Uric acid derived 1/3 from dietary source and 2/3 from purine metabolism
Excess uric acid deposited in interstititum of kiedney
GIT effects due toenterohepatic circulation so long duration drug present in GIT.
What is Arthritis?
There are 127 different kinds of
Rheumatoid arthritis: Severe
inflammation that involves many
joints and moves beyond
Gout: Very painful form of arthritis
characterized by the formation of uric
acid crystals and severe inflammation.
degeneration of joint cartilage. Minor
degree of inflammation.
• Gout is a metabolic disorder of purine
metabolism, characterized by intermittent
• It always preceded by hyperuricaemia (6.0mg/dl)
Hyperuricaemia due to excessive amount of uric
acid production or decreased excretion
• Hyperuricaemia - primary or secondary.
• Primary hyperuricaemia classified as
“Overproducers” or “under execrators”
• Primary Hyperuricemia and
Gout with No Associated
Secondary Hyperuricemia and Gout with
Identifiable Associated Condition
• Uric acid undersecretion(80%–
• develop during course of other diseases
(Leukaemias, lymphomas, chemotherapy)
• Some drug therapy (Thiazide diuretics,
furosamide, ethacrynic acid)
• Urate overproduction (10%–
• HGPRT deficiency
PRPP synthetase overactivity
• Some disorders Diabeticketoacidosis, lead
diseases, Hemolytic anemias, psoriasis
• Dual mechanism
Obesity, Hypoxemia and hypoperfusion
Uric acid production and excretion
URIC ACID (low water soluble)
Deposits of urate crystal
Uric acid freely filtrated through by glomerulus and
reabsorbed by tubular fluid
Pathophysiology of gout
React with sodium
Sodium crystals (tophi)
Deposited in soft tissues and joints
Infiltration of granulocytes that phagocytise the urate crystals
Generate free radicals
Free radical damage the tissue
Release of proteolytic enzyme glycoprotein
Release of lactic acid
Release of lysosomal enzymes
More ppt of urate crystals
Destruction of joints
• Painful arthritic attack of sudden onset.
• Usually occurring at night or in early morning
• Arthritic pain worsen progressively
• Generally involves one or few joints
• Most common site of initial attack metatarsophalangeal
• Other sites ankle, heel, knee, wrist, elbow and fingers.
• Frequency of attacks increases, continuous deposit leads
to damage joints and chronic pain
• Patients may develop large subacutenous tophi (Stones)
in pinna of external ear, eyelids, nose and around joints
• The ureate crystals in kidney leads renal disease.
• Articular cartilage may be destroyed result in joint
• Alkaloid from colchium autumnale. (1973)
• Neither analgesic nor anti inflammatory, but specific
for gouty inflammation.
• It is only effective in prophylaxis of acute gout
• It has no effect on synthesis or promote excretion
• Colchicine binds to intracellular protein ‘Tubulin’ and
causes depolymerisation and disappearance of
microtubules in granulocytes & Inhibit granulocyte
migration so dec phagocytic activity
• Colchicine inhibit glycoprotein release
– Other actions- arrest of mitosis in metaphas “spindle poison”
- increases gut motility.
- Antipyretic , respiratory depressant
- Inhibit histamine , Insulin release
- hypertensive at high dose , Increase vasomotor tone
- direct vasoconstrictor
Colchicine preferred in pts without confirmed diagnosis of
Acute gout-1mg orally followed by 0.25 mg 3 hrly till control.
With safer alternatives NSAIDs use of Colchicine have declined
ADR:- diarrhoea, vomiting, abdominal pain.
Acute toxicity - bloody diarrhoea, throat pain, respiratory
Chornic toxicity- agranulocytosis, peripheral neuritis and
myopathy, renal tubular necrosis.
• Strong anti inflammatory drugs
• Use in patients without contraindication
• Use maximum dose/potent NSAID
e.g., Indomethacin 50 mg po t.i.d.
Diclofenac 50 mg po t.i.d.
Ketorolac 10 mg q4-6hrsr,
• continue until pain/inflammation absent for 48 hours
• MOA: inhibit urate crystal phagocytosis and chemotatic
migration of leukocytes into inflammed joints.
• NSAIDs are not recommended for long term.
• (Salicylates are not used , have tendency to raise uric acid)
Use when NSAIDS/Cholchicine risky or contraindicated
peptic ulcer disease
use when • NSAIDS ineffective
Mode of administration –
• intra articular - Depomedrol 40-80 mg with lidocaine.
• Oral Prednisone 30-40 mg qd for 3-4 days, taper by 5 mg
every 2-3 days & stop over 1-2 wks
• Allopurinol prevents the synthesis of uric acid
by inhibiting the enzyme Xanthine oxidase,
result reduce plasma ureate levels.
• Inc. xanthine ,hypoxanthines are excreted
• Allopurinol short acting competitive inhibitor
• Metabolite alloxanthine is long acting t1/2 24hr.
• Start low 50-100 mg qd
• Increase by 50-100mg every 2-3 weeks according to
– “Average” dose 300 mg daily
– lower dose if renal/hepatic insufficiency
– higher dose in non-responders
– prophylactic colchicine until allopurinol dose stable
In patients 24 hrs urinary acid excretion exceeds 1.1g
For recurrent renal ureate stones.
Allopurinol drug interactions
• Allopurinol prolong ½ life of Vidarabine, Cyclosporin
drugs and increase toxicity
• Dec. metabolism of 6-mercaptopurine, Azothiaprine
inc. its effects.
• Interferes with the mobilization of hepatic iron stores heamtonic should be avoided during allopurinol
Uricosuric drugs: (probencid)
•Highly lipid soluble benzoic acid.
•It blocks reabsorption of urate in proximal tubule by
blocking transport (Bidirectional transport)
•PK: Dose dependent t1/2 life
•Dose -250- 500mg b.d. with plenty of fluids, alkalinization
chronic gout along with NSAIDs / colchicine for
initial 1-2 months.
• It is a Pyrazolone derivaties related to
• Inhibits tubular reabsorption of uric acid at
• Its action is additive with probenecid.
• Use -chronic gout
• Dose :100-200mg BD gradually increase
according to the response.
• It is newer and more potent uricosuric drug
• Used in patients allergic to probenecid or sulfinpyrazone
• It is reversible inhibitor of tubler reabsorption
• Effective dose 60-80mg/day
• With allopurinol more effective
• A 56yrs old male awake in the night with
sudden severe pain in his first
metatarsophalangeal joint which lasted for a
week. Over the next few months, he had
similar acute episode of pain in his ankles and
knees, as well as his big toe. The GP suspected
gout and referred him to specialist
• What treatment should be GP institute for the
acute attacks prior to the specialist diagnosis?
• what test could the rheumatologist do to
confirm the suspected diagnosis?
• What is the cause of gout?
• Which drugs act for acute attacks?
• What would you prescribe for prophylaxis to
reduce recurrent attacks ?