Lesson 26 - Treatment of Gout (CEU 2024/25) PDF

Lesson 26 Treatment of Gout 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25 1. INTRODUCTION Gout is a metabolic disease in which urate crystals are deposited in tissues It is characterised by extremely painful intermittent attacks of acute arthritis...

Lesson 26 Treatment of Gout 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25 1. INTRODUCTION Gout is a metabolic disease in which urate crystals are deposited in tissues It is characterised by extremely painful intermittent attacks of acute arthritis An inflammatory response is evoked THE DISEASE OF KINGS: In the past, only the wealthy could afford diets rich in red meat, seafood, and alcohol, all high in purines. Purines break down into uric acid, and elevated levels of uric acid can lead to gout. Historical figures like King Henry VIII of England and Louis XIV of France, suffered from gout, reinforcing its association with wealth, power, and indulgence. 1. INTRODUCTION Drugs actions: 1. Decreasing uric acid synthesis: allopurinol (the main prophylactic drug) or febuxostat 2. Increasing uric acid excretion (uricosuric agents: probenecid , sulfinpyrazone) 3.Inhibiting leukocyte migration into the joint ( colchicine ) 4. Blocking IL-1: anakinra 5. Exerting a general anti-inflammatory and analgesic effect (NSAIDs and occasionally glucocorticoids). 3  2. Drug treatment ALLOPURINOL Mechanism of action: Inhibition of the synthesis of uric acid by competitive inhibition of xanthine oxidase Main biochemical effects Reduces the concentration of insoluble urates and uric acid in tissues, plasma and urine. Increases the concentration of their more soluble precursors, the xanthines and hypoxanthines. FEBUXOSTAT has a similar pharmacology.  2. Drug treatment ALLOPURINOL Never starting during an acute attack: during an acute attack, allopurinol can exacerbate symptoms as it alters uric acid levels, which may trigger or worsen inflammation in the joints. First choice in the long-term treatment of gout (chronic) When allopurinol is started, it's often combined with an NSAID or colchicine to prevent gout flares. ADRS: Interactions GI disturbances Increases the effect of Rash some chemotherapy agents Some blood alterations  2. Drug treatment URICOSURIC AGENTS →Increase the excretion of uric acid Inhibition of reabsorption Increased secretion Inhibition of The renal proximal tubule is responsible for handling uric postsecretory acid reabsorption and secretion, both of which affect uric reabsorption acid levels in the bloodstream. 3. Drug treatment URICOSURIC AGENTS PROBENECID, SULFINPYRAZONE, BENZBROMARONE Mechanism of action Increase uric acid excretion by a direct action on the renal tubule. Treatment with uricosuric drugs is initiated together with an NSAIDs (not ASPIRIN) SULFINPYRAZONE Useful as prophylaxis for patients with severe recurrent gout who have severe adverse reactions to allopurinol. BENZBROMARONE Treatment of patients with renal impairment 3. Drug treatment URICOSURIC AGENTS pharmacodynamic interaction SALICYLATES Aspirin antagonises the effect of uricosuric agents, do not use them simultaneously What type of interaction is this? 3. Drug treatment URICOLYTIC AGENTS RASBURICASE A preparation containing the enzyme uric acid oxidase Uric acid oxidase is an enzyme that plays a key role in the breakdown of uric acid into allantoin, a more soluble compound that can be more easily excreted by the kidneys. Used for aggressive treatment of gout (iv) Used as prophylaxis due to chemotherapy-induced hyperuricemia 3. Drug treatment COLCHICINE Alkaloid extracted from the autumn crocus. Oral administration Mechanism of action Prevents and relieves acute attack of gout. It prevents migration of neutrophils into the joint Colchicum automnale At higher doses→Inhibits mitosis: risk of serious bone marrow depression (anticancer properties) ADRs: Nausea, vomiting and abdominal pain. Severe diarrhoea gastrointestinal haemorrhage, kidney damage, bone marrow depression and peripheral neuropathy. 3. Drug treatment CORTICOSTEROIDS Systemically or via intraarticular injection brotes Treatment of acute gout flares, when other therapies are contraindicated. Prednisone used for the treatment of acute gout flares should be initiated at a dosage of 30 mg to 40 mg per day until symptom improvement, which should occur in 2 to 5 days. 3. Drug treatment NOVEL THERAPIES ANAKINRA, CANAKINUMAB Mechanism of action: anti-IL-1β IL-1β plays a pivotal role in gout as an inflammatory mediator: Other IL-1 family members are also involved in gout. BERMEKIMAB/MABp1 Mechanism of action:A monoclonal antibody against IL-1α IL-1α is understudied and may play a substantial role in the local initiation and amplification of gouty arthritis. 4. Non-pharmacological intervention Diet low in purine-rich foods, avoiding high-fructose corn syrup, and restricting alcoholic beverages could reduce serum UA in hyperuricemic patients. Additionally, weight loss and exercise should be promoted to reduce serum UA concentrations in candidate patients. Topical ice is recommended as adjuvant therapy during flares to further reduce pain and inflammation. 5. Clinical uses To treat acute gout: for the inflammatory phase An NSAID, e.g. ibuprofen , naproxen. Colchicine is useful if NSAIDs are contraindicated. A glucocorticoid (oral, intramuscular or intra-articular) is an alternative to an NSAID. For prophylaxis Allopurinol ; (must not be started until the patient is asymptomatic): – a uricosuric drug (e.g. probenecid , sulfinpyrazone ), for patients allergic to allopurinol Rasburicase by intravenous infusion for prevention and treatment of acute hyperuricaemia in patients with haematological malignancy at risk of rapid lysis.