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Drugs and Therapeutics
Published in James Sherifi, General Practice Under the NHS, 2023
Prescribed simple antacids were largely made redundant following the introduction of the H2 antagonists. Cimetidine—1976Gastro-Oesophageal Reflux Disease, Peptic Ulcer Introduced in 1976, cimetidine (Smith, Kline & French) became the first blockbuster drug to achieve sales of over US$1 billion per annum, only relinquishing that position ten years later to another H2 antagonist, ranitidine (Glaxo Wellcome, 1981).
Prevention of the Spread and Recurrence of Cancer by Coumarins and Fibrinolytic Agents
Published in László Muszbek, Hemostasis and Cancer, 2019
Cimetidine is a histamine antagonist used in the treatment of peptic ulceration. It has been shown to affect the cellular immune system by lowering suppressor/cytotoxic T lymphocytes. Three patients with advanced melanoma on treatment with coumarin for several months were given cimetidine in addition, and there was a dramatic reduction in tumor within 7 days. The next patient, however, when cimetidine and coumarin were started simultaneously, had a rapid enhancement of tumor growth.33 Five more patients on long-term treatment with coumarin (100 mg daily) were given cimetidine (1000 mg daily) and only one patient responded. She had an absolute lymphocyte count of 3.86 × 109/ℓ (T cells 46%, helper cells 27%, suppressor/cytotoxic cells 20%) prior to cimetidine. After 2 weeks her absolute lymphocyte count had fallen to 1.94 × 109/ℓ (T cells 57%, helper cells 40%, suppressor/cytotoxic cells 18%). Three of the nonresponding patients had low lymphocyte counts below 0.9 × 109/ℓ and low suppressor/cytotoxic cell levels. The remaining patient who failed to respond had cerebral metastasis. Cimetidine given alone to seven other patients with melanoma was ineffective. It appears that the immune system needs to be primed by coumarin and only if suppressor cells are raised could cimetidine be expected to produce a response. The most interesting feature of the tumor reduction was its rapidity without toxicity. The mechanism needs to be further elucidated, but an immunological pathway would seem most likely.
Rheumatic disorders
Published in Anne Lee, Sally Inch, David Finnigan, Therapeutics in Pregnancy and Lactation, 2019
As many as 30% of long-term NSAID users develop gastric or duodenal ulcers.31 The preferred drug for treatment or prophylaxis in pregnancy is ranitidine. Literature reports suggest that cimetidine has anti-androgenic effects in animals and although no problems in human pregnancy are known, its use cannot be recommended. Misoprostol should also be avoided in pregnancy. It can cause uterine contractions, and malformations have been reported following its unsuccessful use as an abortifacient.32–36 There is insufficient information on omeprazole or other proton pump inhibitors to recommend their use in pregnancy.
Verification of a cocktail approach for quantitative drug–drug interaction assessment: a comparative analysis between the results of a single drug and a cocktail drug
Published in Xenobiotica, 2021
Motoyasu Miura, Shinya Uchida, Shimako Tanaka, Chiaki Kamiya, Naoki Katayama, Akio Hakamata, Keiichi Odagiri, Naoki Inui, Junichi Kawakami, Hiroshi Watanabe, Noriyuki Namiki
The cocktail study had an open-label, single-sequence design, and was divided into four phases: a control phase, a rifampicin phase, a cimetidine phase, and a fluvoxamine phase. Each phase was separated by a washout period of at least 2 w. During the control phase, subjects were simultaneously administered five probe drugs as the cocktail drug. Caffeine 100 mg (caffeine; Mylan, Tokyo, Japan), losartan 25 mg (Nu-Lotan; MSD, Tokyo, Japan), omeprazole 20 mg (Omepral; AstraZeneca, Osaka, Japan), dextromethorphan 30 mg (Medicon; Shionogi, Osaka, Japan), and midazolam 15 µg/kg (Dormicum; Astellas Pharma, Tokyo, Japan) were used as reported by Inui et al. (2013). During the rifampicin phase, subjects were administered rifampicin 450 mg (Rifadin capsules, Daiichi Sankyo, Tokyo, Japan) once a day in the morning for 6 d until the day before the study. During the cimetidine phase, the subjects were administered cimetidine 400 mg (Tagamet tablet, Sumitomo Dainippon Pharma, Tokyo, Japan) twice a day before the cocktail study, morning and evening. On the day of the cocktail study, the subjects were administered cimetidine with the cocktail drug. During the fluvoxamine phase, fluvoxamine 25 mg (Depromel tablet, Meiji Seika Pharma, Tokyo, Japan) was administered on the same administration schedule as for the cimetidine phase.
Pharmacological treatments for functional nausea and functional dyspepsia in children: a systematic review
Published in Expert Review of Clinical Pharmacology, 2018
Pamela D. Browne, Sjoerd C. J. Nagelkerke, Faridi S. van Etten-Jamaludin, Marc A. Benninga, Merit M. Tabbers
H2RAs have been shown safe and effective in adults with FD [69]. However, to date, there is limited evidence to support the efficacy H2RAs in children with upper gastro-intestinal complaints [70]. Additionally, a previous study in children with GERD found that the use of H2RAs was related to more adverse events (i.e. gastroenteritis and pneumonia) compared with PPI use [60,71]. Other side effects reported in children due to H2RAs include irritability, headache, anorexia, somnolence, and headache. Particularly cimetidine may cause side effects, because of an increased risk on multiple drug interactions and interference with endocrine functioning [72]. By selectively blocking the histamine-2 receptor in the parietal cells, H2RAs decrease the production of gastric acid and pepsin and consequently increase gastric pH [73].
The inhibition of first-pass metabolism of ethanol by H2-receptor antagonists: a tabulated review
Published in Expert Opinion on Drug Safety, 2018
During the period from 1982 to 2000 several clinical studies were conducted to test whether H2-receptor antagonists could inhibit the metabolism of ethanol to such an extent that co-ingestion would produce a significant increase in the blood alcohol concentration (BAC) that a user of ethanol may unknowingly reach an illegal BAC. In general, it was found that only a slight increase in BAC, no more than 3–7 mg/dL, occurred, that this was mostly observed in postprandial conditions and only with low doses of ethanol (0.15–0.30 g/kg) [1–5]. At the time of these studies, there was considerable controversy over whether this would pose a risk for increasing a person’s BAC sufficiently to exceed limits associated with driving under the influence (DUI). Cimetidine was the prototype of H2-receptor antagonists that include ranitidine, famotidine, and nizatidine. While cimetidine, ranitidine, famotidine, and other H2-receptor antagonists use to treat ulcers has been reduced since the introduction of proton pump inhibitors, they are also used to treat other conditions that increase stomach acid and gastroesophageal reflux disease. Ranitidine (49) and famotidine (127) were on 2018 list of the top 200 drugs (http://clincalc.com/DrugStats/Top200Drugs.aspx).