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• W2016514351 abstract "To The Editor: Various pharmacologic aspects of aging were recently reviewed (1). Other recent papers have appeared dealing exclusively with the clinical problems of drug therapy in the geriatric patient (2, 3). This communication is presented as a brief extension of the observations made previously (1). Because of the extensive use of the double-blind technique of drug evaluation, the literature was searched for possible clues as to the degree of placebo reactions exhibited by elderly patients as compared with younger adults. Lasagna et al. (4), in a study of postoperative patients, found that the mean age of the placebo reactors was five years more than that of the nonreactors. On the other hand, Tibbetts and Hawkings (5) found placebo reactors to be generally younger than nonreactors, and Gliedman et al. (6) observed no age differences between two such groups in their study. The subject of placebo reactions and reactors has recently been reviewed by Honigfeld (7). Ayd reported that extrapyramidal reactions occur more frequently in older patients receiving phenothiazines (8). Earlier, however, Freyhan (9) found that in a series of hospitalized patients treated with either chlorpromazine (541 cases) or reserpine (112 cases) the parkinsonism induced by these drugs was totally unrelated to the particular age levels. Thus he concluded that the development of parkinsonism cannot be connected with the aging process, which favors the development of paralysis agitans. Ayd (10) concluded that the phenothiazines may be used in the ambulatory geriatric patient with a minimum of risk. The effect of epinephrine on the blood nonesterified fatty acid level (NEFA) in rats aged 60, 140, 360 or 720 days has recently been studied (11). The rise in NEFA concentration following intraperitoneal doses of epinephrine was greatest in the youngest age group, and became smaller with increasing age. Incubation of adipose tissue with epinephrine in vitro showed that the youngest age group (60 days) released more NEFA than did the older groups; no differences, however, were found between the three older age groups. It may be concluded that the difference in metabolic responses of rats of different ages to epinephrine, as determined by NEFA release, is due in the early growth period to changes in the adipose tissue itself. Between adult and old rats the difference in NEFA blood levels in response to epinephrine must be attributed to other factors, perhaps changes in blood supply, cell permeability or endocrine-metabolic regulation. In order to assess the consequences of overactive functioning of the parasympathetic nervous system, Hall et al. (12) treated young and old dogs with 50 mg of acetylcholine daily. Clinical evidence of progressive myocardial failure with subsequent death was noted in every animal. However, permanent damage to the heart occurred in all of 4 old dogs, but in only 2 of 4 young dogs. Severe gastrointestinal symptoms—retching, vomiting and diarrhea—were observed in the 4 young dogs, and at autopsy there was very severe congestion of the mucosa of stomach and duodenum. In the old animals no diarrhea was produced, and at autopsy very little congestion was evident. An excess of nitroglycerin administered to the older person may lead to syncope; thus it is especially important to give this agent in small amounts (13). From recent studies it appears that nitroglycerin exerts its beneficial action in relieving the pain of angina, through a reduction in cardiac work rather than the previously supposed elevation in coronary flow (14–16). The reduction in work is achieved through a primary lowering of cardiac output and arterial blood pressure. Thus the efficacy (reduction in work) and side effects (fainting, syncope) resulting from nitroglycerin therapy appear to be linked to the same mechanism, namely, a reduction in venous return. Since the older patient probably responds to a given dose with a greater reduction in work, a reduction in the dose will not compromise the efficacy usually achieved, but should decrease the incidence of secondary effects. Several reports have appeared which deal with the responses of animals of different ages to various hormones. Recently Lohmann and Bock (17) observed that the increase in blood sugar concentration induced by glucagon is reduced as age increases. In addition, in younger patients, the blood sugar level returns to normal earlier than in middle-aged and old patients. These results are consistent with the fact that insulin secretion gradually decreases with age. In weanling, in young adult, and in adult male rats, Smith (18) found that daily cortisone administration resulted in decreased body weight and impaired cutaneous collagen and hexosamine metabolism in each of the three age groups. Differences in the responses of young adult and adult animals were not evident until after fourteen days of treatment, at which time the younger animals exhibited a greater response. Farner (19) evaluated the stimulatory action of two synthetic oxytocin preparations on the surviving uterus of young rats aged 4–5 months and old rats aged 25–26 months. In most cases the uteri of the older rats exhibited spontaneous rhythmic contraction, whereas those of young animals showed none. In the old animals, the oxytocin preparations induced nearly twice the excitation induced in the young animals. It was concluded that the excitability of the uterus for synthetic oxytocin increases with age. The Silberbergs (20) gave estradiol benzoate in a dosage of 0.03 mg per week to growing young adult mice and to old mice (males) for five months. In the younger animals the hormone inhibited the development of articular disease, whereas treatment late in life did not modify the course of the articular lesions. The results suggest that the inhibiting effect of the injected estrogen is exercised through counteracting endogenous testosterone, but it may be due in part to a direct effect on the articular cartilage. With respect to chemotherapeutic agents, Broich and Petzold (21) found no significant change in the absorption and excretion of isoniazid and p-amino-salicylic acid between tuberculous patients less than 30 years old and those more than 60 years old; variability, however, was greater in the older patients. When both groups of patients were given a combination of both compounds, blood levels fell more slowly in the older age group. It was concluded that the dose could be reduced in older patients without reducing blood concentrations. These results are again consistent with the general conclusion that with increasing age the sensitivity to drugs increases with respect to some primary activities and most secondary activities, and that in a few instances the response to a primary activity may be enhanced. It is rare that the tolerance to a secondary activity is increased in the elderly. In this context the term primary refers to activity for which the use of the drug is indicated; secondary is used to describe activities which are usually grouped as side effects. These observed alterations in drug action are reflections of one or more physiologic and pathologic changes which accompany advancing age. Briefly these changes involve 1) absorption; 2) distribution, e.g., cell permeability, tissue blood supply or tissue fat content; 3) metabolism, i.e., detoxication; 4) renal and biliary excretion of the drug; 5) alterations in tissue sensitivity due to a decrease in the number of active cells, pathologic lesions and loss of enzyme substrates or endogenous mediators; and 6) loss of homeostatic mechanisms, resulting in a decreased adaptability to drug-induced changes which is manifested as a decreased tolerance to drugs." @default.
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• W2016514351 date "1964-12-01" @default.
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• W2016514351 title "PHARMACOLOGIC ASPECTS OF AGING: FURTHER OBSERVATIONS" @default.
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• W2016514351 doi "https://doi.org/10.1111/j.1532-5415.1964.tb00677.x" @default.
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