The parasympathetic nervous system is the branch of the autonomic nervous system with nerve functions generally opposite those of the sympathetic nervous system (see Chapters 18 and 19 for a discussion of the sympathetic nervous system). Acetylcholine is the neurotransmitter responsible for the transmission of nerve impulses to effector cells in the parasympathetic nervous system. A cholinergic receptor is one that binds acetylcholine and mediates its actions. This chapter focuses on cholinergic-blocking drugs, which inhibit the effects of the parasympathetic nervous system.

Cholinergic blockers, anticholinergics, parasympatholytics, and antimuscarinic drugs are all terms that refer to the class of drugs that block or inhibit the actions of acetylcholine in the parasympathetic nervous system. These drugs were first discussed in Chapter 15 in relation to treatment of Parkinson’s disease.

Cholinergic blockers have many therapeutic uses and are one of the oldest groups of therapeutic drugs. Originally they were derived from various plant sources, but today they are only part of a larger group of cholinergic blockers that also include synthetic and semisynthetic drugs. Box 21-1 lists the currently available cholinergic blockers.

Cholinergic-blocking drugs block the action of the neurotransmitter acetylcholine at the muscarinic receptors in the parasympathetic nervous system (PNS). Acetylcholine that is released from a stimulated nerve fiber is then unable to bind to the receptor site and fails to produce a cholinergic effect. This is why the cholinergic blockers are also referred to as anticholinergics. Blocking the parasympathetic nerves allows the sympathetic (adrenergic) nervous system to dominate. Because of this, cholinergic blockers have many of the same effects as the adrenergics (see Chapter 18). Figure 21-1 illustrates the site of action of the cholinergic blockers in the parasympathetic nervous system.

The major sites of action of the anticholinergics are the heart, respiratory tract, gastrointestinal (GI) tract, urinary bladder, eye, and exocrine glands (sweat gland, salivary gland). Anticholinergics have the opposite effects of the cholinergics (see Chapter 20) at these sites of action. Anticholinergic effects on the cardiovascular system are seen as an increase in heart rate. Respiratory system effects are dry mucous membranes and bronchial dilation. In the GI tract, cholinergic blockers cause a decrease in GI motility, GI secretions, and salivation. In the genitourinary (GU) system, they lead to decreased bladder contraction, which can result in urinary retention. In the skin they reduce sweating, and finally, anticholinergics cause the pupils to dilate and increase intraocular pressure. This occurs because the ciliary muscles and the sphincter muscle of the iris are innervated by cholinergic nerve fibers. Cholinergic blockers keep the sphincter muscle of the iris from contracting. The result is dilation of the pupil (mydriasis) and paralysis of the ocular lens (cycloplegia). This can be detrimental to patients with glaucoma because it results in increased intraocular pressure (see Chapter 57). These and other effects are listed by body system in Table 21-1. Many of the cholinergic-blocking drugs are available in a variety of forms, including intravenous, intramuscular, oral, and subcutaneous preparations.

In the central nervous system, cholinergic blockers have the therapeutic effect of decreasing muscle rigidity and diminishing tremors. This is of benefit in the treatment of both Parkinson’s disease (see Chapter 15) and drug-induced extrapyramidal reactions such as those associated with antipsychotic drugs (see Chapter 16). These conditions involve dysfunction of the extrapyramidal parts of the brain and include motor dysfunctions such as chorea, dystonia, and dyskinesia.

Cardiovascular effects of anticholinergics are related to their cholinergic-blocking actions on the heart’s conduction system. At low dosages, the anticholinergics may actually slow the heart rate through their effects on the cardiac center in the portion of the brain called the medulla. At high dosages, cholinergic blockers block the inhibitory vagal (i.e., parasympathetic or cholinergic) effects on the pacemaker cells of the sinoatrial and atrioventricular nodes, which leads to acceleration of the heart rate due to unopposed sympathetic activity. Atropine is used primarily in the management of cardiovascular disorders, such as in the diagnosis of sinus node dysfunction, the treatment of patients with symptomatic second-degree atrioventricular block, and provision of advanced life support in the treatment of sinus bradycardia that is accompanied by hemodynamic compromise. It also has ophthalmic uses (see Chapter 57).

When the cholinergic stimulation of the parasympathetic nervous system is blocked by cholinergic blockers, the sympathetic nervous system effects go unopposed. In the respiratory tract, this results in decreased secretions from the nose, mouth, pharynx, and bronchi. It also causes relaxation of the smooth muscles in the bronchi and bronchioles, which results in decreased airway resistance and bronchodilation. Because of this, the cholinergic blockers have proved beneficial in treating exercise-induced bronchospasm, chronic bronchitis, asthma, and chronic obstructive pulmonary disease. They are also used preoperatively to reduce salivary secretions, which aids in intubation and other procedures (e.g., endoscopy) involving the oral cavity.

Gastric secretions and the smooth muscles responsible for producing gastric motility are both controlled by the parasympathetic nervous system, which is primarily under the control of muscarinic receptors. Cholinergic blockers antagonize these receptors, causing reduced secretions, relaxation of smooth muscle, and reduced GI motility and peristalsis. For these reasons, cholinergic blockers are commonly used in the treatment of irritable bowel disease and GI hypersecretory states.

Anticholinergics are useful in the treatment of such GU tract disorders as reflex neurogenic bladder and incontinence. They relax the detrusor muscles of the bladder and increase constriction of the internal sphincter. The ability of cholinergic blockers to decrease glandular secretions also makes them potentially useful drugs for reducing gastric and pancreatic secretions in patients with acute pancreatitis.

Anticholinergic drugs cause widely varied adverse effects, with many body systems affected. The various adverse effects of cholinergic blockers are listed by body system in Table 21-2. Certain patient populations are more susceptible to the effects of the anticholinergics. These populations include infants, children with Down syndrome, those with spastic paralysis or brain damage, and the elderly. The elderly are extremely sensitive to the CNS effects of anticholinergics, and it is not uncommon for elderly patients to develop delirium due to anticholinergic effects.

Drug interactions most commonly reported for the anticholinergics are additive anticholinergic effects when taken with other drugs that possess anticholinergic side effects such as amantadine (see Chapter 15), antihistamines (see Chapter 36), and tricyclic antidepressants (see Chapter 16). Reduced antipsychotic effects of phenothiazines (see Chapter 16) are seen when taken with anticholinergic drugs, and increased effects of digoxin (see Chapter 24) are seen when combined with anticholinergics.

For dosage information on selected cholinergic blockers, see the table on p. 338.