Organophosphorus (OP) Compounds - Complete Clinical Overview

1. Definition and Chemistry

Organophosphorus compounds are esters of phosphoric acid forming two main series:

Alkyl Phosphates	Aryl Phosphates
HETP, TEPP (Tetron), OMPA, Dimefox	Parathion (Folidol/Nitrostigmine)
Malathion (Kill Bug), Sulfotepp	Paraoxon, Methyl-parathion (Metacide)
Demeton, Trichlorfon	Diazinon (Tik-20), Chlorthion

Available as dusts, granules, and liquids. Used as pesticides, insecticides, vermicides, and rodenticides. Nerve agents (sarin, VX) are also OP compounds.

2. Absorption, Distribution, Metabolism

Absorption: Inhalation, ingestion, and through unbroken skin and mucous membranes. Effects can be cumulative.
Distribution: Widely distributed; readily crosses the placenta. Excretion prolonged over a week.
Metabolism: In the liver via cytochrome P450 monooxygenase. Aryl organophosphates (e.g., parathion) require liver activation to become toxic. Metabolites excreted in urine.
Solvent: Compounds are mixed with aromatic solvents (usually "aromax"), producing the characteristic kerosene-like smell in stomach contents, vomit, and body cavities.

3. Mechanism of Action

OP compounds are powerful inhibitors of cholinesterase enzymes:

They phosphorylate acetylcholinesterase (AChE) - the true cholinesterase found in RBCs, nervous tissue, and skeletal muscle.
They also inhibit pseudocholinesterase (BuChE) found in plasma, liver, heart, and pancreas.
With phosphorylation, AChE loses an alkyl group - it cannot spontaneously hydrolyze and becomes permanently inactivated ("aging").
This leads to accumulation of acetylcholine at muscarinic and nicotinic receptors throughout the body.
Toxic symptoms appear when cholinesterase activity drops to ≤30% of normal; severe poisoning when <10% of normal.

4. Clinical Features

Features are divided into three types based on receptor site:

(I) Muscarinic Effects - Remember SLUDGE

Salivation, Lacrimation, Urination, Defecation, Gastrointestinal distress, Emesis

Also called SLUD (Salivation, Lacrimation, Urination, Defecation):

System	Features
Bronchial	Bronchoconstriction, increased secretions, wheezing, dyspnea, pulmonary edema, froth at mouth/nose
GIT	Anorexia, nausea, vomiting, cramps, diarrhea, fecal incontinence, tenesmus; pancreatitis may develop
Glands	Profuse sweating, salivation, lacrimation
CVS	Bradycardia (hallmark), arrhythmias, conduction blocks, hypotension
Eyes	Miosis (pin-point pupils), blurred vision; occasionally unequal or even dilated
Bladder	Urinary incontinence, frequency
Special	Chromogenic (red) tears due to porphyrin accumulation in lacrimal glands

(II) Nicotinic Effects

System	Features
Striated muscle	Fasciculations, cramps, weakness, paralysis (from persistent depolarization), areflexia
Sympathetic ganglia	Pallor, hypertension, tachycardia, mydriasis

(Nicotinic effects seen in only 10-20% of cases)

(III) CNS Effects

Restlessness → irritability → anxiety → headache → tremors (fine fibrillary - hands, eyelids, face, tongue) → confusion → stupor → coma with absent reflexes → convulsions → depression of respiratory and cardiovascular centers.

Order of System Involvement:

Involuntary muscles & secretory glands → Voluntary muscles → Vital brain centers

Onset:

Inhalation: fastest (within 5 minutes)
Skin absorption: slowest
Symptoms maximal at 2 to 8 hours

5. Special Syndromes

Intermediate Syndrome

Occurs 1-4 days after acute poisoning (between acute cholinergic crisis and delayed neuropathy)
Features: cranial nerve palsies, weakness of neck flexors and proximal limb muscles, acute respiratory paresis
Due to prolonged AChE inhibition and muscle necrosis
Does NOT respond to oximes or atropine

Organophosphate-Induced Delayed Polyneuropathy (OPIDP)

Occurs 1-5 weeks after exposure (especially parathion, malathion, trichlorfon)
Begins with paresthesia and pain/cramps in calves
Progresses to ataxia, weakness, toe drop (foot drop)
Due to demyelination of ascending and descending spinal tracts + degeneration of motor horn cells
Damage in delayed paralysis is permanent

6. Treatment

Step 1 - General Measures

Remove patient from exposure; remove contaminated clothing
Wash skin and eyes with copious water (use gloves to avoid self-contamination)
Gastric lavage (if ingested, within 4-6 hours)
Maintain airway; suction secretions; oxygen

Step 2 - Specific Antidotes

A. Atropine (Muscarinic antagonist)

Drug of choice for muscarinic symptoms
Dose: 2 mg IV/IM every 15-30 minutes until signs of atropinization appear
Signs of atropinization: flushed dry skin, dry mouth, dilated pupils, tachycardia, warm skin
Up to 12 mg safely given in the first 2 hours in severe cases
Does NOT reverse nicotinic (muscle) effects

B. Pralidoxime (PAM, P-2-AM) - Cholinesterase Reactivator (Oxime)

Acts by dephosphorylating (reactivating) the inactivated cholinesterase
Must be given early, before "aging" occurs (enzyme becomes irreversibly inactivated)
Dose: 1-2 g IV for adults; 25-50 mg/kg for children as 5% solution in isotonic saline; repeat every 12 hours if symptoms persist
Other oximes: pralidoxime iodide (P-2-I), obidoxime, diacetylmonoxime (DAM)
Supplement to atropine, not a replacement
Does NOT work in intermediate syndrome

Step 3 - Supportive

Diazepam for convulsions/restlessness (avoid morphine, succinylcholine, phenothiazines)
Diuretics and saline purgatives
Exchange transfusion in serious cases

Note: The first 4-6 hours are most critical in acute poisoning.

7. Post-Mortem Findings

Finding	Description
External	Cyanosed face; blood-stained froth at nose and mouth; kerosene-like smell
Stomach	Greenish oily substances (diluents); kerosene/garlic smell; blood-stained contents; congested mucosa
Mucosa	Submucous petechial hemorrhages in gastric mucosa
Systemic	Pulmonary edema; capillary dilatation; petechial hemorrhages; hyperemia of lungs, brain, other organs
Delayed paralysis	Demyelination of ascending/descending spinal tracts + degeneration of motor horn cells

Forensic point: OP compounds resist putrefaction - poisoning can be detected in exhumed bodies. Viscera (stomach, liver, blood, urine) are sent for chemical analysis.

8. Diagnosis

Serum and RBC cholinesterase levels - most specific test
Normal RBC AChE activity ~10 units; toxic when <3 units
Urinary metabolites (alkyl phosphates)
Atropine test: 2 mg atropine IV - if no atropinization (no tachycardia, no dry mouth), OP poisoning is confirmed
Gastric content analysis; gas chromatography

9. Medicolegal Aspects

Mode: Suicidal (most common), accidental (agricultural workers), rarely homicidal
Circumstantial evidence: Empty bottles of pesticide found near body
Parathion is the most commonly implicated agent in suicidal poisoning in India
Resistance to putrefaction makes delayed forensic detection possible

Sources: The Essentials of Forensic Medicine and Toxicology (36th ed.) | Parikh's Textbook of Medical Jurisprudence, Forensic Medicine and Toxicology | Goodman & Gilman's Pharmacological Basis of Therapeutics

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