Dictionary:

arsenic trioxide

  (är'sə-nĭk)

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A poisonous, white amorphous powder, As₂O₃, used in insecticides, rat poisons, and weed killers.

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.

Brand names: Trisenox®

Español:
• Inyección de trióxido de arsénico

Arsenic Trioxide injection

What is arsenic trioxide?

ARSENIC TRIOXIDE (Trisenox™) is used to treat acute promyelocytic leukemia and other diseases such as multiple myeloma and myelodysplastic syndromes. Generic arsenic trioxide injection is not available.

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

They need to know if you have any of these conditions:
• heart failure
• irregular heartbeat
• kidney disease
• an unusual or allergic reaction to arsenic, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I take this medicine?

Arsenic trioxide is given by an infusion into a vein. You will receive arsenic trioxide in a clinic or hospital setting.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What drug(s) may interact with arsenic trioxide?

• astemizole
• certain antibiotics (clarithromycin, erythromycin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, sparfloxacin)
• cisapride
• chloroquine
• daunorubicin or doxorubicin
• dolasetron
• droperidol
• foscarnet
• levomethadyl
• medicines for heart disease
• medicines used to control the heart rhythm (examples: amiodarone, bepridil, disopyramide, flecainide, procainamide, propafenone, quinidine, sotalol)
• medicines used for mental problems, psychosis, or depression (examples: amitriptyline, chlorpromazine, fluphenazine, haloperidol, mesoridazine, perphenazine, pimozide, prochlorperazine, risperidone, thioridazine, ziprasidone)
• methadone
• palonosetron
• pentamidine
• probucol
• terfenadine
• water pills (diuretics)

Tell your prescriber or other health care professional about all other medicines you are taking including nonprescription medicines, nutritional supplements, or herbal products. Also, tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medications.

What should I watch for while taking arsenic?

Visit your prescriber or health care professional for regular checks on your progress. You will need to have regular checks of your heart rate and blood counts.

Call your prescriber or health care professional for advice if you get a fever, chills or cough or experience excessive bleeding or bruising. Do not treat yourself.

Women who are able to have children should use effective birth control methods while receiving arsenic trioxide.

What side effects may I notice from taking arsenic trioxide?

Side effects that you should report to your prescriber or health care professional as soon as possible:
• confusion
• difficulty breathing, shortness of breath, or wheezing
• fever
• irregular heart beat or palpitations
• muscle weakness
• retaining fluid
• seizures
• skin rash
• weight gain

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• cough
• diarrhea
• dizziness
• fatigue
• headache
• itching
• stomach pain

Where can I keep my medicine?

This does not apply. You will receive arsenic trioxide in a hospital or clinic setting.

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.

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

Arsenic trioxide
Other names	Arsenic(III) oxide, Arsenic sesquioxide, Arsenicum album, Arseneous oxide, Arseneous anhydride
Identifiers
CAS number	1327-53-3
PubChem	518740
EINECS number	215-481-4
Properties
Molecular formula	As2O3
Molar mass	197.841 g/mol
Appearance	White solid
Density	3.86 g/cm³, solid.
Melting point	274°C
Boiling point	460°C
Solubility in water	2 g/100 ml (25°C) see text
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
Hazards
MSDS	External MSDS
EU classification	Very toxic (T+) Carc. Cat. 1 Dangerous for the environment (N)
NFPA 704	0 3 2
R-phrases	R45, R28, R34, R50/53
S-phrases	S53, S45, S60, S61
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
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Arsenic trioxide
Systematic (IUPAC) name
2,4,5-trioxa-1,3-diarsabicyclo[1.1.1]pentane
Identifiers
CAS number	1327-53-3
ATC code	L01XX27
PubChem	?
DrugBank	APRD00171
Chemical data
Formula	As2O3
Mol. mass	197.841 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	75% bound
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

Arsenic trioxide is the most important commercial compound of arsenic, and the main starting material for arsenic chemistry. It is the highly toxic byproduct of certain kinds of ore processing, for example gold mining.^[1]

Preparation

• Burning arsenic in air.
• Hydrolysis of arsenic trichloride.
• Roasting of arsenide minerals. (Main industrial route)

Chemical properties

Arsenic trioxide is an amphoteric oxide which shows a marked preponderance for its acidic properties. It dissolves readily in alkaline solutions to give arsenites. It is much less soluble in acids, but will dissolve in hydrochloric acid to give arsenic trichloride or related species. It reacts with oxidizing agents such as ozone, hydrogen peroxide and nitric acid to give arsenic pentoxide, As₂O₅: the reaction with hydrogen peroxide can be explosive. It is also readily reduced to arsenic, and arsine (AsH₃) may also be formed.

Molecular structure

Tetrahedral molecules, As₄O₆, in α-form and in liquid and gas phases.

Uses

• Starting point for the manufacture of arsenic-based pesticides .(sodium arsenite, sodium arsenate, sodium cacodylate).
• Starting point for the manufacture of certain arsenic-based pharamaceuticals (Neosalvarsan) and veterinary products.
• Decolorizing agent for glasses and enamels.
• Preservative for wood.
• Hydrogen recombination poison for metallurgical studies.
• Starting point for the preparation of elemental arsenic, arsenic alloys and arsenide semiconductors.
• Use as a cytostatic in the treatment of refractory promyelocytic (M3) subtype of acute myeloid leukemia. The drug is available as Trisenox® ampules; each containing 10mg to be diluted for i.v. infusion.
• Arsenic trioxide is also used to treat leukemia in patients who have not responded to other medications.

Medical applications

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 trisulfide induces cancer cells to undergo apoptosis. Due to the toxic nature of arsenic, this drug carries significant risks.

The enzyme thioredoxin reductase has recently been identified as a target for arsenic trioxide.^[2]

Toxicology

See also: arsenicosis.

Arsenic trioxide is readily absorbed by the digestive system: toxic effects are also well known after inhalation of the dust or fumes and after skin contact. Elimination is rapid at first (half-life of 1–2 days), by methylation to cacodylic 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.

Cases of acute arsenic poisoning are known after inhalation and after skin contact with arsenic trioxide. The first signs are severe irritation, either of the respiratory tract or of the exposed skin, followed by longer term neurological problems. Even dilute solutions of arsenic trioxide are dangerous on contact with the eyes.

Chronic arsenic poisoning is known as arsenicosis: it is found after professional exposure (for example, in metal 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.

Arsenic trioxide has been shown to be a human carcinogen. 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.

Bibliography

• Institut national de recherche et de sécurité (INRS), Fiche toxicologique nº 89 : Trioxyde de diarsenic, 1989.
• AFHS Database on use as a cytostatic

References

1. ^ Giant Mine - Northwest Territories Region - Indian and Northern Affairs Canada. Retrieved on 2007-08-28.
2. ^ 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. 

External links

• Case Studies in Environmental Medicine: Arsenic Toxicity
• IARC Monograph – Arsenic and Arsenic Compounds
• International Chemical Safety Card 0378
• NIOSH Pocket Guide to Chemical Hazards
• NTP Report on Carcinogens – Inorganic Arsenic Compounds
• Use of Arsenic Trioxide in Multiple Myeloma Treatment
• The use of Arsenic trioxide in medicine.
• Institut national de recherche et de sécurité (1989). "Trioxyde d'arsenic."PDF Fiche toxicologique n° 89. Paris:INRS. (French)

Chemotherapeutic agents/Antineoplastic agents (L01)
Alkylating agents	Nitrogen mustards: (Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan). Nitrosoureas:(Carmustine, Fotemustine, Lomustine, Streptozocin). Platinum: (Carboplatin, Cisplatin, Oxaliplatin, BBR3464). Busulfan, Dacarbazine, Procarbazine, Temozolomide, ThioTEPA, Uramustine
Antimetabolites	Folic acid: (Aminopterin, Methotrexate, Pemetrexed, Raltitrexed). Purine:(Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine). Pyrimidine:(Capecitabine, Cytarabine, Fluorouracil, Floxuridine, Gemcitabine)
Spindle poison/mitotic inhibitor	Taxane: (Docetaxel, Paclitaxel). Vinca: (Vinblastine, Vincristine, Vindesine, Vinorelbine).
Cytotoxic/antitumor antibiotics	Anthracycline family: (Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitoxantrone, Valrubicin) - streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin) - Hydroxyurea
Topoisomerase inhibitors	Camptotheca: (Camptothecin, Topotecan, Irinotecan), Podophyllum:(Etoposide, Teniposide)
CI monoclonal antibodies	Alemtuzumab, Bevacizumab, Cetuximab, Gemtuzumab, Panitumumab, Rituximab, Tositumomab, Trastuzumab
Photosensitizers	Aminolevulinic acid, Methyl aminolevulinate, Porfimer sodium, Verteporfin
Tyrosine kinase inhibitors	Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Nilotinib, Sorafenib, Sunitinib
Other	retinoids (Alitretinoin, Tretinoin) - Altretamine, Amsacrine, Anagrelide, Arsenic trioxide, Asparaginase (Pegaspargase), Bexarotene, Bortezomib, Denileukin diftitox, Estramustine, Masoprocol, Mitotane

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