In this episode, we dive into the story of aspirin and the development of ibuprofen, ending with the experiments that showed the mechanism of how aspirin actually works.

• Intro 0:12
• Review of part 1 0:28
• In this episode 1:04
• Blocking prostaglandins and willow leaves 2:26
• Edward Stone 3:45
• Johann Andreas Buchner 4:16
• The chemical structure of salicylic acid and creating the synthetic compound 4:44
• Dr. TJ MacLagan: The first trial in 1876 and treating acute rheumatism 5:16
• Felix Hoffmann: manipulating salicylic acid and aspirin 8:47
• How widespread was the use of aspirin for rheumatoid arthritis? 12:04
• 1938: problems with aspirin and endoscopies 14:58
• 1950s: long-term use of aspirin and chronic renal impairment 17:12
• Dr. Lawrence Craven: the use of aspirin to treat myocardial infarction 18:13
• Overview of what we've learned so far 20:48
• Stewart Adams: the development of ibuprofen 21:40
• A paper lost to time 23:29
• How do you test if a drug is anti-inflammatory? 25:25
• How do you make better aspirin? 26:55
• 1960: a trial comparing ibuprofen, baby aspirin and prednisone in patients with rheumatoid arthritis 30:03
• Aspirin, ibuprofen and other NSAIDs 32:49
• Nobel Prize winner Dr. John Vane 33:40
• Dr. Vane: what triggered prostaglandin production? 35:42
• Another guinea pig experiment 37:37
• Nobel Prize winner Dr. Bengt Samuelsson 39:00
• Interesting tidbits: early studies looking at the side effects of NSAIDs 40:01
• 1968: gastric ulcer formation and prostaglandins in rats 40:25
• 1973: renal blood flow and prostaglandins in dogs 41:53
• 1974: aspirin vs ibuprofen vs indomethacin for the heart 44:03
• Aspirin vs ibuprofen vs indomethacin 44:20
• On the next episode 46:09
• Thanks for listening 46:37

We'd love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum.

References:

Adams SS. Inflammopharmacology. 1999;doi:10.1007/s10787-999-0002-3.

https://www.aspirin-foundation.com/history/the-aspirin-story/.

Buchanan WW, et al. J Rheumatol. 2002;29(6):1321-3.

Cryer B, et al. Gastroenterology. 1999;doi:10.1016/s0016-5085(99)70545-7.

Desborough MJR, et al. Br J Haematol. 2017;doi:10.1111/bjh.14520.

Halford GM, et al. Platelets. 2012;doi:10.3109/09537104.2011.632032.

Harris SC, Fosdick LS. Theoretical considerations of the mechanisms of antipyretic analgesia. NWU Bull. 1952;53: 6–9.

Jasani MK, et al. Ann Rheum Dis. 1968;doi:10.1136/ard.27.5.457.

Robert A, et al. Gastroenterology. 1968;55(4):481-7.

Disclosures: Brown reports no relevant financial disclosures.