Atropine
145159
225829285
2008-07-15T16:20:09Z
65.80.23.150
{{Drugbox|
|IUPAC_name = (8-methyl-8-azabicyclo[3.2.1]oct-3-yl) 3-hydroxy-2-phenylpropanoate
| image= Atropine.svg
| image2= S-atropine-3D-sticks.png
| width=200
| CAS_number=51-55-8
| ATC_prefix=A03
| ATC_suffix=BA01
| ATC_supplemental={{ATC|S01|FA01}}
| PubChem=174174
| DrugBank=APRD00807
| C = 17 | H = 23 | N = 1 | O = 3
| molecular_weight = 289.369
| bioavailability= 25%
| metabolism = 50% [[hydrolyse]]d to [[tropine]] and [[tropic acid]]
| elimination_half-life= 2 hours
| excretion = 50% excreted unchanged in urine
| pregnancy_US = C
| legal_status = R<sub>x</sub> only
| routes_of_administration= Oral, [[Intravenous therapy|IV]], rectal
}}
'''Atropine''' is a [[tropane]] [[alkaloid]] extracted from [[deadly nightshade]] (''Atropa belladonna''), [[jimsonweed]] (Datura stramonium) and other plants of the family [[Solanaceae]]. It is a [[secondary metabolite]] of these plants and serves as a [[hard drug|drug]] with a wide variety of effects. It is a [[competitive antagonist]] for the [[muscarinic acetylcholine receptor]]. It is classified as an [[anticholinergic drug]]. Being potentially deadly, it derives its name from [[Atropos]], one of the three [[Moirae|Fates]] who, according to Greek mythology, chose how a person was to die. Atropine is a ''core'' medicine in the [[World Health Organization]]'s "[[WHO Model List of Essential Medicines|Essential Drugs List]]", which is a list of minimum medical needs for a basic health care system.<ref name="essentialWHO">{{cite web
| year = March 2005
| url = http://whqlibdoc.who.int/hq/2005/a87017_eng.pdf
| title = WHO Model List of Essential Medicines
| format = PDF
| publisher = World Health Organization
| accessdate = 2006-03-12
}}</ref>
== Physiological effects and uses ==
Increases firing of SA node, conduction thru AV node, opposes vagus nerve, blocks acetylcholine receptor sites, decreases bronchiole secretions.
Generally, atropine lowers the "rest and digest" activity of all [[muscle]]s and [[gland]]s regulated by the [[parasympathetic nervous system]]. This occurs because atropine is a [[competitive antagonist]] of the muscarinic [[acetylcholine receptor]]s ([[Acetylcholine]] is the main [[neurotransmitter]] used by the [[parasympathetic]] nervous system). Therefore, it may cause swallowing difficulties and reduced secretions.
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=== Ophthalmic use ===
[[Topical]] atropine is used as a [[cycloplegic]], to temporarily paralyze the [[accommodation reflex]]; and as a [[mydriatic]], to dilate the [[pupil]]s. Atropine degrades slowly, typically wearing off in 2 to 3 days, so is generally used as a therapeutic mydriatic, whereas [[tropicamide]] (a shorter-acting cholinergic antagonist) or [[phenylephrine]] (an α-adrenergic agonist) are preferred as an aid to ophthalmic examination. The effects of atropine can last up to two weeks. Atropine induces [[mydriasis]] by blocking contraction of the circular [[pupillary sphincter]] muscle, which is normally stimulated by acetylcholine release, thereby allowing the radial [[pupillary dilator]] muscle to contract and dilate the pupil. Atropine is contraindicated in patients predisposed to narrow angle [[glaucoma]].
Atropine can be given to patients who have direct globe trauma.
=== Resuscitation ===
Injections of atropine are used in the treatment of [[bradycardia]] (an extremely low heart rate), [[asystole]] and [[pulseless electrical activity]] (PEA) in [[cardiac arrest]]. This works because the main action of the [[vagus nerve]] of the parasympathetic system on the heart is to slow it down. Atropine blocks that action and therefore may speed up the heart rate. The usual dose of atropine is 0.5 to 1 mg IV push every three to five minutes, up to a maximum dose of 0.04mg/kg.
Atropine is also useful in treating [[Second degree AV block#Type 1 Second degree AV block|second degree heart block Mobitz Type 1 (Wenckebach block)]], and also [[Third degree AV block|third degree heart block]] with a high [[Purkinje fibers|Purkinje]] or [[Atrioventricular node|AV-nodal]] [[escape rhythm]]. It is usually not effective in [[Second degree AV block#Type 2 Second degree AV block|second degree heart block Mobitz type 2]], and in third degree heart block with a low Purkinje or ventricular escape rhythm. Atropine is contraindicated in ischemia-induced conduction block, because the drug increases oxygen demand of the AV nodal tissue, thereby aggravating ischemia and the resulting heart block.
One of the main actions of the [[parasympathetic nervous system]] is to stimulate the [[Muscarinic acetylcholine receptor M2|M<sub>2</sub> muscarinic receptor]] in the heart, but atropine inhibits this action.
=== Secretions and bronchoconstriction ===
Atropine's actions on the parasympathetic nervous system inhibits salivary, sweat, and mucus glands. This can be useful in treating [[hyperhidrosis]] and can prevent the [[death rattle]] of dying patients. Even though it has not been officially indicated for either of these purposes by the FDA, it has been used by physicians for these purposes. <ref>http://www.eperc.mcw.edu/fastFact/ff_109.htm</ref>
=== Antidote for organophosphate poisoning ===
By blocking the action of [[acetylcholine]] at [[muscarinic]] receptors, atropine also serves as an antidote for poisoning by [[organophosphate]] [[insecticide]]s and [[nerve gas]]es, such as [[Tabun (nerve agent)|Tabun]] (GA), [[Sarin]] (GB), [[Soman]] (GD) and [[VX (nerve agent)|VX]]. Troops who are likely to be attacked with [[chemical weapon]]s often carry [[autoinjector]]s with atropine and [[obidoxime]] which can be quickly injected into the thigh. Atropine is often used in conjunction with [[Pralidoxime chloride]].
Atropine is given as an antidote to [[SLUD]]GE ([[Salivation]], [[Lacrimation]], [[Urination]], [[Diaphoresis]], [[Gastrointestinal]] motility, [[Emesis]]) symptoms caused by organophosphate poisoning.
Some of the nerve gases attack and destroy [[acetylcholinesterase]], so the action of acetylcholine becomes prolonged. Therefore, atropine can be used to reduce the effect of acetylcholine.
=== Side effects and overdose ===
Adverse reactions to atropine include ventricular [[fibrillation]], supraventricular or ventricular [[tachycardia]], [[Vertigo (medical)|dizziness]], [[nausea]], blurred vision, loss of balance, dilated pupils, [[photophobia]], and possibly, notably in the elderly, extreme [[confusion]], extreme dissociative [[hallucination]]s, and [[excitation]]. These latter effects are because atropine is able to cross the [[blood-brain barrier]]. Because of the [[Psychedelics, dissociatives and deliriants|hallucinogenic]] properties, some have used the drug [[recreational drugs|recreationally]], though this is very dangerous and often unpleasant.
In overdoses, atropine is [[poison]]ous. Atropine is sometimes added to other potentially addictive drugs, particularly anti-diahorrea opioid drugs such as [[diphenoxylate]] or [[difenoxin]] where the secretion-reducing effects of the atropine can also aid the anti-diahorrea effects. This is supposed to prevent abuse of these drugs, however while the unpleasant side effects produced by the atropine may discourage abuse they certainly do not prevent it entirely,<ref>Rao R, Agrawal A, Pal HR, Mohan I. Lomotil dependence: a note of caution. ''National Medical Journal of India''. 2005 Nov-Dec;18(6):330-1.</ref> and these combination products can be significantly more dangerous than if the opioid was administered by itself.<ref>Thomas TJ, Pauze D, Love JN. Are one or two dangerous? Diphenoxylate-atropine exposure in toddlers. ''Journal of Emergency Medicine''. 2007 Aug 29.</ref>
Although atropine treats [[bradycardia]] (slow heart rate) in emergency settings, it can cause paradoxical heart rate slowing when given at very low doses, presumably as a result of central action in the CNS. <ref>* {{cite book | first = | last =Rang HP, Dale MM, Ritter JM, Flower RJ| authorlink = | coauthors = | year = 2007| month = | title = Rang and Dale's Pharmacology | chapter = Ch. 10| editor = | others = | edition = | pages = 153 | publisher = Elsevier Churchill Livingstone| location = | id = ISBN 0-443-06911-5| url = }}</ref>
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".<ref name="holzman">{{cite web|url=http://www.anesthesiology.org/pt/re/anes/fulltext.00000542-199807000-00030.htm;jsessionid=GSJKLv9vLCdQSmpp6vH3xdhnzWN1hy3s7JqMNFpWkHhLbKJT5vLM!741375937!-949856145!8091!-1#P89|title=The Legacy of Atropos|author=Robert S. Holzman, MD|journal=Anesthesiology|volume=89|issue=1|date=1998-07|pages=241-249|accessdate=2007-05-21}} citing J. Arena, Poisoning: Toxicology-Symptoms-Treatments, 3rd edition. Springfield, Charles C. Thomas, 1974, p 345 </ref> This set of symptoms is known as [[toxidrome#Anticholinergic toxidrome|anticholinergic toxidrome]], and may also be caused by other drugs with anticholinergic effects, such as [[diphenhydramine]], [[phenothiazine]] [[antipsychotic]]s and [[benztropine]].<ref>{{cite web | url = http://www.intox.org/databank/documents/treat/treate/trt05_e.htm | title = Acute anticholinergic syndrome | author = Szajewski J | year = 1995 | publisher = IPCS Intox Databank | accessdate = 2007-05-22}}</ref>
== Chemistry and pharmacology==
Atropine is a [[racemic]] mixture of D-[[hyoscyamine]] and L-hyoscyamine, with most of its physiological effects due to L-hyoscyamine. Its pharmacological effects are due to binding to muscarinic [[acetylcholine receptor]]s. It is an antimuscarinic agent.
The most common atropine compound used in medicine is atropine [[sulfate]] ([[carbon|C]]<sub>17</sub>[[hydrogen|H]]<sub>23</sub>[[Nitrogen|N]][[Oxygen|O]]<sub>3</sub>)<sub>2</sub>·[[sulfate|H<sub>2</sub>SO<sub>4</sub>]]·[[water|H<sub>2</sub>O]], the full chemical name is 1α H, 5α H-Tropan-3-α ol (±)-tropate(ester), sulfate monohydrate.
== History ==
''[[Mandragora]]'' (mandrake) was described by [[Theophrastus]] in the fourth century B.C. for treatment of wounds, gout, and sleeplessness, and as a [[love potion]]. By the first century A.D. [[Dioscorides]] recognized wine of mandrake as an [[anaesthetic]] for treatment of pain or sleeplessness, to be given prior to surgery or cautery.<ref name="holzman" /> The use of [[Solanaceae]] containing [[tropane]] [[alkaloids]] for anesthesia, often in combination with [[opium]], persisted throughout the Roman and Islamic Empires and continued in Europe until superseded by the use of [[ether]], [[chloroform]], and other modern anesthetics.
Atropine extracts from the Egyptian [[henbane]] were used by [[Cleopatra]] in the last century B.C. to dilate her [[pupils]], in the hope that she would appear more alluring. In the [[Renaissance]], women used the juice of the berries of ''[[Atropa belladonna]]'' to enlarge the pupils of their eyes, for cosmetic reasons; "bella donna" is Italian for "beautiful lady".
The mydriatic effects of atropine were studied among others by the [[Germany|German]] [[chemistry|chemist]] [[Friedrich Ferdinand Runge]] ([[1795]]–[[1867]]). In 1831 the pharmacist Mein succeeded the pure crystalline isolation of atropine. The substance was first synthesized by German chemist [[Richard Willstätter]] in 1901.
Atropinic shock therapy, also known as atropinic coma therapy, is an old and rarely used method. It consists of induction of atropinic coma by rapid intravenous infusion of atropine. Atropinic shock treatment is considered safe, but it entails prolonged coma (between four and five hours), with careful monitoring and preparation, and it has many unpleasant side effects, such as blurred vision.{{Fact|date=May 2008}}
== Natural sources ==
Atropine is found in many members of the Solanaceae family. The most commonly found sources are ''[[Atropa belladonna]]'', ''[[Datura inoxia]]'', ''[[Datura metel|D. metel]]'', and ''[[Datura stramonium|D. stramonium]]''. Other sources include members of the ''[[Brugmansia]]'' and ''[[Hyoscyamus]]'' genera. The ''[[Nicotiana]]'' genus (including the tobacco plant, ''[[Nicotiana tabacum|N. tabacum]]'') is also found in the Solanaceae family, but these plants do not contain atropine or other [[tropane]] alkaloids.
==See also==
*[[Mark I NAAK]]
==References==
<references />
{{Drugs for functional gastrointestinal disorders}}
{{Mydriatics and cycloplegics}}
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{{Deliriants}}
{{Emergency medicine}}
[[Category:Natural tropane alkaloids]]
[[Category:Antidotes]]
[[Category:Deliriants]]
[[Category:Muscarinic antagonists]]
[[Category:World Health Organization essential medicines]]
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