Mechanism of Action of Atropine (Muscarinic Antagonist)

Introduction

Atropine is a classic anticholinergic drug that works by competitively inhibiting muscarinic acetylcholine receptors (mAChRs). It is derived from the plant Atropa belladonna and has wide clinical use in bradycardia, organophosphate poisoning, pre-anesthetic medication, and pupil dilation.

Its importance spans autonomic pharmacology, emergency medicine, and toxicology, making it a high-yield topic for USMLE, NCLEX, GPAT, NEET-PG, and NAPLEX aspirants.

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Mechanism of Action of Atropine: Step-by-Step

1. Competitive antagonist at muscarinic receptors (M1–M5)
   Atropine binds competitively and reversibly to all subtypes of muscarinic acetylcholine receptors (M1 to M5) without activating them.
2. Inhibits parasympathetic neurotransmission
   By blocking acetylcholine (ACh) at these receptors, atropine effectively inhibits parasympathetic effects across various organs.
3. Organ-specific effects:
   • Heart (M2): Inhibits vagal tone → increases heart rate
   • Eyes (M3): Causes mydriasis (pupil dilation) and cycloplegia (loss of accommodation)
   • GI tract & bladder (M3): Reduces motility and relieves spasms
   • Respiratory (M3): Bronchodilation and reduction in secretions
   • CNS (M1): Excitatory at high doses; can lead to delirium
4. No effect on nicotinic receptors
   It does not affect nicotinic receptors, so ganglionic and neuromuscular functions remain intact.

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Pharmacokinetic Parameters of Atropine

Parameter	Value
Bioavailability	High (oral/parenteral)
Onset of action	IV: 1–2 min, IM: 30 min
Duration of action	4–6 hrs (ocular effect: 7–14 days)
Half-life	~2–4 hours
Metabolism	Hepatic
Excretion	Renal
CNS penetration	Yes (lipophilic)

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Clinical Uses of Atropine

• Bradycardia (ACLS algorithm)
• Organophosphate or carbamate poisoning
• Pre-anesthetic to reduce secretions
• Ophthalmologic use (mydriasis and cycloplegia)
• Antispasmodic for GI and bladder disorders
• Antidote for muscarinic mushroom poisoning
• AV block and vagal overdrive conditions

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Adverse Effects of Atropine

• Dry mouth
• Blurred vision
• Photophobia
• Tachycardia
• Constipation and urinary retention
• CNS excitation (delirium, hallucination in overdose)
• Hyperthermia (due to decreased sweating)
• Atropine poisoning: “Dry as a bone, red as a beet, blind as a bat, hot as a hare, mad as a hatter”

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Comparative Analysis: Atropine vs Glycopyrrolate

Feature	Atropine	Glycopyrrolate
CNS penetration	Yes (crosses BBB)	No (does not cross BBB)
Duration of action	Shorter	Longer
Use in bradycardia	Yes	Less preferred
Antisecretory use	Yes	Yes (especially in anesthesia)
Use in children	Caution (can cause hyperthermia)	Safer

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Practice MCQs

Q1. Atropine is an antagonist of:
a. Nicotinic receptors
b. Muscarinic receptors ✅
c. Dopamine receptors
d. GABA receptors

Q2. Which organ system effect is due to M2 blockade?
a. Pupil dilation
b. Bradycardia
c. Tachycardia ✅
d. Bronchoconstriction

Q3. Which of the following is NOT a typical effect of atropine?
a. Dry mouth
b. Miosis ✅
c. Tachycardia
d. Urinary retention

Q4. In organophosphate poisoning, atropine is used to counteract:
a. Nicotinic toxicity
b. Muscarinic overstimulation ✅
c. CNS depression
d. Enzyme inhibition

Q5. Atropine causes which ocular change?
a. Miosis
b. Diplopia
c. Mydriasis ✅
d. Conjunctivitis

Q6. What is the antidote for atropine overdose?
a. Naloxone
b. Physostigmine ✅
c. Flumazenil
d. Ativan

Q7. Atropine’s GI effects include:
a. Increased motility
b. Constipation ✅
c. Diarrhea
d. Ulceration

Q8. The mnemonic “Dry as a bone…” refers to toxicity of:
a. Epinephrine
b. Diazepam
c. Atropine ✅
d. Morphine

Q9. Atropine is contraindicated in:
a. Glaucoma ✅
b. AV block
c. Bradycardia
d. Asthma

Q10. Atropine blocks which neurotransmitter?
a. Noradrenaline
b. Serotonin
c. Acetylcholine ✅
d. Dopamine

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FAQs

Q1: Does atropine affect sympathetic nervous system?
No. It blocks parasympathetic (muscarinic) activity only.

Q2: Can atropine be used in children?
Yes, but cautiously — especially due to risk of hyperthermia.

Q3: What’s the dose for bradycardia in ACLS?
0.5 mg IV every 3–5 minutes, max dose: 3 mg.

Q4: Does atropine increase or decrease secretions?
Decreases all secretions – saliva, bronchial, sweat.

Q5: Can atropine be used in asthma?
Rarely used, as better bronchodilators (like ipratropium) exist.

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References

• KD Tripathi – Essentials of Medical Pharmacology
• Goodman & Gilman – The Pharmacological Basis of Therapeutics
• Sparsh Gupta – Review of Pharmacology
• NCBI: https://www.ncbi.nlm.nih.gov/books/NBK537221/