Organophosphates Poisoning

ORGANOPHOSPHATES

• Highly popular insecticides because they are effective, disintegrate within days of application & do not persist in the environment
• Even minute quantities can penetrate the skin & be lethal, as evidenced by the use of organophosphate nerve gases sarin, soman, tabun, & VX in chemical weapons.

ORGANOPHOSPHORUS POISONS

•  Esters of phosphoric acid 2 series of compounds

1. ALKYL PHOSPHATES
2. ARYL PHOSPHATES

• HETP
• TEPP (Tetron)
• OMPA
• Dimefox
• Isopestox
• Malathion (Kill bug; Bugsolin)
• Sulfotepp
• Demeton
• Trichlorfon

• Parathion (nitrostigmine) (Follodol; Kill phos; Ekato)
• Paraoxon
• Methyl-parathion (Metacide)
• Chlorthion
• Diazinon (Diazion; Tik 20)

 Pathophysiology

• The organophosphates irreversibly inhibit acetylcholinesterase, resulting in an overabundance of acetylcholine at synapses & the myoneural junction.
• The acetylcholine initially excites & then paralyzes the CNS, the parasympathetic nerve endings & the sweat glands (muscarinic effects), somatic nerves & ganglionic synapses of autonomic ganglia (nicotinic effects).

 SIGNS AND SYMPTOMS

• Occur when Achestrase levels drop to 30% of its normal activity
• Ocular exposure — persistent miosis
• Onset of systemic symptoms varies with different routes of absorption
• Involuntary Ms + secretory glands are affected first followed by voluntary Ms then brain functions
• Symptoms may begin within 5 min to 2 hrs  And are max in 24 hrs
• Resp. and G.I.T symptoms are more marked depending on the route of entry

 MUSCARINIC MANIFESTATIONS

• Salivation
• Lacrimation
• Urination
• Defaecation
• Distress
• Emesis
• Diaphoresis, diarrhoea,
• Miosis
• Bronchorrhea, bronchospasm
• C.V.S: Bradycardia, hypotension
• Ciliary Body: Blurred vision
• Bladder : Urinary incontinence

NICOTINIC MANIFESTATIONS

• STRIATED MUSCLE: Initial stimulus results in contraction, later there is paralysis due to persistent depolarization
• Ms weakness is due to accumulation of Ach which causes fasciculation, cramps, weakness , areflexia

SYMPATHETIC GANGLIA

• HT, Tachycardia, pallor, mydriasis

 CNS MANIFESTATIONS

• Restlessness, emotional lability, headache, tremor, drowsiness, confusion, slurred speech, ataxia, generalised weakness, coma, convulsion,depression of respiration and CVS centres 

 Severe poisoning:

• SLUDGE and respiratory insufficiency, weakness, fasciculations, coma, paralysis, seizure, autonomic dysfunction.
• Porphyrinemia resulting in CHROMOLACHRYORRHOEA (shedding of red tears) due to accumulation of porphyrin in the lacrimal glands is seen very rarely

 DIAGNOSIS

• 5 ml of heparinised blood for cholinesterase determination
• The cholinesterase activity of blood and plasma fall by 22 to 88%.
• The avg normal values are 77 to 142 in the RBC’s and 41 to 142 in the plasma
• Diagnosis may be confirmed by giving 2 mg of atropine.
• A 25% reduction in red blood cell cholinesterase confirms organophosphate poisoning.

TREATMENT

• Establishing an airway & ensuring proper ventilatory support, cardiac monitoring;
• Gastric Lavage with 1:5000 KMnO4
• Activated Charcoal one gm/kg
• Atropine sulphate arrests the muscarinic and CNS symptoms. It has no effects on the nicotinic symptoms
• 2-4 mg of atropine is given i.v as a test dose
• If no effect this dose is doubled every 5-10 min until secretions are controlled, the skin is dr./ and there is sinus tachycardia.
• An avg patient requires 40 mg per day but upto 1000mg /day have been used’
• Atropine is the mainstay of treatment (antidote of choice).
• Cholinesterase regenerator compounds (oximes)
• Pralidoxime is most commonly used oxime.
• They antagonize only peripheral effects, but not central effects except for diacetylmonoxime (DAM) which crosses BBB and antagonizes central effects also.·