Clinical Observations of Side Effects

Massive doses of sulfanilamide, as well as of other sulfonamides, caused alkaline diuresis as a side effect. From 1940 onwards, the mechanism of this side effect was further investigated it was confirmed that carbonic anhydrase inhibition was responsible for the diuresis. Presenting the whole story of the development of 

In addition to the acceptable clinical side effects of many sulfonamides, some severe toxic effects were observed. In 1942, Marcel Janbon, the head of the medical faculty at Montpellier University, investigated an isopropylthiadiazole derivative of 

Sildenafil (Viagra , Pfizer), the first drug effective in male erectile dysfunction (MED), has a very interesting history. More than 30 years ago, the company May Baker started research on antiallergic xanthine derivatives [19]. Their first leads 27 

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Many drugs in the past resulted from experimental or clinical observation of side effects. 

In the early clinical trials of Pravadoline (248), the Sterling-Winthrop Research group observed CNS side effects. In an effort to circumvent these issues, indenes were explored as an alternative core [197]. The rationale behind this approach came from the observation that sulindac (308), an indene analogue of indomethacin (309), had anti-inflammatory properties comparable to (309) but without the CNS-associated side effects. 

The data on the adverse reactions of the fluoroquinolones which have received the most extensive clinical evaluation (ciprofloxacin, ofloxacin, pefloxacin, norfloxacin and enoxacin), involving about 30,000 patients, have been the subject of a review [54a], An important point noted in this review involves the difficulty in detecting an important severe adverse reaction if it is of relatively low frequency, until there has been a very large patient exposure (some examples are provided in which at least 150,000-300,000 exposures would be required to observe the importance of side-effects, resulting in an alert, which have been discovered with specific drugs). However, the majority of side-effects observed thus far with the fluoroquinolones have been minor,... 

According to Kuhn s observations, the effect of imipramine became apparent in some cases after a few days in other cases several weeks passed before any therapeutic effect could be seen. He estimated his failure rate at 20 25%, but regarded his sample as too small for any reliable estimate to be made. If the medicament was discontinued too soon, there was said to be a danger of relapse. It was also not possible to ascertain from his observations whether imipramine shortened the natural duration of the depressive phase. The best therapeutic successes were recorded in endogenous depression and in cases of depression which first appeared at the menopause, in cases where vital symptoms were clearly in the foreground". Kuhn also provided a comprehensive list of side effects of imipramine. which nevertheless in his view did not appreciably restrict use of the medicament. (None of the claims regarding the clinical pattern of action of imipramine made by Kuhn on the basis of open... 

As extensively reported in the other chapters, in millions of applications of local immunotherapies lethal side effects were not observed and severe side effects were extremely rare [27], However, it should always be our aim to reduce even low numbers and not severe side effects. It might be important to scientifically analyze the correlation of mucosal injuries with the severity of side effects, which was observed in clinical practice. 

If cholestasis is not present, the additional application of ursodeoxycholic acid (UDCA) is worth considering because of its pharmacological properties and lack of side effects or interactions. Initial results on the treatment of chronic hepatitis with UDCA were reported by F. IcHiDA (1961), T. Nakahara et al. (1975) and K. Miyaji (1976). (s. p. 705) In 1988 our study group also noted obvious and permanent effects of UDCA on the course of disease in terms of clinical and laboratory indices in severe acute viral hepatitis B. (s. p. 437) Such observations were confirmed by A. Jorge in 1993. Owing to the multiple mechanisms of action of UDCA, in particular its immunomodulatory effect, adjuvant therapeutic efficacy can be anticipated in autoimmune hepatitis, as reported by P. Janowitz et al. in 1996. In autoimmune-associated chronic hepatitis C, UDCA proved to be a successful therapeutic agent (K. Nakamura et al., 1999). 

The clinical observation of entirely unexpected side-effects constitutes a quasi-inexhaustible source of tracks... 

Continuing clinical studies of dlvlmlnol (II) have shown a favorable ccxnparlson with codeine In potency and lack of side effects. No tolerance development or narcotic side effects were observed. 

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