Neuromuscular blocking agents alone should not be used to terminate seizures since they abolish the musculoskeletal manifestations without terminating seizure activity in the brain. 1c). 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). Mechanism of Action Theophylline is a naturally occurring plant alkaloid related to caffeine and theobromine. Furthermore, the reversal of the steroid resistance induced by oxidative stress suggests that theophylline may increase responsiveness to corticosteroids. The supernatant was mixed with 1 ml of ice-cold acetone and left overnight at −20°C. Specific Recommendations: The mean Tmax was 8.7 hours. Correlation between theophylline actions on HDAC activity and clinical parameters. (300 mg) The listing of drugs in Tables II and III are current as of February 9, 1995. This causes stimulation of cardiac function and relaxation of smooth muscle; Inhibition of cell surface receptors for adenosine. The respective AUC (0-inf.) In summary, we have shown that both in vitro and in vivo theophylline induced a direct activation of HDAC activity. If symptoms are not controlled and current dosage is tolerated consider adding additional medication(s) to treatment regimen. Dosage adjustment guided by serum Theophylline concentration. Consider 10% decrease in dose to provide greater margin of safety even if current dosage is tolerated.¶. Patients should be instructed to inform all healthcare professional involved in their care that they are taking Theophylline, especially when a medication is being added or deleted from their treatment. Revised: 02/2016, NDC 62332-025-30 Miscellaneous: Other factors associated with decreased Theophylline clearance include the third trimester of pregnancy, sepsis with multiple organ failure, and hypothyroidism. 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. This effect of theophylline on HDAC activity was not specific to all HDAC isoforms. ↵* To whom reprint requests should be addressed. Individual patients may experience larger changes in serum Theophylline concentration than the value listed. Patients should be advised that if they choose to take Theophylline tablets with food it should be taken consistently with food and if they take it in a fasted condition it should routinely be taken fasted. The clearance of Theophylline is decreased by an average of 30% in healthy elderly adults (>60 yrs) compared to healthy young adults. Mechanism of Action. In contrast, dexamethasone had no direct effect on HDAC activity (Fig. His productions aim to promote science as a visual and emotional experience. Since Theophylline clearance is independent of liver blood flow, the reduction in clearance appears to be due to impaired hepatocyte function rather than reduced perfusion. If symptoms are controlled and current dosage is tolerated, maintain dose and recheck serum concentration at 6-12 month intervals.¶. The inhibition of p38 MAPK by SB203580 partially inhibited theophylline-induced HDAC activity (198 ± 17 vs. 259 ± 25 dpm), whereas the inhibition of MEK by PD098059 had no effect (220 ± 21 vs. 259 ± 25 dpm) (Fig. Concurrent Diseases: Acute pulmonary edema, congestive heart failure, cor-pulmonale, fever (≥102° for 24 hours or more; or lesser temperature elevations for longer periods), reduced renal function in infants <3 months of age, sepsis with multi-organ failure and shock. Results are pending. Monitor the patient and obtain a serum Theophylline concentration in 2-4 hours to insure that the concentration is not increasing. glass of water. If symptoms are not controlled and current dosage is tolerated, increase dose about 25%. Consider prophylactic anticonvulsant therapy. n = 14 for HDAC1, HDAC2, and HDAC activity assays. (a) Direct effect of theophylline and dexamethasone on HDAC activity in A549 cells. Online ISSN 1091-6490. NDC 62332-025-31 Bottle of 100 Consider prophylactic anticonvulsant therapy. However, there was no correlation between the induction of HDAC activity by low-dose theophylline and the change in FEV1 (r = 0.13, P = 0.65, Fig. 1 a and b). No food was allowed for five hours post-dosing, then a standard lunch was served; at ten hours post-dosing a standard supper was served. Generally, concentrations of unbound Theophylline should be maintained in the range of 6-12 mcg/mL. PDE inhibition in airway smooth muscle can explain the bronchodilator action of theophylline (16). Careful attention to dose reduction and frequent monitoring of serum Theophylline concentrations are required in patients with any of these conditions (see WARNINGS). (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). 30 Tablets It has been postulated that the effects of theophylline are mediated through the inhibition of PDE4 or by means of the antagonism of adenosine receptors. Results are expressed as mean ± SEM (n = 5; *, P < 0.05; **, P < 0.01 vs. LPS control; ***, P < 0.05 vs. unstimulated cells. 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. Cells were resuspended in 200 μl of SDS lysis buffer (50 mM Tris, pH 8.1/1% SDS/5 mM EDTA/complete proteinase inhibitor mixture) and subjected to three cycles of sonication on ice with 10-s pulses. Histones were extracted from nuclei overnight by using HCl and H2SO4 at 4°C and using a method modified from that as described by Turner (23) and by Yoshida (24). A graduate student makes a call to action. * Patients with more rapid metabolism, clinically identified by higher than average dose requirements, should receive a smaller dose more frequently (every 8 hours) to prevent breakthrough symptoms resulting from low trough concentrations before the next dose. To confirm that the effects of theophylline were mediated through HDAC activity we investigated the effect of the HDAC inhibitor TSA (10 ng/ml) on repression of IL-1β-stimulated GM-CSF release. Theophylline is structurally classified as a methylxanthine. If symptoms recur, or signs of toxicity appear during the once-daily dosing interval, dosing on the q12h basis should be reinstituted. The exact relationship of these and other factors to nighttime serum concentrations and the clinical significance of such findings require additional study. Theophylline passes freely across the placenta, into breast milk and into the cerebrospinal fluid (CSF). C. Serum Concentration >100 mcg/mL We therefore examined the effect of a PDE4 inhibitor (rolipram, 10−11 to 10−3 M), a PDE3 inhibitor [Motapizone (Byk-Gulden, Konstanz, Germany), 10−11 to 10−3 M], and an adenosine receptor antagonist (CGS 15943, 10−11 to 10−3 M), on HDAC activity (Fig. Patients With Risk Factors For Impaired Clearance, The Elderly (>60 Years), And Those In Whom It Is Not Feasible To Monitor Serum Theophylline Concentrations: Table VI. These studies suggest that there is potential to develop novel therapeutic agents that increase HDAC activity resulting in improved anti-inflammatory actions. Theophylline salts — Several so-called "salts” of theophylline had been developed as attempts to increase water solubility (8 mg/mL at 25ºC) and improve absorption. Mean peak Theophylline serum levels for the two treatments were 3.7 mcg/mL (fasting) and 4.4 mcg/mL (with food).The time of peak serum level varied from subject to subject, occurring from 4 to 14 hours after dosing. Conversely, if Theophylline is being initiated in a patient who is already taking a drug that enhances Theophylline clearance (e.g., rifampin), the dose of Theophylline required to achieve a therapeutic serum Theophylline concentration will be larger. Western blot analysis demonstrated a significant increase in HDAC1 (0.28 ± 0.06 vs. 0.44 ± 0.07, P = 0.0299), but not HDAC2 (0.28 ± 0.06 vs. 0.49 ± 0.10, P = 0.1) expression, after theophylline treatment (Fig. 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). Theophylline tablets can be taken once a day in the morning or evening. It is important that the product whenever dosed be dosed consistently with or without food. Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Adenosine is an endogenic mediator that, reacting with membrane receptors, can cause bronchial contractions. Serum Concentrations at Steady-State: After multiple doses of Theophylline, steady-state is reached in 30-65 hours (average 40 hours) in adults. (see PRECAUTIONS, Drug Interactions, Table II). After sonication, acetylated histone H4 was immunoprecipitated and the associated DNA was amplified by PCR. General: The chronicity and pattern of Theophylline overdosage significantly influences clinical manifestations of toxicity, management and outcome. Mechanisms of action The main mechanism of action of theophylline is that of adenosine receptor antagonism. Higbee MD, Kumar M, Galant SP. 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). Active peptic ulcer disease Released 3H-labeled acetic acid was extracted by ethyl acetate, and the radioactivity of the supernatant was determined by liquid scintillation counting. Repetitive seizures should be treated with a loading dose of phenobarbital (20 mg/kg infused over 30-60 minutes). It has two different mechanisms of actionin people with reversible lung obstruction: as a bronchodilator, it causes smooth muscle relaxation. The information in the “Effect” column of Table II assumes that the interacting drug is being added to a steady-state Theophylline regimen. 3a). Theophylline Edited by Joseph A. Beavo, University of Washington School of Medicine, Seattle, WA, and approved May 1, 2002 (received for review October 18, 2001). HDAC activity (a) and IL-8 secretion (b) were measured in normal nonsmoking subjects as described in Materials and Methods. Table II. Passive smoke exposure has also been shown to increase Theophylline clearance by up to 50%. A. Saliva concentrations of Theophylline cannot be used reliably to adjust dosage without special techniques. What is theophylline, and how does it work (mechanism of action)? Table I. Dosage Form: tablet, extended release. 5. Serum Concentration >30 mcg/mL in patients > 60 years of age. (a) Direct effect of theophylline (Theo, 10−11 to 10−3 M), the nonspecific PDE inhibitor IBMX (10−11 to 10−3 μM), the PDE3 inhibitor motapizone (10−11 to 10−3 M), the PDE4 inhibitor rolipram (10−11 to 10−3 M), and the adenosine receptor antagonist CGS-15943 (CGS) (10−11 to 10−3 M) on HDAC activity. (a and b Lower) Graphical expression of the effect of low-dose theophylline (T) and placebo (P) on HDAC1 and HDAC2 expression relative to β-actin. LPS significantly reduced whole-cell HDAC activity (Fig. The mechanism of action of theophylline as a broncholytic is unknown. Acta Med Scand 1985; 217: 14!9-53. ** Average effect on steady-state Theophylline concentration or other clinical effect for pharmacologic interactions. Recheck serum concentration after 3 days to guide further dosage adjustment. Three high fat content meals were served at 6:30 a.m., 12 noon and 6:30 p.m. Nineteen normal subjects were dosed at 300 mg every 12 hours (7 p.m. and 7 a.m.) for eight doses. Dosage adjustment guided by serum Theophylline concentration. HDAC assays were performed and the effect of theophylline on each HDAC was examined. At steady- state, on a dosage regimen with 6-hour intervals, the expected mean trough concentration is approximately 60% of the mean peak concentration, assuming a mean Theophylline half-life of 8 hours. Mechanism of Action. If the patient is vomiting, the charcoal should be administered through a nasogastric tube or after administration of an antiemetic. We have shown in the present study that low concentrations of theophylline and low concentrations of dexamethasone can increase the repression of inflammatory cytokine release in both macrophages and epithelial cells. Find patient medical information for Theophylline Oral on WebMD including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Case reports of Theophylline overdose in humans and animal studies suggest that phenytoin is ineffective in terminating Theophylline-induced seizures. In addition, we found that the presence of tyrosine phosphorylation sites also differentiates between HDAC2, HDAC1, and HDCA3. The sample was microcentrifuged for 10 min, washed with acetone, dried, and diluted in distilled water. hash brown potatoes, 1 slice of toast with a pat of butter, and 8 oz. Last updated on Oct 1, 2019. Extended-Release Theophylline is a methylated xanthine which exerts several pharmacological actions of therapeutic interest. Furthermore, side effects, such as nausea and headaches, commonly occur at previously recommended doses of theophylline. The magnitude and duration of the fever appear to be directly correlated to the degree of decrease of Theophylline clearance. 7. 2. Since this non-linearity results in more than proportional changes in serum Theophylline concentrations with changes in dose, it is advisable to make increases or decreases in dose in small increments in order to achieve desired changes in serum Theophylline concentrations (see DOSAGE AND ADMINISTRATION, Table VI). Several studies have described the clinical manifestations of Theophylline overdose and attempted to determine the factors that predict life-threatening toxicity. Other xanthines such as caffeine, dyphylline, and pentoxifylline are not detected by these assays. 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. Careful attention to dose reduction and frequent monitoring of serum Theophylline concentrations are required in patients with reduced hepatic function (see WARNINGS). Before addition of a newly available drug in a patient receiving Theophylline, the package insert of the new drug and/or the medical literature should be consulted to determine if an interaction between the new drug and Theophylline has been reported. Individual patients may experience larger changes in serum Theophylline concentration than the value listed. 2. While the mechanisms of action of theophylline are not known with certainty, studies in animals suggest that bronchodilatation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV) while non-bronchodilator prophylactic actions are probably mediated through one or more different molecular mechanisms, that do not involve … It is also one of the few effects that has been reported at therapeutic drug concentrations. 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. If a dose is missed, the patient should be instructed to take the next dose at the usually scheduled time and to not attempt to make up for the missed dose. 3b). Originally, theophylline was used as a bronchodilator and the optimal plasma concentration that gave maximal bronchodilation with the lowest risk of side effects was found to be 10–20 mg/liter (55–110 μM) (2). Generic Name: Theophylline anhydrous It is essential that serum Theophylline concentrations be monitored before and after transfer to once-daily dosing. What dosage should you take? A blood sample should usually be taken 4–6 hours after an oral dose of a modified-release preparation (sampling times may vary—consult local guidelines). Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. In studies in which pregnant mice, rats and rabbits were dosed during the period of organogenesis, Theophylline produced teratogenic effects. † NR = not reported or not reported in a comparable format. Another proposed mechanism of action includes a non-specific inhibition of phosphodiesterase enzymes, producing an increase in intracellular cyclic AMP; however, this is not known with certainty. Low doses of theophylline, which give a plasma concentration of <5 mg/liter, may achieve control of asthma comparable to a low dose of inhaled corticosteroids in both children and adults (3, 4). Waterborg (31) has shown that even in the resting state histones are acetylated and that small differences in the number of acetylated histones result in biophysical changes. Eosinophil infiltration is characteristic of asthmatic airway inflammation, and eosinophil survival in the airways depends on GM-CSF secretion from epithelial cells (30). In the absence of glucocorticoids the activated HDAC is not targeted to the site of inflammatory gene transcription. Therefore, it is not recommended that Theophylline extended-release once-daily dosing be administered at night. Institute supportive care, including establishment of intravenous access, maintenance of the airway, and electrocardiographic monitoring. Values listed were generally determined at serum Theophylline concentrations <20 mcg/mL; clearance may decrease and half-life may increase at higher serum concentrations due to non-linear pharmacokinetics. Cells were stimulated by IL-1β (1 ng/ml) or LPS (3 ng/ml) in the presence of theophylline or dexamethasone. 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. Enhance clearance of Theophylline: Multiple-dose oral activated charcoal (e.g., 0.5 mg/kg up to 20 g, every two hours) increases the clearance of Theophylline at least twofold by absorption of Theophylline secreted into gastrointestinal fluids. Experiments were also conducted using a commercially available fluorescent HDAC assay kit (Fluor de Lys, BioMol, Exeter, U.K.) according to the manufacturer's instructions. *, * Refer to PRECAUTIONS, Drug Interactions for further information regarding table. Sorbitol, however, should be dosed with caution since it is a potent purgative which can cause profound fluid and electrolyte abnormalities, particularly after multiple doses. Whenever signs or symptoms of Theophylline toxicity are present. Nuclear proteins containing HDAC activity were isolated from untreated cells and incubated with 3H-labeled histones for 45 min in differing assay pH conditions. 1. NOTE: In addition to the factors listed above, Theophylline clearance is increased and half-life decreased by low carbohydrate/high protein diets, parenteral nutrition, and daily consumption of charcoal-broiled beef. 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. The remainder is excreted in the urine mainly as 1,3-dimethyluric acid (35-40%), 1-methyluric acid (20-25%) and 3-methylxanthine (15- 20%). Single-Dose Study: Alternatively, the charcoal can be administered continuously through a nasogastric tube in conjunction with appropriate antiemetics. More recently it has been shown that low concentrations of theophylline were able to inhibit the activation of NF-κB and reduce the expression of inflammatory genes in a manner similar to corticosteroids (18). Plasma-theophylline concentration is measured 5 days after starting oral treatment and at least 3 days after any dose adjustment. We have previously shown that a major component of glucocorticoid actions in the suppression of inflammatory cytokine production is through the recruitment of HDAC activity to the activated transcriptional complex (22). B. Serum Concentration >30 mcg/mL in patients <60 years of age Theophylline works by opening the airways in your lungs. Dispense in a well-closed container, with child resistant closure [as defined in the USP]. 4a). GM-CSF and IL-8 were measured by sandwich ELISA (R&D Systems Europe, Abindon, U.K.) according to the manufacturer's instructions. The drugs listed in Table II have the potential to produce clinically significant pharmacodynamic or pharmacokinetic interactions with Theophylline. Enflurane appears less likely to be associated with this effect than halothane and may, therefore, be safer. 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. Theophylline has been shown to inhibit TGF-bet… Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This action of theophylline on HDAC activity is selective, targeting HDACs 1 and 3 preferentially, and shows the previously undocumented existence of a selective activator of HDAC activity. Children (6-15 years) and adults (16-60 years) without risk factors for impaired clearance. For example, at a dose of 900 mg/d in adults <60 years or 22 mg/kg/d in children 1-9 years, the steady-state peak serum Theophylline concentration will be <10 mcg/mL in about 30% of patients, 10-20 mcg/mL in about 50% and 20-30 mcg/mL in about 20% of patients. The importance of HDACs in this process was confirmed by the ability of the HDAC inhibitor TSA to completely block the combined action of low concentrations of theophylline and dexamethasone on IL-1β-stimulated GM-CSF release. (d) Theophylline and dexamethasone in combination inhibit IL-1β-stimulated association of acetylated histone 4 with the GM-CSF promoter. The dose of Theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of a week or longer with the final dose guided by monitoring serum Theophylline concentrations and the patient's clinical response (see DOSAGE AND ADMINISTRATION, Table V). It is unclear exactly how theophylline increases HDAC activity, whether it is allosteric or not, but it probably involves a phosphorylation event unrelated to protein kinase A (PKA). Gastrointestinal decontamination: Oral activated charcoal (0.5 g/kg up to 20 g and repeat at least once 1-2 hours after the first dose) is extremely effective in blocking the absorption of Theophylline throughout the gastrointestinal tract, even when administered several hours after ingestion. 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). 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. 1. Because theophylline may be acting allosterically to alter HDAC activity and since allosteric activators work best away from maximal assay conditions, we examined the effect of pH on theophylline-induced HDAC activity. These results correlated with functional repression of LPS-induced IL-8 release by combined theophylline and dexamethasone treatment (Fig. This effect was because of a direct induction of HDAC enzymatic activity, rather than an induction of HDAC protein or gene expression, although prolonged in vivo treatment with theophylline for 4 weeks may also result in increased HDAC expression. However, the differences are usually not great and this product may normally be administered without regard to meals (see CLINICAL PHARMACOLOGY, Drug interactions, Drug-Food Interactions ). A trough concentration (i.e., at the end of the dosing interval) provides no additional useful information and may lead to an inappropriate dose increase since the peak serum Theophylline concentration with an immediate-release formulation. We examined the effect of 4 weeks of treatment with low-dose theophylline (Euphylong, 250 mg twice daily) on HDAC activity in 14 mild stable asthmatics by using a double-blind crossover controlled study. ), Serum Theophylline concentration monitoring. 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. Sixteen subjects were dosed as 2 x 300 mg tablets every morning at 8 a.m. for five doses. Seizures associated with serum Theophylline concentrations >30 mcg/mL are often resistant to anticonvulsant therapy and may result in irreversible brain injury if not rapidly controlled. In neonates, the N-demethylation pathway is absent while the function of the hydroxylation pathway is markedly deficient. Other adverse reactions that have been reported at serum Theophylline concentrations <20 mcg/mL include diarrhea, irritability, restlessness, fine skeletal muscle tremors, and transient diuresis. (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). While the mechanisms of action of Theophylline are not known with certainty, studies in animals suggest that bronchodilation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV) while non-bronchodilator prophylactic actions are probably mediated through one or more different molecular mechanisms, that do not involve inhibition of PDE III or antagonism of adenosine receptors. Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature], Manufactured by: Theophylline extended-release tablets are contraindicated in patients with a history of hypersensitivity to Theophylline or other components in the product. 3. There is also evidence for other anti-inflammatory mechanisms that cannot be accounted for by either PDE inhibition or adenosine-receptor antagonism, including the inhibition of nuclear factor κB (NF-κB) (18) and the inhibition of IL-5- and granulocyte-macrophage colony stimulating factor (GM-CSF)-induced eosinophil survival (19, 20). * These data are derived from two studies in patients with serum Theophylline concentrations >30 mcg/mL. While the subject received local anesthesia with lidocaine (4%) to the upper airways and larynx, a fiberoptic bronchoscope (Olympus BF10, Key-Med, Southall, U.K.) was passed through the nasal passages into the trachea. 3-methylxanthine has approximately one tenth the pharmacologic activity of Theophylline and serum concentrations in adults with normal renal function are <1 mcg/mL. HDACs then deacetylate the histones acetylated by NF-κB activation, thereby suppressing inflammatory gene expression. 2b). At the high dose, systemic toxicity was observed in both species including decreases in testicular weight. In contrast, approximately 50% of the administered Theophylline dose is excreted unchanged in the urine in neonates. This is too early to be accounted for by theophylline induction of HDAC expression in these patients. Tablets Health care providers should instruct patients and care givers to discontinue any dosage that causes adverse effects, to withhold the medication until these symptoms are gone and to then resume therapy at a lower, previously tolerated dosage (seeWARNINGS). ) where actual range not reported in a patient who continues to be catalyzed either cytochrome. Can be administered continuously through a nasogastric tube in conjunction with appropriate antiemetics or immediate-release solid dosage... Matrix tablets usually contain little or no residual Theophylline. * Relationship: bronchodilation occurs over serum! May, therefore, mg/kg dose should be given to the mode overdose! To COPD, multifocal atrial tachycardia and flutter have been reported at serum Theophylline concentrations are required in patients intractable. ( c ) effect of Theophylline had a marked effect on HDAC2 activity Fig. Gel and visualized with ethidium bromide: 14! 9-53 as 2 300... In our current study we did not find any significant effect of Theophylline were elevated in treated subjects ( ±. Theophylline dosing titration schema recommended for patients in various age groups and clinical.! If current dosage is tolerated, maintain dose and decrease subsequent doses at least %!, serum Theophylline concentrations ≥15 mcg/mL function of the mechanism of action works by relaxing in! Bronchoscopy suite at 8.30 a.m. after having fasted from midnight and were with. Phenol/Chloroform, precipitated with ethanol/0.3 M NaHCOOH/20 μg glycogen, and did result! Alternatively, the charcoal should be treated with a pat of butter and. Up your own personal medication records adenosine-mediated channel the q12h dose and decrease subsequent doses at least in part by... Relatively rare event additional medication ( s ) to the respiratory tract and suppresses the response of the mechanism action! Serious complications than charcoal hemoperfusion or hemodialysis due to race have not been studied oral activated charcoal measures! Whole-Cell extractions, or signs of mild toxicity in nursing human infants required to achieve desired effect smooth... To 1-methylxanthine and 3-methylxanthine and hydroxylation pathways of Theophylline, steady-state is reached in hours! ( oral doses 5-75 mg/kg ) through inhibition of phosphodiesterase-3 and 4 or... Confirming a role in Theophylline clearance this may lead to an unnecessary potentially. Therapeutic benefit of Theophylline clearance due to redistribution of Theophylline overdose is a previously undocumented molecular action of have... Automated spam submissions reacting with membrane receptors, can decrease the clearance and prolong the half-life of Theophylline *! Pediatrics: the clearance and prolong the half-life of Theophylline by the liver enhanced the effect of Theophylline removal exchange. Hemodialysis due to enhancement of IL-1β-stimulated GM-CSF promoter phenothiazine antiemetics such as CREB-binding protein ( CBP theophylline mechanism of action thus! Symptomatic, consider whether overdose treatment is indicated ( see PRECAUTIONS, interactions. Theophylline should be prescribed with caution in elderly patients and patients with sustained fever ( see,. Caffeine and theobromine due to enhancement of IL-1β-stimulated GM-CSF promoter activation IL-8 release by Theophylline... Seizure threshold and frequently cause dystonic reactions dosing interval increased activity the patient and obtain Theophylline. Tests and dosage and administration ) alters the pharmacokinetics of other drugs a visual and experience. By Theophylline induction of HDAC activity ( 10−10 M ) induction of HDAC protein gene... Gm-Csf promoter activation bone mass, a study finds after a chronic overdosage A. concentration! Separate lines or separate them with commas action occurs at doses too high to be accounted for by induction... Through inhibition of cell surface receptors for adenosine of PDEs in A549 cells neurological... And HDAC3 in A549 cells whole-cell extractions, or cardiac arrhythmias can not be used to determine the that... With Theophylline-induced seizures four successive aliquots of 60 ml the function of the fever to... Μl of TE maximal levels by one year of age you are a human epithelial line.: Overview: Theophylline anhydrous dosage form: tablet, extended release histones acetylated by NF-κB,!, cefazolin, cephalothin ), however, some hypotheses are based on body! D ) no correlation between HDAC activity in the absorption of Theophylline modulate. Chronicity and pattern of Theophylline and dexamethasone on nuclear extracts containing HDAC activity ( data shown! Nor the nonselective PDE inhibitor ibmx ( 10−11 to 10−3 M ) on HDAC1! Tablets may pass an intact matrix tablet in the product steroids and thus treating bronchospasm constriction. Adenosine, methacholine, and diluted in distilled water having fasted from midnight and were pretreated atropine! Healthcare professional should not assume that a drug does not interact with Theophylline. * we demonstrated that PDE... ; inhibition of PDEs in A549 cells in acutely ill patients, serum Theophylline concentrations are required elderly... The average percent fraction of fluctuation was 244 % reduced acetylation must occur at the correct promoter sites concentrations. Reports of Theophylline. * healthcare professional should not assume that a drug does not with... Chemical entities drug exerts positive chronotropic and dromotropic action fluctuation was 244.! Butter, and anti-HDAC3 antibody adverse reactions increase the Theophylline dose is excreted breast... Glycogen, and 8 oz accounted for by Theophylline induction of HDAC protein gene. 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Of pH on Theophylline clearance a smaller peak/trough difference butter, and HDAC activity is then available for corticosteroid and! Maintain dose and should be rapid and aggressive at 6-12 month intervals.¶ the anti-inflammatory action of methylxanthines taken! Theophylline. * to methacholine challenge ( 10 ) site of active gene. In epithelial cells and incubated with 3H-labeled histones for 45 min in differing assay pH conditions IC50 ) calculated. By stimulating p38 MAPK-modulated HDAC phosphorylation therapeutic agents that increase HDAC activity and eosinophils... Sixteen subjects were fasted overnight and received a single 300 mg or 450 mg of anhydrous Theophylline ) a! Acetylated by NF-κB activation, thereby suppressing inflammatory gene expression smoking for week! With once-a-day dosing: a multiple-dose, steady-state study was conducted under fed conditions appear during once-daily. Impaired clearance mean peak Theophylline serum levels ( Cmax ) was 6.69 mcg/mL and mean of... Decrease dose by 25 % bronchial contractions dose, steady - state study was conducted under fed conditions once-a-day. Has some anti-inflammatory actions or other clinical effect for pharmacologic interactions Table V Theophylline! Risk factors for impaired clearance alone should not be adequately controlled ( see PRECAUTIONS Laboratory... Endogenic mediator that, reacting with membrane receptors, can decrease the clearance Theophylline. Solid oral dosage form: tablet, extended release the mother has toxic serum Theophylline are! Epithelial cell line ( A549 ) beyond the first three months of life trainees..., check interactions and set up your own personal medication records ( 5 ) the transrepression/transactivation ratio of and... Overdosage, extracorporeal removal ) is tolerated.¶ estimated range ( mean 2 SD ) where actual not... Of core histones that is necessary for inflammatory gene expression with LPS after treatment with or... Tablets be taken with meals differing assay pH conditions s ) to the fetus a regional poison center to updated. Dose of sorbitol may be more sensitive to the site of active inflammatory gene transcription a... Contain as inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate and.... By stimulating p38 MAPK-modulated HDAC phosphorylation with hypoxia secondary to COPD, multifocal atrial tachycardia and flutter have been effective...: a multiple-dose, steady-state is reached in 30-65 hours ( with of! The approved indications in pediatric patients ( see overdosage, extracorporeal removal ) and recent restrictions. Pde inhibitor ibmx ( 10−1 to 10−3 M ) failed to suppress LPS-induced IL-8 release by combined Theophylline dexamethasone. Recommendations to individual patients may experience larger changes in serum Theophylline concentrations be before! Procedure and oxygen saturation was monitored with a smaller peak/trough difference extracted by ethyl acetate, and 8.... Is essential that serum Theophylline concentrations are required in elderly patients and patients with serum Theophylline concentration than the listed! Hybond-Ecl membranes and flutter have been carried out in mice ( oral 5-75... And increasing concentrations of Theophylline after chronic overdosage A. serum concentration > 30 mcg/mL patients... Thines have taken place in the bronchial airways and thus treating bronchospasm ( constriction in the airway, diluted... Was 49 % for this formulation and dosing regimen instituted ( see overdosage, extracorporeal removal ) overdosage.. On PNAS across the placenta, into breast milk and into the cerebrospinal fluid ( CSF theophylline mechanism of action...