Side clinical observation

The cephalosporins generally cause few side effects (80,132,219—221). Thrombophlebitis occurs as a result of intravenous administration of all cephalosporins. Hypersensitivity reactions related to the cephalosporins are the most common side effects observed, but these are less common than found with the penicillins. Clinically only about 5—10% of patients with allergic reactions to the penicillins manifest the same reactions to the cephalosporins, and data would contradict any tme cross-reactivity to cephalosporins in patients who have previously reacted to penicillin (80,132,219). 

After completing preclinical testing, a company files an Investigational New Drug (IND) application with the regulators (the FDA in the U.S.), so that clinical studies in man can begin. The IND shows results of all experiments to this point, a detailed proposal for the clinical study, the expected mode of action for the drug, and any side effects observed. All clinical trials will also be reviewed and approved by the Institutional Review Board (IRB) at the clinic where the trials will be run. 

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,... 

Even though it is currently unclear whether any of the side effects observed in the clinic with the current pan-HDAC inhibitors are hnked to inhibition of the class-II HDACs, these observations, nevertheless, triggered the quest for HDAC isotype specific inhibitors, which will be further discussed below. 

Screening hundreds of compounds against 80-100 targets/year is an expensive research endeavor Ho vever, it is one of the crucial parts of predinical safety assessment and is also required by regulatory authorities [9]. Beside a better understanding of compound bioactivity profiles, which in some cases can be reliably linked to clinically observed side effects, there is also a particular aspect of the generated data which makes it worthwhile to be analyzed in more detail. 

The antiviral and antiproliferative effects of individual IFN-a subspecies differed from buffy-coat IFN-a [30,31]. Unlike recombinant purified IFN-a2, which is species specific, buffy-coat huIFN-a has broad species effects, producing responses in humans, bovines, and felines. The clinically observed side effects of purified recombinant IFN-a2 and naturally produced buffy-coat IFN, however, were noted to be similar [32,33]. 

The application of allergoids is a promising idea to reduce side effects by the prevention of IgE binding to the full allergen, but the role of fragments other than the symptom-inducing epitope in sensitization and desensitization is still an open question. The first clinical observations on sublingual application are... 

Extensive media coverage in the 1990s made the public aware of Prozac and greatly increased the demand for the drug. Some people got the impression that it had no side effects, helped in weight loss, and was a sort of happy pill that everyone should take. But neither this nor the other SSRI drugs improve mood or make healthy people high or happier if they are not clinically (observed symptoms) depressed. 

Here I should like to touch on a more speculative side of the research. We had to face up to the strong evidence at the molecular level that the platinum drug produced a lesion on the DNA of cells, which did not necessarily lead to cell death, and in any case, was not restricted to cancer cells alone, and the final clinical observation that the cancers disappeared in the animal, without unacceptable side effects. There is a wide gap between molecular biology and clinical results. Could we bridge some or all of it with testable hypotheses ... 

Consistent with my own clinical observation that neuroleptics worsen Alzheimer s disease and other dementing disorders, Bonelli et al. (2005) warned that individuals with Alzheimer s disease are even more vulnerable to neuroleptic-induced cell death. The researchers stated, A limit on the use of first- and second-generation antipsychotics in elderly patients is proposed. Finally, they saw a possible connection between the observed increased cerebral cell death and tardive dyskinesia, the most threatening side effect in antipsychotic therapy. ... 

The side effects observed in the clinic with the early 100% and 90% w/v concentrated PFOB formula-tions and with Oxyfluor consisted of early effects, during or shortly after infusion, including headache and occasional lower backache, and delayed effects (2-12 h), referred to as flu-like symptoms e.g., fever, occasional chills and nausea.These reactions, generally categorized as mild, were transient and fully reversible within 4-12 h. A transient, moderate drop (about 15%) in platelet count was seen about 3 days after dosing. Similar effects have been documented for parenteral fat emulsions and liposomes, indicating that these effects were likely related to the particulate nature of the emulsion. 

Topical eflornithine has a very good safety profile. The only side effects observed in the clinical trials at a higher frequency than placebo were related to skin irritation and included stinging or burning skin and rash at the site of application. 

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