32 Sympathetic Effect
The neurochemistry of the sympathetic system is based on the adrenergic system. Norepinephrine and epinephrine influence target effectors by binding to the α-adrenergic or β-adrenergic receptors. Drugs that affect the sympathetic system affect these chemical systems. The drugs can be classified by whether they enhance the functions of the sympathetic system or interrupt those functions. A drug that enhances adrenergic function is known as a sympathomimetic drug, whereas a drug that interrupts adrenergic function is a sympatholytic drug.
Sympathomimetic Drugs
When the sympathetic system is not functioning correctly or the body is in a state of homeostatic imbalance, these drugs act at postganglionic terminals and synapses in the sympathetic efferent pathway. These drugs either bind to particular adrenergic receptors and mimic norepinephrine at the synapses between sympathetic postganglionic fibers and their targets, or they increase the production and release of norepinephrine from postganglionic fibers. Also, to increase the effectiveness of adrenergic chemicals released from the fibers, some of these drugs may block the removal or reuptake of the neurotransmitter from the synapse.
A common sympathomimetic drug is phenylephrine, which is a common component of decongestants. It can also be used to dilate the pupil and to raise blood pressure. Phenylephrine is known as an α1-adrenergic agonist, meaning that it binds to a specific adrenergic receptor, stimulating a response. In this role, phenylephrine will bind to the adrenergic receptors in bronchioles of the lungs and cause them to dilate. By opening these structures, accumulated mucus can be cleared out of the lower respiratory tract. Phenylephrine is often paired with other pharmaceuticals, such as analgesics, as in the “sinus” version of many over-the-counter drugs, such as Tylenol Sinus® or Excedrin Sinus®, or in expectorants for chest congestion such as in Robitussin CF®.
A related molecule, called pseudoephedrine, was much more commonly used in these applications than was phenylephrine, until the molecule became useful in the illicit production of amphetamines. Phenylephrine is not as effective as a drug because it can be partially broken down in the digestive tract before it is ever absorbed. Like the adrenergic agents, phenylephrine is effective in dilating the pupil, known as mydriasis. Phenylephrine is used during an eye exam in an ophthalmologist’s or optometrist’s office for this purpose. It can also be used to increase blood pressure in situations in which cardiac function is compromised, such as under anesthesia or during septic shock.
Other drugs that enhance adrenergic function are not associated with therapeutic uses, but affect the functions of the sympathetic system in a similar fashion. Cocaine primarily interferes with the uptake of dopamine at the synapse and can also increase adrenergic function. Caffeine is an antagonist to a different neurotransmitter receptor, called the adenosine receptor. Adenosine will suppress adrenergic activity, specifically the release of norepinephrine at synapses, so caffeine indirectly increases adrenergic activity. There is some evidence that caffeine can aid in the therapeutic use of drugs, perhaps by potentiating (increasing) sympathetic function, as is suggested by the inclusion of caffeine in over-the-counter analgesics such as Excedrin®.
