Gout

1. 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.

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

4. Hyper uricaemia 6.8mg/dl
• Excessive amount of uric acid production
• Decreased excretion
• Or both

5. • Primary Hyperuricemia and
Gout
• Uricacid under excretion 80–90%
• Urate over production (10–20%)
• Purine intake shell fish , Red
meat
• Idiopathic
• PRPP synthetase over activity
Secondary Hyperuricemia and Gout
Identifiable Associated Condition
• develop during course of other diseases
(lymphomas, chemotherapy, CKD) cell death
• Some drug therapy (Thiazide diuretics,
furosamide, ethacrynic acid, Aspirin)
• Some disorders Diabetic ketoacidosis, lead
poison, Lymphoproliferative
diseases, Hemolytic anemias, psoriasis
• Dual mechanism
Obesity and hypo perfusion to joint

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

8. Pathophysiology of gout
Uricacid
Blood
React with sodium
Sodium crystals (tophi)
Deposited in soft tissues and joints
Inflammation(ry)
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
More ppt of urate crystals
Indomethacin
Colchicine
Colchicine
ColchicineRelease of lysosomal enzymes
Destruction of joints

9. Symptoms
• Acute joint pain
• Swelling in the joints
• Skin may be in red colour and shiny appearance
• Formation of tyophi

10. Cause and risk factors
• Hereditary factors 40-50 age
• Consumption of alcohol spe..Beer
• Excessive consumption of red meat, internal organs
• Trauma to joints

11. Diagnosis
• Joint fluid aspiration
• Blood test (Serum uric acid levels)
• X-rays

12. 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.

13. 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

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

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

16. 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

17. • Colchicine inhibit glycoprotein release
– Other actions-
- arrest of mitosis in metaphase “spindle poison”
- increases gut motility.
- Antipyretic , respiratory depressant
- Inhibit histamine , Insulin release
- hypertensive at high dose, Increase vasomotor tone

18. 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.

19. 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)

20. 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

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

22. • 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.

23. • 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.

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

25. 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.

26. 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.

27. 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.

28. • It is newer and more potent uricosuric drug
• Used in patients allergic to probenecid or sulfinpyrazone
• It is reversible inhibitor of tubuler reabsorption
• Effective dose 60-80mg/day
• With allopurinol more effective
Benzbromarone

29. • 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?

30. • 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 ?

31. 360umol/L or 6mg/dl