Contraindications?
Inhibits COX1/2 -> decreased prostaglandins
relieve severe pain from acute attack within hours-days
ADR: gastric upset, gastritis, ulceration, acute renal failure (edema, fluid retention)
Contraindications: aspirin, patients taking anti-hypertensives (it decreases activity of it)
Why is low dose naproxen contraindicated in patients with acute gout attacks?
paradoxical effects of renal retention of uric acid, which increases risk of crystal precipitation
Why isn’t colchicine used as a first line of Tx?
When would you use colchicine?
When is colchicine contraindcated?
effective, but has unpleasant side effects (nausea, vomiting, diarrhea)
used if NSAID or steroid is not well tolerated
contradincations: erythromycin and other macrolides may increase risk of toxicity
What is the mechanism of colchine?
not entirely clear
may decrease leukocyte migration, phagocytosis, and inflammatory response that is induced by uric acid crystals
When is prednisone used for treatment of acute gout attacks?
3rd line; used when NSAIDs or colchine is not tolerated
When is Methylprednisolone or Triamcinolone acetonide used for acute gout attacks?
When would you provide it as IV? intraarticular delivery?
** IV** – for patients with multiple joints involved or who can’t take NSAIDs, colchicine, or oral steroids
Intra-articular – for patients with 1-2 joints involved or for patients with multiple joints involved or who can’t take NSAIDs, colchicine, or oral steroids
Patient has acute gout attack but has a history of gout kidney stones. What would you use?
Colchicine
aspirin has a paradoxical effect of renal retention of uric acid, which hrisk of crystal precipitation)
Patient with acute gout attack also has Zollinger Ellison’s Syndrome. What would you treat him with?
Colchicine
Don’t want to treat with naproxen because of gastric upset, gastritis, ulceration
Patient with acute gout attack has multiple joints involved. What would you use to treat him?
What if the patient only had a few joints involved?
multiple: IV
few: intra-articular
What are the 3 drugs used in the chronic management of Gout?
Allopurinol/febuxostat
Probenecid
Pegloticase
How does allopurinol work?
What is important when starting a patient on allopurinol?
What are the side effects?
**xanthine oxidase inhibitor **
MoA: decrease uric acid production, but increase hypoxanthine and xanthine in both blood/urine; may need to give Colchicine at the same time to prevent acute gout flares
ADR:
- TEN/Stevens Johnson syndrome
- hypersensitivity vasculitis
- agranulocytosis
- hepatic necrosis
- can precipitate an acute attack of gout
What is the biggest drug interaction you have to worry about with Allopurinol?
dramatic increase in toxicity of azathioprine and 6-MP; doses need to be reduced to 25-33% of normal
How does Probenecid work?
What are the ADRs of using this drug?
Who is it contraindicated in?
competitively inhibits the active reabsorption of uric acid at the PCT, thereby increasing urinary excretion of uric acid (uricosuric effect)
ADR: risk of aplastic anemia, hepatic necrosis, allergy; can precipitate an acute attack of gout (!!); may result in decreased renal clearance of drugs (PenG, cephalosporin, MTX) - leads to increased serum levels = BAD
Contraindications: sulfa allergy, or uric acid kidney stones
How does Pegloticase work?
When is it used? (indications)
How is it administered? Why?
What are the ADRs of using this drug?
recombinant urate oxidase (uricase)
MoA: catalyzes oxidation of uric acid -> allantoin, a metabolite that is inert, water soluble, and cleared by the kidney
indications: chronic severe symptomatic gout who cannot tolerate first-line therapies
Administration: must be given IV since it is an active enzyme
ADRs
- autoantibodies against recombinant protein develop
- can precipitate acute attacks of gout
- anaphylaxis – give patients antihistamine + corticosteroid prior to infusion OR prophylaxis with an NSAID or colchicine recommended for 6 months
