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PubMed2000

[Effects of nitrates and beta-blockers on platelet aggregation in patients with coronary heart disease].

Our study aimed at evaluating an effect of the selected nitrates and beta adrenoceptor blockers on platelet aggregation in patients (pts) with coronary artery disease (CAD). The study included 168 male patients (M), aged between 33 and 72 years (mean age 51 +/- 7). 61 M given isosorbide dinitrate were divided into three groups: in the group I and II an effect of the drug on the platelet aggregation following a single 10 mg (I) and 20 mg (II) dose has been evaluated; in group III an effect of the drug after a two-week treatment has been evaluated. 14 male patients (group IV) were given 5-mononitrate 40 mg daily for two weeks. 85 male patients, treated with propranolol have also been divided into three groups. In group V and group VII an effect of propranolol on platelet aggregation following a single dose of 40 mg and 80 mg has been evaluated respectively. In the group VII an outcome of a two-week propranolol therapy has been assessed. Eleven patients (group VIII) received nadolol in a dose of 40-80 mg daily for two weeks. Platelet aggregation induced by adenosine diphosphate (ADP) in concentration of 1 mM/ml and 5 mM/ml (groups I, II, III, V, VI, VII) and only of 1 microM/ml (groups IV, VIII) was evaluated with Born's method. In patients with CAD only isosorbide dinitrate inhibits platelet aggregation. This effect has been noted following a single dose as well as a two-week treatment. Other drugs (5-mononitrate, propranolol, nadolol) transiently increase platelet aggregation, but became either ineffective after two-week therapy (5-mononitrate, nadolol) or increase (propranolol) platelet aggregation. Tendency to inhibit (sorbonit) or to increase (propranolol) platelet aggregation has been more pronounced with higher concentration of aggregating factor.

Adrenergic beta-Antagonists↗
PubMed1993

Response of human coronary arteries to serotonin after injury by coronary angioplasty.

BACKGROUND: Atherosclerotic stenoses that have exaggerated vasomotor responses are especially prone to restenosis after coronary angioplasty. Experimental studies show that vasomotor responses in normal vessels are altered by acute mechanical injury, an alteration that in part reflects changes in the functional characteristics of endothelium that has regenerated after injury. METHODS AND RESULTS: We examined, by quantitative coronary arteriography, the response of dilated and control coronary segments to intracoronary infusions of graded doses of serotonin, an endothelium-dependent vasoactive agent, and to intracoronary injection of isosorbide dinitrate, an endothelium-independent smooth muscle dilator in 15 patients who had undergone a single percutaneous transluminal coronary angioplasty procedure and who had no clinical features of variant angina. Dose-dependent constriction to serotonin occurred at all measured sites. The mean +/- SEM diameter reductions, expressed as percent reduction in baseline diameter that was observed at proximal (18.1 +/- 2.9, 18.8 +/- 2.2) and distal (30.9 +/- 4.4, 35.4 +/- 5.3) control sites in the dilated and nondilated vessels, respectively, at the highest dose, were similar. The degree of constriction in distal segments was significantly (P < .01) greater than that in proximal segments. Total or subtotal occlusion occurred at the angioplasty site in 4 patients at the highest infused dose (10(-4) mol/L). The mean percent reduction in baseline diameter at previously dilated sites (53.8 +/- 5.9) at this dose was significantly (P < .05) greater than that observed at the adjacent proximal control sites and similar to that observed at distal control sites. All segments dilated significantly after intracoronary injection of isosorbide dinitrate. CONCLUSIONS: In dilated and nondilated vessels, serotonin caused significantly more marked constriction in distal than in proximal vessel segments. In dilated vessels, the vessel segments that had been subjected to angioplasty had a constrictor response to serotonin that was more marked than at adjacent proximal control sites and equivalent to that in the distal vessel segments. This enhanced constrictor response could be related to changes in endothelial cell function after regeneration or to hyperreactivity of smooth muscle cells at the angioplasty site.

Adult↗
PubMed1984

Hemodynamic and metabolic effects of vasodilator therapy for heart failure in acute myocardial infarction.

Hemodynamic effects of vasodilator agents (molsidomine, nitroglycerin, isosorbide dinitrate or prostaglandin I2) were studied in 53 patients with acute myocardial infarction. In 20 of these patients, effect on cardiac metabolism were also studied. Patients were divided into four groups according to the Forrester subset and hemodynamic effects of these agents were evaluated by the cardiac index (CI)-preload (PAEDP) relationship. In patients of Forrester subset II and IV, vasodilators were capable of producing a considerable reduction in preload without a significant decrease in cardiac output. However, in patients of Forrester subset IV, five of six patients had only a minimal improvement in cardiac performance with vasodilator therapy because of a severe pump failure. In these patients, a combination therapy with dopamine was necessary to maintain the cardiac output. In patients with Forrester subset III, vasodilator therapy decreased cardiac index and preload was also reduced. Thus, for these patients vasodilators could not be indicated but volume infusion may be indicated. In patients with Forrester subset I, although vasodilator therapy decreased cardiac output, coronary sinus flow and myocardial oxygen consumption were also decreased, indicating that the vasodilator therapy is also beneficial for patients even without heart failure because of the protective effect of unloading on ischemic myocardium. Three nitrate agents, i.e., molsidomine, nitroglycerin and isosorbide dinitrate, demonstrated the similar effect on hemodynamics; mean blood pressure and PAEDP decreased by 7-10% and 20-29%, respectively, while systemic vascular resistance was not significantly decreased. In contrast to nitrates, PGI2 decreased mean blood pressure and systemic vascular resistance significantly, whereas a decrease in PAEDP was minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1982

A new two-dimensional echocardiographic technique for evaluating right ventricular size and performance in patients with obstructive lung disease.

To compare two-dimensional (2-D) echocardiographic estimates of right ventricular size and performance to similar determinations from equilibrium radionuclide angiography (RNA) before and after isosorbide dinitrate, we evaluated 19 patients with severe chronic obstructive pulmonary disease. The end-diastolic and end-systolic volumes estimated from subcostal 2-D echocardiographic views of the right ventricle correlated with the RNA end-diastolic and end-systolic counts (r = 0.76 and 0.82, respectively). The 2-D echocardiographic and RNA right ventricular ejection fraction (EF) estimates also correlated (r = 0.80), and the average right ventricular EF measures of 42 +/- 11% and 40 +/- 12%, respectively, did not differ significantly. Nitrate administration produced a significant increase in heart rate (99 +/- 11 to 108 +/- 14 beats/min, p less than 0.001) and a decrease in systolic arterial pressure (139 +/- 23 to 120 +/- 22 mm Hg, p less than 0.001). Nitrates also significantly decreased the average 2-D echocardiographic end-diastolic and end-systolic volumes (22 +/- 16% and 18 +/- 12%, p less than 0.001), as well as RNA end-diastolic and end-systolic counts (33 +/- 17% and 32 +/- 22%, p less than 0.001), but did not significantly decrease the average right ventricular EF values (4 +/- 12% and 4 +/- 24%, respectively). Nevertheless, after isosorbide dinitrate, the 2-D echocardiographic right ventricular end-diastolic and end-systolic volume estimates continued to correlate with the corresponding RNA count measures (r = 0.76 and 0.79, respectively), as did the 2-D echocardiographic and RNA right ventricular EF values (r = 0.75). We conclude that 2-D echocardiographic evaluation of right ventricular size and performance is feasible in selected patients with chronic obstructive pulmonary disease, and that 2-D echocardiographic measures of right ventricular size and performance compare favorably with similar determinations by RNA at rest and after nitrate administration.

Blood Pressure↗
PubMed1996

Impaired endothelial function with essential hypertension assessed by ultrasonography.

The objective of this investigation was to evaluate the role of hypertension in endothelial function, changes in which are known to be an early event of atherosclerosis. We assessed endothelial function in 13 subjects with normal blood pressure and 13 subjects with essential hypertension who had never been treated for hypertension or hyperlipidemia and who had no history of smoking or coronary or cerebrovascular disease. B-mode ultrasonography was used to measure the diameter of the brachial artery. Endothelium-dependent dilatation was assessed as the change in diameter of the artery during reactive hyperemia. Endothelium-independent dilatation was evoked, as a control, by sublingual administration of isosorbide dinitrate. Despite similar ages and lipid and glucose levels in the study groups, endothelium-dependent dilatation was less in patients with hypertension (13.1% +/- 1.6%) than in subjects with normal blood pressure (18.5% +/- 1.9%) (p < 0.05), whereas isosorbide dinitrate-induced changes were similar. Systolic and diastolic blood pressure were significantly correlated with endothelium-dependent vasodilatation (r = -0.57 and r = -0.53, respectively) but not with the change by isosorbide dinitrate. These results suggest that endothelial dysfunction exists in patients with hypertension and precedes overt atherosclerotic disease.

Adult↗
PubMed2002

[A case of intraoperative repeated coronary artery spasm with ST-segment depression].

A 68-year-old man with good left ventricular function underwent subtotal gastrectomy for gastric cancer under general anesthesia. Twenty minutes after the start of surgery, ST-segment depression was noted on the electrocardiogram monitor without change in the hemodynamic state. Intravenous isosorbide dinitrate relieved the electrocardiographic signs of ischemia. Short episodes of the ST-segment depression recurred 5 times despite intravenous isosorbide dinitrate and nicorandil. Echocardiography immediately after the surgery revealed hypokinesia of the anterior, septal and apical segments with an ejection fraction of 48%, suggesting acute myocardial infarction or the "Takotsubo"-shaped cardiomyopathy. However, a day after surgery, echocardiography showed improvement of regional wall motion with an ejection fraction of 57%. Coronary angiography showed normal coronary arteries on the 22nd day after the surgery. Patient manifested occlusive coronary artery spasm on ergonovine provocative test. We would like to stress that perioperative coronary artery spasm may demonstrate ST-segment depression and may result in severe consequences, regressive but relatively prolonged, in left ventricular function.

Aged↗
PubMed1981

[Ergometric study of a new vasodilator agent in angina: molsidomine. Value of combination with beta-blockaders].

Molsidomine, a new venous vasodilator, was studied in 40 cases of stable angina by ergometric stress testing. 1. In 10 patients, one hour after 2 mg molsidomine sublingually, the work inducing a 1 mm ST depression (WST 1) increased by 94% (p less than 0,05), the total work by 52% (p less than 0,005) and the maximum ST depression (ST max) fell by 45% (p less than 0,01). Resting heart rate was unchanged. There was a mild fall in systemic blood pressure. 2. Molsidomine had a significant synergic effect in 3 groups of 10 patients on betablocker therapy but with ischaemic changes on exercise: a) Molsidomine 1 mg sublingually increased WST 1 by 36% (p less than 0,05); at a 2 mg dosage, by 55% (p less than 0,001). ST max decreased from 2,4 +/- 0,4 mm to 1,3 +/- 0,3 (p less than 0,005) and 1,2 +/- 0,33 (p less than 0,001) respectively. The maximal effect was obtained with 1 mg in 5 out of 10 patients. b) One and three hours after 2 mg Molsidomine sublingually or orally: WST 1 increased from 97% to 110% (p less than 0,005): ST max decreased in similar proportions (p less than 0,005). c) 2 mg Molsidomine and 230 mg isosorbide dinitrate orally were compared after two hours: WST 1 increased by 130% after Molsidomine (p less than 0,005) and by 112% after isosorbide (p less than 0,005). ST max decreased in similar proportions (p less than 0,005). The blood pressure fell less with molsidomine. Molsidomine appeared to be better tolerated than isosorbide. (5 cases of mild headache in 40 patients compared to 4 cases out of 10 patients). The results of a preliminary clinical trial are reported. The association of molsidomine (2 mg per os three times daily) reduced the number of anginal attacks by over 50% in 16 out of 17 patients inadequately controlled by betablockade alone. 3 patients complained of headache at the onset of therapy. The efficacity was comparable and the tolerance better than in 28 patients with isosorbide dinitrate and betablockade, and in 10 patients with nifedipine and betablockade. In conclusion, molsidomine is a venous vasodilator with useful pharmacokinetic properties. It seems to be effective and well tolerated in the treatment of angina whether used alone or in association with betablockers.

Administration, Oral↗
PubMedDate not supplied

[Principles and rules of the use of nitrates].

Nitrates, which have been used for more than a century, are the second oldest drug (after digitalis alkaloids) in the cardiological pharmacological arsenal. However, several facets of their mode of use still remain controversial. Their vasodilator and arteriolodilator action (especially in coronary vessels) and their platelet aggregation inhibitory effect make them useful drugs, particularly in all clinical forms of ischaemic heart disease (unstable or stable angina and acute myocardial infarction), for the prevention or treatment of ischaemic episodes (silent or not) and also in heart failure where nitrates are useful not only as symptomatic treatment (alone or associated with diuretics), but also in view of their positive effect on survival (associated with hydralazine: V-Heft I trial). At the present time, nitrates can be administered via the sublingual, oral, intravenous of transdermal routes in the form of nitroglycerin and isosorbide dinitrate or mononitrate (short-acting and sustained-effect forms). Their rare contraindications concern patients suffering from severe hypotension (< 70 mmHg), severe anaemia, glaucoma or intracranial hypertension. The most serious adverse effects are pulsatile headache (which usually disappear after several days), postural hypotension (possibly causing fainting), facial erythema, vertigo, palpitations or nausea and vomiting. Most of these adverse effects can be controlled by dosage adaptation and it is rarely necessary to stop treatment. However, the major problem raised by the use of nitrates concerns the development of a tolerance. The pathophysiology of this multifactorial phenomenon is still unclear. The protagonist role played by loss of SH groups or activation of humoral feedback mechanisms, with an increase of circulating catecholamine levels, activation of the R-A-A system and increased plasma volume, has been postulated. This complication can be avoided by prescribing intermittent treatment, with a drug-free interval of 10-12 hours per day. A single dose of a sustained-release preparation (60 mg of isosorbide dinitrate or 40 to 60 mg of isosorbide mononitrate), or 2 or 3 doses of a short-acting preparation (20-40 mg of isosorbide mononitrate) can be prescribed via the oral route. When the transdermal route is used, the patch should be left in place for 12 hours. Treatment should be started at low doses, which are then gradually increased. The free period is usually at night, which can be covered, when necessary, by other antiischaemic drugs (for example, beta-blockers and/or calcium channel blockers), already usually used in combination with nitrates. This interruption is not accompanied by a rebound phenomenon. It must be remembered that nitrates potentiate the action of other vasodilators and calcium channel blockers and that, in some patients, intravenous nitroglycerin reduces the anticoagulant effect of heparin, while indomethacin can inhibit their vasodilator effect. Nitrates are therefore in very good health despite their advanced age and, when used correctly, they continue to be very useful in the pharmacological treatment of cardiovascular diseases.

Drug Resistance↗
PubMed1993

Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester.

The hypothesis that an arginine-nitric oxide (NO) synthase-NO system mediates the morphine abstinence syndrome was tested in adult male rats implanted subcutaneously for 3 days with one morphine (75 mg) pellet followed by naloxone-precipitated withdrawal (0.5 mg/kg). Injection with a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (NAME, 100 mg/kg subcutaneous), shortly before naloxone-induced withdrawal significantly inhibited abstinence signs by 25-80%. Continuous infusion of NAME via subcutaneous osmotic pumps during the development of morphine physical dependence and during naloxone-precipitated withdrawal also inhibited morphine abstinence signs. In addition, treatment with isosorbide dinitrate, a NO donor, induced a quasi morphine-abstinence syndrome (QMAS) that was significantly suppressed by implantation of a morphine pellet 3 days before isosorbide dinitrate treatment. These results indicate that NO mediates part of the expression of the morphine abstinence syndrome.

Amino Acid Oxidoreductases↗
PubMed1998

How to standardize vasomotor tone in serial studies based on quantitation of coronary dimensions?

In patients with coronary artery disease including those after coronary bypass graft operation and heart transplantation intervention studies based on serial quantitative coronary angiography, in part combined with intravascular ultrasound, are of increasing relevance. Since vasomotor tone of epicardial coronary arteries is influenced by a variety of factors, angiographic follow-up studies require standardization of coronary tone by induction of maximal dilation. We reviewed the effects of the most potent coronary vasodilatory drug groups, calcium antagonists and nitrocompounds, on coronary diameters. Intravenous or intracoronary injections of verapamil, diltiazem, nifedipine, nicardipine, and nisoldipine can cause profound coronary dilation which has been shown to be maximal with verapamil and nisoldipine. Shortcomings of calcium antagonists include short or unknown duration of action after bolus administration, severe drop in blood pressure, and lack of commercial availability of solutions for injection of many substances. Isosorbide dinitrate induces profound coronary dilation; however, after sublingual administration marked blood pressure decrease can occur, and the duration of action and ideal dose of intracoronary isosorbide dinitrate has not been investigated yet. Injections of molsidomine and its active metabolite, SIN-1, cause longlasting, reproducible, maximal coronary dilation, although only after a waiting period of at least 10 minutes; unfortunately, SIN-1 is only commercially available in France. Nitroglycerin induces reproducible maximal coronary dilation and is easy to administer sublingually or as intracoronary bolus injection with rapid onset of action and no major side effects. The short duration of action may require repeated administrations. To date, repeated intracoronary bolus injections of 0.1 mg nitroglycerin every 10 minutes seem to be the optimal known regimen for standardization of coronary vasomotor tone in serial angiographic studies. Further investigations in this field with old and new vasodilatory drugs are recommendable.

Calcium Channel Blockers↗
PubMed1988

Effect of nifedipine, dilazep, dinitrates and propranolol on blood lactate accumulation during intensive graded exercise testing in healthy young subjects.

The aim of the present study was to elucidate the effects of 4 different cardiovascular drugs on blood lactate levels during an intensive graded exercise test in 17 healthy male subjects. In acute studies, isosorbide dinitrate and nifedipine were used. In chronic studies, propranolol dihydrochloride and dilazep dihydrochloride were used. Oxygen uptake (VO2), heart rate, blood pressure and blood lactate were measured at rest and during the final minute of each exercise session. Hemodynamic measurements during submaximum exercise were influenced by all drugs except isosorbide dinitrate. VO2 during submaximum and maximum exercises remained unchanged by all drug treatments. Blood lactate levels at rest and during submaximum and maximum exercise also did not change significantly. Work load corresponding to blood lactate concentration of 4 mM (W4 mM) and the 1st and 2nd break points of lactic acid (WBPLA1 and WBPLA2) were almost the same in all treatments. It is concluded that the 3 criteria of blood lactate obtained during the graded exercise test are not affected by these drugs in healthy males.

Adult↗
PubMed1989

Relaxations to endothelium-derived relaxing factor and the metabolite of molsidomine, SIN-1, in the aorta and the hindquarters of the rat.

The effects of SIN-1 were studied on isolated aortic rings and perfused hindquarters of the rat and were compared with the effects of nitroglycerin and endothelium-derived relaxing factor (EDRF) released by acetylcholine or histamine (aorta) and carbachol (hindquarters). SIN-1 relaxes rat aortic rings in a dose-dependent and endothelium-independent way. Aortic rings made tolerant to nitroglycerin in vitro show cross-tolerance to isosorbide dinitrate but no cross-tolerance to EDRF, sodium nitroprusside, or SIN-1. Aortic rings made tolerant to nitroglycerin by in vivo treatment show an important cross-tolerance to isosorbide dinitrate, a small degree of tolerance to sodium nitroprusside, but no significant tolerance to SIN-1 or EDRF. Also, in the nitroglycerin-tolerant hindquarter vasculature, no cross-tolerance is found to EDRF or SIN-1. In the aorta of renal hypertensive rats, in which the relaxation to EDRF-dependent dilators is impaired, no depression of the maximal response to SIN-1 occurs.

Animals↗
PubMedDate not supplied

End-systolic pressure-volume and end-systolic stress-volume relationships in patients with aortic stenosis and with normal valvular function.

In order to study the effect of left ventricular hypertrophy on the endsystolic pressure-volume relationship, three left ventricular angiograms were performed in ten patients with normal valvular function but with varying left ventricular function (group 1) after 0.15 mg/kg propranolol and 1 mg atropine: at rest, after isosorbide-dinitrate at a decreased afterload and after methoxamine at an enhanced afterload. In eight patients with aortic stenosis (group 2) two left ventricular angiograms were performed: at rest and after isosorbide-dinitrate. Heart rate was kept constant by atrial pacing. Left ventricular mass in group 1 was 89 g/m2 and in group 2 180 g/m2. In group 1 the slope k of the end-systolic pressure-volume relation was related to the ejection fraction (EF) at rest: k = 0.024 . e0.072 EF; r = 0.93. In group 2 this relation was shifted to the left (P less than 0.001): k = 0.135 . e0.057 EF; r = 0.81. The relations, however, between the slope k of the end-systolic stress-volume relation and the ejection fraction were close together in group 1 and in group 2 and crossed at an ejection fraction of 67%. It is concluded: 1. In patients with aortic stenosis the end-systolic pressure-volume relation is steeper than in patients without valvular dysfunction at a given ejection fraction, so the relation between the slope k and the ejection fraction is shifted to the left. 2. The end-systolic stress-volume relationship is not altered in patients with aortic stenosis and seems to be advantageous for the evaluation of left ventricles with substantial hypertrophy due to pressure load.

Adult↗
PubMed2003

Beneficial effect of aqueous garlic extract on the vascular reactivity of streptozotocin-diabetic rats.

The present study evaluated the beneficial effect of aqueous extract of garlic (Allium sativum L.; 100mg/kg/day) on the alterations in vascular reactivity of streptozotocin-diabetic rats. After 8 weeks of treatment, thoracic aortic rings of rats were mounted in organ baths and contractile responses to phenylephrine and relaxant responses to acetylcholine and isosorbide dinitrate were assessed. Induction of diabetes significantly increased contractile responses to phenylephrine and impaired endothelium-dependent relaxations to acetylcholine in aortic rings, but did not change endothelium-independent relaxation to isosorbide dinitrate. Garlic administration significantly improved the impaired endothelium-dependent relaxations and decreased the enhanced contractile response to phenylephrine in diabetic rats. It is concluded that intraperitoneal administration of aqueous garlic extract can improve endothelial dysfunction in insulin-dependent model of uncontrolled diabetes.

Animals↗
PubMed1992

Role of nitrates in angina pectoris.

Nitrates are used extensively for the treatment of angina pectoris. However, continuous therapy with either oral nitrates or nitroglycerin patches leads to rapid development of tolerance, with loss or diminution of antianginal and anti-ischemic effects. The only practical way to avoid the development of tolerance is to use intermittent daily therapy with nitrates. Nitroglycerin patches applied for 10-12 hours during the day increase exercise duration for 8-12 hours, but a rebound increase in anginal attacks during the nitrate-free interval may occur. Oral isosorbide-5-mononitrate, 20 mg twice a day, with the first dose administered in the morning and the second dose 7 hours later, increases exercise duration for at least 12 hours without the development of tolerance to either the morning or afternoon dose. This dosing regimen has been shown not to produce a rebound phenomenon during the periods of low nitrate levels at night and early hours of the morning. Isosorbide dinitrate (30 mg) prescribed at 7 AM and 1 PM does not produce tolerance to the 7 AM dose, but effects of the afternoon dose have not been evaluated. Recent data suggest that isosorbide dinitrate given 3 or 4 times daily produces tolerance and this dosing schedule is inadequate for antianginal prophylaxis. It should be recognized that intermittent oral or patch therapy with nitrates during the day leaves the patient unprotected at night and early hours of the morning. If this is of concern, additional therapy with another class of antianginal agent, preferably a long-acting beta blocker or a long-acting calcium antagonist should be instituted.

Angina Pectoris↗
PubMed1994

An application of the hydrodynamic pore theory to percutaneous absorption of drugs.

Skin permeability of drugs was evaluated based on the hydrodynamic pore theory. Four polar solutes were used, with differing molecular sizes--ethylene glycol, 1,3-butylene glycol, antipyrine and sucrose--and isosorbide dinitrate was also selected as a lipophilic drug. The skin permeations of solvent (D2O) and one of these drugs were measured simultaneously under various osmotic pressures to calculate the reflection coefficient. The clearance of isosorbide dinitrate was independent of the solvent flux, whereas a linear relationship was obtained between the solvent flux and the clearance of each hydrophilic drug except for sucrose. The reflection coefficient of the hydrophilic drugs increased with increasing molecular radius. These results suggest that the convective flow contributes significantly to the total skin permeability of hydrophilic drugs and that the extent of contribution decreases with increasing molecular size of the drugs. The pore radius of the skin barrier could be estimated from the reflection coefficient of the hydrophilic drugs and the resulting value was compared with that for the other absorption sites, jejunum, rectum, and nose. The apparent water influx was also compared to assess the volume occupied by the pores. The pore radius and apparent influx of skin were lower than those for the other absorption sites, which is apparently one reason for low skin permeability of drugs, especially hydrophilic drugs.

Animals↗
PubMed1985

[Screening of single doses of nitrates, calcium antagonists and beta-adrenoblockaders in patients with stenocardia of effort by using pharmacodynamic treadmill studies].

Standard single doses of nitrates, Ca-antagonists and beta-adrenoblockers were studied and compared in 37 patients presenting with stable angina pectoris of effort by repeated treadmill tests coupled with ECG monitoring. The use of isosorbide dinitrate (10 mg), nifedipin (20 mg) and propranolol (40 mg) enabled the effective drug to be screened in 86% of patients. Eleven per cent more of patients responded to the raising of the drug dosage. Isosorbide dinitrate was found to be the most effective in 27% of cases, nifedipin in 19%, and propranolol in 11%. The effect of 2 to 3 drugs was similar in 40% of patients. The data obtained during the screening of the most effective drug in 13 patients, performed by two different methods (treadmill pharmacodynamic and pair bicycle ergomentry tests showed a good agreement in the majority of cases).

Adrenergic beta-Antagonists↗