CHAPTER:2 GOUT BY Mrs. K.SHAILAJA., M. PHARM., LECTURER DEPT OF PHARMACY PRACTICE, SRM COLLEGE OF PHARMACY
DEFINITION Gout is defined as a peripheral arthritis, resulting from the deposition of MSU crystals at one or more joints. Characterized by Hyperuricemia. Known as: Rich man s Disease / Disease of Kings. Poor man s Gout.
Uric acid Product of purine catabolism. Ionized forms of uric acid readily form salt. 98% of Uric acid forms monosodium salts MSU crystals form in synovial fluid when solubility limit are exceeded. These crystals provoke an inflammatory reaction.
EPIDEMIOLOGY Males between the ages of 20 40. Men have higher serum urate levels. Post menopausal women Patients on diuretics. Increase reabsorption Patients with hypertension, diabetes, hyperlipidemia, chronic kidney disease, or the metabolic syndrome.
CLASSIFICATIONS : Primary Gout 90% Overproduction Under excretion Secondary Gout 10% PROGRESSIONS : Asymptomatic hyperuricemia Acute gouty arthritis Intercritical Gout Chronic / Tophaceous Gout
SIGNS AND SYMPTOMS ACUTE GOUT ATTACKS : A rapid onset of pain in the affected joint followed by warmth, swelling, reddish discoloration, and marked tenderness. Bursitis. The small joint at the base of the big toe is the most common site of an acute gout attack. Other joints that can be affected include the ankles, knees, wrists, fingers, and elbows. Intense tenderness: even a blanket touching the skin over the affected joint can be unbearable.
DIET : Beer drinking, High red meat and seafood consumption increases risk. Purine-rich vegetable consumption does not notably increase risk of hyperuricemia and development of gout. Both incidence and Prevalence of Gout is increasing. For example, Data from US managed care reflected an increase in gout prevalence from 2.9 cases per 1000 persons in 1990 to 5.2 cases per 1000 in 1999. Societies such as New Zealand, Taiwan and USA show increasing prevalence. More prevalent among African American Males than European American males.
CAUSES OF GOUT (ETIOLOGY) INHERITANCE OF CERTAIN GENES : Increased V max for the production of PRPP. A lower K m for ribose 5-phosphate. Decreased sensitivity to its purine nucleotide inhibitors. The overall result is increased purine production resulting in high levels of plasma uric acid.
PATHOPHYSIOLOGY Turnover of nucleic acid and coenzymes results in the production of free purine bases (Adenine, hypoxantine and guanine). Decreased activity of HGPRT which catalyzes a reaction of hypoxantine, guanine and adenosine with PRPP to give IMP, GMP and AMP results in the buildup of PRPP and reduced levels of IMP,GMP and AMP. Hence hypoxanthine, guanine and adenine would go towards the production of xanthine which is oxidixed to uric acid leading to hyperuricemia. N.B. InVon Geirke Disease, G6P is shunted to the HMP pathway lead to the increased production of R5P leading to the increased production of PRPP.
DIAGNOSIS Uric acid crystals under polarized light
DIAGNOSIS Radiograph showing sharply "punched out" bony defects of the distal radius and proximal phalange of the middle finger
GOUT TREATMENT OF
There are two essential concepts behind the treatment of Gout: 1. Its is critical in stopping the inflammation caused by the gouty arthritis. 2. It is vital in addressing the long term management of the disease in order to prevent further attacks and shrink crystal deposits. There are basically three ways of treating Gout: 1. Self Care 2. Medications 3. Surgery
SELF CARE Take medications as prescribed. While a joint is hot and swollen, aggravation should be prevented to so as to reduce further discomfort. The following would be helpful: Using of a cane or similar support to keep your weight off that joint. Keep the swollen joint elevated above your chest as much as possible. Ice packs can be helpful in relieving pain and reducing inflammation. Maintaining adequate hydration is key for minimizing attacks and decreasing the formation of kidney stones.
Reduce the consumption of alcohol since: It is known to have a diuretic effects and can contribute to dehydration and precipitate the acute gout attack. Affects uric acid metabolism resulting in hyperuricemia. Dietary changes can help reduce the amount of uric acid in the blood; Purine rich food should be avoided (shellfish and organ meats such as liver, brains, kidneys, and sweetbreads)
MEDICATION There are three aspects/lines of treatment of gout with medication: Pain relievers such as acetaminophen (Tylenol) or other more potent analgesics are used to manage pain. The exact mechanism of action of acetaminophen is not known. Acetaminophen relieves pain by elevating the pain threshold, that is, by requiring a greater amount of pain to develop before a person feels it.
Anti-inflammatory agents such as NSAIDS, colchicine, and corticosteroids, used to decrease joint inflammation. NSAIDS such as:diclofenac, etoricoxib, indomethacin, ketoprofen and naproxen. Most of these drugs function by inhibiting the COX-2 resulting in the reduction of prostaglandins production.
SURGERY Surgery is rarely needed for gout unless significant joint damage has occurred from lack of effective treatment