1. Arsenic toxicity
Domina Petric, MD

2. Arsenic semiconductors
wood preservatives for industrial applications (marine timbers, utility poles)
nonferrous alloys
glass
gel-based insecticidal ant baits
veterinary pharmaceuticals

3. Arsenic
In some regions of the world, ground water may contain high levels of arsenic (from natural mineral deposits).
Arsine (arsenous hydride, AsH3) gas has potent hemolytic effect.
Arsine gas is manufactured predominantly for use in the semiconductor industry.
Arsenic trioxide is sometimes used as orphan drug for the treatment of relapsed acute promyelocytic leukemia.
Melarsoprol (trivalent arsenical) is used in the treatment of advanced African trypanosomiasis.

4. Pharmacokinetics
Soluble arsenic compounds are well absorbed through the respiratory and gastrointestinal tract.
Percutaneus absorption is limited, but it may be clinically significant after heavy exposure to concentrated arsenic reagents.

5. Pharmacokinetics
Most of the absorbed inorganic arsenic undergoes methylation, mainly in the liver.
Methylation products are monomethylarsonic acid and dimethylarsinic acid.
Both acids are excreted together with residual inorganic arsenic, in the urine.

6. Pharmacokinetics
When chronic daily absorption is less than 1000 mcg of soluble inorganic arsenic, two thirds of the absorbed dose is excreted in the urine within 2-3 days.

7. Pharmacokinetics
After massive ingestions, the elimination half-life is prolonged.
Inhalation of arsenic compounds of low solubility may result in prolonged retention in the lung.
It may not be reflected by urinary arsenic excretion.

8. Pharmacokinetics
Arsenic binds to sulfhydryl groups present in keratinized tissue.
Following cessation of exposure, hair, nails and skin may contain elevated levels after urine values have returned to normal.

9. Pharmacodynamics
Interference with enzyme function may result from sulfhydryl group binding by trivalent arsenic or by substitution for phosphate.
Inorganic arsenic or its metabolites may induce oxidative stress, alter gene expression and interfere with cell signal transduction.

10. Pharmacodynamics
Inorganic trivalent arsenic (As3+, arsenite) is generally two to ten times more acutely toxic than inorganic pentavalent arsenic (As5+, arsenate).

11. Pharmacodynamics
Trivalent form of the methylated metabolites (monomethylarsounous acid, MMA) may be more toxic than the inorganic parent compounds.
Reduced efficiency in the methylation of MMA to DMA is associated with an increased risk of chronic adverse effects.

12. Pharmacodynamics
S-adenosylmethionine is a universal methyl donor in the body.
Arsenic methylation also requires
S-adenosylmethionine.

13. Pharmacodynamics
Arsine gas is oxidized in vivo and exerts a potent hemolytic effect associated with alteration of ion flux across the erythrocyte membrane.
It also disrupts cellular respiration in other tissues.

14. Pharmacodynamics
Arsenic is human carcinogen and it has been associated with cancer of the lung, skin and bladder.

15. Major forms of arsenic intoxication
Acute inorganic arsenic poisoning
Chronic inorganic arsenic poisoning
Arsine gas poisoning
Major forms of arsenic intoxication

16. Acute inorganic arsenic poisoning
Acute toxic effects are evident within minutes to hours after exposure to high doses (tens to hundreds of milligrams) of soluble inorganic arsenic compounds.

17. Acute inorganic arsenic poisoning
Initial gastrointestinal signs and symptoms are NAUSEA, VOMITING, DIARRHEA and ABDOMINAL PAIN.
Diffuse capillary leak, combined with gastrointestinal fluid loss, may result in hypotension, shock and death.

18. Acute inorganic arsenic poisoning
Cardiopulmonary toxicity includes CONGESTIVE CARDIOMYOPATHY, CARDIOGENIC OR NONCARDIOGENIC PULMONARY OEDEMA and VENTRICULAR ARRHYTHMIAS.
This may occur promptly or after a delay of several days.

19. Acute inorganic arsenic poisoning
Pancytopenia usually develops within one week.
Basophilic stippling of erythrocytes may be present soon after.

20. Acute inorganic arsenic poisoning
Central nervous system effects:
delirium
encephalopathy
coma
CNS effects may occur within the first few days of intoxication.

21. Acute inorganic arsenic poisoning
An ascending sensorimotor peripheral neuropathy may begin to develop after a delay of 2-6 weeks.
This neuropathy may ultimately involve the proximal musculature and result in neuromuscular respiratory failure.

22. Acute inorganic arsenic poisoning
Months after an acute poisoning, transverse white striae may be visible in the nails.
These striae are called ALDRICH-MEES lines.

23. Thedoc.org

24. Acute inorganic arsenic poisoning
Diagnosis should be considered in patients presenting with:
abrupt onset of gastroenteritis in combination with hypotension and metabolic acidosis
cardiac dysfunction, pancytopenia, peripheral neuropathy

25. Acute inorganic arsenic poisoning
The diagnosis may be confirmed by demonstration of elevated amounts of inorganic arsenic and its metabolites in the urine: several thousand micrograms in the first 2-3 days after acute symptomatic poisoning.

26. Acute inorganic arsenic poisoning
Arsenic disappears rapidly from the blood.

27. Treatment Appropriate gut decontamination! Intensive supportive care!
Prompt chelation with:
UNITHIOL 3-5 mg/kg iv. every 4-6 hours or
DIMERCAPROL 3-5 mg/kg im. every 4-6 hours

28. Treatment
If diagnostic suspicion is high, treatment with chelation should be immediate.

29. Chronic inorganic arsenic poisoning
Overt noncarcinogenic effects may be evident after chronic absorption of more than 0,01 mg/kg/d ( mcg/d in adults).
The time to appearance of symptoms varies with dose and interindividual tolerance.

30. Chronic inorganic arsenic poisoning
fatigue
weight loss
weakness
anemia
nonspecific gastrointestinal complaints
sensorimotor peripheral neuropathy
stocking glove pattern of dysesthesia

31. Chronic inorganic arsenic poisoning
Skin changes develop after years of exposure: raindrop pattern of hyperpigmentation and hyperkeratoses of the hands and feet.

32. Chronic inorganic arsenic poisoning
Peripheral vascular disease and noncirrhotic portal hypertension may also occur.
There may also be link to hypertension, diabetes, chronic nonmalignant respiratory disease and adverse reproductive outcomes.

33. Chronic inorganic arsenic poisoning
Cancer of the lung, skin and bladder may appear years after exposure to arsenic.

34. Chronic inorganic arsenic poisoning
Administration of arsenite in cancer chemotherapy regimens (10-20 mg daily dose) for weeks to a few months may cause:
prolongation of the QT interval
malignant ventricular arrhythmias (torsades de pointes)

35. Treatment Termination of exposure and nonspecific supportive care.
Short term oral chelation unithiol or succimer.
Dietary supplementation of folate.

36. Arsine gas poisoning
After a latent period (2-24 hours postinhalation) massive intravascular hemolysis may occur.
Initial symptoms are:
malaise, headache, dyspnea
weakness, nausea, vomiting
abdominal pain, jaundice
hemoglobinuria

37. Renal failure often appears within 1-3 days.
Arsine gas poisoning
Oliguric renal failure is a consequence of hemoglobin depositions in the renal tubules.
Renal failure often appears within 1-3 days.
In massive exposures, lethal effects on cellular respiration may occur before renal failure.

38. Treatment Intensive supportive care: exchange transfusion
vigorous hydration
hemodialysis in acute renal failure
Chelating agents have not been demostrated to be of clinical value in arsine poisoning.

39. Literature Katzung, Masters, Trevor. Basic and clinical pharmacology.
Organics.org
Pinterest.com
Thedoc.org
Sos-arsenic.net