Acetylsalicylic Acid (ASA)

00:00 Let's talk in detail about aspirin or ASA. ASA is your prototypical cyclooxygenase inhibitor and in fact it was probably one of the first drugs that was commercially available in the world.

00:13 Now COX-1 is found in non-inflammatory cells, and COX-2 is found in activated lymphocyte, polymorphonuclear cells and other inflammatory cells.

00:25 Aspirin reduces thromboxane and prostaglandin formation in the body. Aspirin irreversibly inhibits COX-1 and 2.

00:34 So, non-steroidal anti-inflammatory agents are reversible, aspirin is irreversible. And I'm gonna say this again because I want you to get that into your brain. Aspirin irreversibly inhibits COX-1 and 2.

00:46 Low-dose aspirin, less than 325 milligrams, works on platelet aggregation.

00:52 Medium dose aspirin, between 325 and 4000 milligrams a day, has antipyretic and significant analgesic effects.

01:01 In high doses, that's 4000 to 8000 milligrams a day; there is a strong anti-inflammatory effect.

01:07 Keep in mind these are not hard cutoffs, and there is overlap in the effects of low, medium, and high doses.

01:13 Additionally, the usual maximal dose of aspirin is 4500 mg per day due to the potential for toxicity.

01:20 However, some circumstances may require higher doses for limited periods.

01:24 I was hospitalized with pericarditis after my trip to the Amazon, and the thing that worked the best for me was 650 milligrams twice daily of aspirin.

01:34 It was a very effective anti-inflammatory agent, and I use it almost exclusively in severe inflammatory conditions like pericarditis.

01:43 Now, aspirin works quite well to reduce inflammation without reducing immunity. It does not effect regular tissues, which is why we like it so much. It reduces prostaglandin synthesis in the central nervous system, so that's why it has an anti-fever or antipyretic activity. It's also a great analgesic. We don't know why it works so well as an analgesic, but we know that patients who take aspirin, have reduced pain sensor activity through prostaglandin.

02:14 It may work through a central mechanism as well but we haven't quite figured that out yet. That's suprising considering the drug is a 180 years old. The drug has a half life of about 5 hours. And it's renally excreted. Now remember that type of kinetics that we were talking about. It's a first order kinetic drug at low doses, and zero order at high doses.

02:38 In terms of adverse events with aspirin, they are quite significant and we need to know them well.

02:43 In terms of the long duration treatment, we use it usually for antiplatelet activity, but it does cause an increased bleeding risk.

02:51 There is an increased level of GI toxicity. And that's because aspirin works to reduce gastric protection.

02:59 So in the stomach we release mucous to protect the lining of the stomach. Aspirin reduces that protective layer through prostaglandin and that's how you get more stomach ulcers because now the stomach acid is able to attack the lining of the stomach.

03:16 There is increased renal risk. Once again that is a prostaglandin mediated issue. So you can precipitate acute renal failure and one of the more common causes of interstitial nephritis is actually aspirin.

03:30 You can develop nasal polyps that are associated with hypersensitivity asthma exacerbations.

03:36 And a small drop in prostaglandin results in increased leukotriene synthesis. So you have to be aware of that seesaw action that I was talking about and aspirin's effect in it.

03:47 Now, the other adverse events that I want to talk about with respect to aspirin. At high doses, tinnitus is often seen.

03:56 Vertigo is a hallmark of aspirin toxicity. Hyperventilation is often seen because the patients are acidotic.

04:04 And you develop a secondary respiratory alkalosis. So by the time you usually see these patients in the emergency department they have developed a respiratory alkalosis. At exceedingly high doses, these are patients who have ingested bottles of aspirin, you'll see dehydration, hyperthermia, that's high temperatures, cardiovascular collapse, metabolic acidosis, coma, seizure, death.

04:31 Reye's syndrome is a syndrome that we actually don't see anymore. It's a progressive encephalopathy and liver degeneration that we saw in children who are exposed to aspirin. Aspirin consumption with a viral illness in age 4 to 12, was routinely treated with aspirin when I was a child, and so lots of kids were hospitalized with Reye's syndrome in the 60s and 70s.

04:55 Now that we know about Reye's syndrome, we actually say that aspirin is contraindicated in children, and the old children is now given to adults as 81 milligram aspirin for platelet protection.