Frequent Toxicity from IV Aminophylline Infusions in Critically Ill Patients

1977 ◽  
Vol 11 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Leslie Hendeles ◽  
Lyle Bighley ◽  
Robert H. Richardson ◽  
Charles D. Hepler ◽  
Jan Carmichael
Keyword(s):  
Plasma Concentration ◽  
Strong Relationship ◽  
Constant Infusion ◽  
Poor Correlation ◽  
Chronic Obstructive ◽  
Strongly Correlated ◽  
Theophylline Concentration ◽  
Drug Induced ◽  
Obstructive Pulmonary Disease ◽  
Plasma Theophylline

Use of recommended IV aminophylline dosage regimens in 48 older, acutely ill, hospitalized patients with chronic obstructive pulmonary disease (COPD) resulted in excessive plasma theophylline concentrations in 29 percent of these patients. A mean dose of 0.89 mg/kg/hr produced a plasma concentration which ranged from 7 to 52 mcg/ml with a mean of 21.9 mcg/ml. Plasma theophylline concentration was determined spectrophotometrically from plasma samples drawn at least 12 hours after a loading dose and initiation of a constant infusion. Severity of toxicity strongly correlated with the plasma theophylline concentration in 18 patients. Nausea and/or vomiting preceded life-threatening drug-induced arrhythmias and seizures less than half the time. Tachycardia was found to be the most consistent symptom associated with toxicity. These patients had lower plasma clearances than otherwise healthy younger adult asthmatics and healthy volunteers. Toxicity and identifiable risk factors for excessive plasma levels strongly correlated with reduced plasma clearance. Dosage modifications based upon plasma clearances from COPD patients without concurrent functional abnormalities and those with liver dysfunction and cardiac decompensation ranged from 0.7 to 0.12 mg/kg/hr. This study clearly demonstrates the poor correlation between dose and plasma concentration and the strong relationship between toxicity and plasma concentration. These results as well as those previously reported mandate that the relatively simple, rapid and inexpensive theophylline plasma measurement be used in all patients receiving IV aminophylline for longer than 24 hours in order to prevent toxicity.

Treatment of Chronic Obstructive Pulmonary Disease with Two Sustained-Release Theophylline Preparations

1987 ◽  
Vol 15 (6) ◽  
pp. 352-360
Author(s):  
S. Giosue' ◽  
D Bernocchi ◽  
D. Parola ◽  
R. Munno ◽  
P. Mancini
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Sustained Release ◽  
Slow Release ◽  
Chronic Obstructive ◽  
Theophylline Concentration ◽  
Obstructive Pulmonary Disease ◽  
Blood Samples ◽  
Theophylline Preparation ◽  
Plasma Theophylline ◽  
Sustained Release Theophylline

A sustained-release theophylline preparation in capsule form was compared with standard slow-release theophylline tablets for variation in plasma theophylline concentration, effectiveness and tolerability in 30 adults with chronic broncho-obstructive pathology. They were administered every 12 h and blood samples were collected after 8 days of treatment during the steady-state period. In this double-dummy crossover study, the sequence of the two regimens (sustained-release capsules versus tablets) was selected at random. The results of this study demonstrate that plasma theophylline levels remain within the therapeutic range for both preparations. Effectiveness and tolerability of the two drugs were satisfactory.

Clinafloxacin-Theophylline Drug Interaction

1995 ◽  
Vol 29 (4) ◽  
pp. 378-380 ◽  
Author(s):  
Paul R Matuschka ◽  
Richard S Vissing
Keyword(s):  
Drug Interaction ◽  
Pharmacokinetic Interaction ◽  
Hepatic Metabolism ◽  
Chronic Obstructive ◽  
Serum Concentrations ◽  
Theophylline Concentration ◽  
Serum Theophylline Concentration ◽  
Serum Theophylline ◽  
Obstructive Pulmonary Disease ◽  
The Right

Objective: To report an apparent pharmacokinetic interaction between clinafloxacin and theophylline in a patient with chronic obstructive pulmonary disease (COPD). Case Summary: A patient with a history of COPD was admitted for a fracture of the right femoral neck. Admission medications included extended-release theophylline 400 mg bid. The initial serum theophylline concentration was 81.03 µmol/L (normal 55—110). A subsequent concentration was subtherapeutic (46.62 µmol/L) and the theophylline dosage was increased to 300 mg tid. Therapeutic steady-state concentrations were achieved. The patient later developed pneumonia and was enrolled in a study of nosocomial acquired pneumonia involving clinafloxacin versus ceftazidime. He was randomized to receive clinafloxacin 200 mg iv ql2h. After clinafloxacin therapy was initiated, the serum theophylline concentration increased into the toxic range (155.96 µmol/L). Theophylline administration was held for 2 doses and the dosage then reduced to 200 mg tid. Serum concentrations decreased to within the therapeutic range. Discussion: The fluoroquinolones have been shown to interact with the hepatic metabolism of theophylline and increase serum theophylline concentrations. The quinolone metabolite, 4-oxo-quinolone, inhibits the N-demethylation of theophylline, leading to a decrease in the clearance of theophylline. The resultant rise in theophylline concentrations corresponds with the decrease in clearance and possible toxicity. In our patient, careful monitoring of theophylline concentrations and dosage adjustments resulted in the restoration of therapeutic serum concentrations. Conclusions: The observation of this drug interaction between clinafloxacin and theophylline suggests a need for prudent monitoring of theophylline concentrations. Dosage adjustments may be warranted when this combination of medications is used. Such action may prevent significant toxicities and prolonged hospitalization. Further controlled clinical trials in healthy volunteers are needed to substantiate the interaction between clinafloxacin and theophylline.

Bioavailability of a New Sustained-Release Anhydrous Theophylline Product

1996 ◽  
Vol 24 (4) ◽  
pp. 331-339 ◽  
Author(s):  
G Tatsis ◽  
G Tsoukalas ◽  
A Haviaras ◽  
A Peristerakis ◽  
V Filaditaki ◽  
...  
Keyword(s):  
Sustained Release ◽  
Adverse Reactions ◽  
Chronic Obstructive Lung Disease ◽  
New Product ◽  
Chronic Obstructive ◽  
Maximum Plasma ◽  
Theophylline Concentration ◽  
Time Curve ◽  
Plasma Theophylline ◽  
Anhydrous Theophylline

The bioavailability of a new sustained-release anhydrous theophylline product (Theophylline Lavipharm®) was evaluated and compared with the bioavailability of a well-established product, Theodur®. Two groups of 12 healthy non-smokers were given single doses of 200 or 300 mg of each product and two groups of 12 patients with asthma or chronic obstructive lung disease were given doses of 200 or 300 mg of each product every 12 h for 5-day periods. The values of the area under the plasma theophylline concentration against time curve (AUC), the maximum plasma theophylline concentration ( Cmax) and the time taken to reach Cmax (Tmax) for the two products did not differ significantly in the healthy groups or in the patients. The minimum and the average plasma theophylline concentrations and the fluctuation index were also calculated for the patients and there were no significant differences between the values for the two products. The new anhydrous theophylline product, Theophylline Lavipharm®, appears to show very similar bioavailability to Theodur®. No adverse reactions to the new product were reported.

Medical Management Considerations for Patients With Lung Transplantation

2001 ◽  
Vol 14 (4) ◽  
pp. 258-276 ◽  
Author(s):  
Robert E. Dupuis ◽  
David J. Taber ◽  
Amy L. Fann ◽  
Kevin P. Lumbert
Keyword(s):  
Lung Transplantation ◽  
Immunosuppressive Agents ◽  
Chronic Obstructive ◽  
Drug Induced ◽  
Obstructive Pulmonary Disease ◽  
Drug Regimens ◽  
Short And Long Term ◽  
End Stage

Lung transplantation has become an accepted modality for the treatment of end-stage lung disease. Adult and pediatric patients with a variety of lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis are candidates for lung transplantation. Lung transplantation can extend survival and improve quality of life for these patients. With the introduction of new immunosuppressive agents and enhanced surgical and medical care, both short- and long-term morbidity and mortality in these populations, although not as good as other transplant types, are improving. After lung transplantation, recipients continue to face a number of obstacles including post-operative complications, complex drug regimens, drug-induced toxicities, infection, and rejection. An understanding of the management and monitoring issues after lung transplantation is the focus of this review.

scholarly journals Drug-induced interstitial lung lesions

2018 ◽  
Keyword(s):  
General Condition ◽  
Morphological Changes ◽  
Beta Blockers ◽  
Lung Parenchyma ◽  
Pathological Process ◽  
Chronic Obstructive ◽  
Lung Pathology ◽  
Drug Induced ◽  
Obstructive Pulmonary Disease ◽  
Lung Lesions

Drug-induced interstitial lung lesions (DIILL) are one of the most common forms of drug pneumopathy. DIILL account is about 3% in the structure of the entire interstitial lung pathology. Drugs induce various types of lesions of the lung parenchyma, often combining several histopathological patterns. Diagnostics of DIILL deals with many problems, since there are no specific clinical, morphological changes and specific markers. The diagnosis depends on the chronological dependence between taking the drug and the development of symptoms, and is confirmed by an improvement in the general condition of the patients after discontinuation of treatment. The aim of the work was to study the effect of various drugs on the development of DIILL, clinical diagnostic criteria, characteristic CT (computed tomography) and X-ray features, as well as the prognosis of the future course of the disease. We observed 12 patients with DIILL, which were divided into 2 groups: 1st group consisted of 4 patients with amiodarone lung, 2nd group of 8 patients, in which CT of the chest organs revealed an interstitial lesion of the lung tissue in the form of “frosted glass”. This gave us a reason to diagnose DIILL in patients who had CT scan in connection with suspected bronchocarcinoma in 3 patients, prolonged pneumonia in 3 patients and chronic obstructive pulmonary disease in 3 patients with fever. All patients took antibiotics of different groups a long time, ACE inhibitors, beta-blockers. The diagnosis of DIILL was made on the basis of the anamnesis of the patients, the CT data, as well as the positive dynamics of the general condition of the patients after the cancellation of the above medication. Diagnostic difficulties are often caused by late clinical and radiological manifestations or the lack of improvement after stopping the potentially “guilty” drug. However, timely diagnosis of DIILL is extremely important, since in many cases, the cancellation of the medication contributes to the resolution of the pathological process.

scholarly journals Evaluating Stable Chronic Obstructive Pulmonary Disease by Ultrasound

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Togay Evrin ◽  
Semih Korkut ◽  
Leyla Ozturk Sonmez ◽  
Lukasz Szarpak ◽  
Burak Katipoglu ◽  
...  
Keyword(s):  
Point Of Care ◽  
Left Lung ◽  
Clinical Decision ◽  
University Hospital ◽  
Annual Number ◽  
Chronic Obstructive ◽  
Strongly Correlated ◽  
Obstructive Pulmonary Disease ◽  
Diaphragmatic Function ◽  
Us Findings

Background and Aim. The purpose of the study was to evaluate the relationship between COPD severity and the diaphragmatic function measured by point-of-care US in patients with stable COPD. Method. A total of 61 patients with COPD and 40 healthy subjects who had been admitted to Ufuk University Hospital between December 2018 and May 2019 were enrolled. Point-of-care US was performed, and lung silhouette and anterior, right, and left hemidiaphragm method in M-mode were used to evaluate the diaphragm. Results. The point-of-care US measurements, lung silhouette method right (Lung Sil R), lung silhouette method left (Lung Sil L), right hemidiaphragm US method in B-mode (Ant B-Mode R), and right hemidiaphragm US method in M-mode (Ant M-Mode R), were significantly different among groups (P<0.001 for each). FEV1 was strongly correlated with Lung Sil R, Lung Sil L, Ant B-Mode R, and Ant M-Mode R (r = 0.963, P<0.001; r = 0.956, P<0.001; r = 0.953, P<0.001; and r = 0.917, and P<0.001, respectively). Negative correlations were detected between the number of exacerbations per year and Lung Sil R and the number of exacerbations per year and Ant M-Mode R (r = −0.599, P<0.001 and r = −0.587, and P<0.001, respectively). Conclusion. In this study, FEV1 and annual number of exacerbations turned out to be strongly correlated US findings. The use of US in COPD patients could help to support clinical decision, but further clinical studies are necessary to confirm those findings.

Levofloxacin-Induced Acute Immune-Mediated Thrombocytopenia of Rapid-Onset

2017 ◽  
Vol 31 (2) ◽  
pp. 234-237 ◽  
Author(s):  
Andrew W. Shih ◽  
Andy S. Lam ◽  
Theodore E. Warkentin
Keyword(s):  
Platelet Count ◽  
Drug Exposure ◽  
Rapid Onset ◽  
Chronic Obstructive ◽  
Drug Induced ◽  
Obstructive Pulmonary Disease ◽  
Immune Mediated ◽  
Drug Dependent ◽  
Low Sensitivity ◽  
Count Recovery

Drug-induced immune thrombocytopenia (D-ITP) typically occurs after the patient has been receiving the implicated drug for at least 1 week, due to newly forming drug-dependent antibodies (“typical-onset” D-ITP). A “rapid-onset” form of D-ITP can occur when previous sensitization has occurred, where antibodies have thus already been formed, and a precipitous platelet count fall occurs upon reexposure. Typical-onset D-ITP has been reported after levofloxacin, but the rapid-onset form with a well-documented previous exposure has not been described. We report a 76-year-old male treated with levofloxacin for acute exacerbation of chronic obstructive pulmonary disease. After a single 750 mg oral dose of levofloxacin, his platelet count fell from 187 to 5 × 109/L (nadir) over 4 days. Other causes of thrombocytopenia were ruled out. He had received a previous course of levofloxacin 6 months earlier. Discontinuation of levofloxacin and treatment with intravenous immunoglobulin and dexamethasone resulted in platelet count recovery. Levofloxacin-dependent antibodies were not detectable, consistent with the known low sensitivity of laboratory tests for drug-dependent antibodies, presumably indicating antibodies against levofloxacin metabolites, as is indirectly supported by the abrupt but relatively slow platelet count decline observed. This case illustrates a rapid-onset presentation of levofloxacin-induced D-ITP in the setting of previous drug exposure.

scholarly journals Chronic Neutrophilic Leukemia with Monocytosis

2021 ◽  
Author(s):  
Laila Alromaih ◽  
Leena Abdalla ◽  
Arifa Jamal ◽  
Assim Osman ◽  
Mohanad Bakkar ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Ct Scanning ◽  
Molecular Study ◽  
Chronic Obstructive ◽  
Drug Induced ◽  
Diagnostic Dilemma ◽  
Obstructive Pulmonary Disease ◽  
Genetic Features ◽  
Artery Disease ◽  
Oncology Centre

Chronic neutrophilic leukaemia is a very rare disease with diagnosis based on persistent leucocytosis >25×103/µl and monocytes <1×103/µl. The revised WHO criteria 2016 included CSF3R gene mutations as a diagnostic finding. We report the case of a 77-year-old man who was found to have asymptomatic persistent mature neutrophilic leucocytosis with monocytosis. Molecular study confirmed the presence of a CSF3R gene mutation in the absence of morphological or genetic features of myelodysplasia or other forms of myelodysplastic syndrome. The patient’s medical history was significant for coronary artery disease, hypertension, chronic obstructive pulmonary disease, bilateral cystic bronchiectasis, moderate pulmonary hypertension, tuberculosis treated 27 years previously, hypothyroidism, and a thyroid nodule. He had hepatosplenomegaly but no lymphadenopathy, and no other malignancy was seen on computed tomography (CT) scanning. At the time of evaluation, he was free of symptoms and had no evidence of infection or drug-induced leucocytosis. The patient was referred to an oncology centre and treated with hydroxyurea and subsequently azacitidine. However, he developed pancytopenia with bone marrow aplasia. He died with neutropenia sepsis. The presence of persistent monocytosis in this case created a diagnostic dilemma as to whether the disease was a variant of chronic neutrophilic leukaemia or was reactive monocytosis.

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