Drugs used in
Treatment of
Gout
By the end of this lecture
students will be able to:
⯈ Classify drugs used in the
treatment of gouty arthritis
⯈ Discuss the pharmacology of drugs
used in gouty arthritis
Gout
⯈ Is marked by
transient attacks of
acute arthritis
initiated by
crystallization of
monosodium urate
within and around
joints
May also get
deposited in kidneys
and subcutaneous
tissue (tophi)
Drugs useful in gout
Objective of Drugs
treatment
Relieve NSAIDs,
inflammation and colchicine,
pain glucocorticoids
Prevent NSAIDs, colchicine
inflammatory
responses
Inhibit urate formation Allopurinol,
febuxostat
Augment Probenecid
Drugs useful in Gout
•Acute Gout Chronic Gout
•NSAIDs: Uricosuric:
• Naproxen • Probenecid
• Indomethacin • Lesinurad
• Diclofenac • Benzbromarone
• Sulfinpyrazone
•Colchicine Synthesis inhibitor:
• Allopurinol
• Febuxostat
Increase
• Corticosteroids: metabolism:
• Prednisolone • Pegloticase
• Rasburicase
Colchicine
⯈ Alkaloid derived from C.
autumnale
⯈ Specifically suppresses
gouty inflammation
⯈Faster acting than
NSAIDs
Control of attack 6-12
hrs
Complete resolution 3-
5 days
Colchicine: Mechanism of action
⯈ Acts by:
Inhibitingrelease of
chemotactic
factors and
glycoproteins
Binds to fibrillar steps
• Subsequent
protein and inhibits • Vicious
Inhibited
granulocyte cycle
migration to joints interrupted
⯈ Also has amitotic
action and increases
Colchicine: Pharmacokinetics
⯈ Rapidly absorbed orally
⯈ Partly metabolised by liver and excreted in
bile
Undergoes hepatic circulation
Takes long to get eliminated
Metabolised by CYP3A4 isoenzymes
Drug interactions with enzyme
inhibitors/inducers
⯈ Gets eliminated in urine and faeces
Colchicine: Adverse effects
⯈ Dose limiting side effects:
Nausea,vomiting, abdominal pain,
diarrhoea
⯈ Chronic administration:
Myopathy, neutropenia, aplastic anaemia,
alopecia
⯈ Overdose:
Kidneydamage, CNS depression, intestinal
bleeding
Death: muscular paralysis and respiratory
Colchicine: Uses
⯈ To abort an attack of gout:
0.5-1.5 mg stat
⯈ To control an acute attack of
gout:
Second line, fastest acting
0.5mg 1-3 hourly, 4 doses in
a day
Maximum dose: 6 mg over 3-
4 days
⯈ As maintenance dose in gout:
Probenecid
⯈ Enhances excretion of uric acid
by:
Blocking Urate transporter-1
(URAT-1)
A type of organic anion
transport protein (OATP)
Predominant reabsorption of
uric acid in kidney (PCTs)
Reabsorption of uric acid
in PCT inhibited
Excretion enhanced, blood
Probenecid: Interactions
⯈ Inhibits urinary excretion of:
Indomethacin, naproxen
Penicillin,
sulphonamides,
methotrexate
⯈ Inhibits biliary excretion of
rifampicin
⯈ Inhibits tubular excretion of
nitrofurantoin
⯈ Action of probenecid decreased by:
Pyrazinamide, ethambutol
Probenecid: Indications
⯈ Chronic gout and hyperuricaemia
Second line drug
0.25 mg twice daily 0.5 mg twice
daily
Colchicine/NSAIDs cover needed
⯈ Prolong action of penicillin
Gonorrhoea, Sub Acute Bacterial
Endocarditis
⯈ Prevent cidofovir induced
nephrotoxicity
Probenecid
⯈ Adverse effects:
Generally well tolerated
Dyspepsia
Caution in patients with peptic ulcer
disease
Rashes, other hypersensitivity
reaction
⯈ Avoid in patients with renal
insufficiency, renal calculi
Allopurinol
⯈ Substrate as well as inhibitor of
xanthine
enzym oxidase Purine
e • Short acting s
• Competitive
Allopurino inhibitor
Hypoxanthin
l
Xanthine e
oxidase
Xanthin
Alloxanthin e
Xanthine oxidase
e •• Long
a
Non-competitive
cting
inhibitor Uric
acid
Allopurinol: Mechanism of action
⯈ Inhibits xanthine oxidase (XO)
Directly
By getting converted to alloxanthine
⯈ Decreased concentration of uric acid in
plasma
Hypoxanthine and xanthine
concentration increased
All three metabolites excreted in
urine
⯈ Increase hypoxanthine and xanthine
leads to feedback inhibition of de novo
purine synthesis as well
Allupurinol
⯈ Pharmacokinetics:
Metabolised largely to alloxanthine
Metabolism inhibited on
chronic administration
⯈ Interactions:
Inhibits
degradation of 6-
mercaptopurine, azathioprine,
warfarin, theophylline
Complex interaction with
Allopurinol: Indications
⯈ Chronic gout
First line drug
Given for long duration
100 mg/d 300 mg/d; maximum
600 mg/d
Patients advised to drink plenty of
water
⯈ Secondary hyperuricaemia
⯈ Potentiate 6-MP, azathioprine
Allopurinol: Adverse effects
⯈ Attacks of acute gout during start of
therapy
NSAIDs/Colchicine cover required
⯈ Hypersensitivity reaction, Steven-
Johnson syndrome
Contraindicated
⯈ Gastric irritation, headache,
nausea, dizziness
⯈ Liver damage
Febuxostat
⯈ Non-purine XO inhibitor
⯈ Adverse effect:
Liver damage
Hypersensitivity reaction
Diarrhoea, nausea, headache
⯈ Used as an alternative to allopurinol
Not to be combined with allopurinol
⯈ Dose: 40 mg/d 80 mg/d; maximum
120 mg/d
For uric
acid
Pegloticase
Pegylated Metabolising
enzyme
⯈ Recombinant uricase
Oxidises uric acid to allantoin
Highly soluble
Coupled to methoxy polyethylene
glycol
⯈ Refractory symptomatic gout
Given intravenously, every 2
weeks
⯈ ADRs: infusion reactions,
development of antibodies
NSAIDs in Gout
⯈ Naproxen, indomethacin, diclofenac,
etoricoxib
⯈ Better tolerated than colchicine
⯈ Uses:
To terminate the attack of acute gout
Frequent high doses
Takes 12-24 hours, complete
resolution in 5-10 days
As
a cover till effects of other anti-
gout drug effects develops
NSAIDs in gout
Drug Dose
Naproxen 750 mg stat 250 mg,
three times a day till
attack subsides
Indomethacin 50 mg, three time a day till
attack subsides 25 mg
three time a day for 5-7
days
Diclofenac 50-75 mg, three times a day
Etoricoxib 60-120 mg, once daily
Corticosteroids in gout
⯈ Suppress symptoms of acute gout
⯈ Can be given by:
Intraarterial injection
Triamcinolone 10-30 mg
Avoid crystalline preparation
Indicated when few joints are
involved, those not tolerating
NSAIDs/colchicine
Corticosteroids in gout
⯈ Suppress symptoms of acute gout
⯈ Can be given by:
Systemic administration (oral)
Indicated for patients with renal
failure/peptic ulcer, non-responders,
not tolerating
Prednisolone
40-60 mg tapered
over 1-2 weeks
Conclusion
⯈ NSAIDs are the drug of choice for
treatment of acute gout
Indomethacin, naproxen
⯈ Allopurinol is the drug of choice for
treatment of chronic gout
Probenecid cannot be used in patients
with renal impairment, and is
associated with risk of renal stones
⯈ Any queries?
⯈ Thank you
