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2.
Eksp Klin Farmakol ; 64(2): 45-50, 2001.
Article in Russian | MEDLINE | ID: mdl-11548448

ABSTRACT

The influence of a long-term treatment with losartan (50-100 mg o.d.) and captopril (25-50 mg b.i.d.) followed by the abrupt therapy cessation was studied in an open randomized placebo-controlled parallel group trial. The study was performed on a group of 22 essential (soft to moderate) hypertensive male patients, which entered the trial when a mean daytime diastolic blood pressure was BP > or = 90 Torr. The antihypertensive effect of losartan was more pronounced and homogeneous than the effect of an equivalent dose of captopril. The group-average trough/peak ratios upon the losartan treatment were 61.5 and 61.3% for the systolic and diastolic BP (against 21.2 and 26.9% for captopril), respectively. At the same time, the smoothness index values of the patients treated with losartan and captopril showed no significant difference. Neither treatment with any of the two drugs nor the therapy cessation affected the circadian BP profile or the BP variability. The abrupt termination of the drug administration did not cause a withdrawal syndrome: on the contrary, a significant effect of the captopril and losartan treatment (statistically reliable against the placebo control) persisted for at least four days after the therapy cessation. Taking into account poor homogeneity of the antihypertensive effect of captopril in patients with a stable moderate hypertension treated b.i.d., the drug administration is recommended according to the t.i.d. schedule. In this group of patients, losartan and captopril are probably more expediently administered in combination with other hypertensive drugs.


Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Captopril/therapeutic use , Circadian Rhythm , Hypertension/drug therapy , Losartan/therapeutic use , Substance Withdrawal Syndrome/physiopathology , Adult , Aged , Angiotensin II , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Captopril/adverse effects , Humans , Hypertension/physiopathology , Losartan/adverse effects , Male , Middle Aged , Time
3.
Ter Arkh ; 73(2): 38-43, 2001.
Article in Russian | MEDLINE | ID: mdl-11338852

ABSTRACT

AIM: To investigate 24-h evenness of an antihypertensive effect of angiotensin II receptor blocker losartan vs captopril by four parameters of arterial pressure (AP) monitoring. MATERIAL AND METHODS: An open, cross-over, placebo-controlled trial was made in 22 patients with mild/moderate arterial hypertension (AH). Four parameters of AP monitoring were assessed: TPR, SI, rate of AP morning rise, index of AP morning rise. RESULTS: In losartan treatment TPR for systolic and diastolic AP were 61.5 and 61.3%, respectively, IS made up 0.74 +/- 0.13 and 0.64 +/- 0.09, respectively. For captopril these values reached 21.2 and 26.9%, 0.51 +/- 0.14 and 0.47 +/- 0.10, respectively. Differences by SI between the two drugs were statistically insignificant. Both drugs did not raise the rate and index of AP morning rise significantly. CONCLUSION: When administered in a single daily dose 100 mg, losartan produced a regular antihypertensive effect throughout 24 hours. Captopril (twice a day in a dose 50 mg) effect was not regular enough. This means that some patients need a three-times-a day regimen of captopril. Of the four parameters, SI is most informative for evaluation of antihypertensive effect evenness.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antihypertensive Agents/pharmacology , Blood Pressure Monitoring, Ambulatory , Blood Pressure/drug effects , Captopril/pharmacology , Hypertension/drug therapy , Losartan/pharmacology , Age Factors , Aged , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Captopril/administration & dosage , Captopril/therapeutic use , Humans , Losartan/administration & dosage , Losartan/therapeutic use , Male , Middle Aged , Sex Factors , Time Factors
5.
Ter Arkh ; 72(4): 62-6, 2000.
Article in Russian | MEDLINE | ID: mdl-10833803

ABSTRACT

AIM: To clarify if pain-relieving action of acetylsalicylic acid (ASA) is associated with lowered sensitivity of anginal patients to pain due to myocardial ischemia. MATERIALS AND METHODS: A double blind randomized placebo-controlled trial enrolled 10 males aged 42-69 years with stable effort angina (EA) of functional class II-III. When exposed to exercise tolerance test (treadmill, stress-system Sicard 460S, computed ECG), the patients developed EA attack with at least 1 mm decline of ST segment on ECG. The exercise test was made before, 2 and 4 hours after administration of ASA and placebo. Sensitivity to ischemia was estimated by the total depth of the ST segment decline in 11 ECG leads (sigma ST) registered at the attack onset. Tactile and pain thresholds (TT and PT) were studied with a highly reproducible technique. TT and PT were measured before, 2 and 4 hours after ASA and placebo administration. RESULTS: 2 and 4 hours after intake of 100 mg of ASA, sigma ST and TT significantly rose compared to the baseline level and placebo. PT significantly rose vs the baseline level. CONCLUSION: ASA deteriorates sensitivity of anginal patients to myocardial ischemia, skin tactile and pain sensitivity and thus can deprive the EA patient of the pain attack signal. This leads to the risk of overexercising and emergence of painless myocardial ischemia.


Subject(s)
Angina Pectoris/physiopathology , Aspirin/therapeutic use , Chest Pain/physiopathology , Fibrinolytic Agents/therapeutic use , Pain Threshold/drug effects , Touch/drug effects , Adult , Aged , Angina Pectoris/complications , Angina Pectoris/drug therapy , Chest Pain/drug therapy , Chest Pain/etiology , Double-Blind Method , Electric Stimulation , Electrocardiography , Exercise Test , Humans , Male , Middle Aged , Pain Measurement , Reproducibility of Results
10.
Ter Arkh ; 70(8): 21-5, 1998.
Article in Russian | MEDLINE | ID: mdl-9770738

ABSTRACT

AIM: To compare efficacy of diltiazem and nifedipine in single dose and long-term treatment. MATERIALS AND METHODS: A randomised double-blind cross-over study enrolled 17 patients suffering from coronary heart disease (CHD) with stable angina of effort (SAE). For 1 month, each patient received diltiazem and nifedipine (60-90 mg 4 times a day and 20-30 mg 4 times a day, respectively). The effect was assessed by the pharmacodynamic test after the initial dose and in the end of each treatment course. RESULTS: In 14 eligible patients both drugs reduced the number of SAE attacks and nitroglycerin tablets, diltiazem efficiency being somewhat higher. Single doses of diltiazem and nifedipine produced the same action. In long-term treatment nifedipine effect became shorter, diltiazem effect did not change. Before the morning dose of nifedipine (11.5 hours after the previous dose) exercise tolerance of this drug worsened. This may be due to withdrawal syndrome. As to diltiazem, its exercise tolerance improved. CONCLUSION: In long-term treatment of CHD with SAE diltiasem is more effective and safe than nifedipine.


Subject(s)
Angina Pectoris/drug therapy , Calcium Channel Blockers/administration & dosage , Diltiazem/administration & dosage , Nifedipine/administration & dosage , Physical Exertion , Aged , Angina Pectoris/diagnosis , Calcium Channel Blockers/adverse effects , Chronic Disease , Diltiazem/adverse effects , Double-Blind Method , Drug Tolerance , Exercise Test , Humans , Middle Aged , Nifedipine/adverse effects , Time Factors
11.
Int J Cardiol ; 64(2): 137-44, 1998 Apr 01.
Article in English | MEDLINE | ID: mdl-9688432

ABSTRACT

We compared the effects of abrupt cessation of nifedipine and isosorbide dinitrate therapy in patients with stable angina pectoris. Eighteen males were studied. Each patient received isosorbide dinitrate and nifedipine continuously for 5 weeks by randomised cross-over technique. Exercise treadmill tests were performed before each treatment period, at the beginning of treatment, 4 weeks after initiation of treatment and on the first and eighth days of drug withdrawal. At the end of treatment the antianginal effect of both agents attenuated (versus acute administration). Abrupt cessation of isosorbide dinitrate caused only a tendency towards decrease in exercise tolerance versus pre-treatment level. Alternatively, abrupt cessation of nifedipine resulted in substantial deterioration in exercise tolerance, which was statistically significant 21 and 24 h after the last dose administration. The number of anginal attacks increased >25% in two patients after cessation of isosorbide dinitrate and in eight patients after cessation of nifedipine. In no patient rest angina episodes appeared after stopping of isosorbide dinitrate, however, after stopping of nifedipine rest angina episodes appeared in three patients. We conclude that withdrawal phenomenon of nifedipine is much more pronounced than that of isosorbide dinitrate and may emerge on the first day of drug cessation. Such a phenomenon may be evident even in patients in whom nifedipine effect have attenuated due to the development of tolerance.


Subject(s)
Angina Pectoris/chemically induced , Calcium Channel Blockers/adverse effects , Exercise Tolerance/drug effects , Isosorbide Dinitrate/adverse effects , Nifedipine/adverse effects , Substance Withdrawal Syndrome , Adult , Angina Pectoris/drug therapy , Blood Pressure/drug effects , Exercise Test , Humans , Male , Middle Aged , Single-Blind Method
12.
Ter Arkh ; 70(1): 32-7, 1998.
Article in Russian | MEDLINE | ID: mdl-9532649

ABSTRACT

AIM: Study of the tolerance and pharmacodynamic and pharmacokinetic characteristics of ascolong, a new buccal dosage form of aspirin containing a very low dose of acetylsalicylic acid (ASA): 12.5 mg. MATERIALS AND METHODS: The study was carried out in 43 healthy men (assessment of the drug tolerance) and 19 male patients with coronary disease or cerebrovascular disorders. In 10 patients the antiaggregant efficacy of ascolong administered once or regularly (for 2 weeks) in a dose of 12.5 mg was compared with placebo, in 9 patients a random cross study of 2-week courses of ascolong and Russian aspirin tablets in a dose of 100 mg was carried out. Platelet aggregation was assessed on days 1 and 14 of each course before and 2, 4, and 24 h after the drug intake. RESULTS: Ascolong containing a very low dose of ASA exerts a reliable antiaggregant effect after a single and regular intake, although this effect is less manifest than after aspirin tablets. Profiles of ASA concentrations in the blood were studied. Transbuccal entry of ASA in systemic circulation decelerated its metabolism into a less active metabolite, salicylic acid, due to which fact the ASA microdose had an expressed antiaggregant effect. The drug was sufficiently well tolerated. CONCLUSION: The new buccal film form of aspirin containing a very low dose of ASA possesses a good antiaggregant effect and is promising in subjects with contraindications to oral intake of aspirin.


Subject(s)
Aspirin/administration & dosage , Platelet Aggregation Inhibitors/administration & dosage , Administration, Buccal , Aspirin/pharmacokinetics , Aspirin/therapeutic use , Cerebrovascular Disorders/drug therapy , Cerebrovascular Disorders/metabolism , Chromatography, High Pressure Liquid , Coronary Disease/drug therapy , Coronary Disease/metabolism , Cross-Over Studies , Dosage Forms , Follow-Up Studies , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/pharmacokinetics , Platelet Aggregation Inhibitors/therapeutic use , Safety , Treatment Outcome
13.
Ter Arkh ; 69(1): 43-6, 1997.
Article in Russian | MEDLINE | ID: mdl-9163049

ABSTRACT

The data are presented on the absence of a stable positive trend in echocardiographic characteristics of the left heart and intracardiac hemodynamics after 8 months of controlled antihypertensive therapy, 12-month follow-up and uncontrolled outpatient treatment. 12 months after discontinuation of controlled antihypertensive therapy arterial pressure was much higher than it was at the end of the treatment in patients taking antihypertensive drugs irregularly or not taking them at all. Intracardiac hemodynamics returned to the baseline. As shown by echo-CG, frequency of left ventricular hypertrophy 12 months after the end of antihypertensive treatment rose from 25.8 to 45.2% (p < 0.01), of right ventricular hypertrophy from 14.5 to 17.7%.


Subject(s)
Antihypertensive Agents/therapeutic use , Echocardiography/drug effects , Hypertension/drug therapy , Hypertrophy, Left Ventricular/drug therapy , Chi-Square Distribution , Chronic Disease , Echocardiography/statistics & numerical data , Hemodynamics/drug effects , Humans , Hypertension/complications , Hypertension/diagnostic imaging , Hypertension/physiopathology , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/physiopathology , Male , Middle Aged , Time Factors
15.
Ter Arkh ; 69(9): 47-51, 1997.
Article in Russian | MEDLINE | ID: mdl-9411826

ABSTRACT

Exercise tests were performed in 18 patients with stable angina of effort treated with isosorbide dinitrate (ID) or nifedipine (NF) to see whether sharp discontinuation of the above drugs may entail withdrawal syndrome. Exercise tolerance declined 21 and 24 hours after the last administration of NF, 13 and 18 hours after that of ID. Compared to NF, ID tolerance decreased in a less degree. Some of the patients experienced myocardial ischemia in the course of the exercise tolerance tests, there were more frequent anginal episodes, arterial pressure rose. For ID withdrawal syndrome manifested weaker than for NF.


Subject(s)
Angina Pectoris/complications , Isosorbide Dinitrate/adverse effects , Nifedipine/adverse effects , Substance Withdrawal Syndrome/etiology , Vasodilator Agents/adverse effects , Adult , Aged , Angina Pectoris/drug therapy , Angina Pectoris/physiopathology , Exercise Tolerance/drug effects , Humans , Isosorbide Dinitrate/administration & dosage , Male , Middle Aged , Nifedipine/administration & dosage , Nitroglycerin/administration & dosage , Physical Exertion/drug effects , Substance Withdrawal Syndrome/diagnosis , Substance Withdrawal Syndrome/physiopathology , Time Factors , Vasodilator Agents/administration & dosage
18.
Ter Arkh ; 69(12): 37-40, 1997.
Article in Russian | MEDLINE | ID: mdl-9503532

ABSTRACT

Potential tolerance to isosorbide dinitrate (ID) and molsidomine (M) was studied in 18 ischemic heart disease (IHD) patients with stable angina of effort entered in a double blind cross-over trial. Each drug was administered for 3 weeks 4 times a day in individual effective dose. Single doses of ID and M were similar by effectiveness, but after 3 weeks of regular intake their efficacy fell, ID becoming less potent than M. For ID, tolerance after long-term intake manifested in 7 out of 18 patients, for M--in 5 out of 18. Complete tolerance was registered in 3 of 18 and 1 of 18 patients, respectively. Thus, tolerance is possible for the two drugs, but for M it is less pronounced.


Subject(s)
Isosorbide Dinitrate/therapeutic use , Molsidomine/therapeutic use , Myocardial Ischemia/drug therapy , Vasodilator Agents/therapeutic use , Adult , Aged , Angina Pectoris/diagnosis , Angina Pectoris/drug therapy , Angina Pectoris/physiopathology , Coronary Angiography , Cross-Over Studies , Double-Blind Method , Electrocardiography , Exercise Test , Follow-Up Studies , Humans , Isosorbide Dinitrate/adverse effects , Male , Middle Aged , Molsidomine/adverse effects , Myocardial Ischemia/diagnosis , Myocardial Ischemia/physiopathology , Retrospective Studies , Vasodilator Agents/adverse effects
19.
Eksp Klin Farmakol ; 60(5): 47-50, 1997.
Article in Russian | MEDLINE | ID: mdl-9483406

ABSTRACT

The pharmacokinetics of nadolol in blood serum and its excretion in the urine were studied in 6 male patients (aged from 35 to 59 years) with arterial hypertension for 48 h and, respectively, 72 h after a single per os administration of nadolol in a dose of 80 mg in the morning (9.00 a.m.), in daytime (15.00 p.m.) and in the evening (20.00 p.m.). The concentration of nadolol in the blood serum and urine was determined by high performance liquid chromatography with fluorescence detection. Analysis of the obtained data showed maximum blood serum nadolol concentration and the area under the concentration--time curve to be lower (93 ng/ml and 1786 ng h/ml) in the case of evening medication, and the peroral clearance and kinetic distribution volume to be higher (44.8 l/h and 940 l) than after morning medication (188 ng/ml, 2816 ng h/ml, and 28.4 l/h and 650 l, respectively). The corresponding parameters after daytime medication had intermediate values. The half-life period, mean retention time, and time of achievement of maximum blood serum nadolol concentration did not depend on the time of medication and were in the range of 15.2-15.8 h, 21.1-22.0 h, and 2.9-4.0 h, respectively. The pharmacokinetic parameters characterizing nadolol excretion with the urine were independent of the time of its intake. On the basis of the character of the detected circadian changes in the parameters of nadolol pharmacokinetics it is suggested that these changes reflect the circadian variations in the absorption of the drug in the gastrointestinal tract.


Subject(s)
Antihypertensive Agents/pharmacokinetics , Hypertension/blood , Hypertension/urine , Nadolol/pharmacokinetics , Adult , Antihypertensive Agents/blood , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/urine , Circadian Rhythm , Humans , Hypertension/drug therapy , Male , Middle Aged , Nadolol/blood , Nadolol/therapeutic use , Nadolol/urine
20.
Heart ; 75(5): 447-50, 1996 May.
Article in English | MEDLINE | ID: mdl-8665335

ABSTRACT

OBJECTIVE: To examine by Holter electrocardiographic monitoring the effect of abruptly stopping nitrate treatment in patients with stable angina pectoris. PATIENTS: 12 men with confirmed ischaemic heart disease and stable exertional class 3 angina (Canadian). All had episodes of horizontal or down sloping ST segment depression during 24 hour electrocardiographic monitoring. All were nitrate responders. DESIGN: Each patient was given isosorbide dinitrate (10-30 mg four times a day) and placebo (four times a day) for three days in a randomised crossover trial. There was a washout period of 3-5 days between the two treatment periods. Holter monitoring was performed on the third day of isosorbide dinitrate and placebo administration and on the first day of their withdrawal. RESULTS: When treatment with isosorbide dinitrate was stopped there was a significant increase in the total number and duration of painless episodes of myocardial ischaemia. During placebo and isosorbide dinitrate administration 8 patients had episodes of painless myocardial ischaemia whereas after isosorbide dinitrate cessation they were recorded in all 12 patients. Episodes of silent myocardial ischaemia at rest appeared in 4 patients after isosorbide dinitrate withdrawal. CONCLUSION: Abrupt cessation of short-term continuous nitrate treatment in patients with severe angina may cause a rebound increase in myocardial ischaemia which is predominantly silent.


Subject(s)
Angina Pectoris/drug therapy , Isosorbide Dinitrate/adverse effects , Myocardial Ischemia/chemically induced , Substance Withdrawal Syndrome , Vasodilator Agents/adverse effects , Aged , Angina Pectoris/physiopathology , Cross-Over Studies , Drug Administration Schedule , Electrocardiography, Ambulatory , Exercise Tolerance/drug effects , Humans , Male , Middle Aged , Myocardial Ischemia/diagnosis
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