It includes definition, epidemiology, etiology, pathophysiology, management of Gout and Hyperuricemia

1. Presented by
DR.ZEEL NAIK
1

2. 2

3. 3

4.  Gout is a term that represents a heterogeneous
group of disease usually associated with
Hyperuricemia.
 The Hyperuricemia may be due to an increased
rate of synthesis of purine precursors of uric acid or
to a decreased elimination of uric acid by kidney or
both.
uric acid
4

5.  Gout is caused by elevated levels of uric
acid in the blood which crystallize and are
deposited in joints, tendons, and
surrounding tissues.
5

6. o The term “GOUT” describes a disease spectrum
including Hyperuricemia, recurrent attacks of
acute arthritis associated with monosodium
urate crystals in leukocytes found in synovial
fluid, deposits of monosodium urate
crystals(MSU) in tissue(TOPHI), interstitial renal
disease, and uric acid nephrolithiasis.
o Formation of sharp needle like crystals in areas
with slow blood flow like 1st MTP joint of BIG
TOE.
o GOUT is also known as disease of King.
6

7.  Gout is Crystalline, inflammatory, asymmetrical,
monoarthritis which could be primary or secondary
caused due to overproduction or under excretion of
uric acid that involves small,peripheral joints( 1st
Metatarsophalangeal joint)#MTP-1 due to deposition
of microscopic cyrstals(monosodium urate)#MSU and
more common in male than female(4:1).
 Also known as Crystalline Arthropathy.
 It is the most common inflammatory joint disease in
men and strongly related to age.
 Other commonly affected joints are the ankle, knee,
wrist, elbow and finger joints.
7

8.  Hyperuricemia may be asymptomatic condition,
with an increased serum uric acid concentration
as the only apparent abnormality.
 Normal value
 Male: 3.4-7.0 mg/dl
 Female: 2.4-6.0 mg /dl
 Urine : 250-750 mg/24 hrs
 A urate concentration greater than the normal
value is associated with an increased risk of
GOUT.
8

9.  Although an acute attack is extremely painful, it is usually
self limiting, resolving spontaneously in 1-2 weeks.
 Acute attacks are managed with rest, sometimes with ice
and pharmacological treatment.
 Some patients may only ever experience one attack, but
once a 2nd attack occurs(often within 6-12 months) there is
an increased risk of subsequent attacks.
 Patients with recurrent attacks require long term
prophylaxis with drugs that lower the serum urate level.
 Inappropriate management of gout will lead to chronic
tophaceous gout with polyarticular, joint deformity and
tophi.
9

10.  It is also known as podagra when it involves the
greater toe.
 The metatarsal-phalangeal joint at the base of the
big toe is the most commonly affected
(approximately 80% of cases).
 Wakes up at night and feeling like greater toe on
fire.
10
PODAGRA(Seizing the foot)

11. 11

12. The term gout describes a disease spectrum
including
 Hyperuricemia,
 Recurrent attacks of acute arthritis
associated with monosodium urate
crystals in leukocytes found in synovial
fluid.
12

13.  Deposits of monosodium urate crystals
in tissues (tophi)
 Interstitial renal disease and
 Uric acid nephrolithiasis.
13

14. 14

15.  Population studies have shown that
serum urate concentration (and
consequently the risk of gout) correlates
with
 age, gender
 serum creatinine level,
 blood urea nitrogen level,
 blood pressure,
 Body weight, and
 alcohol intake.
15

16.  The incidence of gout varies from 20 to 35 per
100,000 persons, with an overall prevalence
of 1.6 to 13.6 per thousand.
 Prevalence increases with age, especially in
men.
 Men are affected by gout approximately 10
times more often than women.
 Although no genetic marker has been
isolated for gout.
16

17.  Based on Course
1. Acute Gout(Podagra)
2. Chronic Gout(TOPHI)( Harnson’s Syndrome)
 Based on crystals deposition
1. Gout(Monosodium Urate Crystals)
2. Pseudogout(Calcium Pyrophosphate Dihydrate
crystals)
3. Pseudo PseudoGout[Hyroxyapatite
Arthropathy(HAA)]
 Based On Etiology
1. Primary Gout
2. Secondary Gout
17

18. 1. Male Sex (usually 30-45 years).
2. Genetics
3. Hyperuricemia
4. Renal Disease
5. Osteoarthritis
6. Hypertension
7. Obesity and Diabetes Mellitus.
8. Hyperlipidemia
9. Alchol Consumption(Mainly Beer)
10. Consumption of fatty foods, red meat, organ meat, sea food, soft drinks, fructose containing
drinks.
11. Trauma
12. Surgery
13. Starvation/Dehydration
14. Drugs
a) Diuretics (Loop andThiazide)
b) Aspirin
c) Niacin(Vitamin B3)
d) AntiTB- drugs (Pyrazinamide)
e) Chemotherapy( Cyclosporine, Tacrolimus)
### Gout is not common in premenopausal women because estrogen is uricosuric#protective.
18

19. 19

20.  1. Primary Gout(RARE)
 Inborn error of purine metabolism
e.g i) Lesch- Nyhan Syndrome ( decreased HGPRTase)
ii) Glycogen Storage Diseases
 2. Secondary Gout(Most Common)
 A. Overproduction of Uric Acid(10%)
i. Increase in cell turnover.(Lymphoproliferative and
myeloproliferative disorders)
ii. Chemotherapy
iii. Tumour Lysis Syndrome
iv. Chronic Hemolytic Anemia
v. Psoriasis
vi. G6PD Deficiency
vii. Fructose Ingestion
viii. Red meat, Sea Food, Organ Meat.(High Purine Diet)
ix. Psoriasis
20

21.  B. Under Excretion (90%)
i. Nephropathy( Renal Failure)
ii. Lead Poisoning
iii. Alcholism
iv. Ketacidosis
v. LacticAcidosis
vi. Beer
vii. Red meat, Sea Food, Organ Meat.
viii. Drugs.
ix. Down’s Syndrome
x. Beryllium Poisoning.
xi. Myxoedema.
GOUT ASSOCIATION
1. Urate Nephrolithiasis.
2. Nephropathy
3. Hypertension
4. Lead poisoning causes interstitial nephritis and causes decrease in uric
acid excretion.
21

22. 1. Asymptomatic Hyperuricemia
2. Acute Arthritis
3. Inter-critical Periods
4. ChronicTophaceous Gout
5. Uric Acid Nephropathy “stones”.
## Podagra is limited to 1st MTP of greater toe and
sometimes knee.
##Tophi can be seen in PIP, MTP joints of hands and
feet respectively. Also seen in ear pinna, elbow.
##Tophi are hard, yellowish white chalky nodules
“Rocky” multinucleated giant cells.
22

23. 23

24. 24

25. 25

26. 26

27.  In humans, uric acid is the end product of
the degradation of purines.
 No known physiologic purpose and
therefore is regarded as a waste product.
 In lower animals, the enzyme uricase
breaks down uric acid to the more
soluble allantoin, and thus uric acid does
not accumulate.
 Gout occurs exclusively in humans in
whom a miscible pool of uric acid exists.
27

28.  Under normal conditions, the amount of
accumulated uric acid is about 1200 mg in
men and about 600 mg in women.
 The size of the urate pool is increased several
fold in individuals with gout.
 This excess accumulation may result from
either overproduction or
underexcretion
28

29.  The purines from which uric acid is
produced originate from three sources:
1. Dietary purine,
2. Conversion of tissue nucleic acid to
purine nucleotides, and
3. De novo synthesis of purine bases.
29

30.  The purines derived from these three
sources enter a common metabolic
pathway leading to the production of
either nucleic acid or uric acid
 Several enzyme systems regulate purine
metabolism.
30

31. Uric acid also may be overproduced as a
consequence of
 increased breakdown of tissue nucleic
acids,
 as with myeloproliferative and
 lymphoproliferative disorders.
 Dietary purines play an important role in
the generation of hyperuricemia .
31

32.  Two enzyme abnormalities resulting in an
overproduction of uric acid.
 The first is an increase in the activity of
phosphoribosyl pyrophosphate (PRPP)
synthetase which leads to an increased
concentration of PRPP.
32

33.  PRPP is a key determinant of purine
synthesis and thus uric acid production.
 The second is a deficiency of hypoxanthine
guanine phosphoribosyl transferase
(HGPRT).
 HGPRT is responsible for the conversion of
guanine to guanylic acid and hypoxanthine
to inosinic acid
33

34.  These two conversions require PRPP as
the cosubstrate and are important
reutilization reactions involved in the
synthesis of nucleic acids.
 A deficiency in the HGPRT enzyme leads
to increased metabolism of guanine and
hypoxanthine to uric acid and more
PRPP to interact with glutamine in the
first step of the purine pathway.
34

35. 35

36.  Uric acid does not accumulate as long as
uric acid production is balanced with
elimination.
 Uric acid is eliminated in two ways.
 About two-thirds of the uric acid
produced each day is excreted in the
urine.
 The rest is eliminated through the
gastrointestinal tract after enzymatic
degradation by colonic bacteria.
36

37.  A decline in the urinary excretion of uric
acid to a level below the rate of
production leads to hyperuricemia and
an increased miscible pool of sodium
urate.
 Almost all the urate in plasma is freely
filtered across the glomerulus.
 Approximately 90% of filtered uric acid is
reabsorbed in the proximal tubule.
37

38.  There is a close linkage between proximal
tubular sodium reabsorption and uric acid
reabsorption, so states that enhance
sodium reabsorption (e.g.dehydration) also
lead to increased uric acid reabsorption.
 Factors that decrease uric acid clearance or
increase its production will result in an
increase in serum urate concentration.
38

39.  Diuretics
 Ethanol
 Ethambutol
 Nicotinic acid
 Pyrazinamide
 Cytotoxic drugs
 Salicylates (<2 g/day)
 Levodopa
 Cyclosporine
39

40.  The pathophysiologic approach to the
evaluation of hyperuricemia requires
determining whether the patient is
overproducing or underexcreting uric acid.
 This can be accomplished by placing the
patient on a purine-free diet for 3 to 5 days
and then measuring the amount of uric acid
excreted in the urine in 24 hours.
40

41. 41

42.  Gouty arthritis is due to the crystallization and deposition of poorly
soluble urate.
 Uric acid arises from the metabolism of endogenous purines, either from
excess nucleic acids or increased cell death as in certain disease
states(cancer).
 The purines are metabolised to hypoxanthine which then undergoes
further metabolism by the enzyme xanthine oxidase to xanthine, which
is again oxidized by xanthine oxidase to uric acid.
 The urate may deposit in soft tissues, such as the skin, as urate tophus, or
in joints.
 Crystals of urate in the joint undergo phagocytosis by local synoviocytes.
 This releases prostaglandins, IL-1 and other inflammatory markers
causing inflammatory response.
 Urate is highly filtered through the glomerulus.
 Additionally, it is actively secreted in the tubules.
 If urinary conditions are conductive, the urate may crystallize in the
urine, forming urinary tract calculi.
42

43. 43
X-rays

44. 44

45.  Acute attacks of gouty arthritis are characterized by rapid onset of
excruciating pain, swelling, and inflammation.
 The attack typically is monarticular at first.
 Most often affecting the first metatarsophalangeal joint
(Podagra) and then in order of frequency, insteps, ankles , heels,
knees, wrists, fingers and elbows.
 Attacks commonly begin at night with patient awakening from
sleep with severe pain.
 The affected joints are erythematous, warm, and swollen.
 Fever and leukocytosis are common.
 Untreated attacks may last from 3-14 days before spontaneous
recovery.
 Although acute attacks of gouty arthritis may occur without
apparent provocation, attacks may be precipitated by stress,
trauma, alcohol ingestion, infection, surgery, rapid lowering of
serum uric acid by ingestion of uric acid lowering agents.
45

46.  At night, water is reabsorbed from the joint
space, leaving behind a supersaturated
solution of monosodium urate, which can
precipitate attacks of acute arthritis.
 Attacks generally begin at night with the
patient awakening from sleep in excruciating
pain.
46

47.  The development of crystal-induced inflammation
involves a number of chemical mediators causing
vasodilation, increased vascular permeability, and
chemotactic activity for polymorphonuclear
leukocytes.
 Phagocytosis of urate crystals by the leukocytes
results in rapid lysis of cells and a discharge of
proteolytic enzymes into the cytoplasm.
 The asymptomatic periods between acute gout
attacks are called inter-critical periods.
 There is an elevation in CRP and ESR.
47

48.  Anorexia, nausea or change in mood is common.
 After resolution of the attack, there may be
pruritus and desquamation of the overlying skin
on the affected joint.
 Monosodium urate crystals preferentially form
in cartilage and fibrous tissue, where they are
protected from contact with inflammatory
mediators.
 The deposition of crystals may continue for
months or years without causing symptoms; it is
only when the crystals are shed into joint space
or bursa that results in an acute attack of gout.
48

49.  Chronic gout is an uncommon but relatively severe complication
of long standing, inadequately treated disease.
 This form of gout is characterized by visible deposition of urate
crystals(TOPHI) in connective tissues and joint structures that
result in a destructive arthropathy and secondary osteoarthritis.
 Levels of uric acid from 10-11 mg/dl have been reported to be
associated with moderate tophi.
 It is estimated that 20% of patients with gout will develop uric acid
kidney stones at some point of their illness.
 Uric acid nephropathy results in large –scale deposition of uric acid
crystals in the collecting tubules, resulting in acute kidney
injury(AKI).
 Renal damage usually occurs when there is coexisting diabetes,
hypertension, glomerulonephritis.
49

50. 1. Patient History
2. Physical Examination
3. Laboratory Analysis
a) Joint Aspiration or
Arthrocentesis(Rheumatologist will
perform)
b) Uric Acid Level(Pathologist will perform)
c) Imaging (Radiologist will perform)
50

51.  Male Gender
 Age : 30-45 years
 Meat and sea food in diet.
 Beer
 Medical and medication history.
 Trauma
 Surgery
 Cold drinks
51

52.  Acute Gouty Arthritis
 Warm, red, swollen joint mainly 1st
Metatarsalphalangeal joint (1st MTP)
 Pain to the patient even on small touch to the
affected joint.
52

53. PARAMETERS NORMAL Joint Gout
Viscosity of fluid Normal i.e. thick Decreased
Volume <3.5 ml >3.5 ml
Clarity Transparent or Clear Translucent or opaque
Colour Colorless or straw color Yellow to opalescent
WBCS <200 cells/mm3 2,000-75,000 cells/mm3
PMNS
(PolyMorphoNuclear
Leucocytes)
Neutrophils
Eosinophils
Basophils
<25% >50%
CultureTest Negative Negative

54.  Intracellular needle shaped monosodium
urate crystals are observed under polarized
light microscope.
 Yellow color crystal – Gout
 Blue Color Crystal - Pseudogout
54

55.  Measure the amount of uric acid in the urine in a
24 hour period.
1. Decreased uric acid in urine than normal(less
than 200 mg/24 hours) indicates under
excretion.
2. Increased uric acid in urine than normal ( more
than 800 mg/dl) indicates over production.
 Serum Uric Acid Level
 Elevated ESR, CRP and Leukocytes than
normal.
55

56.  X-ray
 Ultrasound Sonography .
56

57.  The diagnosis is best accomplished by
aspiration of synovial fluid from the
affected joint and identification of
intracellular crystals of monosodium urate
monohydrate in synovial fluid leukocytes.
57

58.  Other crystal-induced arthropathies that
may resemble gout on clinical presentation
are caused by calcium pyrophosphate
dihydrate crystals (pseudogout) and
calcium hydroxyapatite crystals.
 MSU crystals are large (10-20 mm) and
needle shape.
 CPPD crystals are small in size and
rhomboid shape.
58

59. Gout Pseudogout
Ratio of men to women 4:1 1:1.5
Age group affected Men >40 years old
Postmenopausal women
Elderly
Serum urate Elevated Normal
Joints involved First metatarsophalangeal
(MTP) joint,, knees, wrists,
fingers.
Knees, wrists, ankles
Involvement of first MTP
(podagra)
Common Rare
Tophi Present Rare tophi-like deposits
Radiographic findings Erosions with overhanging
edges
Chondrocalcinosis
Crystals Needle-shaped Rhomboid-shaped
59

60.  Nephrolithiasis occurs in 10% to 25% of
patients with gout.
 Factors that predispose individuals to
uric acid nephrolithiasis include
excessive urinary excretion of uric acid,
an acidic urine, and a highly
concentrated urine.
60

61.  The risk of renal calculi approaches 50% in
individuals whose renal excretion of uric
acid exceeds 1100 mg/day.
 In addition to pure uric acid stones,
hyperuricosuric individuals are at
increased risk for mixed uric acid–calcium
oxalate stones and pure calcium oxalate
stones.
61

62.  In addition to pure uric acid stones,
hyperuricosuric individuals are at increased
risk for mixed uric acid–calcium oxalate stones
and pure calcium oxalate stones.
 Uric acid stones are usually small, round, and
radiolucent.
 Therefore when the urine is acidic, uric acid
exists primarily in the un-ionized, less soluble
form.
62

63.  At a urine pH of 5.0, urine is saturated at a
uric acid level of 15 mg/dL.
 When the urine pH is 7.0, the solubility of
uric acid in urine is increased to 200 mg/dL.
 In patients with uric acid nephrolithiasis,
urinary pH typically is less than 6.0 and
frequently less than 5.5.
 When an acidic urine is saturated with uric
acid, spontaneous precipitation of stones
may occur.
63

64.  There are two types of gouty nephropathy: acute
uric acid nephropathy and chronic urate
nephropathy.
 In acute uric acid nephropathy, acute renal failure
occurs as a result of blockage of urine flow
secondary to massive precipitation of uric acid
crystals in the collecting ducts and ureters.
 This syndrome is a well-recognized complication in
patients with myeloproliferative or
lymphoproliferative disorders and is a result of
massive malignant cell turnover, particularly after
initiation of chemotherapy. 64

65. 65

66.  Tophi (urate deposits) are uncommon in the
general population of gouty subjects and are a
late complication of hyperuricemia.
 The most common sites of tophaceous
deposits in patients with recurrent acute gouty
arthritis are the base of the great toe, helix of
the ear, knees, wrists, and hands.
 Eventually, even the hips, shoulders, and spine
may be affected.
66

67. 67

68.  In addition to causing obvious deformities,
tophi may damage surrounding soft tissue,
cause joint destruction and pain, and even
lead to nerve compression syndromes
including carpal tunnel syndrome.
68

69.  A. Presence of characteristic urate crystals
in the joint fluid, or
 B. Presence of a tophus proven to contain
urate crystals by chemical means or
polarized light microscopy, or
 C. Presence of six of the following clinical,
laboratory, and radiographic phenomena:
1.More than one attack of acute arthritis.
2.Development of maximal inflammation
within 1 day.
3.Attack of monarticular arthritis.
69

70. 4. Observation of joint redness.
5. Pain or swelling in first metatarsophalangeal
joint.
6. Unilateral attack involving first
metatarsophalangeal joint.
7. Unilateral attack involving tarsal joint.
8. Suspected tophus.
9. Hyperuricemia.
10. Asymmetric swelling within a joint on x-ray.
11. Subcortical cysts without erosions on x-ray.
12. Negative culture of joint fluid for
microorganisms during attack of joint
inflammation.
70

71. 71

72.  The goals in the treatment of gout are to terminate
the acute attack.
 Prevent recurrent attacks of gouty arthritis,
and prevent complications associated with chronic
deposition of urate crystals in tissues.
 Patients should be advised to reduce their dietary
intake of saturated fats and meats high in purine
(e.g., organ meats, red meat).
 Lower serum uric acid levels to below saturation
point.
 Reduce risk of co morbidities.
 Lifestyle modification.
72

73. 73

74. 74

75. 75

76.  Acute attacks of gouty arthritis may be
treated successfully with
 Colchicines or any of a variety of nonsteroidal
anti-inflammatory drugs (NSAIDs).
76

77. 77
TREATMENTALGORITHM FOR
ACUTE GOUTY ARTHRITIS

78. 78

79. 79

80.  Colchicine is an alkaloid isolated from the autumn
crocus, Colchicum autumnale.
 It is anti-mitotic.
 It prevents cell division.
 Colchicine can be given orally or parenterally.
 Unless contraindications exist or the patient has
renal insufficiency, the usual oral dose is 1 mg
initially, followed by 0.5 mg every 2 hours until the
joint symptoms subside, until the patient develops
abdominal discomfort or diarrhea, or until a total
dose of 8 mg has been administered.
80

81.  About 75% to 95% of patients with acute
gouty arthritis respond favorably to
colchicines when ingestion of the drug is
begun within 24 to 48 hours of the onset of
joint symptoms.
 If the initiation of colchicine is delayed longer
than 48 hours after the onset of acute
symptoms, the probability of success with
the drug diminishes substantially.
81

82.  The major problem associated with the use of
oral colchicines is that it causes gastrointestinal
side effects in 50% to 80% of patients before the
relief of the attack.
 Side effects of colchicine most commonly
encountered are diarrhea, nausea , vomiting and
abdominal cramping.
 Burning pain in throat, bloody diarrhea, shock,
hematuria, oligouria and CNS depression can
occur due to acute toxicity.
 It has no effect on plasma or urine uric acid level.
 It has no analgesic effect.
82

83.  This high incidence of gastrointestinal side
effects may be circumvented by
administering colchicine intravenously.
 Except in patients with renal insufficiency,
the initial intravenous dose of colchicine is 2
mg.
 If relief is not obtained, an additional 1-mg
dose may be given at 6 and 12 hours to a total
dose of 4 mg for a specific attack.
83

84.  Indomethacin is as effective as colchicine in the
treatment of acute gouty arthritis.
 Because acute gastrointestinal toxicity occurs far
less frequently with indomethacin than with
colchicine, it is preferred.
 Side effects unique to indomethacin include
headache and dizziness.
 All NSAIDs have been implicated in the cause of
gastric ulceration and bleeding, but with short-
term therapy, this is not likely.
84

85.  For treatment of acute gouty arthritis,
indomethacin may be begun with a relatively
large dose for the first 24 to 48 hours and
then tapered over 3 to 4 days to minimize the
risk of recurrent attacks.
 For example, 75 mg of indomethacin should
be given initially, followed by 50 mg every 6
hours for 2 days and then 50 mg every 8
hours for 1 or 2 days.
85

86.  A number of other NSAIDs (e.g., naproxen,
fenoprofen, ibuprofen, and piroxicam) are
also effective in relieving the inflammation of
acute gout.
 There is no evidence that any given NSAID is
superior to all the others in the management
of acute gout.
86

87.  All NSAIDs should be used with caution in
individuals with a history of acid peptic
disease, heart failure, chronic renal failure, or
coronary artery disease.
 Selective cyclooxygenase-2 inhibitors, such
as celecoxib and valdecoxib,can be used as an
alternative for patients who cannot tolerate
nonselective cyclooxygenase inhibitors .
87

88. Corticosteroids may be used to treat acute attacks
of gouty arthritis,but they are reserved primarily for
resistant cases or for patients with a contraindication
to colchicine and NSAID therapy.
 Doses of 40 to 80 USP units of adrenocorticotropic
hormone gel are given intramuscularly every 6 to 8
hours for 2 to 3 days, and then the doses are reduced
in stepwise fashion and discontinued.
 Intraarticular administration of triamcinolone
hexacetonide in a dose of 20 to 40 mg may be useful
in treating acute gout limited to one or two joints.
88

89.  Prednisone may be administered orally in
doses of 30 to 60 mg for 3 to 5 days in
patients with multiple-join involvement.
 Because rebound attacks may occur on
steroid withdrawal, the dose should be
tapered gradually by 5-mg decreases over 10
to 14 days and discontinued.
89

90.  The medical management of uric acid
nephrolithiasis includes hydration sufficient
to maintain a urine volume of 2 to 3L/day,
 Alkalinization of urine,
 Avoidance of purine rich foods,
 Moderation of protein intake.
 Alkalinizing agents should be used with the
objective of making the urine less acidic.
 Urine pH should be maintained at 6 to 6.5.
 In this pH range, up to 85% of uric acid will be
in the form of the soluble urate ion.
90

91.  1. Hypouremic Agent(XanthineOxidase
Inhibitors)
a) Allopurinol
b) Febuxostat
 2. Uricosuric Agents
a) Probenecid
b) Sulfinpyrazone
 3. Uricases/ Uricolytics
a) Pegloticase
b) Rasburicase
91

92.  It is currently the most commonly used agent for the long term control of
chronic gout.
 It is the choice of drug in overproduction of uric acid.
 It works by inhibiting xanthine oxidase, the enzyme that catalyse the
conversion of xanthine to uric acid and hypoxanthine to xanthine.
 This mechanism reduces the formation of urate.
 Allopurinol will reduce both plasma and urinary concentration of urate.
 It is not effective in acute attack
 Side effects include GI upset(N,V,D) which are most common and bone
marrow depression, aplastic anemia, neuritis,vasculitis, nephrotoxicity,
hepatotoxicity and cataracts(due to deposition of allopurinol on the
lens), STEVEN JOHNSON SYNDROME.
 It is indicated for patient with chronic gout and hyperuricemia and urate
nephrolithiasis.
 Uric acid level starts to decline within 1-2 days after starting allopurinol
therapy and highest effect is seen within 7-14 days.
 DOSE: 100-300 mg orally per day.
 For moderate to severe tophaceous gout, 400-600 mg/day in divided
doses may be needed.
92

93.  In patient with renal impairment(GFR less
than 30 ml/min) this should be reduced to 50
mg once a day.
 The dissolution of tophi may take up to 1 year
with effective therapy.
 Azothioprine and mercaptopurine are
metabolised by xanthine oxidase;
coadministration of allopurinol reduces the
metabolism of these 2 drugs and increases
their toxicity.
93

94.  It is a more selective and potent inhibitor of xanthine oxidase than
allopurinol, and it has no effect of other enzymes involved in
purine metabolism.
 It is used in chronic gout and chronic hyperuricemia.
 It is the 2nd line therapy in patient who are intolerant of allopurinol
or for whom allopurinol is contraindicated.
 It is more effective than allopurinol in lowering uric acid
concentrations.
 The recommended dose for febuoxostat is 80 mg once daily.
 It can be increased to 120 mg/day.
 It is contraindicated in patient with IHD or CHF because of CVS
side effects.
 ADRs: Respiratory Infection, diarrhea, head ache and liver
function abnormalities, Steven Johnson syndrome , epidermal
necrolysis.
 Contraindicated with antimetabolite therapy of cancer.
94

95.  Uricosuric drugs increase the renal
clearance of uric acid by inhibiting the renal
tubular reabsorption of uric acid.
 Therapy with uricosuric drugs should be
started at a low dose to avoid marked
uricosuria and possible stone formation.
 The maintenance of adequate urine flow
and alkalinization of the urine with sodium
bicarbonate or Shohl’s solution during the
first several days of uricosuric therapy
further diminish the possibility of uric acid
stone formation.
95

96.  It is less effective than the other agents and it is
generally reserved for those who cannot tolerate
or fail to achieve target serum urate level with
XOIs.
 The combination of allopurinol and probenecid
can provide additional urate lowering than
either agent alone.
 DOSE: 0.5-2.0 g/day.
 Not recommended in creatinine clearance less
than 50 ml/min.
 Dyspepsia and reflux may occur.
 It is banned in UK.
96

97.  It is a potent uricosuric agent that acts via the
renal transporters.
 It is highly hepatotoxic.
 Banned in UK.
 Dose : 50-200 mg/day.
 Contraindicated in kidney disease.
 Diarrhea is common side effect of this drug.
97

98.  It is effective in reducing the frequency of
gout attack, tophi and plasma urate levels at
a dosage of 200-800 mg/day.
 ADRs: GI ulceration, ARF, fluid retention,
elevated liver enzymes and blood disorders.
98

99.  Probenecid is given initially at a dose of 250 mg
twice a day for 1 to 2 weeks and then 500 mg
twice a day for 2 weeks.
 Thereafter the daily dose is increased by 500-mg
increments every 1 to 2 weeks until satisfactory
control is achieved or a maximum dose of 2 g is
reached.
 The initial dose of sulfinpyrazone is 50 mg twice
a day for 3 to 4 days and then 100 mg twice a
day, increasing the daily dose by 100-mg
increments each week up to 800 mg/day.
99

100.  The major side effects associated with uricosuric
therapy are gastrointestinal irritation, rash and
hypersensitivity, precipitation of acute gouty
arthritis, and stone formation.
 These drugs are contraindicated in patients who
are allergic to them and in patients with
impaired renal function (a creatinine
clearance<50 mL/min), a history of renal calculi,
and in patients who are overproducers of uric
acid; for such patients, allopurinol should be
used.
100

101.  Febuxostat ,allopurinol and its major
metabolite, oxypurinol,are xanthine
oxidase inhibitors and thus impair the
conversion of hypoxanthine to xanthine
and xanthine to uric acid.
101

102.  Allopurinol also lowers the intracellular
concentration of PRPP.
 Because of the long half-life of its metabolite,
allopurinol can be given once daily.
 An oral daily dose of 300 mg usually is
sufficient. Occasionally, as much as 600 to 800
mg/day may be necessary.
102

103.  The major side effects of allopurinol are skin
rash, leukopenia, occasional gastrointestinal
toxicity, and increased frequency of acute gouty
attacks with the initiation of therapy.
 An allopurinol hypersensitivity syndrome
characterized by fever, eosinophilia, dermatitis,
vasculitis,and renal and hepatic dysfunction is a
rare side effect, but is associated with a 20%
mortality rate.
103

104.  Febuxostat and allopurinol have similar
action.
 But the maximum dose of febuxostat is
more effective in reducing uric acid levels
than allopurinol (committee of the
British National Institute for Health and
Clinical Excellence) .The FDA approved
febuxostat in February 2009.
104

105.  DOSING:The recommended dose is 40 or 80
mg daily. It may be administered with or
without food, and it can be taken with
antacids. Flares of gout may increase after
febuxostat is started as uric acid moves out of
tissues.These gout flares may be prevented
with non-steroidal anti-inflammatory drugs
(for example, indomethacin ) or colchicine.
105

106.  Side effects-Nausea, joint pain , rash , chest
pain, shortness of breath,slow or difficult
speech, dizziness, weakness or numbness of
an arm or leg.
 Drug INT-Febuxostat may increase blood
levels of mercaptopurine, azathioprine, and
theophylline.
106

107.  These are the antihyperuricemic drug of choice
in patients with a history of urinary stones or
impaired renal function, in patients who have
lymphoproliferative or myeloproliferative
disorders and need pretreatment with a
xanthine oxidase inhibitor before initiation of
cytotoxic therapy to protect against acute uric
acid nephropathy,and in patients with gout who
are overproducers of uric acid.
107

108. Recurrences of acute gouty arthritis may be
prevented with continuous low-dose daily oral
colchicine or by uric acid–lowering therapy with
either uricosuric agents or inhibition of xanthine
oxidase with allopurinol.
 Combination therapy consisting of colchicine
plus a uricosuric agent or allopurinol may be
employed in resistant cases.
 The choice of treatment depends on the serum
urate concentration, the amount of uric acid
excreted in a 24-hour period, and the renal
function status of the patient.
108

109.  Prophylactic therapy with low-dose oral
colchicine, 0.5 to 0.6 mg twice daily, may be
effective in preventing recurrent arthritis in
patients with no evidence of visible tophi and
a normal or slightly elevated serum urate
concentration.
 Patients do not become resistant to or
tolerant of daily colchicine, and if they sense
the beginning of an acute attack, they should
increase the dose to 1 mg every 2 hours; in
most instances the attack will abort after 1 or
2 mg of colchicine.
109

110.  If the serum urate concentration is within the
normal range and the patient has been
symptom-free for 1 year, maintenance
colchicine may be discontinued.
 The patient should be advised, however, that
discontinuation of the treatment program may
be followed by an exacerbation of acute gouty
arthritis.
 Patients with a history of recurrent acute gouty
arthritis and a significantly elevated serum uric
acid concentration probably are best managed
with uric acid–lowering therapy.
110

111.  Colchicine at a dose of 0.5 mg twice daily
should be administered during the first 6 to
12 months of antihyperuricemic therapy to
minimize the risk of acute attacks that may
occur during initiation of uric acid–lowering
therapy.
 The therapeutic objective of
antihyperuricemic therapy is to reduce the
serum urate concentration below 6 mg/dL,
well below the saturation point.
111

112.  In human and the great apes, uric acid is the
end product of purine degradation, but in
other mammals , uric acid is further degraded
by the enzyme uricase to allantoin, which is
highly soluble.
 It is very costly and use is limited to severe
case of gout.
112

113.  It is recombinant form of the enzyme urate
oxidase or uricase.
 Dose: IV 0.2 mg/kg in short course for 5-7
days.
 ADR: Fever, Nausea, vomiting, rash, diarrhea,
headache, allergic reaction.
113

114. 114

115. 115