Pharmacotherapy of _____GOUT AND HYPERURICEMIA___



Pharmacotherapy of _____GOUT AND HYPERURICEMIA___

Thomas Tran, PharmD Candidate 2007

|Epidemiology |( A direct correlation is seen between serum uric acid concentration and both incidence and prevalence of gout |

| |- 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 |

|Disease State | ( Gout describes a disease spectrum including: |

|Definition |-Hyperuricemia |

| |-Recurrent attacks of acute arthritis |

| |-Presence of urate crystals in synovial fluid |

| |-Deposits of urate crystals in tissues (tophi) |

| |-Interstitial renal disease |

| | |

| |( Gout is a rapid onset of excruciating pain, swelling, and inflammation of a joint, |

| |particularly the metatarsal phalanges of first toe. |

| | |

| |( Hyperuricemia may be an asymptomatic condition with an increased serum uric acid level as the only apparent abnormality. |

| | |

| |( Normal serum urate concentration values are 6.8 mg/dL for men and 6.0 mg/dL for women |

| | |

| |( Serum urate concentration values for hyperuricemia |

| |-Men: > 7 mg/dL |

| |-Women: > 6 mg/dL |

|Patho-physiology |( Determine whether the patient is an overproducer or underexcretor of uric acid |

| | |

| |( About 10% of the patients who develop gout are overproducers and the rest are |

| |underexcretors. |

| | |

| |( Purines from which uric acid is produced originates from 3 sources: |

| |Dietary purine |

| |Conversion of tissue nucleic acid to purine nucleotides |

| |De novo synthesis of purine bases. |

| | |

| |( There are two enzymatic abnormalities which result in the overproduction of uric acid |

| |Increase in the activity of phosphoribosyl pyrophosphate (PRPP) synthetase, which leads to increased PRPP concentration, and thus increased|

| |uric acid production. |

| |Deficiency of hypoxanthine guanine phosphoribosyl transferase(HGPRT) which leads to increased metabolism of guanine and hypoxanthine to |

| |uric acid. |

| | |

| |( Underexcretion of uric acid occurs when the decline in urinary excretion of uric acid is |

| |below the rate of production |

| | |

| |( Some factors which can contribute to the underexcretion of urate include: |

| |-Renal insufficiency |

| |-Lead intoxication |

| |-Ethanol |

| |-Diuretics |

| |-Hypothyroidism |

| | |

|Clinical Presentation |Asymptomatic Hyperuricemia |

| |( Is defined as an abnormally high serum urate level, without gouty arthritis or nephrolithiasis. |

| |( Hyperuricemia predisposes patients to both gout and nephrolithiasis, but does not warrant therapy in the asymptomatic patient. |

| | |

| |Acute Gouty Arthritis |

| |( Characterized by the sudden onset of pain, erythema, limited ROM and swelling of the involved joint. |

| |( The peak incidence of acute gout occurs between 30 and 50 years of age. |

| |( First attacks are monoarticular in 90 percent. |

| |( In more than 50% of patients, the first MTP joint is the initial joint involved. |

| |( Joint involvement includes the MTP joint, the instep/forefoot, the ankle, the knee, the wrist |

| |and the fingers. |

| |( Conditions that can precipitate an attack include: |

| |-Stress and trauma |

| |-Alcohol ingestion |

| |-Infections and surgery |

| |-Uric acid-lowering agents that can rapidly lower serum uric acid levels |

| |-Drugs known to elevate serum uric acid concentrations |

| | |

| |Intercritical Gout |

| |( Consists of the asymptomatic phase of the disease following recovery from acute gouty |

| |arthritis. |

| | |

| |Tophaceous Gout |

| | |

| |( Recurrent acute attacks can lead to chronic tophaceous gout. |

| |( It consists of progressive cartilage and bone erosion and deposition of tophi |

| |( Tophi are deposits of sodium urate (large enough to be seen on radiographs) and may occur |

| |at any site. |

| |( Common sites of occurrence include: |

| |Joints of hands or feet |

| |Helix of the ear |

| |Olecranon bursa |

| |Achilles tendon. |

|Risk Factors | ( Serum urate concentration correlates with age, Scr, BUN, male gender, blood pressure, |

| |body wt, and alcohol intake |

| | |

| |( Dietary sources of purines |

| | |

| |( Disease states: Obesity, CHF, hyperparathyroidism, hypothyroidism, psoriasis, etc (Refer |

| |to attached table 1 for Conditions Associated with Hyperuricemia) |

| | |

| |( Medications: diuretics (thiazides), salicylates (< 2g/day), cyclosporine, etc (Refer to |

| |attached table 2 for Drugs Capable of Inducing Hyperuricemia and Gout) |

| | |

| |( Although no genetic marker has been isolated for gout, the familial nature of gout |

| |strongly suggests an interaction between genetic and environmental factors |

|Diagnosis |Presence of urate crystals in synovial fluid |

| |A tophus proven with urate crystals by chemical means or polarized light microscopy |

| |OR |

| |Presence of 6 of the following 12 clinical lab and X-ray findings: |

| |More than 1 attack of acute arthritis |

| |Maximum inflammation within 1 day |

| |Attack of mono-articular arthritis |

| |Joint redness observed |

| |First MTP joint painful or swollen |

| |Unilateral attack involving 1st MTP joint |

| |Unilateral attack involving tarsal joint |

| |Suspected tophus |

| |Hyperuricemia |

| |Asymmetric swelling within a joint |

| |Subcortical cysts without erosion |

| |Negative culture of joint fluid for microorganisms during attack of acute inflammation |

|Desired Therapeutic |Acute Gouty Arthritis |

|Outcomes* |Relieve acute pain |

| |Relieve acute inflammation |

| | |

| |Recurrent gout |

| |Relieve acute attacks |

| |Prevent acute attacks |

| | |

| |Hyperuricemia |

| |Reduce serum uric acid concentrations to normal ranges |

| |Prevent complications of hyperuricemia |

| |Prevent acute gout attacks |

| |Prevent uric acid nephropathy |

| |Reduce tophi if present |

| | |

| |-DiPiro JT, Talbert RL, Yee GC et al., eds. Pharmacotherapy: A pathophysiological approach. 6th ed |

|*Reference of |-ISAT class notes on Gout and Hyperuricemia |

|Guidelines Used |- Harris MD, Siegel LB, Alloway JA. Gout and hyperuricemia. American Family Physician. 1999; 59:925-34 |

| |-Chan PD, Johnson MT. Treatment Guidelines for medicine and primary care. Current Clinical Strategies Publishing 2006. 268. |

|Treatment Options** | |

| |Non-drug therapy: |

|(Non-drug and Drug |( Dietary changes |

|Therapy – include all |-Low protein/purine diet (stay away from foods like red meat, seafood, tofu, beans) |

|therapeutic |-Drink 2-3 liters a day of fluid |

|classes/agents |( Lifestyle changes |

|available and |-Weight reduction (obesity increases risk of hyperuricemia and gout) |

|preferences per |-Avoid drugs capable of inducing hyperuricemia and gout |

|treatment guidelines) |-Alcohol avoidance |

| | |

| |Drug therapy: |

| |( NSAIDs |

| |( Colchicine |

| |( Xanthine Oxidase Inhibitor |

| |( Uricosuric agents |

|**See Treatment Options|( Corticosteroids |

|Table | |

| | |

| | |

|Monitoring | |

| | |

|(Efficacy and Toxicity |**See Treatment Options Table |

|Parameters) | |

Table 1 Conditions Associated with Hyperuricemia

|Primary gout |Obesity |

|Diabetic ketoacidosis |Sarcoidosis |

|Myeloproliferative disorders |Congestive heart failure |

|Lactic acidosis |Renal dysfunction |

|Lymphoproliferative disorders |Down syndrome |

|Starvation |Lead toxicity |

|Chronic hemolytic anemia |Hyperparathyroidism |

|Toxemia of pregnancy |Acute alcoholism |

|Pernicious anemia |Hypoparathyroidism |

|Glycogen storage disease type 1 |Acromegaly |

|Psoriasis |Hypothyroidism |

TABLE 2 Drugs Capable of Inducing Hyperuricemia and Gout

|Diuretics |Ethanol |Ethambutol |

|Nicotinic acid |Pyrazinamide |Cytotoxic drugs |

|Salicylates ( ................
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