HISTORY OF MEDICINE
Year : 2018 | Volume
: 16 | Issue : 4 | Page : 161--163
A brief history of some medications used in modern medicine
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. A brief history of some medications used in modern medicine.Curr Med Issues 2018;16:161-163
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. A brief history of some medications used in modern medicine. Curr Med Issues [serial online] 2018 [cited 2020 Feb 21 ];16:161-163
Available from: http://www.cmijournal.org/text.asp?2018/16/4/161/256322
Source: CMC Pharmacy Bulletin, a Publication of the Pharmacy Service (DISH), CMC, Vellore.
In the 1800s, cocaine became the first substance to be identified to possess local anesthetic properties. The German Chemist Albert Niemann was the first to isolate cocaine from coca leaves brought to Europe from South America in the mid-1800s. In 1884, Carl Koller, an ophthalmologist, experimented using cocaine as eye drops during ophthalmic procedures and subsequently published his findings. Soon after, cocaine was widely embraced as a local anesthetic throughout Europe. As the medical use of cocaine geared up, however, it is undesirable effects became noticeable. The psychoanalyst Sigmund Freud, who had been using cocaine on his patients, himself became addicted to cocaine. Because of the negative effects of cocaine, a need for a safer local anesthetic arose.
Albert Einhorn, a Chemist from the University of Munich who proposed a chemical structure for cocaine in 1892, also synthesized several aromatic compounds imitating cocaine. He was unsuccessful in his attempt to reduce the benzene ring to obtain his desired cyclohexane derivatives which he thought will solve the problems with cocaine. Rather than abandoning all the aromatic compounds he synthesized, Einhorn reasoned that as cocaine and some of its active analogs were benzoyl esters, it would be worthwhile to test them in patients. He sent material to his former colleague Robert Heinz, who had moved to the University of Erlangen. To his surprise, several of his esters turned out to be effective, and this was the indication of useful local anesthetic activity in synthetic compounds. Einhorn continued his research in making esters and sent for initial screening by Biberfield at the Pharmacological Institute in Breslau. One of his esters was most promising, which he later named as procaine. In 1905, Einhorn et al. reported their discovery of procaine, an ester-based synthetic local anesthetic. Subsequently, procaine was sent to Heinrich Braun for clinical evaluation. It was found to be significant but with less duration of action. However, Braun combined Einhorn's procaine with the newly introduced adrenaline and overcame the problem of its short duration of action and first marketed as Novocaine. Procaine was immediately accepted as a safe substitute for cocaine. Its safety, lack of irritancy, and overall efficacy with adrenaline ensured that it dominated the field of local anesthesia for half a century. The discovery of procaine is considered to mark the beginning of the modern era of regional anesthesia.
Johnson S. Cocaine to Procaine: An Unexpected History Of Local Anaesthesia. Biomed J Sci&Tech Res 7(2)- 2018. BJSTR.MS.ID.001467. DOI: 10.26717/ BJSTR.2018.07.001467.Sneader W. Drug Discovery: A History. John Wiley & Sons; 2005. p. 484.Local Anesthetics in Dentistry. PDF. [Internet]. [cited 2018 Nov 17<http://www.endoexperience.com/filecabinet/Clinical%20Endodontics/Anesthesia/Local%20Anesthetics%20in%20Dentistry.pdf>.Hadda SE. Procaine: Alfred Einhorn's ideal substitute for cocaine. J Am Dent Assoc 1962;64:841-5.
Hans Meyer and Josef Malley did not know that the molecule they synthesized as part of their doctoral thesis in 1912 was going to be a blockbuster treatment for tuberculosis (TB). Contemporarily, only streptomycin was used to treat TB. For over 40 years, the molecule isoniazid (INH) synthesized by Meyer and Malley was almost forgotten. The antitubercular activity of INH was accidentally discovered during a random screening of drugs in mice infected with tubercle Bacilli. In 1951, it was demonstrated simultaneously and independently in three different laboratories including Bayer, Squibb, and Roche that INH had a high degree of antituberculous activity bothin vivo and in vitro. Immediately after, both Squibb and Roche started clinical investigation of INH in the US. Clinical trials also proved the efficacy of INH. Roche marketed INH as Rimifon in 1953. On clinical use, the psychostimulative side effect of INH became evident. This side effect of INH pointed its probable use in psychiatry as an anti-depressant drug. An animal experiment also showed the mood-elevating effect of INH. Nathan Kline, a psychiatrist at New York, began a clinical trial of INH and published his positive findings in 1957. A year later, the drug was brought to the market as an anti-depressant drug, even though it had been given to over 400,000 depressed patients by that time.
Before that, only streptomycin was used for TB, but the development of resistance lowered its effectiveness. However, the discovery of INH established a combination drug regimen necessary for effective treatment against TB. The combination of streptomycin, INH, and p-aminosalicylate allowed the successful treatment of TB. After 70 years of its discovery, INH is still employed as a first-line treatment of TB.
Verma AK, Kalra OP. Discovery of new drugs against tuberculosis: History guides. Arch Clin Infect Dis 2012;7:109-12.Isoniazid Medicine, Health, and History. [Internet]. [cited 2018 Dec 19] <https://adoseofhistory.com/tag/isoniazid/>.McDermott W. The story of INH. J Infect Dis 1969;119:678-83.
More than two billion people (about one-third of the world population) are estimated to be infected with Mycobacterium tuberculosis. Prompt diagnosis of active TB facilitates timely therapeutic intervention and minimizes transmission. Goals of TB treatment include eradication of M. tuberculosis infection, preventing transmission, preventing relapse of disease, and preventing the development of drug resistance. First-line drugs include INH, rifampicin, pyrazinamide, and ethambutol. Most patients receive 6 months of treatment (intensive phase of 2 months and continuation phase of 4 months).
Rifampicin is well tolerated but can induce hepatotoxicityIdeally, taken on an empty stomach to ensure complete absorptionThe usual dose is 10 mg/kg once daily.
INH is generally well toleratedIdeally, taken on an empty stomach (improve absorption)INH tablets may be crushed and mixed with palatable food to improve adherenceThe usual dose is 5 mg/kg once dailyAdverse reactions include hepatitis, gastrointestinal (GI) disturbances, peripheral neuropathy, and skin rashesMonitoring of liver function is recommended.
Used during the initial phase of therapy (generally, the first 2 months of treatment)The usual dose is 20–30 mg/kg once dailyThe dose may need adjustment with renal or hepatic dysfunctionAdverse effects include hepatotoxicity, GI intolerance, polyarthralgia, and hyperuricemiaBaseline and periodic monitoring of liver function is recommended.
Used during the initial phase of therapy ( first 2 months)The usual dose is 15–20 mg/kg once dailyOptic neuropathy is the most important toxicityEthambutol is generally not known to induce hepatitis
Reference: Antituberculous Drugs: An Overview – UpToDate. [Internet][cited 2018 Dec 22].<https://www.uptodate.com/contents/antituberculous-drugs-an-overview>