AntiGout Flashcards
a metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium
urate in joints and cartilage
Gout
Gout is a metabolic disease characterized by recurrent episodes of _____________ due to deposits of monosodium
urate in joints and cartilage
acute athritis; monosodium
urate
a systemic disease caused by the buildup of uric acid in the joints, causes inflammation, swelling and pain
Gout
urate level > 8mg/dL in men and 7 mg/dL in women
Hyperuricemia
ost common first symptom of gout
Pain in one joint of the lower extremity
end product of purine metabolism
Uric acid
rate limiting step in the formation of the uric
acids
Xanthine oxidase
serves no known biological functions, but the body has
content of 1.0-.2g
Uric acid
Approximately ________ of Uric acid is excreted via the ________
70-80%; kidneys
result of an innate defect in purine metabolism of uric acid excretion
Primary gout
Causes of primary gout
Uric acid overproduction (overproducers)
Impaired renal clearance of uric acid (underexcreters)
Combination of both
causes of Secondary gout
- Hematologic disorders
- Drug induced – salicylates,diuretics (thiazide), ethambutol, pyrazinamide, nicotinic acid, ethanol, niacin and cyclosporine
Treatment Goals for gout
- Relieve pain and inflammation
- Reduce serum uric acid concentration (urate lithiasis)
- Prevent recurrent gout attacks
Treatment for acute gouty athritis attack
- Colchicine
- NSAIDs
- Corticosteroids
Antimitotic drug that is highly effective in relieving acute gout attack
Colchicine
Has low –benefit to toxicity ratio, thus it is used less often than NSAIDs
Colchicine
Colchicine is most effective when initiated within ____________ of the attack
12-36 hours
T/F: Colchicine’s likelihood of success increase substantially if treatment is delayed longer than 48 hours after symptom onset.
false: decrease
type of colchicine that causes dose-dependent GI adverse effect (nausea, vomiting, bloating, emesis and diarrhea) that occur in up to 80% of patients
oral colchicine
first-line drugs for acute gout
NSAIDs, corticosteroids, or
was the primary treatment for many years due to its efficacy in treating and preventing acute gout flares
colchicine
Colchicine can be taken with or without food and is sometimes given in combination with
NSAIDs
True
Colchicine is an alkaloid isolated from the autumn crocus, ______________
Colchicum autumnale
relieves the pain and inflammation of gouty arthritis in 12–24 hours without altering urate metabolism or excretion and without other analgesic effects
Colchicine
Colchicine relieves the pain and inflammation of gouty arthritis in ________ without altering ___________ and without other analgesic effects
12–24 hours; urate metabolism or excretion
Colchicine relieves the pain and inflammation of gouty arthritis in 12–24 hours _________ (with/without) altering urate metabolism or excretion and without other analgesic effects
without
mainstay of therapy because of their excellent efficacy and minimal
toxicity with short-term use.
NSAIDs
NSAIDs Therapy should be initiated with ____________ (maximum/minimum) recommended dose for gout at the onset of symptoms and continued for ______- after resolution of an acute attack, then tapered quickly over _____
maximum; 24 hours; 2-3 days
NSAID most common adverse effects involve _____
GI system
most extensively studied NSAID in the treatment of an acute gouty arthritis attack
Indomethacin
In addition to inhibiting prostaglandin synthase, __________ inhibit urate crystal phagocytosis and reduce inflammation and pain in acute gout flare
NSAIDs
NSAIDs inhibit
-prostaglandin synthase
-urate crystal phagocytosis
Why is Aspirin not used in Gout treatment?
because it causes renal retention of uric acid at lower doses (≤2.6 g/d); it is uricosuric at doses >3.6 g/d.
T/F: All NSAIDs except aspirin, salicylates, and tolmetin have been successfully used to treat acute gouty episodes
true
lowers serum uric acid, is theoretically a good choice and all NSAIDs appear to be as effective and safe as the older drugs like indomethacin
Oxaprozin
equivalent to NSAIDs for treatment of acute gout flares
Corticosteroids
Corticosteroids are effective when given _________
intra-articulary, IV or orally.
Oral Corticosteroid
Prednisone
long acting corticosteroid, IM, ntra-articular (can be given if the patient is unable to take oral medications)
Triamcinolone acetonide or methlyprednisolone
decrease activation, proliferation, and survival of various inflammatory cells
corticosteroids
decrease the migration of neutrophils, and they inhibit prostaglandins and proinflammatory cytokines such as IL-1β.
corticosteroids
a good alternative for patients in whom NSAIDs or colchicine are contraindicated and in those with renal impairment or chronic kidney disease.
Corticosteroids
sometimes used in the treatment of severe symptomatic gout, by oral, intra-articular, systemic, or subcutaneous routes.
Corticosteroids
The goal of _____________ is to achieve and maintain a serum uric acid concentration < 6mg/dL and preferably < 5mg/dL
urate lowering therapy
Reduction of the serum urate concentration un Uric Acid Lowering Therapy can be accomplished b
- decreasing uric acid synthesis (xanthine oxidase inhibitor)
- Increasing the renal excretion of the uric acid (uricosurics)
Uric Acid Lowering therapy are not be used during as ______
acute gouty arthritis attack
Allopurinol, Febuxostat
Xanthine Oxidase Inhibitors
reduce uric acids by impairing the conversion of hypoxanthine to xanthine and xanthine to uric acid.
Xanthine Oxidase Inhibitors
effective in both overproducers and underexcretion of uric acids
Xanthine Oxidase Inhibitors
most widely prescribed agents for long-term prevention of recurrent gout attacks
Xanthine Oxidase Inhibitors
responsible for the conversion of xanthine and hypoxanthine to uric acid
Xanthine oxidase
a purine analogue that inhibits this enzyme, resulting in a fall in the plasma urate level and a decrease in the overall urate burden.
Allopurinol
Allopurinol is a _________ analogue that inhibits this enzyme, resulting in a fall in the _________ and a decrease in the _____
purine; plasma urate level; overall urate burden
The result of xanthine oxidase inhibition is
build-up of its substrates, the more soluble xanthine and hypoxanthine
The result of xanthine oxidase inhibition is a build-up of its substrates, the _______ (more/less) soluble xanthine and hypoxanthine.
more
is often the first-line agent for the treatment of chronic gout in the period between attacks, and it tends to prolong the intercritical period
Allopurinol
Allopurinol is often the first-line agent for the treatment of chronic gout in the period between attacks, and it tends to prolong the ________
intercritical period
T/F: Allopurinol Therapy is continued for years if not for life.
true
a potent and selective non-purine inhibitor of xanthine oxidase thereby reducing the formation of xanthine and uric acid without affecting other enzymes in the purine or pyrimidine metabolic pathway
Febuxostat
Febuxostat is a potent and ___________ non-purine inhibitor of xanthine oxidase thereby reducing the formation of _______ without affecting other enzymes in the ________
selective; xanthine and uric acid; purine or pyrimidine metabolic pathway
Febuxostat is a potent and selective __________ inhibitor of xanthine oxidase thereby reducing the formation of xanthine and uric acid ________ (with/without) affecting other enzymes in the purine or pyrimidine metabolic pathway
non-purine; without
uricosuric agent have been discontinued in the USA
Sulfinpyrazone and Lesinurad
Probenecid
Uricosuric Drug
They increase the renal clearance of uric acid by inhibiting the postsecretory renal proximal tubular reabsorption of uric acid.
Uricosuric Drugs
should be initiated in gouty patients with underexcretion of uric acid when allopurinol or febuxostat is contraindicated
Uricosuric therapy (Probenecid)
Uricosuric therapy (Probenecid) should be initiated in gouty patients with underexcretion of uric acid when ________ or _________ is contraindicated
allopurinol; febuxostat
T/F: Probenecid can be used as monotherapy or in combination with a xanthine oxidase inhibitor
True
Canakinumab, Anakinra,
and Rilonacept
INTERLEUKIN 1 INHIBITORS IN GOUT
inhibit the IL-1 receptor pathway
INTERLEUKIN 1 INHIBITORS IN GOUT
main proinflammatory cytokine responsible for the crystal-induced inflammation of gout.
IL-1β
T/F: Canakinumab, Anakinra,
and Rilonacept are not yet FDA-approved for the treatment of gout.
True
All three IL-1 inhibitors are administered
subcutaneously
