Atropine

Atropine is a tropane alkaloid extracted from the deadly nightshade (Atropa belladonna) 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. 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.

Physiological effects and uses
Generally, atropine lowers the "rest and digest" 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 2 to 3 days, so tropicamide and phenylephrine are generally preferred as mydriatics. The effects of atropine can last up to two weeks. In atropine-induced mydriasis, the mechanism of action involves blocking the 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 0.5-1 mg every three to five minutes, up to a maximum dose of 3mg.

Atropine is also useful in treating first degree heart block, 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 ischaemia-induced conduction block, because the drug increases oxygen demand of the AV nodal tissue, thereby aggravating ischaemia 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 it has not been officially indicated for either of these purposes by the FDA, it has been used by physicians for these purposes.

Antidote for organophosphate poisoning
By blocking the action of acetylcholine at muscarinic receptors, atropine also serves as an antidote for poisoning by organophosphate insecticides and nerve gases. Troops who are likely to be attacked with chemical weapons often carry autoinjectors with atropine and obidoxime which can be quickly injected into the thigh. It is often used in conjunction with Pralidoxime chloride.

Atropine is given as an antidote to SLUDGE (Salivation, Lacrimation, Urination, Diaphoresis, Gastrointestinal distress, 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 overdoses
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, hallucinations, and excitation. These latter effects are due to the fact that atropine is able to cross the blood-brain barrier. Because of the hallucinogenic properties, some have used the drug recreationally, though this is very dangerous and often unpleasant.

In overdoses, atropine is poisonous. Atropine is sometimes added to other potentially addictive drugs; abuse of those drugs is then prevented by the unpleasant effects of atropine overdose.

Although atropine treats bradycardia (slow heart rate) in emergency settings, it can cause heart rate slowing when given at very low doses, presumably as a result of a weak partial agonist effect at the cardiac muscarinic receptors.

The antidote to atropine is physostigmine or pilocarpine.

Mnemonic for Side Effects
A commonly used mnemonic used to described the physiologic manifestions of atropine overdose is: "Hot as a Hare, Dry as a Bone, Red as a Beet, Mad as a Hatter, Blind as a Bat.

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.

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
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".

Atropine and its mydriatic effects were discovered in 1833 by the German chemist Friedrich Ferdinand Runge (1795-1867).

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.