Why this drug is interesting

Atropine has an unusually clear mechanism and an unusually common pattern of misuse. It blocks vagal input to the sino-atrial and atrioventricular nodes, so it works where excessive vagal tone is the cause of the bradycardia — and predictably fails where the problem lies below the AV node, in tissue the vagus does not innervate.

Two things follow, and both are frequently got wrong. First, doses below 500 micrograms can slow the heart further, through a central and presynaptic effect. Second, in Mobitz II or complete heart block with broad complexes, atropine is unlikely to work — and giving it repeatedly while the patient deteriorates delays the pacing that will.

Pharmacology

Mechanism

Atropine is a tertiary amine belladonna alkaloid and a competitive antagonist at muscarinic acetylcholine receptors. It has no effect on nicotinic receptors — a distinction that matters greatly in organophosphate poisoning, where the nicotinic features are untouched by atropine.

In the heart, blocking M2 receptors removes parasympathetic restraint on the sinus node and on AV nodal conduction, increasing rate and improving conduction. Elsewhere, antagonism produces the familiar antimuscarinic picture: reduced secretions, bronchodilatation, pupillary dilatation, reduced gut motility, urinary retention and, because atropine crosses the blood–brain barrier, central effects.

Why small doses may do the opposite — classical teaching

Doses below about 500 micrograms are long taught to produce paradoxical bradycardia, through a central vagal effect and blockade of presynaptic inhibitory M1 autoreceptors that increases acetylcholine release before postsynaptic blockade dominates. The practical corollary is that there is no such thing as a cautious small test dose of atropine — a hesitant 200 micrograms in an unwell bradycardic patient may make things worse.

Attribution matters here. This is long-standing teaching that appeared in older resuscitation material. It is not stated in the current UK atropine SmPCs, nor in the RCUK 2025 bradyarrhythmia algorithm. The 500 microgram dose is what the guideline specifies regardless, so nothing changes at the bedside — but present it as convention rather than as current guidance.

Kinetics

Onset, IV: Within 1 minute; peak effect 2–4 minutes
Half-life: 2–5 hours
Metabolism: Hepatic hydrolysis, with renal excretion of drug and metabolites
CNS penetration: Yes — hence confusion and delirium, particularly in the elderly

Bradycardia — the RCUK algorithm

The RCUK 2025 adult bradyarrhythmia algorithm gives a single first step and then a set of interim measures.³

First

Atropine 500 micrograms IV. Reassess the response.

If the response is unsatisfactory — interim measures

Atropine 500 micrograms IV, repeated to a maximum of 3 mg
Isoprenaline 5 micrograms/minute IV
Adrenaline 2–10 micrograms/minute IV — see Adrenaline
Alternative drugs — for example in beta-blocker or calcium channel blocker overdose
and/or transcutaneous pacing

Then: monitor, treat the underlying cause, consider transvenous pacing, and seek expert help.

Risk of asystole

The algorithm identifies features that mark a high risk of asystole and should prompt urgent escalation rather than repeated drug dosing:

Recent asystole
Mobitz II AV block
Complete heart block with broad QRS
Ventricular pause greater than 3 seconds

Other uses

Organophosphate and nerve agent poisoning

Here atropine is used at doses that bear no relation to the cardiac ones. Cholinesterase inhibition produces an overwhelming cholinergic crisis, and atropine is titrated in large, repeated and rapidly escalating doses — often doubling — against a physiological endpoint.

Beta-blocker and calcium channel blocker overdose

Atropine is a reasonable first step for the associated bradycardia but is frequently ineffective, since the mechanism is not vagal. It should not delay the specific measures — glucagon, high-dose insulin, calcium salts and vasopressors. See Bisoprolol and Verapamil.

As an antisialagogue

Historically co-administered with ketamine to reduce hypersalivation. Routine use has largely been abandoned, since the evidence does not show a reduction in airway adverse events and it adds antimuscarinic burden.

Why it left the cardiac arrest algorithm

Atropine was removed from the adult cardiac arrest algorithm in the 2010 guidelines. In asystole and PEA, excessive vagal tone is not the operative problem, and no benefit was demonstrated. Its absence is deliberate, and it does not appear in the current ALS algorithm.

Adverse effects and cautions

Antimuscarinic effects

Predictable from the mechanism, and summarised by the traditional aphorism — dry as a bone, blind as a bat, red as a beet, mad as a hatter, hot as a hare:

Dry mouth and reduced secretions
Blurred vision and photophobia from pupillary dilatation and loss of accommodation
Urinary retention — particularly in men with prostatic enlargement
Confusion, agitation and delirium — especially in the elderly; often missed as a drug effect
Tachycardia
Flushing, reduced sweating and hyperthermia
Constipation and ileus

Cautions

Angle-closure glaucoma — pupillary dilatation may precipitate an attack
Prostatic enlargement — urinary retention
Myasthenia gravis
Elderly patients — cumulative anticholinergic burden and delirium risk; glycopyrrolate is often preferable
Cardiac ischaemia — the induced tachycardia raises myocardial oxygen demand
Pyrexia and hot environments — impaired sweating

Critical appraisal

The evidence base is old and thin, and largely physiological. Atropine's place in the bradycardia algorithm rests on a well-understood mechanism and long clinical experience rather than randomised trials against pacing or chronotropic infusions. That is defensible for a drug this well characterised, but it should not be mistaken for trial evidence.
The 3 mg maximum is a pharmacological ceiling, not a therapeutic target. It marks the point of full vagal blockade beyond which more drug adds only toxicity. Reaching it is a signal to escalate, not an achievement.
Its removal from the arrest algorithm was well justified and is a good example of guidelines subtracting an ineffective intervention — something they do less often than adding one.
The paradoxical bradycardia effect is under-taught relative to how easily it is triggered, particularly by clinicians drawing up a cautious partial dose in an unwell patient.
Glycopyrrolate is probably under-used in the elderly. Where the algorithm explicitly permits it and the patient is at high risk of delirium, the case for choosing it is stronger than practice reflects.

References

1
Atropine sulfate injection — Summary of Product Characteristics. Consult the preparation stocked locally via the electronic Medicines Compendium.
2
Atropine sulfate — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk
3
Resuscitation Council UK. Adult bradyarrhythmia algorithm, 2025. resus.org.uk — mirrored at lifesupport.resusdoc.uk. Atropine 500 micrograms IV, repeated to a maximum of 3 mg; isoprenaline 5 micrograms/min; adrenaline 2–10 micrograms/min; transcutaneous pacing; glycopyrrolate may be used instead of atropine. Verified 20 Aug 2026.
4
Resuscitation Council UK. Adult advanced life support guidelines, 2025. resus.org.uk. Source of the instructions not to give atropine in high-degree AV block with wide QRS, and not to give it after cardiac transplant (use aminophylline). Atropine does not appear in the cardiac arrest algorithm; it was removed in the 2010 guidelines. Verified 21 Aug 2026.
5
Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet 2008;371(9612):597–607.
6
TOXBASE — organophosphate and carbamate poisoning. National Poisons Information Service. toxbase.org (NHS login required.)

Atropine

At a glance