Effects Of Terbutaline Research Articles

Can Terbutaline Be Used as a Nebuliser instead of Intravenous Injection for Inhibition of Uterine Activity?

Terbutaline, a betamimetic drug, is used as bolus of 0.25 mg intravenously to inhibit uterine activity when encountered with uterine hyperstimulation and associated fetal heart rate changes. The effect of terbutaline used as a nebuliser in 1- and 2-mg doses on uterine activity in labor was investigated. It did not show any significant inhibition of the uterine activity in spontaneous term labor. Although convenient and easy to administer especially in an emergency, 1 or 2 mg terbutaline used in the form of nebuliser did not give the desired effect like 0.25 mg of terbutaline given intravenously for inhibition of uterine activity in term labor.

Unequal Day-Night Terbutaline I.V. Dosing in Acute Severe Asthma: Effect on Nocturnal Bronchial Patency, Heart Rate, and Arterial Pressure

Our study investigated the differential effects of continuous or unequal day-night terbutaline dosing on circadian bronchial patency, heart rate, and arterial pressure in severe acute asthma. Forty-five hospitalized asthmatic patients (19 women and 26 men, mean age 45.4 years, mean weight 63.5 kg) were included in this multicenter study. Three groups of patients (corresponding to three dosing schedules) were randomized; the three groups were comparable, since no statistically significant difference was detected in the age, weight, or peak expiratory flow values at the beginning of the study. In order to reach immediately the concentrations of terbutaline corresponding to the desired unequal day-night concentrations, a theoretical pharmacokinetic simulation was done to predict the outcome in terms of the plasma concentrations after the three dosing regimens; the results of this simulation allowed us to calculate the initial bolus dose to be given over 5 min to groups A, B, and C, i.e., 1.47, 2.94, and 4.41 micrograms/kg, respectively. This bolus was given to all patients at 0700 h, the beginning of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Normal responsiveness of superficial hand veins to alpha- and beta-adrenergic stimuli in allergic asthma: Effects of terbutaline and prednisolone on beta-adrenergic responsiveness

Impaired function of the adrenergic-receptor system has been postulated to contribute to the pathogenesis of bronchial asthma. Using the dorsal hand-vein compliance technique, we compared the changes in diameter of superficial hand veins in response to phenylephrine, an alpha-adrenoceptor agonist, and to isoproterenol, a beta-adrenoceptor agonist, in 14 untreated patients with allergic asthma and in 16 nonatopic control subjects. There were no significant differences in the median effective dose of phenylephrine that produced 50% of maximal venoconstriction (ED50) or in the maximal response (Emax) between the two groups. Bronchial hyperreactivity (assessed by methacholine-challenge tests) in the patients with asthma was uncorrelated with the ED50 or Emax of isoproterenol. These results demonstrate no evidence for a generalized change in alpha- or beta-adrenergic responsiveness on smooth muscle cells in asthma. Hand-vein responsiveness to isoproterenol was unchanged after treatment for 7 days with oral terbutaline (5 mg three times per day). Thus, unlike leukocytes, smooth muscle appears not readily susceptible to beta-adrenoceptor desensitization in vivo. Local infusions of prednisolone or dexamethasone during 2 hours and systemic administration of dexamethasone (24 hours) caused a significant fall in the Emax for isoproterenol. The mechanism of attenuation of beta-adrenoceptor responsiveness by corticosteroids remains to be determined.

Antigen‐induced dyspnea in Sprague Dawley rats

We wanted to study the effect of anti-asthma drugs on antigen-induced dyspnea in conscious Sprague Dawley (S.D.) rats. A line of dyspnea bred rats was produced, where all immunized animals respond with dyspnea when challenged with aerosolized ovalbumin (OA). The animals were immunized intraperitoneally (i.p.) with OA (10 micrograms) together with Al(OH)3 (100 mg) and challenged 2 to 3 weeks later with OA aerosol. We examined the effects of terbutaline (TERB), disodium cromoglycate (DSCG), atropine (ATRO), theophylline (THEO), a 5-HT receptor antagonist methysergide (METH), and two glucocorticosteroids (GCS) budesonide (BUD) and dexamethasone (DEX), on this response. The drugs were given locally either by intratracheal (i.t.) instillation or by aerosol. The rats were placed one by one in an air tight box and the breathing pattern was recorded. Parameters such as time of onset of dyspnea after end of challenge (elapsed time), duration and occurrence of dyspnea, were used to quantify the response. In the vehicle- treated group nearly all animals responded to OA with signs of dyspnea. TERB was the only drug effective when given as an aerosol, whereas when given i.t., also DEX and METH inhibited the dyspnea. Dyspnea is a serious response and can only be alleviated by the most effective anti-asthma drugs.

Effects of Intravenous Terbutaline on Maternal Circulation and Fetal Heart Activity

The effects of terbutaline on maternal circulation and fetal heart activity were studied in 15 healthy pregnant women admitted for external cephalic version. The two-step infusion of terbutaline (5-10 micrograms/min) resulted in increases in maternal heart rate (p less than 0.001), cardiac output (p less than 0.001), systolic arterial pressure (p less than 0.001) and pulse pressure (p less than 0.001), while diastolic arterial pressure (p less than 0.001) and total peripheral vascular resistance (p less than 0.001) were reduced. Mean arterial pressure was unchanged after the infusion. Fetal heart activity assessed by cardiotocography showed a gradual increase in baseline fetal heart rate (p less than 0.01) and an increased percentage acceleration time (p less than 0.05). Fetal movements also increased during the infusion (p less than 0.05). The terbutaline infusion had a positive inotropic effect and produced decreased systemic vascular resistance in the pregnant woman, and placental transfer of the drug resulted in increased fetal heart activity. The potential influence of the drug-induced changes in maternal hemodynamics on utero-placental perfusion require further investigation.

Comparison of Outpatient Nebulized vs Metered Dose Inhaler Terbutaline in Chronic Airflow Obstruction

Eighteen patients (nine asthmatic patients and nine with poorly reversible airflow obstruction) with stable, severe chronic airflow obstruction, completed a four-week randomized, doubled-blind, placebo-control, crossover trial comparing the acute and chronic effects of terbutaline administered by metered-dose inhaler (MDI) and nebulizer (NEB). Equipotent doses of terbutaline were selected from the comparison of separate cumulative dose-response curves for MDI and NEB. The MDI and NEB given acutely produced similar bronchodilatation and improvement in exercise performance. Spirometric indices, 6 min walking distance, symptom scores and extra beta-agonist use were no different between MDI and NEB treatment fortnights in the outpatient study. We conclude that the degree of bronchodilatation achieved in these patients is a reflection of the dose of bronchodilator administered and not the mode of administration. There is no justification for the preferred outpatient use of nebulized bronchodilators in patients with stable chronic airflow obstruction who can use adequate doses of bronchodilators via a metered-dose inhaler.

Effect of terbutaline on human eustachian tube function.

Terbutaline, a beta 2-adrenoceptor agonist, was administered subcutaneously to 10 healthy adult subjects. The pressure opening level (Pol) of the Eustachian tube (ET) and the remaining middle ear pressure when the ET closed (Pcl) after passive equilibration were measured as well as parameters for active tubal function. A quantitative impedance method in combination with a pressure chamber was used. Pol was reduced by 0.29 +/- 0.10 (-7.3%) kPa 90 min after injection of terbutaline 5 micrograms/kg body weight. There was also a decrease in Pcl, 0.17 +/- 0.06 kPa (-14.0%). No such decrease was seen after saline solution injected subcutaneously. It is suggested that terbutaline facilitates the ET opening by stimulating the secretion of surface tension lowering substances.

Pharmacodynamic and Pharmacokinetic Aspects on the Transport of Bronchodilator Drugs Through the Tracheal Epithelium of the Guinea‐Pig

An isolated vagus nerve-trachea tube preparation from guinea-pig was used to study the effect kinetics of bronchodilating beta-adrenoceptor agonists. The test compounds were added either into the fluid-filled lumen or into the external medium and they all inhibited, dose-dependently and completely, the vagally induced contractions. The hydrophilic compounds isoprenaline, salbutamol and terbutaline were much less potent when administered intratracheally as compared with extratracheal administration indicating a slow transport through the epithelial layer. For the lipophilic compound, D2489 (the resorcinol derivative of salmeterol), this difference was less pronounced. When terbutaline was administered as its lipophilic diisobutyrate ester prodrug, ibuterol, the difference between the routes of administration was largely eliminated. The inhibitory effect of terbutaline, but not D2489, was readily reversed by washing. Measurements of terbutaline and D2489 in the tracheal tissue and in the external medium after the intratracheal administration of the compounds support the view that a hydrophilic compound slowly passes the epithelium and is not retained in the tissue, whereas a lipophilic compound rapidly passes the epithelium and is retained by the tissue. The isolated vagus nerve-trachea tube preparation of the guinea-pig is well suited for the concommitant study of pharmacodynamic and pharmacokinetic properties of bronchodilator drugs.

THE EFFECT OF TERBUTALINE ON EXOCRINE FUNCTION IN THE DENERVATED CANINE PANCREAS

This study was designed to evaluate the effects of the beta adrenergic agonist, terbutaline, on pancreatic exocrine secretion in the denervated canine pancreas. In vitro assessment was performed by evaluating the effect of terbutaline on 10(-8) OP-CCK stimulated amylase release of pancreatic tissue slices incubated at 37 degrees C in Krebs-bicarbonate media. In vivo assessment was accomplished in animals with pancreatic autografts and functioning pancreaticocystostomies, by evaluating the effect of intravenous terbutaline (0.075 mg/kg over 15 min) on the basal, and OP-CCK (125 ng/kg/hr)--stimulated, rate of secretion of urinary (autograft) amylase and bicarbonate. Incubation of tissue slices with terbutaline had no significant effect on OP-CCK-stimulated amylase release. The intravenous terbutaline infusion resulted in a decrease in the basal rate of amylase (U/min) and bicarbonate (mmol/min) secretion, with the bicarbonate inhibition being significantly decreased, when compared with controls (0.073 +/- .04 vs. 000 +/- .00; P less than 0.05). Following the terbutaline infusion, there was also a significant decrease in OP-CCK-stimulated amylase (140.3 +/- 23.3 vs. 24.6 +/- 11.9; P less than 0.005) and bicarbonate release (.069 +/- .03 vs. .003 +/- .001; P less than 0.05). This inhibition persisted until the study was terminated 3 hr after the terbutaline infusion. These studies demonstrate that terbutaline causes a significant and prolonged decrease in autograft exocrine secretion--and, as a result, may have a therapeutic role in reducing the exocrine complications associated with pancreatic transplantation. The mechanism of action of this agent in the denervated pancreas requires further elucidation.

Effect of terbutaline, a β2-adrenoreceptor agonist, on gastric acid secretion and serum gastrin concentrations in humans

Because β-adrenoreceptor agonists inhibit gastrinstimulated gastric acid secretion in animals, we postulated that the β2-adrenoreceptor agonist, terbutaline, would inhibit pentagastrin-stimulated acid secretion in humans. Moreover, we hypothesized that terbutaline might inhibit food-stimulated acid secretion, as gastrin is a major mediator of food-stimulated acid secretion. Subcutaneous terbutaline (0.25 mg) reduced acid secretion during intravenous infusion of a submaximal dose of pentagastrin by 30%–40% (p < 0.005), even though terbutaline increased serum gastrin levels (p < 0.05). Furthermore, subcutaneous (0.25 mg) or oral (5 mg) terbutaline, given before a homogenized steak meal was infused into the stomach, lowered mean food-stimulated acid secretion rates, despite enhanced postprandial serum gastrin concentrations. Terbutaline also increased serum gastrin concentrations in patients with Zollinger-Ellison syndrome and in vagotomized individuals. Thus, β2-adrenoreceptor agonists enhance gastrin release while at the same time inhibiting gastrin-stimulated acid secretion in humans.

Mechanisms of terbutaline-induced inhibition of exocrine pancreatic secretion in humans.

Terbutaline, a selective beta 2-adrenoreceptor agonist, has recently been advocated as a potential agent for treating patients with pancreatic fistulae. In the present study, we attempted to quantify the presumed effects of terbutaline on exocrine pancreatic secretion in humans and to characterize possible mechanisms of action. In six healthy volunteers, the pancreas was stimulated by infusion of graded doses of secretin (15.5-250 ng/kg/h) or by infusion of secretin (15.5 ng/kg/h) plus graded doses of caerulein (3.3-30 ng/kg/h). The experiments were repeated in each subject without and with administration of terbutaline. Pancreatic secretion was assessed by a marker perfusion technique and plasma somatostatin and pancreatic polypeptide (PP) levels by radioimmunoassay. Terbutaline had no significant effect on secretin-stimulated pancreatic secretion, but significantly inhibited caerulein-stimulated pancreatic fluid secretion and trypsin output. Plasma somatostatin and PP levels were not affected by terbutaline. The inhibitory effect required the administration of pharmacologically large doses of terbutaline. We conclude that the weak inhibitory effect of terbutaline on exocrine pancreatic secretion is not mediated via somatostatin nor PP and that our data do not support a major role for beta-adrenergic mechanism as regulator of pancreatic secretion.

Beta 2-mediated changes in central haemodynamics, coronary circulation and myocardial metabolism in canine.

The combined effect of terbutaline on systemic and coronary circulation was investigated in dogs to clarify its influence on myocardial oxygen supply and lactate balance. The dogs were anaesthetized and the chest opened. Coronary sinus blood flow and cardiac output were monitored by thermodilution, aortic pressure was measured by tip-transducer and heart rate by RR-interval on ECG, coronary sinus blood were analyzed for lactate, oxygen and carbon dioxide. Terbutaline caused a substantial systemic vasodilation and an increased heart rate, the total external cardiac work increased to a minor degree. Terbutaline increased arterial lactate concentration. Coronary vascular resistance was reduced after terbutaline. Even if myocardial perfusion pressure was reduced and an increased external cardiac work was present, no signs of myocardial distress was observed in lactate metabolism or coronary sinus oxygen content. In fact a tendency to increased myocardial aerobic metabolism was observed, as myocardial lactate consumption increased after terbutaline. Terbutaline seems to be a coronary vasodilator in dogs. However, the demand for oxygen secondary to both an increase in cardiac work and aerobic metabolism can be hazardous to the potentially ischaemic myocardium.

Magnesiuric and calciuric effects of terbutaline in man.

1. The effect of terbutaline infusion over 4 h on serum levels of potassium, ionized calcium, phosphate and magnesium and urinary excretion of potassium, calcium, magnesium and adenosine 3':5'-cyclic monophosphate was studied in six healthy volunteers. 2. Serum levels of potassium, calcium, phosphate and magnesium decreased. Urinary excretion of potassium decreased, whereas those of calcium, magnesium and adenosine 3':5'-cyclic monophosphate increased. 3. These results indicate that the hypocalcaemic and hypomagnesaemic effects of terbutaline can, at least partly, be explained by enhanced urinary excretion of calcium and magnesium. This may have important implications for the short-term terbutaline treatment of patients with, for example, cardiac disease.

Effects of terbutaline and atenolol on large and small airways in asthmatic patients

In order to localize the main site of action of the beta 2-adrenoceptor selective agonist terbutaline and the beta 1-adrenoceptor selective antagonist atenolol in the airways of asthmatic patients, we compared the effects of these drugs on maximal expiratory flow-volume (MEFV) curves when breathing air and when breathing a helium-oxygen (HeO2) mixture. To investigate whether a shift in localization of the bronchodilator effect occurs when terbutaline is inhaled repeatedly, dose-response curves with terbutaline were performed for parameters derived from MEFV curves when breathing air and for density dependence of expiratory airflow. By measurement of MEFV curves when the patients were breathing air alone, it was not possible to determine whether there is a difference in the bronchoconstrictor effect of atenolol between large and small airways. Inhalation of terbutaline to a cumulative dose of 2.0 mg induced a stepwise improvement in expiratory airflow parameters for large and small airways function when breathing air. Doubling the dose of inhaled terbutaline to 4 mg did not result in any further improvement of lung function. Neither atenolol nor terbutaline induced significant mean changes in density dependence of expiratory airflow. This was partly due to large inter- and intra-individual variations of this parameter. Another possibility is that atenolol and terbutaline effect large and small airways function equally.

Nocturnal asthma: effects of slow-release terbutaline on spirometry and arterial blood-gases

The effect of terbutaline, in a slow-release preparation, on spirometry and arterial blood-gases, was studied in fourteen patients with nocturnal asthma. The patients were treated with either 15 mg of slow-release terbutaline or placebo given as a single dose at 10 pm for eight days in a double-blind crossover trial. The patients were studied in the hospital for one night at the end of each treatment period. During active treatment the patients had a significantly higher FEV1 and PaO2 compared with placebo. Tolerance to the high single dose was good and none of the patients discontinued treatment because of side-effects. In patients with nocturnal asthma treatment with a high dose of slow-release terbutaline given as a single dose in the evening appears to be effective.

Terbutaline in diagnosis of interstitial fallopian tube obstruction.

Effectiveness of terbutaline, a potent uterine muscle relaxant, for differentiation of temporary and anatomic interstitial fallopian tube obstruction (IFTO) at hysterosalpingography (HSG) was explored. In 43 IFTO evaluated, HSG after terbutaline showed patency in only one of 16 tubes in which IFTO was caused by spasm or other temporary cause. We conclude that terbutaline is not helpful in differentiating temporary from anatomic tubal obstruction during HSG.

Age-dependent effects of beta 2-adrenergic-stimulating drugs on fetal rabbit lung liquid and adrenal catecholamines.

The effects of the beta 2-adrenergic-stimulating drug, terbutaline, were studied on fetal rabbit lung liquid (FLL) at gestational ages between 25 and 30 days. At delivery terbutaline reduced FLL in rabbit fetuses with a gestational age of 26-30 days. The most pronounced reduction of FLL was seen at 28 days. Terbutaline administration reduced the wet lung weight/body weight (WLW/BW) ratio at delivery in the 28- and 30-day-old rabbit pups. In the 26-day-old animals, beta 2-adrenergic stimulation had no significant effect on the WLW/BW ratio and at 25 days of gestational age the ratio was increased. After parturition, however, the difference in WLW/BW between the terbutaline and control animals, seen at birth, was attenuated and, at 60 min of postnatal age, the difference was no longer observed. Terbutaline decreased the adrenal content of noradrenaline and adrenaline most marked at 28 days of gestational age, but did not alter the adrenaline/noradrenaline ratio. Furthermore, adrenal dopamine was decreased after terbutaline, suggesting a decreased catecholamine synthesis. Our data show that a positive effect of terbutaline on FLL in rabbit pups was most marked during late but not early gestational age. beta 2-Adrenergic treatment may, however, reduce adrenal catecholamines.

A study on intrauterine fetal resuscitation with terbutaline

A randomized study on the effect of terbutaline on fetal distress was carried out in 20 patients who showed evidence of ominous fetal heart rate patterns and fetal scalp blood pH values of less than 7.25. Of those, 11 received terbutaline (study group) and nine did not (control group). There was a significant improvement in the acid-base status of the fetus in the study group compared with those in the control group (p less than 0.01). No significant maternal or fetal morbidity occurred in the study group. Apgar scores at 1 minute were 7 or greater in 10 of the 11 study subjects whereas only four of the nine control subjects had a score of 7 or greater. These results suggest that terbutaline may become a useful agent in the treatment of intrauterine fetal distress.

The roles of Ca2+ and adenosine 3',5'-monophosphate in the regulation of progesterone production by human placental tissue.

The effects of Ca2+ and cAMP on progesterone production by placental tissue were studied. Term placentas obtained from normal pregnant women were perfused with sterile saline to remove blood, and the minced trophoblastic tissue was incubated in vitro. The rate of progesterone secretion by the trophoblastic tissue was 47.5 +/- 5.0 (+/- SE) ng/mg cell protein X h (control) at 450 micrograms low density lipoprotein/mL. The rates of progesterone production and cAMP accumulation were accelerated 3.0- and 1.7-fold, respectively, by 10(-5) M terbutaline, and the terbutaline effect was blocked by the addition of 50 microM N-(6-aminohexyl)5-chloro-1-naphthalenesulfonamide (W-7) or 50 microM trifluoperazine. Whereas progesterone secretion by placental explants cultured in medium containing low density lipoprotein with 1 microM A23187 (calcium ionophore) reached a rate of 128.5 +/- 8.5 ng/mg cell protein X h, incubation of placental explants with A23187 caused a highly significant, dose-related decrease in terbutaline-stimulated cAMP accumulation in the presence of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor. Inhibition by A23187 was Ca2+ dependent, since incubation in a Ca2+-free medium with EGTA blocked its effect. Intracellular Ca2+ is apparently necessary for placental progesterone production; enhancement of progesterone production by beta2-stimulation is mediated by intracellular Ca2+ and cAMP.

Beta-Adrenergic Inhibition of Pancreatic Secretion in Dogs

Terbutaline, a beta-adrenergic agonist, administered subcutaneously inhibits pancreatic exocrine secretion. We studied the effects of intravenous terbutaline and propranolol on cholecystokinin-stimulated pancreatic secretion in conscious dogs. Terbutaline inhibited pancreatic juice volume, bicarbonate concentration, bicarbonate output and protein output, but had no effect on protein concentration. Propranolol blocked this inhibition and had no effect on the response to cholecystokinin. These observations suggest that (1) terbutaline inhibits pancreatic secretion by a beta-adrenergic mechanism and (2) the primary effect of terbutaline on canine exocrine pancreas is inhibition of water and bicarbonate secretion.