Organophosphate Intoxication and Detoxification

Organophosphate Intoxication and Detoxification

• Organophosphates induce intoxication by inhibiting acetylcholinesterase (AChE)
• AChE breaks down acetylcholine (ACh)
• Inhibition of AChE leads to accumulation of ACh
• Accumulation of ACh overstimulates muscarinic and nicotinic receptors
• This results in a range of symptoms

Experimental Purposes

• Observe symptoms of organophosphate intoxication
• Observe the efficacy of atropine and pralidoxime methiodide (PAM) in detoxification
• Compare the effectiveness of atropine and PAM as treatments

Experimental Principle

• Investigate the mechanism and symptoms of organophosphate poisoning
• Determine the mechanisms of action of antidotes

Mechanism of Organophosphate Intoxication

• AChE hydrolyses acetylcholine into choline and acetic acid
• Organophosphates bind irreversibly to the active site of AChE
• This prevents the break down of ACh
• The buildup of ACh overstimulates muscarinic and nicotinic receptors
• This results in symptoms

Muscarinic Symptoms

• Blurred vision, miosis resulting from the affect pupil
• Increased lacrimation (tearing) from the effect on glands
• Bradycardia (slow heart rate), hypotension (low blood pressure) from the effect on the cardiovascular system
• Severe respiratory distress resulting from the effect on the respiratory system
• Nausea and vomiting, abdominal pain, diarrhea, fecal incontinence from the effect on the gastrointestinal system
• Urine incontinence from the effect on the genitourinary system

Nicotinic Symptoms

• Hypertension (high blood pressure)
• Decreased muscular tension, muscular twitching

CNS Effects

• Anxiety
• Seizures
• Coma

Antidotes and Their Mechanisms

• Atropine
  • Muscarinic antagonist
  • Relieves muscarinic symptoms like miosis, hypersalivation, fecal and urinary incontinence
  • Inhibits the cardiovascular system
• PAM (pralidoxime methiodide)
  • Cholinesterase reactivator
  • Reactivates inhibited AChE enzyme by breaking down the organophosphate bond
  • Reverses the effects of organophosphate intoxication

Experimental Material

• Animal: Rabbits (2-3 kg)
• Instruments: Rabbit cages, syringes
• Drugs:
  • 0.08% dichlorovinyl dimethyl phosphate (DDV)
  • 0.1% atropine
  • 2.5% PAM

Experimental Procedure

• Weigh the rabbit and record normal readings (respiration, pupils, salivation, feces, urine, muscle tension, muscle twitching)
• Administer 0.08% DDV (1 ml/kg, intramuscular injection) and observe reactions to the drug
• When obvious symptoms (e.g., seizures) appear, inject atropine (1 mL/kg, intravenous injection) and observe further reactions
• After muscarinic symptoms subside, inject PAM (2 mL/kg, intravenous injection) and monitor changes

Results and Analysis

• Data table to record normal readings, readings after DDV, readings after atropine, and readings after PAM.

Questions

• Analyze the mechanism of organophosphate intoxication.
• Analyze the detoxification mechanisms of atropine and PAM.