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 rheuminationspodcast@healio.com. 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.