Blood pressure and heart rate and withdrawal of antihypertensive drugs.

The immediate effects on heart rate and blood pressure of withdrawing antihypertensive drugs were studied over three-day periods in 26 patients. Four groups of drugs were studied. After withdrawal all patients taking clonidine showed a considerable increase in heart rate and blood pressure with intense ectopic activity. Patients taking postganglionic neurone-blocking drugs showed a similar but less pronounced reaction with increased ventricular ectopic activity. No alarming reactions were seen after withdrawal of methyldopa or beta-blocking drugs. Methyldopa and, especially, beta-blocking drugs are less likely to produce withdrawal reactions than clonidine or the postganglionic neurone-blocking drugs, and patients taking these drugs are therefore less likely to suffer violent reactions if they forget to take their tablets.     

TREATMENT OF ALCOHOLISM—Problems Arising from the Substitution of Other Drugs in Therapy

Of the 139 patients admitted to hospital for chronic alcoholism, 32 had been taking other drugs also, and 17 were addicted to the drugs. Of the 32 patients, 16 used barbiturates, and 8 were addicted. Five took large amounts in suicidal attempt.Ten patients combined still other drugs with alcohol and barbiturates; and seven of them were addicted to barbiturates. Of the six patients combining alcohol with drugs other than barbiturates, two were addicted to the use.Of the 16 patients who used drugs other than barbiturates, eight used one or more opiates such as meperidine, morphine, codeine or dihydromorphinone. Four used stimulants such as benzedrine or dexedrine, alone or in combination. Still other drugs were used in some combination by 32 patients.     

Treatment of alcoholism; problems arising from the substitution of other drugs in therapy

Of the 139 patients admitted to hospital for chronic alcoholism, 32 had been taking other drugs also, and 17 were addicted to the drugs. Of the 32 patients, 16 used barbiturates, and 8 were addicted. Five took large amounts in suicidal attempt. Ten patients combined still other drugs with alcohol and barbiturates; and seven of them were addicted to barbiturates. Of the six patients combining alcohol with drugs other than barbiturates, two were addicted to the use. Of the 16 patients who used drugs other than barbiturates, eight used one or more opiates such as meperidine, morphine, codeine or dihydromorphinone. Four used stimulants such as benzedrine or dexedrine, alone or in combination. Still other drugs were used in some combination by 32 patients.     

生物技术药物药代动力学研究的方法学和实验设计

生物技术药物由于自身具有的特点 ,使得其在体内的药代动力学机制比传统药物更为复杂。近年来 ,对于这类药物在体内的代谢机制的研究日趋增加 ,研究方法也日趋成熟。概述了生物技术药物的药代动力学研究方法以及实验设计的特点。     

Proton nuclear magnetic resonance study on the multimode interactions of human serum albumin with drug molecules

The interactions of human serum albumin (HSA) with a number of ligands (mostly drugs) were examined by proton nuclear magnetic resonance spectroscopy. Ligand presence-absence difference spectra of HSA solutions were measured. Nonspecifically bound drugs such as tiaramide showed difference spectrum patterns which were similar to the spectra of the drugs themselves but were broadened as to the line-widths of signals. Thus, the difference spectra of these drugs reflect only the changes in the surroundings of the drug molecules, that is, between the bound and free states. In contrast, specifically bound drugs like ibuprofen and warfarin showed difference spectra in which signals from the HSA molecule only were observed. Furthermore, according to the characteristic peaks in these difference spectrum patterns, specifically bound drugs may be classified into several groups; the drugs in the first group bind to the ibuprofen binding site, those in the second group to the warfarin binding site, and those in the third group to sites other than the warfarin and ibuprofen sites. These findings suggest that the specific binding of drugs to HSA brings about a conformational change of this protein which is specifically correlated to the binding site.     

Kinetics and mechanisms of cholesterol esterase inhibition by cardiovascular drugs in vitro

Cardiovascular drugs such as lovastatin, simvastatin, amlodipine besylate, nifedipine, and hydralazine hydrochloride inhibit cholesterol esterase (CEase) in vitro. In the present paper, an attempt was made to determine kinetically the reaction mechanism for CEase inhibition by these drugs. The inhibition constant, Ki, for the mixed-type inhibition of CEase by these drugs in the presence of triton-X-100 or taurochloate were measured. Moreover, the pKi values were correlated with the molecular weights of these drugs. In conclusion, the fact that these drugs lower cholesterol levels in the plasma low-density lipoprotein may be partially due to the CEase inhibition by these drugs.     

Quality of cardiovascular drugs prescribing in Croatia 2003-2008

The aim of the study was to determine cardiovascular drugs utilization and quality of prescribing in Croatia from 2003 to 2008. Data on the outpatient utilization of cardiovascular drugs in Croatia were collected during 2003-2008. Data on the size and number of packages, were obtained from Croatian institute for Health Insurance (CIHI). Based on the data obtained, the numbers of DDD and DDD per 1000 inhabitants per day (DDD/1000/day) were calculated for all cardiovascular drugs. Quality of drugs prescribing was assessing using Drug Utilization 90% (DU90%) method. Renin-angiotensin system agents showed highest share in the utilization of group C drugs, followed by calcium channel blockers. These two groups of drugs accounted for half of the overall cardiovascular drug utilization. Greatest changes were observed in the groups of renin-angiotensin system agents and hypolipemics. The number of drugs within DU90% segment increased between 2003 and 2008. In the same period Cost/DDD decreased.     

多肽药物的发展现状

随着生物技术与多肽合成技术的日臻成熟,越来越多的多肽药物被开发并应用于临床。因适应证广、安全性高且疗效显著,多肽药物目前已广泛应用于肿瘤、肝炎、糖尿病、艾滋病等疾病的预防、诊断和治疗,具有广阔的开发前景。简介多肽药物的来源与特点及制备方法,重点综述国内外多肽药物的研发概况、国外近年获准上市的主要多肽药物和我国自主研发并进入临床研究的主要多肽药物,旨在为该类新药的研发提供参考。     

The influence of in vitro and in vivo exposure to antibiotics on mitogen-induced proliferation of lymphoid cells in rainbow trout (Oncorhynchus mykiss)

The influence of five different antimicrobial drugs on mitogen-induced lymphoid cell proliferation in vitro and after oral administration of the drugs was studied in rainbow trout (Oncorhynchus mykiss). The drugs tested were: oxolinic acid, oxytetracycline, florfenicol and trimethoprim in combination with sulfadiazine in ratio 1:5. In the in vitro tests, trimethoprim:sulfadiazine increased the 3H-thymidine incorporation into the DNA of phytohaemagglutinin and lipopolysaccharide-stimulated lymphoid cells while all the other drugs tested interfered negatively with the incorporation in a dose dependent manner. In the experiment with oral drug administration, the fish were fed 10 days with a therapeutic dose of the drugs. After the drug treatment, lymphoid cells were isolated from the head kidney of the fish and tested for proliferating capacity. All drugs except trimethoprim+sulfadiazine, suppressed the mitogenic response of the head kidney cells. The suppression of the response was more severe in phytohaemagglutinin-stimulated than in lipopolysaccharide-stimulated cells indicating that the T-cells were more vulnerable to the toxic effects of the drugs than B-cells.     

Sensitivity to antibiotics and antibacterial preparations of conditionally pathogenic bacteria isolated from patients with gastrointestinal tract dysfunctions]

Sensitivity of 690 cultures of the conditionally pathogenic microbes of Enterobacteriaceae and Pseudomonadaceae to 17 drugs was studied with the agar diffusion method. It was found that 98.6 per cent of the cultures had multiple resistance to 2--10 drugs. Most of the cultures were resistant to erythromycin, carbenicillin and ampicillin. Different species of the conditionally pathogenic microorganisms were resistant to different numbers of the drugs. Thus, Ps. aeruginosa cultures were resistant to 6--10 drugs, the cultures of Citrobacter were resistant to 3--8 drugs and the cultures of Kl. pneumonia were resistant to 2--5 drugs. Levomycetin, tetracycline, streptomycin and biseptol proved to be the most active antibacterial drugs.     

Correlations between changes of the right and left atrial pressures following intravenous injections of pressor and depressor drugs in cats

In acute experiments on anesthetized cats, intravenous injection of the pressor drugs (epinephrine and norepinephrine) and depressor drugs (acetylcholine, histamine, isadrin) caused different changes of right and left atrial pressures. Following catecholamine injection, right atrial pressure decreased in most cases, whereas left atrial pressure increased. In case of injection of the depressor drugs, right atrial pressure increased in most cases, and left atrial pressure decreased. Thus, changes of atrial pressures following intravenous injections of pressor and depressor drugs were reciprocal. The percent changes of the right atrial pressure in case of intravenous injections of pressor drugs were lesser than in the left atrial pressure. In case of intravenous injection of depressor drugs, if both right and left atrial pressures were decreased, then the percent changes of the right atrial pressure were more significant than in the left atrial pressure. If both right and left atrial pressure were increased their percent changes were equal. The increasing of inferior vena cava flow following catecholamine injection was less significant if atrial pressures were increased, whereas in case of depressor drugs injection superior vena cava flow was less significant if atrial pressures were increased. The character of changes of the right and left atrial pressures had no linear correlation with the directions of the shifts of the venous return and cardiac output.     

Follow-up of Cases of Opiate Addiction from the Time of Notification to the Home Office

Follow-up of 108 opiate addicts for a period of six to seven years showed that 35 were still being prescribed opiates, 25 were off drugs, 19 were dead, and for 29 it was not certain whether they were on or off drugs. Most patients who came off drugs did so in the first two years after notification to the Home Office. Clearly treatment is more likely to be successful if given early in the life history of the addict, when it is appropriate to give treatment based on withdrawal of drugs rather than substitution.     

Grampian Health Board's joint drug formulary.

OBJECTIVE--To develop a model for creating a joint general practice-hospital formulary, using the example of ulcer healing drugs. DESIGN--A joint formulary development group produced draft guidelines based on an earlier hospital formulary, which were sent to interested local general practitioners for consultation. Revised guidelines were then drawn up and forwarded to the health board''s medicines committee for approval and distribution. SETTING--Grampian Health Board. SUBJECTS--Nine members of joint formulary development group plus local general practitioners who were invited to comment on a list of 11 ulcer healing drugs. MAIN OUTCOME MEASURE--Degree of coincidence of drugs selected by hospital doctors and general practitioners. RESULTS--The ulcer healing drugs selected by the panel of general practitioners and by hospital doctors were highly coincident. The cost of one day''s treatment with drugs varied considerably between hospital and general practice--for example, one drug cost 46p in hospital and 1 pounds in general practice and another cost 1.26 pounds in hospital and 1.01 pounds in general practice. Overall, six drugs cost more in hospital and five cost more in general practice. CONCLUSIONS--A joint formulary for use in hospitals and general practice in a health board can be devised fairly simply by consultation as virtually the same drugs are used in both types of practice. It should influence the health board''s expenditure on drugs and affect the choice of drugs when a patient is discharged from hospital or is referred to any hospital in the region.     

Effect of colour of drugs: systematic review of perceived effect of drugs and of their effectiveness.

OBJECTIVE: To assess the impact of the colour of a drug''s formulation on its perceived effect and its effectiveness and to examine whether antidepressant drugs available in the Netherlands are different in colour from hypnotic, sedative, and anxiolytic drugs. DESIGN: Systematic review of 12 published studies. Six studies examined the perceived action of different coloured drugs and six the influence of the colour of a drug on its effectiveness. The colours of samples of 49 drugs affecting the central nervous system were assessed using a colour atlas. MAIN OUTCOME MEASURES: Perceived stimulant action versus perceived depressant action of colour of drugs; the trials that assessed the effect of drugs in different colours were done in patients with different diseases and had different outcome measures. RESULTS: The studies on perceived action of coloured drugs showed that red, yellow, and orange are associated with a stimulant effect, while blue and green are related to a tranquillising effect. The trials that assessed the impact of the colour of drugs on their effectiveness showed inconsistent differences between colours. The quality of the methods of these trials was variable. Hypnotic, sedative, and anxiolytic drugs were more likely than antidepressants to be green, blue, or purple. CONCLUSIONS: Colours affect the perceived action of a drug and seem to influence the effectiveness of a drug. Moreover, a relation exists between the colouring of drugs that affect the central nervous system and the indications for which they are used. Research contributing to a better understanding of the effect of the colour of drugs is warranted.     

靶向共价键药物的研究进展

药物与靶标的结合是启动药理作用的本源,共价键药物是以共享电子的方式来实现与靶标的结合,其中大多为抗感染、抗肿瘤以及心脑血管、神经系统和代谢类药物。简介共价键药物与非共价键药物的区别以及既往的重磅级共价键药物与靶标的结合特点,分类综述靶向共价键药物的理性设计及与靶标的结合反应。