AUTONOMIC NERVOUS SYSTEM

Principles of Neuropharmacology and Synaptic Transmission

  • Target Sites in Neuropharmacology:

    • Drugs affecting the nervous system act specifically by altering the axon, synaptic transmission, or receptors.

  • Sequential Steps in Synaptic Transmission:

    • Neurotransmitter Synthesis:

      1. SYNTHESIS = Neurotransmitters are synthesized within the presynaptic cell.

      2. STORAGE = They are prepackaged and stored in vesicles, rather than produced on demand, ensuring immediate release when signaled.

      3. RELEASE = Triggered by an action potential, the presynaptic cell releases neurotransmitters into the synaptic cleft.

      4. BINDING = Transmitters diffuse across the synapse and bind to specific post-junctional receptors on the postsynaptic cell or target organ.

      5. TERMINATION = Neurotransmitter action is terminated to clear the synapse through one of three physiological mechanisms:

        • Reuptake: Active pump mechanisms pull the intact neurotransmitter back into the presynaptic neuron.

        • Enzymatic Degradation: Specific enzymes in the synaptic cleft break down the neurotransmitter.

        • Diffusion: Molecules diffuse away from the immediate synaptic cleft, moving far enough from receptors that they can no longer elicit an effect.

Autonomic Nervous System Overview and Physiological Functions

  • Three Principal Functions of the Autonomic Nervous System (ANS):

    1. Cardiovascular Regulation: Regulates the heart and systemic cardiovascular system.

    2. Glandular Secretion Regulation: Regulates secretory glands, including salivary, gastric, sweat, and bronchial glands.

    3. Smooth Muscle Regulation: Regulates smooth muscle across the pulmonary system (lungs), vascular system (blood vessels), urogenital system, and gastrointestinal (GI) tract.

Physiological Comparisons: Parasympathetic vs. Sympathetic Nervous System

  • Parasympathetic Nervous System (PNS):

    • "rest and digest" division

    • Primary actions include:

      • Slower, resting heart rate.

      • Promoted gastric and digestive secretions.

      • Facilitated emptying of the bowel and urinary bladder.

      • Accommodation of the eye for near vision and pupil constriction (miosis).

      • Contraction of bronchial smooth muscle (bronchoconstriction), as reduced oxygen demand eliminates the need for wide, open airways.


  • Sympathetic Nervous System (SNS):

    • "fight or flight" division

    • Baseline/Continuous Functions:

      • Cardiovascular system regulation

        • Maintaining adequate blood flow to the brain at all times.

        • Redistributing blood flow dynamically to demands (e.g., shunting blood away from digestion toward skeletal muscle during physical exertion or stress)

        • Compensating for acute blood loss during hemorrhage to sustain life initially.

      • Body temp. regulation

        • Regulating cutaneous blood flow

        • Stimulating sweat gland secretions

        • Inducing piloerection ("goosebumps")

      • “Fight or Flight”

        • Increasing heart rate and systemic blood pressure.

        • Shunting blood away from non-essential regions (skin and visceral organs) toward vital organs and active skeletal muscle.

        • Dilating bronchial airways (bronchodilation) to optimize oxygen delivery.

        • Dilating pupils (mydriasis) to maximize distant visual field acuity (e.g., scanning for threats).

        • Mobilizing stored energy reserves by rapidly stimulating hepatic glucose release into the bloodstream.

Systemic Organ Effects of the ANS

  • Eyes:

    • SNS: Pupil dilation (mydriasis) to focus on distant vision.

    • PNS: Pupil constriction (miosis) and vision accommodation for near vision.

  • Salivary Glands:

    • SNS: Produces sparse, thicker, mucus-rich secretions.

    • PNS: Produces abundant, watery, profuse salivation.

  • Sweat Glands:

    • SNS: Significantly increases sweat production (mediated uniquely via acetylcholine binding to muscarinic receptors).

    • PNS: No functional innervation or effect.

  • Peripheral Blood Vessels:

    • SNS: Vasoconstriction secondary to alpha-1 receptor stimulation, elevating systemic vascular resistance.

    • PNS: Minimal to no direct functional innervation.

  • Heart:

    • SNS: Increases heart rate (chronotropy), myocardial contractility (inotropy), and electrical conduction velocity (dromotropy).

    • PNS: Decreases heart rate and slows electrical conduction through the AV node.

  • Lungs:

    • SNS: Promotes bronchodilation to open airways.

    • PNS: Promotes bronchoconstriction and increases bronchial mucosal secretions.

  • Gastrointestinal (GI) Tract:

    • SNS: Decreases GI motility and tone; contracts digestive sphincters to prevent passage of contents.

    • PNS: Increases GI motility, increases digestive secretions, and relaxes sphincters to facilitate digestion and transit.

  • Liver:

    • SNS: Rapidly mobilizes glucose by stimulating gluconeogenesis and glycogenolysis.

    • PNS: No direct functional effect.

  • Kidney:

    • SNS: Stimulates renin release (activating the renin-angiotensin-aldosterone system) and alters renal blood flow via vascular tone.

    • PNS: No direct functional effect.

  • Urinary Bladder:

    • SNS: Promotes urinary retention by relaxing the detrusor muscle and contracting the bladder neck and internal sphincter.

    • PNS: Promotes bladder emptying by contracting the detrusor muscle and relaxing the sphincter.

  • Reproductive System:

    • Ejaculation and erection represent the sole physiological instance where the SNS and PNS act cooperatively/complementarily toward a shared biological goal.

    • Parasympathetic nervous system controls penile/clitoral erection.

    • The sympathetic nervous system controls ejaculation/orgasm.

    • Mnemonic Memory Aid: "Point and Shoot"

    • Point = Parasympathetic = Erection

    • Shoot = Sympathetic = Ejaculation

Anatomical Organization and Dual Innervation Patterns

  • Patterns of Autonomic Innervation:

    • Dual Opposing Innervation: (input produces opposite effect)

      • Most autonomic organs receive continuous input from both the parasympathetic and sympathetic divisions, producing opposite physiological effects.

    • Dual Complementary Innervation: (input produces the same effect)

      • The reproductive system is innervated by both divisions, which work together toward the same ultimate goal.

    • Single Division Innervation:

      • Arterioles, systemic veins, and sweat glands are innervated almost exclusively by the sympathetic nervous system


  • Autonomic Tone:

    • Represents the steady, baseline balance (rest) maintained by continuous regulatory impulses from both ANS divisions.

    • Predominant tone at baseline based on division:

      • arterioles = SYMPATHETIC (adrenergic)

      • veins = SYMPATHETIC (adrenergic)

      • Heart = PARASYMPATHETIC (cholinergic)

      • Iris = PARASYMPATHETIC (cholinergic)

      • Ciliary muscle = PARASYMPATHETIC (cholinergic)

      • GI tract = PARASYMPATHETIC (cholinergic)

      • Urinary bladder = PARASYMPATHETIC (cholinergic)

      • Salivary glands = PARASYMPATHETIC (cholinergic)

      • Sweat glands = SYMPATHETIC (cholinergic)

  • Physiological Impact of Receptor Blockade:

    • Blocking an autonomic pathway removes the normal resting influence supplied by that division rather than actively driving an opposing pathway.

    • Blocking vascular alpha-1 receptors removes the baseline constrictive signal, allowing smooth muscle to relax (vasodilation).

    • This effect is like pulling one's foot off the gas pedal rather than stepping on the brake.


Feedback regulation

  • Baroreceptor reflex

    • Baroreceptor = pressure receptor

    • Reflex triggered by the body when medications suddenly change blood pressure