Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tacrine was initially synthesised in 1945 as part of a project seeking antibacterial drugs to treat infected wounds in soldiers. However, it was inactive in vitro against common strains of bacteria. Serendipitously, it was injected in vivo into dogs anaesthetised with chloroform and morphine and noted to immediately counter the respiratory rate depression caused by morphine but not block analgesia. Subsequent studies showed that tacrine was an acetylcholinesterase inhibitor. When combined with morphine in ampoules it was possible to inject larger doses of morphine without causing respiratory depression and it was marketed for 10 years in Australia. Tacrine was also used alone for treating acute anticholinergic syndrome in the 1980s. Shortly after this, it was hypothesised by William Summers that it could be of benefit in treating the early stages of Alzheimer's dementia and an IND was granted by the US Food and Drug Administration and a use patent awarded to Summers. It was the first of four anticholinesterases to be approved for treating this condition although its variable pharmacokinetics was a disadvantage.
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PMID:Tacrine: In vivo veritas. 2804 May 33

Background The United States Civil War (1861-1865) pitted the more populous industrialized North (Union) against the mainly agricultural slaveholding South (Confederacy). This conflict cost an enormous number of lives, with recent estimates mentioning a total mortality greater than 700,000 combatants [1]. Although sulfuric ether (ETH) and chloroform (CHL) were available since Morton's use of the former in 1846 and the employment of the latter in 1847, and even though inhalational agents were used in Crimean war (1853-1856) and the Mexican-American War (1846-1848), the United States Civil War gave military surgeons on both sides the opportunity to experience the use of these two agents because of the large number of casualties. Methods Research of historic archives illustrates the dramatic control of surgical pain made possible with introduction of two general anesthetic and analgesic drugs in 1846 and 1847. Results An appreciation of the importance of anesthesia during surgical procedures can be noted in the poignant and at times hair raising cases of two left arm amputations carried out under appalling circumstances during the United States Civil War. In the first-case the amputation was delayed for nearly five days after the wounding of Private Winchell who served in an elite sharpshooter brigade and was captured by the Confederate Army during battle. The amputation was performed without anesthesia and the voice of the Private himself narrates his dreadful experience. The postoperative course was incredible as he received no analgesia and survived a delirious comatose state lying on the ground in the intense summer heat. Thomas Jonathan "Stonewall" Jackson was a famous ascetic Confederate General who helped defeat the Union forces at the Battle of Chancellorsville on May 2, 1863. In the ensuing near-darkness, Jackson was fired upon by his own friendly troops where he suffered multiple gunshot wounds on his right hand as well as a ball in the upper humerus of the left arm similar to that of Private Winchell. Transported to a field hospital about thirty miles away, the evacuation was carried out under artillery fire and the General dropped from the stretcher at least twice before arriving at the field hospital. There, a team of surgeons operated on "Stonewall", using open drop chloroform, the surgery taking 50 min, anesthesia times of one hour with General Jackson awake and speaking with clarity shortly after the termination of the anesthesia. A brief explanation of the use of anesthetics in the military environment during the Crimean, Mexican American and the United States Civil War is also presented. Conclusion and implications Two case stories illustrate the profound improvement in surgical pain made possible with ether and chloroform only 160 years ago. Surgeons and patients nowadays have no ideas what these most important improvements in modern medicine means, unless "reliving" the true hell of pain surgery was before ether and chloroform.
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PMID:In praise of anesthesia: Two case studies of pain and suffering during major surgical procedures with and without anesthesia in the United States Civil War-1861-65. 2991 23

The administration of chloroform by John Snow to Queen Victoria to provide analgesia for the delivery of her children was a pivotal moment in the development of anaesthesia. It has long been thought that this was the only occasion she had experienced anaesthesia but examination of her diaries shows this to be untrue.
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PMID:A non-obstetric exposure to chloroform for Queen Victoria. 3329 55


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