Management of Chemical and Heavy Metal Poisonings

Management of Chemical and Heavy Metal Poisonings

Insecticides

• Definition: Chemicals used to control insects by killing them or preventing undesirable/destructive behaviors.

• Types of Insecticides:

  1. Hydrocarbon Insecticides

     • DDT (Dichlorodiphenyltrichloroethane):

       • Highly toxic to a variety of insects.

       • Acts as a contact poison.

       • Mechanism of Action (MOA): Apparently disorganizes the nervous system.

     • Benzene Hexachlorides: An organochlorine chemical.

       • Widely used as an agricultural insecticide.

       • Also used as a pharmaceutical treatment for scabies and lice.

     • Cyclodienes:

       • Differ in their biotransformation and capacity of storage in tissues.

       • Absorption: Through skin, inhalation, or oral ingestion.

  • Toxic Effects of (Hydrocarbon) Insecticides:

    • Cause convulsions and tremors due to Central Nervous System (CNS) stimulation.

    • MOA:

      • Interfere with inactivation of the sodium channel in excitable membranes.

      • Inhibit calcium ion transportation.

  1. Organophosphates (OPs)

     • Definition: A group of human-made chemicals (man-made insecticides) that poison insects and mammals.

     • Mechanism of Action (MOA):

       • Irreversibly bind to AChE (acetylcholinesterase). This prevents the breakdown of ACh (acetylcholine).

       • ACh is the main neurotransmitter found in both the peripheral nervous system (PNS) and central nervous system (CNS) and has functions in both.

     • Examples: Malathion, Dibrom.

     • Availability: Found in pesticides.

     • Absorption: Through lungs, skin, gastrointestinal tract (GIT), eyes.

     • Effects:

       • Inhibit acetylcholine esterase, the enzyme that hydrolyzes acetylcholine to choline and acetic acid.

       • Causes prolonged muscle and nerve stimulation by ACh.

     • Clinical Manifestations of Organophosphate Toxicity:

       • Muscarinic Effects (due to excess ACh at muscarinic receptors):

         • Hypersecretion (e.g., increased sweating, salivation).

         • Constricted pupils (miosis).

         • Bronchoconstriction.

         • Vomiting.

         • Diarrhea.

         • Urinary incontinence.

       • Nicotinic Effects (due to excess ACh at nicotinic receptors):

         • Muscle weakness.

         • Tachycardia.

         • Hypertension.

         • Mydriasis (dilated pupils) may occur where nicotinic effects override muscarinic effects.

       • CNS Effects (due to excess ACh in the CNS):

         • Restlessness.

         • Anxiety.

         • Headaches.

         • Convulsions.

         • Coma (often with respiratory center depression).

     • Organophosphate Poisoning Treatment:

       • Decontamination:

         • Administer activated charcoal within 1-2 hours of ingestion.

         • Remove contaminated clothing and wash skin with soap and water.

       • Atropine: To reverse peripheral muscarinic effects.

         • Adult dose: 1-2 mg IV.

         • Child dose: 0.05 mg/kg every 15 minutes until bronchial secretions dry up.

         • Maintenance therapy: 0.05 mg/kg/hr.

         • Discontinuation: Done gradually over 24 hours with monitoring for rebound organophosphate toxicity.

       • Monitoring:

         • Blood pressure (BP), pulse, Electrocardiogram (ECG), pupil size.

         • Plasma cholinesterase levels (Adult Normal: 3000-8500 U/L).

       • Diazepam:

         • Controls confusion and convulsions resulting from organophosphates or from excess atropine.

       • Cholinesterase Reactivators:

         • Examples: Obidoxime, Pralidoxime.

         • May be added to atropine therapy in organophosphate poisoning.

         • Contraindicated: In carbamate poisoning.

     • Antidotes (Cholinesterase Reactivators):

       • Pralidoxime:

         • Competitively reactivates cholinesterase.

         • Quickens the breakdown of accumulated acetylcholine at both nicotinic and muscarinic sites.

         • Dose: 1 g 4 hourly intramuscularly (IM) or as a slow intravenous (IV) infusion.

         • Efficacy: Greatest within 12 hours of poisoning, then falls off steadily.

       • Obidoxime:

         • Also a cholinesterase reactivator used in acute organophosphate poisoning therapy.

         • MOA: Reverses phosphorylation of the cholinesterase enzyme.

         • Timing: Must be started 5 minutes after the first atropine dose and no later than 24 hours after poison ingestion.

         • Adult Dose: 250 mg IV, repeat once or twice every 2 hours, depending on response.

         • Side Effects (S/Es): Facial flushing, pain at injection site, hypertension, tachycardia, and decreased pain sensitivity.

  2. Botanical Insecticides

     • Definition: Insecticides used to kill or repel insects, consisting of dried, ground plant materials or chemicals isolated from plants.

     • Derived from: Nicotine and rotenone plants.

     • Why they are toxic:

       • Nicotine: Reacts with ACh receptors, leading to membrane depolarization.

       • Toxic doses (which occur in high amounts as they are naturally derived) cause rapid stimulation followed by blockage of transmission.

     • Treatment: Maintain vital signs and suppress convulsions.

Mycotoxins

• Definition: A toxic secondary metabolite produced by fungi that can cause diseases and death in humans and animals.

• Management Strategy: Identification of the specific fungi can aid in management.

Heavy Metals

• Common Poisonings: Acute and chronic lead, mercury, and arsenic (a metalloid) poisonings are relatively common.

• Antidotes: Dimercaprol, Penicillamine, Sodium calcium edetate, Succimer.

• Chelating Agents:

  • Used in the treatment of heavy metal poisoning.

  • Have a greater affinity for metals compared to endogenous enzymes, facilitating their removal from the body.

Types of Heavy Metal Poisoning

• Arsenic Poisoning:

  • Presentation: Hyperpigmentation (brown rain-drop pigments) on palms and soles.

  • Commonly used for: Chronic homicidal poisoning or criminal abortion.

  • Post-mortem finding: Fatty yellow liver.

• Mercury Poisoning:

  • Presentation: Tremors first occur in hands, then progress to lips, and finally arms. A bluish line over the gums.

  • Sources: Dry cell batteries, thermometers, disinfectants, paints, dental fillings, pesticides, fish.

Chelating Agents / Antidotes for Heavy Metals

1. Dimercaprol (British Anti-Lewisite - BAL)

   • Mechanism of Action (MOA): Sulfhydryl groups in dimercaprol form chelation complexes with certain metals, enhancing their excretion in urine.

   • Effective Antidote for: Acute mercury, arsenic, and gold poisoning.

   • Use in Lead Poisoning: May be used with calcium disodium edetate in the treatment of lead poisoning in children, especially in cases of lead encephalopathy.

   • Administration: Administered intramuscularly (IM) as a 10\% solution in oil.

   • Metabolism/Excretion: Uncomplexed portion is rapidly metabolized and excreted (within 4 hours).

   • Efficacy: Most effective when administered early after poisoning.

   • Side Effects (S.E.): May be minimized by allowing 4-hour intervals between doses.

     • Can make the patient feel quite ill.

     • Frequently causes hypertension, accompanied by tachycardia.

     • Nausea, vomiting, sweating.

     • Burning of eyes, lips, mouth, and throat; lacrimation, conjunctivitis, salivation.

     • Muscle spasm and pain, abdominal pain, tingling of extremities, headache.

     • Tightening of chest and throat.

     • Injections are often painful and abscesses may form.

   • Contraindications:

     • Iron, cadmium, selenium, and uranium poisoning (complexes formed with these metals are toxic to kidneys).

     • Hepatic dysfunction.

     • Hypertension.

     • Renal impairment.

   • Adult Dose:

     • 400-800 mg in divided doses on day 1.

     • 200-400 mg on day 2-3.

     • Then 100-200 mg on subsequent days.

2. Sodium Calcium Edetate (CaNa$_2$EDTA)

   • Primary Chelating Agent: Parenteral chelating agent of choice for acute or chronic lead poisoning.

   • Route of Administration:

     • IM route is preferred in lead encephalopathy and cerebral edema.

     • Reason: IV administration in these cases may cause a lethal increase in cranial pressure.

   • Primary Adverse Effect: Nephrotoxicity (ensure adequate urine production before and during treatment).

   • Adult Dose: 1 g IM or IV twice daily for 5 days, followed by a 2-day interruption if a repeat dose is required.

3. Penicillamine

   • Indications: Treatment of copper, zinc, mercury, arsenic, and lead poisoning.

   • Chelation Therapy Adult Dose: Usually 0.5 to 1.5 g daily in 4 divided doses.

4. Succimer (2,3-Dimercaptosuccinic acid)

   • Administration: Orally active chelating agent.

   • Indications: Used for the treatment of lead poisoning.

   • Action: Produces lead diuresis with subsequent lowering of blood lead levels.

   • Chemical Relation: Chemically related to dimercaprol but has a more favorable side effect profile.

   • Monitoring: Patients with a history of liver damage should be monitored closely.

Summary of Heavy Metal Poisoning by Type