Parasympathetic Nervous System

Overview of the Autonomic Nervous System (ANS)

• The Autonomic Nervous System (ANS) is the part of the Peripheral Nervous System (PNS) that acts as a control system.
• The ANS controls visceral functions, largely below the level of consciousness.
• The Somatic Nervous System (SNS) controls activities of voluntary muscles, i.e., skeletal muscles.
• The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, pupil diameter, urination (micturition), and sexual arousal.
• The ANS is classically divided into two subsystems: the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS).
• Functionally, the ANS can be divided into sensory (afferent) and motor (efferent) subsystems.
• The ANS contains inhibitory and excitatory synapses between neurons.

Nervous System Organization

• The nervous system is divided into the central nervous system (CNS) and the peripheral nervous system (PNS).
• The CNS consists of the brain and spinal cord.
• The PNS includes sensory and motor pathways, with the motor pathways further divided into somatic (voluntary) and autonomic (involuntary) nervous systems.
• The autonomic nervous system has sympathetic and parasympathetic divisions.
• The brain receives and processes sensory information, initiates responses, stores memories, and generates thoughts and emotions.
• The spinal cord conducts signals to and from the brain and controls reflex activities.
• The somatic nervous system controls voluntary movements, while the autonomic nervous system controls involuntary responses.
• The sympathetic division is associated with "fight or flight," and the parasympathetic division with "rest and digest".
• The sympathetic and parasympathetic divisions typically function in opposition to each other, but this opposition is complementary rather than antagonistic.
• The sympathetic division is like an "accelerator," while the parasympathetic division is like a "brake".
• The sympathetic division is for actions requiring quick responses.
• The parasympathetic division is for actions not requiring immediate reaction.

Sympathetic Nervous System

• Promotes a "fight or flight" response, corresponds with arousal and energy generation, and inhibits digestion.
• Diverts blood flow away from the gastrointestinal tract and skin via vasoconstriction.
• Maintains and enhances blood flow to skeletal muscles and the lungs (increasing skeletal muscle blood flow by as much as 1200%).
• Dilates bronchioles of the lung, which allows for greater alveolar oxygen exchange.
• Increases heart rate and contractility of cardiac cells (myocytes), which provides enhanced blood flow to skeletal muscles.
• Dilates pupils, relaxes the lens allowing more light to enter the eye.
• Provides vasodilation for the coronary vessels of the heart.
• Constricts all the intestinal sphincters and the urinary sphincter.
• Inhibits peristalsis.

Parasympathetic Nervous System

• Promotes a "rest and digest" response.
• It promotes calming of the nerves, returns to regular function, and enhances digestion.
• Dilates blood vessels leading to the GI tract, which increases blood flow, especially important after eating.
• Can constrict the bronchiolar diameter when less oxygen is needed.
• Dedicated cardiac branches of the Vagus and thoracic Spinal Accessory nerves impart Parasympathetic control of the Heart or Myocardium.
• Causes constriction of the pupil and lens during accommodation.
• Stimulates salivary gland secretion and accelerates peristalsis.
• Mediates digestion of food and indirectly, absorption of nutrients.
• Is involved in erection of genitals through the pelvic splanchnic nerves.

ANS Neurotransmitters and Pharmacology

• Acetylcholine is the preganglionic neurotransmitter for both divisions of the ANS.
• Acetylcholine is a postganglionic neurotransmitter of parasympathetic neurons.
• Nerves that release acetylcholine are cholinergic.
• Ganglionic neurons use acetylcholine to stimulate muscarinic receptors in the parasympathetic system.
• Sympathetic ganglionic neurons release noradrenaline (norepinephrine) to act on adrenergic receptors at the effector organs, excluding sweat glands and the adrenal medulla.
• At the adrenal cortex, the presynaptic neuron releases acetylcholine to act on nicotinic receptors.
• Stimulation of the adrenal medulla releases adrenaline (epinephrine) into the bloodstream, acting on adrenoceptors and causing a widespread increase in sympathetic activity.

Cholinergic Receptors

• Two families of cholinergic receptors exist: muscarinic and nicotinic receptors.

Muscarinic (M) receptors

• Muscarinic Receptors belong to the class of G protein-coupled receptors (metabotropic receptors).
• In addition to binding ACh, they also recognize muscarine (from mushrooms).
• Subtypes include M1, M2, M3, M4, and M5.
• These receptors are found on ganglia of the peripheral nervous system and autonomic effector organs such as the heart, smooth muscle, brain, and exocrine glands.
• M1 receptors are also found on gastric parietal cells.
• M2 receptors are on cardiac cells and smooth muscle.
• M3 receptors are on the bladder, exocrine glands, and smooth muscle.

Nicotinic Receptors

• These receptors recognize nicotine in addition to binding ACh, but show little affinity for muscarine.
• The nicotinic receptor is composed of 5 subunits and functions as a ligand-gated ion channel.
• Nicotinic receptors are located in the CNS, adrenal medulla, autonomic ganglia, and neuromuscular junction (NMJ) in skeletal muscles.

Adrenergic Receptors

• Two main receptor families are α and β receptors.
• Primarily bind norepinephrine (NE) and epinephrine (EN).
• Subtypes include α1, α2, β1, and β2.
• Adrenergically innervated organs and tissues usually have a predominant receptor type.
• For example, skeletal muscle vasculature has both α1 and β2 receptors, but β2 predominates.
• The heart predominantly contains β1 receptors.

Receptor and Organs functions

• The ciliary epithelium produces aqueous humor through β1 receptors.
• Sympathetic activity stimulates the alpha receptors on the iris to contract longitudinally.
• The ciliary muscle and sphincter are stimulated by parasympathetic neurons releasing acetylcholine (Ach), binding muscarinic (M) receptors.
• Under high stress, sympathetics release NE, which increases aqueous humor production (via α and β receptors) and dilates the pupil.
• The parasympathetic nervous system constricts the pupil and drains the anterior chamber after stress.
• B₂ receptor stimulation from the lungs causes bronchodilation of the airways and decreases airway secretions, while Ach stimulates M receptors, causing bronchoconstriction of the airways, also increases airway secretion.
• The lungs contains many other receptors/ mediators that are not directly involved in the SNS/PNS.
• B₁ receptor stimulation of the Heart increases heart rate, contractility, AV nodal conduction and cardiac output, while muscarinic (M) receptor stimulation decreases SA nodal firing, decrease AV node Conduction and decrease CO.
• Blood vessels express α, β, dopamine (DA), histamine (H), and muscarinic (M) receptors which function in a more complex system.
  • NE (α, β₁), and epinephrine(a1, a2, β₁, ẞ2) and dopamine (DA) are released.
  • a₁ vasoconstricts vessels, mainly at the arterioles.

Gastrointestinal Tract (GIT)

• It is a very complex and poorly understood system
• Parasympathetic activity stimulates muscarinic receptors (M).
• Activation of the M receptors increases GI motility, opens sphincters, and increase secretions.
• Sympathetic activity stimulates α and β receptors then slows GI motility, increases sphincter tone, and decreases GI secretions.
• DA receptor activation causes increased GI motility, stimulates secretion, and decreases sphincter tone.
• Opioids also need consideration, they will promptly decrease GI motility, decrease secretions, and increase sphincter tone, inducing Constipation.

Bladder

• Alpha-receptors prevent bladder contraction by relaxing it and contracting the internal sphincter, while muscarinic receptors stimulate bladder contraction and relax the internal sphincter.

Drugs Related to ANS

• The main disease of the eye discussed in pharmacology is Glaucoma - a disease that can result in blindness.
  • The cause of glaucoma is the increase in pressure in the intraocular space (increased production and decreased drainage of aqueous humor).
  • Glaucoma is addressed using:
    • Cholinomimetics
    • B-blockers
    • Epinephrine +Cholinomimetics are based on their chemistry.
  • Tertiary amines such as pilocarpine and physostigmine are uncharged and have distinct mechanisms.
    • Pilocarpine passes easily through the cornea, stimulates M receptors, and opens of the canal of Schlemm.
    • Physostigmine passes through the cornea easily and inhibits cholinesterase. This increase of local Ach, increases ciliary and sphincter muscle Contraction. +Pilocyarpine is the drug of choice. +Timolol: a beta-blocker that blocks synthesis of aqueous humor by blocking B receptors of the ciliary epithelium. +Acetazolamide is a diuretic that blocks carbonic anhydrase activity and prevents aqueous humor production.
  • Antimuscarinics are not used, as these would worsen glaucoma, but they are used to dilate eyes for eye exams.
  • Atropine is the prototype that blocks muscarinic receptors; others= homatropine, cyclopentolate, and tropicamide".

Drugs affecting the lungs

• The two main actions:

  • Affecting Airway Diameter by either bronchodilation or bronchocostriction. -Bronchodilation is a Sympathetic activity. -Epinephrine and dopamine are very effective by stimulating B2. -Results in bronchial smooth muscle dilation and decreased secretions in Lungs.
  • Affecting Airway Secretions:

• A decrease in Sympathetic activity or withdrawals of the agents increase secretions and relaxation.

  • An Antimuscarinic is very effective in Blocking muscarinic bronchoconstriction and increased secretion.
  • Ipratropium is a quaternary amine, crosses membranes poorly, and a great inhalation agent with minimal side effects".

• Ephinephrine and Dopamine is effective where increase ventillation needed,but is not a long term solution.

• Nonepinephrine is specific for B1 and has little Affect.

• Bronchoconstriction happens by Muscarinic receptors,little used Drugs affecting the Heart:

• Activity is controlled thru B1 and M receptors

• B1 stimulation increases HR, contractility and CO: ephineprine, NONE, Dopamine or isoproterenol".

• Muscarinic Agonists and anti-Cholinerase slows HR, decreased contractility and AV conduction. -But few agents to stimulate M receptors instead Beta blockers

• Know atenolol and metoprolol a B1 specific: and best for asthmatics Beta blockers

• Both labetolol and carvedilol has A and B1 and carvediol decreases afterload In CHF -Beta Blockers to exacerbate asthma attach drugs affecting the blood vessels:

• Receptor Reflex:

• ANYTHING THAT AFFECTS arterial pressure will decrease HR by stimulating the brainstem nucleus tractus Solitarius (NTS) to decrease stimulation of the heart

• A change will affect Nonephinephrine Release and heart Contractility Altered is also

• If a DECREASE happens, the SIGNAL for NTS to increased Sympathetic tone is sent out. But an INCREASE causes it be to inhabited therefore rate and contractivity all drop

a1 stimulate, increases arterial and Decreases heart rate

The GI System

• Alpha and Beta, DA. M, opioid, and serotonin are ALL expressed..

• Sympathomimetic to down regulate Gl: decrease Motitiy and Increase Secretal -Beta blocker and the likes

• Antidominergic increase as well

• Muscarin reduce

• Andomsetron is as 5HT which blocks Gl and prevent these

The Bladder

• the 6th one*
• A and M receptors
• A anatanogis increases mituration and releasexs sphincters

Examine scenarios related to the parasympathetic nervous system. This includes the effects of drugs mimicking parasympathetic actions and the impact of toxins on nerve function. Also covers cholinergic receptors and pharmacological interventions.