Anticholinergics

Definition

Anticholinergics are a class of medications that inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movements of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, etc. Anticholinergics are divided into three categories in accordance with their specific targets in the central and/or peripheral nervous system : antimuscarinic agents, ganglionic blockers, and neuromuscular blockers .

Purpose

Anticholinergic drugs are used to treat a variety of disorders such as gastrointestinal cramps, urinary bladder spasm, asthma, motion sickness, muscular spasms, poisoning with certain toxic compounds, and as an aid to anesthesia.

Description

Antimuscarinic agents are so called because they block muscarine, a poisonous substance found in the Amanita muscaria, a nonedible mushroom species. Muscarine is a toxic compound that competes with acetylcholine for the same cholinoreceptors. Antimuscarinic agents are atropine, scopolamine, and ipratropium bromide. Atropine and scopolamine are alkaloids naturally occurring in Atropa belladonna and Datura stramonium plants, whereas ipratropium bromide is a derivative of atropine used to treat asthma.

Under the form of atropine sulfate, atropine is used in the treatment of gastrointestinal and bladder spasm, cardiac arrhythmias, and poisoning by cholinergic toxins such as organophosphates or muscarine. Atropine is used in ophthalmology as well when the measurement of eye refractive errors (i.e., cyclopegia) is required, due to its papillary dilation properties. Scopolamine shows an effect in the peripheral nervous system similar to those of atropine. However, scopolamine is a central nervous system (CNS) depressant and constitutes a highly effective treatment to prevent motion sickness, although at high doses it causes CNS excitement with side effects similar to those caused by high doses of atropine. Its use in ophthalmology is identical in purpose to that of atropine. The main use of ipratropium is for asthma treatment. Ipratropium is also administered to patients with chronic obstructive pulmonary disease.

Benapryzine, benzhexol, orphenadrine, and bornaprine are other examples of anticholinergic drugs used alone or in combination with other medications in Parkinson's disease to improve motor function. Disturbances in dopaminergic transmissions are associated with the symptoms observed in Parkinson's disease. The beneficial effects of anticholinergics in this disease are due to the resulting imbalance between dopamine and acetylcholine ratio in neurons (e.g., levels of acetylcholine lower than dopamine levels). These anticholinergic agents may interfere with mood and also decrease gastrointestinal movements, causing constipation; and the positive effects on motor functions vary among patients. Other classes of drugs available today that act on the pathways of dopamine and its receptors to treat Parkinson's disease, such as levodopa, tolcapone, and pramipexol, effectively increase the levels of dopamine at dopaminergic receptors in neurons.

Ganglionic blockers are anticholinergic agents that target nicotinic receptors in nerve cells of either sympathetic or parasympathetic systems. The most used ganglionic blockers are trimethaphan and mecamylamine. Trimethaphan is administered by intravenous infusion for the emergency short-term control of extreme high blood pressure caused by pulmonary edema, or in surgeries that require a controlled lower blood pressure, such as the repair of an aortic aneurysm. Mecamylamine is used to treat moderately severe and severe hypertension (high blood pressure), as the drug is easily absorbed when taken orally.

Neuromuscular anticholinergic agents act on motornerve cholinoreceptors. They prevent the transmission of signals from motor nerves to neuromuscular structures of the skeletal muscle. Neuromuscular blockers are very useful as muscle relaxants in several surgical procedures, either as an adjuvant to anesthesia or as a pre-anesthetic. Their main therapeutic use is in surgical procedures. Examples of the first group are mivacurium, tubocurarine, metocurine, doxacurium, and atracurium; the second group consists of rocuronium, vecuronium, pipercuronion, and pancuronium.

Precautions

Atropine should be avoided by persons suffering from hepatitis, glaucoma, gastrointestinal obstruction, decreased liver or kidney function, and allergy to anticholinergic agents. Scopolamine is not indicated in cases of glaucoma, asthma, severe colitis, genitourinary or gastrointestinal obstruction, and myasthenia gravis , as well as people with hypersensitivity to cholinergic blockers.

The prescription of ganglionic blockers to patients with kidney insufficiency, or coronary or cerebrovascular disorders requires special caution and should only be a choice when other agents cannot be used instead.

Side effects

Atropine may cause severe adverse effects with dose-dependent degrees of severity. Overdoses of atropine, for instance, may induce delirium , hallucinations, coma, circulatory and respiratory collapse, and death. Rapid heart rate, dilation of pupils and blurred vision, restlessness, burning pain in the throat, marked mouth dryness, and urinary retention are observed with higher doses, while lower dosages may result in decreased salivary, respiratory, and perspiration secretions. Sometimes surgeons administer atropine prior to surgery due to this antisecretory property. Scopolamine's main side effects are similar to those observed with atropine.

The adverse effects of ganglionic blockers include paralysis of gastrointestinal movements, nausea, gastritis, urinary retention, and blurred vision.

Neuromuscular blockers'adverse effects may include apnea (failure in breathing) due to paralysis of the diaphragm, hypotension (low blood pressure), tachycardia, post-surgery muscle pain, increased intraocular pressure, and malignant hyperthermia (uncontrolled high fever).

Resources

BOOKS

Champe, Pamela C., and Richard A. Harvey (eds). Pharmacology, 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2000.

OTHER

"Anticholinergics/Antispasmodics (Systemic)." Yahoo! Health Drug Index. May 14, 2004 (May 22, 2004). <http://health.yahoo.com/health/drug/202049/>.

"Anticholinergics/Antispasmodics (Systemic)." Medline Plus. National Library of Medicine. May 15, 2004 (May 22, 2004). <http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202049.html>.

Sandra Galeotti, MS