Initial Bradycardia with Atropine

 

MECHANISM OF INITIAL BRADYCARDIA WITH ATROPINE

Normal cholinergic transmission

Acetylcholine is stored in vesicles in the presynaptic neuron

When impulse reaches the pre-synaptic neuron, acetylcholine is released in the synaptic cleft.

Cholinergic receptors are present both on the presynaptic (auto-receptors)  and post-synaptic neuron.

Cholinergic action occurs when acetylcholine binds with the post-synaptic neuron.

Acetylcholine also binds with the auto-receptors causing “feedback” inhibition of the release of acetylcholine from the pre-synaptic neuron.

Atropine blockade

Atropine is a non-selective competitive muscarinic antagonist

Auto-receptors are more sensitive to atropine than the post-synaptic receptors

At low dose of atropine (or initial dose), the auto-receptors are more actively blocked than the post-synaptic receptors.

Inhibition of the “feedback” inhibition at the auto-receptors, results in increase in release of acetylcholine from the pre-synaptic neuron. This increases cholinergic effect and is the cause of initial bradycardia.

At higher dose of atropine, the post-synaptic receptors are completely blocked and are unsurmountable with the physiological amount of acetylcholine in the synaptic cleft. Thereafter, tachycardia prevails.