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Gout 130718051351 Phpapp01
Gout 130718051351 Phpapp01
Prepared by :
Farjana Rahman B.Pharm, Southeast University M.Pharm, East West University, Bangladesh
Introduction
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.
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
But in leukemia myeloid metaplasia lymphoma Polycythemia And in rapid weight loss (dieting)
Male Postmenopausal female Old aged people Hypertension Pharmaceuticals: Diuretics, ASA, cyclosporine
Transplant Alcohol intake Highest with beer Not increased with wine High BMI (obesity) Diet high in meat & seafood
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.
Clinical Manifestations
Flares Intervals
Silent tissue deposition & Hidden Damage may also occur in gouty attack
Advanced Gout
Chronic Arthritis Polyarticular acute flares with upper extremities more involved
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
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
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
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
Diagnosing [Cont..]
X-rays Synovial
The
Gold standard Crystals intracellular during attacks Needle & rod shapes Strong negative birefringence
X-rays
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.
New drugs
Febuxostat Rasburicase pegloticase
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.
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 )
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
-Anticonvulsants -Anti-diabetic -Antifungals -Bronchodilators -Digoxin - HIV protease inhibitors -Liver vaccines - Macrolides - Methotrexate - Nonsteroidal anti-inflammatory drugs -Rifampicin -Diuretics -Ephedrine
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?
Life Style
Obesity is a major risk factor for gout, and losing weight is an important goal towards achieving normal urate levels. It needs to be emphasized to the aircrew that the weight loss is to be achieved by regular exercise and dietary discretion and not by starvation or fad diet. Though the dietary intervention guidelines for patients with gout and hyperuricemia have evolved over time, it is still not known as to which combination of foods is the best. The following general dietary guidelines are to be explained to all aircrew with hyperuricemia.
c) What life style and preventive therapy will you suggest to this aircrew? (Cont.)
Preventive therapy
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.
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.
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.
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.
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.