Atropine is a competitive antagonist of acetylcholine which binds to the muscarinic receptor in order to inhibit the parasympathetic nervous system. It causes a reversible blockade of the action of acetylcholine and it can be overcome by increasing the concentration of acetylcholine at receptor sites of the effectors organ (e.g. by using the anticholinesterase agents which inhibit the destruction of acetylcholine). Atropine is an alkaloid or an extremely poisonous drug derived from a plant called atropia belladonna, also known as deadly nightshade. "Belladonna" is Italian word which means beautiful woman. In the Renaissance, woman used the juice of berries of atropia belladonna to dilate pupils as it was perceived as more attractive.
Eye - Atropine acts in the eye to block the action of acetylcholine, relaxing the cholinergically innervated sphincter muscles of the iris. This results in dilation of the pupil (mydriasis). The cholinergic stimulation of accommodative ciliary muscle of the lens in the eye is also blocked. This results in paralysis of accommodation (cycloplegia). Besides, the elevation of intraocular pressure (IOP) occurs when the anterior chamber is narrow. It will further raise IOP in glaucoma patients because it will obstruct evacuation of aqueous humor by the Schlemm channel. Atropine is thus contraindicated in these patients. Another effect of antimuscarinic drugs is to reduce lacrimal secretion which produces dryness in eyes.
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Atropine has a slower onset and more prolonged effect in eye as maximum mydriatic effect occurs around 30 to 40 minutes and maximum cycloplegia takes several hours. Mydriasis usually lasts 7 to 12 days and cycloplegia may persist for 14 days or longer.
Cardiovascular system - The vagus (parasympathetic) nerves that innervate the heart release acetylcholine (ACh) as their primary neurotransmitter to slow the heart rate. ACh binds to muscarinic receptors (M2) that are found on cells comprising the sinoatrial (SA) and atrioventricular (AV) nodes.
Atropine has a potent and prolonged effect on the heart muscle. It inhibits the effect of excessive vagal nerve activation on the heart like sinus bradycardia and AV nodal block (delay in the conduction of electrical impulses at the AV node of the heart) by binding to muscarinic receptors in order to prevent ACh from binding to and activating the receptor. Thus, atropine speeds up the heart rate and increases conduction velocity as it very effectively blocks the effects of parasympathetic nerve activity on the heart. There are little effects on blood pressure since most resistance blood vessels do not have cholinergic innervations. Small doses of atropine used may decrease the heart rate, yet, large doses used definitely causes increasing of the heart rate.
Central nervous system - Atropine has minimal stimulant effects on the central nervous system, especially medullary centers, and a slower, longer-lasting sedative effect on the brain. Low doses atropine may produce mild restlessness and higher doses may produce agitation and hallucination. With still larger doses, stimulation is followed by depression leading to circulatory collapse and respiratory failure after a period of paralysis and coma.
Respiratory tract - The parasympathetic nervous system regulate bronchomotor tone and secretionary glands of the airway. Since atropine is an antagonist muscarinic drug, it inhibits the secretion of nose, mouth, pharynx and bronchi, and thus dries the mucous membranes of the respiratory tract. And it also relaxes bronchial smooth muscle, producing bronchodilation and decreasing airway resistance. The effect is more important in patients with airway disease like asthma.
Gastrointestinal tract - Motility and secretions of gastrointestinal tract are declined by atropine. GI smooth muscle motility is affected from the stomach to the colon by decreasing tone, amplitude and frequency of the peristaltic contractions. However, the gastric secretion is only slightly reduced.
Genitourinary tract - The antimuscarinic action of atropine relaxes smooth muscle of the ureters and bladder wall in order to decrease the normal tone and amplitude of contractions of the ureters and bladder. Atropine has not significant effect on the uterus.
Sweat glands - Small doses of atropine inhibit the activity of sweat glands, producing hot and dry on the skin. Sweating may be sufficiently depressed and this will elevate the body temperature if using the larger doses in adult or at high environmental temperatures. For the infant or children who are administered large doses or even ordinary doses may cause "atropine fever".
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Atropine is rapidly and well absorbed from the gastrointestinal tract, mucosal membrane, conjunctival membranes, and to some extent through intact skin when given by oral route, solution, ointment or injection route (directly goes into muscle or vein). Pharmacological activity of paranteral administration is 2-3 times greater than enteral route.
Atropine is rapidly cleared from the blood and is distributed throughout the body. It crosses the blood-brain barrier and placenta. Peak plasma concentrations of atropine are reached within 30 minutes. The duration of action of atropine administered by general route would be approximately 4 -6 hours.
After administration, atropine disappears rapidly from the blood with a half-life of 2 hours. The half-life of atropine is slightly shorter in females than males. Then it is metabolized in the liver by oxidation and conjugation to give inactive metabolites.
The drug's effect on parasympathetic function declines rapidly in all organs except the eye. Effects on the iris and ciliary muscle persist for more than 3 days. About 50% of the dose is excreted within 4 hours and 90% in 24 hours in the urine, about 30 to 50% as unchanged drug.
As preanaesthetic medicationts
Atropine is used to block two effects in particular during anaesthesia, secretions in the respiratory tract in response to the irritating nature of some inhalant anaesthetics, and bradycardia (slowing of the heart) which accompanies most anaesthetics due to the block of muscarinic receptors in the heart. Overall, atropine can reduce the risk of airway obstruction and increase the heart beat when anaesthetic drug is going to be used.
Topical atropine is used as a cycloplegic (temporarily paralyze the accommodation) and as a mydriatic (dilate the pupils) for accurate measurement of refractive error in patients. A second use is to prevent synechiae (adhesion) formation in uveitis and iritis. After local administration in the form of ophthalmic solution, the onset of atropine is around 30 minutes and it effects last very long: dilation of pupil can persist several days.
Injection of atropine is used in the treatment of bradycardia (an extremely low heart rate) due to excessive vagal tone on the SA and AV node. It accelerates the cardiac rate by reduction of vagal tone and suppression of reflex bradycardia during arterial hypertension. In addition, atropine is also used primary for sinus node dysfunction (inappropriate atrial rates) and symptomatic second-degree heart block (irregularities in the electrical conduction system of the heart).
Parenteral atropine can be used as a preoperative medication to suppress bronchiolar secretions when anaesthetics are used. It can be used to treat asthma, chronic bronchitis and chronic obstructive pulmonary disease.
Atropine is seldom used to treat pepti-ulcer nowadays. Atropine can provide some relief in the treatment of common traveler's diarrhea (irritable bowel movement). It is often combined with an opioid antidiarrheal drug in order to discourage abuse of the opioid agent.
Atropine is used to relieve bladder spasm after urologic surgery and for treating urinary urgency caused by minor inflammatory bladder disorder.
It is an excessive and profuse perspiration. Atropine can reduce the secretion of sweat glands by inhibiting the Ach binds to the muscarinic receptors.
By blocking the action of ACh, atropine also can be used as an antidote for organophosphate poisoning caused by inhibition of cholinesterase and nerve gases. The atropine serves as an effective blocking agent for the excess ACh but does nothing to reverse the inhibition of cholinesterase. Troops, who are likely to be attacked with chemical weapons often carry autoinjectiors with atropine and obidoxime which can be quickly injected into the thigh. It is the only known antidote for VX nerve gas. Some of the nerve gases attack and destroy acetycholinesterase (an enzyme hydrolyzes ACh to give choline), so the action of acetylcholine becomes prolonged. Therefore, atropine can be used to depress the effect of ACh.
Atropine is used to treat the symptom of Parkinson such as drooling sweating rigidity and tremors. However, with the wide array of uses and side effects that atropine has, it has been replaced by several other medicines that are more effectively in treating Parkinson's.
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Atropine and its possible side effect can affect individual people in various ways. The following are some of the side effects that are known to be associated with atropine. Not all the patients using this antimuscarinic drug will experience the same effects. These effects are intensified as the dosages are increased.
General - chest pain, excessive thirst, weakness, dehydration, feeling hot, injection site reaction, fever.
Eye - dilation pupil, pupil poorly reactive to light, photophobia, blurred vision, decreased accommodation, decreased contrast sensitivity, decreased visual acuity, dry eyes or dry conjunctiva, acute angle closure glaucoma, irritated eyes, allergic conjunctivitis or blepharoconjunctivitis, heterophoria, red eye due to excess blood supply (hyperaemia).
Psychiatric - hallucination, mental confusion, agitation, restlessness, anxiety, excitement especially in elderly, fatigue.
Central nervous system - headache, nervousness, dizziness, drowsiness, muscle twitching, abnormal movement, coma, difficult concentrating, insomnia, amnesia, ataxia (loss of the ability to coordinate muscular movement).
Cardiovascular - tachycardia (increasing in heartbeat), acute myocardial infarction, cardiac dilation, atrial arrhythmias, paradoxical Bradycardia (if low does Atropine used), asystole (absence of heart beat), increased blood pressure or decreased blood pressure.
Respiratory - slow respiration, breathing difficulty, pulmonary edema, respiratory failure.
Gastrointestinal - nausea, abdomen pain, vomiting, decreased bowel sounds, decreased food absorption, delayed gastric emptying, reduction of salivary secretions, loss of taste, bloated feeling.
Genitourinary - urinary retention, urine urgency, bed-wetting, difficult in micturation.
Dermatologic - dry mucous membrane, dry warm skin, flushed skin, oral lesion, anhidrosis (absence of sweating), dermatitis, rash, hyperthermia (elevated of body temperature)
Overdose and Treatment
Widespread paralysis of parasympathetically innervated organs can characterize serious over dosage with atropine. Dry mucous membranes, widely dilated and nonresponsive pupils, tachycardia, fever, hallucination and flushed skin are mental and neurological symptoms which may last 48 hours or longer. Severe intoxication, respiratory depression, blood pressure declines, coma, circulatory collapse and death may occur with over dosage of atropine.