Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given intravenously or by injection into a muscle. Eye drops are also available which are used to treat uveitis and early amblyopia. The intravenous solution usually begins working within a minute and lasts half an hour to an hour. Large doses may be required to treat some poisonings.
Common side effects include dry mouth, abnormally large pupils, urinary retention, constipation, and a fast heart rate. It should generally not be used in people with closed-angle glaucoma. While there is no evidence that its use during pregnancy causes birth defects, this has not been well studied so sound clinical judgment should be used. It is likely safe during breastfeeding. It is an antimuscarinic (a type of anticholinergic) that works by inhibiting the parasympathetic nervous system.
Atropine occurs naturally in a number of plants of the nightshade family, including deadly nightshade (Atropa belladonna), jimsonweed (Datura stramonium), mandrake (Mandragora officinarum) and angel's trumpet (Brugmansia). Atropine was first isolated in 1833. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.
Medical uses
Eyes Topical atropine is used as a cycloplegic, to temporarily paralyze the accommodation reflex, and as a mydriatic, to dilate the pupils. Atropine degrades slowly, typically wearing off in 7 to 14 days, so it is generally used as a therapeutic mydriatic, whereas tropicamide (a shorter-acting anticholinergic) or phenylephrine (an α-adrenergic agonist) is preferred as an aid to ophthalmic examination.
In refractive and accommodative amblyopia, when occlusion is not appropriate sometimes atropine is given to induce blur in the good eye. Evidence suggests that atropine penalization is just as effective as occlusion in improving visual acuity.
Antimuscarinic topical medication is effective in slowing myopia progression in children; accommodation difficulties and papillae and follicles are possible side effects. All doses of atropine appear similarly effective, while higher doses have greater side effects. The lower dose of 0.01% is thus generally recommended due to fewer side effects and potential less rebound worsening when the atropine is stopped.
Heart Injections of atropine are used in the treatment of symptomatic or unstable bradycardia.
Atropine was previously included in international resuscitation guidelines for use in cardiac arrest associated with asystole and PEA but was removed from these guidelines in 2010 due to a lack of evidence for its effectiveness. For symptomatic bradycardia, the usual dosage is 0.5 to 1 mg IV push; this may be repeated every 3 to 5 minutes, up to a total dose of 3 mg (maximum 0.04 mg/kg).*
Atropine is also useful in treating second-degree heart block Mobitz type 1 (Wenckebach block), and also third-degree heart block with a high Purkinje or AV-nodal escape rhythm. It is usually not effective in second-degree heart block Mobitz type 2, and in third-degree heart block with a low Purkinje or ventricular escape rhythm.
Atropine has also been used to prevent a low heart rate during intubation of children; however, the evidence does not support this use.
Secretions Atropine's actions on the parasympathetic nervous system inhibit salivary and mucous glands. The drug may also inhibit sweating via the sympathetic nervous system. This can be useful in treating hyperhidrosis, and can prevent the death rattle of dying patients. Even though atropine has not been officially indicated for either of these purposes by the FDA, it has been used by physicians for these purposes.
Poisonings Atropine acts as an antagonist for organophosphate poisoning by blocking the action of acetylcholine at muscarinic receptors caused by organophosphate insecticides and nerve agents, such as tabun (GA), sarin (GB), soman (GD), and VX. Troops who are likely to be attacked with chemical weapons often carry autoinjectors with atropine and oxime, for rapid injection into the muscles of the thigh. In a developed case of nerve gas poisoning, maximum atropinization is desirable. Atropine is often used in conjunction with the oxime pralidoxime chloride.
Some of the nerve agents attack and destroy acetylcholinesterase by phosphorylation, so the action of acetylcholine becomes excessive and prolonged. Pralidoxime (2-PAM) can be effective against organophosphate poisoning because it can re-cleave this phosphorylation. Atropine can be used to reduce the effect of the poisoning by blocking muscarinic acetylcholine receptors, which would otherwise be overstimulated, by excessive acetylcholine accumulation.
Atropine or diphenhydramine can be used to treat muscarine intoxication.
Atropine was added to cafeteria salt shakers in an attempt to poison the staff of Radio Free Europe during the Cold War.The Battle Over Hearts and Minds A Cold War of Spies: Episode 4 |https://www.imdb.com/title/tt27484449/?ref_=ttep_ep4
Irinotecan-induced diarrhea Atropine has been observed to prevent or treat irinotecan induced acute diarrhea.
Contraindications It is generally contraindicated in people with glaucoma, pyloric stenosis, or prostatic hypertrophy, except in doses ordinarily used for preanesthesia.
Side effects Adverse reactions to atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, dry mouth and potentially extreme confusion, deliriant hallucinations, and excitation especially among the elderly. These latter effects are because atropine can cross the blood–brain barrier. Because of the hallucinogenic properties, some have used the drug recreationally, though this is potentially dangerous and often unpleasant.
In overdoses, atropine is poisonous. Atropine is sometimes added to potentially addictive drugs, particularly antidiarrhea opioid drugs such as diphenoxylate or difenoxin, wherein the secretion-reducing effects of the atropine can also aid the antidiarrhea effects.
Although atropine treats bradycardia (slow heart rate) in emergency settings, it can cause paradoxical heart rate slowing when given at very low doses (less than 0.5 mg), presumably as a result of central action in the CNS.* One proposed mechanism for atropine's paradoxical bradycardia effect at low doses involves blockade of inhibitory presynaptic muscarinic autoreceptors, thereby blocking a system that inhibits the parasympathetic response.
Atropine is incapacitating at doses of 10 to 20 mg per person. Its LD50 is estimated to be 453 mg per person (by mouth) with a probit slope of 1.8. The antidote to atropine is physostigmine or pilocarpine.
A common mnemonic used to describe the physiologic manifestations of atropine overdose is: "hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter". citing J. Arena, Poisoning: Toxicology-Symptoms-Treatments, 3rd edition. Springfield, Charles C. Thomas, 1974, p 345 These associations reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased lacrimation, vasodilation, and central nervous system effects on muscarinic receptors, type 4 and 5. This set of symptoms is known as anticholinergic toxidrome, and may also be caused by other drugs with anticholinergic effects, such as hyoscine hydrobromide (scopolamine), diphenhydramine, phenothiazine antipsychotics and benztropine.
Pharmacology
In general, atropine counters the "rest and digest" activity of glands regulated by the parasympathetic nervous system, producing clinical effects such as increased heart rate and delayed gastric emptying. This occurs because atropine is a competitive, reversible antagonist of the muscarinic acetylcholine receptors (acetylcholine being the main neurotransmitter used by the parasympathetic nervous system).
Atropine is a competitive antagonist of the muscarinic acetylcholine receptor types M1, M2, M3, M4 and M5. It is classified as an anticholinergic drug (parasympatholytic).
In cardiac uses, it works as a nonselective muscarinic acetylcholinergic antagonist, increasing firing of the sinoatrial node (SA) and conduction through the atrioventricular node (AV) of the heart, opposes the actions of the vagus nerve, blocks acetylcholine receptor sites, and decreases bronchial secretions.
In the eye, atropine induces mydriasis by blocking the contraction of the circular pupillary sphincter muscle, which is normally stimulated by acetylcholine release, thereby allowing the radial iris dilator muscle to contract and dilate the pupil. Atropine induces cycloplegia by paralyzing the ciliary muscles, whose action inhibits accommodation to allow accurate refraction in children, helps to relieve pain associated with iridocyclitis, and treats ciliary block (malignant) glaucoma.
The vagus (parasympathetic) nerves that innervate the heart release acetylcholine (ACh) as their primary neurotransmitter. ACh binds to muscarinic receptors (M2) that are found principally on cells comprising the sinoatrial (SA) and atrioventricular (AV) nodes. Muscarinic receptors are coupled to the Gi subunit; therefore, vagal activation decreases cAMP. Gi-protein activation also leads to the activation of KACh channels that increase potassium efflux and hyperpolarizes the cells.
Increases in vagal activities to the SA node decrease the firing rate of the pacemaker cells by decreasing the slope of the pacemaker potential (phase 4 of the action potential); this decreases heart rate (negative chronotropy). The change in phase 4 slope results from alterations in potassium and calcium currents, as well as the slow-inward sodium current that is thought to be responsible for the pacemaker current (If). By hyperpolarizing the cells, vagal activation increases the cell's threshold for firing, which contributes to the reduction in the firing rate. Similar electrophysiological effects also occur at the AV node; however, in this tissue, these changes are manifested as a reduction in impulse conduction velocity through the AV node (negative dromotropy). In the resting state, there is a large degree of vagal tone in the heart, which is responsible for low resting heart rates.
There is also some vagal innervation of the atrial muscle, and to a much lesser extent, the ventricular muscle. Vagus activation, therefore, results in modest reductions in atrial contractility (inotropy) and even smaller decreases in ventricular contractility.
Muscarinic receptor antagonists bind to muscarinic receptors thereby preventing ACh from binding to and activating the receptor. By blocking the actions of ACh, muscarinic receptor antagonists very effectively block the effects of vagal nerve activity on the heart. By doing so, they increase heart rate and conduction velocity.
Chemistry