Module 2 Section 3 (Sympathetic Nervous System)

Question 1

What is the sympathetic nervous system?

Answer 1

The sympathetic nervous system is a second division of the autonomic nervous system, alongside the parasympathetic nervous system.

In response to a perceived threat, the body specifically activates the sympathetic nervous system and prepares for fight or flight.

Question 2

What occurs when the SNS is activated?

Answer 2

• Increased heart rate
• Increased blood pressure
• Increased blood supply to the tissues
• Increased rate of cell metabolism
• Increased blood glucose

Question 3

Where do the neurons of the SNS originate?

Answer 3

The neurons of the SNS originate from the thoracic and lumbar regions of the spinal cord. These two sections constitute the middle portions of the spinal cord.

Question 4

Describe the structure of the preganglionic neurons of the SNS. What do the fibres release?

Answer 4

The sympathetic nervous system has short preganglionic neurons that release ACh at the ganglia.

Question 5

What happens when ACh binds to and activated NN receptors?

Answer 5

The acetylcholine binds to and activates NN receptors at the sympathetic ganglia, conducting the signal to the long postganglionic neurons of the sympathetic nervous system.

Question 6

Describe the structure of the postganglionic neurons of the SNS. What do the fibres release?

Answer 6

The sympathetic postganglionic neurons predominantly release norepinephrine at the target organ, which binds to alpha (α) or beta (β) receptors.
- Exceptions to this rule are the sympathetic postganglionic neurons that innervate sweat glands and renal vascular smooth muscle, as they release acetylcholine (binds to M receptors) and dopamine (binds to D receptors) respectively.

Question 7

List the characteristics and neurotransmitters relating to sympathetic regulation.

Preganglionic fibre
- SNS:

Postganglionic fibre
- SNS:

Neurotransmitters released from preganglionic fibre
- SNS:

Neurotransmitters released from postganglionic fibre
- SNS:

Fibre type
- SNS:

Answer 7

Preganglionic fibre
- SNS: short

Postganglionic fibre
- SNS: long

Neurotransmitters released from preganglionic fibre
- SNS: ACh

Neurotransmitters released from postganglionic fibre
- SNS: NE (mostly) and Epi

Fibre type
- SNS: adrenergic (G-protein coupled receptors)

Question 8

What are the autonomic nerve origins for the SNS?

Answer 8

SNS

• Fibres originate: thoracid and lumbar regions of the spinal cord
• Preganglionic fibres = short and end in ganglia located in chains down both sides of the spinal cord. Some, however, end in ganglia that’s located halfway b/w the CNS and effector organ
• Postganglionic fibres = long and end on the effector organs.

Question 9

What organs are influenced by the SNS?

Answer 9

• Sweat glands
• Cardiac muscle
• Smooth muscle
• Nerve terminals
• Gland cells
• Adrenal medulla

Question 10

What is the role of the adrenal medulla?

Answer 10

The adrenal medulla is a specialized organ that essentially functions as a sympathetic autonomic ganglion.

The adrenal medulla is the centre portion of the adrenal gland, surrounded by the adrenal cortex.

Question 11

What is the adrenal medulla innervated by? What occurs when it is activated?

Answer 11

It is innervated by sympathetic preganglionic fibres.

When these sympathetic preganglionic fibres are activated, they release acetylcholine, which binds to NN receptors on the adrenal medulla. Activation of these NN receptors results in the release of predominantly epinephrine (also known as adrenaline; 80%), but also norepinephrine (20%) from the adrenal medulla.

• The released Epi and NE travel through the blood and interact with α and β receptors throughout the body, causing varying effects.
• Since the neurotransmitters released by the adrenal medulla act via the circulation at distant sites, they are considered to act like hormones.

Question 12

True or false: stress can stimulate the adrenal medulla, releasing epinephrine and norepinephrine, leading to a prolonged sympathetic effect.

Answer 12

True

Question 13

Which one of the following effects listed is mediated by increased activity of the SNS?

a) Inhibition of the adrenal glands
b) Increased digestion
c) Increased heart rate
d) Constriction of the pupils

Answer 13

c) Increased heart rate

Question 14

What are the subtypes of alpha receptors? What occurs when they’re activated?

Answer 14

α1 receptors are located post-synaptically, predominantly on smooth muscle (e.g. blood vessels, GI muscle, and uterus).

• Activation of α1 receptors predominantly leads to contraction of the muscle.
• Multiple subtypes of α1receptors exist which are organ selective and drugs can be designed to target a specific subclass of α1 receptors, allowing for drug selectivity

α2 receptors are located post-synaptically on smooth muscle as well as pre-synaptically (auto-receptors) on the neuronal membrane.

• The effects listed for activation of α1receptors also apply to activation of α2 receptors that are located post-synaptically.
• Activation of α2 autoreceptors, however, leads to a decrease in the release of NE from the presynaptic nerve, thereby decreasing sympathetic activation. These receptors are only targeted in specific situations.

Question 15

What are the subtypes of beta receptors? What occurs when they’re activated?

Answer 15

β1 receptors are found predominantly in the heart and GI muscle, and when activated, increase the force and rate of contraction of the heart, and relax GI smooth muscle.

β2 receptors are found in the lungs, blood vessels, GI muscle, and uterus. Activation of these receptors leads to muscle relaxation.

Question 16

Which receptor corresponds to the primary locations listed?

a) Pre-synpatic neuronal membrane
b) Heart and gastrointestinal muscle
c) Lungs, blood vessels, gastrointestinal muscle, and uterus

Answer 16

a) Pre-synpatic neuronal membrane = a2
b) Heart and gastrointestinal muscle = β1
c) Lungs, blood vessels, gastrointestinal muscle, and uterus = β2

Question 17

Which receptor corresponds to the responses listed?

a) Relaxes smooth muscle
b) Contracts smooth muscle in the vessels and uterus and decreases motility and tone in the gastrointestinal tract
c) Increases heart rate and force of contraction
d) Decreases the release of norepinephrine from the presynaptic neuron

Answer 17

a) Relaxes smooth muscle = β2
b) Contracts smooth muscle in the vessels and uterus and decreases motility and tone in the gastrointestinal tract = a1
c) Increases heart rate and force of contraction = β1
d) Decreases the release of norepinephrine from the presynaptic neuron = a2

Question 18

True or false: Norepinephrine binds to α1or β receptors in the postsynaptic membrane to exert its action.

Answer 18

True

Question 19

How is the activity of NE terminated?

Answer 19

The activity of norepinephrine is terminated by reuptake back into the presynaptic neuron followed by enzyme degradation within the neuron.

Question 20

Drugs acting directly or indirectly on the SNS can mimic the actions of NE, thereby appearing to increase the activity of the sympathetic nervous system. What are the 3 mechanisms that allow this to occur? Provide examples.

Answer 20

1) Direct stimulation: the drug binds directly to the receptor and produces an effect.
- Ex: epinephrine, which works by directly binding to alpha and beta receptors.

2) Indirect stimulation: the drug increases the release of NE from the presynaptic neuron.
- Ex: Amphetamines act in this way.

3) Combination of the two: the drug binds directly to the receptor AND increases release of NE. Drugs can stimulate one or both of alpha and beta receptors.
- Ex: the drug ephedrine which is used as a decongestant.

Question 21

True or false: many drugs that activate the sympathetic nervous system target more than one receptor subtype.

Answer 21

True

Question 22

True or false: clinically, drugs that activate processes normally controlled by the SNS are primarily used for their effects on the heart, blood pressure, bronchial tree, and nasal passages.

Answer 22

True

These drugs produce similar effects to the anticholinergics, but due to the receptor subtypes (α1, β1,β2), the actions of these drugs are more specific and predictable depending on which receptor subtype is activated.

Question 23

What are the clinical indications for adrenergic drugs? (5)

Answer 23

Anaphylaxis:

• The treatment for these severe allergic reactions isepinephrine (e.g. EpiPen), which causes bronchodilation and constriction of blood vessels, relieving the symptoms.
• Epinephrine will also increase heart rate and the force of contraction of the heart, thereby increasing blood pressure if the person happens to go into shock.

Cardiac applications:

• Adrenergic drugs, such as epinephrine, increase heart rate and the force of contraction of the heart by activating β receptors.
• These drugs can be used for temporary emergency management of complete heart block or cardiac arrest.

Nasal congestion:

• α1 agonists constrict blood vessels and are therefore useful in the treatment of nasal congestion.
• Ex: Phenylephrine and pseudoephedrine

Ophthalmic:
- When given in the eye, α1 agonists such as phenylephrine dilate the pupil, facilitating retinal examination.

Pulmonary:

• β2-selective drugs, such as salbutamol, produce bronchodilation, which is an effective treatment for someone suffering from asthma.
• Both short-acting and long-acting β2 agonists are available. These drugs can also be used to treat chronic obstructive pulmonary disease (COPD).

Question 24

Which one of the conditions listed is the correct clinical indication for a beta 2 receptor agonist?

a) Congestive heart failure
b) Asthma
c) Nasal congestion
d) Benign prostatic hyperplasia

Answer 24

b) Asthma

Question 25

What are some adverse effects of adrenergic drugs

Answer 25

CNS: headache, restlessness, mild tremors, nervousness, dizziness, excitement, insomnia, euphoria.

Cardiovascular: palpitations, tachycardia, vasoconstriction, hypertension.

Other: anorexia, dry mouth, nausea, vomiting, muscle cramps.

Question 26

What are antiadrenergic drugs? What do they act on?

Answer 26

Drugs that inhibit the function of the sympathetic nervous system produce characteristics of “rest and relaxation” and have a wide therapeutic application.

Antiadrenergic drugs can specifically block either α or β receptors, or they can block both classes of receptors.

Question 27

True or false: the most widely prescribed drugs that target the autonomic nervous system are those drugs that block the sympathetic nervous system, called antiadrenergic drugs.

Answer 27

True

Question 28

What are some common indications of antiadrenergic drugs?

Answer 28

Pheochromocytoma: it’s a tumour of the adrenal medulla, the organ responsible for secreting epinephrine and norepinephrine in response to stress.

• The tumour secretes Epi and NE without the stimulus of stress, resulting in unwanted increases in sympathetic activity.
• Symptoms include intermittent or sustained high blood pressure, headache, palpitations, and increased sweating.
• Surgical resection of the tumour is the first-line treatment for pheochromocytoma, however an anti-adrenergic is first given to block the sympathetic receptors to prevent intra-operative hypertension.

Benign prostatic hyperplasia (BPH): BPH is a non-cancerous growth of the prostate gland that is common in older men.

• Symptoms include frequency, difficulty voiding, urgency, and voiding at night.
• Treatment includes α1 receptor antagonists, which work by relaxing smooth muscle in the prostate and bladder, facilitating urination.

Angina and congestive heart failure: angina is chest pain due to poor oxygen supply to the heart, while congestive heart failure is a condition where cardiac pumping is impaired due to weakening or death of part of the heart muscle.
- Treatment for both conditions can include selective β1 receptor antagonists. Blocking β1 receptors in the heart reduces heart rate and the force of contraction of the heart, resulting in a decrease in oxygen demand and blood pressure, thereby relieving the pain.

Glaucoma: a disease of the eye, often associated with increased intraocular pressure, which can damage the optic nerve and lead to loss of vision.

• β-blocking drugs are also useful in the treatment of glaucoma.
• Topical application of either non-selective or beta 1-selective beta blockers reduce the production of the aqueous humor, which in turn reduces intraocular pressure.

Neurological diseases: β-blockers are also useful in the treatment of a number of neurological diseases.
- Ex: β-blockers can reduce the frequency and intensity of migraines, reduce tremors in Parkinson’s Disease, and reduce anxiety. They may also benefit patients undergoing alcohol withdrawal.

Question 29

What is an adverse effect of antiadrenergic drugs?

Answer 29

Orthostatic hypotension is the decrease in blood pressure that occurs when moving from a laying or sitting position to a standing position.

This is a common adverse effect, as constriction of blood vessels is a normal process for maintaining blood pressure. With the use of antiadrenergic drugs, the ability of blood vessels to constrict is impaired, as is the ability of the heart to increase contractions, leading to decreased blood pressure.

Question 30

Since the transmission of messages in the synaptic junctions of the autonomic nervous system is chemical in nature, these junctions can be targets for drug action. Many drugs modify these systems, but they are often categorized into four general types. What are the 4 categories?

Answer 30

1) Drugs that mimic the effects of the sympathetic system.
2) Drugs that block the effects of the sympathetic system.
3) Drugs that mimic the effects of the parasympathetic system.
4) Drugs that block the effects of the parasympathetic system.

Thus, drugs that block the activity of one system can often “unmask” the activity of the other system.

Question 31

You are provided with the mechanism of action for 4 drugs. State whether each option mimics/blocks the SNS or PNS. Categorize the drugs according to the types of drugs that target the ANS:

a) Epinephrine: activates alpha and beta receptors
b) Propranolol: blocks beta receptors in the heart
c) Methacholine: activates muscarinic receptors
d) Atropine: blocks muscarinic receptor

Answer 31

a) Epinephrine: activates alpha and beta receptors = Drugs that mimic the effects of the sympathetic system
b) Propranolol: blocks beta receptors in the heart = Drugs that block the effects of the sympathetic system
c) Methacholine: activates muscarinic receptors = Drugs that mimic the effects of the parasympathetic system
d) Atropine: blocks muscarinic receptor = Drugs that block the effects of the parasympathetic system

Question 32

The activity of the autonomic nervous system also can be modified by drugs acting on the brain. How is this done?

Answer 32

Central stimulants (e.g. amphetamine) can increase sympathetic and parasympathetic activity (excitation), and central depressants can decrease the activity of these two systems (inhibition).

Question 33

Which neurotransmitter and receptor are correctly matched?

a) Acetylcholine: alpha 1 receptors
b) Norepinephrine: beta 1 receptors
c) Dopamine: beta 2 receptors
d) Epinephrine: nicotinic receptor

Answer 33

b) Norepinephrine: beta 1 receptors

Question 34

Which one of the statements regarding the sympathetic nervous system is correct?

a) Beta 1 receptors are predominantly found in the heart
b) The sympathetic nervous system has long preganglionic fibres
c) The adrenal medulla secretes epinephrine during relaxed states
d) Beta 2 receptors are found on pre-synaptic neuronal membranes

Answer 34

a) Beta 1 receptors are predominantly found in the heart