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Biomedical subjects

C Tantucci

Publications and source records attributed to C Tantucci.

At least 55 records · Page 3Linked to original sources

Acute ventilatory and gas-exchange effects of a new beta-2 agonist, broxaterol, in asthmatics.

The ventilatory and gas-exchange effects of broxaterol, a new selective beta 2-adrenoceptor agonist, were investigated in ten asthmatics following intravenous administration of a single dose of 200 mcg. Broxaterol elicited a prompt and marked bronchodilating effect (increase in forced expiratory volume in one second and specific conductance), maintained at least up to the sixtieth minute. Minute ventilation and the mean expiratory flow did not increase significantly, the pattern of breathing showing a reduction of expiratory time, without modification of inspiratory time. On the other hand, occlusion pressure did not show any significant rise at all times of observation. Furthermore, the partial arterial oxygen and carbon dioxide pressures and alveolar-arterial difference in oxygen and physiological dead space remained unchanged, when measured at 20 min. The results demonstrated that broxaterol was an effective bronchodilating agent, also when rapidly injected, causing a prompt relief of bronchospasm. With respect to other beta 2-adrenoceptor agonists, this compound did not appear to increase minute ventilation or to induce an impairment of ventilation/perfusion ratio, at least after 20 min, when the bronchodilation was still evident. Finally, no side-effects or alterations of heart rate or blood pressure were reported.

Adrenergic beta-Agonists↗

Round table on antiasthmatic drugs; beta-agonists and theophylline. Workshop on pathogenesis and therapy of bronchial asthma Cortina d'Ampezzo/1-4 April, 1987.

Beta 2-agonists and theophylline compounds are first line drugs and are extensively used in the treatment of acute bronchial asthma. Beta 2-agonists are continuously expanding as a class of drugs. Recent research has increased the available knowledge of their cardiovascular and metabolic effects. Cardiovascular effects might be due to direct stimulation of beta 2-receptors sited in the atrial muscle. Metabolic effects (i.e. increase in blood glucose, insulin and non-esterified fatty acid (NEFA), decrease in plasma potassium) are, at least partly, a consequence of direct or reflex stimulation. Despite recent progress, slow-release theophylline compounds remain a basic approach to asthma management. Future progress in this field will probably be concerned with a more complete knowledge of 'ultra-slow' theophylline compounds (level of the plasma concentration fluctuation and patient compliance) and more complete results regarding the influence exerted by food (and gastric pH) on the rate and extent of absorption.

Adrenergic beta-Agonists↗

Metabolic and hormonal effects of preferential beta 1 and beta 2-adrenoceptor stimulation in man.

The changes of blood glucose, serum potassium (K+), plasma non-esterified fatty acids (NEFA), plasma insulin and plasma renin activity (PRA) following the preferential stimulation of beta-1 and beta-2 adrenoceptors were studied in 7 healthy subjects during a 60-min infusion of prenalterol, a new, relatively beta-1 selective agonist and salbutamol, a well known, relatively beta-2 selective agonist. Two different high and low doses were used for both agents: 300 micrograms and 600 micrograms and 1 mg and 2 mg for salbutamol and prenalterol, respectively. The levels of PRA seemed equally increased by the two agents in proportion to the dose infused, thus suggesting an equally important role for beta-1 and beta-2 adrenoceptors in renin release. Blood glucose did not change during prenalterol infusions, while increased by 12 +/- 2 mg/100 ml (mean +/- SE; p less than 0.01) and 25 +/- 3 mg/100 ml (p less than 0.01) on salbutamol, at low and high dose, respectively. Similarly the decrement of serum K+ was significantly more pronounced (p less than 0.01) after salbutamol infusion (0.6 +/- 0.07 mEq/L and 1.0 less than 0.09 mEq/L, at low and high dose, respectively) than after prenalterol (0.1 +/- 0.07 mEq/L and 0.3 +/- 0.05 mEq/L). These metabolic effects should suggest a main beta-2 adrenoceptor involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sympathetic activation on effort in patients with chronic heart failure. Long term effects of captopril.

Ten patients with congestive heart failure (CHF) (NYHA II-IV) on adjusted doses of digitalis and diuretics underwent a careful clinical assessment including an evaluation of exertion dyspnoea and the usual echocardiographic indices of cardiac performance. A cardiopulmonary exercise test with an increment of 20W every 3 minutes was prolonged until exhaustion. Systemic arterial pressure, ECG, VO2, VCO2 and VE were monitored throughout. Gas tensions, plasma catecholamines and lactate were measured in blood samples taken at the first and third minute of each exercise stage. The above measurements were carried out before and after 3 months of treatment with Captopril, 50 mg b.i.d. or t.i.d. A highly significant correlation between arterial lactate and plasma norepinephrine (NE) was observed in each patient during both exercise tests (r = 0.77 to 0.99; p less than 0.05 at least). Left ventricular end-diastolic dimensions were reduced by Captopril (from 69.9 +/- 1.7 to 65.2 +/- 1.4 mm, p less than 0.01) along with a concomitant increase in percent fractional shortening. Most of the patients were reclassified at a lower NYHA class and a significant decrease in dyspnoea score was observed. The exercise time was significantly increased (from 11.2 +/- 1.8 to 12.9 +/- 1.9 min; p less than 0.05), but the peak values of NE, arterial lactate and VO2 were not affected by the treatment. The predicted value of VE at a VCO2 of 1 L/min, regarded as an index of dyspnoea, was significantly decreased by Captopril (from 41.4 +/- 2.9 to 38.9 +/- 2.7 L/min; p less than 0.05). The positive effects of long-term treatment with Captopril on cardiac performance in CHF are confirmed. Sympathetic activity is linked to anaerobic muscular metabolism during exercise and seems to be independent of pharmacological ACE inhibition. The discrepancy between the exercise tolerance and the peak VO2 might be explained by a better utilization of the available energy.

Adult↗

Buprenorphine vs. morphine via the epidural route: a controlled comparative clinical study of respiratory effects and analgesic activity.

Twelve patients with intense or very intense pain of the non-incident type, secondary to neoplasia, were divided at random into two groups and treated with an epidural dose of 3 mg of morphine in 10 ml of glucose solution (6 patients = group M) or with 0.3 mg of buprenorphine in the same vehicle (6 patients = group B). None of the patients had previously been treated with opioids by any route. After first determining basal values, the following assessments were carried out: (1) evaluation of the analgesic effect of the drugs with checks at 30 min and at 1, 2, 3, 4, 6 and 18 h after administration, using a visual analogue scale, a numerical rating scale and a simple descriptive scale; and (2) evaluation of effects on respiration by means of checks at 30 and 90 min and at 6 and 18 h, on control of breathing indices (P0.1; VE; VA; Ti/Ttot; VT/Ti; RR), gas exchange indices (delta(A-a)O2; VD/VT; pAO2; R) and blood gas and acid-base indices (paO2; paCO2; pH; HCO3-). The data obtained were analyzed statistically using analysis of variance and Student's t test. The study results showed very similar analgesic efficacy for both treatments at a single dosage level of morphine (3 mg) compared to buprenorphine (0.3 mg), which was approximately 3 times greater than an equivalent parenteral dose of morphine (10 mg). Analysis of the results revealed statistically, though not clinically, significant changes in respiratory function indices, only in the buprenorphine-treated group. The effects of buprenorphine on respiratory function, when administered epidurally at the above dosage, are less favourable than those of morphine in the early measurements, probably because of its greater systemic absorption; nevertheless, the risk of delayed respiratory depression appears to be less after buprenorphine than after morphine.

Aged↗

Influence of the carotid body on gas exchange during exercise.

The role of the carotid body in the ventilatory changes of exercise is reviewed. Peripheral chemoreceptor function was studied in 20 patients with chronic airways obstruction. The patients were treated double-blind and randomly allocated to placebo and almitrine bismesylate 50 mg b.d. before undertaking an exercise programme at day 0 and after 30 and 60 days of therapy. Patients on almitrine therapy had an improved resting arterial oxygen tension (PaO2) which was maintained during exercise. A statistically significant improvement of effort tolerance was observed after 60 days treatment with almitrine.

Aged↗

Acute on chronic comparative effects of a combination of fenoterol-ipratropium bromide and terbutaline in patients with chronic obstructive lung disease.

Twenty patients suffering from chronic obstructive lung disease (COLD) were examined in a randomized intra-individual single-blind study in order to compare the ventilatory response, tolerance and side-effects of a combination of 40 micrograms ipratropium bromide and 100 micrograms fenoterol (Duovent) with 250 micrograms terbutaline, both given by inhalation (2 puffs) three times a day. The ventilatory parameters FVC, FEV1, sGaw, RV and PaO2, tested on the 7th and 14th days at 0, 30, and 240 min after the morning administration of the two drugs, showed significant differences between treatments, revealing a greater persistence of bronchodilator effect and a more prolonged duration of action with Duovent than with terbutaline. We believe that the results obtained suggest the usefulness of a combination of anti-cholinergic and beta 2-agonist drugs in the treatment of reversible bronchial obstruction in COLD, where even the parasympathetic nervous system seems to play an important role. The observed clinico-functional effects (intensity and duration of bronchodilatation) together with the lack of side-effects permit us to affirm that Duovent is a rational pharmacologic combination which represents real progress in the difficult treatment of COLD patients.

Adult↗

Oral beta 2-selective adrenergic bronchodilators.

Oral beta 2-agonists (carbuterol, pirbuterol, procaterol, bitolterol, clenbuterol) are drugs widely used as bronchodilators. The efficacy and selectivity of bronchodilators drugs depend on their intrinsic pharmacological properties and on the route of administration. The characteristics of the oral route are easy usage, precise dosage and assured effects. Consequently, disadvantages (delayed onset of action, more frequent side-effects) and the indications, (patients with severe chronic airways obstruction, nocturnal asthmatic attacks, and children and elderly subjects) are clearly evident. The most recent beta 2-agonists have an efficient and prolonged bronchodilating action with well-known side-effects. In order to control drug efficiency in a large population and identify type and degree of adverse reactions, a post-marketing surveillance study was programmed for clenbuterol. The results available confirms that long-term treatment with oral clenbuterol is an effective and safe therapeutical approach. During long-term treatment, tachyphylaxis (a diminished responsiveness) develops. This complex biological phenomenon can be studied, in several ways i.e. functional response of target-organ, appropriate biochemical-metabolical indices, and functional evaluation of the cellular beta-receptors in vitro. Also in the light of evaluation of serum levels of cyclic nucleotides (cyclic adenosine and guanosine monophosphates) it appears that the clinical importance of tachyphylaxis is mild and that chronic therapy with beta 2-agonists is safe and effective when used in selected patients.

Administration, Oral↗

A review of clinical studies carried out in Italy with almitrine bismesylate.

The authors refer to a double-blind versus placebo multicentric study, carried out in Italy on 128 hypoxaemic patients suffering from COLD, with Almitrine bismesylate, a new chemoreceptor stimulant drug, given by mouth for a period of two months. Almitrine induced significant changes (p less than 0.001) of PaO2, with a mean increase of 7.6 mmHg, and of PaCO2, with a mean decrease of 4.1 mmHg, without variations of lung volumes and caliber of large and/or small airways. Almitrine, well tolerated within the time limits of this trial, seems an effective oral respiratory drug, acting through a favourable effect on V/Q mismatching due mainly to a reduction of the shunt effect, but also to an improvement of the ventilatory pattern.

Almitrine↗

Acute effects of captopril in hypoxic pulmonary hypertension. Comparison with transient oxygen administration.

The present study was carried out to test the hypothesis of a possible effectiveness of captopril--an enzymatic inhibitor of both angiotensin II formation and bradykinin degradation--on hypoxic pulmonary hypertension. In 6 patients with this clinical condition, captopril-induced changes in pulmonary hemodynamics were observed after the acute administration of the drug with and without a short period of oxygen therapy at a flow rate sufficient to keep the PaO2 over 60 mm Hg. In our patients, captopril significantly lowered pulmonary arterial pressure and vascular resistance only when combined with oxygen, suggesting that an increase in bradykinin availability and/or a decrease in angiotensin II synthesis might be important factors in reversing pulmonary arterial hypertension only after blunting of the hypoxic stimulus on pulmonary circulation. Moreover, the authors suggest that the employment of vasodilators in the setting of hypoxic pulmonary hypertension should be considered not only as a means of relieving vasoconstriction but also as a possible tool for maintaining cardiac output and, in turn, peripheral oxygen delivery.

Aged↗

Serum theophylline and ventilatory function in chronic obstructive lung disease. Comparison between two slow-release formulations of theophylline.

Pharmacokinetics and ventilatory response to Theodur (Th) was compared to that of Aminomal R (AR) in a randomized within-patient double-blind study, carried out in patients with chronic obstructive lung disease. Both slow-release preparations of theophylline were given every 12 hours for 14 days each at the end of a placebo wash-out period. Th and AR did not differ significantly in their bronchodilating effect at 3 and 12 hours after intake. Salbutamol consumption was not dissimilar in the 2 preparations. Mean serum theophylline levels remained within the therapeutic range at 2, 3 and 12 hours after sustained administration of both Th and AR, but were slightly lower and less fluctuating after Th. Gastrointestinal side effects such as epigastric discomfort, nausea, abdominal pain and diarrhea were more common after AR, a result likely due to its higher content of anhydrous theophylline per tablet (474 mg vs 300 mg in Th). In conclusion, we failed to detect differences between Th and AR in their bronchodilating effect after sustained treatment in patients with chronic obstructive lung disease. Th, however, although containing less theophylline per tablet, resulted in comparable theophylline levels with similar ventilatory response, in presence of a better gastrointestinal tolerability. These results suggest a better bioavailability of Th, likely accounted for by a more advanced pharmaceutical technology.

Albuterol↗

Noninvasive assessment of chronotropic and inotropic response to preferential beta-1 and beta-2 adrenoceptor stimulation.

The relative chronotropic and inotropic activity of preferential beta 1- and beta 2-adrenoceptor stimulation was investigated in seven healthy male subjects in a randomized within-subject, single-blind study. Two doses of beta 1-selective agonist prenalterol (1 mg/hr or 2 mg/hr) and of beta 2-selective agonist salbutamol (300 micrograms/hr or 600 micrograms/hr) were infused intravenously in four separate sessions, with intervals of at least 48 hr between sessions. At each session cuff blood pressure and heart rate (HR) were measured and some hemodynamic information on the inotropic state were derived by echocardiography. Both prenalterol and salbutamol induced increases in HR, but tachycardia was greater after salbutamol, whereas the positive inotropic response to beta-stimulation was greater after prenalterol. At comparable HR rises (prenalterol, from 66.0 +/- 5.5 to 72.2 +/- 4 bpm; salbutamol, from 64.6 +/- 6 to 70.0 +/- 7 bpm), inotropic response seemed to be greater after prenalterol than after salbutamol (systolic blood pressure [SBP]: 133.5 +/- 8 and 120.7 +/- 8 mm Hg; mean velocity of circumferential fiber shortening [Vcf]: 1.54 +/- 0.13 and 1.31 +/- 0.12 c/s; ejection fraction [EF]: 72.4% +/- 5% and 69.5% +/- 4%; stroke index: 47.4 +/- 4 and 41.7 +/- 3 ml/m2). In presence of a chronotropic effect (HR from 64.6 +/- 6 to 70.0 +/- 7 bpm), the low salbutamol dose did not induce any changes in the indices of inotropism (SBP: from 119.2 +/- 6 to 120.7 +/- 8 mm Hg; mean Vcf: from 1.28 +/- 0.11 to 1.31 +/- 0.12 c/s; EF: from 68.1% +/- 5% to 69.5% +/- 4%; stroke index: from 40.2 +/- 3 to 41.7 +/- 3 ml/m2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

Ventilatory effects of selective beta 1-(prenalterol) or beta 2-(salbutamol) adrenoceptor agonism in man.

We compared the ventilatory effects of prenalterol (beta 1-selective adrenoceptor agonist) with those of salbutamol (beta 2-selective adrenoceptor agonist) in 6 healthy volunteers. Two intravenous doses of prenalterol (1 mg/60 min, 2 mg/60 min) and of salbutamol (300 micrograms/60 min, 600 micrograms/60 min) were given in random order in 4 separate sessions of 60 minutes each. Pulmonary ventilation per minute (V'E) increased only on the high dose of salbutamol. Mouth occlusion pressure (P0.1) did not vary either on prenalterol or on salbutamol. Only the high dose of salbutamol induced (1) an increase in tidal volume (VT) without changes in respiratory rate (RR), (2) an increase in mean inspiratory flow (VT/Ti) without changes in the fraction of inspiratory time to total cycle duration (Ti/Ttot). During forced expiration, salbutamol elicited a small bronchodilating effect at the level of both large (FEV1, FEF25-75, FEF50) and small (FEV3, FEF75-85, FEF75) airways. Prenalterol induced a very small dilatation of the large airways, and a somewhat more pronounced effect at the level of the small airways. Neither the indexes of ventilatory pattern nor those of bronchial tone showed any statistical or biological differences between values on prenalterol and values on salbutamol. However, both the former and the latter indexes showed a trend to be higher on salbutamol than on prenalterol. Results suggest that salbutamol-induced increase in pulmonary ventilation per minute in subjects without bronchial obstruction is likely the result of a reduced bronchomotor tone at rest, leading to an increase in tidal volume because of the rise in the VT/Ti ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

[Alpha 1-antitrypsin deficiency: the Brescia clinical study].

In a longitudinal clinical study, two hundred subjects have been evaluated in order to identify alpha 1-antitrypsin deficiency patients. According to their serum alpha 1-antitrypsin levels, they have been divided into three groups: 25 patients with severe deficiency (with both pathological alleles--ZZ, SZ or Z and rare deficiency allele--and, if clinically suggested, to be treated with augmentation therapy), 92 patients with intermediate deficiency (with one pathological allele, to be followed up in order to evaluate the risk to develop deficiency related disease) and 63 healthy subjects (normal alleles MM). They performed lung function test (including cardiopulmonary exercise test and methacholine bronchial challenge) chest X-ray and high resolution computed tomography, blood tests. Severe deficiency patients also performed perfusional lung scan to detect early disorders of blood flow, evaluation of arterial blood gases and liver echotomography. Expiratory flow limitation, the prevalence of vascular disease, the amount of urine elastin products and correlations between the amount of nitric oxide exhaled and bronchial hyperresponsiveness have been also investigated. The study showed that in Brescia county the deficiency is more common than expected and that evaluation of liver and vessels might be as useful as lung function tests. In addition, beneficial effect on local system has been observed. The longitudinal study might permit to detect early organ damage and to eliminate additive risk factors.

Adolescent↗