Antigout medications

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Introduction0:00–0:41

Antigout 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.
Antigout 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.

Physiology0:41–1:42

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 1.5-6 mg/dL for women and 2.5-8 mg/dL for men.
Urate crystal deposition occurs when concentration of circulating uric acid exceeds its rate of solubility, which is about 6.8 mg/dL.
Now, antigout 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 Meds1:42–2:25

Chronic gout medications include xanthine oxidase inhibitors, such as allopurinol and febuxostat; uricosuric medications, such as probenecid and sulfinpyrazone; and recombinant urate oxidases, such as rasburicase and pegloticase.
On the other hand, acute gout medications include non-steroidal anti-inflammatory drugs (or NSAIDs), glucocorticoids, and colchicine.
Alright, let’s start with xanthine oxidase inhibitors. Allopurinol is a purine analog that works by competitive inhibition of xanthine oxidase.

Allopurinol2:25–3:43

But, besides being an inhibitor, allopurinol is also a substrate; meaning that it’s converted by xanthine oxidase into its active metabolite called oxypurinol.
Moreover, oxypurinol which is also known as alloxanthine, is a non-competitive inhibitor of xanthine oxidase. This way, allopurinol and oxypurinol 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 allopurinol 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 allopurinol include gastrointestinal problems and rash. On the other hand, febuxostat is a non-purine inhibitor of xanthine oxidase and it’s reserved for individuals who can’t tolerate allopurinol.

Febuxostat3:43–4:37

Common side effects of febuxostat 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 (WBCs).
In order to prevent this, the dose of the immunosuppressive medication should be reduced when there’s concurrent use of allopurinol.
Let’s switch gears and shift our focus on to uricosuric medications like probenecid and sulfinpyrazone, which work by inhibiting renal tubular reabsorption of uric acid; thereby increasing its excretion.

Uricosuric Meds4:37–5:21

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, uricosuric 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 pegloticase and rasburicase. These medications are actually enzymes that oxidize uric acid to allantoin, which is a more-soluble product, therefore easier to excrete.

Recombinant Urate Oxidases5:21–6:07

For medicine-specific indications, pegloticase is used to treat chronic refractory gout; while rasburicase is used to treat tumor lysis syndrome in lymphoma and leukemia patients who are receiving anticancer therapy.
Common side effects include anaphylaxis, methemoglobinemia, and hemolysis in individuals with glucose-6-phosphate dehydrogenase (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.

Acute Gout Meds6:07–7:03

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.

Colchicine7:03–7:58

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’ll help you efficiently memorize and retain all these pharm facts! Let’s use a scene in a restaurant.

Memory Palace7:58–12:15

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 oxypurinol and allopurinol. Behind them is their boss who’s a fabulous fox, for febuxostat.
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 GI 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 the uricosuric 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 “pyro” zone for sulfinpyrazone. In the sink there’s a discarded pen and a spring, representing penicillin and aspirin, which clog up the drain, so they should not be used with uricosuric drugs.
Finally, the back door to the kitchen is where we keep the recombinant urate oxidase medications. So let’s have the restaurant owners be a pig and a raccoon, carrying briefcases.
These two represent pegloticase and rasburicase. For specific indications, the pig’s carrying a urate crystal for gout, while the raccoon’s 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 6 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 methemoglobinemia when using these medications, which results in chocolate colored blood, so let’s make the door a giant bar of chocolate.
Now let’s look at the treatment for acute gout in the dining area. 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 peta 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. Antigout medications are used to treat gout, which is a form of inflammatory arthritis caused by urate acid crystal build up in joints.

Review12:15–13:03

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 allopurinol and febuxostat, uricosuric medications like probenecid and sulfinpyrazone, and recombinant urate oxidases like rasburicase and pegloticase.
On the other hand, acute gout medications include non-steroidal anti-inflammatory drugs, glucocorticoids, and colchicine.
But wait, there’s more: Here’s a mind map with all of the mnemonics. Go ahead and pause the video so you can test yourself to see what you remember.

Mind Map13:03–13:13

Stay tuned for the answers after the credits.