Op poisoning moa easy way to score more
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Here's a clean, exam-focused breakdown of Organophosphate (OP) Poisoning MOA - easy to score on:
Organophosphate Poisoning - Mechanism of Action
Core MOA (1 line answer)
OPs irreversibly inhibit acetylcholinesterase (AChE) → ACh accumulates → cholinergic crisis.
Step-by-Step Mechanism
| Step | What happens |
|---|---|
| 1 | OP compound (pesticide/nerve agent) binds to the serine residue of AChE at the esteratic site |
| 2 | Phosphorylates the enzyme → AChE is inactivated (irreversibly) |
| 3 | ACh cannot be broken down → accumulates at synapses |
| 4 | Overstimulation of muscarinic + nicotinic + CNS receptors |
- "Aging" = over time the phosphorylated enzyme becomes resistant to reactivation (harder to reverse)
Clinical Effects - Score Points with DUMBELS
Muscarinic (parasympathetic overflow) - use mnemonic DUMBELS:
| Letter | Effect |
|---|---|
| D | Diarrhea / Defecation |
| U | Urination |
| M | Miosis |
| B | Bradycardia, Bronchospasm, Bronchorrhea |
| E | Emesis |
| L | Lacrimation |
| S | Salivation / Sweating |
Nicotinic effects (NMJ + autonomic ganglia):
- Muscle fasciculations → weakness → paralysis
- Tachycardia (early, ganglionic stimulation)
- Hypertension
CNS effects:
- Anxiety, seizures, convulsions, coma
Three Phases of Toxicity (exam favorite!)
| Phase | Timing | Features |
|---|---|---|
| Acute cholinergic | Immediately | DUMBELS + fasciculations + seizures |
| Intermediate syndrome | 24-96 h later | Proximal limb weakness, neck flexor weakness, respiratory muscle paralysis |
| Delayed neuropathy (OPIDP) | 2-5 weeks later | Distal symmetrical sensorimotor polyneuropathy |
Antidotes - Must Know
| Drug | Mechanism | Treats |
|---|---|---|
| Atropine | Muscarinic antagonist | Muscarinic symptoms (DUMBELS) - does NOT treat nicotinic effects |
| Pralidoxime (2-PAM) | Reactivates AChE by displacing the phosphate group (if given BEFORE aging) | Both muscarinic + nicotinic peripheral effects - does NOT penetrate CNS |
| Diazepam | Benzodiazepine | Seizures/convulsions |
Key point: Pralidoxime must be given EARLY before "aging" of the enzyme occurs. With newer nerve agents (e.g. sarin), aging happens within seconds, making 2-PAM less effective.
One-Line Summary for MCQs
OP poisoning = irreversible AChE inhibition → ACh excess → cholinergic crisis → treat with atropine (muscarinic) + pralidoxime (AChE reactivation) + diazepam (seizures).
Sources: Lippincott Illustrated Reviews Pharmacology; Ganong's Review of Medical Physiology; Adams and Victor's Principles of Neurology, 12th Ed.
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