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GOUT
Dr.B.V.Venkataraman
Professor in Pharmacology
Faculti Perubatan,
International Medical School,
New BEL Road, Bangalore-560054
[email protected]
GOUT
Gout is a disorder of purine metabolism. Excess
production or slow excretion (3.5-7.5mg/dl normal)
Uric acid has low solubility in acidic urine
Common in big toe, mid foot, ankle, knee
Pathology of gout
Lactic acid
production
Reasons for Gout
Genetic factor – Men get more than females
Excessive alcohol consumption,
Diet rich in purine (meat preparations)
Lead poisoning
kidney disease
Anticancer drugs, diuretics,
Management of acute gout
NSAIDs
Corticosteroids
Colchicine
Management of Chronic gout
Allopurinol
Uricosurics – probenecid, sulfinpyrazole
Newer drugs
Anakinra
Urate reasbsorbtion blocker (presently called
RDEA594)
COLCHICINE
Source: colchicum autumnale
It binds to tubulin, and causes its depolymerisation.
This decreases the mobility of granulocytes into the
affected area.
decreases lactic acid production
thereby reducing the deposition of urate crystals
that perpetuates the inflammatory response
Lactic acid production
Phagocytosis and release
Inhibited by COLCHICINE
Colchicine (contd)
Lack - analgesic, anti pyretic and uricosuric
rapidly absorbed orally
recycled in the bile
excreted unchanged in the faeces and urine
Indications of Colchicine
prevention of acute attack and prophylaxis of
intermittent attacks.
replaced by NSAIDs and steroids in acute attack
treatment, as it requires very high dose.
IV dose does not produce diarrhoea.
Diarrhoea occurs with oral route.
Side effects of Colchicine
diarrhea (not on iv route)
occasionally cause nausea, vomiting, and abdominal
pain.
On chronic use
rarely cause hair loss and bone marrow depression
peripheral neuritis and myopathy.
NSAIDs:
Indomethacin is potent
Relief is quick
Minimal side effects during acute treatment 25-50 mg
every 4 hr.
Other NSAIDs (except salicylates) are also effective.
NSAIDs
CORTICOSTEROIDS:
Effective and rapid in action
Prednisone or methyl prednisone better than long
acting anti inflammatory steroids
Combined with indomethacin or colchicine. 40
mg/day till the attack subsides
steroids should be tapered after acute phase.
Local injections possible if one or two joint
swellings
CORTICOSTEROIDS
CHRONIC GOUT
Aim of the treatment
Decrease uric acid synthesis (xanthine
oxidase inhibitors)
Increase the uric acid excretion (uricosuric
drugs)
Xanthine Oxidase Inhibitors
Allopurinol
Prototype - useful in all types of gout
Pharmacokinetics of allopurinol
well absorbed orally
metabolised into alloxanthine
Both allopurinol and alloxanthine inhibit the uric acid
synthesis
has longer duration of action
single dose is enough to maintain the inhibitory
effect.
Dose: 100 mg single dose after food.
Side effects of allopurinol
Most frequent treatment-related - liver function
abnormalities, diarrhea, headache, and nausea
Not used in acute attack, as it flares up the attack in
some people
Even in chronic treatment initial administration
precipitate acute attack. So combine with colchicine
or NSAIDs.
Therapy should be always with plenty of fluid to
avoid renal calculi.
Febuxostat - well tolerated in patientsof allopurinol
intolerance.
Allopurinol interactions
Inhibits metabolism of mercaptopurine, azothioprine
and other xanthine alkaloids (theophylline) - doses
should be reduced.
Higher incidence of hypersensitivity reaction with
ampicillin
Inhibits metabolism of the oral anti coagulants prolongs bleeding
URICOSURIC DRUGS
increase the excretion of uric acid in the urine
Probenecid and sulfinpyrazone - standard
uricosurics.
Competes with uric acid for tubular reabsorption
Side effects
Hypersensitivity reaction
gastric irritation
Use
Chronic gout
URICOSURIC DRUGS (Contd)
Drug interaction
Uricosuric drugs decrease the excretion of oral
hypoglycaemic agents, sulphonamides, penicillin
group of antibiotics, indomethacin
Precaution
Not suitable for acute attack
Not used in high uric acid level
ANAKINRA
block the receptor, interleukin 1-beta - an important
inflammatory chemical (cytokine)
Urate reabsorbtion blocker
a direct blocker of URAT1 - transporter of uric acid
from the urine back into the body
Decrease uric acid level even in acid urine
RDEA594 (coded drug)
ANAKINRA