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181.
A new type of ultra-short acting -blocker which might prove advantageous in treating acute arrhythmias was designed, synthesized and investigated. Based on the soft drug inactive metabolite approach, the inactive phenylacetic acid metabolite of both metoprolol and atenolol was reactivated by esterification with sulfur-containing aliphatic alcohols. Since the sulfur-containing moieties are labile to the ubiquitous esterases, the new compounds should be inactivated by a one step enzymatic cleavage back to the inactive phenylacetic acid derivative. Pharmacological and pharmacokinetic profiles of the new compounds were evaluated in rats and rabbits. Isoproterenol-induced tachycardia was inhibited with short-term infusion of each compound. This tachycardia blocking effect rapidly disappeared upon termination of infusion, while -blocking activity was 2–4-fold longer after comparable doses of the short-acting -blocker, esmolol. The rapid recovery from the -receptor blockade is believed due to fast hydrolysis of the soft drugs in the body. This is supported from in vitro results showing the tl/2 of esmolol is about 10-fold longer than the new soft drugs in rat, rabbit, dog and human blood. Hydrolysis studies in phosphate buffered solutions indicated that the esters are labile to base-catalyzed hydrolysis. However, the relative t1/2 values measured in biological media compared to phosphate buffered solution clearly support rapid enzymatic cleavage of the soft drugs. Interestingly, one of the soft -blockers, the sulfonyl ester derivative, showed a unique property of exhibiting good -receptor blocking activity without significant hypotensive action. 相似文献
182.
徐倍倍 《新疆医科大学学报》1999,22(4):285-287
目的:观察中药配合低能量氦-氖激光血管内照射为主治疗缺血性中风疗效。方法:治疗组:用中药配合低量氦-氖激光血管内照射为主治疗缺血性中风69例;对照组:用降纤酶、尼莫通治疗缺血性中风42 例。结果:治疗组基本痊愈48 例,显效8例,有效7例,无效5 例,恶化1 例,有效率为91.30% 。对照组基本痊愈20例,显效1例,有效9 例,无效11 例,恶化1例,有效率为71.43% 。经χ2 检验,χ2= 7.6,Ρ< 0.01,有显著差异。结论:治疗组中药配合低能量氦-氖激光血管内照射为主治疗缺血性中风综合疗效明显优于对照组用降纤酶和尼莫通治疗缺血性中风 相似文献
183.
RATIONALE AND OBJECTIVES: The authors evaluated the cardiac tolerability of paramagnetic contrast agents for magnetic resonance (MR) angiography in an in vitro model of ischemic rat heart. MATERIALS AND METHODS: The left anterior descending coronary artery was temporarily occluded in a perfused rat heart model to induce cardiac ischemia and reperfusion. A dose of 0.4 mL of gadobenate dimeglumine, of gadopentetate dimeglumine, or of D-mannitol was injected directly into the aorta both during the ischemia and during the reperfusion period. The left ventricular pressure and heart rate were recorded. RESULTS: Myocardial ischemia resulted in decreased cardiac activity, with a reduction in left ventricular pressure and heart rate. A further decrease in cardiac activity was temporarily induced by injection of contrast medium during both the ischemic and early reperfusion phases. Less marked responses were induced by a hyperosmolal solution of mannitol. CONCLUSION: These results suggest that the transient cardiac effects induced by bolus injection of paramagnetic contrast medium may be regarded as the combined effects of the osmotoxicity of the contrast medium solution and the chemotoxicity of the contrast medium molecule. 相似文献
184.
The long QT syndrome (LQTS) is associated with syncopal attacks or even sudden death at a young age due to ventricular fibrillation. We report a patient with an undiagnosed LQTS who had an episode of cardiac arrest during the final part of general anesthesia, immediately after the drugs for reversal of the neuromuscular blockade were given. We suggest that the administration of glycopyrronium might have been the provoking factor in this patient. 相似文献
185.
186.
Corsonello A Pedone C Corica F Malara A Carosella L Sgadari A Mauro VN Ceruso D Pahor M Carbonin P 《European journal of epidemiology》1999,15(10):893-901
We performed this case–control study to evaluate the risk of hypoglycemia associated with the use of antihypertensive drugs in older hospitalized diabetic patients treated with sulfonylureas and/or insulin. All diabetic patients admitted during 4 months in 1988, 1 month in 1991, 4 months in 1993 and 4 months in 1995 (n = 3477, mean age 71.4 ± 0.2 years, 1542 males and 1935 females) were enrolled in the study. During the four annual surveys 86 patients (mean age 71.1 ± 1.4 years, 33 males and 53 females) presented hypoglycemia during hospital stay. The patients who presented hypoglycemia were less frequently users of sulfonylureas and more frequently users of a combination of insulin and sulfonylureas. Use of antihypertensive drugs was similar in the two groups studied, and among potentially interacting drugs considered in the analysis, sulfonamides were more frequently used in patients who experienced hypoglycemia. Moreover, patients with hypoglycemia used a higher number of drugs, had a longer length of stay and had a greater prevalence of hypoglycemia as admission problem. Finally, although not significant, liver and renal diseases were more frequent among patients with hypoglycemia. In the multivariate analysis, contemporary use of insulin and sulfonylureas, liver disease and length of stay were significantly associated with hypoglycemia, while none of the antihypertensive drugs showed a significant association with the occurrence of hypoglycemia during hospital stay. Our results indicate that antihypertensive drugs do not increase the risk of hypoglycemia in elderly diabetic patients. 相似文献
187.
关于中医辛润法的理论思考 总被引:9,自引:0,他引:9
王殿华 《山东中医药大学学报》1999,23(3):169-172
探讨辛润源流,剖析辛味药物,指出辛味药在整体上不具备润养功效,不应与能散、能行相提并论。若把辛润理解为个别药物的润养作用,有失辛润之旨,更无法选药组方应用于临床。因此,当把辛润立之为法,即辛润法。燥证的发病机制,是外燥邪气、痰饮瘀血、气郁邪阻而致津血运行输布障碍,形体失却濡养。辛润机制,赖其辛味行散之功,宣肺祛邪,散饮化瘀,行气除滞,疏通腠理,布津行血而实现 相似文献
188.
Merlo J Lindberg G Lindblad U Lindgren A Råstam L Melander A 《European journal of clinical pharmacology》1999,55(1):69-76
Objective: To perform an ecological study in an effort to generate questions concerning the preventive impact of various cardiovascular
drugs on mortality from stroke and ischaemic heart disease (IHD) in the community, and to explore the association between
sales of nitrates and mortality from stroke and IHD.
Methods: Out-patient drug utilization (sales) of blood pressure lowering drugs, lipid lowering drugs and nitrates were categorized
in four groups of equal size by quartiles and compared with mortality from IHD and stroke, using the group of municipalities
with the lowest utilization as reference, from 1989 to 1993 in 283 of Sweden's 288 municipalities, by Poisson regression.
Adjustments were made for population size, age and gender proportions, the utilization rate of cardiovascular drugs other
than the tested drug group and location of the municipality.
Results: Compared with the group of municipalities with the lowest sales and adjusting only for population size, mortality from IHD
and stroke increased with the extent of utilization of blood pressure lowering drugs and nitrates. In contrast, mortality
decreased with increased utilization of lipid lowering drugs. After further adjustments by percentage of men, age structure,
geographical location (mid-points) of the municipalities, and, as a proxy for cardiovascular disease, the sales of cardiovascular
drugs other than the tested drug group, the increased risk associated with blood pressure lowering drugs disappeared, and
there was a dose-response association between sales of diuretics and old antihypertensives and decreasing mortality, sales
of nitrates continued to be associated with an increased risk, and the low mortality risk associated with sales of lipid lowering
drugs persisted.
Conclusion: Lipid lowering drugs may have a preventive impact in the general population, but the preventive impact of blood pressure
lowering drugs, with the exception of diuretics and old antihypertensives, may be low in many municipalities. The safety of
nitrates needs more investigation at the individual level.
Received: 16 April 1998 / Accepted in revised form: 10 November 1998 相似文献
189.
R. B. Dickson M. D. Johnson M. Maemura J. Low 《Breast cancer research and treatment》1996,38(1):121-132
Summary Most of the pharmaceuticals in clinical practice today for treatment of breast and other cancers are cytotoxic or cytostatic inhibitors of tumor growth. While this type of drug has found its place, along with surgery and radiotherapy, in treatment of disease, the breast cancer death rate has not decreased. This appears to be the result of rising incidence, resistance to therapy, and metastasis of the disease. Since distant metastasis (usually indicated by lymph node involvement) of breast cancer is related only indirectly to tumor size, it would appear that a concerted effort should be made to discover drugs which directly interfere with this complex process. Metastasis appears to depend upon tumor cell motility, dedifferen-tiation, local invasion, and angiogenesis. Significant progress has been recently made in the creation of new animal models of metastasis and in identifying several new drugs which may be suitable for clinical inhibition of this process. This article reviews current findings on anti-invasion/metastasis drugs with a focus on breast cancer.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb. 相似文献
190.
Background: The pharmacokinetic variables of drug clearance and volume of distribution are usually corrected for body weight
or surface area. Only recently have the relationships which exist between body size, physiologic function and pharmacokinetic
variables been evaluated in the obese population. These effects are not widely known, and data on this and the effects of
bariatric surgical procedures are scantily documented in the surgical literature. Methods: Literature review. Results: Drugs
with a low or moderate affinity for adipose tissue have a moderate increase in the volume of distribution (Vd), and this correlates
with the increase in lean body mass (LBM). Highly lipophilic drugs, with some exceptions, show the expected increase in Vd
and prolongation of elimination half-life, indicating a marked distribution into adipose tissue. Drug absorption, in general,
is slowed by delayed gastric emptying and is normal when gastric emptying is normal or increased. Most drug absorption occurs
in the small intestine where duration of drug/mucosal contact is the most important factor. Conclusions: Drugs whose distribution
is restricted to LBM should utilize a loading dose based on ideal body weight (IBW). For those drugs which distribute freely
into adipose tissue, the loading dose should be based on total body weight (TBW). Adjustment of the maintenance dose depends
on clearance rates. In a few cases dosage adjustment depends on pharmacodynamic data, since drug clearance does not conform
to these recommendations, for reasons which remain to be defined. Following bariatric surgery, in the absence of delayed gastric
emptying or uncontrolled diarrhea, drug absorption rates are usually comparable to the non-operated patient. 相似文献