Advances in Pharmacology by Silvio Garattini and Parkhurst A. Shore (Eds.) PDF
By Silvio Garattini and Parkhurst A. Shore (Eds.)
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Histopathology. , 1961) indicates that a t least 13, but usually 16-20 or more, different organs are prepared for histological evaluation. This represents a very extensive effort and attests to the high importance of the morphological method for the final judgment of drug safety. Experience has shown that most of the organs usually are unchanged. Thus, in order to save part of the expensive technical work, i t is permissible to restrict the preparation and evaluation of slides initially to the tissues of animals treated with the highest dose, together with 25-50% of the controls.
Most of the work rcported in the literature deals with acute drug effects, such as LD,,,, conJTulsive, and hypnotic action. , 19591. Froin this, one niuy conclude that c h g a could \,e inore 1l:tngerous in warm diniates, mi 01)servation which is certainly true for atropine and other :~iitirIiolincrgic~. 42 GERHARD ZBINDEN It has d s o been found that acute exposure to low teiiipersture may increase drug toxicity (Setnikar and Temelcou, 19621. , 1961). If high doses of kanamycin or bacitracin are administered twice daily for 9 days to rats, a mild degree of nephrocalcinosis is seen in 40% of the animals.
Route and frequencp of drug administration. Compounds should be administered by the same route as projected for the therapeutic use in humans. If a drug is to be tested both orally and parenterally, the parenteral toxicity trial can often be shortened to about one-third of the oral study. Repeated injections of large amounts of a drug often cause severe tissue irritation and obliteration of the veins. ) route, and if a drug is very irritating, the experiment should be terminated before chronic peritonitis or subcutaneous necrosis cause severe, nonspecific damage to blood and tissue.
Advances in Pharmacology by Silvio Garattini and Parkhurst A. Shore (Eds.)