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2. Gout andGout and
HyperuricaemiaHyperuricaemia

3. Prepared by :
Farjana Rahman
B.Pharm, Southeast University
M.Pharm, East West University, Bangladesh

4. IntroductionIntroduction
Gout is characterized biochemically as a disorder of uric
acid metabolism and clinically by hyperuricaemia and
recurrent attacks of acute arthritis. Gouty arthritis is most
frequently seen as an acute inflammation primarily in the
large toe, instep, ankle, or heel,less often in the knee or
elbow.

5. Most hyperuricemic persons are asymptomatic between
acute attacks.Uric acid stones may form in the lumen of the
urinary tract, and progressive renal failure often occurs in the
later stages of untreated Gout.
► Urate: end product of purine metabolism
► Gout: deposition of monosodium urate crystals in tissues
► Hyperuricemia: serum urate > urate solubility (> 6.8
mg/dl)

6. Pathways of uric acid

8. But in…
► leukemia
►myeloid metaplasia
► lymphoma
► Polycythemia
► And in rapid weight loss (dieting)
Breakdown of cellular nucleoprotein is increased
Excess formation of uric acid

9.  MaleMale
 PostmenopausalPostmenopausal
femalefemale
 Old aged peopleOld aged people
 HypertensionHypertension
 Pharmaceuticals:Pharmaceuticals:
Diuretics, ASA,Diuretics, ASA,
cyclosporinecyclosporine
 TransplantTransplant
 Alcohol intakeAlcohol intake
Highest with beerHighest with beer
Not increased withNot increased with
winewine
 High BMI (obesity)High BMI (obesity)
 Diet high in meat &Diet high in meat &
seafoodseafood

10. Complications
• Arthritis
• Tophi
• Urinary Calculi
• Gouty Nephropathy
It is essential to identify the condition early to
avoid the complications that result from a
prolonged elevated uricaemia.

11. Clinical Manifestations
• Asymptomatic hyperuricemia
• Acute gouty arthritis
• Chronic gout
• Chronic tophaeceous gout
• Advanced Gout & Complications

12. Acute Gouty Flares
• Abrupt onset of severe joint inflammation,
often nocturnal; Warmth, swelling, erythema,
&
• pain;Possibly fever
• Untreated? Resolves in 3-10 days
• 90% 1st
attacks are monoarticular
• 50% are podagra

13.  90% of gout patients eventually
have podagra :1st MTP joint
Sites of Acute Gouty Flares
Fig: Acute Attack of Gout
(MTP) joint

14. Can occur in other joints, bursa & tendons

15. Flares Intervals
• Silent tissue deposition & Hidden Damage may
also occur in gouty attack

16. Advanced Gout
• Chronic Arthritis
• Polyarticular acute flares with upper
extremities more involved

17.  Solid urate deposits in
tissues
 Irregular & destructive

18. Investigation,Diagnosis & Treatment

19. Investigation
• The diagnosis of acute gout can
only be made through
examination of synovial fluid
aspirated from the inflamed
joint
• Sudden onset of acute
inflammatory monoarthritis,
particularly in the foot or ankle,
should always raise the
suspicion of gout

20. Investigation [cont..]
• In 10% of patients acute gouty arthritis is
polyarticular
• Hyperuricaemia alone is not diagnostic of gout
as many hyper-patients with acute gout have a
normal serum uric acid concentration
• The diagnosis of gout is thus confirmed only by
microscopic examination of synovial fluid
aspirated from the affected joint

21. Diagnosis
• The differential diagnosis
in acute gouty arthritis
must include septic
arthritis
• Patients with commonly
present with acute
swelling and tenderness
of the joint with a fever

22. Diagnosis [Cont..]
• Patients with joint sepsis are usually more ill
and have other systemic signs of infection
such as a swinging fever and severe malaise
• Large joint are most frequently infected, and
the joint is hot

23. Diagnosing [Cont..]
X-raysX-rays
Synovial fluid analysis (Polarized Light Microscopy)Synovial fluid analysis (Polarized Light Microscopy)
The Gold standard
Crystals intracellular during attacks
Needle & rod shapes
Strong negative birefringence

24. X-raysX-rays Synovial fluidSynovial fluid
analysisanalysis

25. Treatment
• Initial treatment of gout and its
associated hyperuricemia must
involve therapy directed
toward terminating painful
inflammatory process that is a
prominent feature of acute
gouty arthritis.
• A variety of nonsteroidal
antiinflammatory compounds
(e.g.,indomethacin,
oxyphenbutazone, ibuprofen,
naproxen, sulindac) can be
administered either alone or in
combination with colchicine, a
relatively specific agent for use
acute gouty attacks.

27. Clinically used drugs ( for gout and
hyperuracemia)
Pain reliver
•Colchicine
• NSAIDs (indomethacin, ibuprofen & naproxen )
•Azapropazone
•Corticosteroids
•Narcotic Pain Relievers
Improves uric acid removal
•Probenecid
•Sulfinpyrazone
Block uric acid production
•Allopurinol
•Phenylbutazone
•Oxyphenbutazone
New drugs
•Febuxostat
•Rasburicase
•pegloticase

28. Adverse Effects
Colchicine
-gastrointestinal diarrhea, nausea, vomiting, hemorrhagic
colitis, occurs in 70-80% of patients on oral therapy, less
frequent with IV therapy but may see with high doses
-bone marrow depression: cumulative toxicity
-renal dysfunction: toxic side effect seen after large doses,
Hematuria , oliguria .
-necrosis of soft tissue after extravasation : do not give IM/SQ
Corticosteroids
-may include thinning bones, poor wound healing and a
decreased ability to fight infection.

29. Adverse Effects (continue……)
NSAIDs( Indomethacin, Ibuprofen and
Naproxen)
-nausea, vomiting , diarrhea constipation ,
decreased appetite, rash, dizziness ,
headache, and drowsiness.
-NSAIDs may also cause fluid retention, leading
to edema.
-The most serious side effects are kidney failure,
liver failure, ulcers and prolonged bleeding
after an injury or surgery.

30. Adverse Effects (continue….)
Probenecid
-hypersensitivity: rashes +/- fever, anaphylaxis
-gastrointestinal: take with food or milk
- stomach pain and kidney stones.
Sulfinpyrazone
-hypersensitivity reactions (uncommon) rash, may cause
bronchoconstriction in patients with ASA intolerance,
contraindicated in patients allergic to phenylbutazone /
pyrazoles
-gastrointestinal irritation: take with food or milk

31. Adverse Effects (continue……)
Allopurinol
-hypersensitivity rash
-usually occurs within 1st
5 weeks with ampicillin
treatment
-severe hypersensitivity more common in pts
with impaired renal function
-gastrointestinal: nausea, vomiting, abdominal
pain
-hepatomegaly/nephritis: may be manifestation
of a hypersensitivity reaction

32. Drug interaction
Colchicine
penicillin, or other beta-lactams,
clarithromycin, erythromycin, cyclosporine,
verapamil
NSAIDs
Lithim, methotrexate and warfarin
Probenecid
sulfonamides and sulfonylureas , methotrexate
rifampin , penicillin antibiotics , salicylates (large doses
(>2 gms) inhibit the uricosuric effect of probenecid )

33. Drug interaction (continue……)
Sulfinpyrazone
-salicylates
-warfarin
Allopurinol
-asthma drugs (aminophylline, theophylline)
azathioprine,
-"blood thinners" (e.g., warfarin), chlorpropamide,
cyclosporine, mercaptopurine,
-"water pills" (e.g., thiazide diuretics such as
hydrochlorothiazide).
-ampicillin
-ACE inhibitors

34. Drug interaction (continue……)
Corticosteroids
-Anticoagulants
-Anticonvulsants
-Anti-diabetic
-Antifungals
-Bronchodilators
-Digoxin
- HIV protease inhibitors
-Liver vaccines
- Macrolides
- Methotrexate
- Nonsteroidal anti-inflammatory drugs
-Rifampicin
-Diuretics
-Ephedrine

35. Case Study-1
A 45 years old asymptomatic aircrew reported for periodic
medical examination. Except for being overweight (BMI:
27kg/m2), the general and systemic examination was within
normal limits. The routine laboratory investigations revealed
a serum uric acid of 8.8 mg/dl. The individual denied
consumption of alcohol/ medication and had no symptoms
referable to joints. The various issues involved in the
aeromedical decision making in this aircrew are as follows -
a) Does he require medication for his condition?
b)What are the underlying pathology and the prognosis?
c) What life style and preventive therapy will you suggest
to this aircrew?

36. a) Does he require medication for
his condition
• The serum uric acid level in the body is a function of
balance between the breakdown of purine and the
rate of urate excretion.
• The normal serum uric acid as measured by
automated enzymatic (uricase) method is less than
7.0 mg/dl for adult male and any value more than 7.0
mg/dl is considered to represent hyperuricemia.
• As the air crew has a creatinine level more than the
normal level (8.8 mg/dl), Yess, he needs some
pharmacological treatment.

37. b) What are the underlying pathology
and the prognosis?
• The laboratory investigations can be divided in to the
following heads:
1. Test directed towards establishing the diagnosis
(a) Serum uric acid
(b) Joint aspiration and demonstration of strongly
birefringent needle shaped intra and extracellular crystals in
cases of gout.
2. Test directed towards the pathophysiology
- 24 hours urinary uric acid estimation: Excretion of >800
mg of uric acid per 24hr on a regular diet suggests
overproduction of purine as the etiology. It is also useful in
assessing the risk of stone formation. and in deciding whether
to start uricosuric therapy or not.

38. b) What are the underlying pathology and
the prognosis?
3. Tests directed towards establishing the etiology
(a) Complete blood counts: for hemolytic anemia or hematological
malignancies
(b) Liver function test: base line liver function is required before initiation
of allopurinol therapy. It also aids in the detection of metabolic disorders.
(c) Blood sugars: for underlying diabetes mellitus and glycogen storage
disorders.
(d) Renal function test and serum electrolytes: for underlying renal
disease and acidosis
(e) Serum calcium and phosphate: for hyperparathyroidism, sarcoidosis
and myeloma.
(f) Thyroid stimulating hormone: to rule out hypothyroidism.
4. Radiological evaluation
Radiological feature of advanced chronic gouty arthritis includes soft tissue
masses, cystic changes and well-defined erosions with sclerotic margins
and overhanging bony edges.

39. c) What life style and preventive therapy will
you suggest to this aircrew?
Life StyleLife Style

40. c) What life style and preventive therapy will
you suggest to this aircrew? (Cont.)
a) High protein diet is associated with increase
urinary uric acid excretion and may reduce the
serum uric acid level. The amount of red meat
and seafood however has to be reduced. Diet
should include, consumption of more of low
fat dairy product and complex carbohydrate
which helps in reducing the serum uric acid
levels.
Preventive therapyPreventive therapy

41. b) Purine rich vegetables (peas, lentils, spinach, mushroom,
cauliflower) may not affect serum uric acid to desirable
extent and hence purine restricted diet is rarely necessary.
Vitamin C in dosages of 500mg/ day has mild urate lowering
effect.
(c) High-fructose corn syrup containing foods and drinks increase
blood urate levels and are hence not recommended to be
consumed. Coffee may decrease the risk of gout attacks .
(d) Alcohol increases the urate levels by increasing the
production of uric acid as well as by impairing its excretion.
Beer with its high purine content causes more elevation of
serum urate levels than wine.
Preventive therapy (Cont.)Preventive therapy (Cont.)

42. Case Study- 2
• A 52-year-old male presented with severe pain in his wrists
and right big toe, which was accompanied by inflammation
and erythema of the joints. The patient had previously been
diagnosed with acute gouty arthritis approximately 7 years
ago, but had not experienced another acute attack since his
original diagnosis. He had been taking simvastatin 40 mg
nightly for hyperlipidemia for 7 years, 20 mg lisinopril daily for
hypertension for 10 years, and hydrochlorothiazide 25 mg,
also for hypertension, which was recently added two months
ago. The patient had been steadily gaining weight over the
last few years and was now about 50 lbs overweight. He
stated that he drinks about a six pack of beer every day.

43. Nonpharmacological Treatment
• Gout is influenced by numerous factors, including overeating,
obesity, alcohol abuse, hyperlipidemia, and insulin resistance
syndrome.
• A low purine and protein diet along with alcohol restriction,
weight loss through caloric restriction, and management of
associated disease, may be extremely beneficial.
• Also, since patients with gout are at an increased risk for
developing nephrolithiasis, health care providers should
emphasize the importance of increasing fluid intake and
decreasing salt consumption.
• In addition, joint rest and local application of ice may be
beneficial.

44. Pharmacological Treatment
• Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the
primary therapy for acute gouty arthritis for patients without
complications or contraindications.
• Although ketoprofen and ibuprofen are often used, the FDA
currently has approved only three NSAIDs for treatment of
acute gouty arthritis: indomethacin, naproxen, and sulindac.
• The most important determinant of therapeutic success is
probably not which NSAID is selected, but rather how soon
NSAID therapy is initiated.

45. • In patients with contraindications to NSAIDs, Colchicine is a
highly effective alternative treatment. Colchicine, which has
been used for gout for a rather long time, interferes with the
migration of neutrophils to the inflammation site, inhibiting
the underlying inflammatory cascade.
• Corticosteroids can also be used for acute gouty arthritis but
generally are reserved as the last treatment option because
of their associated short- and long-term side effects.
• Corticosteroids can either be injected into the involved
intraarticular joints or administered systemically. Because
rapid removal of corticosteroids can precipitate a rebound
attack, steroid withdrawal should be done gradually.

46. Question And
Answering