Most anticholinergic medications are either tertiary amines or quaternary amines in their chemical structure.
Tertiary amines are uncharged lipid-soluble molecules. Atropine and scopolamine are tertiary amines and therefore are able to cross cell membranes readily. They are well absorbed from the gastrointestinal (GI) tract and conjunctiva and they cross the blood–brain barrier. Tertiary amines are excreted in the urine. Some belladonna derivatives and synthetic anticholinergics are quaternary amines. These drugs carry a positive charge and are lipid insoluble. Consequently, they do not readily cross cell membranes. They are poorly absorbed from the GI tract and do not cross the blood–brain barrier. Quaternary amines are excreted largely in the feces.
Mechanism of Action and Effects
These drugs act by occupying receptor sites at parasympathetic nerve endings, thereby leaving fewer receptor
sites free to respond to acetylcholine . Parasympathetic response is absent or decreased, depending on the number of receptors blocked by anticholinergic drugs and the underlying degree of parasympathetic activity. Since cholinergic muscarinic receptors are widely distributed in the body, anticholinergic drugs produce effects in a variety of locations, including the central nervous system, heart, smooth muscle,glands, and the eye.
Specific effects on body tissues and organs include:
1. Central nervous system (CNS) stimulation followed by depression, which may result in coma and death.This is most likely to occur with large doses of anticholinergic drugs that cross the blood–brain barrier (atropine,scopolamine, and antiparkinson agents).
2. Decreased cardiovascular response to parasympathetic (vagal) stimulation that slows heart rate. Atropine is the anticholinergic drug most often used for its cardiovascular effects. According to Advanced Cardiac Life Support (ACLS) protocol (2000), atropine is the drug of choice to treat symptomatic sinus bradycardia.
Low doses (<0.5 mg) may produce a slight and temporary decrease in heart rate; however, moderate to large doses (0.5 to 1 mg) increase heart rate by blocking parasympathetic vagal stimulation. Although the increase in heart rate may be therapeutic in bradycardia, it can be an adverse effect in patients with other types of heart disease because atropine increases the myocardial oxygen demand. Atropine usually has little or no effect on blood pressure. Large doses cause facial flushing be cause of dilation of blood vessels in the neck.
3.Bronchodilation and decreased respiratory tract secretions. Bronchodilating effects result from blocking the bronchoconstrictive effects of acetylcholine.When anticholinergic drugs are given systemically, spiratorysecretions decrease and may become viscous, resulting in mucous plugging of small respiratory passages.Administering the medications by inhalation decreases this effect while preserving the beneficial bronchodilation effect.
4. Antispasmodic effects in the GI tract due to decreased muscle tone and motility. The drugs have little inhibitory effect on gastric acid secretion with usual doses and insignificant effects on pancreatic and
intestinal secretions.
5. Mydriasis and cycloplegia in the eye. Normally, anticholinergics do not change intraocular pressure, but with narrow-angle glaucoma, they may increase intraocular pressure and precipitate an episode of acute glaucoma. When the pupil is fully dilated, photophobia may be bothersome, and reflexes to light and accommodation may disappear.
6. Miscellaneous effects include decreased secretions from salivary and sweat glands; relaxation of ureters,
urinary bladder, and the detrusor muscle; and relaxation of smooth muscle in the gallbladder and bile ducts.
The clinical usefulness of anticholinergic drugs is limited by their widespread effects. Consequently, several synthetic drugs have been developed in an effort to increase selectivity of action on particular body tissues, especially to retain the antispasmodic and antisecretory effects of atropine while eliminating its adverse effects. This effort has been less than successful—all the synthetic drugs produce atropine like adverse effects when given in sufficient dosage.
One group of synthetic drugs is used for antispasmodic effects in GI disorders. Another group of synthetic drugs includes centrally active anticholinergics used in the treatment of Parkinson’s disease . They balance the relative cholinergic dominance that causes the movement disorders associated with parkinsonism.
Indications for Use
Anticholinergic drugs are used for disorders in many body systems. Clinical indications for use of anticholinergic drugs include GI, genitourinary, ophthalmic and respiratory disorders, bradycardia,and Parkinson’s disease. They also are used before surgery and bronchoscopy. Drugs at a Glance:
Selected Anticholinergic Drugs describes the therapeutic use,dosage and route of administration of selected anticholinergic medications.
• GI disorders in which anticholinergics have been used include peptic ulcer disease, gastritis,pylorospasm, diverticulitis, ileitis, and ulcerative colitis. These conditions are often characterized by excessive gastric acid and abdominal pain because of increased motility and spasm of GI smooth muscle. In peptic ulcer disease more effective drugs have been developed,and anti cholinergics are rarely used. The drugs are weak inhibitors
of gastric acid secretion even in maximal doses (which usually produce intolerable adverse effects).
Although they do not heal peptic ulcers, they may relieve abdominal pain by relaxing GI smooth muscle.
Anticholinergics may be helpful in treating irritable colon or colitis, but they may be contraindicated in chronic inflammatory disorders (eg, diverticulitis, ulcer ative colitis) or acute intestinal infections (eg, bacterial viral, amebic). Other drugs are used to decrease diarrhea and intestinal motility in these conditions.
• In genitourinary disorders, anticholinergic drugs may be given for their antispasmodic effects on smooth muscle to relieve the symptoms of urinary incontinence and frequency that accompany an overactive bladder. In infections such as cystitis, urethritis,and prostatitis, the drugs decrease the frequency and pain of urination. The drugs are also given to increase bladder capacity in enuresis, paraplegia, or neurogenic bladder.
• In ophthalmology, anticholinergic drugs are applied topically for mydriatic and cycloplegic effects to aid examination or surgery. They are also used to treat some inflammatory disorders. Anticholinergic preparations used in ophthalmology
• In respiratory disorders characterized by bronchoconstriction (ie, asthma, chronic bronchitis), ipratropium
(Atrovent) may be given by inhalation for bronchodilating effects .
• In cardiology, atropine may be given to increase heart rate in bradycardia and heart block characterized by hypotension and shock.
• In Parkinson’s disease, anticholinergic drugs are given for their central effects in decreasing salivation,spasticity, and tremors. They are used mainly in clients who have minimal symptoms, who do not respond to levodopa, or who cannot tolerate levodopa because of adverse reactions or contraindications. An additional use of anticholinergic drugs is to relieve Parkinson-like symptoms that occur with older antipsychotic drugs.
• Before surgery, anticholinergics are given to prevent vagal stimulation and potential bradycardia, hypotension, and cardiac arrest. They are also given to reduce respiratory tract secretions, especially in head and neck surgery and bronchoscopy.
Contraindications to Use
Contraindications to the use of anticholinergic drugs include any condition characterized by symptoms that would be aggravated by the drugs. Some of these are prostatic hypertrophy,myasthenia gravis, hyperthyroidism, glaucoma, tachyarrhythmias, myocardial infarction, and heart failure unless bradycardia is present. They should not be given in hiatal hernia or otherconditions contributing to reflux esophagitis because the drugs delay gastric emptying, relax the cardioesophageal sphincter,and increase esophageal reflux.
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