Atropine

Emma Farrell

Mechanism of Action:
Muscarinic acetylcholine receptor (mAChR) antagonist [anti-muscarinic, anti-cholinergic]. mAChRs are 7TM GPCRs (7 transmembrane G-protein coupled receptors) which are activated by the endogenous neurotransmitter, acetylcholine (cholinergic receptor). Atropine is relatively selective for mAChRs, which are generally associated with the parasympathetic nervous system, and also cholinergic transmission in the CNS for atropine crosses the blood brain barrier. There are 5 subtypes of receptors, of which the function of 3 are well-established. Their excitatory functions (M1, 3) include CNS excitation (e.g. tremor, hypothermia), gastric acid secretion, glandular secretions (e.g. salivary, bronchial, sweat) and contraction of visceral smooth muscle (e.g. GI tract, eye-constrictor pupillae and ciliary muscle, bronchial). Examples of inhibitory functions (M2, 3) are cardiac inhibition (slow heartbeat) and the relaxation of smooth muscle (mainly vascular). Note that the other major class of cholinergic receptor (nicotinic) – at which atropine has little effect – is responsible for neurotransmission in autonomic ganglia and at the neuromuscular junction.

Lecture and CAL materials:

Drug specifics

Alternative drug name atropine sulphate
Effects Atropine decreases intestinal motility and has been used for the treatment of diarrhoea, colic, irritable bowel syndrome, and diverticulosis. It is now obsolete for these indications and has been replaced by other anticholinergic drugs. The antimuscarinic action has also been used to reduce acid secretion in peptic ulcer disease, to reduce bronchial secretions in terminal care and to prevent motion sickness. Atropine-like drugs are also used to control bed-wetting and frequent urination. The only common clinical use of atropine itself is the emergency treatment of cardiac bradyarrhythmias.
Adverse actions Atropine is associated with a classic group of antimuscarinic side-effects: dry mouth, blurred vision, tachycardia, confusion, constipation, urine retention (especially in elderly men with prostatic enlargement). Similar adverse effects are seen with other anti-muscarinic drugs such as anti-Parkinsonian drugs and some anti-psychotics.
Dose Well absorbed orally. It should be taken 30 minutes before meals. Used IV in cardiovascular emergencies.
Interactions The most obvious interactions are with those drugs that also have an antimuscarinic action such as anti-Parkinsonian drugs, drugs for bladder instability (e.g. tolterodine), some anti-psychotics (e.g. chlorpromazine) and some antidepressants (e.g. amitriptyline).
Contraindications not specified
Comments Atropine is a naturally occurring compound in the deadly nightshade Atropa belladonna. Its antidote is anti-cholinesterase drugs such as physostigmine which prevent ACh breakdown. Some poisons such as organophosphates (pesticides, ‘nerve’ gas) are anti-cholinesterases that stimulate cholinergic transmission leading to vomiting, diarrhoea, hypersecretion, and in these circumstances atropine is the antidote. Also used to treat bradycardia after myocardial infarction (excessive vagal tone), for cardiopulmonary resuscitation (blocks vagal activity), mydriasis (pupil dilation for ophthalmologic examination) and in surgery to reduce salivation and mucous secretion as well as to prevent vagal reflexes triggered by surgical trauma to visceral organs. It is also used as an antidote to muscarine poisoning from certain species of mushrooms. The drug is contraindicated for ophthalmic use in patients with glaucoma as the relaxation of the constrictor pupillae of the iris impairs the drainage of aqueous humour leading to further increases in intra-ocular pressure. Hyoscine is a very similar antimuscarinic drug to atropine often used to control secretions. Pirenzipine is another muscarinic receptor antagonist (selective for M1 subtype) which inhibits gastric acid stimulation produced by parasympathetic nervous activity. It was formerly used as an anti-ulcer drug but has been superseded by other more effective drugs.
Contributors