McKenna's Pharmacology for Nursing, 2e

488 P A R T 5  Drugs acting on the autonomic nervous system C holinergic agonists act at the same site as the neuro- transmitter acetylcholine (ACh) and increase the activity of the ACh receptor sites throughout the body. Because these sites are found extensively throughout the para- sympathetic nervous system, their stimulation produces a response similar to what is seen when the parasym- pathetic system is activated. As a result, these drugs are often called parasympathomimetic because their action mimics the action of the parasympathetic nervous system. Because the action of these drugs cannot be limited to a specific site, their effects can be widespread throughout the body, and they are usually associated with many undesirable systemic effects. Cholinergic agonists work either directly or indi- rectly. Direct-acting cholinergic agonists occupy receptor sites for ACh on the membranes of the effector cells of the postganglionic cholinergic nerves, causing increased stimulation of the cholinergic receptor. In contrast, indirect-acting cholinergic agonists cause increased stimulation of the ACh receptor sites by reacting with the enzyme acetylcholinesterase and preventing it from breaking down the ACh that was released from the nerve. These drugs produce their effects indirectly by producing an increase in the level of ACh in the synaptic

cleft, leading to increased stimulation of the cholinergic receptor site (Figure 32.1). See Box 32.1 for use of these drugs across the lifespan.

DIRECT-ACTING CHOLINERGIC AGONISTS The direct-acting cholinergic agonists are similar to ACh and react directly with receptor sites to cause the same reaction as if ACh had stimulated the receptor sites. These drugs usually stimulate muscarinic recep- tors within the parasympathetic system. They are used as systemic agents to increase bladder tone, urinary excretion and GI secretions, and as ophthalmic agents to induce miosis to relieve the increased intraocular pressure of glaucoma (see Table 32.1). Systemic absorp- tion usually does not occur when these drugs are used ophthalmically. Direct-acting cholinergic agonists include bethane- chol ( Urocarb ), carbachol ( Isopto Carbachol , Miostat ) and pilocarpine ( Isopto Carpine ). These agents are used infrequently today because of their widespread para- sympathetic activity. More-specific and less-toxic drugs are now available and preferred.

Effects of cholinergic drugs

Pharmacodynamics of cholinergic drugs

Lens accommodation Pupil constriction lacrimal secretions and salivation synaptate effect

1 2

Acetyl CoA + Choline (from diet)

3

Nerve terminal

4

Enzyme

secretions rate contractility conduction

ACh

Choline + Acetic acid

ACh

Indirect-acting cholinergic drugs block acetylcholin- esterase leading to increased ACh in synapse

Ca +

secretions

Ca +

motility

Muscarinic or nicotinic cholinergic receptor

Acetylcholinesterase

sphincter constriction

Direct-acting cholinergic drugs stimulate receptor directly

Muscle contraction

Sphincter relaxation

Neuron or effector cell

Vasodilation

Neuromuscular junction; causes muscle contraction

5

Oculomotor n. Facial n. Glossopharygeal n.

1

2

3

Vagus n. Pelvic n.

4 5

FIGURE 32.1  Pharmacodynamics of cholinergic drugs and associated physiological responses.