Classification of Cholinergic Drugs

I. Cholinomimetic drugs

1. M,N-cholinomimetic with direct action. This group includes acetylcholine and carbacholine.

2. M-cholinomimetic with direct action. This group includes pilocarpine and aceclidine.

3. N- cholinomimetic with direct action: nicotine, lobeline and cytitonum.

4. M,N-cholinomimetic with indirect action, or cholinesterase inhibitors: galantamine, physostigmine, proserinum (neostigmine), pyridostigmine, oxazylum (ambenonium), distigmine, armin.

II. Cholinolytic drugs

1. M-cholinolytic drugs. This group includes atropine sulfate, scopolamine, plathyphyllin, metacinum, ipratropium bromide, pirenzepine, homatropine, tropicamide.

2. N_n-cholinolytic drugs (ganglion blocking drugs): benzohexonium, pentaminum, hygronium, arfonade, pirilenum, pachycarpine.

3. N_m-cholinolytic drugs (myorelaxation drugs): tubocurarine, pipecuronium, pancuronium, dithylinum dioxonium.

M,N-Cholinomimetics with Direct Action

Acetylcholine is a quaternary ammonium compound that cannot penetrate membranes. Acetylcholine has both muscarinic and nicotinic activity. Let’s consider the influence of acetylcholine on organs and systems.

1. The actions of acetylcholine on the heart mimics effects of vagal stimulation. Activation of M₂-receptors increases the potassium permeability and reduces cAMP levels, slowing the rate of depolarization and decreasing the excitability of SA- and AV- node. This results in marked bradycardia and a slowing of AV conduction that can override the stimulation of the heart by catecholamines released during sympathetic stimulation. In fact, very high doses of a muscarinic agonist can produce lethal bradycardia and AV block.

2. Acetylcholine causes vasodilatation and lowering of blood pressure. These responses result from the stimulation of muscarinic receptors on vascular endothelial cells. Activation of these receptors causes the endothelial cells to synthesize and release nitric oxide. Nitric oxide can diffuse into neighboring vascular smooth muscle cells, where it activates soluble guanylyl cyclase, thereby increasing the synthesis of cyclic guanosine monophosphate (cGMP) and relaxing the muscle fibers. Most of the resistance vasculature is not innervated by cholinergic neurons, and the physiological function of the endothelial muscarinic receptors is not known. However, activation of these receptors by directly acting cholinomimetic drugs has major pharmacological significance, as the potentially dangerous hypotension produced by their activation is an important limitation to the systemic administration of muscarinic agonists.

3. Acetylcholine increases secretion of all excretory glands, such as salivary, sweat, gastric and other ones.

4. Bronchiolar secretion is stimulated too. The tone of bronchioles increases.

5. Acetylcholine stimulates motility and tone of gastrointestinal tract.

6. The tone of the detrusor muscle of the bladder is increased.

7. In the eye acetylcholine causes contraction of the smooth muscle in two important structures, the iris sphincter and the ciliary muscles. Contraction of the iris sphincter decreases the diameter of the pupil (miosis). The intraocular pressure is lowered because in the pupil sphincter contraction the spaces of the iris angle (the Fontana’s spaces) are widening. It provides the outflow of the aqueous humor from the anterior chamber of the eye into the venous sinus of the sclera (the Schlemm channel). Contraction of the circular fibers of the ciliary muscle, which encircles the lens, reduces the tension on the suspensory ligaments that normally stretch and flatten the lens, allowing the highly elastic lens to spontaneously round up and focus for near vision (accommodation for near vision).

8. Acetylcholine causes increasing of the ganglion transmission and adrenaline discharging in blood from adrenal glands.

9. Acetylcholine causes the improvement of neuromuscular transmission.

Acetylcholine rapidly hydrolyzed by cholinesterase. Its action continues 5-15 min in the subcutaneous introduction. In such a way, acetylcholine has multiplicity of actions and very short duration of action. That’s way acetylcholine is therapeutically of no importance.

Carbacholine (Carbachol) is synthetic ester of choline and carbamic acid and a poor substrate for acetylcholinesterase. It is destroyed slowly and it acts about one hour. Actions of carbachol are similar to acetylcholine. Carbachol is rarely used therapeutically. One is sometimes effective in treating cases of open-angle glaucoma that are resistant to pilocarpine. The medical membranes or eye drops with Carbachol could be placed on the mucous membrane of the eyes.

M-Cholinomimetic Drugs

The mechanism of action of these drugs is associated with direct stimulation of the M-cholinoceptors.

The alkaloid pilocarpine is a tertiary amine and is stable to hydrolysis by acetylcholinesterase. Pilocarpine is one of the most potent stimulators of secretions such as sweat, tears, and saliva but it is not used for internal and parenteral administration. Pilocarpine is the drug of choice in the emergency lowering of intraocular pressure in glaucoma. Pilocarpine is the first choice among cholinomimetics for the treatment of glaucoma. Pilocarpine can be applied to the eye as a gel (Pilopine HS Gel) or timerelease system (Ocusert) for the chronic treatment of open-angle glaucoma, or as drops for an acute reduction of intraocular pressure, as in the emergency management of angle-closure glaucoma. This action of pilocarpine lasts up to 1 day.

The action of aceclidine is accompanied by pupil narrowing, decrease of the intraocular pressure, spasm of accommodation, strengthening of tone of the smooth muscles of bronchi, gastrointestinal tract, biliferous and urinary tracts, stimulation of the bronchial, digestive and sudoriferous glands secretion, lowering of automatism, excitability, conduction and contractility of heart; dilation of the vessels of skeletal muscles and of genital organs, decrease of the arterial pressure. Among these effects only decrease of the intraocular pressure and strengthening of the tone of the intestinal and urinary bladder have the importance in medical practice. The Aceclidine is used in the treatment of glaucoma, intestinal and bladder postsurgical atony.

Adverse effects of M-cholinomimetics. Potentially severe adverse effects can result from systemic administration of cholinomimetic drugs, and none should be administered by intravenous injection. If significant amounts of these drugs enter the circulation, nausea, abdominal cramps, diarrhea, salivation, hypotension with reflex tachycardia, cutaneous vasodilation, sweating, and bronchoconstriction can result. Pilocarpine can cross the blood-brain barrier and affect cognitive function. Even the topical application of cholinomimetics to the eyes can present some risk, and the escape of cholinomimetics into the circulatory system topical application to the eye can minimized by pressure applied to the lacrimal duct.

M-cholinomimetics are contrindicated in bronchial asthma, disorders of the cardiac conduction, coronary artery disease, hyperthyroidism, Parkinsonism, epilepsy, hyperkynesia, pregnancy.

The poisonings by M-cholinomimetics are most commonly caused by bly-agaric. The urgent aid: gastric lavage, introduction of atropine.

Cholinesterase Inhibitors

Depending on the character of action upon enzyme cholinesterase inhibitors are divided into the substances with reversible and irreversible action. The reversible ones cause the reversible inactivation of enzyme, because they form the unstable bond with it. The irreversible drugs form the firm covalent bond with cholinesterase so the inhibition of enzyme has the irreversible character. The bond is slowly hydrolyzed by water (about 20 days).

Acetylcholinesterase is located both pre- and postsynaptically in the nerve terminal, where it is membrane bound. The active center of cholinesterase has two areas that interact with acetylcholine: the anionic site and the esteratic site. The anionic site contains a negatively charged amino acid that binds the positively charged quaternary ammonium group of acetylcholine. This probably serves to bring the ester linkage of acetylcholine close to the esteratic site of the enzyme. The esteratic site contains a serine residue. The nucleophilic oxygen of the serine reacts with the carbonyl carbon of acetylcholine, thereby breaking the ester linkage. During this reaction, choline is liberated and an acetylated enzyme is formed. The latter intermediate is rapidly hydrolyzed to release acetic acid and regenerate the active enzyme. The entire process takes about 150 microseconds, one of the fastest enzymatic reactions known.

Inhibitors of acetylcholinesterase indirectly provide a cholinergic action by prolonging the lifetime of acetylcholine produced endogenously at the cholinergic nerve endings. This results in the accumulation of acetylcholine in the synaptic space. These drugs can thus provoke a response at all cholinoceptors in the body, including both muscarinic and nicotinic receptors of the autonomic nervous system as well as the neuromuscular junction and the brain. However, the action of the cholinesterase inhibitors upon CNS depends on the ability for permeation through the hematoencephalic barrier. The substances containing a tertiary ammonium group (physostigmine, galantamine) easily penetrate into the brain and act upon the CNS.

The typical effects of anticholinesterase drugs similar to actions of M,N-cholinomimetics with direct action.

Let’s consider the anticholinesterase drugs which are most commonly used in medical practice.

Physostigmine is an alkaloid of plants and a tertiary amine. Its duration of action is about 2-4 hours. Physostigmine can enter and stimulate the CNS. The drug increases intestinal and bladder motility, which serve as its therapeutic action in atony of either organ. Placed topically in the eye, it produces a lowering of intraocular pressure. That’s way it is used to treat glaucoma. Physostigmine is also used in the treatment of overdoses of drugs with anticholinergic actions such as atropine, scopolamine, tricyclic antidepressants, phenothiazines, and antihistamines. The drug can use in the residual effects after poliomyelitis, craniocerebral injuries, and cerebral hemorrhages, Alzheimer’s disease. Alzheimer’s disease is a slowly developing neurodegenerative disease that produces loss of memory and cognitive function, that is, dementia. These functional changes appear to result primarily from the loss of cholinergic transmission in the neocortex. However, physostigmine can produce cardiac arrhythmias and other serious toxic effects. Galantamine is similar to the physostigmine, but ones not used in treatment of glaucoma.

Proserinum is a synthetic compound. Proserinum is polar and therefore does not enter the CNS. Its effect on skeletal muscles is greater than that of physostigmine, and it can stimulate contractility. The duration of action of proserinum is 2-4 hours. It is used to stimulate the bladder and intestinal, and is also used as an antidote for tubocurarine and other competitive neuromuscular blocking agents. The drug used in symptomatic treatment of myasthenia gravis. Myasthenia gravis is an autoimmune disease in which antibodies recognize nicotinic cholinoreceptors on skeletal muscle. This decreases the number of functional receptors and consequently decreases the sensitivily of the muscle to acetylcholine. Muscle weakness and rapid fatigue of muscles are characteristics of the disease. Anticholinesterase agents play a key role in the diagnosis and therapy of myasthenia gravis, because they increase muscle strength. Proserinum also used in glaucoma.

The duration of action of pyridostigmine is longer than that of proserinum. It used in myasthenia gravis.

Adverse effects of these drugs include the salivation, flushing, decreased blood pressure, nausea, abdominal pain, diarrhea, bronchospasm, bradycardia.

They are contraindicated in bronchial asthma, cardiac diseases with disorders of conduction, pregnancy.

A number of synthetic organophosphate compounds have the capacity to bind covalently to acetylcholinesterase. The result is a long lasting increase in acetylcholine at all where it is released. In medical practice an ophthalmic ointment and drops of armin is used topically in the eye for the treatment of glaucoma. Its effects may last up to one week after a single administration.

Accidental poisoning by cholinesterase inhibitors can arise in many settings, since these agents are not only used clinically but also used as agricultural and household insecticides, and accidental poisoning sometimes occurs during their manufacture and use. Many of these drugs are extremely toxic and were developed by the military as nerve agents. The acute toxicity of all of these agents results from the accumulation of acetylcholine at cholinergic synapses. With increaseng inhibition of acetylcholinesterase and accumulation of acetylcholine, the first signs are muscarinic stimulation, followed by nicotinic receptor stimulation and then desensitization of nicotinic receptors. Excessive inhibition can ultimately lead to a cholinergic crisis that includes gastrointestinal distress (nausea, vomiting, diarrhea, excessive salivation), respiratory distress (bronchospasm and increased bronchial secretions), cardiovascular distress (bradycardia or tachycardia, AV-block, hypotension), visual disturbanse (miosis, blurred vision), sweating, and loss of skeletal motor function (progressing through incoordination, muscle cramps, weakness, fasciculation, and paralysis). CNS symptoms include agitation, dizziness, and mental confusion. Death usually results from paralysis of skeletal muscles required for respiration but may also result from cardiac arrest. The first step in treatment of anticholinesterase poisoning should be injection of increasing doses of atropine sulfate to block all adverse effects resulting from stimulation of muscarinic receptors. Since atropine will not alleviate skeletal and respiratory muscle paralysis, mechanical respiratory support may be required. If the poisoning is due to an organophosphate, prompt administration of dipyroxime, isonitrosine or alloxime will result in dephosphorylation of cholinesterase.

N-Cholinomimetics

N-cholinomimetics include nicotine, lobeline and cytitonum.

Nicotine is the active ingredient in tobacco. Nicotine remains important because it is second only to caffeine as the most widely used CNS stimulant and is second to alcohol as the most abused drug. In combination with the tars and carbon monoxide found in cigarette smoke, nicotine represents a serious risk factor for lung and cardiovascular disease, various cancers, diseases of the gastrointestinal tract (ulcers, gastritis).

In low doses nicotine causes ganglionic stimulation by depolarization. At high doses, nicotine causes ganglionic blockade. Low doses of nicotine produces some degree of euphoria, and arousal. High doses of nicotine result in central respiratory paralysis and severe hypotension caused by medullary paralysis. The peripheral effects of nicotine are complex. Stimulation of sympathetic ganglia increases blood pressure and heart rate. Thus use of tobacco is particularly harmful in hypertensive patients. Nicotine induced vasoconstriction can decrease coronary blood flow. Stimulation of parasympathetic ganglia also increases motor activity of the bowel. At higher doses, blood pressure falls and activity ceases in both the gastrointestinal tract and bladder musculature as a result of a nicotine-induced block of parasympathetic ganglia.

Nicotine produces myriad effects on the central nervous system, almost all of which appear to be mediated through nicotinic receptors. Additionally, nicotine influences multiple neuronal systems. One of its most prominent effects is stimulated release of dopamine, particularly in the nucleus accumbens, which is a major component of the reward system. Nicotine also stimulates the release of endogenous opioids and glucocorticoids.

Nicotine is highly-lipid soluble. Nicotine crosses the placental membrane and is secreted in the milk of lactating women. Most cigarettes contain 6 to 8 mg of nicotine. The acute lethal dose is 60 mg. Over 60% of nicotine inhaled in smoke is absorbed. Tolerance to the toxic effects of nicotine develops rapidly, often within days after beginning usage. Physical dependence on nicotine develops rapidly and is severe. Withdrawal is characterized by irritability, anxiety, restlessness, difficulty in concentrating, headaches, and insomnia. Smoking cessation programs that combine pharmacologic and behavioral therapy are the most successful in helping individuals to stop smoking. The transdermal patch and chewing gum containing nicotine have been shown to reduce nicotine-withdrawal symptoms and to help smokers stop smoking.

As the drugs lobeline and cytitonum are used in medicinal practice. The practical importance of lobeline and cytitonum is in excitation of the N-cholinoceptors of the carotid glomeruli that is accompanied by reflex stimulation of the respiratory center. That’s why they are used as breathing stimulants. Their effect is short (2-3 min) and it’s manifested only in the intravenous introduction. At the same time the cardiac output and the arterial pressure are increased as a result of secretion of epinephrine from the adrenal glands and of speeding of the impulse conduction in the sympathetic ganglia. These drugs are administered in the depression of breathing in poisonings by carbon monoxide, in drowning, postnatal asphyxia (asphyxia of newborn), and cerebral injuries; for prevention of atelectasis and pneumonia.

Drug’s name	Average therapeutic doses and routes of administration	Manufactured forms
Proserinum	Orally 0.01-0.015 g; Subcutaneously 0.0005 g; In eyes 1-2 drops	Tablets 0.015g; Ampoules with 1 ml of 0.05% solution; eye drops: 0.5% solution
Galanthamini hydrobromidum	Subcutaneously 0.0025-0.005 g	Ampoules with 1 ml of 0.1%, 0.25%, 0.5% or 1% solution
Pilocarpini hydrochloridum	In eyes: 1-2% solution (1-2 drops) or eye ointment	Eye drops: 1 or 2% solution in bottles 5 or 10 ml; 1% or 2% eye ointment
Aceclidinum	In eyes: 2-5% solution (1-2 drops) or 3-5% eye ointment; Subcutaneously 0.002 g	2-5% solution of eye drops; 3% and 5% eye ointment; Ampoules with 1 or 2 ml of 0.2% solution
Carbacholinum	In eye 1-2 drops of 0.5-1% solution	Eye drops: 0.5% or 1% solution in bottles 5 or 10 ml
Dipiroximum	Subcutaneously, intramuscularly or intravenously 0.15-0.3 g	Ampoules with 1 ml of 15% solution
Lobelini hydrochloridum	Intravenously slowly 0.005 g	Ampoules with 1 ml of 1% solution
Cytitonum	Intravenously slowly 0.5 ml	Ampoules 1 ml

M-Cholinoblockers

(Muscarinic Antagonists, Muscarinic Receptor-Blocking Drugs)

These agents selectively block M-cholinergic receptors and prevent the acethylcholine action. M-cholinoblockers are divided into alkaloids (atropine, extract or tincture of Belladonna, scopolamine, platyphyllin) and synthetic agents (metacinium, ipratropium bromide, pirenzepine, homatropine, tropicamide).

Naturally occurring substances with antimuscarinic effects have been known and used for millennia as medicines, poisons, and cosmetics. The prototype of this group is atropine. Atropine (hyoscyamine) is tertiary amine alkaloid ester of tropic acid, which is contained in the plant Atropa belladonna (deadly nightshade) and in Datura Stramonium (jimsonweed or thorn apple). Scopolamine occurs in Hyoscyamus niger, or henbane. Platyphyllin is alkaloid of Senecio rhomboides, Senecio platyphyllus or Senecio planus.

Mechanism of action. Naturally occurring atropine is
l(-) -hyoscyamine, but the pharmaceutical compound is racemic
d,l -hyoscyamine. The l(-) -isomer of alkaloid is at least 100 times more potent than the d(+) -isomer. The peripheral effects are predominantly result of action of l(-) -isomer, but the central effects are result of d(+) -isomer action.

Atropine interacts with anionic site of M cholinergic receptor. As result, the interaction between acetylcholine and receptor becomes impossible. The affinity of atropine to M cholinergic receptors is 1000 times more than affinity of acetylcholine. A molecule of atropine prevents the stimulation of 4 receptors by acetylcholine. Therefore, the antagonism between atropine and acetylcholine has one-way character. Atropine does not distinguish between the M₁, M₂, and M₃ subgroups of muscarinic receptors.

When low doses of atropine are administered, the short-term phase of stimulation of postsynaptic M cholinergic receptors precedes the phase of blockade. This short-term phase develops owing to the blockade by low doses of atropine of the presynaptic M₂ cholinergic receptors. Blockade of these receptors results in increase of neurotransmitter releasing into synaptic cleft. Thus, administration of low dose of atropine often results in initial tachycardia before the effects of peripheral vagal block become manifest.

Effects of Muscarinic Antagonists

Eye. The effects of antimuscarinic agents in the eye are opposite to effects of muscarinic agonists. Antimuscarinic antagonists block the M cholinergic receptors of pupillary constrictor muscle and cause the mydriasis. The blockage of M-cholinergic receptors of ciliary muscle results in cycloplegia (paralysis of accommodation). The atropinized eye cannot focus for near vision. In result of mydriasis and cycloplegia, the outflow of the aqueous humor from the anterior chamber is worsening. It is potentially dangerous phenomenon in patient with narrow anterior chamber angle, because can result in acute glaucoma attack.

Сardiovascular system. The sinoatrial node is very sensitive to muscarinic blockade. Therefore atropine administration results in tachycardia. But as it is noted above, the low dose of atropine can cause the initial bradycardia. The degree of increasing of heart rate depends from atropine’s dose and initial vagal tone. The children and old patients commonly exhibit the natural high heart rate, and the administration of muscarinic antagonists at them isn’t accompanied by appreciable tachycardia. The maximal tachycardia is observed in age group from 17 till 22 years.

In the presence of high vagal tone, atropine significantly facilitates the conduction through atrioventricular node and reduces the PR interval of the ECG. Because of a lesser degree of muscarinic control, the ventricles are less affected by antimuscarinic drugs at therapeutic doses. In toxic concentrations, the drugs can cause intraventricular conduction block by an unknown mechanism.

Respiratory system. Administration of antimuscarinic agents causes the bronchodilation and reduces the secretion of bronchial glands. It is necessary to note, that M-blockers are more effective in bronchospasm which is caused by cholinesterase inhibitors or by direct M-cholinomimetics. In treatment of bronchial asthma, the effect of antimuscarinic agents is less than effect of adrenomimetics.

Antimuscarinic agents are frequently used prior to administration of inhalant anesthetics to reduce the accumulation of secretions in the trachea and the possibility of laryngospasm.

Gastrointestinal tract. The muscarinic antagonists exhibit the antispasmodic action upon the gastrointestinal tract. In result of M-cholinoblockers action, both tone and motility (propulsive movements) of gastrointestinal tract are decreased. Therefore, gastric emptying time is prolonged, and intestinal transit time is lengthened. Diarrhea owing to overdose with muscarinic agonists is readily stopped, and even that caused by nonautonomic agents can usually be temporarily controlled. Antimuscaronic agents also decrease the tone of the gallbladder and sphincters of bile ducts. It results in the increase of bile discharge into intestine. Muscarinic antagonists markedly suppress the salivary secretion (dry mouth). Gastric secretion is decreased in less degree. Basal secretion is blocked more effectively than that stimulated by food, nicotine, or alcohol. Because the pancreatic and intestinal secretions are primarily under hormonal control rather than vagal one, these processes are little affected by antimuscarinic agents.

Genitourinary tract. M cholinergic antagonists relax the smooth muscles of the urinary tract and bladder wall and slow voiding. This action is useful in the treatment of spastic conditions of urinary tract which can be induced by inflammation, urolithiasis, and surgery. But antimuscarinic agents can precipitate urinary retention in patients with prostatic hyperplasia. Atropine and other muscarinic antagonists decrease the tone of uterus neck, but have no significant effect on the uterus.

Central nervous system. The usual therapeutic doses of atropine have minimal stimulant effects in central nervous system. Scopolamine has more marked effects and produces the drowsiness and amnesia (in sensitive individuals). In toxic doses, both agents can cause excitement, agitation, hallucinations, and coma. Scopolamine reduces the tremor in patients with Parkinson’s disease. Also, scopolamine is effective agent for prevention or elimination of vestibular disturbances in patients with motion sickness.

Sweat glands. Sympathetic cholinergic nerves innervate sweat glands, and their M-cholinergic receptors are readily accessible to muscarinic antagonists. Therefore, M-cholinergic blockers cause suppression of sweating. In adults, body temperature is elevated by this effect only if large doses of atropine are administered. But in infants and children even ordinary doses may result in “atropine fever”.

M-cholinoblockers differ in degree of influence upon different organs. Metacinium and atropine cause most marked bronchodilation. Platyphyllin and scopolamine have less influence upon tone of smooth muscles of bronchi. The antispasmodic action upon the smooth muscles of biliferous or urinary tracts and upon the intestine is more marked in scopolamine, atropine, and metacinium than in platyphyllin. But additionally to M-choliblockering action, platyphyllin has direct antispasmodic action. Also, platyphyllin blocks the ganglia and suppresses the vasomotor center. The action of scopolamine upon the eye and glands’ secretion is more potent than action of atropine. But duration of scopolamine's effects is less. Atropine has the longest effects upon the eye.

Metacinium is synthetic agent containing tertiary atom of nitrogen. Therefore, metacinium acts only upon peripheral M-cholinergic receptors.

Ipratropium bromide is polar water-soluble synthetic agent used only as inhalations in patients with bronchial asthma.

Pirenzepine (marketed by Boehringer Ingelheim under the trade-name Gastrozepin) is used in the treatment of peptic ulcers, as it reduces gastric acid secretion and reduces muscle spasm.

Synthetic agent homatropine is used only in ophthalmology.

The muscarinic antagonists with predominantly blocking action upon central M-cholinergic receptors (such as amizyl, benztropine mesylate) also are used in medical practice.

Therapeutic Applications

1. Atropine, metacinium, and scopolamine are used as preanesthetics (for so-called premedication). An administration of these agents prior to inhalant anesthetics decreases the accumulation of secretions in the trachea, reduces the possibility of laryngospasm, and prevents reflexive heart arrest.

2. M-blockers (atropine, metacinium, ipratropium, and tiotropium) are used for treatment of patients with bronchial asthma and patients who suffer from chronic obstructive pulmonary disease (a condition that occurs with higher frequency in older patients, particularly chronic smokers.

2. Atropine is used in bradiarrhythmias owing to disturbances of atrioventricular conduction or in marked sinus bradycardia, including arising in initial stage of myocardial infarction.

4. Atropine, plathyphyllin, metacinium, and Belladonna-containing drugs (such as tincture or extract of Belladonna) are used in spasms of smooth muscles of bowel, urinary and biliferous tracts. In case of urinary or biliary colics, agents are administered parenterally. Antimuscarinic agents also can be used in patients with diarrhea (especially in traveler’s diarrhea).

5. Nowadays, non-selective M-cholinergic blockers are rarely used for treatment of hyperacidic gastritis or of ulcer disease of stomach and duodenum. Pirenzepine (selective M₁ antagonist which blocks the presynaptic excitatory receptors on vagal nerve endings) is used in therapy of these diseases.

6. Scopolamine and central antimuscarinic agents (such as benztropine mesylate) are used in Parkinson’s disease.

7. Motion sickness is vestibular disorder respond to antimuscarinic drugs. scopolamine is one of the oldest agents for motion sickness. It can be administered by injection, by mouth, or as transdermal patch. The longest action is typical for patch – from 48 till 72 hours.

8. Antimuscarinic agents are widely used in ophthalmology with diagnostic and therapeutic aims: for examination of eye fundus, selection of spectacles, for treatment of iridocyclitis or eye’s traumas (in inflammation of iris the local using of M-cholinergic blockers prevents the accreting of iris with capsule of lens. The doctor should remember that the duration of atropine’s eye effects lasts up to 7-10 days. Effects of scopolamine lasts from 3 till 7 days; eye effects of homatropine - 1-3 days; action of tropicamide - about 6 hours.

9. Atropine is used in medical emergency for treatment of persons poisoned by cholinesterase inhibitors or muscarine.

Adverse effects

Treatment with M-blockers directed at one organ almost always induces undesirable effects in other organs. Thus, administration of antimuscarinic agents can result in dry mouth, cycloplegia, mydriasis, tachycardia, and urinary retention.

Contraindications

Contraindications to the use of muscarinic antagonists are relative, not absolute. Muscarinic antagonists are contraindicated in patients with glaucoma (especially angle-closure glaucoma), prostatic hyperplasia, dismenorrhea, ulcerative gingivitis, and stomatitis.

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