PHAR: Gout Flashcards
The breakdown of WHAT leads to uric acid biosynthesis?
Purines.
What is the most common gout presentation?
Extremely painful big toe.
Failing NSAIDs (eg if the patient has a bad reaction), what is most ideal for treatment of acute gout?
Colchicine.
Is having hyperuricemia synonymous with having gout?
No. About 10% of people with hyperuricemia develop gout at some point in their lifetimes.
What proportion of uric acid is derived from our diet?
About 1/3.
- What is the mechanism of action for colchicine?
- What does this effect? (3 things from lecture slides)
- Inhibition of microtubule assembly by binding to tubulin.
- Cell division.
- Neutrophil motility.
- Chemokine production (decreases).
- NET ANTI-INFLAMMATORY EFFECT.
What problems are associated with colchicine?
- Narrow therapeutic window (fine line between therapeutic and toxic).
What are the major adverse effects of colchicine? What are the rarer adverse effects of colchicine?
MAJOR - NVD (nausea, vomiting, diarrhoea). RARE - Muscle damage - Myelosuppression - Multiple organ failure
What is the drug of choice for long term treatment of chronic gout?
Allopurinol.
What is the mechanism of action of allopurinol.
Xanthine oxidase inhibitor. - Decreases uric acid synthesis.
Who are groups at risk to consider when prescribing allopurinol?
- People with the HLA-B*5801 allele i.e. East Asians.
- People currently being treated with mercaptopurine and azathioprine (purine analogues that act as cancer and autoimmune drugs).
- Allopurinol increases the effects of these two drugs.
Purines are broken down into uric acid with the assistance of the xanthine oxidase enzyme. At what steps does xanthine oxidase act in this sequence?
USED IN BOTH STEPS Hypoxanthine –> Xanthine Xanthine –> Uric acid
- What reaction does the enzyme urate oxidase/uricase catalyse? - Does it exist in the human body?
- Oxidation of urate to allantoin. - No.
In what two locations is uric acid metabolised?
- The kidney (renal, ~2/3) - The gut (enteric, ~1/3)
What are three risks groups associated with gout?
- The obese (more tissue = more turnover = more purines)
- People who consume excess sweet soft drink.
- Ageing population.
ALSO
- hypertension
- men
- metabolic syndromes
- kidney failure
- transplant patients
- Failing NSAIDs and colchicine (oral treatment), what would be the next line of treatment for relieving the pain in acute gout?
- When would this line of therapy be taken?
- Intra-articular glucocorticoid injection.
- If the joint wasn’t septic.
Why does gout occur in the extremities e.g. in the big toe?
- Uric acid has lower solubility in lower temperatures.
- Large crystals of uric acid form here (tophi).
- Is it safe to begin treatment for chronic gout during an acute attack?
- Why may it be prudent to do so?
- Yes.
- Ensures therapeutic adherence.
Xanthine oxidase converts allopurinol to the metabolite form oxypurinol. Name two ways that it differs from allopurinol.
- Oxypurinol has a longer half-life (18-30 hrs vs 2-3 hrs).
- Oxypurinol non-competitively inhibits xanthine oxidase.
- Note: The pharmacological action of allopurinol is largely due to oxypurinol.
What are the three categories of treatment for chronic gout?
- Describe their mechanism briefly.
- Give an example of each.
- Xanthine oxidase inhibitors.
- Competitively inhibits XO to decrease uric acid synthesis.
- Allopurinol.
- Uricase agents.
- Oxidises uric acid to allantoin.
- Uricase is also called urate oxidase.
- Uricase is absent in the human body.
- Rasburicase.
- Oxidises uric acid to allantoin.
- Uricosuric agents.
- Blocks urine reuptake in the proximal tubule, increasing uric acid excretion in urine.
- Probenecid.
What is thought to be the genetic component to Gout?
Genetic renal undersecretors.
As a small, unbound molecule 100% of the uric acid passes through the glomerulus, 99% is reabsorbed in proximal tubule, 6-10% is secreted in the distal tubule.
Undersecretion = too much uric acid -> Gout
