The Toxic Analogy


'Blind as a bat, Hot as a hare, Red as a beet
Mad as a hatter, Dry as a bone' - 
So goes the saying that describes a person poisoned with Atropine.

Atropine is an anticholinergic drug which was first extracted from the plant Atropa belladona, hence the name.

The nervous system includes the central, peripheral and autonomic system of nerves.The autonomic nervous system is composed of sympathetic and parasympathetic nerves. The parasympathetic nervous system mainly relaxes the body and inhibits or slows certain functions whereas the sympathetic nervous system has opposite actions.

Acetylcholine, the chief neurotransmitter of the parasympathetic nervous system acts on Nicotinic and Muscarinic acetylcholine receptors. The actions of Acetylcholine varies depending on the receptor on which it acts, classified as its nicotinic and muscarinic actions. 

Atropine acts by blocking the muscarinic acetylcholine receptors, thereby preventing the muscarinic actions of acetylcholine. Therefore, it is classified as an anticholinergic (anti-acetylcholine) drug.

Atropine poisoning can occur by ingestion of plant products that contain hyoscyamine, a component of atropine (or) by drug overdosage. 

The effects of atropine poisoning can be elucidated by first understanding the muscarinic effects of acetylcholine. 

The muscarinic effects of acetylcholine further depends on its receptor subtypes and the location of action. Given below is a list of muscarinic receptors, their location and response to the parasympathetic neurotransmitter acetylcholine.

Target/
Location
Receptor
RESPONSE
Eyes

M3
M3

Contraction – Miosis
Contraction – Accommodation for near vision
Heart

M2
M2

↓Heart rate
↓Conduction velocity
No effects on ventricles, Purkinje system
Lungs

M3
M3

Contraction – Bronchospasm
Secretion
G.I.tract

M3
M1
M3

↑Motility-cramps
Secretion
Contraction-diarrhea, involuntary defecation
Bladder

M3
M3

Contraction of detrusor muscle
Relaxation of trigone/sphincter
Sphincters
M3
Relaxation,
except lower esophageal, which contracts
Glands
M3
Secretions including sweat(thermoregulatory), salivation,
and lacrimation.
Blood vessels (endothelium)
M3
Dilation (via NO/endothelium-derived relaxing factor) –
no parasympathetic innervations,
 no effects of indirect agonists
Central nervous system
M1 – M5
CNS excitation


After learning the muscarinic effects of acetylcholine, one can easily analyse the effects of atropine, the drug which blocks the muscarinic receptors.
When a person is intoxicated with atropine, the effects seen are quite opposite to the actions of acetylcholine.
The effects of atropine poisoning are described using certain analogies and classic descriptions as follows:
  • Blind as a bat ( Defective vision due to_Mydriasis<dilated pupils> & Absent accommodation reflex)
  • Red as a beet (Vasodilation with skin hyperemia_flushed skin)
  • Hot as a hare (Hyperthermia_febrile)
  • Mad as a hatter (CNSexcitation_delirium, hallucinations,restlessness, irritability,disorientation)
  • Dry as a bone (Absent secretions_dry skin & mucous membranes)

  • Full as a flask (Urinary retention_can't urinate)
  • Tacky (Tachycardic_increased heart rate)
  • Slurred and monotonous speech
  • Wool gathering (Phantom behaviors)
  • Automatic behaviors (Perseveration, disrobing, phantom behavior)
  • The hallucinations are described as Lilliputian hallucinations where people appear greatly reduced in size.

Atropine poisoning is treated using the drug Physostigmine
Physostigmine is a reversible cholinesterase inhibitor. Cholinesterase is an enzyme that breaks down acetylcholine. Due to inhibition of cholinesterase, there is an increase in the amount of acetylcholine acting on the muscarinic receptors. Thereby, the effects of atropine can be greatly reduced. 


Remember that, the drug atropine itself is an antidote for a certain other poisoning, which is organophosphate poisoning. In yet another post, we will learn about the organophosphates. 



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