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arsenic trioxide

 
Dictionary: ar·se·nic trioxide   (är'sə-nĭk) pronunciation
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n.
A poisonous, white amorphous powder, As2O3, used in insecticides, rat poisons, and weed killers.


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Oncology Encyclopedia: Arsenic Trioxide
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Definition

Arsenic trioxide, also known by the trade name Trisenox, is an antitumor agent used for a specific type of leukemia known as acute promyelocytic leukemia.

Purpose

Arsenic trioxide is used to treat acute promyelocytic leukemia in patients who have not responded to standard treatment.

Description

Arsenic trioxide, like many other antineoplastic (antitumor) agents, acts by interfering with the growth of cells. Unfortunately, these drugs affect the growth of normal cells and tumor cells. In some patients the drug may have to be discontinued because normal cell growth is too severely affected. For example, a patient taking a large dose of arsenic trioxide might see tumor growth stop. However, the dosage might be high enough to also stop the body's normal growth of platelet cells. The loss of platelets might cause severe internal bleeding–a consequence more immediately toxic than the tumor.

Recommended Dosage

Doses vary from individual to individual and depend on body weight as well as other medications the patient is taking. For acute promyelocytic leukemia dosages for adults and children five years of age and older are up to 60 injections of 0.15 mg/kg of body weight until bone marrow remission occurs.

Precautions

Arsenic trioxide has been shown to cause fetal abnormalities and miscarriage in animals. Women who might become pregnant should take precautions to ensure they do not become pregnant while taking this drug. Women who are nursing their infants should discontinue nursing while this medication is in their system.

Patients with bone marrow problems, heart problems, kidney problems, or low levels of magnesium or potassium in the blood should notify their physician before taking any of this medicine. Patients should notify their physician of any illnesses they may have before taking arsenic trioxide.

Because persons taking arsenic trioxide may have decreased immunity, it is important for them to avoid infection. Caution should be taken to avoid unnecessary exposure to crowds and people with infections.

Patients may experience unusual or excessive bruising and/or bleeding and should avoid situations in which it is likely they could cut or bruise themselves. Patients should consult their physician immediately if they have any indication of excessive bleeding or bruising, including black and tarry stools, blood in the urine or stools, unusual bleeding or bruising, pinpoint red marks on their skin, vomit containing blood or what appears to be coffee grounds (dried blood). Severe symptoms may indicate a medical emergency.

Side Effects

Symptoms include unusual heartbeat (fast, slow, irregular, or pounding), chest pain, high blood pressure, trouble breathing, bluish lips, skin, palms, or skin underneath the fingernails, muscle cramps, numbness or tingling, headache, acting or feeling drunk, confusion, fainting, dizziness, eye pain, blurred vision, excessive weakness, excessive fatigue, or excessive drowsiness.

Patients should also contact their physician immediately if they experience a fruity odor in their mouth, a dry mouth, excessive sweating, flushing, urine retention, excessive urination, increased appetite or thirst, abdominal pain, loss of appetite, unexplained weight gain or loss, or severe nausea.

Patients may have vomiting, nausea, diarrhea, insomnia, sour stomach, heartburn, constipation, gas, neck pain, back pain, bone pain, bloating, swelling, pain or swelling at the injection site, joint, muscle, or limb pain, depression, or nosebleeds.

Patients should always notify their physician about any unusual symptoms they experience while on medication.

Interactions

Patients should tell their doctors if they have a known allergic reaction to arsenic trioxide or any other medications or substances, such as foods and preservatives. Before taking any new medications, including non-prescription medications, vitamins, and herbal medications, the patients should notify their doctors.

—Michael Zuck, Ph.D.

Drug Info: Arsenic Trioxide
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Brand names: Trisenox®



Arsenic Trioxide Solution for injection

What is this medicine?

ARSENIC TRIOXIDE (AR se nik trye OX ide) is a chemotherapy drug. It slows the growth of cancer cells. This medicine is used to treat acute promyelocytic leukemia (APL).
 
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•irregular heartbeat
•kidney disease
•low levels of potassium, calcium, or magnesium in the blood
•an unusual or allergic reaction to arsenic, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

This drug is given as an infusion into a vein. It is administered in a hospital or clinic by a specially trained health care professional.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

Do not take this medicine with any of the following medications:
•cisapride
•droperidol
•herbal or dietary supplements with hawthorn, Crataegus laevigata
•medicines for irregular heart beat like amiodarone, bepridil, dofetilide, encainide, flecainide, propafenone, quinidine
•methadone
•phenothiazines like chlorpromazine, mesoridazine, prochlorperazine, thioridazine
•ranolazine
•sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous
•some medicines for infection like chloroquine, gatifloxacin, gemifloxacin, halofantrine, levofloxacin, moxifloxacin, pentamidine, troleandomycin
•some medicines for mental problems like haloperidol, pimozide, ziprasidone
•some medicines to treat cancer like dasatinib, lapatinib, sunitinib, vorinostat

This medicine may also interact with the following medications:
•alfuzosin
•cyclobenzaprine
•dolasetron
•medicines for depression, anxiety, or psychotic disturbances
•medicines for numbness, pain prevention, or sleep during surgery
•octreotide
•some medicines for infection like, clarithromycin, erythromycin, mefloquine, norfloxacin, ofloxacin
•some medicines to treat cancer like daunorubicin, doxorubicin
•tacrolimus
•vardenafil

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor for checks on your progress. This drug may make you feel generally unwell. This is not uncommon, as chemotherapy can affect healthy cells as well as cancer cells. Report any side effects. Continue your course of treatment even though you feel ill unless your doctor tells you to stop.

This medicine may affect blood sugar levels. If you have diabetes, check with your doctor or health care professional before you change your diet or the dose of your diabetic medicine.

Avoid taking products that contain aspirin, acetaminophen, ibuprofen, naproxen, or ketoprofen unless instructed by your doctor. These medicines may hide a fever.

Do not become pregnant while taking this medicine. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. Talk to your health care professional or pharmacist for more information. Do not breast-feed an infant while taking this medicine.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•signs of infection - fever or chills, cough, sore throat, pain or difficulty passing urine
•breathing problems
•chest pain, tightness
•confusion
•fast, irregular heartbeat
•feeling faint or lightheaded, falls
•muscle weakness
•pain, tingling, numbness in the hands or feet
•seizures
•swelling of the ankles, feet, hands
•unusual bleeding or bruising
•weight gain

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•aches, pains
•diarrhea
•headache
•nausea, vomiting
•pain at site where injected
•stomach pain
•trouble sleeping

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

This drug is given in a hospital or clinic and will not be stored at home.

Last updated: 7/13/2005 11:01:00 AM

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

WordNet: arsenic trioxide
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Note: click on a word meaning below to see its connections and related words.

The noun has one meaning:

Meaning #1: a white powdered poisonous trioxide of arsenic; used in manufacturing glass and as a pesticide and weed killer
  Synonyms: arsenic, arsenous anhydride, arsenous oxide

Wikipedia: Arsenic trioxide
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Arsenic trioxide
Arsenic trioxide
Ball-and-stick model of the As4O6 molecule
Other names Arsenic(III) oxide,
Arsenic sesquioxide,
Arsenicum album,
Arseneous oxide,
Arseneous anhydride,
White arsenic[1]
Identifiers
CAS number 1327-53-3 Yes check.svgY
PubChem 261004
EC number 215-481-4
DrugBank APRD00171
RTECS number CG3325000
ATC code L01XX27
SMILES
InChI
InChI key GOLCXWYRSKYTSP-UHFFFAOYAM
ChemSpider ID 452539
Properties
Molecular formula As2O3
Molar mass 197.841 g/mol
Appearance White solid
Density 3.74 g/cm3
Melting point

312.2°C
Boiling point

465°C
Solubility in water 2 g/100 ml (25°C)
see text
Solubility soluble in dilute acids and alkalies, practically insoluble in organic solvents [2]
Acidity (pKa) 9.2
Structure
Crystal structure cubic (α)<180°C
monoclinic (β) >180°C
Molecular shape See Text
Dipole moment Zero
Thermochemistry
Std enthalpy of
formation ΔfHo298		 −657.4 kJ/mol
Standard molar
entropy So298		  ? J.K–1.mol–1
Pharmacology
Protein binding 75% bound
Hazards
MSDS External MSDS
EU classification Very toxic (T+)
Carc. Cat. 1
Dangerous for the
environment (N)
R-phrases R45, R28, R34,
R50/53
S-phrases S53, S45, S60,
S61
NFPA 704
NFPA 704.svg
0
3
0
 
LD50 14.6 mg/kg (rat, oral)
Related compounds
Other anions Arsenic trisulfide
Other cations Phosphorus trioxide
Antimony trioxide
Related compounds Arsenic pentoxide
Arsenous acid
Supplementary data page
Structure and
properties		 n, εr, etc.
Thermodynamic
data		 Phase behaviour
Solid, liquid, gas
Spectral data UV, IR, NMR, MS
 Yes check.svgY (what is this?)  (verify)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Arsenic trioxide is the inorganic compound with the formula As2O3. This commercially important oxide of arsenic is the main precursor to other arsenic compounds, including organoarsenic compounds. Approximately 50,000 tons are produced annually.[3] Many applications are controversial given the high toxicity of arsenic compounds.

Contents

Preparation and properties

Arsenic trioxide can be generated via many routine processing of arsenic compounds including the oxidation (combustion) of arsenic and arsenic-containing minerals in air. Illustrative is the roasting of orpiment, a typical arsenic sulfide ore.

2 As2S3 + 9 O2 → 2 As2O3 + 6 SO2

Most arsenic oxide is, however, obtained as a volatile by-product of the processing of other ores. For example, arsenopyrite, a common impurity in gold- and copper-containing ores, liberates arsenic trioxide upon heating in air. The processing of such minerals has led to numerous cases of poisonings.[4] Only in China are arsenic ores intentionally mined.[3]

Arsenic trioxide is an amphoteric oxide, and its aqueous solutions are weakly acidic. Thus, it dissolves readily in alkaline solutions to give arsenites. It is less soluble in acids, although it will dissolve in hydrochloric acid, giving chloro compounds, ultimately arsenic trichloride with concentrated acid. Only with strong oxidizing agents such as ozone, hydrogen peroxide, and nitric acid does it give arsenic pentoxide, As2O5. Reduction gives elemental arsenic or arsine (AsH3) depending on conditions. In this regard, arsenic trioxide differs from phosphorus trioxide which readily combusts to phosphorus pentoxide.

Structure

In the liquid and in the gas phase below 800 °C, arsenic trioxide has the formula As4O6 and is isostructural with P4O6). Above 800 °C As4O6 significantly dissociated into molecular As2O3, which adopts the same structure as N2O3. Three forms (polymorphs) are known in the solid state: cubic As4O6, containing molecular As4O6, and two related polymeric forms. The polymers, which both crystallized as monoclinic crystals, feature sheets of pyramidal AsO3 units that share O atoms.[5]

Arsenolite-xtal-3D-balls-D.png Claudetite-I-layer-3D-balls.png Claudetite-II-layer-3D-balls.png
arsenolite
(cubic)
claudetite I
(monoclinic)
claudetite II
(monoclinic)

Uses

Large scale applications include its use as a precursor to forestry products, in colorless glass production, and in electronics.[3] Being the main compound of arsenic, the trioxide is the precursor to elemental arsenic, arsenic alloys, and arsenide semiconductors. Organoarsenic compounds, e.g. feed additives (Roxarsone) and pharmaceuticals (Neosalvarsan), are derived from arsenic trioxide. Bulk arsenic-based compounds sodium arsenite and sodium cacodylate are derived from the trioxide.

A variety of applications exploit arsenic's toxicity, including the use of the oxide as a wood preservative. Copper arsenates, which are derived from arsenic trioxide, are used on a large scale as a wood preservative in the US and Malaysia, but such materials are banned in many parts of the world. This practice remains controversial.[3] In combination with copper(II) acetate arsenic trioxide gives the vibrant pigment known as paris green used both in paints and as a rodenticide. This application has been discontinued.

Medical applications

Despite the well known toxicity of arsenic, arsenic trioxide has long been of biomedical interest, dating to traditional Chinese medicine, where it is known as Pi Shuang and is still used to treat cancer and other conditions.[6] Some discredited patent medicines, e.g., Fowler's solution, contained derivatives of arsenic oxide. Arsenic trioxide under the trade name Trisenox (manufacturer: Cephalon) is a chemotheraputic agent of idiopathic function used to treat leukemia that is unresponsive to "first line" agents. It is suspected that arsenic trioxide induces cancer cells to undergo apoptosis. Due to the toxic nature of arsenic, this drug carries significant risks. Use as a cytostatic in the treatment of refractory promyelocytic (M3) subtype of acute myeloid leukemia.[7][8] The combination therapy of arsenic trioxide and all-trans retinoic acid (ATRA) has been approved by the U.S. Food and Drug Administration (FDA) for treatment of certain leukemias.[9]

Arsenic trioxide also appears to be a promising therapeutic agent for autoimmune diseases.[10]

The enzyme thioredoxin reductase has recently been identified as a target for arsenic trioxide.[11]

Natural occurrence

Two minerals are known to possess the As2O3 chemical formula: arsenolite(regular) and claudetite (monoclinic). Both are relatively rare secondary minerals found in oxidation zones of As-rich ore deposits (these are often Co-, Ni-, Ag- and U-bearing, too).

Toxicology

See also: arsenicosis.

Arsenic trioxide is readily absorbed by the digestive system: toxic effects are also well known upon inhalation or upon skin contact. Elimination is rapid at first (half-life of 1–2 days), by methylation to monomethylarsonic acid and dimethylarsonic acid, and excretion in the urine, but a certain amount (30–40% in the case of repeated exposure) is incorporated into the bones, muscles, skin, hair and nails (all tissues rich in keratin) and eliminated over a period of weeks or months.

The first symptoms of acute arsenic poisoning by ingestion are digestive problems: vomiting, abdominal pains, diarrhea often accompanied by bleeding. Sub-lethal doses can lead to convulsions, cardiovascular problems, inflammation of the liver and kidneys and abnormalities in the coagulation of the blood. These are followed by the appearance of characteristic white lines (Mees stripes) on the nails and by hair loss. Lower doses lead to liver and kidney problems and to changes in the pigmentation of the skin. Even dilute solutions of arsenic trioxide are dangerous on contact with the eyes.

The poisonous properties are legendary and the subject of an extensive literature.[12][13][13][14]

Chronic arsenic poisoning is known as arsenicosis. This disorder affects workers in smelters, in populations whose drinking water contains high levels of arsenic (0.3–0.4 ppm), and in patients treated for long periods with arsenic-based pharmaceuticals. Similarly, studies on workers exposed in copper foundries in the U.S., Japan and Sweden indicate a risk of lung cancer 6–10 times higher for the most exposed workers compared with the general population. Long-term ingestion of arsenic trioxide either in drinking water or as a medical treatment can lead to skin cancer. Reproductive problems (high incidence of miscarriage, low birth weight, congenital deformations) have also been indicated in one study of women exposed to arsenic trioxide dust as employees or neighbours of a copper foundry.

In Austria there lived the so called "arsenic eaters", who ingested doses far beyond the lethal dose of arsenic trioxide without any apparent harm. Arsenic is thought to enable strenuous work at high altitudes, e.g. in the Alps.[15][16][17]

The current OSHA 1910.1018 occupational permissible exposure limit for inorganic arsenic compounds in breathing zone air is 0.010 mg/m3.

References

  1. ^ Shakhashiri BZ, "Chemical of the Week: Arsenic", University of Wisconsin-Madison Chemistry Dept.
  2. ^ Pradyot Patnaik. Handbook of Inorganic Chemicals. McGraw-Hill, 2002, ISBN 0-07-049439-8
  3. ^ a b c d Sabina C. Grund, Kunibert Hanusch, Hans Uwe Wolf "Arsenic and Arsenic Compounds" in Ullmann's Encyclopedia of Industrial Chemistry, VCH-Wiley, 2008, Weinheim.
  4. ^ "Giant Mine - Northwest Territories Region - Indian and Northern Affairs Canada". http://nwt-tno.inac-ainc.gc.ca/giant/atg_e.html. Retrieved 2007-08-28. 
  5. ^ Holleman, A. F.; Wiberg, E. "Inorganic Chemistry" Academic Press: San Diego, 2001. ISBN 0-12-352651-5.
  6. ^ Marcel Gielen, Edward R. T. Tiekink (2005). Metallotherapeutic Drugs and Metal-Based Diagnostic Agents. Wiley. p. 298. 
  7. ^ Steven L. Soignet et al. (2001). "United States Multicenter Study of Arsenic Trioxide in Relapsed Acute Promyelocytic Leukemia". Journal of Clinical Oncology 19 (18): 3852–3860. 
  8. ^ Antman, K. H. (2001). "Introduction: The history of arsenic trioxide in cancer therapy". Oncologist 6(Suppl. 2) (1–2): 2006. 
  9. ^ Jun Zhu, Zhu Chen,Valérie Lallemand-Breitenbach, Hugues de Thé "How Acute Promyelocytic Leukaemia Revived Arsenic," Nature Reviews Cancer 2002, volume 2, 1-9.
  10. ^ Bobé Pierre, Bonardelle Danielle, Benihoud Karim, Opolon Paule, Chelbi-Alix Mounira (2006). "Arsenic trioxide: A promising novel therapeutic agent for lymphoproliferative and autoimmune syndromes in MRL/lpr mice.". Blood 108 (13): 3967-3975.. 
  11. ^ Lu J, Chew EH, Holmgren A (2007). "Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide". Proc. Natl. Acad. Sci. U.S.A. 104 (30): 12288–93. doi:10.1073/pnas.0701549104. PMID 17640917. 
  12. ^ "Stanton v Benzler 9716830". U.S. 9th Circuit Court of Appeals. 1998-06-17. http://caselaw.lp.findlaw.com/scripts/getcase.pl?navby=search&case=/data2/circs/9th/9716830.html&friend=usatoday. Retrieved 2008-06-09. "(...) convicted by a jury of first degree murder for poisoning her ex-husband. Her ex-husband's body was found with traces of arsenic trioxide in it." 
  13. ^ a b Emsley, John (2006). "Arsenic". The Elements of Murder: A History of Poison. Oxford University Press. pp. 93 –197. ISBN 9780192806000. 
  14. ^ Madame Bovary by Flaubert
  15. ^ Arsenic Eaters — New York Times July 26, 1885
  16. ^ Richard M. Allesch. Arsenik. Seine Geschichte in Österreich. 54. Band. Klagenfurt: Kleinmayr 1959.
  17. ^ G. Przygoda, J. Feldmann, W. R. Cullen (2001). "The arsenic eaters of Styria: a different picture of people who were chronically exposed to arsenic". Applied Organometallic Chemistry 15 (6): 457–462. doi:10.1002/aoc.126. http://doi.wiley.com/10.1002/aoc.126. 

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Dictionary. The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2009. Published by Houghton Mifflin Company. All rights reserved.  Read more
Oncology Encyclopedia. Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved.  Read more
Drug Info. Gold Standard. Copyright © 2008 by Gold Standard. All rights reserved.  Read more
WordNet. WordNet 1.7.1 Copyright © 2001 by Princeton University. All rights reserved.  Read more
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