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

Autonomic Nervous System

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Function of the Autonomic Nervous System

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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

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Divisions of the Autonomic Nervous System

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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

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Sympathetic Division of the Autonomic Nervous System

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Sympathetic Division of the Autonomic Nervous System

• Maintains vital functions

• Responds when there is a critical threat to the integrity

• “Fight or flight response”

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Fight or Flight Response

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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

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Parasympathetic Division of the Autonomic Nervous System

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Parasympathetic Division of the Autonomic Nervous System

• Concerned with conservation of energy

• Resource replenishment

• Maintenance of organ function during inactivity

• “Rest and digest”

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Rest and Digest Response

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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.

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Patterns of Innervation and Control of the ANS

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• 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

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16Lehne, 2009, Pharmacology for Nursing Care, 7th ed., Elsevier, p. 107

Structure of Both Divisions of the ANS

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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).

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The Peripheral Nervous System

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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.20

Comparison of Somatic and Autonomic Nervous Systems

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• 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) 22

Comparison of the Nervous Systems

Somatic Nervous System

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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

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Parasympathetic Nervous System

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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 organ26


Sympathetic Nervous System

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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 effects28


Diagram with Neurotransmitters

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Comparison of Somatic and Autonomic Nervous SystemsDiagram with Neurotransmitters


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 muscarinic3. 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)

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Neurotransmitters of the Autonomic Nervous System

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Neurotransmitters of the Autonomic Nervous System

• Acetylcholine

• Norepinephrine

• Epinephrine

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Acetylcholine

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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

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Norepinephrine

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Norepinephrine

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

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Epinephrine

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Epinephrine

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

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The Sympathetic Nervous System

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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

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Sympathetic Pathways

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Sympathetic Pathways

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Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 755.

Sympathetic PathwayThe Adrenal Medulla

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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.)

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The Parasympathetic System

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The Parasympathetic System

• Two CNS centers– The brainstem– The sacral cord

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The Parasympathetic SystemThe Brainstem Centers

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The Parasympathetic SystemThe Brainstem Centers

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•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

The Parasympathetic SystemSacral Parasympathetic Outflow

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The Parasympathetic SystemSacral Parasympathetic Outflow

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•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.

The Parasympathetic SystemParasympathetic End Organs

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The Parasympathetic SystemParasympathetic End Organs

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•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.

Transmitters and Receptors of the Autonomic Nervous System

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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 muscle3. 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

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Transmitters and Receptors of the ANS


Comparison of the SNS and PNS

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Comparison of the SNS and PNS

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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

ANS End Organs

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ANS End Organs

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Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 858

Adrenergic Receptor Subtypes

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Adrenergic Receptor Subtypes

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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 RelaxationAdapted from Lehne, 2009, Pharmacology for Nursing Care, 7th ed., Elsevier, p. 115.

Which of the Following is a Result of SNS Stimulation?

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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

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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 system3. The SNS is concerned with

conservation of energy.4. The PNS responds when

there is a critical threat to the integrity of the organism

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What of the Following is a True Statement?

• The ANS is a motor system

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Alpha-1 Receptor DrugsAgonists

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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

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Alpha-1 Receptor DrugsAntagonists

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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)

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Therapeutic Applications of Alpha-1 Antagonists

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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.

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Adverse Effects of Alpha-1 Blockade

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Adverse Effects of Alpha-1 Blockade

• Orthostatic hypotension

• Reflex tachycardia

• Nasal congestion

• Inhibition of ejaculation– Can still have an erection but cannot ejaculate

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Adverse Effects of Alpha-1 BlockadeOrthostatic Hypotension

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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.

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Adverse Effects of Alpha-1 BlockadeReflex Tachycardia

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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 can’t 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.

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Adverse Effects of Alpha-1 BlockadeNasal Congestion

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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.

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Beta-1 Receptor DrugsAgonists

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

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83


• 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

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Beta Receptor DrugsAntagonists (Beta Blockers)

85


• Beta-1 specific (cardioselective)

• Nonspecific beta blockers

• Beta blockers with ISA

• Alpha/beta blockers

86


Beta-1 Specific (Cardioselective)

87


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

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Beta Receptor DrugsAntagonists (Beta Blockers)Nonspecific Beta Blockers

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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

90


Beta Blockers with ISA

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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.

92


Alpha/Beta Blockers

93


Alpha/Beta Blockers

94

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

Important Effects of Beta Blockers

95


• 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).

96


Heart Rate

97

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

98


Renin Release

99

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.

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Bronchoconstriction

101

Important Effects of Beta BlockersBronchoconstriction

• May worsen asthma in susceptible individuals.

102

Therapeutic Uses of Beta Blockers

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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

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Adverse Effects of Beta BlockadeBeta-1 Blockade

105


• 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

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107


• Bronchoconstriction

• Inhibition of glycogen breakdown– May cause diabetic patients to have increased

incidence of hypoglycemia

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Acetylcholine (Cholinergic) Receptor Subtypes

Description

109


Description

• 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

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Chart

111

Acetylcholine (Cholinergic) Receptor SubtypesChart

112

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 secretionsAdapted from Lehne, 2009, Pharmacology for Nursing Care, 7th ed., Elsevier, p. 114.

Muscarinic Agonists

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Muscarinic Agonists

114

•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.

Muscarinic Antagonists

115

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– Can’t see

• Relaxation dilates pupil• Dry eyes

– Can’t pee• Constricts bladder sphincter

– Can’t spit• Dries up mouth

– Can’t shit (defecate)• Stop GI secretions and motility

• In the brain• Also can cause confusion and/or delirium.

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Uses of Muscarinic Antagonists

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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.)

118

Types of Muscarinic Antagonists

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Types of Muscarinic Antagonists• Atropine

• Scopolamine– Used for motion sickness

• Glycopyrolate– Does not get into the brain so it does not cause

confusion

• Others120

Cholinergic CrisisToo Much Cholinergic

Neurotransmission

121

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 muscles122

Atropine for Bradycardia or Heart Block

123

Atropine for Bradycardia or Heart Block

124

•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.

Muscarinic Antagonists for Urinary Incontinence

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Muscarinic Antagonists for Urinary Incontinence

126

•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

Drugs That Affect Nicotinic Receptors

127

Drugs That Affect Nicotinic Receptors

128

•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.

Which of the Following is a Therapeutic Application of

Alpha-1 Blockade?

129

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

1. Angina2. Cardiac Dysrrhythmias3. Benign prostatic

hypertrophy4. Myocardial Infarction

(heart attack)5. Stage fright 6. Glaucoma – given

topically for this indication

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Which of the Following Medications Would be used

when a Patient has Bradycardia or Heart Block?

131

Which of the Following Medications Would be used when a Patient has Bradycardia or

Heart Block?

1. Pilocarpine- Muscarinic agonist- Treat glaucoma

2. Bethanecol- Muscarinic agonist- Treat dry mouth and

urinary retention3. Atropine4. Tolterodine [Detrol®]

- Muscarinic agonist- Used to treat urinary

incontinence 132

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Disorder of ANS due to Spinal Cord Injury: Autonomic

Hyperreflexia

133

Disorder of ANS due to Spinal Cord Injury: Autonomic Hyperreflexia

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

134

Autonomic HyperreflexiaCauses

135

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.

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Autonomic HyperreflexiaEffects

137

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

138

Autonomic Hyperreflexia

139

Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 818.

Autonomic HyperreflexiaTreatment

140

141

Autonomic HyperreflexiaTreatment

•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.

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.

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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. True2. False

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Somatic Nervous System

144

Somatic Nervous System and Neuromuscular Blockers

145

Somatic Nervous System and Neuromuscular Blockers

146

•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.

Uses of Neuromuscular Blockers

147

Uses of Neuromuscular Blockers

148

•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

Muscle Contraction

149

Muscle Contraction


Motor End Plate

151

Motor End Plate


Nondepolarizing Neuromuscular Blockers

153

154

•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

Nondepolarizing Neuromuscular Blockers

Lehne, 2009, Pharmacology for Nursing Care, 7th ed., Elsevier, p. 142

Nondepolarizing Neuromuscular Blocker

Tubocurarine

155

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

•BUT—hearing, thought processes, sensation not affected.

•Sedate ventilated patients and possibly administer an analgesic 156

Neuromuscular BlockadeSuccinylcholine

157

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 158

Acetylcholinesterase Inhibitors

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Acetylcholinesterase Inhibitors

160

•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.


Inhibition of Cholinesterase by Reversible and Irreversible

Inhibitors

161

162


Pharmacologic Acetylcholinesterase Inhibitors

163

Pharmacologic Acetylcholinesterase Inhibitors

164

•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 Alzheimer’s disease.

NeostigmineUses

165

NeostigmineUses

166

• 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.

NeostigmineWinning the Competition

167

NeostigmineWinning the Competition

168

• 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 can’t degrade acetylcholine.• The concentration of acetylcholine in the synapse

increases such that it “wins the competition” for the receptor, displacing the neuromuscular blocking drug.

NeostigmineAdverse Effects

169

NeostigmineAdverse Effects

170

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.

NeostigmineQuestions

171

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 doesn’t bind to?– Increase in function when neostigmine is given

172

Acetylcholinesterase InhibitorsNerve Agents

173

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.

174

Nerve Agent or Insecticide PoisoningSymptoms

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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.

176

Nerve Agent or Insecticide PoisoningAntidote

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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.

178

Which of the Following Drugs would Reverse Neuromuscular

Blockade?

179

Which of the Following Drugs would Reverse Neuromuscular Blockade?

1. Neostigmine2. Tubocurarine

- Nondepolarizing neuronmusclar blocker

3. Succinylcholine- polarizing nm blocker

1. Pilocarpine

180

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CNS Stimulants

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Agents that Stimulate Neurotransmitter Release

182

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.

183

Central Nervous System Stimulants and the Synapse

184

Central Nervous System Stimulants and the Synapse

185Porth, Pathophysiology, Concepts of Altered Health States, 7th ed., 2005, Lippincott, p. 1121.

CNS stimulants cause neurotransmitter release and blocks the neurotransmitter reuptake pump, leading to more neurotransmitter in the synapse

CNS Stimulants

186

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.

187

Methylphenidate (Ritalin)

188

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.

189

MethylphenidateNursing Implications

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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!191

Methylxanthines

192

Methylxanthines

193

•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.


Dogs and Chocolate

194

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

195

Caffeine

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Caffeine

197

•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.

A Nursing Consideration for the Administration of

Methylphenidate (Ritalin) is...?

198

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

199

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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 200

Documents

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