Autonomic Nervous System and Drugs

• The autonomic nervous system (ANS) and the endocrine system coordinate bodily functions, with the ANS using rapid electrical impulses and neuromediator substances, while the endocrine system uses blood-borne hormones.
• Autonomic drugs exert their effects by either stimulating or blocking the actions of the ANS.
• The nervous system is divided into the central nervous system (CNS), comprising the brain and spinal cord, and the peripheral nervous system, which includes neurons outside the CNS.
• The peripheral nervous system has efferent neurons that carry signals from the CNS to the periphery and afferent neurons that bring information from the periphery to the CNS.
• Afferent neurons provide sensory input that modulates the efferent division through reflex arcs.

Functional Divisions of the Nervous System

• The efferent portion of the peripheral nervous system is divided into the somatic nervous system (voluntary control of skeletal muscles) and the ANS (involuntary regulation of vital functions).
• The ANS, also known as the visceral, vegetative, or involuntary nervous system, controls smooth muscle, cardiac muscle, vasculature, and exocrine glands, regulating digestion, cardiac output, blood flow, and glandular secretions.

Anatomy of the ANS

• The ANS uses two types of efferent neurons: preganglionic neurons (cell body in the CNS) and postganglionic neurons (cell body in ganglia outside the CNS), with ganglia acting as relay stations.
• Afferent neurons in the ANS are crucial for reflex regulation and signaling the CNS to influence the efferent branch.
• The efferent ANS consists of the sympathetic, parasympathetic, and enteric nervous systems, each originating in different regions of the CNS.
• Sympathetic preganglionic neurons originate in the thoracic and lumbar regions (T1 to L2) of the spinal cord and synapse in ganglia close to the spinal cord; they are short compared to the postganglionic neurons.
• Sympathetic preganglionic nerve endings are highly branched, allowing one neuron to interact with many postganglionic neurons, enabling activation of numerous effector organs simultaneously.
• The adrenal medulla receives preganglionic fibers from the sympathetic system and secretes epinephrine (adrenaline) and norepinephrine into the blood upon stimulation by acetylcholine.
• Parasympathetic preganglionic fibers arise from cranial nerves III, VII, IX, and X, as well as the sacral region (S2 to S4) of the spinal cord, synapsing in ganglia near or on the effector organs.
• Parasympathetic preganglionic fibers are long, and postganglionic fibers are short, with a one-to-one connection between preganglionic and postganglionic neurons, allowing for discrete responses.
• The enteric nervous system, the third division of the ANS, innervates the GI tract, pancreas, and gallbladder, functioning independently of the CNS to control motility, secretions, and microcirculation; it is modulated by the sympathetic and parasympathetic systems.

Functions of the Sympathetic Nervous System

• The sympathetic division adjusts in response to stressors like trauma, fear, hypoglycemia, cold, and exercise.
• Stimulation of the sympathetic division increases heart rate and blood pressure, mobilizes energy stores, and increases blood flow to skeletal muscles and the heart while diverting flow from the skin and internal organs.
• Sympathetic stimulation dilates pupils and bronchioles and affects GI motility, bladder function, and sexual organs.
• The fight-or-flight response is triggered by direct sympathetic activation and stimulation of the adrenal medulla to release epinephrine and norepinephrine, promoting responses in adrenergic receptors.
• The sympathetic nervous system functions as a unit, often discharging as a complete system during severe exercise or fear reactions, and is involved in a wide range of physiologic activities.
• While not essential for survival, the sympathetic system prepares the body to handle uncertain situations and unexpected stimuli.

Functions of the Parasympathetic Nervous System

• The parasympathetic division maintains homeostasis within the body and is required for essential bodily functions like digestion and waste elimination.
• The parasympathetic division opposes or balances the actions of the sympathetic division, predominating in "rest-and-digest" situations.
• The parasympathetic system never discharges as a complete system.
• Parasympathetic fibers innervating specific organs are activated separately to affect those organs individually.

Role of the CNS in Autonomic Functions

• The ANS requires sensory input from peripheral structures to provide information on the body's current state.
• Afferent impulses from viscera and other autonomically innervated structures travel to integrating centers in the CNS, such as the hypothalamus, medulla oblongata, and spinal cord which respond with efferent reflex impulses via the ANS.

Innervation by the ANS

• Most organs are innervated by both the sympathetic and parasympathetic divisions, with one system usually predominating, such as the vagus nerve in controlling heart rate.
• Dynamic antagonism between the two systems is fine-tuned to control homeostatic organ functions.
• Some effector organs, like the adrenal medulla, kidney, pilomotor muscles, and sweat glands, receive innervation only from the sympathetic system.

Somatic Nervous System

• The efferent somatic nervous system consists of a single myelinated motor neuron originating in the CNS and traveling directly to skeletal muscle without ganglia mediation.
• The somatic nervous system is under voluntary control, whereas the ANS is involuntary.
• Responses in the somatic division are generally faster than those in the ANS.
• The sympathetic nervous system is widely distributed, innervating practically all effector systems, while the parasympathetic division is more limited.
• Sympathetic preganglionic fibers have a broader influence and synapse with more postganglionic fibers, allowing for a diffuse discharge.
• The parasympathetic division is more circumscribed, with mostly one-to-one interactions, and ganglia close to or within organs, limiting branching.

Chemical Signaling Between Cells

• Neurotransmission in the ANS is an example of chemical signaling between cells, including hormone secretion and local mediator release.
• Hormones are secreted into the bloodstream and exert effects on broadly distributed target cells.
• Local mediators act locally on cells in the immediate environment and are rapidly destroyed or removed (examples: histamine and prostaglandins).
• Neurotransmitters are released from nerve terminals, triggered by action potentials, and diffuse across the synaptic cleft to combine with specific receptors on the postsynaptic cell.
• Neurotransmitters, hormones, and local mediators bind to specific receptors on the cell surface of target organs.
• Common neurotransmitters include norepinephrine, epinephrine, acetylcholine, dopamine, serotonin, histamine, glutamate, and γ-aminobutyric acid.
• Acetylcholine and norepinephrine are the primary chemical signals in the ANS, while a wide variety of neurotransmitters function in the CNS.
• Cholinergic neurons mediate transmission via acetylcholine at autonomic ganglia, the adrenal medulla, parasympathetic postganglionic nerves to effector organs, and the neuromuscular junction in the somatic nervous system.
• Adrenergic fibers use norepinephrine and epinephrine as neurotransmitters, with norepinephrine mediating transmission from sympathetic postganglionic nerves to effector organs.

Signal Transduction in the Effector Cell

• Binding of chemical signals to receptors activates enzymatic processes, resulting in cellular responses like phosphorylation of intracellular proteins or changes in ion channel conductivity.
• Second messenger molecules translate the extracellular signal into a response, often amplified within the cell.

Membrane Receptors Affecting Ion Permeability (Ionotropic Receptors)

• Some receptors are directly linked to membrane ion channels, leading to rapid changes in ion permeability upon neurotransmitter binding.
• These types of receptors are known as ionotropic receptors.

Membrane Receptors Coupled to Second Messengers (Metabotropic Receptors)

• Many receptors signal neurotransmitter recognition by initiating a series of reactions that result in a specific intracellular response.
• Second messenger molecules intervene between the neurotransmitter and the cellular effect, often involving a G protein.
• The two most widely recognized second messenger systems are the adenylyl cyclase system and the calcium/phosphatidylinositol system.
• Receptors coupled to the second messenger system are known as metabotropic receptors (examples: muscarinic and adrenergic receptors).