GOUT

Gout is an inflammatory condition of the arthritis-type that results from deposition of monosodium urate crystals in joint spaces or surrounding tissues, leading to an inflammatory reaction that causes intense pain, erythema, and joint swelling.
It is associated with hyperuricemia, defined as a Serum Uric Acid (SUA) level of 6.8 mg/dL (404 μmol/L) or greater, but not all patients with hyperuricemia demonstrate symptoms.
Inflammation of arthritis type
Hyperuricemia
Metatarsophalangeal joint
Pharmacotherapeutics
M.Pharmacy
Pharmacy practice
Unit 05

1. GOUT PRESENTED BY: LINCY ASHA.S M.PHARM SEMESTER I PHARMACY PRACTICE 1

2. DEFINITION Gout is an inflammatory condition of the arthritis-type that results from deposition of monosodium urate crystals in joint spaces or surrounding tissues, leading to an inflammatory reaction that causes intense pain, erythema, and joint swelling. It is associated with hyperuricemia , defined as a Serum Uric Acid (SUA) level of 6.8 mg/dL (404 μmol /L) or greater, but not all patients with hyperuricemia demonstrate symptoms. Gout usually presents as a monoarthritis in the first metatarsophalangeal joint (big toe of the foot) Areas of the body that can be affected by gout include: Joints - mid-foot, ankle, wrist, knee & finger joints Bursae Tendon sheaths Kidneys 2

3. STAGES OF GOUT Stage 1: Asymptomatic hyperuricemia In this stage, a person has elevated levels of uric acid in the blood (hyperuricemia), but no other symptoms . Treatment is usually not required. Stage 2: Acute gout, or acute gouty arthritis In this stage, hyperuricemia has caused the deposit of uric acid crystals in joint spaces . This leads to a sudden onset of intense pain and swelling in the joints, which also may be warm and very tender . An acute attack commonly occurs at night and can be triggered by stressful events, alcohol or drugs, or the presence of another illness. Attacks usually subside within 3 to 10 days, even without treatment, and the next attack may not occur for months or even years. Over time, however, attacks can last longer and occur more frequently. 3

4. Stage 3: Interval or inter critical gout This is the period between acute attacks. In this stage, a person does not have any symptoms. Stage 4: Chronic tophaceous gout This is the most disabling stage of gout. It usually develops over a long period , such as 10 years. Gout pain is frequent and tophi form in joints. In this stage, the disease may have caused permanent damage to the affected joints and sometimes to the kidneys. With proper treatment, most people with gout do not progress to this advanced stage. 4

5. ETIOLOGY Having high urate levels Having a family history of gout. Increasing age. Drinking alcohol. Eating foods that are rich in purines (usually from animal sources), a substance that breaks down into urate. Drinking beverages that have high-fructose corn syrup, such as soda. 5

6. Some health conditions may increase the risk of developing gout such as: Obesity Chronic kidney disease P soriasis, hemolytic anemia Metabolic syndrome - high blood pressure, high blood sugar, abnormal cholesterol levels, and excess body fat around the waist. Some medications can increase the risk of developing gout such as Some drugs can cause hyperuricemia and precipitate gout, such as thiazide and loop diuretics, niacin, pyrazinamide, cyclosporine and low dose aspirin. 6

7. EPIDEMIOLOGY Gout is the most common inflammatory arthritis in men, with a male:female incidence of about 4:1. About 10% of population with hyperuricemia, develop gout at some point in their lifetimes. More common in males over 40 years of age. In women, it tends to develop after menopause when levels of oestrogen , a known uricosuric fall. HOW URIC ACID IS FORMED? 7

8. PATHOPHYSIOLOGY Gout is caused by an abnormality in uric acid metabolism. Uric acid is a waste product of purine breakdown contained in the DNA of degraded body cells and dietary protein. It is water soluble and excreted primarily by the kidneys. Increased levels of uric acid in the blood and other body fluids ( eg.synovium ) lead to the precipitation of monosodium urate crystals. This in turn triggers a chain of events that culminate in joint injury. 8

9. The precipitated crystals are directly chemotactic and can also activate complement to generate chemotactic C3a and C5a fragments. This leads to a local accumulation of neutrophils and macrophages in the joints and synovial membranes in attempting to phagocytize the crystals, these cells become activated leading to the release of host additional mediators including chemokines, toxic free radicals, and leukotrienes particularly leukotriene B4. The activated neutrophils also liberate destructive lysosomal enzymes . Macrophages participate in joint injury by secreting a variety of proinflammatory mediators such as IL-1, IL-6 and TNF. While intensifying the inflammatory response, these cytokines can also directly activate synovial cells and cartilage cells to release proteases ( eg. Collagenase) that cause tissue injury . 9

10. SIGNS AND SYMPTOMS Always occur suddenly, and often at night. They include: Intense joint pain.  Gout usually affects the big toe , but it can occur in any joint. Other commonly affected joints include the ankles, knees, elbows, wrists and fingers. The pain is likely to be most severe within the first four to 12 hours after it begins. Lingering discomfort.  After the most severe pain subsides, some joint discomfort may last from a few days to a few weeks. Inflammation and redness.  The affected joint or joints become swollen, tender, warm and red. Limited range of motion.  As gout progresses, the individual may not be able to move the joints normally. 10

11. The attack is usually monoarticular ; the most common site is the metatarsophalangeal joint (Podagra). Mild fever may be present. Tophi (usually on hands, wrists, elbows, or knees) may be present in chronic, severe disease. 11

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13. DIAGNOSIS Joint fluid test.   Fluid is taken from the painful joint with a needle. The fluid is studied under a microscope to see if the uric acid crystals are there. Blood test.  A blood test can check the level of uric acid. A high level of uric acid doesn’t always mean gout. Urine test : A 24 hour urine sample is collected to measure uric acid levels. X-ray : Joint damage from gout may not be visible until years after the onset of gout symptoms, so the primary benefit of X-rays in diagnosing gout is to rule out other potential causes of joint pain . Ultrasound : Ultrasound uses sound waves to create pictures of structures inside the body . It may be used to detect urate crystals in the joints or deposits of uric acid crystals that form hard, visible lumps in or near the joints, called tophi. Dual energy CT scan : A test that combines X-ray images from many different angles, DECT may be used to see uric acid crystals in the joints. Radiography : A cloudy area of increased opacity may be seen in patient who has had multiple episodes of gouty arthritis in the same joint. 13

14. TREATMENT Treatment of gout involves: acute relief of a gouty arthritis attack with topical application of ice and drug therapy commonly including NSAIDs, colchicine, corticosteroids, or a combination thereof, and In some patients, long-term prophylactic treatment with urate-lowering therapy (ULT) to prevent subsequent attacks. NON PHARMACOLOGICAL TREATMENT: Patients may be advised to reduce their intake of foods high in purines (e.g., organ meats), avoid alcohol, increase fluid intake, and lose weight if obese. Joint rest for 1 to 2 days should be encouraged. Local application of ice packs to the joint is most effective in decreasing pain and swelling. 14

15. PHARMACOLOGICAL TREATMENT Pharmacotherapy Regimens for Acute Gout Treatment 15 CATEGORY DRUG USUAL DOSAGE RANGE NSAIDs (1 st line) Etodolac 300–500 mg po two times daily Fenoprofen 400–600 mg po three to four times daily Ibuprofen 400–800 mg po three to four times daily Indomethacin 50 mg po three times daily initially until pain is tolerable, then quickly taper to discontinue Ketoprofen 50 mg po four times daily or 75 mg po three times daily Naproxen 750 mg po initially, then 250 mg po every 8 hours Piroxicam 20 mg po once daily or 10 mg po twice daily Sulindac 150–200 mg po two times daily for 7–10 days Celecoxib 800 mg po followed by 400 mg po on day 1, then 400 mg po twice daily for 1 week

16. CATEGORY DRUG USUAL DOSAGE RANGE Colchicum alkaloids Colchicine (2 nd line) 1.2 mg po at the onset of attack, then 0.6 mg po 1 hour later Corticosteroids (3 rd line) Local corticosteroid Triamcinolone acetonide 10–40 mg (large joint), 5–20 mg (small joint) for one dose by intraarticular injection Systemic corticosteroid Prednisone 30–60 mg po once daily for 3–5 days, then taper to discontinue by 5 mg decrements over 10–14 days Triamcinolone acetonide 60 mg by IM injection for one dose Methylprednisolone 100–150 mg by IM injection once daily for 1–2 days 16 Adrenocorticotropic hormone Corticotropin 40–80 units IM or SC every 24–72 hours Interleukin-1 Inhibitors Anakinra 100 mg SC once daily for 3 days Canakinumab 150 mg SC for 1 dose

17. Combination therapy In severe polyarticular attacks, particularly attacks involving multiple large joints colchicine may be used in combination with an NSAID or oral corticosteroid . Intraarticular corticosteroid injections may be used in combination with NSAID/ colchicine/ oral corticosteroid. Pharmacotherapy regimens for intercritical gout 17 DRUG TYPICAL REGIMEN NSAIDs Lowest effective dosage Oral colchicine 0.6-1.2 mg daily to every other day Xanthine oxidase inhibitor (Allopurinol) 50-300 mg daily

18. Pharmacotherapy Regimens for Urate Lowering 18 CATEGORY DRUG USUAL DOSAGE RANGE Xanthine Oxidase Inhibitors Allopurinol (1 st line) 100 mg po initially, then titrate to achieve SUA level < 6 mg/dL (357 μmol /L); maximum 800 mg po daily Febuxostat (2 nd line) 40 mg po once daily initially, then increase to 80 mg po once daily if SUA does not decline to 6 mg/dL (357 μmol /L) or lower after 2 weeks of treatment Uricosurics Probenecid 250 mg po two times daily for 1 week, then 500 mg po twice daily; may increase by 500 mg every 4 weeks to achieve SUA level < 6 mg/dL (357 μmol /L); maximum 2 g po daily Lesinurad 200 mg po once daily in combination with a xanthine oxidase inhibitor Sulfinpyrazone 50 mg twice daily, titrated up to 100-400 mg/day Other Pegloticase 8 mg given as an IV infusion over at least 2 hours once every 2 weeks, optimal duration unknown

19. REFERENCES https://www.niams.nih.gov/health-topics/gout https://www.webmd.com/arthritis/do-i-have-gout https://www.healthline.com/health/gout-diagnosis#diagnosis https://www.arthritis.org/diseases/more-about/testing-for-gout https://www.goutshare.com/the-four-stages-of-gout/ Pharmacotherapy principles & practice by Marie A.Chisholm -Burns, Terry L.Schwinghammer , Patrick M.Malone , Jill M.Kolesar , Kelly C.Lee , P.Brandon Bookstaver – 5 th edition. Clinical pharmacy and Therapeutics edited by Roger Walker and Cate Whittlesea - 5 th Edition 19

20. THANK YOU 20