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Anti-Gout Medications: Key Points

anti-gout medications as their name implies are medications used to treat gout which is a form of inflammatory arthritis the underlying cause of gout is hyperuricemia which is too much uric acid in the blood resulting in the formation of monosodium urate crystals these sharp needle-like crystals deposit in areas of slow blood flow such as joint spaces or kidney filtration tubules anti-gout medications work by preventing the buildup of uric acid or by reducing inflammation now uric acid is a natural waste product of purines which are one of the building blocks of dna and rna during their metabolism purines are first degraded to hypoxanthine which is then oxidized twice by xanthine oxidase first to become xanthine and then finally to uric acid uric acid circulates in the bloodstream until it reaches the kidneys where it's secreted into the proximal tubules and eventually excreted in the urine now hyperuricemia occurs when levels of circulating uric acid exceed normal levels which is around 1.5 to 6 milligrams per deciliter for women and 2.5 to 8 milligrams per deciliter for men urate crystal deposition occurs when concentrations of circulating uric acid exceeds its rate of solubility which is about 6.8 milligrams per deciliter now anti-gout medications are subdivided into two main groups chronic gout medications which are used to prevent the buildup of uric acid in the blood and acute gout medications which are used to reduce inflammation chronic gout medications include xanthine oxidase inhibitors such as allopurinol and phoboxastat uracosuric medications such as probenicid and sulfin pyrozone and recombinant urate oxidases such as resburicase and plagoticase on the other hand acute gout medications include non-steroidal anti-inflammatory drugs or nsaids glucocorticoids and colchicine all right let's start with xanthine oxidase inhibitors allopurinol is a purine analog that works by competitive inhibition of xanthine oxidase but besides being an inhibitor aloperinol is also a substrate meaning that it's converted by xanthine oxidase into its active metabolite called oxypurinol moreover oxypyranol which is also known as alazanthine is a non-competitive inhibitor of xanthine oxidase this way allopurinol and oxypyranol decrease levels of uric acid by increasing levels of hypoxanthine and xanthine which are more soluble compounds and therefore easier to excrete as a result there's a smaller chance of crystals depositing in joints and tissues other indications for aloperinol include individuals with lymphoma or leukemia who are receiving anti-cancer therapy these individuals are expected to experience tumor lysis resulting in significant production of uric acid from purines that are released by the death of neoplastic cells common side effects of allopyranol include gastrointestinal problems and rash on the other hand phoboxastat is a non-purine inhibitor of xanthine oxidase and it's reserved for individuals who can't tolerate allopurinol common side effects of fabulostat include gastrointestinal disturbance headache and liver problems it's important to note that xanthine oxidase inhibitors can cause bone marrow suppression in individuals treated with immunosuppressive medications such as azathioprine and 6 mercaptopurine these medications are normally metabolized by xanthine oxidase therefore inhibition of their metabolism will increase their effect which are known to decrease replication and induce apoptosis of white blood cells in order to prevent this the dose of the immunosuppressive medication should be reduced when there's concurrent use of allopuranol let's switch gears and shift our focus onto your kashurik medications like probenicid and sulfin pyrozone which work by inhibiting renal tubular reabsorption of uric acid thereby increasing its excretion but because they're weak acids in low doses these medications may compete with uric acid for secretion in the proximal tubules thereby elevating rather than reducing concentration of uric acid in the blood likewise urecasuric medications can compete with other weak acids that are normally secreted in the proximal tubules such as penicillin cephalosporins and aspirin so combinations of these drugs should be avoided let's move on to recombinant urate oxidases which include pagloticase and resburicase these medications are actually enzymes that oxidize uric acid to a lantern which is a more soluble product therefore easier to excrete for medicine specific indications paglotticase is used to treat chronic refractory gout while resburicase is used to treat tumor lysis syndrome in lymphoma and leukemia patients who are receiving anti-cancer therapy common side effects include anaphylaxis hemoglobinemia and hemolysis in individuals with glucose 6-phosphate dehydrogenase or g6pd deficiency okay let's move on to the treatment of acute gout the first line treatment is a non-steroidal anti-inflammatory drug such as indomethacin or ibuprofen these medications work by reversible inhibition of cyclooxygenase which is an enzyme responsible for the production of prostaglandins that cause inflammation it's important to note that aspirin and other salicylates should be avoided in gout because they're weak acids therefore they can compete with uric acid for secretion in the proximal tubules on the other hand glucocorticoids such as methylprednisolone and prednisone work by inhibiting phospholipase a2 which is another enzyme responsible for the production of prostaglandins moreover these medications can be administered orally parenterally or by intra-articular administration the last medication in this group is colchicine which works by binding tubulin and inhibiting microtubule polymerization thereby inhibiting neutrophil migration in joints and reducing inflammation other indications for colchicine include prophylaxis of gout attacks and familial mediterranean fever which is a condition characterized by fever arthritis hepatitis peritonitis and pleuritis colchicine is contraindicated in individuals with kidney liver or gastrointestinal problems moreover it should be used only when nsaids or corticosteroids are contraindicated or ineffective because colchicine has a high rate of side effects including nausea vomiting diarrhea peripheral neuropathy rhabdomyolysis kidney damage and bone marrow suppression now we want to make a simple and fun mnemonic that that'll help you efficiently memorize and retain all of these farm facts let's use a scene in a restaurant we can put the chronic gout medications in the kitchen and the acute gout medications in the dining area in the kitchen we can start with the xanthine oxidase inhibitors first we have the chefs an ox and an owl pouring oil into a pan representing oxapyranol and alopyranol behind them is their boss who's a fabulous fox for fubuxostat there's a chopped up tumor in the pan since these drugs are used to treat tumor lysis syndrome which could increase uric acid levels for side effects they're both wearing dirty chef's hats to help you remember eating their food can cause gastrointestinal distress these hats also have red dots all over them to represent a rash next to the pan there's a pile of discarded bones and dead white blood cells because these drugs cause bone marrow suppression when used with immunosuppressants okay let's move on to the sink for urecashuric medications that decrease tubular reabsorption of uric acid here we have a butterfly trying to drink from the sink with its long proboscis for probenecid next the edge of the sink is on fire creating a pyrozone for sulfin pyrozone in the sink there's a discarded pen and a spring representing penicillin and aspirin which clog up the drain so they shouldn't be used with urecashuric drugs finally just like with all restaurants the back door to the kitchen is where we keep the recombinant uret oxidase medications so let's have the restaurant owners be a pig and a raccoon carrying briefcases these two represent piglotticase and rasbura case for specific indications the pig is carrying a urate crystal for gout while the raccoon is carrying a plate of chopped up tumor for tumor lysis syndrome both have swollen faces for anaphylaxis for contraindications let's put the flags of the six countries that lead the eu called the g6 above the doorway to help you remember these medications are contraindicated for people with g6pd now these people can get hemoglobinemia when using these medications which results in chocolate colored blood so let's make the door a giant bar of chocolate so at the first table we have the first line acute gout medications which are nsaids like ibuprofen represented by an egyptian ibis and indomethacin which is a lump of unbaked dough a spring for aspirin has been discarded under the table to help you remember this particular nsaid is contraindicated at the next table we have the glucocorticoids so here let's put someone's son dressed up as a predatory shark for prednisone both glucocorticoids and nsaids have anti-inflammatory effects so let's have a restaurant staff put out their flaming creme brulees with a fire extinguisher okay moving on to the last table which has a plate of cold uncooked chicken for colchicine this table is last since it's only used when the person doesn't respond to nsaids or glucocorticoids the chicken is pre-cooked to help you remember it could also be used to prevent gout there's a pita bread that's on fire next to the chicken to help you remember that another indication is mediterranean fever for side effects the person who ate this chicken is vomiting to represent gi distress his hands got burned by the flaming pita so they're wrapped in bandages for peripheral neuropathy and the muscles in his arms are red and swollen for rhabdomyolysis there's a pile of chicken bones next to him for bone marrow suppression and in the pile is a dead kidney for renal toxicity all right as a quick recap anti-gout medications are used to treat gout which is a form of inflammatory arthritis caused by urate acid crystal buildup in joints they're subdivided into two main groups chronic gout medications which prevent the buildup of uric acid in the blood and acute gout medications which reduce inflammation chronic gout medications include xanthine oxidase inhibitors like aloperinol and phoboxastat uracoshuric medications like probenacid and sulfonpyrozone and recombinant urae oxidases like resburicase and paglotticase on the other hand acute gout medications include non-steroidal anti-inflammatory drugs glucocorticoids and colchicine but wait there's more here is a mind map with all of the mnemonics go ahead and pause the video so you can test yourself and see what you remember stay tuned for the answers after the credits