Bronchodilation occurs over the serum theophylline concentration range of 520 mcgml. The apparent volume of distribution of theophylline is approximately 0. Drug interactions may lead to decreased theophylline metabolism, and thus increased serum levels. Rare causes of hypercalcemia the journal of clinical. Oct 08, 2006 the molecular formula of anhydrous theophylline is c 7 h 8 n 4 o 2 with a molecular weight of 180. Theophylline metabolism was accelerated in 11 of normal male volunteers who received theophylline for 1 week in usual therapeutic doses 3 mgkg orally t.
Theophylline definition of theophylline by medical. Dailymed theophylline theophylline, anhydrous capsule. 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. At a high theophylline concentration of 10 mm four cyps 1a1, 1a2, 2d6, 2e1 catalyzed the metabolism of theophylline. Pdf caffeine, urinary calcium, calcium metabolism and bone. Aminophylline is 80% theophylline 100 mg aminophylline 80 mg theophylline.
Theophylline is a bronchodilator that is used to treat symptoms of asthma, bronchitis, emphysema, and other breathing problems. Mean theophylline clearance increased 24% and mean salivary elimination half. A significant increase in serum calcium levels associated with therapeutic levels of theophylline in normal volunteers was reversed by propranolol. Theophylline 3methyxanthine has been used to treat airway diseases for over 70 years. 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 increases the force of contraction of diaphragmatic muscles. 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.
The present paper reports studies on the fate of theophylline in man and describes the iso lation and characterization of 1,3. 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 appears to inhibit phosphodiesterase and prostaglandin production, regulate calcium flux and intracellular calcium distribution, and antagonize adenosine. Abstract oral doses of caffeine increase the urinary excretion of calcium, magnesium, sodium and chloride for at least 3 h after consumption. Many drugs interact with theophylline by inhibiting or potentiating its metabolism by cyp1a2 see commonlyused drugs that interact with theophylline. Metabolism metabolized in the liver to its metabolites by demethylation and oxidation. Never use theophylline in larger amounts, or for longer than prescribed. As a member of the xanthine family, it bears structural and pharmacological similarity to theobromine and caffeine, and is readily. However, the treatment of normoxic slices with 80fjm theophylline increased the calcium up take index in the mitochondria table 1 and. Theophylline passes freely across the placenta, into breast milk and into cerebrospinal fluid. This action appears to be due to enhancement of calcium uptake through an adenosinemediated channel. 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.
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 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. Effects of theophylline on the serum calcium of rats after. 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. Theophylline fda prescribing information, side effects and uses. Caffeine, urinary calcium, calcium metabolism and bone12. It appears that flavonoids found in grapefruit juice but not in orange juice may inhibit the cyp3a4 isozyme. 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. If apnea events continue, consult health care professional.
Neither have similar interactions been seen with orange juice4. Theophylline may also be used for purposes not listed in this medication guide. Other types of interactions with calcium metabolism in cells have also been found 2. Sep 10, 2019 theophylline is a bronchodilator that is used to treat symptoms of asthma, bronchitis, emphysema, and other breathing problems. Unbound theophylline distributes throughout body water, but distributes poorly into body fat. Methods estimation of theophylline in urine theophylline is isolated for analy. See what others have said about theophylline, including the effectiveness, ease of use and side effects. Theophylline in dextrose theophylline injection, solution. Dose should be determined by theophylline serum level monitoring. Serum calcium levels also fell significantly in three additional patients with theophylline toxicity, although the initial serum calcium concentration was not outside normal limits. Feb 18, 2016 the molecular formula of anhydrous theophylline is c 7 h 8 n 4 o 2 with a molecular weight of 180. The molecular formula of anhydrous theophylline is c 7 h 8 n 4 o 2 with a molecular weight of 180. Effect of theophylline on calcium metabolism and circulating. Theophylline, a drug to treat asthma increases risk of.
Clinical relevance of the interaction of theophylline with. The primary route of metabolism is mediated via the cytochrome p450 system theophylline s halflife varies widely 3. Although the anhydrous theophylline content varies greatly between products, there is similar excellent oral bioavailability. The major flavonoid found in grapefruit juice, the glycoside naringin. Learn who its for, how it works, its side effects, warnings, and more. The ultrastructure of the cal region and the localization of calcium was not changed by the addition of adenosine to norm oxic slices. More recently it has been shown to have antiinflammatory effects in asthma and copd at lower concentrations. Neither xanthine shifted the calcium doseresponse when pmns. Theophylline had the highest affinity apparent km range 0. Insufficient levels of vitamin d are common among adolescents and the elderly. Dailymed theophylline anhydrous theophylline tablet. Effect of theophylline on calcium metabolism and circulating vitamin d metabolites. 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.
Ultrastructural localization of calcium in ischemic hippocampal slices. It must be used regularly to prevent wheezing and shortness of breath. Ultrastructural localization of calcium in ischemic. Theophyllineinduced hypercalcemia citeseerx penn state. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. 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. Loading dose should be decreased or eliminated if theophylline preparation has been used in preceding 24 hr. Theophylline is an oral medication used to treat asthma and other lung diseases. Seek medical attention if your breathing problems get worse.
Each extendedrelease tablet for oral administration, contains 400 mg or 600 mg of anhydrous theophylline. Theophylline, a methylxanthine drug is a bronchodialator dilates airways of lungs and also has antiinflammatory property and thus mitigates the distressing. 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. Aminophylline is 80% theophylline 100 mg aminophylline 80 mg. Patientfamilyteaching instruct parent on correct technique for administration. Vitamin d plays a significant role with calcium in bone metabolism the process of building up and breaking down bone in the body. Theophylline definition of theophylline by medical dictionary. This action appears to be due to enhancement of calcium.
Theophylline distributes rapidly into fatfree tissues and body water. Oral doses of caffeine increase the urinary excretion of calcium, magnesium, sodium and chloride for at least 3 h after consumption. Theo24theophylline anhydrous extendedrelease capsules. Theophylline comes as an extendedrelease longacting tablet, extendedrelease capsule, and a solution liquid to take by mouth. Theophylline is metabolized in the liver by the cytochrome p450 microsomal enzyme system, and a large number of factors may influence hepatic metabolism. 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. Aug 14, 2019 theolair theophylline tablets tablets. All methylxanthines are eliminated by hepatic metabolism. Theophylline is a bronchodilator used for the relief of asthma that has a number of other pharmacological. 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. Theophyllineinduced hypercalcemia annals of internal.
Pdf effect of calcium channel blockers on theophylline. 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. Distribution once theophylline enters the systemic circulation, about 40% is bound to plasma protein, primarily albumin. Calcium deposits were rarely observed in the cytoplasm fig. Pdf disturbances in mineral homeostasis are common in the neonatal period, especially in premature infants and infants who are.
Theophyllineinduced hypercalcemia annals of internal medicine. It appears that theophylline causes elevation of serum calcium by a system. The drug is metabolised in the liver by cytochrome p450 isoenzymes, principally cyp1a2, to demethylated and hydroxylated products. Effect of theophylline on calcium metabolism and circulating vitamin. This drug release calcium from sarcoplasmic reticulam, especially in cardiac muscles and results increased cardiac muscle contraction. Therapeutic concentrations of theophylline and enprofylline. Theophylline salts several socalled salts of theophylline had been developed as attempts to increase water solubility 8 mgml at 25. Clinical pharmacokinetics of theophylline springerlink. Such preparations, often with a mild sedative added, dominated the market for oral theophylline products until 1975 when the. While salts of theophylline may be formed with a base at high ph, theophylline is only slightly ionized at physiological ph pk a 8.
It also has myocardial stimulant, coronary vasodilator. On the mechanism of action of theophylline and caffeine. Low levels contribute to the development of osteoporosis thin, brittle bones and are associated with an increased risk for fractures. Theophylline is used to treat lung diseases such as asthma and copd bronchitis, emphysema. Bronchodilators theophylline calciumchannel blockers diltiazem felodipine nifedipine nimodipine.
Theophylline is a natural alkaloid derivative of xanthine isolated from the plants camellia sinensis and coffea arabica. 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. Theophylline fda prescribing information, side effects. The hypercalciuric effect can be blocked by adenosine receptor. The primary route of metabolism is mediated via the cytochrome p450 system theophyllines halflife varies widely 3. 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. An average 96% range 75 to 105% of an uncoated theophylline tablet is. The combination of theophylline and ephedrine was described in a 1940 publication. The influence of adenosine and theophylline erno dux, peter schubert, and georg w.
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