Mechanism of action: inhibition of acetylcholinesterase (AChE is an enzyme that
degrades the neurotransmitter acetylcholine (ACh)). Once AChE has been inactivated, ACh accumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic receptors: ENDOGENOUS INTOXICATION WITH ACh Clinics: Muscarinic effects Cardiovascular - Bradycardia, hypotension Respiratory - Rhinorrhea, bronchorrhea, bronchospasm, cough, severe respiratory distress Gastrointestinal - Hypersalivation, nausea and vomiting, abdominal pain, diarrhea, fecal incontinence Genitourinary - Incontinence Ocular - Blurred vision, miosis Glands - Increased lacrimation, diaphoresis Nicotinic signs muscle fasciculations cramping weakness diaphragmatic failure. CNS effects headaches, dizziness, paralysis, tremor, anxiety, seizures, coma 1
Organophosphate (OP) toxicity is a anamnestic and clinical diagnosis.
Confirmation of organophosphate poisoning is based on the measurement of cholinesterase activity in red blood cells. NON SPECIFIC TREATMENT Adequate oxygenation Intubation may be necessary in cases of respiratory distress due to laryngospasm, bronchospasm, bronchorrhea Continuous cardiac monitoring and pulse oximetry should be established Remove all clothing and gently cleanse patients suspected of organophosphate exposure with soap and water because organophosphates are hydrolyzed readily in aqueous solutions with a high pH. Consider clothing as hazardous waste and discard accordingly!!!! SPECIFIC TREATMENT 1) Competitive antagonists at the muscarinic cholinergic receptors in both the central and the peripheral nervous system. i. Atropine IV/IM, 1 ampoule=1mg, 1-2 mg in mild intoxication till 100mg in very severe intoxications ii. The endpoint for atropinization is dried pulmonary secretions, tachycardia and mydriasis. The main concern with OP toxicity is respiratory failure from excessive airway secretions. 2) Reactivators of Ach esterase activity i. Pralidoxime (Contration): 25-50mg/Kg in 30 minutes, iv ii. Obidoxin (Toxogonin): 1 ampoule =250 mg, 1 -2 ampoules i.v. or i.m., can be repeated after 6 hours iii. Nucleophilic agent that reactivates the phosphorylated AChE by binding to the OP molecule. iv. Used as an antidote to reverse muscle paralysis resulting from OP AChE pesticide poisoning v. Current recommendation is administration within 48 h of OP poisoning vi. Because of risks of respiratory compromise or recurrent symptoms, hospitalizing all symptomatic patients for at least 24 hours in a high acuity setting is recommended. 3) AchE lyophilised enzyme 4) Fresh plasma that contains the enzyme 2