Introduction to Autonomic Pharmacology

Introduction to Autonomic Pharmacology

The nervous system is conventionally divided into the central nervous system (CNS; the brain and spinal cord) and the periph-eral nervous system (PNS; neuronal tissues outside the CNS). The motor (efferent) portion of the nervous system can be divided into two major subdivisions: autonomic and somatic. The autonomic nervous system (ANS) is largely independent (autonomous) in that its activities are not under direct conscious control. It is concerned primarily with visceral functions such as cardiac output, blood flow to various organs, and digestion, which are necessary for life. Evidence is accumulating that the ANS, especially the vagus nerve, also influences immune func-tion and some CNS functions such as seizure discharge. The somatic subdivision is largely concerned with consciously con-trolled functions such as movement, respiration, and posture. Both systems have important afferent (sensory) inputs that pro-vide information regarding the internal and external environments and modify motor output through reflex arcs of varying size and complexity. The nervous system has several properties in common with the endocrine system, which is the other major system for control of body function. These include high-level integration in the brain, the ability to influence processes in distant regions of the body, and extensive use of negative feedback. Both systems use chemi-cals for the transmission of information. In the nervous system, chemical transmission occurs between nerve cells and between nerve cells and their effector cells. Chemical transmission takes place through the release of small amounts of transmitter sub-stances from the nerve terminals into the synaptic cleft. The trans-mitter crosses the cleft by diffusion and activates or inhibits the postsynaptic cell by binding to a specialized receptor molecule. In a few cases, retrograde transmission may occur from the postsyn-aptic cell to the presynaptic neuron terminal and modify its sub-sequent activity.By using drugs that mimic or block the actions of chemical transmitters, we can selectively modify many autonomic functions. These functions involve a variety of effector tissues, including cardiac muscle, smooth muscle, vascular endothelium, exocrine glands, and presynaptic nerve terminals. Autonomic drugs are use-ful in many clinical conditions. Unfortunately, a very large num-ber of drugs used for other purposes have unwanted effects on autonomic function (see Case Study).

CASE STUDY

A teenage boy is seen at the office of a dental surgeon for extraction of an impacted wisdom tooth. He is so nervous that the dentist decides to administer a sedative to calm the boy. After intravenous administration of the sedative (pro-methazine), the boy relaxes and the extraction is accom-plished with no complications. However, when the boy stands up from the dental chair, he turns very pale and faints. Lying on the floor, he rapidly regains consciousness, but has a rapid heart rate of 120 bpm and a blood pressure of only 110/70 mm Hg. When he sits up, his heart rate increases to 140 bpm, his pressure drops to 80/40 mm Hg, and he com-plains of faintness. He is helped to a couch in the reception area, where he rests for 30 minutes. At the end of this time the boy is able to sit up without symptoms and, after an addi-tional 15 minutes, is able to stand without difficulty. What autonomic effects might promethazine have that would explain the patient’s signs and symptoms? Why did his heart rate increase when his blood pressure dropped?