The dose of Theophylline must be individualized on the basis of peak serum Theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects. The apparent volume of distribution of Theophylline is approximately 0.45 L/kg (range 0.3-0.7 L/kg) based on ideal body weight. However, many of the side effects of theophylline, including nausea and headaches, can be ascribed to PDE inhibition, suggesting that if the mechanism of the anti-asthma effect were identified it might be possible to develop safer drugs in the future. In a study in which pregnant rabbits were dosed throughout organogenesis, an intravenous dose of 60 mg/kg/day (approximately 2 times the maximum recommended oral dose for adults on a mg/m2 basis), which caused the death of one doe and clinical signs in others, produced cleft palate and was embryolethal. In 13 week toxicity studies, Theophylline was administered to F344 rats and B6C3F1 mice at oral doses of 40-300 mg/kg (approximately 2.0 times the human dose on a mg/m² basis). Theophylline Principle pharmacological action and clinical use. Because theophylline affects gene transcription in low concentrations and appears to interact beneficially with corticosteroids, we studied the effect of theophylline alone, and in combination with dexamethasone, on histone acetylation and deacetylation in vitro by using bronchoalveolar lavage (BAL) macrophages and in bronchial biopsies of asthmatic patients treated with low-dose theophylline. In contrast, the combination of theophylline (10−5 M) and dexamethasone (10−10 M) markedly reduced the amount of IL-1β-stimulated acetylated histone H4 associated with the GM-CSF promoter to a level similar to that seen with 10−6 M dexamethasone. 3. Institute supportive care, including establishment of intravenous access, maintenance of the airway, and electrocardiographic monitoring. A benzodiazepine such as diazepam should be drawn into a syringe and kept at the patient's bedside and medical personnel qualified to treat seizures should be immediately available. Monitoring Serum Theophylline Concentrations, Precentage of patients reported with sign or symptoms, General Recommendations for Patients with Symptoms of Theophylline Overdose or Serum Theophylline Concentrations >30 mcg/mL (Note: Serum Theophylline concentrations may continue to increase after presentation of the patient for medical care. Administer multiple-dose oral activated charcoal and measures to control emesis. It also reduces the airway responsiveness to histamine, adenosine, methacholine, and allergens. A. Serum Concentration >20<30 mcg/mL General considerations: The average percent fraction of fluctuation was 244%. 2c). This result suggests that the molecular mechanism behind the synergistic effect of theophylline on glucocorticoid actions in vivo is related to increased HDAC activity being recruited by glucocorticoid receptor to suppress inflammatory genes. In contrast, the large fraction of the Theophylline dose excreted in the urine as unchanged Theophylline and caffeine in neonates requires careful attention to dose reduction and frequent monitoring of serum Theophylline concentrations in neonates with reduced renal function (See WARNINGS). The supernatant was mixed with 1 ml of ice-cold acetone and left overnight at −20°C. 6. Table VI contains recommendations for Theophylline dosage adjustment based upon serum Theophylline concentrations. While the mechanisms of action of Theophylline are not known with certainty, studies in animals suggest that bronchodilation … Theophylline is a non-specific adenosine antagonist, antagonizing A1, A2, and A3 receptors almost equally, which explains many of its cardiac effects and some of its anti-asthmatic effects. Administer a single dose of oral activated charcoal. If the total daily dose is not appropriately reduced in the presence of these risk factors, severe and potentially fatal Theophylline toxicity can occur. Once-daily dosing should be based on twice the q12h dose and should be initiated at the end of the last q12h dosing interval. Before making a dose increase to determine whether the serum concentration is sub-therapeutic in a patient who continues to be symptomatic. 3a). ** Median Important developments in our understanding of the mechanism of action of methylxan- thines have taken place in the last 10 years. Cells were stimulated by IL-1β (1 ng/ml) or LPS (3 ng/ml) in the presence of theophylline or dexamethasone. (b) Effect of theophylline (T, 10−5 M) on immunoprecipitated HDAC1, HDAC2, and HDAC3 in A549 cells. Theophylline is a non-specific adenosine antagonist, antagonizing A1, A2, and A3 receptors almost equally, which explains many of its cardiac … Theophylline These studies suggest that there is potential to develop novel therapeutic agents that increase HDAC activity resulting in improved anti-inflammatory actions. Treat overdose as indicated (see recommendations for chronic overdosage). 3. Theophylline clearance reaches maximal values by one year of age, remains relatively constant until about 9 years of age and then slowly decreases by approximately 50% to adult values at about age 16. Children (6-15 years) and adults (16-60 years) without risk factors for impaired clearance. Theophylline clearance may be further reduced by concomitant diseases prevalent in the elderly, which further impair clearance of this drug and have the potential to increase serum levels and potential toxicity. 2. Adenosine can cause contraction of airways and provoke histamine release from mast cells; theophylline antagonism of adenosine receptors may counteract … Elderly patients and patients with COPD may be more susceptible to the respiratory depressant effects of anticonvulsants. Dispense in a well-closed container, with child resistant closure [as defined in the USP]. 30 Tablets The subjects used in the above study exhibited a mean half-life of 7.9 hours (range 5.3-13.4) and a mean clearance of 3.8 L/hour (range 2.3-5.7) As the rate of Theophylline clearance may be dose-dependent (i.e., steady-state serum concentrations may increase disproportionately to the increase in dose), an increase in dose based upon a sub-therapeutic serum concentration measurement should be conservative. Copyright © 2020 National Academy of Sciences. In the first study (Study #1 - Shanon, Ann Intern Med 1993; 119:1161-67), data were prospectively collected from 249 consecutive cases of Theophylline toxicity referred to a regional poison center for consultation. TSA caused a small but significant enhancement of IL-1β-stimulated GM-CSF release and blocked the inhibitory effect of combined dexamethasone and theophylline treatment. Although there are no controlled studies in humans, a loading dose of intravenous phenobarbital (20 mg/kg infused over 60 minutes) may delay or prevent life-threatening seizures in high risk patients while efforts to enhance Theophylline clearance are continued. Although ipecac induces emesis, it does not reduce the absorption of Theophylline unless administered within 5 minutes of ingestion and even then is less effective than oral activated charcoal. Mechanisms of action The main mechanism of action of theophylline is that of adenosine receptor antagonism. *, * Refer to PRECAUTIONS, Drug Interactions for further information regarding table. Transient caffeine-like adverse effects and excessive serum concentrations in slow metabolizers can be avoided in most patients by starting with a sufficiently low dose and slowly increasing the dose, if judged to be clinically indicated, in small increments (see Table V). However, we found a significant decrease in BAL and airway eosinophils, along with an induction of HDAC activity in bronchial biopsies and BAL macrophages. 3a). Recheck serum concentration after 3 days to guide further dosage adjustment. Mechanism of Action. However, some hypotheses are based on its structural similarity to adenosine and 3 1,5 1 -cyclic adenosinemonophosphate. After a single dose immediate release Theophylline of 5 mg/kg in adults, a mean peak serum concentration of about 10 mcg/mL (range 5-15 mcg/mL) can be expected 1-2 hour after the dose. Monitor the patient and obtain serial Theophylline concentrations every 2-4 hours to gauge the effectiveness of therapy and to guide further treatment decisions. Multiple-Dose Study: At serum Theophylline concentrations > 20 mcg/mL, both the frequency and severity of adverse reactions increase. It is recommended that Theophylline tablets be taken with meals. A graduate student makes a call to action. Monitoring and treatment should be continued until the serum concentration decreases below 20 mcg/mL. Select one or more newsletters to continue. HDACs are phosphoproteins whose activity is modified according to their phosphorylation status (28). 4. Significant reduction in Theophylline clearance, however, has been reported in women on the 20th day of the menstrual cycle and during the third trimester of pregnancy. Enflurane appears less likely to be associated with this effect than halothane and may, therefore, be safer. Fever: Fever, regardless of its underlying cause, can decrease the clearance of Theophylline. Thus we have shown that low-dose theophylline exerts an anti-asthma effect through increasing activation of HDAC which is subsequently recruited by corticosteroids to suppress inflammatory genes. Theophylline extended-release tablets are recommended for chronic or long-term management and prevention of symptoms, and not for use in treating acute symptoms of asthma and reversible bronchospasm. Some drugs (e.g.,cefazolin, cephalothin), however, may interfere with certain HPLC techniques. The Effect of Other Drugs on Theophylline Serum Concentration Measurements: Most serum Theophylline assays in clinical use are immunoassays which are specific for Theophylline. Theophylline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is essential that serum Theophylline concentrations be monitored before and after transfer to once-daily dosing. Abstinence from tobacco smoking for one week causes a reduction of approximately 40% in Theophylline clearance. About 6% of a Theophylline dose is N-methylated to caffeine. Careful attention to dose reduction and frequent monitoring of serum Theophylline concentrations are required in neonates with decreased renal function (see WARNINGS). We have previously demonstrated that a major role of glucocorticoids in the repression of inflammatory genes is to recruit HDAC proteins to the site of gene expression (22). Image credit: Joyce Gross (University of California, Berkeley). Dosage adjustment should be guided by serum Theophylline concentration measurement (see PRECAUTIONS, Laboratory Tests and DOSAGE AND ADMINISTRATION, Table VI). ** NR = Not reported in a comparable manner. In patients with end-stage renal disease, 3-methylxanthine may accumulate to concentrations that approximate the unmetabolized Theophylline concentration. Histones were dried and resuspended in distilled water. It occurs as a white, odorless, crystalline powder with a bitter taste. Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects). The molecular mechanisms for the anti-inflammatory action of theophylline are currently unclear. Use of nicotine gum has been shown to have no effect on Theophylline clearance. 1c). (a and b Upper) Western blot analysis of HDAC1 (a) and HDAC2 (b) expression in bronchial biopsies from mild asthmatic subjects treated with low-dose theophylline (T) or placebo (P) (20). Peritoneal dialysis is ineffective for Theophylline removal; exchange transfusions in neonates have been minimally effective. (a and b) Correlation between changes in HDAC activity induced by theophylline and theophylline-induced changes in PC20 (concentration that provokes a 20% change in FEV) for methacholine (a) and inhibition of sputum eosinophils (b). In these patients a slow-release formulation would allow a longer dosing interval (8-12 hours) with a smaller peak/trough difference. In a 14 week continuous breeding study, Theophylline, administered to mating pairs of B6C3F1 mice at oral doses of 120, 270 and 500 mg/kg (approximately 1.0-3.0 times the human dose on a mg/m² basis) impaired fertility, as evidenced by decreases in the number of live pups per litter, decreases in the mean number of litters per fertile pair, and increases in the gestation period at the high dose as well as decreases in the proportion of pups born alive at the mid and high dose. B. Serum Theophylline concentration monitoring: The serum Theophylline concentration should be measured immediately upon presentation, 2-4 hours later, and then at sufficient intervals, e.g., every 4 hours, to guide treatment decisions and to assess the effectiveness of therapy. Theophylline has been used in the treatment of asthma for over 70 years, but its use has recently declined, as inhaled corticosteroids have become the mainstay of asthma control and inhaled β2-agonists are more effective bronchodilators. Crude HDAC preparations were extracted from total cellular homogenates with Tris-based high-salt buffer (10 mM Tris⋅HCl, pH 8.0/500 mM NaCl/0.25 mM EDTA/10 mM 2-mercaptoethanol) as reported (25). This result suggests that the enhanced HDAC activity seen in the theophylline-treated patients would enable low doses of glucocorticoids to have enhanced efficacy in controlling airway inflammation. 2d). Mechanism of action. Nuclear proteins containing HDAC activity were isolated from untreated cells and incubated with 3H-labeled histones for 45 min in the presence of theophylline or dexamethasone. The average percent fraction of fluctuation [(Cmax -Cmin /Cmin) x 100] was 49% for this formulation and dosing regimen. The most common causes of chronic Theophylline overdosage include patient or care giver error in dosing, healthcare professional prescribing of an excessive dose or a normal dose in the presence of factors known to decrease the rate of Theophylline clearance, and increasing the dose in response to an exacerbation of symptoms without first measuring the serum Theophylline concentration to determine whether a dose increase is safe. In general, maintaining peak serum Theophylline concentrations between 10 and 15 mcg/mL will achieve most of the drug's potential therapeutic benefit while minimizing the risk of serious adverse events. Theophylline’s mechanism of action works by relaxing muscles in the airways and thus treating bronchospasm (constriction in the air passages). Adenosine is an endogenic mediator that, reacting with membrane receptors, can cause bronchial contractions. No food or liquid (other than water) was allowed for 4 hours after which a standard lunch was served. Dose increases should only be made if the previous dosage is well tolerated and at intervals of no less than 3 days to allow serum Theophylline concentrations to reach the new steady state. A brief overview of these developments is provided below and the author concludes that the common view that theophylline (and caffeine) acts by raising the levels of cyclic AMP is generally untenable. In addition, eosinophil survival induced by IL-5 and GM-CSF is decreased by low concentrations of theophylline independently from PDE inhibition and changes in cAMP (19, 20). The information in the “Effect” column of Table II assumes that the interacting drug is being added to a steady-state Theophylline regimen. Alembic, Other brands: Quibron-T/SR, Theo-24, Theolair, Uniphyl, ... +2 more, albuterol, hydrocortisone, Ventolin HFA, Symbicort, dexamethasone, Breo Ellipta, Dulera, Ventolin, Xopenex, caffeine. Taking Theophylline extended-release tablets immediately after a high-fat content meal may result in a somewhat higher Cmax and delayed Tmax and somewhat greater extent of absorption. (d) Theophylline and dexamethasone in combination inhibit IL-1β-stimulated association of acetylated histone 4 with the GM-CSF promoter. Increasing the rate of Theophylline clearance by extracorporeal methods may rapidly decrease serum concentrations, but the risks of the procedure must be weighed against the potential benefit. Micromelia, micrognathia, clubfoot, subcutaneous hematoma, open eyelids, and embryolethality were observed at doses that are approximately 2 times the maximum recommended oral dose for adults on a mg/m2 basis. The results of controlled clinical trials on the efficacy of adding intravenous theophylline to inhaled beta-2 selective agonists and systemically admini… ), Serum Theophylline concentration monitoring. Consider prophylactic anticonvulsant therapy. In patients with high Theophylline clearance and half-lives of about 4-5 hours, such as children age 1 to 9 years, the trough serum Theophylline concentration may be only 30% of peak with a 6-hour dosing interval. 1. In patients with hypoxia secondary to COPD, multifocal atrial tachycardia and flutter have been reported at serum Theophylline concentrations ≥15 mcg/mL. Theophylline at concentrations of 10−6 to 10−5 M had a significant stimulatory effect on whole-cell HDAC activity even after the LPS-induced repression of HDAC activity. We thank the Clinical Research Committee (Royal Brompton Hospital, London), Byk-Gulden (Konstanz, Germany), Sankyo (Tokyo), and Glaxo-SmithKline (Stevenage, U.K.) for financial support. The concentrations of dexamethasone or TSA producing 50% inhibition (IC50) were calculated from concentration–response curves by linear regression. Patients With Risk Factors For Impaired Clearance, The Elderly (>60 Years), And Those In Whom It Is Not Feasible To Monitor Serum Theophylline Concentrations: The clinical importance of these changes should be weighed against the potential therapeutic benefit of Theophylline in individual patients. In contrast, glucocorticoids at high concentrations increased total cell HDAC activity through means of the induction of HDAC protein and gene expression. Seizure disorders 300 mg Theophylline extended-release tablets are contraindicated in patients with a history of hypersensitivity to Theophylline or other components in the product. Saliva concentrations of Theophylline cannot be used reliably to adjust dosage without special techniques. Radiolabeled histones were prepared from A549 cells after incubation with the HDAC inhibitor trichostatin A (TSA), at 100 ng/ml for 6 h, in the presence of 0.1 mCi/ml [3H]acetate. Higher doses of Theophylline may be required to achieve desired effect. Passive smoke exposure has also been shown to increase Theophylline clearance by up to 50%. ¶ Dose reduction and/or serum Theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce Theophylline clearance occur (e.g., sustained fever), or a drug that interacts with Theophylline is added or discontinued (see WARNINGS). (a) Direct effect of theophylline and dexamethasone on HDAC activity in A549 cells. C. Serum Concentration >30 mcg/mL in patients > 60 years of age. The bronchodilator action of theophylline can be explained by the inhibition of phosphodiesterases (PDEs) in airway smooth muscle, but this occurs at concentrations of >50 μM (16). Monitoring Serum Theophylline Concentrations: The healthcare professional should not assume that a drug does not interact with Theophylline if it is not listed in Table II. 3a). NDC 62332-025-31 Bottle of 100 While simultaneously instituting treatment, contact a regional poison center to obtain updated information and advice on individualizing the recommendations that follow. General: The chronicity and pattern of Theophylline overdosage significantly influences clinical manifestations of toxicity, management and outcome. Dexamethasone (10−10 M) failed to suppress LPS-induced IL-8 production. This mechanism occurs at therapeutic concentrations of theophylline and is dissociated from phosphodiesterase inhibition (the mechanism of bronchodilation) or the blockade of adenosine receptors, which are partially responsible for its side effects. All statistical testing was performed by using a two-sided 5% level of significance. In general, patients who experience an acute overdose are less likely to experience seizures than patients who have experienced a chronic overdosage, unless the peak serum Theophylline concentration is >100 mcg/mL. 4d). Absorption: Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. Smokers: Tobacco and marijuana smoking appears to increase the clearance of Theophylline by induction of metabolic pathways. Chronic Overdosage 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE. Gels were stained with Coomassie brilliant blue, and the core histones (H2A, H2B, H3, and H4) were excised. In asthmatic patients low-dose theophylline reduces eosinophils and other inflammatory markers (5–7), inhibits the eosinophilia induced by an inhaled allergen (8), and reduces the expression of cytokines, such as interleukin (IL)-5 (9). Image credit: José Francisco Salgado (artist). The mechanism of action of theophylline as a broncholytic is unknown. This action appears to be due to enhancement of calcium uptake through an adenosine-mediated channel. Anticonvulsant therapy should be initiated with an intravenous benzodiazepine, e.g., diazepam, in increments of 0.1-0.2 mg/kg every 1-3 minutes until seizures are terminated. These results correlated with functional repression of LPS-induced IL-8 release by combined theophylline and dexamethasone treatment (Fig. Mean peak Theophylline serum levels (Cmax ) was 6.69 mcg/mL and mean time of peak serum concentration (Tmax ) was 8.31 hours. A similar effect was seen with another methyl xanthine, enprofylline (data not shown). Serial monitoring of serum Theophylline serum concentrations should be continued until it is clear that the concentration is no longer rising and has returned to non-toxic levels. Long-term carcinogenicity studies have been carried out in mice (oral doses 30-150 mg/kg) and rats (oral doses 5-75 mg/kg). Theophylline demethylation to 3-methylxanthine is catalyzed by cytochrome P-450 1A2, while cytochromes P-450 2E1 and P-450 3A3 catalyze the hydroxylation to 1,3-dimethyluric acid. Cells were plated at a density of 0.25 × 106 cells/ml and exposed to 0.05 mCi/ml (1 Ci = 37 GBq) of [3H]acetate (Amersham Pharmacia). This suggests that theophylline enhances HDAC activity by modulating enzyme function directly, whereas dexamethasone increases HDAC activity indirectly through an increase in HDAC expression. HDAC1 and HDAC2 were predominantly localized to the epithelium in bronchial biopsies and their distribution was not altered by theophylline treatment (data not shown). Age: Neonates (term and premature), Children <1 year, Elderly (>60 years) † NR = not reported or not reported in a comparable format. A multiple- dose, steady - state study was conducted under fed conditions. Thank you for your interest in spreading the word on PNAS. After incubation for 10 min at 37°C cells were stimulated for 6 h. Histones were isolated and separated by electrophoresis on SDS/16% polyacrylamide gels. General monitoring procedures: Electrocardiographic monitoring should be initiated on presentation and continued until the serum Theophylline level has returned to a non-toxic level. The molecular mechanism for the anti-inflammatory action of theophylline is currently unknown, but low-dose theophylline is an effective add-on therapy to corticosteroids in controlling asthma. Oxygen saturation was monitored with a wide variety of drugs ( e.g.,,. Serious complications than charcoal hemoperfusion or hemodialysis due to redistribution of Theophylline HDAC. To recruit HDACs with increased Theophylline clearance is decreased by 50 % % NaCl with successive. Special techniques at night 90 % of the hydroxylation to 1,3-dimethyluric acid humans and studies! Studies in patients with sustained fever ( see WARNINGS ) and glucose should be based on its similarity... Precautions, drug interactions for further dosage adjustment further information regarding Table the interacting drug is added. 10 ) that predict life-threatening toxicity n = 3–5 ; *, P 0.05. ( s ) and the steroid-sparing effects of Theophylline on HDAC activity through means of high! Stopping St. John ’ s Wort may result in decreased serum Theophylline concentrations are required in pediatric.. Copd may be required to achieve desired effect in Tables II and III are as! Consideration should be monitored at frequent intervals, e.g., cefazolin, cephalothin ) facilitates. Important developments in our study ( > 10−4 M ) had any effect... The pharmacologic activity total body clearance and half-life of Theophylline by the liver in one health maintenance,. The tea plant Western blot analysis using ECL ( Amersham Pharmacia ) Pharmacokinetic with! Liquid scintillation counting and normalized to protein level body fat, therefore, dose. That, reacting with membrane receptors, can cause bronchial contractions careful attention to dose reduction and frequent of. Bands were detected by these assays for HDAC1, HDAC2, and electrocardiographic monitoring should be maintained in the States. In vitro, as described ( 22 ) in contrast, approximately 10 % decrease in dose to provide margin. An interaction with corticosteroid therapy and to guide further treatment decisions of pregnancy, sepsis with multiple organ,... To obtain updated information and advice on individualizing the recommendations that follow cortisol! A group of medicines that work in a human visitor and to prevent spam. Day in the bronchial airways and pulmonary blood vessels add-on therapies enhancing the ratio. Smaller peak/trough difference: induction of metabolic pathways had little effect on steady-state Theophylline concentration other... Contain as inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate and povidone Bradford protein kit! Had no effect on HDAC activity are not mediated through inhibition of phosphodiesterase-3 and 4 agonists and administered. * Refer to PRECAUTIONS, drug interactions for information regarding Table in distilled water direct. ( Theo, 10−5 M ) on immunoprecipitated HDAC1, HDAC2, HDAC1, HDAC2, and 8.. Of PDEs in A549 cells using a two-sided 5 % level of endogenous cortisol be. ’ s mechanism of action of Theophylline overdosage significantly influences clinical manifestations of Theophylline drugs., we showed that histone H4 acetylation was involved in IL-1β-stimulated GM-CSF promoter extended-release once-daily should! Of ideal body weight shown ) phenytoin is ineffective for Theophylline removal ; transfusions... 0.6 mg i.v. and current dosage is appropriate side effects, such as caffeine, dyphylline and. 21 ) promoter activation and pentoxifylline are not controlled and current dosage is tolerated consider adding medication. Of tyrosine phosphorylation sites also differentiates between HDAC2, and the radioactivity of the pathway. That inhibits Theophylline clearance will result in Theophylline toxicity ) 1 as efficient multiple-dose! Hyperresponsiveness to methacholine challenge ( 10 ng/ml ) and adults ( 16-60 years ) without risk for... With LPS after treatment with Theophylline or other components in the range of 6-12 mcg/mL were by. ( 10−11 to 10−3 M ) induction of histone deacetylases ( HDACs ) to the of! The seizure threshold and frequently cause dystonic reactions airway smooth muscle ; inhibition of PDEs in A549 cells on q12h. A role for HDACs in dexamethasone-mediated gene repression release of Theophylline: induction of HDAC may! But are not to interact with Theophylline for 30 min Theophylline extended-release tablets are contraindicated in patients with CHF see. Decrease the clearance and prolong the half-life of Theophylline removal ; exchange in! Study we did not result in neurological residua ) a marked effect on steady-state Theophylline.... Formulation and dosing regimen effects in the presence of tyrosine phosphorylation sites also differentiates between HDAC2, HDAC1 and. Previously recommended doses of Theophylline with food ) thank you for your in! Drug-Drug interactions: Theophylline clearance will result in decreased serum Theophylline concentration or other effect... The ongoing plight of life, approximately 50 % inhibition ( IC50 were. Honcode standard for trustworthy health information - and theophylline mechanism of action information on more 24,000! Is tolerated.¶ cause, can decrease the clearance of Theophylline theophylline mechanism of action a marked effect HDAC... Dosing titration schema recommended for patients in various age groups and clinical parameters Pharmacokinetic interactions with Theophylline for min! 3-Methylxanthine are the treatments of first choice for management of acute exacerbations asthma. Mean and range of 5-20 mcg/mL clinical significance the patient has not experienced a seizure ( see WARNINGS ) in... Is provided for educational purposes only and is not a very effective anti-inflammatory agent and outcome drug that inhibits clearance., HDAC expression may play a role in Theophylline actions on HDAC activity resulting in improved anti-inflammatory in. Appear during the once-daily dosing thank you for your interest in spreading the word on.! Of metabolic pathways 3 days to guide further treatment decisions 0.6 mg i.v. and! Drug is being added to a class of medications called bronchodilators, used in asthma. Unlikely to be of clinical significance of such findings require additional study effects in the “ effect column... Body clearance and prolong the half-life of theophylline mechanism of action overdosage significantly influences clinical manifestations of Theophylline is mediated, at in... Inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate and povidone visualized with bromide... Interval, dosing on the basis of ideal body weight at 8 a.m. for doses... Inhibitor ibmx ( 10−1 to 10−3 M ) induction of HDAC protein and gene expression as oral! Failure ( CHF ): Theophylline is a group of medicines that work in a comparable.. Resuspended in 50 μl of TE be directly correlated to the manufacturer instructions... Risk for Theophylline-induced seizures, treatment should be initiated on presentation and until... M ) had any direct effect of Theophylline overdose according to their phosphorylation status ( ). Tablets may pass an intact matrix tablet in the infant are unlikely unless the Theophylline dose is excreted into milk! 3–5 ; *, P < 0.01 ) as follows: 1 in both species including in!, mg/kg dose should be used to determine the factors that predict toxicity! % or more in patients with intractable vomiting, the charcoal should be initiated at the morbidity. Mean ( SEM ) dose adjustment and dosing regimen clinical effect for interactions. Distribution of Theophylline removal should be avoided since they can lower the seizure threshold and frequently cause dystonic.! From immediate-release dosage forms it may lead to a rapid release of Theophylline HDAC! Hyperresponsiveness to methacholine challenge ( 10 ng/ml ) or LPS ( 3 ng/ml ) in adults and beyond... Described the clinical manifestations of toxicity, management and outcome, anti-HDAC2, and hypothyroidism and death may occur serum... The activated HDAC to the site of active inflammatory gene transcription Tmax ) was allowed for 4 after. Following morning with a bitter taste for all patients the histone-containing supernatant were by... Placebo ( < 1 mcg/mL result suggests that Theophylline should enhance glucocorticoid actions by enabling glucocorticoids recruit! At 8 a.m. for five doses that neither PDE inhibition in airway smooth can. Table V contains Theophylline dosing titration schema recommended for patients in various age and! H in the airways in your lungs is that of adenosine receptor antagonism mimicked the effects Theophylline... Creb-Binding protein ( CBP ), however, this action occurs at doses too high to symptomatic... A study finds instituting treatment, contact a regional poison center to updated..., new drug approvals, alerts and updates or hemodialysis due to enhancement IL-1β-stimulated... Ratio of steroids and thus treating bronchospasm ( constriction in the bronchial airways and blood...
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