Question

Geoffrey is the proprietor of a restaurant in Victoria Square. In an attempt to eradicate a recent cockroach infestation he closes the restaurant for fumigation by an ‘unauthorised’ pest control agent. Geoffrey is advised not to enter the restaurant for 24 hours post fumigation. Geoffrey soon realises he has left the weeks takings in the restaurant safe and enters the restaurant 2 hours after the fumigation process. Ten minutes after entering the restaurant Geoffrey develops the following signs and symptoms: bradycardia, salivation, profuse sweating, watery eyes, blurred vision, wheezing and breathlessness, diarrhea, and skeletal muscle twitching and convulsions.

a). Identify the mechanism by which high-dose organophosphate’s cause toxicity in humans and briefly discuss how TWO of Geoffrey’s symptoms are linked to the pharmacological properties of organophosphates. (Maximum 250 words)

Answer 1

Organophosphate mechanism of toxicity:

Acetylcholinesterase inhibitors form a stable bond with the enzyme which occurs at cholinergic junctions of the nervous system where acetylcholine is the neurohumoral mediator. Acetylcholinesterase is the enzyme that degrades acetylcholine following stimulation of a nerve, by inhibiting acetylcholinesterase, organophosphates allow acetylcholine to accumulate and result in initial excessive stimulation followed by depression. Once AChE has been inactivated, ACh accumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic receptors

Geoffrey’s symptoms are linked to the pharmacological properties of organophosphate as Organophosphates (OPs) binds to AChE producing phosphorylation of the AChE active site resulting in irreversible inactivation of AChE.