Mg Of Aminophylline Research Articles

P175 PARADOXICAL RESPONSE DURING DOBUTAMINE STRESS ECHOCARDIOGRAPHY: A CASE REPORT

Abstract Background Dobutamine Stress Echo (DSE) is a test widely used in the diagnosis of ischemic heart disease. The purpose of the following work is to describe a clinical case with uncommon behaviour. Case Description: 63–year–old female with dyspnoea on mild exertion, and history of NSTEMI–ACS 5 years prior with Coronary Angiography (CA) finding of 3–vessel coronary artery disease, treated with PCI + stent (DES) of right coronary artery (CDX), untreated disease sub–occlusion of the first marginal obtuse (OM1), and chronic occlusion of the anterior interventricular artery (IVA). We decide for DSE. During 20 mcg/kg/min infusion, the patient reported dyspnoea and paradoxical bradycardia (BP) was documented on the ECG, in the absence of ST changes, with the appearance of akinesia of the basal and mid posterolateral segments and worsening of the inferior hypokinesia, present in basal conditions on Echocardiograms (EC). The BP and the alterations of the ventricular motion (VCA) did not respond to the administration of Atropine (1+1 mg) while the administration of 240 mg of Aminophylline (AM) restored the HR and the VCA to baseline values. The CA demonstrated patency of the CDX with the presence of collateral circulation for IVA and occluded OM1. Discussion This case is characterized by the presence of a double paradox: the BP and the Atropine–Resistance (AR). BP during DEB, as demonstrated in previous studies, occurred in 8% of cases, with signs of significant coronary artery disease in 57% of cases. The BP is an expression of ischemia only in just over half of the patients, in the rest of the cases it appeared referable to the Bezold–Jarish reflex, a vagal reflex determined by the stimulation of the intracardiac mechanoreceptors. In our case, the presence of AR seems to exclude the possibility that bradycardia is due to this reflex. The appearance of paradoxical bradycardia during DSE is a rare complication and can lead to premature termination of the test with inconclusive results. In our case, the BP and the AR confirm the positivity of the test also in consideration of the response to the AM antagonist of Adenosine, which accumulates during ischemia. Conclusions This uncommon response to DSE, where AR and AM response in addition to BP could identify patients with severe coronary artery disease in whom the ischemic response is driven by adenosine accumulation, rather than a vagal reflex responding to atropine administration.

Impact of a regimented aminophylline administration protocol on the burden of regadenoson-induced ischemia detected by SPECT myocardial perfusion imaging

BackgroundIn patients undergoing regadenoson SPECT myocardial perfusion imaging (MPI), it is unknown how soon and at which dose intravenous aminophylline can be administered to reverse regadenoson-related adverse effects without blunting stress-induced myocardial ischemia. Methods and ResultsWe analyzed the pooled database of the ASSUAGE and ASSUAGE-CKD trials (n = 548). These were double-blinded, placebo-controlled, randomized clinical trials in which 75 mg of aminophylline or placebo was administered intravenously 90 seconds following 99mTc-tetrofosmin injection. There were no statistically significant differences in summed difference score (SDS) burden (P = .87) and in the rates of myocardial ischemia (SDS ≥ 2) (P = .93) between the aminophylline (n = 274) and placebo (n = 274) groups. There was no interaction between aminophylline use and SDS as a determinant of the composite endpoint of cardiac death or MI (P = .32) or the composite endpoint of cardiac death, MI, or coronary revascularization (P = .92). ConclusionIn patients undergoing regadenoson-stress SPECT-MPI, the intravenous administration of 75 mg of aminophylline as early as 90 seconds after radioisotope injection does not seem to attenuate the burden of myocardial ischemia.

The Effect of Aminophylline on Renal Colic: A Randomized Double Blind Controlled Trial

To evaluate the efficacy of aminophylline infusion as a painkiller compared with placebo in patients with acute renal colic. From March to August 2005, 141 patients with clinical renal colic, who were under 60 years of age, had no history of heart or hepatic failure, asthma, theophylline or beta blocker use, reaction to methylxantines, pregnancy or breast feeding, and were not prescribed spasmolytic or analgesics, entered our study. They were randomly assigned to receive either 375 mg of aminophylline or placebo infusion under double blind conditions. Pain intensity was recorded using a visual analog scale (VAS), before drug administration and 30 and 60 minutes afterwards. The drug effectiveness was defined as > or =40% decrease in pain intensity 60 minutes after the onset of infusion, without exacerbation during the following 4 hours. Seventy patients received aminophylline; it was effective in 45 (64%; 95% confidence interval 52-75%). Alternatively, placebo was effective in 12 of 71 control patients (17%; 95% confidence interval 9-28%); (P < 0.001). Thirty and 60 minutes after administration, aminophylline reduced pain by 24% and 39% respectively, as compared with 6% and 8% pain reduction in the placebo group. This prospective study provides remarkable information about the efficacy of aminophylline on pain relief and decreasing narcotic usage in symptomatic urinary calculi. It is safe, inexpensive, with minute side effects and can be considered a good alternative or additive to narcotic analgesics in the management of renal colic.

Effect of aminophylline on complete atrioventricular block with ventricular asystole following blunt chest trauma

A 39-year-old man was the driver of a car involved in an accident, in which he was thrown forward against the steering wheel. On presentation to the emergency room of a local hospital, he was hypotensive and in respiratory distress. The electrocardiogram (ECG), as reported, showed sinus tachycardia. He was intubated, stabilized and transferred to our institution 5 h later. Upon arrival, his pulse was faint and slow. The ECG showed evidence of complete AV-block with ventricular asystole (Fig. 1A). He received 1 mg of atropine IV three times at 3 min intervals and 1 mg of epinephrine IV to no avail. Arrangements for internal cardiac pacing were made, however, following the administration of 500 mg of aminophylline IV, his heart rate increased to 75 (Fig. 1B) and then 150 beats/min (Fig. 1C), at 3 and 5 min, respectively. His ECG reverted to normal sinus rhythm (Fig. 2) with left anterior hemiblock (LAHB) and T-wave inversion in I and aVL 10 min later with a blood pressure of 120/80 mmHg. Echocardiography revealed flailing of the anterior leaflet of the tricuspid valve with severe tricuspid regurgitation. He was admitted to the intensive care unit with a smooth course. Two months later, he was asymptomatic but with persistent LAHB and grade II–III tricuspid regurgitation.

FORMULATION AND EVALUATION OF CONTROLLED RELEASE AMINOPHYLLINE MATRIX TABLETS

Three matrix excipients namely: Hydroxypropylmethylcellulose (HPMC), sodium carboxymethyl cellulose (NaCMC) and egg albumin (EA) were utilized for the preparation of controlled release matrix tablets containing 200 mg of aminophylline. The prepared tablets were evaluated with respect to physical parameters and dissolution rate. All formulations showed acceptable physical parameters. The release rate was variable depending on the composition of the matrix tablet. There was no significant difference between the dissolution rates of the matrix tablets prepared with HPMC or EA. The lowest release rate was observed in case of the matrix tablets prepared using NaCMC either alone or in combination with either HPMC or EA. The dissolution data of the drug from most matrix tablets formulation were fitted to Higuchi diffusion model.

Aminophylline fails to improve the outcome of cardiopulmonary resuscitation from prolonged ventricular fibrillation: A placebo-controlled, randomized, blinded experimental study

Objectives. The purpose of this study was to evaluate systematically the effects of the adenosine antagonist aminophylline on resuscitation outcome In a canine model of postcardioversion nonperfusing rhythm.Background. Theoretic considerations and experimental studies indicate that myocardial adenosine accumulation during prologged ventricular fibrillation might play a significant role in postcardioversion asystole and electromechanical dissociation. A recent uncontrolled clinical trial has suggested that the adenosine antagonist aminophylline might improve the outcome of cardiopulmonary resuscitation from refractory bradyasystolic cardiac arrest.Methods. Two placebo-controlled, randomized, blinded experimental studies were performed. In protocol 1 (20 dogs), ventricular fibrillation was induced and maintained for 7.5 min. Sixty seconds before cardioversion, dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In protocol 2 (20 dogs), dogs were cardioverted to electromechanical dissociation after 5 min of unsupported ventricular fibrillation. Sixty seconds later, all dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In both experiments, resuscitation efforts were continued until return of spontaneous circulation, or up to 30 min. The primary end point was survival to 1 h.Results. In protocol 1, 4 of 10 dogs survived in the aminophylline group, whereas 7 of 10 dogs survived in the placebo group, a nonsignificant trend toward unfavorable outcome from aminophylline. Pretreatment with aminophylline increased the number of cardioversion applications required to terminate ventricular fibrillation. In protocol 2, 5 of 10 and 6 of 10 dogs survived in the aminophylline and placebo groups, respectively.Conclusions. The results of this study suggest that aminophylline fails to improve the outcome of resuscitation from prolonged ventricular fibrillation. It does not reverse established electronic-chemical dissection and may in fact increase the number of cardioversion applications required to terminate ventricular fibrillation. The rationale for conducting clinical trials with aminophylline during cardiopulmonary resuscitation is questionable.

Severe bronchospasm following cardiopulmonary bypass in an asthmatic

Severe bronchospasm following cardiopulmonary bypass in an asthmatic

Aminophylline blood levels with concomitant erythromycin therapy in relapsed chronic obstructive lung disease.

Sixty patients affected by chronic obstructive lung disease (COLD) in relapse were treated with erythromycin and aminophylline. The patients were divided into three groups: Group A received 2 g erythromycin and 1200 mg aminophylline daily, and Group B and C received 2 g erythromycin with respectively 800 mg and 600 mg of aminophylline daily, administered as two oral doses in each case. On day 5 of therapy, we chromatographically evaluated aminophylline in a serum sample taken two hours after morning drug administration which corresponds to the peak plasma level. We also evaluated certain biohumoral, microbiological, radiological and electrocardiographic parameters both before and after therapy. Statistical analysis of the data was performed by the Student's t test. Our data confirm that 600-800 mg oral aminophylline administered simultaneously with erythromycin induce an improvement in the respiratory function of patients with relapsed COLD without elevating blood aminophylline levels and without side-effects.

Maternal-fetal transfer of aminophylline.

Ten women with normal pregnancies who underwent an elective cesarean section received orally 200 mg of aminophylline every 6 hours for 24 - 36 hours prior to surgery. The levels of aminophylline and caffeine were measured in maternal and cord sera and in amniotic fluids. The mean level of aminophylline (+/- SD) in maternal serum was 10.4 +/- 1.74 micrograms/ml, and in cord serum 11.2 +/- 1.25 micrograms/ml. The mean aminophylline level in amniotic fluids was 8.2 +/- 1.42 micrograms/ml. The serum aminophylline levels were within the therapeutic level range. Caffeine levels in those specimens ranged between traces to 6 micrograms/ml which correspond to the normal dietary range.

The effects of aminophylline on adenosine and ATP actions on sinoatrial conduction in the isolated, blood-perfused dog atrium

The effects of adenosine and adenosine triphosphate (ATP) on sinus cycle length (SCL) and sinoatrial conduction time (SACT) estimated by constant atrial pacing were studied in isolated, blood-perfused canine right atria. Adenosine and ATP were infused into the sinus node artery at a rate of 1, 2 and 4 μg/min. Both adenosine and ATP caused an increase in SCL and SACT in a dose-dependent manner and decreased atrial developed tension. There was no significant difference between the effect of adenosine and that of ATP on SCL and SACT. The prolongation of SACT induced by 4 μg/min of adenosine and ATP was significantly inhibited by a single injection of 1 to 3 mg of aminophylline, although this dose level of aminophylline did not significantly suppress the prolongation of SCL produced by adenosine and ATP. From these results it is concluded that both adenosine and ATP lengthen SCL and SACT in a dose-related manner, and that aminophylline blocks the increase in SACT much more easily than that in SCL.

Effects of nicardipine on pancreatic exocrine secretion in the dog.

1. The effects of nicardipine on the secretion of pancreatic juice were investigated in dog isolated, blood-perfused pancreas, and compared with those of papaverine, aminophylline and secretin. 2. Intra-arterial administration of nicardipine (1-10 micrograms) elicited a dose-dependent increase in pancreatic secretion. Papaverine (0.1-1 mg), aminophylline (0.3-3 mg) and secretin (0.03-0.1 units) also elicited increased secretion. The secretory activity of nicardipine (10 micrograms) was approximately equal to that of 0.5 mg of papaverine, 1.5 mg of aminophylline and 0.03 units of secretin. 3. The concentration of bicarbonate in the pancreatic juice induced by nicardipine was increased, but the protein concentration was only increased slightly. These effects are analogous to those of secretin. 4. Nicardipine-induced secretion was not modified by pretreatment with relatively large doses of phentolamine, propranolol, atropine, guanethidine, haloperidol or metiamide. 5. Secretin-induced secretion was significantly potentiated by infusion of papaverine, but not by infusion of nicardipine or aminophylline. 6. These results suggest that nicardipine acts on the exocrine cells in the dog pancreas, at least in part, through the increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.

Effect of Caffeine on Circulating Theophylline Levels in Beagle Dogs

The pharmacokinetic interactions of caffeine with theophylline were examined in two beagle dogs by administering 100mg of aminophylline intravenously, 3 weeks before and immediately after repeated oral doses of caffeine. Serial plasma samples were analyzed for caffeine and theophylline simultaneously by high-performance liquid chromatography. Upon multiple oral dosing, 100mg every 12hr for 7 days, the caffeine half-life increased slightly in one dog but decreased in the other. As predicted from single-dose data, caffeine accumulation in plasma after repeated doses was slight, while plasma levels of the N- demethylated metabolite, theophylline, rose to about three times the initial values. After rapid intravenous doses of aminophylline, the theophylline half-life was 5-7 hr, which decreased slightly when the drug was administered concomitantly with caffeine during steady state of caffeine. The theophylline volume of distribution (0.75 liter/kg) was unaffected by caffeine. On the other hand, an acute aminophylline injection prolonged the elimination half-life and increased the apparent volume of distribution of caffeine, causing little overall change in its plasma clearance. The results suggested that interactions between theophylline and caffeine may be attributed to changes in drug distribution and drug elimination characteristics.

Effects of parenteral aminophylline on lung mechanics in normal human.

We studied the effects of an intravenous injection of 5.0 mg of aminophylline per kg of body weight on lung mechanics in 8 normal subjects. No change occurred in lung volumes, airway resistance, and maximal expiratory flow-volume and lung pressure-volume curves. Restudy of 4 of the subjects before and after an injection of 8.0 mg/kg of aminophylline did not modify the pattern of response to the drug, despite a serum concentration range of 15.1 to 19.3 mg/l. These findings were, therefore, in contrast with those observed after the administration of atropine or beta-2 adrenergic derivatives. They suggested that the bronchodilator effects of aminophylline may not be due to a direct action of the drug on the bronchial smooth muscle.

Effect of an antacid on gastrointestinal absorption of theophylline

The effect of a magnesium-aluminum hydroxide antacid (Maalox) on the oral absorption of aminophylline tablets was studied. Twelve healthy adults were administered 200 mg of aminophylline alone or with 30 ml of antacid in a complete crossover study. Blood samples were drawn at 0.33, 0.67, 1, 2, 4, 8, 12, and 24 hours following theophylline (as aminophylline) administration. Theophylline plasma levels were measured by high-performance liquid chromatography. The plasma theophylline concentrations of the group receiving theophylline only were significantly greater than those of the group receiving theophylline plus antacid at the 0.67- and 1-hour sample times only (p less than 0.05). The extent of theophylline absorption and the eliminated rate constant were not significantly affected by the antacid. Antacid significantly decreased theophylline's absorption rate constant (p less than 0.05), indicating a slower absorption of theophylline with antacid. Concurrent administration of the antacid Maalox should not significantly change theophylline's clinical effect.

SERUM CONCENTRATIONS OF THEOPHYLLINE IN CHILDREN FOLLOWING THE ADMINISTRATION OF DOSES GENERALLY RECOMMENDED:NEW DOSAGE REGIMEN REQUIRED

Serum concentrations of theophylline following intravenous and oral administration of aminophylline were studied in asthmatic children, 2--17 years of age. The biological half-life (t 1/2 beta) of theophylline varied between 165 and 495 min. The results revealed that an intravenous loading dose of 6 mg of aminophylline per kg body weight was necessary in order to obtain therapeutic concentrations in children who had not received the drug for the last 6 to 8 hours. The maintenance dose should be determined and controlled by use of serum concentration determinations. In a group of children receiving 5 mg of aminophylline per kg body weight 3 times a day orally, none had concentrations within the therapeutic range in the morning, and only 39% reached therapeutic levels 2 h after the morning dose. No correlation was found between the serum concentration of theophylline and the amount of drug given per kg body weight. The results show that theophylline concentration analysis is necessary to obtain adequate therapeutic levels in children without risking toxic effects.

Disposition of theophylline after a single intravenous infusion of aminophylline.

Theophylline serum concentration and disposition after a single 30-min intravenous infusion of 7.4 ± 1 mg of anhydrous theophylline per kg of body weight were determined in 20 otherwise healthy adult asthmatic volunteers using high-pressure cation-exchange chromatography. This dose resulted in a mean peak serum concentration of 18 ± 3.3 μg per ml, which remained > 10 μg per ml for 6 hours and > 5 μg per ml for the entire 12-hour period of observation. The rate of theophylline elimination in these subjects was generally slower than previously reported. Among the 4 cigarette smokers, however, theophylline plasma clearance was significantly (P < 0.001) more rapid than that observed in the 16 nonsmokers. Theophylline clearance was highly correlated with elimination half-life (r = 0.83, P < 0.001). These data support previous recommendations for an intravenous loading dose of 5 mg of theophylline per kg of body weight (6 mg of aminophylline per kg) when a mean increase in serum concentration of approximately 1...

W10294A: a new bronchodilator.

Eight subjects with asthma were given, orally, increasing doses of W10294A (100, 200, 300 and 400 mg), 300 mg aminophylline and placebo on separate days. Forced expiratory flow rates were measured at hourly intervals for 6 h. Significant increases in mean forced expiratory volume in one second (FEV1) were recorded with the 300 and 400 mg W10294A and 300 mg aminophylline doses compared to placebo. The peak effect of W10294A was recorded at 3 h. The 400 mg W10294A dose resulted in mean FEV1 increases similar to those recorded after the 300 mg aminophylline dose. The mean FEV1 was significantly improved for 6 h by the W10294A. Small but significant increases in mean pulse rate were seen with all doses of W10294A and 300 mg of aminophylline when compared to placebo. Mild headaches or drowsiness were reported by 6 of the 8 subjects after being given W10294A. No headache or drowsiness was reported after 300 mg aminophylline or placebo. We conclude that W10294A causes a dose-related improvement in forced expiratory flow rates and is an effective long-acting bronchodilator with tolerable side-effects when given in single oral doses to asthmatic subjects.

Aminophylline, a Weak Bilirubin Displacer

We have examined the bilirubin-displacing effect of aminophylline, using the peroxidase method.1 It was found that the free bilirubin concentration is increased by 1% for each 2 mg of aminophylline per liter of blood plasma. The results are practically independent of varying concentrations of albumin and fatty acid, within the usual limits. Control experiments indicated that aminophylline does not interfere with the reagents of the test and does not form a bilirubin complex in significant amounts.

Relationship of urinary metabolites of theophylline to serum theophylline levels.

Using high‐pressure liquid chromatography, we have quantitated the theophylline metabolites in the 24‐hr urines of 15 patients in a clinical ward who had been receiving 800 or 1,200 mg of aminophylline /24 hr in divided oral doses. Mean values for the theophylline‐derived urine products were as follows: unchanged theophylline, 7.7 ± 6.1%; 3‐methylxanthine, 36.2 ± 7.3%; 1,3‐dimethyluric acid, 39.6 ± 4.5%; and 1‐methyluric acid, 16.5 ± 3.3%. These data are consistent with those earlier reported for theophylline metabolism in man with other methodology. The fractional contents of urine products were variably related to trough serum theophylline levels, the latter determined by the Schack and Waxler method. There was a significant direct correlation between serum theophylline levels and the urine theophylline fraction, and a significant inverse correlation between serum theophylline and the urine 3‐methylxanthine fraction. Urinary 3‐methylxanthine and 1,3‐dimethyluric acid were inversely related, implicating competition for substrate. The urine content of 1,3‐dimethyluric acid and 1‐methyluric acid diverged as serum theophylline increased, suggesting that the former may give rise to the latter by a rate‐limiting demethylation reaction. The data suggest that the 1‐demethylation of theophylline to 3‐methylxanthine is the dominant reaction determining serum theophylline.

The effect of aminophylline on insulin release induced by secretin and cholecystokinin-pancreozymin in normal humans.

ABSTRACT The purpose of this study is to search the possibility that insulin-secretion, induced by the administration of pharmacological doses of relatively purified preparations of secretin and cholecystokinin–pancreozymin (CCK-PZ), might be mediated through the activation of the adenyl-cyclase system in the β-cell of normal humans. To test this hypothesis the effect of a 15-min infusion of 250 mg of aminophylline on insulin release induced by cholecystokinin-pancreozymin (CCK-PZ) and secretin was studied in 12 normal subjects. CCK-PZ (2 U/kg/body wt) iv administered to 6 subjects provoked a quick and transient insulin release. In a second test aminophylline (250 mg) was infused for 15 min before CCK-PZ (2U/kg/body wt) was given; in this test a significantly enhanced insulin secretion was observed in every subject. The effect of secretin was tested in an identical way in 6 subjects. It was observed that the infusion of aminophylline previous to the secretin injection (2 U/kg/body wt) elicited a significa...