Heavy Metal Toxicity (Arsenic) Presented by:-

Heavy metal antagonist (Chelating Agents) These agents are designed specifically to compete with these groups for the metals and prevent or reverse toxic effects and enhance the excretion of metals.

e.g- British antilewisite (BAL), Ca-EDTA<br>

Chelate Chelate is complex formed between a metal and a compound that contains two or more potential ligand, the stability of chelate varies with the metal the ligand atoms.

e.g- lead and mercury have greater affinities for sulphur and nitrogen than for oxygen.<br>

Ideal Properties of a chelating agent The most important property of chelating agent is its greater affinity to metal atom than the metal atom towards the ligands.
It should have high solubility in water.
Should have resistance to metabolic degradation.
should have ability to penetrate at site of metal storage.
Capacity to form nontoxic complex with toxic metals.
Ability to retain chelating activity at the high PH of body fluid.
Readily excretion of chelate.<br>

Arsenic Toxicity Source :-

* Arsenic poisoning is caused by different types of inorganic and organic arsenical compound.

* Poisoning occurs due to arsenic trioxide & arsenic pentaoxide.

* Trivalent arsenicals are more soluble and hence more toxic than pentavalent.

* It is used as rodenticides, herbicide and pesticide.( Lead arsenate is used as taenicide in sheep)

* Used in mining operations (for smelting), so in industrialized area air is polluted with arsenic.<br>

Toxicokinetic Soluble forms of arsenic compounds are well absorbed orally, & distributes to several tissues.

The highest levels found in liver, kidneys, heart, and lungs.

In chronic exposures, arsenic accumulates in skin, nails, hooves, sweat glands, and hair.

It does not crosses blood brain barrier (BBB).

It crosses placental barrier & cause foetal damage.

The majority of the absorbed arsenic is excreted in the bile, milk, saliva, sweat urine & faeces.<br>

Mechanism of action Tissues that are rich in oxidative enzymes such as the GI tract, liver, kidneys, lungs, endothelium, and epidermis are considered more vulnerable to arsenic damage.

Trivalent arsenic compounds exert their toxicity by interacting with sulfhydryl group of enzymes( alpha-lipoic acid), resulting in disruption of cellular metabolism.

Pentavalent arsenic can uncouple oxidation phosphorylation.

Effect of arsenic on GIT is due to its local corrosive effect.<br>

Clinical signs Acute poisoning :-
Poisoning is usually acute with major effects on the GI tract and cardiovascular system.

watery diarrhoea(rice water diarrhoea), sometimes tinged with blood, is characteristic, as are severe colic, dehydration, weakness,

Arsenic has a direct effect on the capillaries. There is transudation of plasma, loss of blood and severe fall of B.P, hypovolemic shock. Profuse depression, weak pulse, and cardiovascular collapse.<br>

Continue…. Chronic Poisoning:-
Chronic cases are rare and are characterized by ---
* poor appetite
* Digestive disorder
* Wasting
* Brick-red mucous membrane
* Weak and irregular pulse<br>

Post-mortem changes Inflammation and reddening of GI mucosa.

Extravasations of blood from the blood vessels.

Adipose degeneration of liver kidney, lung and other organs.

In case of cutaneous exposure the skin may exhibit necrosis and be dry and leathery.<br>

Treatment BAL (British anti-lewisite ) @ 3 mg/kg, IM, every 4 hr for the first 2 days, every 6 hr for the third day, and 12 hrly f for the next 10 days or until recovery.

Supportive therapy may be of even greater value, particularly when cardiovascular collapse is imminent, and should involve IV fluids to restore blood volume and correct dehydration.<br>