Sympathomimetic Agents

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Sympathomimetic Agents

• By Jim Clarke

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The Nervous System

• Autonomic Control
• Sympathomimetic side
• Chief chemical neurotransmitter at the
  post-ganglionic sites is nor-epinephrine
• Chief chemical neurotransmitter at the
  pre-ganglionic sites is acetylcholine
• Parasympathomimetic side
• Chief chemical neurotransmitter is acetylcholine
• Somatic Control
• Motor control is mediated at the target organ by
  acetylchline

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Diagram of Central Peripheral Nervous System
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How 2 Branches Differ

• Adrenergic
• Fight or Flight
• Gearing system up
• Increases glycogen breakdown
• Improves blood flow to major muscles heart
• Dilates the eyes
• Fast acting very widespread

• Cholinergic
• Feed or Bread
• Increases digestive functions
• Increases urinary function
• Increases bronchial secretions
• Slower acting more focused

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Nerve Signal Transmission

• Efferent limbs of nerves transmit impulses from
  the brain or spinal cord to the target organ
• Afferent limbs of nerves transmit impulses from
  the organ system to the brain and spinal cord

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Sympathetic Characteristic

• Sympathetic branch arises from thoraco-lumbar
  portion of the spinal cord
• Postganglionic fibers may stimulate many sites
• adrenal gland heart lungs liver
• sympathetic stimulation causes widespread effects
  because of the action of the adrenal gland on the
  entire body

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Parasympathetic Characteristics

• Arises from the cranio-sacral portions of spinal
  column
• Postganglionic fibers are able to closely target
  effector sites (heart lungs gut)
• Effects tend to be limited to the effector sites
  and are not widely distributed

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Parasympathetic Effects

• Organ Site
• Heart
• SA Node
• Contractility
• Conduction Velocity
• Bronchi
• Smooth Muscle
• Mucous glands

• Cholinergic Effect
• Slowing of rate
• Decreased Atrial force
• Decreased conduction
• Bronchoconstriction
• Increased mucus production

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Parasympathetic Effects

• Effect
• No direct effect
• Vasodilation
• No effect
• No effect

• Organ Site
• Vascular Smooth Muscle
• Skin Mucosa
• Pulmonary
• Skeletal muscle
• Coronary

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Cholinergic Receptors

• Muscarinic Receptors are located at
• exocrine glands (bronchial glands)
• cardiac muscles
• GI tract smooth muscle
• Acetylcholine working at these sites produce
  Muscarinic effects
• Increase in secretions may occur when drugs
  effecting these lung sites are given

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Cholinergic Receptors

• Nicotinic Receptors are located at autonomic
  ganglia and in skeletal muscles
• Stimulation of these receptors cause increases in
  blood pressure and muscle tremors

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Parasympathetic Agents

• Indirect acting agents inhibit the action of
  cholinestarase. This increases the action of
  the remaining acetylcholine
• Reversible inhibitors neostigmine (Prostigmine)
  edrophonium (Tensilon) pryridostigmine
  (Mestinon)
• These agents are used to either reverse the
  actions of certain other drugs or to test the
  bodys ability to increase muscle strength

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Parasympathetic Agents

• Irreversible inhibitors - these are primarily the
  organophosphate pesticides (Malathion Diazanon
  Parathion) except for
• Phospholine - used as a pupillary constrictor in
  the treatment of glaucoma
• Atropine can be used to reverse the effects of
  both reversible and irreversible inhibitors.
  The have limited effect on organophosphates
• Protopam may be used in first 24 hours to treat
  pesticide poisoning

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Parasympatholytic Agents

• These agents block acetylcholine receptors at the
  neuroeffector site
• Atropine is the common agent in this group
• Used to accomplish the following
• Bronchodilation
• Antidiarrhea
• Tx of bradycardia
• Pre-operative drying of secretions

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Sympathetic Effects

• Organ Site
• Heart
• SA Node
• Contractility
• Conduction Velocity
• Bronchi
• Smooth Muscle
• Mucous glands

• Effect
• Increasing of rate
• Increased Atrial force
• Increased conduction
• Bronchorelaxation
• Increased secretion

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Sympathetic Effects

• Effect
• Vasoconstriction
• Dilation/Constriction
• Dilation
• Dilation/Constriction

• Organ Site
• Vascular Smooth Muscle
• Skin Mucosa
• Pulmonary
• Skeletal muscle
• Coronary

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Inactivation of Adrenergic Agents

• Catechol-O-methyl Transferase (COMT)
• deactivates adrenergic agents called
  catecholamines by changing one of the side-groups
  on the cathechol ring
• Mono Amine Oxidase (MAO)
• deactivates adrenergic agents by removing the
  amine group from the side-chain
• Since MAO is found in the stomach, many
  adrenergics cannot be orally administered

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Alpha Beta Receptors

• Alpha receptors - generally excite (except in GI
  tract in the CNS where inhibition or relaxation
  occurs)
• Alpha 1 and Alpha 2 receptors
• Beta Receptors - generally inhibit or relax
  (except in the heart ---gt stimulation)
• Beta 1 and Beta 2 receptors

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Adrenergic Receptor Locations

• Receptor Type
• Alpha 1
• Alpha 2
• Beta 1
• Beta 2
• Beta 3

• Location
• Peripheral blood vessels
• Presynaptic receptors
• Heart
• Smooth Muscle cardiac muscle
• Lipocytes

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Key Aspects of Receptors

• Alpha 1 and Beta 1 receptors excite
• Alpha 2 and Beta 2 receptors inhibit

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Receptor Locations Actions

• Alpha 1 receptors are located at the
  post-synaptic smooth muscle are excitatory
• Alpha 2 receptors are located at the pre-synaptic
  ganglia are inhibitory

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Adrenergic Control in the Lungs

• There is no direct adrenergic control exerted in
  the lungs
• All control occurs through circulating agents
  like epinephrine nor-epinephrine acting on
  alpha beta receptors located throughout the
  lungs

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Locations of Receptors

• Beta 2 receptors exist throughout all airways in
  the lung
• Beta 1 Receptors are located primarily in the
  heart. There are some Beta 1 lung receptors
• Alpha Receptors exist in the lung in lessor
  quantity than Beta Receptors
• Have limited airway effects (some studies suggest
  stimulation of lung alpha receptors may actually
  cause bronchospasm).

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Adrenergic Receptor Affect on Lung Blood Flow

• Alpha 1 stimulation will cause vasoconstriction
  resulting in decrease in blood flow and an
  increase in blood pressure
• Beta stimulation in the lung can cause
  relaxation of vessels causing vasodilation and
  increased blood flow

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Cholinergic Lung Effects

• Vagus nerve stimulation causes Muscarinic
  receptors (located mainly in larger airways) to
  induce bronchospasm
• Receptors active in the lung are
• M1
• M2
• M3 - responsible for causing bronchospasm

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Other Sources of Nervous Control

• Nonadrenergic Noncholinergic Inhibitory and
  Excitatory Nerves
• Not well understood at this point
• One possible neurotransmitter working in this
  system may be Nitric Oxide
• Nitric Oxide administration causes vasodilation
  in the lungs

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View of Airway Control Mechanisms
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Adrenergic Bronchodilators
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Specific Adrenergic Agents

• Catecholamines
• Resourcinals
• Saligenins
• Other non-catecholamines
• Pirbuterol
• Bitolterol (pro-drug)

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Characteristics of Catecholamines
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Characteristics of Non-Catecholamines
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Drug Names Forms
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Drug Names Forms Cont
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Advantages of Inhalation

• Quick Onset
• Smaller doses are needed compared to p.o.
• Fewer side effects
• less Beta 1 fewer tremors
• Direct dosing to airway
• Safe and painless

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Continuous Inhalational Dosing

• Albuterol
• 12 mg/hr (average dose)
• 10 - 20 mg/hr (dose ranges)
• Length 4 hours (average)
• Length 1 - 10 hours (range of time)

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Side Effects of Beta Agonists

• Tremors
• Tachycardia palpitations
• Headache
• Insomnia
• Increase in BP
• Nervousness
• Nausea

• Tachyphylaxis
• Decrease in PaO2
• Hypokalemia (only with continuous dosing)
• Propellant induced bronchospasm
• Sulfite Sensitivity

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End of Week 4 - Thursday