[Comparative study of spirapril (quadropril) and amlodipine efficacy. Results of randomized trial in patients with mild to moderate arterial hypertension]. / Sravnitel'noe izuchenie éffektivnosti spiraprila (kvadropril) i amlodipina. Rezul'taty randomizirovannogo issledovaniia u bol'nykh miagkoi i umerennoi arterial'noi gipertoniei.

AIM: To compare in the non-blind randomised parallel study the efficiency of quadropril and amlodipine in the treatment of mild to moderate arterial hypertension. MATERIAL AND METHODS: A total of 80 patients (57.6 +/- 1.0 years) were included in this study. The patients were randomised in two groups, 40 patients each. Patients of group 1 received monotherapy with quadropril, while those of group 2 were treated with amlodipine. The treatment duration was 8 weeks in both groups. Quadropril was given in a fixed dose of 6 mg once daily. The initial dose of amlodipine was 5 mg/day. In case of insufficient effect the dose was elevated to 10 mg/day. The efficacy was evaluated by changes in blood pressure (BP) measured at rest. Moreover, in 50 randomly chosen patients 24-h monitoring of BP was performed at the start and end of the treatment. RESULTS: In the quadropril group baseline systolic BP reached 158.6 +/- 2.1 mm Hg, diastolic BP--101.8 +/- 0.8 mm Hg, heart rate was 74.3 +/- 1.6 beats/min. In the amlodipine group baseline systolic BP was 159.9 +/- 2.4 mm Hg, diastolic BP--101.8 +/- 1.0 mm Hg, heart rate was 71.3 +/- 1.0 beats/min. Systolic BP decreased at the end of quadropril therapy to 138.5 +/- 2.2 mm Hg, diastolic BP to 88.1 +/- 1.4 mm Hg. No significant change of the heart rate was observed. Under 5 mg of amlodipine systolic BP decreased to 137.9 +/- 2.5 mm Hg and diastolic BP to 87.1 +/- 1.6 mm Hg. Heart rate increased to 73.3 +/- 2.2 beats/min. Under therapy with 10 mg amlodipine systolic BP decreased to 145.9 +/- 3.8 mm Hg, diastolic BP to 89.7 +/- 3.4 mm Hg. Heart rate increased to 77.3 +/- 4.0 beats/min (p < 0.01). The hypotensive effect of quadropril remained stable while the effect of amlodipine decreased by the 8th week of therapy (p < 0.01). Side effects were observed significantly more often in the amlodipine group, then in the quadropril group. The main quadropril side effect was cough. Side effects observed in the amlodipine group were edemas, tachycardia, weakness. CONCLUSION: Both quadropril and amlodipine demonstrated a comparable antihypertensive effect although in 11 of 40 patients in the amlodipine group a dose increase was necessary and tolerability of quadropril was better.

[Ramipril effects on 24 hour profile of blood pressure in patients with mild and moderate hypertension]. / Vliianie ramiprila na sutochnyi profil' arterial'nogo davleniia u bol'nykh miagkoi i umerennoi arterial'noi gipertoniei.

AIM: The study of the effects of the inhibitor of angiotensin converting enzyme ramipril (tritace) on the 24-h profile of blood pressure (BP) in patients with mild and moderate arterial hypertension. MATERIALS AND METHODS: Ramipril was given to 21 males aged 45-68 years with essential hypertension stage II (WHO criteria) with stable elevated diastolic blood pressure (95-114 mm Hg) in a single dose 2.5-10 mg/day. Captopril controls received 100 mg twice a day. BP was monitored using "SpaceLabs Medical" unit (model 90207, USA). RESULTS: Compared to placebo, ramipril lowered systolic and diastolic blood pressure both for the 24-h period and in the day time; captopril lowered only diastolic BP in the day time. Side effects of long-term application of ramipril occurred 2 times less frequently than in application of captopril. CONCLUSION: Long-term treatment with ramipril in the above regimen provides more effective control of BP than captopril in the above doses in patients with mild and moderate hypertension.

[The clinical pharmacology of antianginal agents]. / Klinicheskaia farmakologiia antianginal'nykh sredstv.

This paper provides the basic advances made in studying the clinical pharmacology of antianginal agents (AAs), demonstrates the contribution of current tools for evaluating their antianginal effects, namely pharmacodynamic studies using pair bicycle ergometry and repeated treadmill exercises, 24-hour ECG monitoring, pharmacokinetic studies. It shows that AAs can be chosen on an individual basis. The authors present pharmacodynamic characteristics of a number of new AAs from nitrates (trinitrolong, dinitrosorbilong, etc.), calcium antagonists, beta-adrenoblockers (proxodolol, etc.). They have developed a method for assessing the biological equivalence of AAs. The paper discusses the tolerance that can be developed to nitrates and how it can be prevented. It first demonstrates that nifedipine tolerance can develop and that the withdrawal syndrome can occur if nitrates and calcium antagonists are discontinued. There are screening data on various combinations of AAs. A two-stage scheme for choosing an AA therapy is given.

[The pharmacokinetic interaction of propranolol and nifedipine in patients with angina of effort]. / Izuchenie farmakokineticheskogo vzaimodeistviia propranolola i nifedipina u bol'nykh so stenokardiei napriazheniia.

A comprehensive study was undertaken to examine the pharmacokinetic and pharmacodynamic interaction of propranolol and nifedipine in 11 patients with stable angina of effort who were treated for a long time. It was shown that when the agents were given in combination, the patient's plasma generated the same profiles of their concentrations as used alone. This suggests that the propranolol + nifedipine combination is safe from the point of their pharmacokinetic interaction. The latter occurs at the level of their pharmacodynamic effects.

[Methodologic approaches to evaluation of interaction of anti-anginal agents in their combined use in patients with exercise-induced angina]. / Metodicheskie podkhody k otsenke vzaimodeistviia antianginalnykh preparatov pri ikh kombinirovannom primenenii u bolnykh so stenokardiei napriazheniia.

The paper shows methodological approaches to assessing the interaction (antagonism and synergism) of antianginal agents in their combination used in 15 patients with stable angina. Each patient underwent paired bicycle ergometry with placebo, isosorbide dinitrate, 10 mg (ID), nifedipine, 20 mg (N), propranolol, 40 mg (P), and a combination of the drugs: ID, 10 mg, +P, 40 mg; N, 20 mg, +P, 40 mg; ID, 10 mg+N, 20 mg. The results were processed by two-dimensional dispersion analysis. Based on the findings, it was concluded that the interaction of drugs in all combinations was statistically insignificant in patients. At the same time the developed individual criteria for assessing the interaction allowed patients both with synergic and antagonistic interaction of antianginal drugs to be revealed.

[Treatment of patients with stable angina by combination of trinitrolong and propranolol]. / Lechenie bolnykh stabilnoi stenokardiei kombinatsiei trinitrolonga i propranolola.

Trinitrolong (TNL), a long-acting nitroglycerin for application on the gingiva, was comparatively assessed for effect on stable angina pectoris in monotherapy and in combination with beta-adrenoblocker propranolol. A total of 11 anginal patients received the combination the efficacy of which was verified by paired bicycle ergometry. A high antianginal effect of TNL was established. However, its combination with propranolol entails neither higher exercise tolerance nor less frequent anginal attacks. An increment in the effect was not seen either when the combination was used in single and course doses in one-third of the patients.

[The single-dose screening of nitrates, calcium antagonists, beta-adrenoblockaders and their combinations in patients with stenocardia of effort by using the paired bicycle ergometry method]. / Skrining razovykh doz nitratov, antagonistov kal'tsiia, beta-adrenoblokatorov i ikh kombinatsii u bol'nykh stenokardiei napriazheniia s pomoshch'iu metoda parnykh veloérgometrii.

Fifteen males with stable angina pectoris were screened for efficacy of antianginal drugs in single doses (isosorbide dinitrate, 10 mg; nifedipine, 20 mg; propranolol, 40 mg) and in combinations (ID+Pr, ID+Nf, Nf+Pr, Nf+Pr+ID). The findings at paired bicycle ergometries indicated that ID was most beneficial in monotherapy. Only two combinations (Nf+Pr and Nf+Pr+ID) were superior when compared to single drugs. Combinations ID+Pr and ID+Nf had the same efficacy as ID. Interaction of the drugs assessed with two-dimensional variance analysis was insignificant in all the combinations. Nf+Pr+ID combination had no advantages over two-drug combinations and induced worse tolerance.

[A comparison of the efficacy of nitrogranulong and other prolonged-action nitrates by using paired bicycle ergometry in patients with stenocardia]. / Sravnenie éffektivnosti nitrogranulonga i drugikh nitratov prolongirovannogo deistviia s pomoshch'iu parnykh veloérgometrii u bol'nykh so stenokardiei.

The efficacy of single doses of nitrogranulong, 5.2 mg, trinitrolong, 2 mg, nitrong 6.5 mg, and placebo was evaluated in 10 males aged 46-62 years who had Functional Classes II-III angina on effort. For this, paired bicycle ergometry was employed. In patients in whom nitrogranulong, 5.2 mg, turned out to be ineffective, the effective dose was evaluated as 10.4 mg. The effect of a drug was evaluated from an increase in exercise duration before the occurrence of a moderate anginal attack and/or 1 mm or more ST-segment depression in bicycle ergometry performed when the maximum effect of the single dose was expected than that in bicycle ergometry performed before achieving the same criteria for exercise discontinuation on the same day before the drug use (delta T threshold). The single dose of a drug was considered to be beneficial at delta T threshold > or = 120 sec (individual effects). Trinitrolong in a dose of 2 mg turned out be the most effective: there was the most mean value of delta T threshold and the individual effect was seen in 100% of the patients. According to the accepted criterion, nitrogranulong, 5.2 mg, and nitrong, 6.5 mg, were effective in 20%. Nitrogranulong, 10.4 mg, was beneficial in more 40% of patients; in all the first and the second doses of the drug were beneficial in 60%.