GOUT Subject Name: Clinical Pharmacy - II Subject Code: 280006

Mr. Kamal Modh Click to edit Master subtitle style Assistant Professor Shri Sarvajanik Pharmacy College (245) Mehsana

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Definition

Gout is caused by an abnormality in uric acid metabolism Gout is a heterogeneous disorder that results in the deposition of uric acid salts and crystals in and around joints and soft tissues or crystallization of uric acid in the urinary tract. Uric acid is the normal end product of the degradation of purine compounds Uric acid is water soluble and excreted primarily by the kidneys and GI tract The solubility of uric acid depends on concentration and temperature. Humans lack the enzyme uricase to break down uric acid into more soluble form

Click tohigh serum concentrations, lower body style At edit Master subtitle temperature
monosodium urate crystals

causes the precipitation of

Collections of these crystals (called microtophi) can form in joint spaces in the distal extremities

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Predisposing factors
Heredity Drug usage Renal failure Hematologic Disease Hyperuricaemia Trauma Alcohol use Psoriasis Poisoning Obesity Hypertension

Pathophysiology
Gout results from deposition of uric acid crystals in joint spaces, leading to an inflammatory reaction that causes intense pain, erythema, and joint swelling Free urate crystals Activate several proinflammatory mediators, including TNF-) iIL-1 and IL-8 Activated mediators signals chemotactic movement of neutrophils into the joint space Ingest monosodium urate crystals via phagocytosis These neutrophils then are lysed and release proteolytic enzymes Trigger the clinical manifestations of an acute gout attack such as pain and swelling

Click to edit Master subtitle styleto cartilage and joint destruction Lead

Organ transplantation Surgery

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Purine metabolism and mechanisms for uric acid imbalance

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The increased serum uric acid involves either the underexcretion of uric acid (80% of patients) or its overproduction Primary gout is caused by inborn defects in purine metabolism or inherited defects of the renal tubular secretion of urate Secondary gout is caused by acquired disorders that result in increased turnover of nucleic acids, by defects in renal excretion of uric acid salts such as persistently acidic urine and hyperuricemia, uric acid nephrolithiasis and by the effects of certain drugs such as thiazide diuretics, niacin, pyrazinamide, cyclosporine, and low-dose aspirin

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Signs and symptoms

Symptoms Severe pain, swelling, and warmth in the affected joint(s) The attack is usually monarticular, and the most common sites are the metatarsophalangeal of the great toe and knee joints (podagra) In elderly patients, gouty attacks may be atypical with insidious onset and polyarticular, often involving hand or wrist joints Signs Affected joint(s) are warm, erythematous, and swollen Mild fever may be present Microtophi (usually on hands, wrists, elbows, or knees) may be present in chronic, severe disease

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Diagnosis

Laboratory Tests

Previous family history, medication history and physical examination Examination of synovial fluid for the presence of MSU crystals Urate crystals are characteristically needle-shaped and negatively birefringent when viewed under a polarized light microscope The white blood cell (WBC) count in peripheral blood may be only mildly elevated The serum uric acid level often is elevated but may be normal during an acute attack Other laboratory markers of inflammation [e.g., erythrocyte sedimentation rate (ESR)] are often present. increased

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Therapeutic plan

The goals of treatment in gout

Terminating attacks Providing control of pain and inflammation Preventing future attacks Preventing complications such as renal stones, tophi, and destructive arthropathy

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Therapeutic plan

Nonpharmacologic Therapy

Patients should receive education about the nonpharmacologic and pharmacologic measures to help manage RA Certain forms of nonpharmacologic therapy benefit all levels of severity Rest and exercise need to be balanced. Rest serves to spare joints and decrease inflammation which may lead to repair of damaged tissues Occupational and physical therapy may help patients to preserve joint function, extend joint range of motion, and strengthen joints and muscles through strengthening exercises Patients with joint deformities may benefit from the use of mobility or assistive devices that help to minimize disability and allow continued activities of daily living Proper nutrition is important in helping patients lose weight if overweight but must have sufficient protein intake to maintain or enhance muscle mass and sufficient calcium intake to potentially diminish the periarticular osteopenia that may occur In situations where the disease has progressed to a severe form with extensive joint erosions, surgery to replace or reconstruct the joint may be necessary

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Therapeutic plan

Pharmacologic Therapy

Analgesics NSAIDs Glucocorticoids Disease Modifying AntiRheumatic Drugs (DMARD)

Anticytokine therapy Click to edit Master subtitle style

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Therapeutic plan- Non pharmacologic plan

Immobilization of Joint Ice Packs Abstinence of Alcohol

Consumption can increase serum urate levels by increasing uric acid production. When used in excess it can be converted to lactic acid which inhibits uric acid excretion in the kidney

Dietary modification

Low carbohydrates Increase in protein and unsaturated fats Decrease in dietary purine-meat and seafood. Dairy and vegetables do not seem to affect uric acid

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Therapeutic plan- Pharmacologic plan

NSAIDs
Most commonly used No NSAID found to work better than others Regimens: Indocin 50 mg po bid-tid for 2-3 days and then taper Ibuprofen 400 mg po q4-6 hr max 3.2 g/day Ketorolac 60 mg IM or 30mg IV X1 dose in patients<65 30 mg IM or 15mg IV in single dose in patients >65yo, or with patients who are renally impaired Continue medicines until pain and inflammation have resolved for 48hr

Colchicine
Inhibits microtubule aggregation which disrupts chemotaxis and phagocytosis Inhibts crystal-induced production of chemotatic factors Administered orally in hourly doses of 0.5 to 0.6mg until pain and inflammation have resolved or until GI side effects prevent further use. Max dose 6mg/24hr 2mg IV then 0.5mg q6 until cumulative dose of 4mg over 24hr

Click to edit Master subtitle style NSAID/colchicine therapy Patients who cannot tolerate NSAIDs, or failed
Daily doses of prednisone 40-60mg a day for 3-5 days then taper 1-2 weeks Improvement seen in 12-24hr

Corticosteriods

ACTH
Peripheral anti-inflammatory effects and induction of adrenal glucocorticoid release 40-80IU IM followed by second dose if necessary

Intra-articular injection with steroids

Beneficial in patient with one or two large joints affected Good option for elderly patient with renal or peptic ulcer disease or other illness Triamcinolone 10-40mg or Dexamethasone 2-10mg alone or in combination with Lidocaine

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Gout prophylaxis

Frequent attacks >3/year, tophi development or urate overproduction Avoid use of medications that contribute to hyperuricemia: Thiazide and loop diuretics, low-dose salicylates, niacin, cyclosporine, ethambutol Losartan promotes urate diuresis and may even normalize urate levels. This action does not extend to other members of the ARB class Useful in elderly with HTN and gout

Colchicine

Colchicine 0.6mg qd-bid Use alone or in combination with urate lowering drugs Prophylaxis without urate lowering drugs may allow tophi to develop

Urate Lowering drugs

Used for documented urate overproduction Goal is for serum urate concentration to 6mg/dL or less Start of therapy can precipitate acute attack; therefore, may need to use colchicine as a long as six months

Xanthine oxidase inhibitors

Allopurinol: blocks conversion of xanthine to uric acid. works for underexcretors and overproducers Start typically 300mg/day and titrate weekly 100mg/day until optimal urate levels achieved Start lower doses with renally impaired patients

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Uricosuric drugs

Probenecid or Sulfinpyrazone: increase renal clearance of uric acid by inhibiting tubular absorption Side effects may prohibit use-GI and kidney stones Need measurement of 24hr urine in anyone for whom Probenecid therapy is initiated

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