TOX 7 - Arsenic Flashcards
Arsenic compounds
Elemental is basically harmless
forms which enter the body:
- Inorganic arsenic salts:
- Trivalent arsenite- highly toxic, poor solute, but can be absorbed through skin
- Pentavalent - less toxic, more soluble
- or arsenates
Pharmacodynamics
Binds to SH groups (sulfhydryl ) and inhibits enzymes–> interfering with oxidative phosphorylation
Strong capillary poison
Possible carcinogenic
Acute intoxication symptoms
initial - nausea, vomiting, dizziness
mid - latency period
late - severe vomiting and diarrhoea (rice water stool) -> severe dehydration
- gastroenteritis, hematemesis, severe diarrhea → hypovolemic shock; arrhythmias,
- CNS symptoms (encephalopathy, delirium, coma), pancytopenia
- weeks later – ascending peripheral neuropathy (may result neuromuscular respiratory failure)
- month later - transverse white striate on the nails
Treatment of acute intox
Gastric lavage
Chelation therapy (dimercaprol)
Supportive treatment
Chronic intoxiaction
Skin change, anorexia, cachexia, GI problems etc -> death
- weakness,
- peripheral neuropathy (socking-glove pattern),
- anemia,
- liver and kidney damage,
- skin changes - hyperkeratosis, hyperpigmentation, general cachexia
Arsine gas poisoning (ASH3)
Very powerful haemolytic agent - fever, icterus, renal damage
Supportive treatment
Most frequent source of intoxication- arsenic
- industry,
- agriculture (herbicides, insecticides),
- wood, preservatives,
Major route of absorption - arsenic
- respiratory and
- GI tract
distribution of arsenic
Distribution
- soft tissues,
- first of all liver and kidney,
- later skin, hair, nail
Arsenic poisoning mechanism
Interferes with over 200 enzymes in the body
- ATP depletion
- Carcinogenic: Interfere with base and nucleotide excision repair –> cancer risk increases
- Oxidative stress
- Disrupts signal transduction pathways
- Atherosclerosis
- Diabetes
- Acute lethal dose: 70 – 200mg or 1 mg/kg/day
arsenic acute lethal dose
• Acute lethal dose: 70 – 200mg or 1 mg/kg/day
arsenic poisoning diagnosis
Diagnosis:
- Measurement of arsenic in blood, urine, hair and fingernails
- Symptoms
- Drinking water measurements
treatment of arsenic poisoning
Treatment:
- Supportive treatment
- Chelation: Dimercaprol Dimercaptosuccinic acid
- Calcium sodium edetate