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medicine: atropine
atropine description
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Atropine is a tropane alkaloid extracted from deadly nightshade (Atropa belladonna), jimsonweed (Datura stramonium), mandrake (Mandragora officinarum) and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a 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 Fates who, according to Greek mythology, chose how a person was to die. Atropine is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.
Physiological effects and uses
Atropine increases 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 general, atropine lowers the parasympathetic activity of all muscles and glands regulated by the parasympathetic nervous system. This occurs because atropine is a competitive antagonist of the muscarinic acetylcholine receptors (Acetylcholine is the main neurotransmitter used by the parasympathetic nervous system). Therefore, it may cause swallowing difficulties and reduced secretions.
Ophthalmic use
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 cholinergic antagonist) or phenylephrine (an α-adrenergic agonist) is preferred as an aid to ophthalmic examination. 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 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. Atropine is contraindicated in patients pre-disposed 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 decrease heart rate. Atropine blocks this action and, therefore, may speed up the heart rate. The usual dosage of atropine in bradyasystolic arrest is 0.5 to 1 mg IV push every three to five minutes, up to a maximum dose of 0.04 mg/kg. For symptomatic bradycardia, the usual dosage is 0.5 to 1.0 mg IV push, may repeat every 3 to 5 minutes up to a maximum dose of 3.0 mg.
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 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 M2 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 atropine has not been officially indicated for either of these purposes by the FDA, it has been used by physicians for these purposes.
Treatment for organophosphate poisoning
Atropine is not an actual antidote for organophosphate poisoning. However, by blocking the action of acetylcholine at muscarinic receptors, atropine also serves as a treatment for poisoning by organophosphate insecticides and nerve gases, such as Tabun (GA), Sarin (GB), Soman (GD) and VX. Troops that are likely to be attacked with chemical weapons often carry autoinjectors 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 a treatment for SLUDGE (Salivation, Lacrimation, Urination, Diaphoresis, Gastrointestinal motility, Emesis) symptoms caused by organophosphate poisoning. Another mnemonic is DUMBBELSS, which stands for Diarrhea, Urination, Miosis, Bradycardia, Bronchoconstriction, Excitation (as of muscle in the form of fasciculations and CNS), Lacrimation, Salivation, and Sweating (only sympathetic innervation using Musc receptors).
Some of the nerve agents attack and destroy acetylcholinesterase by phosphorylation, so the action of acetylcholine becomes prolonged, pralidoxime (2-PAM) is the cure for organophosphate poisoning because it can cleave this phosphorylation. Atropine can be used to reduce the effect of the poisoning by mimicking acetylcholine.
Optical penalisation
In refractive and accommodative amblyopia, when occlusion is not appropriate sometimes atropine is given to induce blur in the good eye.
Side-effects and overdose
Adverse reactions to atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, and, possibly, notably in the elderly, extreme confusion, extreme dissociative hallucinations, and excitation. These latter effects are because atropine is able to 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 anti-diarrhea opioid drugs such as diphenoxylate or difenoxin, wherein the secretion-reducing effects of the atropine can also aid the anti-diarrhea effects.
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.
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". These associations reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased sweating/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 diphenhydramine, phenothiazine antipsychotics and benztropine.
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 receptors. It is an antimuscarinic agent.
The most common atropine compound used in medicine is atropine sulfate (C17H23NO3)2·H2SO4·H2O, 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. 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". This practice resumed briefly in the late nineteenth- and early twentieth-century in Paris.
The mydriatic effects of atropine were studied among others by the German 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 with careful monitoring and preparation, but it entails prolonged coma (between four and five hours), and it has many unpleasant side-effects, such as blurred vision.
Natural sources
Atropine is found in many members of the Solanaceae family. The most commonly-found sources are Atropa belladonna, Datura inoxia, D. metel, and D. stramonium. Other sources include members of the Brugmansia and Hyoscyamus genera. The Nicotiana genus (including the tobacco plant, N. tabacum) is also found in the Solanaceae family, but these plants do not contain atropine or other tropane alkaloids.
Synthesis
Atropine can be synthesized by the reaction of tropine with tropic acid in the presence of hydrochloric acid.
See also
Mark I NAAKAtropine coma therapy
| Name | Information | Price* | Quantity |
| Atropine Eye Drops 1% | 5 ml | $11 | 5 ml |
| Atropine Eye Ointment 1% | Discontinued | N/A | |
| Atropine Sulfate Eye Drops 1% | 10 ml | $15 | 10 ml |
| Generic Belladonna Alkaloids-Phenobarbitol 0.0194-0.1037-16.2-0.0065mg | (atropine Sulfate/hyoscyamine hydrobromide/ phenobarbital/scopolamine hydrobromide) discontinued | N/A | |
| Isopto Homatropine 2% | 15 ml (homatropine) | $33 | 15 ml |
| Isopto Homatropine 5% | 15 ml (homatropine) | $31 | 15 ml |
*) Prices related to some of online drugstores. There are only approximate prices. For some of drugs is needed a prescription.
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