Aminophylline

Last updated
Aminophylline
Aminophylline.svg
Clinical data
AHFS/Drugs.com Professional Drug Facts
MedlinePlus a601015
Pregnancy
category
  • AU:A
Routes of
administration 		By mouth, intravenous therapy (IV)
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 60%
Elimination half-life 7–9 hours
Identifiers
  • 1,3-Dimethyl-7H-purine-2,6-dione; ethane-1,2-diamine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.005.696 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C16H24N10O4
Molar mass 420.434 g·mol−1
3D model (JSmol)
  • Cn2c(=O)c1nc[nH]c1n(C)c2=O.Cn2c(=O)c1nc[nH]c1n(C)c2=O.NCCN
  • InChI=1S/2C7H8N4O2.C2H8N2/c2*1-10-5-4(8-3-9-5)6(12)11(2)7(10)13;3-1-2-4/h2*3H,1-2H3,(H,8,9);1-4H2 Yes check.svgY
  • Key:FQPFAHBPWDRTLU-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Aminophylline is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate. [2]

Contents

Aminophylline is less potent and shorter-acting than theophylline. Its most common use is in the treatment of airway obstruction from asthma or COPD. Aminophylline is a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor. [3]

Medical uses

Intravenous aminophylline can be used for acute exacerbation of symptoms and reversible airway obstruction in asthma and other chronic lung disease such as COPD, emphysema and chronic bronchitis. It is used as an adjunct to inhaled beta-2 selective agonists and systemically administered corticosteroids. [4]

Aminophylline is used to reverse regadenoson, dipyridamole or adenosine based infusions during nuclear cardiology stress testing. Aminophylline has also been reported to be effective in preventing slow heart rates during complex cardiovascular interventions (atherectomy of the right coronary artery). [5] It is also used in the treatment of heart block due to acute inferior myocardial infarction. It can also cause cardiac arrest.

Aminophylline has shown some promise as a bodyfat reducer when used as a topical cream. [6] Aminophylline is also a treatment option for anaphylactic shock. [7]

While it has been suggested for use in cardiac arrest evidence does not support a benefit. [8] [9]

Side effects

Aminophylline can lead to theophylline toxicity. Aminophylline has been found to decrease the sedative effects of propofol [10] and decrease topiramate antiseizure action. [11]

Properties

It is more soluble in water than theophylline. White or slightly yellowish granules or powder, having a slight ammoniacal odor and a bitter taste. Upon exposure to air, it gradually loses ethylenediamine and absorbs carbon dioxide with the liberation of free theophylline. Its solutions are alkaline. 1 g dissolves in 25 mL of water to give a clear solution; 1 g dissolved in 5 mL of water crystallizes upon standing, but redissolves when a small amount of ethylenediamine is added. Insoluble in alcohol and in ether.

Pharmacology

Like other methylated xanthine derivatives, aminophylline is both a

  1. competitive nonselective phosphodiesterase inhibitor [12] which raises intracellular cAMP, activates PKA, inhibits TNF-alpha [13] [14] and leukotriene [15] synthesis, and reduces inflammation and innate immunity [15] and
  2. nonselective adenosine receptor antagonist. [16]

Aminophylline causes bronchodilation, diuresis†, central nervous system and cardiac stimulation, and gastric acid secretion by blocking phosphodiesterase which increases tissue concentrations of cyclic adenosine monophosphate (cAMP) which in turn promotes catecholamine stimulation of lipolysis, glycogenolysis, and gluconeogenesis, and induces release of epinephrine from adrenal medulla cells.
†Note that diuresis is caused by an increase in cAMP which acts in the CNS to inhibit the release of antidiuretic hormone (arginine-vasopressin).

Adenosine is an endogenous extracellular messenger that can regulate myocardial oxygen needs. [3] [17] It acts through cellular surface receptors which effect intracellular signalling pathways to increase coronary artery blood flow, slow heart rate, block atrioventricular node conduction, suppress cardiac automaticity, and decrease β-adrenergic effects on contractility. [3] [17] Adenosine also antagonizes chronotropic and ionotropic effects of circulating catecholamines. [18] Overall, adenosine decreases the heart’s rate and force of contraction, which increases blood supply to the cardiac muscle. Given specific circumstances this mechanism (which is intended to protect the heart) may cause atropine-resistant refractory bradyasystole. [3] Adenosine's effects are concentration-dependent. Adenosine’s receptors are competitively antagonized by methylxanthines such as aminophylline. [3] [17] [18] Aminophylline competitively antagonizes the cardiac actions of adenosine at the cell surface receptors. [17] Thus, it increases heart rate and contractility.

Brand names

Related Research Articles

<span class="mw-page-title-main">Phosphodiesterase inhibitor</span> Drug

A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s). The ubiquitous presence of this enzyme means that non-specific inhibitors have a wide range of actions, the actions in the heart, and lungs being some of the first to find a therapeutic use.

<span class="mw-page-title-main">Xanthine</span> Chemical compound

Xanthine is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine, theophylline, and theobromine.

<span class="mw-page-title-main">Theophylline</span> Drug used to treat respiratory diseases

Theophylline, also known as 1,3-dimethylxanthine, is a drug that inhibits phosphodiesterase and blocks adenosine receptors. It is used to treat chronic obstructive pulmonary disease (COPD) and asthma. Its pharmacology is similar to other methylxanthine drugs. Trace amounts of theophylline are naturally present in tea, coffee, chocolate, yerba maté, guarana, and kola nut.

<span class="mw-page-title-main">Adenosine</span> Chemical compound

Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building blocks of RNA (and its derivative deoxyadenosine is a building block of DNA), which are essential for all life on earth. Its derivatives include the energy carriers adenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP. Cyclic adenosine monophosphate (cAMP) is pervasive in signal transduction. Adenosine is used as an intravenous medication for some cardiac arrhythmias.

An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effective in the arterial circulation where classical Vitamin K antagonist anticoagulants have minimal effect.

<span class="mw-page-title-main">Adenosine receptor</span> Class of four receptor proteins to the molecule adenosine

The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand. There are four known types of adenosine receptors in humans: A1, A2A, A2B and A3; each is encoded by a different gene.

cGMP-specific phosphodiesterase type 5 Mammalian protein found in Homo sapiens

Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to play a vital role in the cardiovascular system.

<span class="mw-page-title-main">Pentoxifylline</span> Chemical compound

Pentoxifylline, also known as oxpentifylline, is a xanthine derivative used as a drug to treat muscle pain in people with peripheral artery disease. It is generic and sold under many brand names worldwide.

<span class="mw-page-title-main">Paraxanthine</span> Chemical compound

Paraxanthine, also known as 1,7-dimethylxanthine, is a metabolite of theophylline and theobromine, two well-known stimulants found in coffee, tea, and chocolate. It is a member of the xanthine family of alkaloids, which includes theophylline, theobromine and caffeine.

Adenosine A<sub>1</sub> receptor Cell surface receptor found in humans

The adenosine A1 receptor (A1AR) is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as endogenous ligand.

<span class="mw-page-title-main">IBMX</span> Chemical compound

IBMX (3-isobutyl-1-methylxanthine), like other methylated xanthine derivatives, is both a:

  1. competitive non-selective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits TNFα and leukotriene synthesis, and reduces inflammation and innate immunity, and
  2. nonselective adenosine receptor antagonist.
<span class="mw-page-title-main">PDE3 inhibitor</span>

A PDE3 inhibitor is a drug which inhibits the action of the phosphodiesterase enzyme PDE3. They are used for the therapy of acute heart failure and cardiogenic shock.

Adenosine A<sub>2A</sub> receptor Cell surface receptor found in humans

The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and also denotes the human gene encoding it.

<span class="mw-page-title-main">Doxofylline</span> Chemical compound

Doxofylline is a phosphodiesterase inhibiting bronchodilator used in the treatment of chronic respiratory diseases such as asthma and COPD. Like theophylline, it is a xanthine derivative.

<span class="mw-page-title-main">Bamifylline</span> Chemical compound

Bamifylline is a drug of the xanthine chemical class which acts as a selective adenosine A1 receptor antagonist.

Management of heart failure requires a multimodal approach. It involves a combination of lifestyle modifications, medications, and possibly the use of devices or surgery.

<span class="mw-page-title-main">8-Phenyltheophylline</span> Chemical compound

8-Phenyltheophylline (8-phenyl-1,3-dimethylxanthine, 8-PT) is a drug derived from the xanthine family which acts as a potent and selective antagonist for the adenosine receptors A1 and A2A, but unlike other xanthine derivatives has virtually no activity as a phosphodiesterase inhibitor. It has stimulant effects in animals with similar potency to caffeine. Coincidentally 8-phenyltheophylline has also been found to be a potent and selective inhibitor of the liver enzyme CYP1A2 which makes it likely to cause interactions with other drugs which are normally metabolised by CYP1A2.

<span class="mw-page-title-main">Purinergic signalling</span> Signalling complex involving purine nucleosides and their receptors

Purinergic signalling is a form of extracellular signalling mediated by purine nucleotides and nucleosides such as adenosine and ATP. It involves the activation of purinergic receptors in the cell and/or in nearby cells, thereby regulating cellular functions.

<span class="mw-page-title-main">Epinephrine (medication)</span> Hormone used as a medicine

Epinephrine, also known as adrenaline, is a medication and hormone. As a medication, it is used to treat several conditions, including anaphylaxis, cardiac arrest, asthma, and superficial bleeding. Inhaled epinephrine may be used to improve the symptoms of croup. It may also be used for asthma when other treatments are not effective. It is given intravenously, by injection into a muscle, by inhalation, or by injection just under the skin.

Tedral is a medicine formerly used to treat respiratory diseases such as asthma, chronic obstructive lung disease (COPD), chronic bronchitis, and emphysema. It is a combination drug containing three active ingredients - theophylline, ephedrine, phenobarbital. This medication relaxes the smooth muscle of the airways, making breathing easier. The common side effects of Tedral include gastrointestinal disturbances, dizziness, headache and lightheadedness. However, at high dose, it may lead to cardiac arrhythmias, hypertension, seizures or other serious cardiovascular and/or central nervous system adverse effects. Tedral is contraindicated in individuals with hypersensitivity to theophylline, ephedrine and/or phenobarbital. It should be also used in caution in patients with cardiovascular complications, such as ischemic heart disease and heart failure and/or other disease conditions. It can cause a lot of drug–drug interactions. Therefore, before prescribing patient with Tedral, drug interactions profile should be carefully checked if the patient had other concurrent medication(s). Being used as a treatment option for respiratory diseases for decades, Tedral was withdrawn from the US market in 2006 due to safety concerns.

References

  1. ↑ "FDA-Approved Drugs Abbreviated New Drug Application (ANDA): 087242". fda.gov. October 26, 1983. Retrieved December 2, 2023.
  2. ↑ "Aminophylline Professional Monograph". Drugs.com.
  3. 1 2 3 4 5 Mader TJ, Smithline HA, Durkin L, Scriver G (March 2003). "A randomized controlled trial of intravenous aminophylline for atropine-resistant out-of-hospital asystolic cardiac arrest". Academic Emergency Medicine. 10 (3): 192–197. doi: 10.1197/aemj.10.3.192 . PMID   12615581.
  4. ↑ "Aminophylline Injection". Drugs.com. Retrieved 6 January 2018.
  5. ↑ "Aminophylline for Preventing Bradyarrhythmias During Orbital or Rotational Atherectomy of the Right Coronary Artery". invasivecardiology.com. Archived from the original on 2020-08-03. Retrieved 2018-06-15.
  6. ↑ Caruso MK, Pekarovic S, Raum WJ, Greenway F (May 2007). "Topical fat reduction from the waist". Diabetes, Obesity & Metabolism. 9 (3): 300–303. doi:10.1111/j.1463-1326.2006.00600.x. PMID   17391155. S2CID   988473.
  7. ↑ Blackbourne LH. Surgical Recall. Lippincott Williams and Wilkins, 2009. pp169
  8. ↑ Hayward E, Showler L, Soar J (August 2007). "Aminophylline in bradyasystolic cardiac arrest". Emergency Medicine Journal. 24 (8): 582–583. doi:10.1136/emj.2007.051342. PMC   2660094 . PMID   17652689.
  9. ↑ Hurley KF, Magee K, Green R (November 2015). "Aminophylline for bradyasystolic cardiac arrest in adults". The Cochrane Database of Systematic Reviews. 2015 (11): CD006781. doi:10.1002/14651858.CD006781.pub3. PMC   8454042 . PMID   26593309.
  10. ↑ Turan A, Kasuya Y, Govinda R, Obal D, Rauch S, Dalton JE, et al. (February 2010). "The effect of aminophylline on loss of consciousness, bispectral index, propofol requirement, and minimum alveolar concentration of desflurane in volunteers". Anesthesia and Analgesia. 110 (2): 449–454. doi: 10.1213/ane.0b013e3181c6be7e . PMID   19955506. S2CID   29111498.
  11. ↑ Luszczki JJ, Jankiewicz K, Jankiewicz M, Czuczwar SJ (May 2007). "Pharmacokinetic and pharmacodynamic interactions of aminophylline and topiramate in the mouse maximal electroshock-induced seizure model". European Journal of Pharmacology. 562 (1–2): 53–59. doi:10.1016/j.ejphar.2007.01.038. PMID   17320861.
  12. ↑ Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): 671–680. doi:10.1067/mai.2001.119555. PMID   11692087.
  13. ↑ Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R (June 2008). "Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition". Clinics. 63 (3): 321–328. doi:10.1590/S1807-59322008000300006. PMC   2664230 . PMID   18568240.
  14. ↑ Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (February 1999). "Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages". American Journal of Respiratory and Critical Care Medicine. 159 (2): 508–511. doi:10.1164/ajrccm.159.2.9804085. PMID   9927365.
  15. 1 2 Peters-Golden M, Canetti C, Mancuso P, Coffey MJ (January 2005). "Leukotrienes: underappreciated mediators of innate immune responses". Journal of Immunology. 174 (2): 589–594. doi: 10.4049/jimmunol.174.2.589 . PMID   15634873.
  16. ↑ Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Progress in Clinical and Biological Research. 230 (1): 41–63. PMID   3588607.
  17. 1 2 3 4 Mader TJ, Gibson P (August 1997). "Adenosine receptor antagonism in refractory asystolic cardiac arrest: results of a human pilot study". Resuscitation. 35 (1): 3–7. doi:10.1016/s0300-9572(97)01097-6. PMID   9259053.
  18. 1 2 Perouansky M, Shamir M, Hershkowitz E, Donchin Y (July 1998). "Successful resuscitation using aminophylline in refractory cardiac arrest with asystole". Resuscitation. 38 (1): 39–41. doi:10.1016/s0300-9572(98)00079-3. PMID   9783508.
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