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[3] 06 Gout Medication Colchicine, Uric Acid and More

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Let’s move on to a completely different topic let’s move on to colchicine now coltracine is a selective inhibitor of microtubule assembly now what happens is is that you’re inhibiting tubulin which is necessary for cell division and motility so what is tubulin we can think of tubulin as a combination of a girder or something that holds a building up and a

Communication tube that moves one thing to another from one part of the cell to another inhibiting tubulin production actually inhibits a lot of cell function we call this a general mitotic poison so in actual fact we can use these agents in cancer but in our particular discussion today we’re going to be talking about how it reduces migration in phagocytosis by

Macrophages this also helps reduce interleukin b4 which i mentioned to you in our slide before this also decreases free radical formation which is also a mediator of pain and inflammation so where do we use colchicine it’s used in acute gout attacks it’s often associated with diarrhea and in fact the way that we prescribe this medication is we tell patients

Take 0.1 milligram every hour until you develop diarrhea then slow down and it sounds kind of flippant but it’s true it’s a very effective agent it’s very very potent except for the fact that it causes diarrhea it would be a perfect drug for treating gout chronic gout prevention is treated with 0.6 milligrams once a day now we also use this for pericarditis

Treatment and prevention what we do is we start off with 0.6 milligrams a day or sometimes even twice a day and then we go down to once a day for three months so treating a patient for three months with colchicine actually reduces the recurrence of pericarditis in a patient who had pericardius pericarditis before interestingly enough we also use this for a

Disease called familial mediterranean fever and that treatment dose is 0.6 milligrams twice a day the toxicity of colchicine and overdose can cause liver kidney and other organ failure remember that toxicity can be fatal so if you have a patient show up in your er who’s taken a lot of colchicine you have to pay close attention to these patients other drugs

Used in gout include the uricosurix probenocid is your prototypical agent it is a weak acid and it competes with uric acid for reabsorption at the proximal tubule inside the kidney when you give a patient probenicid the uric acid is released in the urine so here’s an example of how uric acid is reabsorbed you filter about a hundred liters a day of blood into

The glomerulus ninety 90 of the uric acid is reabsorbed at the proximal convoluted tubule allowing a small amount of uric acid excretion at the end this weak acid transporter or what is what picks up these weak acids and brings them back into the blood by administering uric acid agents such as probenecid you actually increase the amount of reabsorption of those

Drugs like probenecid and the uric acid is therefore released into the urine unchanged and not reabsorbed now at low doses these uricoceric agents also compete with uric acid for secretion so that causes an increase in uric acid levels as well so a similar phenomena also occurs with aspirin this causes an elevation of uric acid so the bottom line is this is

That these drugs are uracosyric they do promote um release of your uric acid in the urine however they can also predict or promote an acute gout attack too so you have to be very careful using these drugs and you don’t want to slam people with these medications just without thinking about them because you can precipitate a gout attack the uses of the uricosurix

Is treatment of acute pardon me of chronic gout let’s talk about the xanthine oxidase inhibitors at one time these were the mainstay of gout treatment let’s look at the physiology behind allopurinol allopyranol is converted to allozanthine by xanthine oxidase this is a suicide inhibitor of xanthine oxidase so uric acid production is cut dramatically because

Xanthine oxidase is also needed to produce uric acid now we sometimes use aloperinol in chemotherapy of cancer patients to reduce uric acid production from purines that are released during the cell death of all those cancer cells so this is an important consideration in cancer chemotherapy when we’re killing cells there’s all this stuff being generated as the

Cells are dying one of them are purines and that can cause gout attacks that’s why you have to be very careful in cancer patients and that’s why we use allopurinol in them other non-purine inhibitors of xanthine oxidase are out on the market now they are more selective they’re quite a bit more expensive and we’re just starting to get a feel for them over time

In terms of toxicity of allopuranol i think the problem the most commonly thing that we see is gastrointestinal upset we often see gi upset in low doses of allopurinol usage a rash vasculitis and peripheral neuritis are often seen i’ve had many patients who’ve developed rash on allopuranol a rare but very feared complication of allopurinol toxicity is aplastic

Anemia so if you start to see some abnormalities with your white counts and your red counts be very aware that your allopurinol may be inducing a serious disease with respect to the newer xanthine oxidase agents these agents can cause gastrointox gastrointestinal upset as well as liver function abnormalities and of course you can get a headache you

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[3] 06 Gout Medication Colchicine, Uric Acid and More By JP Educare