Molecular basis of the mechanism of action
At the biochemical level, Atropinum acts as a typical competitive inhibitor. This means the drug molecule has structural similarity to the endogenous ligand and competes with it for the binding site.
The sequence of events in the synapse is as follows:
- The atropine molecule recognizes the active site of the M-cholinergic receptor and reversibly binds to it.
- The natural neurotransmitter of the parasympathetic nervous system (acetylcholine) loses its ability to bind to the occupied receptor.
- As a result, nerve impulse transmission in parasympathetic synapses is completely blocked, leading to systemic changes in internal organ function.
Clinical application of the drug
Understanding the mechanism of competitive blockade of M-cholinergic receptors allows this belladonna alkaloid to be used in various medical fields:
- Ophthalmology: receptor blockade in the eye causes relaxation of the circular iris muscle (pupillary sphincter). This leads to persistent pupil dilation (mydriasis), which is necessary for a thorough fundus examination.
- Anesthesiology: the drug is administered during premedication. It reliably reduces bronchial and salivary gland secretion and prevents dangerous reflexive cardiac arrest during anesthesia.
- Cardiology: the drug's ability to block parasympathetic influences on the myocardium is used to treat bradycardia and atrioventricular (AV) blocks.
- Gastroenterology: atropine acts as a powerful antispasmodic, relieving painful spasms of the gastrointestinal smooth muscle.
- Toxicology: it serves as a vital antidote for muscarine and organophosphate (OP) poisoning.
Principles of overdose management
Since atropine is a competitive antagonist, its effects can be overcome. The main biochemical goal in an overdose is to maximize the concentration of acetylcholine in the synaptic cleft.
According to the law of mass action, an excess of substrate (acetylcholine) will simply displace the inhibitor (atropine) from its receptor binding.
To achieve this goal, specific antidote drugs are used — acetylcholinesterase inhibitors (e.g., physostigmine or neostigmine). These substances temporarily block the enzyme that normally degrades acetylcholine. As a result, the endogenous neurotransmitter rapidly accumulates in huge amounts within the synapse and restores nerve impulse transmission by displacing the toxin molecules.
Briefly: answers to topical questions
What clinical symptoms occur in atropine overdose?
The clinical presentation of atropine overdose develops due to M-cholinergic receptor blockade and includes peripheral and central manifestations.
- Secretory and thermoregulatory disorders — severe thirst, dry mucous membranes and skin, flushing of the face and trunk, pronounced hyperthermia.
- Cardiovascular disorders — tachycardia up to 160–190 bpm, extrasystoles, decreased blood pressure, risk of myocardial ischemia.
- Ocular symptoms — pupil dilation (mydriasis) and absence of light reaction.
- Neurological and somatic disorders — headache, dizziness, acute urinary retention.
- Psychoneurological status — "atropine psychosis" with visual and auditory hallucinations, delirium and agitation, as well as clonic-tonic seizures.
In the terminal stage, coma ensues, and death occurs due to paralysis of the respiratory center.
What are the pathways of biotransformation and elimination of atropine from the body?
Biotransformation of atropine occurs in the liver, and elimination is carried out by the kidneys.
- Metabolism — the substance undergoes hydrolysis, breaking down into tropine and tropic acid.
- Elimination — via the kidneys; 30–50% of the substance is excreted unchanged.
The half-life is approximately 2 hours.
Remembering the essence of competitive inhibition in overdose is simple: "Whoever has the majority occupies the receptor." To drive out atropine (the inhibitor), you need to accumulate acetylcholine (the substrate) by blocking the enzyme that "consumes" it (acetylcholinesterase).
Class and exam questions
Why does atropine cause pupil dilation?
It blocks M-cholinergic receptors in the circular iris muscle. As a result, the sphincter muscle relaxes, and the pupil dilates (mydriasis occurs).
Can the effect of atropine be reversed, and how does it work?
Yes, it is possible. Since the inhibition is competitive, the level of the natural neurotransmitter must be increased. For this purpose, neostigmine or physostigmine is administered — they prevent acetylcholine breakdown, allowing it to displace atropine.
Why is atropine included in premedication before surgery?
It "dries out" the respiratory tract by suppressing salivary and bronchial gland secretion, and also protects the heart from reflexive arrest during surgical manipulations.
What else to study on this topic
- Biochemical structure of muscarinic receptors and their subtypes (M1-M5)
- Mechanism of toxic action of organophosphates (OPs)
- Synthesis, release, and enzymatic degradation of acetylcholine
- Differences between M-cholinergic and N-cholinergic receptors
- Pharmacokinetics of belladonna alkaloids in the human body
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