Gout Flashcards
What are the steps to the pharmacologic treatment of Gout, and some associated medications?
Suppresses the acute attack
– NSAIDs – especially *indomethacin, ibuprofen or other propionic acid derivatives
– *Colchicine
– *Corticosteroids - especially prednisone** or
**methyprednisolone
Increase excretion of uric acid
– ***Probenecid **(Benemid)
– Sulfinpyrazone (Anturane)
Inhibit the formation of uric acid
– Allopurinol **(Xyloprim)
– **Febuxostat (Uloric)
How do NSAIDS help with Gout attacks?
example NSAIDs, mechanism, side effects and toxicities
*NSAIDS - Especially *Indomethacin (Indocin) or *Ibuprofen (Motrin, etc)
– These agents have good anti-inflammatory activity and, in many cases, can stop the acute gout attack within a few days.
– Mechanism of action - inhibition of prostaglandin synthesis.
– Side effects and toxicities
GI irritation - contraindicated in patients with peptic ulcer disease.
Indomethacin causes CNS side effects in many patients.
-headache, drowsiness, dizziness and confusion.
What NSAID do you avoid in Gout patients, and why?
aspirin because of its
biphasic effect on uric acid excretion.
Ketorlolac (Toradol)
type, use, main side effect
injectible NSAID that is mainly used for pain mananagement, instead of inflammation.
It is becoming widely used in treating acute gout attacks, where its analgesic and anti-inflammatory effects are very strong.
GI irritation is the main problem!
Colchicine
type, use and mechanism
– Naturally occurring alkaloid isolated from the autumn crocus
– Has a unique antiinflammatory activity that is specific for gout
– Mechanism of action
It binds to tubulin and prevents it’s polymerization to microtubules. This leads to a reduction in leukocyte migration, phagocytosis
and mitosis.
In addition, it inhibits the production and release of proinflammatory glycoproteins from neutrophils
Side effects of Colchicine
mild, severe, acute v. chronic use side effects
Side effects - may be severe even at therapeutic doses
– diarrhea
– GI upset - nausea, vomiting, etc..
– In overdose situations, severe burning, throat pain, bloody diarrhea and CNS depression occur.
– transient leukopenia (with acute usage)
– risk of agranulocytosis, aplastic anemia, alopecia, myopathies and neuropathies with chronic use.
Pharmacokinetics of Colchicine
route and dosage
– usually administered orally although it is can be given IV for acute attack.
– Dose - 0.5 - 1.0 mg every 2 hours until symptoms are relieved, or the patient craps their brains out! Lower, less frequent doses
are sometimes used to prevent recurrence of attacks.
What is colchicine’s place in therapy with other Gout medications?
traditionally been the preferred drug for alleviating the acute gout attack. Most patients experience significant relief of pain and swelling within 12- 24 hours. The beneficial effect of colchicine is
so specific for gout that it is almost diagnostic.
However, the GI side effects can be quite severe. At present, most physicians will first try to treat an acute attack with NSAIDs (especially indomethacin or ibuprofin) and corticosteroids. Low doses of colchicine are also sometimes used chronically to prevent the recurrence of gout attacks.
Allopurinol
mechanism, use, half-life
Allopurinol acts by inhibiting the enzyme xanthine oxidase and
reducing the formation of uric acid.
By lowering the level of uric acid below its limit of solubility, allopurinol can keep sodium urate crystals from forming and facilitate the dissolution of existing crystals.
Allopurinol does not stop an acute gout attack, but over time it can greatly reduce the potential for future attacks.
An active metabolite, oxypurinol has a long half life and may play a role in the effects during long-term therapy.
Side effects and toxicities of Allopurinol
generally well-tolerated
increased frequency of gout attacks during early stages of therapy.
-This is probably due to breakdown of crystals as the
uric acid blood levels begin to fall.
The acute attacks may necessitate the concomitant use of colchicine or other agents.
elevation of liver enzymes – monitor liver function
allergic reactions - mainly dermatologic, may be severe.
drug interactions of allopurinol
↑ half life and uricose uric effect of probenecid
– Inhibition of the hepatic metabolism of many drugs
– ↑ half life of theophylline
Febuxostat
type, effects, side effects,
– Newer xanthine oxidase inhibitor approved for treatment of gout.
– Touted as having fewer dermatologic and hepatic effects.
– Generally similar to allopurinol, but is much more expensive.
– Some reports suggest it may be more effective than allopurinol.
Probenecid
effect
Effect on Uric Acid Excretion - Probenecid inhibits both the secretion and the reabsorption of organic acids. Since more uric acid is reabsorbed than secreted by the tubule, the net effect of probenecid is to increase uric acid excretion.
Pharmacokinetics, side effects and toxicities of Probenecid
route, t1/2, dose, side effects, toxicities
Pharmacokinetics
– oral administration, peak blood levels 2-4 hours, elimination half life is 5-8 hours. Usually titrate patient 250 mg 2x/day for one week followed by 500 mg 2x/day chronically.
Side effects and toxicities
– generally well tolerated
– GI upset (~2% of patient) - use caution in patients with peptic ulcer disease
– skin rashes (2-4% of patients)
– overdose - CNS effects (seizures and death)
Probenecid contraindications
an increased risk of stone formation in the kidney as the concentration of urate in the tubular fluid/urine rises. It is contraindicated in patients with kidney stones (i.e. gouty
nephropathy).
- Note: important for patients taking uricosurgic agents to drink adequate fluids to maintain urine flow and prevent formation of urate crystals in the kidney
not effective for treating acute attacks. In fact it may trigger gout attacks early in therapy as existing urate crystals begin to dissolve.
