Autonomic Nervous System

1
Autonomic Nervous System
2
Function of the Autonomic Nervous System
3
Function of the Autonomic Nervous System

• Automatic because the autonomous autonomic
  nervous system regulates them
• Regulating, adjusting, and coordinating vital
  visceral functions
• Blood pressure and blood flow
• Body temperature
• Diameter of bronchi
• Digestion
• Metabolism
• Elimination

4
Divisions of the Autonomic Nervous System
5
Divisions of the Autonomic Nervous System

• The ANS is a motor system it innervates smooth
  muscles, cardiac muscle, and glands.
• Information comes from the CNS to the periphery
• Does not innervate skeletal muscle
• The somatic nervous system innervates skeletal
  muscle
• Divisions
• Sympathetic nervous system
• Parasympathetic nervous system

6
Sympathetic Division of the Autonomic Nervous
System
7
Sympathetic Division of the Autonomic Nervous
System

• Maintains vital functions
• Responds when there is a critical threat to the
  integrity
• Fight or flight response

8
Fight or Flight Response
9
Flight or Fight Response

• Increased heart rate and BP.
• Shunting of blood away from the skin and viscera
  and into skeletal muscles.
• Dilation of bronchi.
• Leads to deep breaths
• Dilation of pupils.
• Help you see the threat better
• Mobilization of stored energy to provide glucose
  and fatty acids for the brain and skeletal
  muscles.
• 1 molecule ATP for one cross bridge of skeletal
  muscle to contract
• Thousands of cross bridges to move and entire
  muscle
• In the fight or flight response, the brain must
  be active, even though it is not involved in the
  autonomic nervous system
• ANS is in the PNS

10
Parasympathetic Division of the Autonomic Nervous
System
11
Parasympathetic Division of the Autonomic Nervous
System

• Concerned with conservation of energy
• Resource replenishment
• Maintenance of organ function during inactivity
• Rest and digest

12
Rest and Digest Response
13
Rest and Digest Response

• Conservation of energy and resources/maintenance
  of organ function.
• Slowing of heart rate.
• Increased gastric and intestinal secretion and
  motility.
• How we acquire energy
• Emptying of the bladder.
• Emptying of bowels.
• Constriction of the pupil.
• Contraction of bronchial smooth muscle.

14
Patterns of Innervation and Control of the ANS
15
Patterns of Innervation and Control of the ANS

• Both divisions of the ANS innervate an organ and
  the effects of the two divisions are opposed.
• Ex. regulation of heart rate
• Sympathetic nervous system speeds it up and
  parasympathetic nervous system slows it down
• Innervation by both divisions of the ANS in which
  the effects of the two divisions are
  complementary.
• Ex. micturition and defecation needs activity
  from both systems
• Innervation and regulation by only one division
  of the autonomic nervous system.
• Ex. regulation of contractility of the left
  ventricle is only affected by the sympathetic
  nervous system

16
Patterns of Innervation and Control of the ANS
Lehne, 2009, Pharmacology for Nursing Care, 7th
ed., Elsevier, p. 107
17
Structure of Both Divisions of the ANS
18
Structure of Both Divisions of the ANS

• Both divisions of the ANS have a two-neuron
  pathway
• Two-neuron pathway
• Preganglionic neuron cell bodies reside in the
  brain or spinal cord and axons go out into the
  periphery.
• The preganglionic neuron and the postganglionic
  neuron meet at the ganglion
• Postganglionic neuron cell body is in an
  autonomic ganglion and axon goes out to the end
  organ (smooth muscle, cardiac muscle, or gland).

19
The Peripheral Nervous System
20
The Peripheral Nervous System

• Consists of spinal and cranial nerves
• Carry motor and sensory fibers
• Motor impulses are coming out of the CNS
• Sensory impulses are going into the CNS
• There are two motor systems
• The voluntary motor system that controls skeletal
  muscles
• The autonomic motor system that controls smooth
  muscles, cardiac muscle, and glands.
• Both motor systems use acetylcholine as a
  neurotransmitter.

21
Comparison of Somatic and Autonomic Nervous
Systems
22
Comparison of Somatic and Autonomic Nervous
Systems

• Somatic nervous system
• One neuron
• Spinal cord ACh (skeletal muscle)
• Autonomic nervous system
• Sympathetic nervous system
• Two neurons
• Three subtypes
• ACh-NE and Epi (organs)
• ACh-ACh (sweat glands)
• ACh-Epi (through the adrenal medulla at organs)
• Parasympathetic nervous system
• Two neurons
• One subtype
• ACh-ACh (organs)

23
Comparison of the Nervous SystemsSomatic Nervous
System
24
Comparison of the Nervous SystemsSomatic Nervous
System

• Only one neuron in the pathway from the spinal
  cord to the muscles innervated by somatic motor
  nerves
• There is only one site of action at the
  neuromuscular junction

25
Comparison of the Nervous SystemsParasympathetic
Nervous System
26
Comparison of the Nervous SystemsParasympathetic
Nervous System

• The junction between the preganglionic neuron and
  the postganglionic neuron occurs within a
  ganglion (a lump created by a group of nerve cell
  bodies)
• Two general sites at which drugs can act
• The synapse between the preganglionic neuron and
  the postganglionic neuron
• The junction between the postganglionic neurons
  and the effector organ

27
Comparison of the Nervous SystemsSympathetic
Nervous System
28
Comparison of the Nervous SystemsSympathetic
Nervous System

• Most are similar to the parasympathetic nervous
  system
• Spinal cord preganglionic neuron ganglion
  postganglioninc neuron organs
• In some cases, the adrenal medulla can act as a
  postganglioninc neuron
• Influences the body by releasing epinephrine into
  the bloodstream, which then produces effects

29
Comparison of Somatic and Autonomic Nervous
SystemsDiagram with Neurotransmitters
30
Comparison of Somatic and Autonomic Nervous
SystemsDiagram with Neurotransmitters
Lehne, 2009, Pharmacology for Nursing Care, 7th
ed., Elsevier, p. 110
31
Summary of Transmitters Employed at Junctions of
the PNS

• 1. All preganglionic neurons of the
  parasympathetic and sympathetic nervous systems
  release acetylcholine as their transmitter
• 2. All postganglionic neurons of the
  parasympathetic nervous system release
  acetylcholine as their transmitter
• - Receptors are muscarinic
• 3. Most postganglionic neurons of the sympathetic
  nervous system release norepinephrine as their
  transmitter
• - Receptors are adrenergic (alpha, beta, or both)
• 4. Postganglionic neurons of the sympathetic
  nervous system that innervate sweat glands
  release acetylcholine as their transmitter
• - Receptors are muscarinic
• 5. Epinephrine is the principal transmitter
  released by the adrenal medulla
• - Receptors are adrenergic (alpha or beta)
• 6. All motor neurons to skeletal muscles release
  acetylcholine as their transmitter
• - Receptors are nicotinic m (for muscle)

32
Neurotransmitters of the Autonomic Nervous System
33
Neurotransmitters of the Autonomic Nervous System

• Acetylcholine
• Norepinephrine
• Epinephrine

34
Acetylcholine
35
Acetylcholine

• Neurotransmitter for preganglionic neurons for
  both ANS divisions
• The receptor is the nicotinic n postganglionic
  acetylcholine receptor.
• Neurotransmitter for the postganglionic neurons
  of the parasympathetic nervous system and for
  some in the sympathetic nervous system (sweat
  glands)
• The receptor on the end organ is a muscarinic
  receptor

36
Norepinephrine
37
Norepinephrine

• Neurotransmitter for the sympathetic
  postganglionic neurons.
• Receptors on end organs can be alpha or beta.

38
Epinephrine
39
Epinephrine

• In the sympathetic nervous system, the adrenal
  medulla produces epinephrine, which affects
  various organs

40
The Sympathetic Nervous System
41
The Sympathetic Nervous System

• Preganglionic nerve cell bodies are in the
  thoraco/lumbar cord from T1 to L2.
• Axons exit the cord at each level and immediately
  synapse at a paraspinal sympathetic ganglion.
• Axons of postganglionic sympathetic neurons leave
  the paraspinal ganglia and innervate target
  smooth muscle, cardiac muscle, and glands.
• The various sympathetic neurons are
  interconnected
• Allows unitary activation from the sympathetic
  nervous system
• Can cause all body functions to occur at the same
  time, rather than one at a time

42
Sympathetic Pathways
43
Sympathetic Pathways
Porth, 2007, Essential of Pathophysiology, 2nd
ed., Lippincott, p. 755.
44
Sympathetic PathwayThe Adrenal Medulla
45
Sympathetic PathwayThe Adrenal Medulla

• Preganglionic axons from the sympathetic centers
  in the thoracolumbar cord go directly to the
  adrenal medulla where they innervate cells called
  enterochromaffin cells.
• Enterochromaffin cells can be thought of as
  quasi-postganglionic neurons.
• But in addition to small amounts of
  norepinephrine, they synthesize mostly
  epinephrine.
• Activates all sympathetic (alpha and beta)
  receptors
• Important that it activates beta 2 receptors
• Both these products are secreted into the
  bloodstream rather than being released into a
  synapse.
• Epinephrine from the adrenal medulla circulates
  and activates beta-2 receptors that are not
  innervated by the SNS. (Epinephrine can also
  activate beta-1 receptors and alpha receptors but
  they are more likely to be activated by
  norepinephrine that is released from
  postganglionic axon terminals into their synapse
  at the end organs of the SNS.)

46
The Parasympathetic System
47
The Parasympathetic System

• Two CNS centers
• The brainstem
• The sacral cord

48
The Parasympathetic SystemThe Brainstem Centers
49
The Parasympathetic SystemThe Brainstem Centers

• Separate from one another
• Brain centers supply CN III (constrict the
  pupil), CN VII, (salivary, nasal and lacrimal
  glands), CN IX (salivary glands), and most
  importantly, CN X, the vagus nerve.
• Preganglionic axons in the vagus nerve supply the
  heart, trachea, lungs, esophagus, stomach, small
  intestine and some of the colon, liver,
  gallbladder, pancreas, kidneys, and upper
  ureters.
• The vagus nerve is important because it supplies
  many parts of the body
• The parasympathetic centers in the brain that
  supply the various cranial nerves are separate
  by distance and by function.
• Although there may be communication between them,
  they can act independently.
• Not like the sympathetic nervous system where
  there is unitary activation

50
The Parasympathetic SystemSacral Parasympathetic
Outflow
51
The Parasympathetic SystemSacral Parasympathetic
Outflow

• Preganglionic axons go out from the cord at S2-S4
  levels to supply the bladder, uterus, urethra,
  prostate, distal colon, rectum, and vasculature
  of the genitalia.
• The sacral and cranial parts of the
  parasympathetic system are relatively independent
  of each other.
• The relative independence of the cranial centers
  from each other and from the sacral centers
  contrasts with the sympathetic system, whose
  various levels are highly interconnected in the
  sympathetic chain.

52
The Parasympathetic SystemParasympathetic End
Organs
53
The Parasympathetic SystemParasympathetic End
Organs

• When the parasympathetic preganglionic axons
  reach the end organs, they synapse with
  postganglionic neurons in ganglia that are within
  or very near to the end organ
• Usually are within the organ wall
• Neurotransmitter is always acetylcholine
• Receptors are nicotinic and muscarinic
• The postganglionic neurons send short axons to
  individual cells in the end organ.
• When the postganglionic axons fire, they release
  acetylcholine into the synapse, which activates
  muscarinic receptors on the cells of the end
  organ.

54
Transmitters and Receptors of the Autonomic
Nervous System
55
Transmitters and Receptors of the Autonomic
Nervous System

1. Nicotinic n receptors are located on the cell
   bodies of all postganglionic neurons of the
   parasympathetic and sympathetic nervous systems,
   including the adrenal medulla
2. Nicotinic m receptors are located on skeletal
   muscle
3. Muscarinic receptors are located on all organs
   regulated by the parasympathetic nervous system
   and on sweat glands controlled by the sympathetic
   nervous system with ACh
4. Adrenergic receptors (alpha, beta, or both) are
   located on all organs (except glands) regulated
   by the sympathetic nervous system, including
   organs regulated by epinephrine released from the
   adrenal medulla

56
Transmitters and Receptors of the ANS
Lehne, 2009, Pharmacology for Nursing Care, 7th
ed., Elsevier, p. 113
57
Comparison of the SNS and PNS
58
Comparison of the SNS and PNS
Characteristic Sympathetic Parasympathetic
Location of preganglionic cell bodies Thoracic region T1-L2 CN III, IX, X, S2-S4
Length of preganglionic axons Short to sympathetic ganglion or adrenal Long, to postganglionic neuron in or near end organ - Originating in the cranial nerves, so they must be longer
General function Catabolic mobilizes resources for flight or fight Anabolic conservation, renewal, and storage of nutrients
Nature of peripheral response Generalized (b/c of interconnected ganglia) Localized
Preganglionic neurotransmitter Ach Nicotinic N (actually is located on the postganglionic ganglionic) Ach Nicotinic N
Postganglionic neurotransmitter NE most synapses Ach sweat glands NE and epi adrenal Ach
Receptors on end organs NE and epi alpha and beta - Beta-1, beta-2, alpha-1, alpha-2 Ach muscarinic Muscarinic
59
ANS End Organs
60
ANS End Organs
Porth, 2007, Essential of Pathophysiology, 2nd
ed., Lippincott, p. 858
61
Adrenergic Receptor Subtypes
62
Adrenergic Receptor Subtypes
Location Response to agonist or neurotransmitter
Alpha-1 activated with norepi
Arteries and veins Constriction
Bladder neck (internal sphincter) Constriction
Alpha-2 activated with norepi
Central nervous system Inhibits sympathetic outflow
Beta-1 activated with norepi
Heart, SA node Increases heart rate (positive chronotropic effect)
Heart, AV node Increases speed of conduction (positive dromotropic effect)
Heart, ventricular muscle Increased contractility (positive inotropic effect)
Kidney Release of renin - Leads to thicker blood and vasoconstriction (through angiotensin II) - ultimately leads to increased blood pressure - do not need to pee
Beta-2 activated with only epi
Arterioles in skeletal muscle beds Dilation to bring more blood to muscles
Bronchi Dilation
Uterus Relaxation
Adapted from Lehne, 2009, Pharmacology for
Nursing Care, 7th ed., Elsevier, p. 115.
63
Which of the Following is a Result of SNS
Stimulation?
64
Which of the Following is a Result of SNS
Stimulation?

1. Slowing of heart rate.
2. Increased gastric and intestinal secretion and
   motility.
3. Constriction of the pupil.
4. Dilation of bronchi

65
Which of the Following is a True Statement?

1. The structure of the ANS is a one-neuron pathway
2. The ANS is a motor system
3. The SNS is concerned with conservation of energy.
4. The PNS responds when there is a critical threat
   to the integrity of the organism

66
What of the Following is a True Statement?

• The ANS is a motor system

67
Alpha-1 Receptor DrugsAgonists
68
Alpha-1 Receptor DrugsAgonists

• Alpha-1 agonists are used as pressors (raise BP)
  or as decongestants.
• The decongestants are used to shrink the dilated
  blood vessels in the nose
• Phenylephrine (Neo-synephrine) nose drops,
  spray, or pill
• Oxymetazoline (Afrin) spray
• Pseudoephedrine (Sudafed)
• Can be used as a precursor for illegal
  amphetamines

69
Alpha-1 Receptor DrugsAntagonists
70
Alpha-1 Receptor DrugsAntagonists

• Alpha-1 antagonists are used for hypertension and
  for urinary retention in benign prostatic
  hypertrophy.
• Prevent the activity of norepinephrine and
  epinephrine at the alpha-1 receptor, leading to
  vasodilation
• Prazosin (Minipres)
• Terazosin (Hytrin)
• Doxazosin (Cardura)

71
Therapeutic Applications of Alpha-1 Antagonists
72
Therapeutic Applications of Alpha-1 Antagonists

• Hypertension
• Dilation of arterioles by alpha-1 blockade
  reduces BP directly.
• Dilation of veins by alpha-1 blockade reduces
  venous return to the heart, which reduces cardiac
  output, which reduces blood pressure.
• Benign prostatic hypertrophy
• As the prostate enlarges, it compresses the
  urethra, making urination difficult.
• Blocking alpha-1 receptors reduces contraction of
  smooth muscles in the bladder neck, making
  urination easier
• Pheochromocytoma a catecholamine-secreting
  tumor derived from the adrenal medulla
• Epinephrine and norepinephrine from the tumor
  produce extremely high BP and blocking alpha
  receptors reduces it.
• A beta blocker might also be given to lower the
  HR.

73
Adverse Effects of Alpha-1 Blockade
74
Adverse Effects of Alpha-1 Blockade

• Orthostatic hypotension
• Reflex tachycardia
• Nasal congestion
• Inhibition of ejaculation
• Can still have an erection but cannot ejaculate

75
Adverse Effects of Alpha-1 BlockadeOrthostatic
Hypotension
76
Adverse Effects of Alpha-1 BlockadeOrthostatic
Hypotension

• Normally, when a person stands up, the
  sympathetic ns is activated, forcing blood to be
  up in the head due to vasoconstriction in
  extremities
• If you block the alpha-1 receptors, this does not
  happen and the blood remains in the feet, leading
  to dizziness
• When a person stands up, their sympathetic
  nervous system is activated and their alpha-1
  receptors are stimulated with norepinephrine.
• This constricts their arteries and veins,
  increases venous return to the heart and arterial
  blood pressure and enables them to maintain blood
  flow to the brain.
• Alpha-1 blockade prevents this compensation and
  the person may feel dizzy or faint on standing
  up.

77
Adverse Effects of Alpha-1 BlockadeReflex
Tachycardia
78
Adverse Effects of Alpha-1 BlockadeReflex
Tachycardia

• As the blood pressure drops because of the
  alpha-1 blockade, the baroreceptor reflex is
  activated to raise the BP back up.
• Sympathetic tone is increased but arterioles and
  veins cant constrict b/c of the alpha-1
  blockade.
• Beta receptors on the heart can be activated,
  causing tachycardia.
• This can be prevented by giving a beta blocker
  with the alpha blocker.

79
Adverse Effects of Alpha-1 BlockadeNasal
Congestion
80
Adverse Effects of Alpha-1 BlockadeNasal
Congestion

• Blockade of alpha-1 receptors on blood vessels in
  the nose dilates those vessels and produces nasal
  congestion.

81
Beta-1 Receptor DrugsAgonists
82
Beta-1 Receptor DrugsAgonists

• Beta-1 agonists used to increase heart rate or
  strength of contraction.
• Used in the cardiac care unit
• Isoproterenol, dobutamine

83
Beta-2 Receptor DrugsAgonists
84
Beta-2 Receptor DrugsAgonists

• Beta-2 agonists used to dilate bronchioles or
  to stop preterm labor.
• A lot of them are inhaled
• Terbutaline
• Ritodrine
• Albuterol and others for asthma
• Relaxes the uterus to prevent pre-term labor

85
Beta Receptor DrugsAntagonists (Beta Blockers)
86
Beta Receptor DrugsAntagonists (Beta Blockers)

• Beta-1 specific (cardioselective)
• Nonspecific beta blockers
• Beta blockers with ISA
• Alpha/beta blockers

87
Beta Receptor DrugsAntagonists (Beta
Blockers)Beta-1 Specific (Cardioselective)
88
Beta Receptor DrugsAntagonists (Beta
Blockers)Beta-1 Specific (Cardioselective)

• Beta-1 specific (cardioselective) metoprolol
  and others their selectivity is not absolute
  and they may cause bronchospasm in some
  individuals.
• Beta-1 specific but can bind a little bit to
  beta-2

89
Beta Receptor DrugsAntagonists (Beta
Blockers)Nonspecific Beta Blockers
90
Beta Receptor DrugsAntagonists (Beta
Blockers)Nonspecific Beta Blockers

• Nonspecific beta blockers propranolol and
  others more likely to cause bronchospasm than
  cardioselective beta blockers because they
  antagoinze the beta-2 receptors

91
Beta Receptor DrugsAntagonists (Beta
Blockers)Beta Blockers with ISA
92
Beta Receptor DrugsAntagonists (Beta
Blockers)Beta Blockers with ISA

• Beta blockers with ISA (Intrinsic sympathomimetic
  activity) are really partial agonists. These
  drugs have little effect on resting heart rate or
  cardiac output.

93
Beta Receptor DrugsAntagonists (Beta
Blockers)Alpha/Beta Blockers
94
Beta Receptor DrugsAntagonists (Beta
Blockers)Alpha/Beta Blockers

• Alpha/Beta blockers labetolol and carvedilol
  used for hypertension or heart failure.

95
Important Effects of Beta Blockers
96
Important Effects of Beta Blockers

• Reduce heart rate, speed of conduction in the AV
  node, and ventricular contractility (beta-1).
• Reduce renin release from the kidney (beta-1).
• Cause bronchoconstriction (beta-2).

97
Important Effects of Beta BlockersHeart Rate
98
Important Effects of Beta BlockersHeart Rate

• These are all due to the blockade of beta-1
• Can cause symptomatic bradycardia
• Can cause lack of perfusion of brain and fainting
• Can cause heart block where the impulse does not
  go through the IV at all
• Can exacerbate heart failure
• The heart cannot pump enough to fulfill the
  demands of the body

99
Important Effects of Beta BlockersRenin Release
100
Important Effects of Beta BlockersRenin Release

• Leads to lowered blood pressure because of less
  angiotensin II.
• Lessens aldosterone release due to less
  angiotensin II, which lowers the blood pressure.

101
Important Effects of Beta BlockersBronchoconstric
tion
102
Important Effects of Beta BlockersBronchoconstric
tion

• May worsen asthma in susceptible individuals.

103
Therapeutic Uses of Beta Blockers
104
Therapeutic Uses of Beta Blockers

• Angina
• Decrease the workload on the heart by lowering HR
  and contractility.
• Decreases oxygen demand and helps the angina
• Hypertension
• Reduce peripheral vascular resistance.
• Cardiac Dysrrhythmias
• Have been shown to prevent sudden death in
  post-MI patients.
• Myocardial Infarction (heart attack)
• Reduce infarct size and risk of 2nd heart attack
  (re-infarction).
• Stage fright and test anxiety prevent
  tremulousness
• Glaucoma given topically for this indication

105
Adverse Effects of Beta BlockadeBeta-1 Blockade
106
Adverse Effects of Beta BlockadeBeta-1 Blockade

• Symptomatic bradycardia
• Reduced cardiac output/exacerbation of heart
  failure
• AV heart block
• Rebound cardiac excitation when the beta blocker
  is stopped abruptly may even lead to a heart
  attack
• The beta receptors have been upregulated by the
  blockade so when the drug is removed, the
  norepinephrine from the sympathetic nervous binds
  to all of the receptors and can lead to increased
  heart rate

107
Adverse Effects of Beta BlockadeBeta-2 Blockade
108
Adverse Effects of Beta BlockadeBeta-2 Blockade

• Bronchoconstriction
• Inhibition of glycogen breakdown
• May cause diabetic patients to have increased
  incidence of hypoglycemia

109
Acetylcholine (Cholinergic) Receptor
SubtypesDescription
110
Acetylcholine (Cholinergic) Receptor
SubtypesDescription

• Acetylcholinergic receptors subtypes include
• Nicotinic N receptors in the ganglion between the
  preganglionic neuron and the postganglionic
  neuron in the autonomic nervous system
• Muscarinic receptors at the effector organ in the
  parasympathetic nervous system and the sweat
  glands of the sympathetic nervous system
• Nicotinic M receptors at the muscle in the
  somatic motor system

111
Acetylcholine (Cholinergic) Receptor
SubtypesChart
112
Acetylcholine (Cholinergic) Receptor
SubtypesChart
Location Response to agonist
Nicotinic (neuronal) NN
On the postganglionic neurons of the autonomic system Stimulation of post-ganglionic sympathetic or parasympathetic transmission. Stimulation of epinephrine norepinephrine release from adrenal medulla.
Nicotinic (skeletal muscle) NM
On the skeletal muscle cells in the neuromuscular junction Skeletal muscle contraction
Muscarinic in parasympathetic nervous system
Heart, SA node Decreased heart rate (negative chronotropic)
Heart, AV node Decreased speed of conduction (negative dromotropic)
Bronchioles Bronchiolar constriction and increased secretion
Bladder Constriction (micturition)
GI tract Increased motility and increased secretions
Adapted from Lehne, 2009, Pharmacology for
Nursing Care, 7th ed., Elsevier, p. 114.
113
Muscarinic Agonists
114
Muscarinic Agonists

• These drugs are not used systemically very often
  since they have multiple unpleasant effects.
• Ex. micturation, increased secretions and
  motility, bronchiolar constriction
• Pilocarpine
• A muscarinic agonist that is used as an eye drop
  for glaucoma.
• Bethanecol
• A muscarinic agonist that is used for urinary
  retention but not very often
• Can be used orally for dry mouth.

115
Muscarinic Antagonists
116
Muscarinic Antagonists

• These drugs are frequently referred to as
  anticholinergic a misnomer.
• This is a misnomer because it only blocks
  musarinic receptors, in the effector organs in
  the parasympathetic nervous system and sweat
  glands of the sympathetic nervous system, not all
  cholinergic receptors
• Peripheral side effects
• Cant see
• Relaxation dilates pupil
• Dry eyes
• Cant pee
• Constricts bladder sphincter
• Cant spit
• Dries up mouth
• Cant shit (defecate)
• Stop GI secretions and motility
• In the brain
• Also can cause confusion and/or delirium.

117
Uses of Muscarinic Antagonists
118
Uses of Muscarinic Antagonists

• Used to dry up secretions preoperatively
• Dilate pupils (eye drops)
• Speed up the heart or ameliorate a heart block
• They were previously used as anti-diarrheals.
• (Relate these uses to activity of the
  parasympathetic nervous system at muscarinic
  receptors.)

119
Types of Muscarinic Antagonists
120
Types of Muscarinic Antagonists

• Atropine
• Scopolamine
• Used for motion sickness
• Glycopyrolate
• Does not get into the brain so it does not cause
  confusion
• Others

121
Cholinergic CrisisToo Much Cholinergic
Neurotransmission
122
Cholinergic CrisisToo Much Cholinergic
Neurotransmission

• Cholinergic crisis occurs when the muscarinic
  receptors are activated too much
• Ex. Nerve gases increase ACh
• Respond by giving muscarinic antagonist like
  atropine
• Leads to SLUDGE symptoms caused by activity of
  acetylcholine on muscarinic receptors of the
  parasympathetic nervous system.
• Salivation,
• Lacrimation
• Urination
• Defecation
• GI distress
• Emesis
• CNS depression coma, stupor, confusion caused
  by activity of acetylcholine on muscarinic or
  nicotinic receptors in the brain.
• Muscle symptoms fasciculations, fatigue, spasm
  caused by activity of acetylcholine on the
  nicotinic skeletal muscle receptors.
• Due to nicotinic m receptors on muscles

123
Atropine for Bradycardia or Heart Block
124
Atropine for Bradycardia or Heart Block

• Cause of Bradycardia and Heart Block
• Acetylcholine from parasympathetic nerve
  terminals binds to muscarinic receptors in the SA
  node and AV node and blocks them
• In the SA node, this slows the heart rate
  (negative chronotropic effect)
• In the AV node, this slows the speed of
  conduction (negative dromotropic effect).
• Role of Atropine
• Atropine blocks the effects of acetylcholine at
  muscarinic receptors, speeding the HR and
  speeding conduction through the AV node.
• Atropine may reverse bradycardia by removing the
  parasympathetic influence.
• May speed conduction in the AV node in heart
  block.
• This only works if parasympathetic stimulation is
  important in causing the bradycardia or heart
  block.

125
Muscarinic Antagonists for Urinary Incontinence
126
Muscarinic Antagonists for Urinary Incontinence

• Sometimes due to irritable bladder
• Irritable bladder occurs when the parasympathetic
  centers in the sacral cord respond too vigorously
  to a small amount of bladder stretch by
  initiating micturition.
• The motor portion of this reflex is mediated by
  muscarinic receptors.
• Several antimuscarinic drugs (oxybutynin
  Ditropan and tolterodine Detrol) are
  marketed to ameliorate this problem.
• Effect is modest
• Multiple side effects common to muscarinic
  antagonists

127
Drugs That Affect Nicotinic Receptors
128
Drugs That Affect Nicotinic Receptors

• Drugs that affect ganglionic nicotinic receptors
  are not in common use we will not cover them.
• Drugs that activate or block skeletal muscle
  nicotinic receptors (somatic nervous system) will
  be covered in a minute.

129
Which of the Following is a Therapeutic
Application of Alpha-1 Blockade?
130
Which of the Following is a Therapeutic
Application of Alpha-1 Blockade?

1. Angina
2. Cardiac Dysrrhythmias
3. Benign prostatic hypertrophy
4. Myocardial Infarction (heart attack)
5. Stage fright
6. Glaucoma given topically for this indication

131
Which of the Following Medications Would be used
when a Patient has Bradycardia or Heart Block?
132
Which of the Following Medications Would be used
when a Patient has Bradycardia or Heart Block?

• Pilocarpine
• Muscarinic agonist
• Treat glaucoma
• Bethanecol
• Muscarinic agonist
• Treat dry mouth and urinary retention
• Atropine
• Tolterodine Detrol
• Muscarinic agonist
• Used to treat urinary incontinence

133
Disorder of ANS due to Spinal Cord Injury
Autonomic Hyperreflexia
134
Disorder of ANS due to Spinal Cord Injury
Autonomic Hyperreflexia

• Autonomic hyperreflexia is a dangerous condition
  in patients with high spinal cord injuries.

135
Autonomic HyperreflexiaCauses
136
Autonomic HyperreflexiaCauses

• It arises because the sympathetic centers in the
  thoracolumbar cord (from T1-L2 below the spinal
  cord injury) are cut off from communication with
  the brain but the vagus nerve still carries motor
  impulses from the brain to organs in the
  chest/high abdomen.
• There becomes an imbalance between the
  sympathetic nervous system (operating
  autonomously) and the parasympathetic nervous
  system (which operates normally from the brain)
• It is usually triggered by a sensory stimulus in
  the lower part of the body (full bladder) that
  provokes a response from sympathetic centers in
  the spinal cord
• This is ameliorated in higher parts of the body
  by the parasympathetic system but not in lower
  parts of the body.

137
Autonomic HyperreflexiaEffects
138
Autonomic HyperreflexiaEffects

• The full bladder causes vasoconstriction and a
  rise in blood pressure
• Above the level of the injury you have
  vasodilation, decreased heart rate, and sweating
• Hypertension in lower part, vasodilation in upper
  body, and sweating
• Can lead to serious damage

139
Autonomic Hyperreflexia
Porth, 2007, Essential of Pathophysiology, 2nd
ed., Lippincott, p. 818.
140
Autonomic HyperreflexiaTreatment
141
Autonomic Hyperreflexia Treatment

• Initial treatment should be to remove the
  triggering sensory stimulus (i.e. catheterize the
  patient to empty the bladder).
• Strategies to lower the blood pressure, including
  pharmacologic treatment, may have to be employed.

142
True or False Autonomic hyperreflexia arises
because the sympathetic centers in the
thoracolumbar cord are cut off from communication
with the brain but the vagus nerve still carries
motor impulses from the brain to organs in the
chest/high abdomen.
143
True or False Autonomic hyperreflexia arises
because the sympathetic centers in the
thoracolumbar cord are cut off from communication
with the brain but the vagus nerve still carries
motor impulses from the brain to organs in the
chest/high abdomen.

1. True
2. False

144
Somatic Nervous System
145
Somatic Nervous System and Neuromuscular Blockers
146
Somatic Nervous System and Neuromuscular Blockers

• The somatic nervous synapse innervates the
  skeletal muscles
• The neuromuscular junction is a cholinergic
  synapse but it is not part of the ANS!
• It is the linkage between a motor nerve and a
  skeletal muscle it promotes voluntary movement.

147
Uses of Neuromuscular Blockers
148
Uses of Neuromuscular Blockers

• As adjunct to general anesthesia to facilitate
  endotracheal intubation and surgery.
• Paralyzes the patient to facilitate intubation
  and surgery
• With mechanically ventilated patients to conserve
  energy/prevent fighting the respirator.
• The patient is paralyzed but can think and feel.
• A sedative/analgesic or inhalation anesthetic
  MUST be used at the same time to make it so that
  the patient is sleeping rather than being awake
  and thinking and feeling

149
Muscle Contraction
150
Muscle Contraction
Lehne, 2007, Pharmacology for Nursing Care, 6th
ed., Elsevier, p. 140
151
Motor End Plate
152
Motor End Plate
Lehne, 2009, Pharmacology for Nursing Care, 7th
ed., Elsevier, p. 140
153
Nondepolarizing Neuromuscular Blockers
154
Nondepolarizing Neuromuscular Blockers

• Nondepolarizing neuromuscular blocking drugs are
  really antagonists at the nicotinic skeletal
  muscle acetylcholine receptor
• They block acetylcholine from binding and
  activating the receptor to cause muscle
  contraction.
• Causes the muscle to not contract

Lehne, 2009, Pharmacology for Nursing Care, 7th
ed., Elsevier, p. 142
155
Nondepolarizing Neuromuscular Blocker
Tubocurarine
156
Nondepolarizing Neuromuscular Blocker Tubocurarine
MOA ACh antagonist at neuromuscular junction?motor response?flaccid paralysis. Reversible with acetylcholinesterase inhibitors No CNS depression
Uses With mechanically ventilated patients to conserve energy/prevent fighting the respirator As adjunct to general anesthesia to facilitate endotracheal intubation and surgery
Nsg Patient cannot speak, move, or breathe unassisted BUThearing, thought processes, sensation not affected. Sedate ventilated patients and possibly administer an analgesic
157
Neuromuscular BlockadeSuccinylcholine
158
Neuromuscular BlockadeSuccinylcholine
Class Depolarizing neuromuscular blocker
MOA An ACh agonist at neuromuscular junction but is not rapidly degraded like acetylcholine is. It activates the nicotinic skeletal muscle acetylcholine receptor and first produces rapid fire depolarizations/muscle fasciculations. After causing these initial depolarizations, the succinylcholine remains bound and the muscle membrane becomes refractory to further depolarization and this produces paralysis. Not reversible with acetylcholinesterase inhibitors.
Uses Rapid inductions Endoscopy Used in the same ways as the nondepolarized neuromuscular blockers
Nsg Assess/manage airway/breathing Assess/manage pain
159
Acetylcholinesterase Inhibitors
160
Acetylcholinesterase Inhibitors

• Acetylcholinesterase is the enzyme that degrades
  acetylcholine in the synapse, halting its ability
  to bind with its receptor.
• Acetylcholinesterase inhibis the activity of
  acetylcholine
• Inhibitors of acetylcholinesterase will prevent
  the degradation of acetylcholine and thereby
  increase its duration of activity.
• This might be desirable or undesirable, depending
  on what you want to do.

Lehne, 2009, Pharmacology for Nursing Care, 7th
ed., Elsevier, p. 132
161
Inhibition of Cholinesterase by Reversible and
Irreversible Inhibitors
162
Lehne, 2009, Pharmacology for Nursing Care, 7th
ed., Elsevier, p. 132
163
Pharmacologic Acetylcholinesterase Inhibitors
164
Pharmacologic Acetylcholinesterase Inhibitors

• Examples
• Neostigmine
• Edrophonium
• Physostigmine
• Pyridostigmine
• Tacrine
• Usage depends on half-life.
• Short reversal of nondepolarizing neuromuscular
  blockers.
• Intermediate or long treatment of myasthenia
  gravis or Alzheimers disease.

165
NeostigmineUses
166
NeostigmineUses

• Used for reversal of neuromuscular blockade (IV)
  and for myasthenia gravis (po).
• Reversal of neuromuscular blockade
• The neuromuscular blocker competitively binds to
  the skeletal muscle nicotinic receptor meaning
  that bound drug and unbound drug are in a
  competition with acetylcholine, the
  neurotransmitter.

167
NeostigmineWinning the Competition
168
NeostigmineWinning the Competition

• Before neostigmine is given, the neuromuscular
  blocker is winning the competition for 2
  reasons.
• It is present in high concentration.
• Acetylcholine in the synapse is being degraded by
  acetylcholinesterase, lowering its concentration
• When neostigmine is given, acetylcholinesterase
  is inhibited so that it cant degrade
  acetylcholine.
• The concentration of acetylcholine in the synapse
  increases such that it wins the competition for
  the receptor, displacing the neuromuscular
  blocking drug.

169
NeostigmineAdverse Effects
170
NeostigmineAdverse Effects
Adverse effects SLUDGE symptoms (why?)
counteract with a muscarinic antagonist (atropine
or other). If given mistakenly to a patient who
has been paralyzed with succinylcholine instead
of a nondepolarizing agent, neostigmine will
worsen or prolong the paralysis Myasthenia
gravis is relatively rare we will not discuss
its treatment, although it is in Lehne, p. 136.
171
NeostigmineQuestions
172
NeostigmineQuestions

• Question What would happen if the neuromuscular
  blocker had a longer half-life than neostigmine?
• Would be a response and then would go back to
  being paralyzed
• Question What happens at other acetylcholine
  receptors (muscarinic and ganglionic nicotinic)
  that the neuromuscular blocker doesnt bind to?
• Increase in function when neostigmine is given

173
Acetylcholinesterase InhibitorsNerve Agents
174
Acetylcholinesterase InhibitorsNerve Agents
Examples Sarin Tabun
Route Inhalation contact
MOA Irreversible acetylcholinesterase inhibitors. Acetylcholine is increased in the synapse all over the body, which causes a polarizing neuromuscular blockade similar to that obtained with succinylcholine
Note Organophosphate insecticides also work by this mechanism, but they are more specific for acetylcholinesterase of insects and thus do not affect people except in high concentration.
175
Nerve Agent or Insecticide PoisoningSymptoms
176
Nerve Agent or Insecticide PoisoningSymptoms

• Immediate symptoms
• Respiratory arrest mediated by the ACh in the
  brain
• SLUDGE
• All are a part of the parasympathetic system
• Twitching/convulsing due to nicotinic m receptors
• Multi-organ involvement
• Possible coma and stupor.

177
Nerve Agent or Insecticide PoisoningAntidote
178
Nerve Agent or Insecticide PoisoningAntidote

• Must receive antidote
• The medicine reactivates the enzyme
• Atropine decreases secretions and other SLUDGE
  symptoms by blocking muscarinic receptors.
• Pralidoxime chloride (2-PAM Chloride or Protopam
  chloride)
• reactivates acetylcholinesterase at neuromuscular
  junction
• most critical effect muscles of respiration.
• Anticonvulsant lorazepam.

179
Which of the Following Drugs would Reverse
Neuromuscular Blockade?
180
Which of the Following Drugs would Reverse
Neuromuscular Blockade?

• Neostigmine
• Tubocurarine
• - Nondepolarizing neuronmusclar blocker
• Succinylcholine
• - polarizing nm blocker
• Pilocarpine

181
CNS Stimulants
182
Agents that Stimulate Neurotransmitter Release
183
Agents that Stimulate Neurotransmitter Release

• Most of the CNS stimulants stimulate
  neurotransmitter release
• Drugs that stimulate the release of
  norepinephrine from sympathetic nerve terminals
  have similar activity to norepinephrine itself.
• In fact, few such drugs act on noradrenergic
  nerve terminals only
• Most cause the release of all the catecholamine
  neurotransmitters (dopamine, norepinephrine, and
  epinephrine) from their respective nerve
  terminals, both in the periphery and in the CNS.
• Also inhibit the reuptake pumps that remove
  catecholamines from the synapse.
• Causes increased concentration of
  neurotransmitter in the synapse and increased
  activation of norepinephrine and dopamine
  receptors.

184
Central Nervous System Stimulants and the Synapse
185
Central Nervous System Stimulants and the Synapse
CNS stimulants cause neurotransmitter release and
blocks the neurotransmitter reuptake pump,
leading to more neurotransmitter in the synapse
Porth, Pathophysiology, Concepts of Altered
Health States, 7th ed., 2005, Lippincott, p. 1121.
186
CNS Stimulants
187
CNS Stimulants

• Drugs that increase catecholamine release and
  inhibit reuptake are known as CNS stimulants and
  have very specific therapeutic uses.
• Unfortunately, they are subject to widespread
  abuse, and are controlled substances.

188
Methylphenidate (Ritalin)
189
Methylphenidate (Ritalin)

• Classification CNS stimulant.
• Uses Attention Deficit-Hyperactivity Disorder.
• MOA Increases catecholamine (norepinephrine and
  dopamine) release into the synapse and inhibits
  their reuptake ?
• Increased attentiveness
• Increased concentration
• Decreased impulsivity and purposeless activity
• Various short-acting, intermediate-acting, or
  long-acting formulations are available.

190
MethylphenidateNursing Implications
191
MethylphenidateNursing Implications

• School nurse may have to administer and obtain
  baseline growth and development, height, weight,
  vital signs as well as monitor changes.
• Evaluate med effects in natural settings.
• Last dose 6h before bedtime
• Will keep the child awake
• Avoid caffeine-containing foods/beverages
• Have similar stimulant effects
• High abuse potential, esp. middle/high school.
• Drug holiday in summers or over Christmas
  vacation prevents the development of tolerance
  and also affords opportunity for assessment of
  the need for continued therapy.
• The child may not need to take the drug anymore
  and this offers the opportunity to assess for it
• Abrupt discontinuation may result in extreme
  fatigue and depression taper slowly!

192
Methylxanthines
193
Methylxanthines

• Caffeine and related compounds.
• All are derivatives of xanthine, a precursor to
  the nucleotide bases, adenine and guanine.
• One member of this class, theophylline, is used
  as a bronchodilator.

Lehne, 2009, Pharmacology for Nursing Care, 7th
ed., Elsevier, p. 394
194
Dogs and Chocolate
195
Dogs and Chocolate

• Dogs should not ingest chocolate because it is
  rich in theobromine
• A naturally occurring stimulant in the cocoa bean
• Increases urination and affects the CNS and heart
  muscle
• Symptoms
• Vomiting, diarrhea, hyperactivity, tachycardia,
  arrhythmia, muscle twitching, increased
  urination, excessive panting, hyperthermia,
  muscle tremors, seizures, coma, and death if
  enough is ingested

196
Caffeine
197
Caffeine

• Caffeine is used as a CNS stimulant throughout
  the world.
• The mechanism of action of caffeine and other
  methylxanthines is unclear.
• The most likely mechanism is that caffeine is an
  adenosine receptor antagonist.
• Adenosine receptors produce inhibitory/sedating
  effects, so blocking them produces stimulant
  effects.
• In spite of many research studies, no harmful
  effects have been associated with usual
  quantities of caffeine obtained by drinking
  caffeinated beverages.

198
A Nursing Consideration for the Administration of
Methylphenidate (Ritalin) is...?
199
A Nursing Consideration for the Administration of
Methylphenidate (Ritalin) is...?

1. Last dose should be taken 1 hour before bedtime
2. Should be taken with caffeine-containing
   foods/beverages
3. It has a low abuse potential
4. Abrupt discontinuation may result in extreme
   fatigue and depression

200
Things to Look for or Ask

• Slide 60 explain the diagram
• Slide 62
• Does norepinephrine activate all of the
  adrenergic receptor subtypes?
• Explain how the release of renin leads to
  increased blood pressure
• Slide 70
• Alpha-1 antagonists prevent the activity of __ at
  the __ receptor, leading to vasodilation
• Slide 150
• What should I know about this slide?
• Slide 152
• What should I know about this slide?
• Slide 162
• Explain the slide