Gout Flashcards
Aim to treat acute attacks of gout
Aim –> control pain and limit joint inflammation
Aim to treat long-term managment of chronic gout
Aim –> modify purine metabolism or excretion to achieve normal concentrations of plasma urate
drugs used to treat an acute goute attack
-
NSAIDs (e.g. ibuprofen, naproxen, indomethacin)
- Selective NSAIDs –> in case of GI bleeding history.
-Aspirin is contraindicated in Gout.
2. Microtubule inhibitor –> e.g. colchicine is useful if NSAIDs are contraindicated.
3. Glucocorticoids –> e.g. hydrocortisone {oral, intramuscular or intra-articular} is an alternative to NSAIDs and colchicine.
4. Combinations –> used in severe acute attacks with polyarticular involvement.
cateogory of Ibuprofen/ Naproxen/ Indomethacin
NS-NSAIDS
Indication of Ibuprofen/ Naproxen/ Indomethacin
- Used in patients with no GI bleeding history.
note:
* S-NSAIDs are used in case of a patient with GI
bleeding history –> celecoxib
S-NSAIDs used in case of a patient with GI bleeding history?
celecoxib
MoA of Ibuprofen/ Naproxen/ Indomethacin
Effective in inhibiting the
inflammation of acute
gouty arthritis.
PK/PD of indomethacine/ Ibuprofen/Naproxen
Act through the reduction of prostaglandins formation and the inhibition of crystal phagocytosis by macrophages.
category of Clochicine
Microtubule Inhibitor
Indication of Colchicine
- Acute attacks of gout.
- Lower doses are used to prevent attacks of gout in patients with history of multiple acute attacks.
MoA of Colchicine
A selective inhibitor of microtubule assembly – ↓ microtubule polymerization.
AE of Colchicine
Acute use:
1. Nausea, vomiting, diarrhea and GI pain.
Longer use:
1. Hepatic necrosis, acute renal failure, hematuria, (rarely may cause alopecia, myelosuppression and
peripheral neuropathy).
–> Can severely damage the liver and kidney -> monitoring patient is a MUST.
PK/PD of Colchicine
1) Given for prophylactic treatment when drugs for chronic management of gout
are introduced.
2) Colchicine doses required to treat acute attacks cause significant GI disturbance
(abdominal pain and diarrhea).
Category of Hydrocortisone
Natural Glucocorticoid
indication of Hydrocortisone in the Tx of gout
Used as an
alternative to
NSAIDs and
colchicine.
MoA of Hydrocortisone
reduce the synthesis of inflammatory mediators in the gouty joint (intraarticular injections).
drugs used to treat Chronic gout
1) 1st line: Xanthine oxidase inhibitors –> reducing the conversion of purines to uric acid by Xanthine oxidase (e.g. allopurinol or
Febuxostat)
2) 2nd line; Uricosuric drugs –> accelerating renal excretion of uric acid (e.g. probenecid or sulfinpyrazone)
Category of Allopurinol
Xanthine oxidase inhibitors
Indication of Allopurinol
1st line treatment for Chronic Gout
–> Administered in combo with NSAIDs or Colchicine to avoid and acute attack.
MoA of Allopurinol
Inhibition of xanthine
oxidase (XO) –> ↓ uric acid production
PK/PD of Allopurinol
1) A prodrug –> given orally and is well absorbed.
2) Its half-life is 2-3h –> its active metabolite alloxanthine has a half-life of 18 – 30 h.
3) Renal excretion.
4) It inhibits the metabolism of azathioprine and 6-mercaptopurine (6-MP), drugs that depend on XO for their elimination.
5) increases the production of Xanthine and Hypoxanthine –> ↓ uric acid production
Adverse effects of Allopurinol
–> Formation of renal stones is inhibited
(hypoxanthine stones might be formed).
Toxicities:
1. GI disturbances, allergic reactions (rashes), peripheral neuropathy, vasculitis, or bone marrow dysfunction.
2. Rare –> potentially fatal skin conditions
such as Stevens Johnson Syndrome (HLAB*5801 testing recommended in some
Asian populations).
category of Febuxostat
Xanthine oxidase inhibitors
indication Febuxostate
- Used if allopurinol is not effective or not
tolerated
–> in combo with NSAIDs or colchicine.
MoA of Febuxostat
A non-purine reversible
inhibitor of XO that is more selective.
PK/PD Febuxostat
- Clinical trials show that it is more effective in treating
chronic gout than Allopurinol.
2. Contraindicated in CV patients.
AE of Febuxostat
- Some studies showed higher risk of CVD
deaths
Can cause liver function abnormalities, headache,
and GI upset.
Category of Probenecid/ Sulfinpyrazone
Uricosuric drugs
Indication of Probenecid/ Sulfinpyrazone
Used orally to treat chronic gout,
caused by underexcretion of uric acid
MoA of Probenecid/ Sulfinpyrazone
-
Compete with uric acid for reabsorption by
the weak acid transport mechanism (URAT1) in
the proximal tubules –> This results in an
increased uric acid renal excretion
*therofore, ineffective if patient has renal damage
AE of Probenecid/ Sulfinpyrazone
- GI irritation, nephrotic syndrome.
- Can precipitate an attack of acute gout
in early phase of their action.
–> To avoid this – simultaneously administering NSAIDs (e.g. indomethacin or colchicine). - Crystallization (kidney stones) might occur if high excretion of uric acid takes place.
-
Alkalizing the urine to reduce risk of
stone formation. - Maintain high urine volume.
PK/PD of Probenecid/ Sulfinpyrazone
- At low doses, these drugs compete with uric acid for secretion by the tubule –> can
elevate, rather than reduce, serum uric acid concentration. -
Not used in acute gout attack – used in combination with NSAIDs or colchicine
4. Aspirin –> causes elevation
of uric acid levels by this mechanism – contraindicated
5. Inhibit the secretion of a large number of other weak acids (e.g. penicillin or
methotrexate) - These drugs are of no value in acute episodes.
- Ineffective if GFR <50 mL/min (renal failure)
Drugs contraindicated in Gout Tx, why?
Aspirin –> casues elevation of uric acid levels
