arsenic trioxide


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arsenic

 (As) [ahr´sĕ-nik]
a chemical element, atomic number 33, atomic weight 74.92. (See Appendix 6.) It is toxic by inhalation or ingestion, and carcinogenic (see arsenic poisoning). In nature it occurs usually as one of its salts; in human environments it is often a pollutant in mining regions, and is used in dyes, household pesticides, and compounds used in agriculture. Arsenic compounds called arsenicals were formerly widely used in medicine.
arsenic poisoning poisoning due to systemic exposure to inorganic pentavalent arsenic. Arsenic is cumulative, storing permanently in hair, nails, and bone, and children are particularly susceptible. Arsenic is odorless and flavorless and has been found in elevated levels in the drinking water that flows through arsenic-rich rocks, leading to serious health problems in some countries. The antidote for arsenic poisoning is dimercaprol. Acute arsenic poisoning, which may result in shock and death, is marked by skin eruptions, swelling of eyelids and limbs, vomiting, diarrhea, and cramps. Chronic arsenic poisoning (called also arsenism), due to ingestion of small amounts over a long period of time, is marked by skin pigmentation with scaling, keratosis of the palms and soles, white lines on the fingernails, peripheral neuropathy, and confusion.
arsenic trioxide an oxidized form of arsenic, used in weed killers and rodenticides. It is also administered intravenously as an antineoplastic in the treatment of acute promyelocytic leukemia.

arsenic trioxide

Trisenox

Pharmacologic class: Nonmetallic element, white arsenic

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Give under supervision of physician experienced in managing patients with acute leukemia.

• Some patients with acute promyelocytic leukemia (APL) treated with drug have had symptoms similar to retinoic-acid-acute promyelocytic leukemia (RA-APL) or APL differentiation syndrome, marked by fever, dyspnea, weight gain, pulmonary infiltrates, and pleural or pericardial effusions. Syndrome can be fatal; at first sign, give high-dose steroids immediately, regardless of patient's white blood cell count; continue steroids for at least 3 days or longer until signs and symptoms abate. Most patients don't require arsenic trioxide termination during treatment of APL differentiation syndrome.

• Drug may prolong QT interval and cause complete atrioventricular block. QT prolongation can lead to torsades de pointes-type ventricular arrhythmia, which can be fatal.

• Before starting therapy, obtain 12-lead ECG and assess serum electrolyte (potassium, calcium, and magnesium) and creatinine levels. Correct electrolyte abnormalities and, if possible, discontinue drugs known to cause QT prolongation. During therapy, maintain potassium level above 4 mEq/L and magnesium level above 1.8 mg/dL. If patient reaches absolute QT interval value above 500 msec, reassess and take immediate action to correct concomitant risk factors.

Action

Unclear. May cause morphologic changes and DNA fragmentation in promyelocytic leukemia cells, causing cell death and degradation of or damage to PML/RAR alpha (a fusion protein).

Availability

Injection: 1 mg/ml

Indications and dosages

APL in patients who have relapsed or are refractory to retinoid and anthracycline chemotherapy

Adults and children ages 5 and older: Induction phase-0.15 mg/kg I.V. daily until bone marrow remission occurs, to a maximum of 60 doses. Consolidation phase-0.15 mg/kg I.V. daily for 25 doses over 5 weeks, starting 3 to 6 weeks after completion of induction phase.

Contraindications

• Hypersensitivity to drug

• Pregnancy

Precautions

Use cautiously in:

• renal impairment, cardiac abnormalities

• elderly patients

• breastfeeding patients

• children.

Administration

Know that drug is carcinogenic. Follow facility policy for preparing and handling antineoplastics.

• Dilute in 100 to 250 ml of dextrose 5% in water or normal saline solution.

• Don't mix with other drugs.

• Infuse over 1 to 2 hours (may infuse over 4 hours if patient has vasomotor reaction).

Adverse reactions

CNS: headache, insomnia, paresthesia, dizziness, tremor, drowsiness, anxiety, confusion, agitation, rigors, weakness, seizures, coma

CV: ECG abnormalities, palpitations, chest pain, hypotension, hypertension, tachycardia, prolonged QT interval, torsades de pointes

EENT: blurred vision, painful red eye, dry eyes, eye irritation, swollen eyelids, tinnitus, earache, nasopharyngitis, postnasal drip, epistaxis, sinusitis, sore throat

GI: nausea, vomiting, constipation, diarrhea, abdominal pain, fecal incontinence, dyspepsia, dry mouth, mouth blisters, oral candidiasis, anorexia, GI hemorrhage

GU: urinary incontinence, intermenstrual bleeding, renal impairment, oliguria, renal failure, vaginal hemorrhage

Hematologic: anemia, lymphadenopathy, leukocytosis, thrombocytopenia, neutropenia, disseminated intravascular coagulation, hemorrhage

Metabolic: hypokalemia, hypomagnesemia, hyperglycemia, acidosis, hypoglycemia, hyperkalemia Musculoskeletal: joint, muscle, bone, back, neck, or limb pain

Respiratory: dyspnea, cough, hypoxia, wheezing, crackles, tachypnea, decreased breath sounds, crepitation, hemoptysis, rhonchi, upper respiratory tract infection, pleural effusion

Skin: flushing, erythema, pallor, bruising, petechiae, pruritus, dermatitis, dry skin, hyperpigmentation, urticaria, skin lesions, herpes simplex infection, local exfoliation, diaphoresis, night sweats

Other: fever, facial edema, weight gain or loss, bacterial infection, pain and edema at injection site, hypersensitivity reaction, sepsis

Interactions

Drug-drug. Drugs that can cause electrolyte abnormalities (such as amphotericin B, diuretics): increased risk of electrolyte abnormalities

Drugs that can prolong QT interval (antiarrhythmics, thioridazines, some quinolones): increased QT-interval prolongation

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, calcium, magnesium, white blood cells: increased levels

Glucose, potassium: altered levels

Hemoglobin, neutrophils, platelets: decreased values

Patient monitoring

Watch for signs and symptoms of APL differentiation syndrome (fever, dyspnea, weight gain, pulmonary infiltrates, and pleural or pericardial effusions).

• Evaluate vital signs and neurologic status.

Obtain baseline ECG; monitor ECG at least weekly.

• Assess for arrhythmias and conduction disorders.

Discontinue drug and notify prescriber if patient develops syncope, tachycardia, or arrhythmias.

• Monitor serum electrolyte levels, CBC, and coagulation studies.

• Assess for hypoglycemia and hyperglycemia if patient is diabetic.

Patient teaching

Watch for signs and symptoms of APL differentiation syndrome.

• Tell patient that drug increases risk of serious infection. Instruct him to report signs or symptoms of infection.

Emphasize importance of avoiding pregnancy during therapy.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Tell patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

• Advise patient to establish effective bedtime routine to minimize insomnia.

• Notify patient that he'll undergo regular blood testing during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

ar·se·nic tri·ox·ide

As2O3; dissolves in water to produce arsenous acid, H3AsO3; used in the treatment of skin diseases and historically for malaria and as a tonic; also used externally as a caustic.

Trisenox

A chemotherapeutic agent used for patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterised by the t(15;17) translocation or by PML/RAR-alpha gene expression.

Adverse effects
QT interval prolongation; complete atrioventricular block; APL differentiation (retinoic acid); syndrome-like symptoms (fever, dyspnoea, weight gain, pulmonary infiltrates, pleural or pericardial effusions, ± leukocytosis) which may be fatal.

arsenic trioxide

Oncology An anticancer drug that induces apoptosis in certain cancer cells

ar·sen·ic tri·ox·ide

(ahrsĕ-nik trī-oksīd)
H3AsO3; used in the treatment of skin diseases and historically for malaria and as a tonic; also used externally as a caustic.
References in periodicals archive ?
2002, Arsenic trioxide promotes histone H3 phosphoacetylation at the chromatin of CASPASE-10 in acute promyelocytic leukemia cells.
Characterization of cytotoxicity induced by arsenic trioxide (a potent anti-APL drug) in rat cardiac myocytes.
Figure 4 shows that the oral administration of arsenic trioxide caused an abnormal liver function in the treated rats.
Arsenic trioxide (ATO) comes under the class of medications known as antineoplastics.
Attenuation of arsenic trioxide induced cardiotoxicity through flaxseed oil in experimental rats (abstract).
Further, we found no experimental studies that focused on cardiovascular outcomes associated with inhalation of arsenic trioxide. Little is known about how inorganic arsenic absorption differs between ingestion and inhalation routes, although arsenic trioxide is readily soluble in the lungs (WHO 2001).
Douer et al., "United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia," Journal of Clinical Oncology, vol.
Obecnie w leczeniu ostrej bialaczki promielocytowej wykorzystuje sie kwas all-trans retinowy (all-trans terinoic acid--ATRA) w polaczeniu z chemioterapia, a takze trojtlenek arsenu (arsenic trioxide - ATO) [6].
The weathering of rocks converts the arsenic sulfides in these minerals to arsenic trioxide that then enters into the environment as dust and dissolves in rain, rivers, and groundwater (Mandal & Suzuki, 2002; U.S.
Arsenic stock solution was prepared by dissolving arsenic trioxide (As2O3) salt dried at 105-110 oC for one hour then 1.32 gm of it was added in 100 ml of demineralized water containing 4 gm of sodium hydroxide (NaOH) reagent grade salt in one liter measuring flask.
In this study multiple replications of this model were employed using controls and a 45X homoeopathic potency of arsenic trioxide succussed 4, 8, 16, 32, 40, 70 and 100 times.
The early alchemists subsequently extracted from the sulphides a third compound, arsenic trioxide, the deadly white powder that is still most typically associated with murder mystery assassins.