- Gout is caused by elevated uric acid levels in the blood (hyperuricemia) which can lead to the deposition of urate crystals in the joints, causing inflammation and pain. - There are different treatments for the acute attacks and long-term management. For acute attacks, NSAIDs or corticosteroids can be used to reduce pain and inflammation. Colchicine may also be used. - For long-term management and prevention of recurrent attacks, allopurinol is commonly prescribed to lower uric acid levels by inhibiting its production. Probenecid or other uricosuric

1. What is Arthritis?
 There are 127 different kinds of
arthritis!
 Rheumatoid arthritis: Severe
inflammation that involves many
joints and moves beyond
musculoskeletal system.
 Gout: Very painful form of arthritis
characterized by the formation of uric
acid crystals and severe inflammation.
 Osteoarthritis: progressive
degeneration of joint cartilage. Minor
degree of inflammation.
1

2. GOUT

3. • Gout is a metabolic disorder of purine
metabolism, characterized by intermittent
attacks
of
acute
pain,
swelling
and
inflammation.
• It always preceded by hyperuricaemia (6.0mg/dl)
Hyperuricaemia due to excessive amount of uric
acid production or decreased excretion

4. • Hyperuricaemia - primary or secondary.
• Primary hyperuricaemia classified as
“Overproducers” or “under execrators”

5. • Primary Hyperuricemia and
Gout with No Associated
Condition
Secondary Hyperuricemia and Gout with
Identifiable Associated Condition
• Uric acid undersecretion(80%–
90%)
• develop during course of other diseases
(Leukaemias, lymphomas, chemotherapy)
• Idiopathic
• Some drug therapy (Thiazide diuretics,
furosamide, ethacrynic acid)
• Urate overproduction (10%–
20%)
• HGPRT deficiency
•
•
PRPP synthetase overactivity
(Phasphoribosyl pyrophosphate)
• Some disorders Diabeticketoacidosis, lead
poison, Lymphoproliferative
diseases, Hemolytic anemias, psoriasis
• Dual mechanism
Obesity, Hypoxemia and hypoperfusion

6. Uric acid production and excretion
RNA,DNA
PURINES
PRPP
HYPOXANTHINES
Xanthine oxidase
XANTHINES
Xanthine oxidase
URIC ACID (low water soluble)
Hyperuricemia
Gout
Deposits of urate crystal
Nephrolithiasis
Uric acid freely filtrated through by glomerulus and
reabsorbed by tubular fluid
Probencid

7. Pathophysiology of gout
Uricacid
Blood
React with sodium
Sodium crystals (tophi)
Deposited in soft tissues and joints
Inflammation(ry)
Indomethacin
Colchicine
Infiltration of granulocytes that phagocytise the urate crystals
Generate free radicals
Free radical damage the tissue
Colchicine
Release of proteolytic enzyme glycoprotein
Release of lactic acid
Release of lysosomal enzymes
More ppt of urate crystals
Destruction of joints
Colchicine

8. Acute gout
• 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
joint.
• Other sites ankle, heel, knee, wrist, elbow and fingers.

9. Chronic gout
• 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
deformities

10. GOUT - TREATMENT
GOALS:
1. terminate acute attack
2. provide rapid, safe pain/anti-inflammatory relief
3. prevent complications
• destructive arthropathy
• tophi
• renal stones

11. Classification of drugs used in gout
ACUTE GOUT :
1. NSAIDS
2. Corticosteroids
3. Colchicine
CHRONIC GOUT:
•
•
Inhibit uric acid synthesis:- Allopurinol, febuxostate
(Urostatic)
Increase uric acid excretion:- Probencid, Sulphinpyrazole
(Urosuric)

12. Colchicine
• 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
• MOA
• Colchicine binds to intracellular protein ‘Tubulin’ and
causes depolymerisation and disappearance of
microtubules in granulocytes & Inhibit granulocyte
migration so dec phagocytic activity

13. • 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

14. Uses
 Colchicine preferred in pts without confirmed diagnosis of
gout.
 Acute gout-1mg orally followed by 0.25 mg 3 hrly till control.
 (EHC) 3-7days
 With safer alternatives NSAIDs use of Colchicine have declined
ADR:- diarrhoea, vomiting, abdominal pain.
 Acute toxicity - bloody diarrhoea, throat pain, respiratory
depression, haematuria.
 Chornic toxicity- agranulocytosis, peripheral neuritis and
myopathy, renal tubular necrosis.

15. NSAIDs
• 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,
Napoxen, Piroxicam
• 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)

16. Corticosteroid
Use when NSAIDS/Cholchicine risky or contraindicated
e.g.,: elderly
hypertensive
peptic ulcer disease
renal impairment
liver impairment
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

17. Drugs for chronic gout
• Uric acid synthesis inhibitors:- Allopurinol
(Xanthine oxidase inhibitor)
• Hypoxanthine
Xanthine
Uric acid
Xanthine oxidase
-
Allopurinol

18. • Allopurinol prevents the synthesis of uric acid
by inhibiting the enzyme Xanthine oxidase,
result reduce plasma ureate levels.
• Inc. xanthine ,hypoxanthines are excreted
through urine
• Allopurinol short acting competitive inhibitor
• Metabolite alloxanthine is long acting t1/2 24hr.

19. • Start low 50-100 mg qd
• Increase by 50-100mg every 2-3 weeks according to
symptoms
– “Average” dose 300 mg daily
– lower dose if renal/hepatic insufficiency
– higher dose in non-responders
– prophylactic colchicine until allopurinol dose stable
•
•
•
•
Indications:
Chronic gout
In patients 24 hrs urinary acid excretion exceeds 1.1g
For recurrent renal ureate stones.

20. Allopurinol side effects
• GI upset, alopecia, cataract.
• Allopurinol Hypersensitivity:
Pruritic papular skin rash, fever, hepatitis,
eosinophilia, renal impairment
• CI:–
–
–
–
–
Chidrens
Elderly patients
Pregnancy
Lacation
Liver and kidney diseases.

21. 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
therapy.

22. 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
of urine.
Uses :
chronic gout along with NSAIDs / colchicine for
initial 1-2 months.

23. Sulfinpyrazone
• It is a Pyrazolone derivaties related to
Phenylbutazone.
• Inhibits tubular reabsorption of uric acid at
therapeutic doses.
• Its action is additive with probenecid.
• Use -chronic gout
• Dose :100-200mg BD gradually increase
according to the response.

24. Benzbromarone
• 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

25. • 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?

26. • 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 ?