Chapter 19: Cholinergic Drugs

INTRODUCTION

Cholinergic drugs affect the activity at cholinergic synapses—that is, synapses using acetylcholine as a neurotransmitter. Cholinergic synapses are important in several physiological systems. As discussed in Chapter 18, acetylcholine is one of the primary neurotransmitters in the autonomic nervous system (ANS), especially in the parasympathetic autonomic division. Consequently, physicians administer many of the drugs discussed in this chapter to alter the response of various tissues to autonomic parasympathetic control. Acetylcholine is also the neurotransmitter at the skeletal neuromuscular junction. Certain cholinergic stimulants are used to treat a specific problem at the skeletal neuromuscular junction (e.g., myasthenia gravis). The brain contains cholinergic synapses in specific areas, and some anticholinergic drugs decrease the symptoms of diverse problems such as parkinsonism and motion sickness. Cholinergic stimulants effectively increase activity at acetylcholine synapses, whereas anticholinergic drugs decrease synaptic activity. Cholinergic stimulants and anticholinergic agents can be further characterized according to functional or pharmacodynamic criteria, and these criteria will be discussed as well.

Considering the diverse clinical applications of cholinergic and anticholinergic agents, you will likely encounter patients taking these drugs. Knowledge of the pharmacodynamics of these medications will enable you to understand the therapeutic rationale behind drug administration as well as the patient’s response to the drug.

CHOLINERGIC RECEPTORS

Many autonomic cholinergic drugs affect synaptic activity by interacting with the acetylcholine receptor located on the postsynaptic membrane. At each cholinergic synapse, postsynaptic receptors are responsible for recognizing the acetylcholine molecule and transducing the chemical signal into a postsynaptic response. As discussed in Chapter 18, cholinergic receptors can be subdivided into muscarinic and nicotinic receptors according to their affinity for certain drugs.¹

Muscarinic cholinergic receptors are generally found on the peripheral tissues supplied by parasympathetic postganglionic neurons—that is, on effector organs such as the gastrointestinal (GI) tract, urinary bladder, heart, eye, and so on. Acetylcholine synapses found in specific areas of the central nervous system (CNS) also use the muscarinic subtype of cholinergic receptor. Nicotinic cholinergic receptors are located in the autonomic ganglia (i.e., the N_N nicotinic subtype) and at the skeletal neuromuscular junction (the N_M nicotinic subtype). Refer to Chapter 18 for a more detailed discussion of cholinergic receptor subclassification.

The existence of these different varieties of cholinergic receptors is important pharmacologically. Some drugs are relatively specific for a certain cholinergic receptor subtype, whereas others tend to bind rather indiscriminately to all cholinergic receptors. Obviously, specific drugs are preferable because they tend to produce a more precise response with fewer side effects. However, specificity is only a relative term, and drugs that bind preferentially to one receptor subtype may still produce a variety of responses.

CHOLINERGIC STIMULANTS

Cholinergic stimulants increase activity at acetylcholine synapses. Chemically, many agents are capable of potently and effectively stimulating cholinergic activity. However, only a few drugs exhibit sufficient safety and ...