Treatment of Gout Flashcards
Colchicine
• Use in treatment of gout
• Is this a short term or long term tx
• MOA
• Side effects
Colchicine is used to treat:
• acute gout attack (within 48 hours of onset - because this is when PMNs are migrating, remember immuno…)
• Prophylaxis of gout attack (e.g. starting allopurinol)
MOA:
• Prevents depolimerization of microtubules, this is effective because PMNs need microtubules to migrate
Side Effects:
• GI disturbances
• Blood Dyscrasias (Chronic use)
Indomethacin
• Use in treatment of gout
• Is this a short term or long term tx
• MOA
• Side effects
Indomethacine is used in the acute treatment of gout and is only used on a short term basis
MOA:
• COX 1/2 inhibitor (with COX-1 preference) + Phospholipase-2 (PLP2) inhibitor that works as an analgesic and antipyretic while inhibiting leukocyte motility
Side Effects:
• 50% of patients get GI upset with N/V/ulcers
• CNS severe frontal headache
• Hematopoietic Disorders (long term)
Allopurinol
• Use in treatment of gout
• Is this a short term or long term tx
• MOA
• Side effects
Allopurinol is widely used in gout as a drug that treats 1Primary Hyperuricemia due to enzyme abnormalities (PRPP, HGPRT), 2Kids with fam hx. of uric acid stones in the kidney, 3secondary hyperuricemia due to cell proliferation and death (cancer/chemo), or 4patients with recurrent gout.
MOA:
• Suicide inhibitor of Xanthine Oxidase by 1st acting to non-competivitely inhibit and is then acted on a second time to irreversibly inhibit.
Side Effects:
• Increased incidence of gout due to disruption of urate stores in tissue (proflaxis with colchicine)
• Hypersensitivity reactions like dermatitis and exfoliative dermatitis
• Hard on the Liver
• Can’t give to ppl. with Renal Impairment
Probenicid
• Use in treatment of gout
• Is this a short term or long term tx
• MOA
• Side effects
These drugs are indicated for people who underexcrete uric acid (less than 1 g per day) but have otherwise NORMAL kidney function.
MOA:
• Competes with uric acid for reabosorption at the brush border transporter
Side Effects:
• None mentioned, but just don’t give NSAIDs or Asprin to these people because it will inhibit the uricouric action of probenecid
Febuxostat
• Use in treatment of gout
• Is this a short term or long term tx
• MOA
• Side effects
Typically given as an alternative if people have adverse reactions to allopurinol or don’t have the renal capacity to handle allopurinol
MOA:
• Inhibits BOTH Oxidized and Reduced forms of Xanthine Oxidase
Side Effects:
• Very Mild Side effects, but you still need to give Colchicine when starting this drug
• Elevates Liver Enzymes
• Contraindicated with SEVERE renal impairment
Pegloticase
• Use in treatment of gout
• Is this a short term or long term tx
• MOA
• Side effects
Controls the consequences of gout in patients that cannot be treated by any other methods, these people may have tophi that can’t be dissolved by other agents
MOA:
• This is a pegylated (to promote longevity) pig uricase enzyme that converts uric acid to allantoin
Side Effects:
• Massive dissolution of Tophi WILL lead to flare-ups so you need to give these people Colchicine, NSAIDs, or glucocorticoids prophylactically.
• People develop antibodies to the PEG so drug is only effective for a limited time (like a year)
What serum level of urate defines gout?
7 mg/dL
Does Colchicine have any anti-inflammatory, anti-pyretic, or urate lowering properties?
• what is its use in the treatment of gout?
NO - it is used in the acute treatment of gout to prevent neutrophil chemotaxis only
T or F: if a gout attack is mild you can used NSAIDs like Ibuprofen to treat it.
True
Why is prevention of neutrophil chemotaxis so important in gout and how does this happen?
- Sharp Crystals causes immune activation and PMNs migrate and die because they can’t dissolve uric acid
- When PMNs die they release their contents (ROS, proteases, etc.) causing tissue damage and pain.
What drugs should be worried about giving allopurinol with concurrently and why?
Ampicillin and related antibiotics (amoxicillin etc) may cause increased incidence of exfoliative dermatitis (Dr. Sweatman says this is not a true contraindication)
6-mercaptopurine is also metabolized by HGPRT so you should reduce 6-MP dose to 1/4 if given with allopurinol
You have a kid with Lesch-Nyhan and prescibe allopurinol. His skin become extremely red and sheds. What should you do next?
Desensitize the kid to the drug because this is his best treatment option
Note: you can desensitize with allopurinol or oxypurinol (oxypurinol seems to elicit less of an immune response so it might be a good one to start with)
Blood levels of what metabolites would be high in someone treated with allopurinol?
• Is there a risk of precipitation?
• Do these people have increased risk of gout for kidney stones?
Hypoxanthine and Xanthine will be elevated but they are extemely soluble in the urine. Since urate is not generated and these metabolites are so soluble these drugs can be given in kids that have hyperuricemic nephropathy
How does uric acid transport work in the kidney?
- 100% is filtered through the glomerulus, then 99% is reabsorbed by the Proximal Convoluted Tubule
- Uric acid is then Resecreted into the tubular Lumen an OAT (organic acid transporter)
- Absoprtion then happens in the Brush Border Transporter
**After the Proximal Convoluted Tubule Uric Acid levels do not change in the kidney**
In general how do the uricosuric agents work?
These agents get freely filtered like urea and are reabsorbed like urea, then resecreted (note: that the first absorption and second secretion do not compete with urea) at the 3rd absorption at the Brush Border Transporter is where prevent uric acid from getting reabsorbed.
