OPC poisoning

ORGANOPHOSPHORUS POISONS

They are esters of phosphoric acid and form two series of compounds.

Classification of Organophosphorus Compound

A) Alkyl phosphates:

1) HETP (Hexaethyltetraphosphate)

2) TEPP (Tetron) (tetraethyl-pyrophosphate)

3) OMPA (octamethylpyrophos-phoramide)

4) Dimefox

5) Isopestox

6) Malathion (Kill bug; Bugsoline)

7) Sulfotepp

8) Demeton

9) Trichlorfon

B) Aryl phosphates:

1) Parathion (nitrostigrnine) (Follidol; Kill phos; Ekato)

2) Paraoxon

3) Methyl- parathion (Metacide)

4) Chlorthion

5) Diazinon

They are available as dusts, granules and liquids.

Absorption:

They are absorbed by inhalation, through the skin, mucous membranes and the gastrointestinal tract. When sprayed in air, absorption in the plants occurs through leaves and stems.

Metabolism occurs in the liver. Detoxification occurs via cytochrome P450 monooxygenase. The aryl organophosphates require liver activation to become toxic. Excretion of metabolites occurs in the urine.

They are mixed with a solvent, usually aromax, which is responsible for kerosine-like smell in the body cavities, stomach contents, vomit, froth, etc.

Fatal Dose:

  1. TEPP: 50 mg I/M or 100 mg. orally.
  2. OMPA: 80 mg I/M or 175 mg. orally.
  3. Parathion: 80 mg I/M or 175 mg. orally.
  4. HETP: 60 mg I/M or 350 mg. orally.
  5. Malathion and diazinon one gm orally.

Fatal Period:

Death usually occurs within 24 hours in untreated cases, and within 10 days in those treated cases when treatment is not successful. In non- fatal cases, the acute effects last for 6 - 30 hours which disappear in 2 to 3 days, but may sometimes persist for 2 weeks. Complete recovery occurs in 10 days in patients treated early, unless hypoxic encephalopathy intervenes.

Mechanism of Action:

Normally

Acetylcholine is produced at the myoneural junction, and acts as a chemical signal transmitter at synapses (neurotransmitter) which is hydrolysed to choline and acetic acid spontaneously. Hydrolysis is greatly increased by cholinesterases, which are present in plasma and on the membranes, or within the cytoplasm of many cells.

Organophosphorus compounds are powerful inhibitors of carboxylic esterase enzymes, including acetylcholinesterase

Organophosphorus compounds bind firmly to the esterase enzyme, inactivating it by phosphorylation, at the myoneural junctions and synapses of the ganglions.

Phosphorylated acetylcholinesterase loses an alkyl group, due to which the enzyme cannot spontaneously hydrolyze and becomes permanently inactivated. They are called cholinesterase inhibitors.

Organic phosphates inhibit AChE in all parts of the body, due to which acetylcholine accumulates at the parasympathetic, sympathetic and somatic sites. This produces a syndrome of over-activity due to unhdrolysed acetylcholine with continued stimulation of local receptors and eventual paralysis of nerve or muscle.

The inactivation of cholinesterase enzymes becomes irreversible after 24 to 36 hours. Symptoms appear in both the sympathetic and parasympathetic nervous system.

Mechanism of Action of OPC/ Mechanism of Respiratory Failure in OPC Poisoning (Ref-Endeavor)

From site of administration (eg.GIT or Skin), OPC absorbed into blood

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Goes to neuromuscular junction & synapses of ganglion

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Binds firmly with enzymes acetyl-cholinesterase

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Phosphorylation & inhibition of enzyme occur

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Prevention of breakdown of Acetylcholine (Ach)

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Increase concentration of Acetylcholine

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Over activity of Acetylcholine (acetylcholine excess)

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Signs symptoms of excess/over activity of Acetylcholine

Or

Paralysis of respiratory muscle, bronchospasm

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Convulsion

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Coma

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Death

Signs & Symptoms of OPC poisoning

1) Muscarinic manifestations:

These symptoms can be easily remembered by the acronym SLUDGE: Salivation, lacrimation, urination, defection, gastrointestinal distress, and emesis (Vomit).

 

1) Bronchial tree: Broncho-constriction, increased bronchial secretions, dyspnoea, cyanosis, pulmonary edema

2) G.I.T.: Anorexia, salivation, nausea, vomiting, cramps, diarrhea, faecal incontinence, tenesmus. Pancreatitis may develop.

3) C.V.S.: Bradycardia, arrhythmias, conduction blocks, hypotension

4) Sweat glands: Increased sweating

5) Salivary glands: Increased salivation

6) Lacrimal glands: Increased lacrimation

7) Pupils: Miosis (constriction)

8) Ciliary body: Blurred vision

9) Bladder: Urinary incontinence

 

2) Nicotinic manifestations:

1) Striated muscle: Initial stimulus results in contraction. Later there is paralysis due to persistent depolarization. Muscle weakness is due to accumulation of acetylcholine. Muscular fasciculations (muscle twitching), cramps, weakness, areflexia (absence of deep reflexes)

2) Sympathetic ganglia: Hypertension, tachycardia, pallor, mydriasis.

 

3) CNS manifestations:

Restlessness, emotional lability, headache, tremors, anxiety, drowsiness, confusion, slurred speech, ataxia, generalized weakness, coma, convulsions, depression of respiratory and cardiovascular centers.

Cause of Death:

Death is caused by paralysis of respiratory muscles, respiratory arrest due to failure of respiratory centre, or intense broncho-constriction. Late death, as long as 15 days after acute ingestion may be caused by ventricular arrhythmias.

Diagnosis

Diagnosis may be confirmed by giving two mg. of atropine. In a normal person this causes marked atropinization, but in a case of poisoning by organophosphorus, symptoms are relieved without atropinizing.

Estimations of cholinesterase in erythrocytes & at myoneural junction are confirmatory.

Treatment in case of OPC Poisoning:

  1. General management

1) The patient is removed from the source of exposure, the contaminated clothing removed and the exposed areas are washed with soap and water, followed by ethanol and water, or some alkaline solution.

 

If eye is contaminated irrigate the conjunctival recesses, cornea, bulbar conjunctiva, internal and external palpebral surfaces.

2) The airway should be kept patent. Tracheostomy may be required.

3) When the poison is ingested, the stomach should be washed with 1:5,000 potassium permanganate solution.

4) When cyanosis is present, maximal oxygenation should be achieved before atropine is given for avoiding increased risk of ventricular tachy-arrhythmias associated with hypoxia.

 

  1. Specific Management

1. Atropine (I/V) 2-4 mg is given IV as a test dose.

If there is no effect, this dose may be doubled every 10 to 15 min until muscarinic symptoms are relieved.

Atropine should be continued until the tracheobronchial tree is cleared of the secretions and most secretions are dried, but not pupillary status.

Once signs of adequate atropinization occur, the dose should be adjusted to maintain this effect for at least 24 hours.

2.  Pralidoxine (I/V) - 1gm I/V bolus over 30 minutes & then infusion 0.5 gm/hour or 30 mg/kg body weight. (Ref Endeavor)

Oximes reactivate inhibited cholinesterase, remove the block at neuromuscular junction, prevent formation of phosphorylated enzyme, and directly detoxify organophosphates.

3. Convulsions can be controlled with I/V diazepam

4. Pulmonary edema and bronchospasm should be treated with oxygen, intubation, atropine and positive pressure ventilation.

5. Antibiotics to prevent pulmonary infections.

 

Atropinization: (Ref-Endeavor)

The act or process of treating with atropine or can be defined as the physiological condition of being under the influence of atropine.

 

Signs of atropinization

  1. Dilated pupil/mydriasis
  2. Loss of light reflex
  3. Tachycardia
  4. Dry mouth
  5. Dry skin
  6. Raised temperature
  7. Patient become restlessness

 

Postmortem Appearances in case of OPC Poisoning:

External finding

Signs of asphyxia are found.

The face is congested and there is cyanosis of the lips, fingers and nose.

Bloodstained forth is seen at the mouth and nose.

Kerosene like smell from mouth (due to solvent used called ‘aromex’

 

Internal finding

Stomach contents may smell of kerosene.

Mucosa of the stomach is congested with sub-mucous petechial hemorrhages.

Respiratory passages are congested and contain frothy hemorrhagic exudate.

Lungs show gross congestion, excessive edema and sub-pleural petechiae.

Heart is sometimes soft and flabby.

The brain is congested and edematous; meninges are congested. Petechial hemorrhages are present.

The internal organs are congested.

 

Nice To Know

Porphyrinaemia, resulting in chromo-dacryorrhoea (shedding of red tears) due to accumulation of porphyrin in the lacrimal glands is seen very rarely.

Intermediate Syndrome:

In some cases after one to four days muscle weakness and paralysis characterized by motor cranial nerve plasies, weakness of neck flexor and proximal limb muscles, and acute respiratory paresis are seen due to prolonged cholinesterase inhibition and muscle necrosis. It does not respond to oximes or atropine.

Delayed Sequelae:

Delayed peripheral neuropathy can occur one to 5 weeks after exposure to certain compounds, such as parathion, malathion, trichlorfon, etc . It begins with paraesthesia and pain or cramps in the calves followed by ataxia, weakness, and toe drop. It rapidly progresses to a flaccid paresis which can ascend similar to Guillain-Barre syndrome. Reflexes are diminished. The disease may progress for 2 to 3 months, and muscle wasting occurs.

Just To Know (Ref-Wikipedia)

Acetylcholine is the neurotransmitter used at the neuromuscular junction—in other words, it is the chemical that motor neurons of the nervous system release in order to activate muscles.

Acetylcholine is also a neurotransmitter in the autonomic nervous system, both as an internal transmitter for the sympathetic nervous system and as the final product released by the parasympathetic nervous system. Acetylcholine is the primary neurotransmitter of the parasympathetic nervous system.

Acetylcholine exerts its effects by binding to and activating receptors located on the surface of cells. There are two main classes of acetylcholine receptor, nicotinic and muscarinic. They are named for chemicals that can selectively activate each type of receptor without activating the other: muscarine is a compound found in the mushroom Amanita muscaria; nicotine is found in tobacco.

 

Nicotinic acetylcholine receptors are ligand-gated ion channels permeable to sodium, potassium, and calcium ions. In other words, they are ion channels embedded in cell membranes, capable of switching from a closed to an open state when acetylcholine binds to them; in the open state they allow ions to pass through. Nicotinic receptors come in two main types, known as muscle-type and neuronal-type.