Effect of theophylline on calcium metabolism and circulating. Theophylline distributes rapidly into fatfree tissues and body water. Mean theophylline clearance increased 24% and mean salivary elimination half. If apnea events continue, consult health care professional. Theophyllineinduced hypercalcemia citeseerx penn state. See what others have said about theophylline, including the effectiveness, ease of use and side effects. Theophylline fda prescribing information, side effects. Many drugs interact with theophylline by inhibiting or potentiating its metabolism by cyp1a2 see commonlyused drugs that interact with theophylline. The combination of theophylline and ephedrine was described in a 1940 publication. The ultrastructure of the cal region and the localization of calcium was not changed by the addition of adenosine to norm oxic slices. Theophylline, administered for up to 3 weeks, has been shown to disturb psgrecorded sleep in healthy subjects, 217, 218 patients with asthma, 219 children with cystic fibrosis, 220 and patients with sleep apnea 221 or chronic obstructive pulmonary disease. Oct 08, 2006 the molecular formula of anhydrous theophylline is c 7 h 8 n 4 o 2 with a molecular weight of 180. It appears that theophylline causes elevation of serum calcium by a system.
The results of previously published studies indicate that calcium channel blockers are capable of competitively inhibiting cytochrome p450 activity in hepatic microsomes, the pathway of theophylline metabolism. Also, a curious aspect of their study was the finding that the ophylline did not potentiate the calciummobilizing effect of small doses of parathyroid hormone, although according to present thinking, if parathyroid hormone does act by increasing 3,5 amp levels, then theophylline should potentiate its. Bronchodilators theophylline calciumchannel blockers diltiazem felodipine nifedipine nimodipine. All methylxanthines are eliminated by hepatic metabolism. The drug is metabolised in the liver by cytochrome p450 isoenzymes, principally cyp1a2, to demethylated and hydroxylated products. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. As a member of the xanthine family, it bears structural and pharmacological similarity to theobromine and caffeine, and is readily found in nature, being present in tea camellia. The hypercalciuric effect can be blocked by adenosine receptor. The influence of adenosine and theophylline erno dux, peter schubert, and georg w. Since theophylline administration alters the metabolism of cyclic amp in many tissues, these results suggest that cyclic amp may be involved in the action of parathyroid hormone and, therefore, in the regulation of blood calcium.
Theophylline is metabolized in the liver by the cytochrome p450 microsomal enzyme system, and a large number of factors may influence hepatic metabolism. Theophylline fda prescribing information, side effects and uses. Dec 15, 2012 knowledge acquired of the kinetic disposition and effects of theophylline over the past 8 years has increased the clinical utility of the drug in the treatment of cardiorespiratory disorders. Theophylline had the highest affinity apparent km range 0. It also has myocardial stimulant, coronary vasodilator. Neither xanthine shifted the calcium doseresponse when pmns. Rare causes of hypercalcemia the journal of clinical. Never use theophylline in larger amounts, or for longer than prescribed.
Aug 14, 2019 theolair theophylline tablets tablets. Knowledge acquired of the kinetic disposition and effects of theophylline over the past 8 years has increased the clinical utility of the drug in the treatment of cardiorespiratory disorders. Dailymed theophylline theophylline, anhydrous capsule. Theophylline, a drug to treat asthma increases risk of. Distribution once theophylline enters the systemic circulation, about 40% is bound to plasma protein, primarily albumin. Each extendedrelease tablet for oral administration, contains 400 mg or 600 mg of anhydrous theophylline. Low levels contribute to the development of osteoporosis thin, brittle bones and are associated with an increased risk for fractures. Unbound theophylline distributes throughout body water, but distributes poorly into body fat. Aminophylline is 80% theophylline 100 mg aminophylline 80 mg theophylline. Methods estimation of theophylline in urine theophylline is isolated for analy. Ultrastructural localization of calcium in ischemic. The primary route of metabolism is mediated via the cytochrome p450 system theophylline s halflife varies widely 3.
Aminophylline is 80% theophylline 100 mg aminophylline 80 mg. As a member of the xanthine family, it bears structural and pharmacological similarity to theobromine and caffeine, and is readily. Pdf effect of calcium channel blockers on theophylline. It was originally used as a bronchodilator but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled. The primary route of metabolism is mediated via the cytochrome p450 system theophyllines halflife varies widely 3. Theophylline salts several socalled salts of theophylline had been developed as attempts to increase water solubility 8 mgml at 25. Theophylline 3methyxanthine has been used to treat airway diseases for over 70 years. Learn who its for, how it works, its side effects, warnings, and more. Serum calcium levels also fell significantly in three additional patients with theophylline toxicity, although the initial serum calcium concentration was not outside normal limits. At a high theophylline concentration of 10 mm four cyps 1a1, 1a2, 2d6, 2e1 catalyzed the metabolism of theophylline.
Therapeutic concentrations of theophylline and enprofylline. In addition, case reports have suggested that theophylline serum concentrations change when a calcium channel blocker has been added to or deleted from a stable theophylline regimen. Theophylline, also known as 1,3dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease copd and asthma under a variety of brand names. Theophylline comes as an extendedrelease longacting tablet, extendedrelease capsule, and a solution liquid to take by mouth. Theo24theophylline anhydrous extendedrelease capsules. Theophyllineinduced hypercalcemia annals of internal. The molecular formula of anhydrous theophylline is c 7 h 8 n 4 o 2 with a molecular weight of 180. This drug release calcium from sarcoplasmic reticulam, especially in cardiac muscles and results increased cardiac muscle contraction. Theophylline metabolism was accelerated in 11 of normal male volunteers who received theophylline for 1 week in usual therapeutic doses 3 mgkg orally t. Abstract oral doses of caffeine increase the urinary excretion of calcium, magnesium, sodium and chloride for at least 3 h after consumption. Dose should be determined by theophylline serum level monitoring. Pdf caffeine, urinary calcium, calcium metabolism and bone. Calcium deposits were rarely observed in the cytoplasm fig. Theophylline is a natural alkaloid derivative of xanthine isolated from the plants camellia sinensis and coffea arabica.
Dailymed theophylline anhydrous theophylline tablet. Theophylline in dextrose theophylline injection, solution. The apparent volume of distribution of theophylline is approximately 0. Theophylline definition of theophylline by medical dictionary. Theophyllineinduced hypercalcemia annals of internal medicine. Theophylline is used to treat lung diseases such as asthma and copd bronchitis, emphysema.
Vitamin d plays a significant role with calcium in bone metabolism the process of building up and breaking down bone in the body. It appears that flavonoids found in grapefruit juice but not in orange juice may inhibit the cyp3a4 isozyme. Ultrastructural localization of calcium in ischemic hippocampal slices. Oral doses of caffeine increase the urinary excretion of calcium, magnesium, sodium and chloride for at least 3 h after consumption. Bronchodilation occurs over the serum theophylline concentration range of 520 mcgml. Apr 05, 2016 theophylline, a drug to treat asthma increases risk of fracture and causes vitamin d deficiency not surprisingly, the major burden of copd of the world is shared by these two countries. These other causes of hypercalcemia, including vitamin d intoxication, sarcoidosis, tuberculosis, some fungal infections, thyrotoxicosis, addisons disease, milkalkali syndrome related to the prescription of absorbable alkali and calcium, vitamin a intoxication, therapy with thiazide diuretics or lithium carbonate, familial hypocalciuric. More recently it has been shown to have antiinflammatory effects in asthma and copd at lower concentrations. Theophylline passes freely across the placenta, into breast milk and into cerebrospinal fluid. Sep 10, 2019 theophylline is a bronchodilator that is used to treat symptoms of asthma, bronchitis, emphysema, and other breathing problems. Seek medical attention if your breathing problems get worse. It must be used regularly to prevent wheezing and shortness of breath. Other types of interactions with calcium metabolism in cells have also been found 2.
Effect of theophylline on calcium metabolism and circulating vitamin. Loading dose should be decreased or eliminated if theophylline preparation has been used in preceding 24 hr. Brodie, julius axelrod, and jules reichenthal from the section on chemical pharmacology, national heart institute, national institutes of health, united states public health service, bethesda, maryland received for publication, august 17, 1951. Update on the pharmacodynamics and pharmacokinetics of. Theophylline definition of theophylline by medical. Clinical pharmacokinetics of theophylline springerlink. Caffeine, urinary calcium, calcium metabolism and bone12.
Mar 18, 2010 theophylline is rapidly and completely absorbed, but there are large interindividual variations in clearance, due to differences in hepatic metabolism table 2. Theophylline was first identified as having potential for asthma as a bronchodilator in 1921 and 1922, but general use as a bronchodilator was not seen until the 1930s. Clinical relevance of the interaction of theophylline with. Patientfamilyteaching instruct parent on correct technique for administration. While salts of theophylline may be formed with a base at high ph, theophylline is only slightly ionized at physiological ph pk a 8. This action appears to be due to enhancement of calcium uptake through an adenosinemediated channel. Metabolism metabolized in the liver to its metabolites by demethylation and oxidation. Theophylline is an oral medication used to treat asthma and other lung diseases. Insufficient levels of vitamin d are common among adolescents and the elderly. The major flavonoid found in grapefruit juice, the glycoside naringin. Theophylline is a bronchodilator used for the relief of asthma that has a number of other pharmacological. Theophylline may also be used for purposes not listed in this medication guide. Although the anhydrous theophylline content varies greatly between products, there is similar excellent oral bioavailability.
A significant increase in serum calcium levels associated with therapeutic levels of theophylline in normal volunteers was reversed by propranolol. Pdf disturbances in mineral homeostasis are common in the neonatal period, especially in premature infants and infants who are. Since theophylline is a potentially toxic drug, 28 particularly in copd patients, who may be more sensitive to its arrythmogenic effects and at risk of accumulating excessive serum concentrations as a result of impaired metabolism from cor pulmonale, 32 the small potential benefit must be weighed against the potential risk oftoxicity. Theophylline, a methylxanthine drug is a bronchodialator dilates airways of lungs and also has antiinflammatory property and thus mitigates the distressing. Theophylline is a bronchodilator that is used to treat symptoms of asthma, bronchitis, emphysema, and other breathing problems. Drug interactions may lead to decreased theophylline metabolism, and thus increased serum levels. Effect of theophylline on calcium metabolism and circulating vitamin d metabolites. On the mechanism of action of theophylline and caffeine. Theophylline increases the force of contraction of diaphragmatic muscles. An average 96% range 75 to 105% of an uncoated theophylline tablet is. This action appears to be due to enhancement of calcium.
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