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ORGANIZATION OF CLASS

Although I have titled this chapter “Cholinergic Agonists,” this chapter, in fact, considers all the drugs that increase activity in cholinergic neurons, sometimes called cholinomimetics (because they mimic the action of acetylcholine). There are two main targets of drug action: the postsynaptic receptor and the acetylcholinesterase enzyme, which breaks down acetylcholine.

Cholinergic agonists have a direct action on the receptor for acetylcholine. Some drugs are specific for the muscarinic receptor; others are specific for the nicotinic receptor.

First, remind yourself where the nicotinic and muscarinic receptors are found:

  • Nicotinic receptors are found in autonomic ganglia and at the neuromuscular junction.

  • Muscarinic receptors are found on the target organs of the parasympathetic nervous system.

Of course, there are other cholinergic receptors, such as those located in the central nervous system (CNS) and in sweat glands innervated by the sympathetic nervous system. Concentrate on learning the basics and add the others later.

The cholinesterase inhibitors act by blocking the metabolism of acetylcholine. These drugs effectively increase the concentration of acetylcholine at all cholinergic synapses.

The enzyme that is specific for acetylcholine is called acetylcholinesterase, and it is found on both the pre- and postsynaptic membranes. There are other cholinesterases (pseudocholinesterase or nonspecific cholinesterase) that are abundant in the liver and can metabolize acetylcholine and drugs with related structures. The structure and biochemistry of acetylcholinesterase is well studied and an interesting story. Details can be found in most textbooks.

First, review the actions of cholinergic receptor activation.

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Activation of Muscarinic Receptors

Eye

Cardiovascular

Respiratory

Gastrointestinal (GI)

Genitourinary (GU)

Glands

Miosis (constriction of pupil)

Decrease in heart rate

Bronchial constriction and increased secretions

Increased motility, relaxation of sphincters

Relaxation of sphincters and bladder wall contraction

Increased secretions

Activation of Nicotinic Receptors
Muscle Fasciculations and weakness

CHOLINERGIC AGONISTS

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ESTERS ALKALOIDS

BETHANECHOL

carbachol

methacholine

cevimeline (ring structure)

arecoline

muscarine

pilocarpine

These drugs are traditionally divided into two groups: esters of choline that are structurally related to acetylcholine (indicated by “-chol-” in their names), and alkaloids that are not related to acetylcholine and are generally plant derivatives. The only reason that this distinction is important is that the alkaloids, because of their complex structure, are not metabolized by cholinesterases.

The effects of all of these agents are exclusively muscarinic.

The preceding statement is sweeping and not entirely true. However, the therapeutically useful drugs in reasonable concentrations are muscarinic. The effects of these drugs were listed earlier, but also can be deduced from your knowledge of the parasympathetic nervous system. The differences between the drugs are related to their resistance to cholinesterase activity and any activity at ...

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