Peripheral Nervous System

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Peripheral Nervous System

• Principles to Neuropharmacology

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Objectives

• Identify two primary divisions of the nervous
  system
• Compare and contrast the actions of the
  sympathetic and parasympathetic nervous system
• Describe three parts of a synapse
• Identify neurotransmitters important to the
  autonomic nervous system and the types of nerves
  with which they are associated with

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Objectives

• Compare and contrast nicotinic and muscarinic
  receptors
• Compare and contrast nicotinic and muscarinic
  receptors
• Compare and contrast the types of effects when a
  drug stimulates alpha1, alpha2, beta1, beta 2,
  adrenergic receptors.

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Basic Principles of Neuropharmacology

• Neuropharmacology is the study of the drugs that
  alter processes controlled by the nervous system

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Neuropharmacologic Agents

• There are two categories of neuropharmacologicagen
  ts
• Peripheral Nervous system drugs
• Central Nervous system drugs

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Synapses are Common Sites of Drug Action

• Neuron- Basic functional cell of the nervous
  system
• Synapse- As a nervous impulse travels along a
  nerve, it encounters a structure at the end of
  the nerve
• Synaptic Cleft- Open space which must be bridged
  in order for the impulse to reach the next nerve

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Continued

• Presynaptic Nerve- Nerve generating the original
  impulse
• Postsynaptic Nerve- Nerve waiting to receive the
  impulse
• Neurotransmitters- Physical space of the synaptic
  cleft bridged by chemicals

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Transmitter Synthesis

• Drugs can
• Increase transmitter synthesis
• Decrease transmitter synthesis
• Enhance the effect of the transmitter

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Receptor Binding

• Neuropharmacologic drugs that act directly to the
  receptors can bind and
• Cause activation/Morphine
• Prevent Activation/Naloxone
• Enhance Activation/Diazepam

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Physiology of the Peripheral Nervous System

• Divisions of the Nervous System
• Central Nervous System
• Brain Spinal Cord
• Peripheral Nervous System
• Somatic Motor/Autonomic
• Sympathetic/Parasympathetic

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Parasympathetic Nervous System

• The functions of the PNS affect
• Heart rate
• Gastric Secretions
• Bladder and bowel
• Vision
• Bronchial Smooth Muscle

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Sympathetic Nervous System

• Main functions of the SNS
• Regulation of cardio system
• Regulation of body temp
• Implementation of fight or flight reaction

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Transmitters of the PNS

• Principal neurotransmitters of PNS are
• Acetylcholine
• Norepinephrine
• Epinephrine
• Dopamine

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Receptors of the PNS

• Cholinergic
• Mediated by acetylcholine
• Adrenergic
• Mediated by norepinephrine and epinephrine

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Subtypes of Cholinergic and Adrenergic Receptors

• Cholinergic Receptor
• Nicotinic n/Nicotinic m
• Muscarinic
• Adrenergic
• Alpha 1 and alpha 2
• Beta 1 and beta 2
• Dopamine

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Functions of Cholinergic Receptor Subtypes

• Nicotinic n (nueronal)
• Promotes ganglia transmission
• Promotes release of epinephrine
• Nicotinic m (muscle)
• Contraction of skeletal muscle
• Muscarinic
• Activates parasympathetic nervous system

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Functions of Adrenergic Receptor Subtypes (Cont)

• Beta 1
• Heart
• Increases heart rate
• Force of contraction
• Velocity of conduction in AV node
• Kidney
• Renin release

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Muscarinic Agonist and Antagonist

• Muscarinic Agonist
• Bethanechol-direct acting
• Uses
• Urinary retention
• GERD
• Ileus
• Post-operative abdominal distention

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Muscarinic Poisoning

• Source
• Ingestion of mushrooms
• Overdose
• Direct acting muscarinic agonist
• Cholinesterase inhibitors
• Treatment
• Muscarinic blocking agent- Atropine

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Muscarinic Antagonist

• Drug that blocks the action of acetylcholine at
  muscarinic receptors
• Atropine

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Atropine

• Actions
• Increases heart rate
• Decreases Secretions
• Relaxes bronchi
• Decreases bladder tone
• Decreases GI tone and motility
• Dilates the pupil

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Atropine

• Uses
• Eye exam and surgery
• Heart Block
• Increased gastric motility
• Muscarinic agonist poisoning
• Asthma
• Peptic Ulcer Disease

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Atropine

• Adverse Affects
• Dry Mouth
• Blurred Vision
• Light sensitivity
• Increased IOP
• Urinary retention
• Constipation
• Tachycardia

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Anti-Muscarinic Poisoning

• Sources
• Antihistamines
• Phenothiazines
• Tricyclic antidepressants
• Atropine
• Scopolamine
• Treatment-Cholinesterase inhibitor-physostigimine

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Cholinesterase Inhibitors

• Peripheral Nervous System

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Cholinesterase Inhibitors

• They prevent the breakdown of acetylcholine by
  acetylcholinesterase
• Two basic categories of cholinesterase inhibitors
• Reversible
• Irreversible

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Reversible Cholinesterase Inhibitor Neostigimine

• Clinical applications
• Myasthenia gravies
• Glaucoma
• Alzheimers disease
• Muscarinic Poisoning

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Irreversible Cholinesterase Inhibitors

• Same action as reversible cholinesterase
  inhibitors
• Are longer acting
• Used primarily in the treatment of glaucoma
• Commonly found in insecticides

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Poisoning-Organophosphate Cholinesterase
Inhibitors

• Produces a state of cholinergic crisis
• Treatment includes
• 02
• Mechanical ventilation
• Atropine
• Diazepam

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Myasthenia Crisis

• Myasthenic crisis occurs when clients are
  inadequately medicated
• Medical treatment
• Respiratory support
• Neostigmine

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Neuromuscular and Ganglionic Blocking Agents

• Peripheral Nervous System

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Neuromuscular and Ganglionic Blocking Agents

• Neuromuscular blocking agents
• Block nicotinic m receptors
• Cause muscle relaxation
• Commonly used during
• Surgery
• ET intubation
• Mechanical ventilation
• Diagnostic Procedures

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Muscle Contraction

• Basic Concepts
• Polarization
• Depolarization
• Repolarization

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Classification of Neuromuscular Blocking Agents

• Neuromuscular blocking agents are classified
  according to
• Mechanism of action
• Time course of action

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Neuromuscular Blocking Agents

• Mechanism of Action
• Nondepolarizing neuromuscular blocker I
• Turbocarine
• Nondepolarizing neuromuscular blocker II
• Doxacurium
• Atracurium
• Mivacurium
• Depolarizing neuromuscular blocker
• Succinylcholine

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Neuromuscular Blocking Agents (cont)

• Time Course of Action
• Long acting-doxacurium
• Intermediate acting-pancuronium
• Short acting-mivacurium
• Ultra short acting-succinylcholine

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Ganglionic Blocking Agents

• Block nicotinic n autonomic ganglia
• Used for essential hypertension
• Side effects
• Antimuscarinic-parasympathetic blockade
• Hypotentsion-sympathetic blockade

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Adrenergic Agonists

• Peripheral Nervous System

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Adrenergic Agonists

• Produce their effects by activating adrenergic
  receptors
• Adrenergic receptors are
• Alpha 1
• Alpha 2
• Beta 1
• Beta 2
• Dopamine

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Basic Mechanisms of Adrenergic Receptor Activation

• Direct receptor binding
• Promotion of norepinephrine release
• Blockage of norepinephrine reuptake
• Inhibition of norepinephrine in activation

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Adrenergic Agonists

• Chemical Classification
• Catecholamines
• Non-catecholamines
• Differences in catecholamines and
  non-catecholamines
• Oral usability
• Duration of action
• Action in central nervous system

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Alpha I Receptor Activation

• Therapeutic uses
• Constriction of blood vessels
• Mydriasis
• Hemostasis
• Nasal decongestion
• Adjunct to local anesthesia
• Adverse effects
• Hypertension/Bradycardia/Necrosis

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Beta I Receptor Activation

• Therapeutic uses
• Cardiac arrest
• Heart Failure
• Shock
• AV Block
• Adverse effects
• Tachycardia
• Dysrhythmias
• Angina Pectoris

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Beta II Receptor Activation

• Therapeutic uses
• Asthma
• Delay of preterm labor
• Adverse effects
• Hyperglycemia
• Tremors

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Dopamine Receptor Activation

• Therapeutic uses
• Dilates renal vasculature
• Enhances cardiac performance

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Anaphylactic Shock

• Cause-severe allergy
• Signs and Symptoms
• Hypotension
• Bronchial constriction
• Edema of glottis
• Treatment
• Epinephrine

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Adrenergic Antagonists

• Peripheral Nervous System

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Adrenergic Antagonists

• Direct blockade of adrenergic receptors
• Two major groups of adrenergic receptors
• Alpha-adrenergic blocking agent
• Beta-adrenergic blocking agent

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Alpha Blockade- Uses

• Therapeutic
• Essential hypertension
• Benign prostatic hyperplasia
• Pheochromocytoma
• Raynauds disease
• Overdose of alpha 1 agonist

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Alpha Adrenergic Blocking Agents

• Non-selective
• Produces alpha-1 and alpha-2 blockade
• Phentolamine (Regitine)
• Selective
• Produces alpha-1 blockade
• Prozasin (Minipres)

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Alpha Blockade

• Adverse Effects
• Orthostatic hypotension
• Reflex tachycardia
• Nasal congestion
• Inhibition of ejaculation
• Sodium retention

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Anaphylactic Shock

• Cause-severe allergy
• Signs and symptoms
• Hypotension
• Bronchial constriction
• Edema of glottis
• Treatment- Epinephrine

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Beta-Adrenergic Blocking Agents

• Nonselective
• Blocks beta1 and beta 2 receptors
• Proranolol (Inderal)
• Cardioselective
• Blocks beta 1 receptors
• Metoprolol (Lopressor)

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Beta Blockade

• Therapeutic effects
• Reduced heart rate
• Reduced force of contraction
• Reduced velocity of impulse conduction

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Beta Blockade

• Therapeutic uses
• Angina Pectoris
• Hypertension
• Cardiac dysrhythmias
• MI
• Migraine
• Hyperthyroidism
• Stage fright
• Glaucoma

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Beta Blockade (cont.)

• Adverse effects
• Bradycardia
• Reduced cardiac output
• Heart failure
• AV block
• Bronchial constriction

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Indirect-Acting Antiadrenergic Agents

• Peripheral Nervous System

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Indirect-Acting Antiadrenergic Agents

• Prevents stimulation of peripheral adrenergic
  receptors
• Two groups
• Adrenergic neuron-blocking agents
• Decrease norepinephrine release
• Centrally acting alpha agonists
• Reduce impulse along the sympathetic nerves

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Adrenergic Neuron-Blocking Agents

• Reserpine
• Primary indication-hypertension
• Mechanism of action-depletion of norepinephrine
• From post ganglionic sympathetic neuron synthesis

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Centrally Acting Alpha-2 Agonists

• Clonidine (Catapress)
• Selective stimulation of alpha receptors
• Primary indication-hypertension
• Causes
• Bradycardia
• Decreased cardiac output
• Decreased blood pressure

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Centrally Acting Alpha-2 Agonists (cont)

• Adverse Effects
• Drowsiness
• Xersotomia(mouth dryness)
• Rebound hypertension
• Embryotoxic