Module 2 Section 2 (Parasympathetic Nervous System))

Question 1

Where do the neurons of the PNS originate?

Answer 1

The neurons of the parasympathetic nervous system originate from the cervical (top region) and sacral (bottom region) of the spinal cord.

Question 2

Describe the structure of the preganglionic fibres of the PNS. What does it release?

Answer 2

The parasympathetic nervous system has long preganglionic fibres that release acetylcholine, which binds to the nicotinic receptors (NN) in the ganglia.

Question 3

What happens after activation of the nicotinic receptors?

Answer 3

Activation of the NN receptors on the postsynaptic membrane results in depolarization and propagation of the impulse along the postganglionic fibre.

Question 4

Describe the structure of the postganglionic fibres of the PNS. What does it release?

Answer 4

The postganglionic fibres are short and also release acetylcholine, which binds to muscarinic receptors (M) on the target organ.

Question 5

List the characteristics and neurotransmitters relating parasympathetic regulation.

Preganglionic fibre
- PNS:

Postganglionic fibre
- PNS:

Neurotransmitters released from preganglionic fibre
- PNS:

Neurotransmitters released from postganglionic fibre
- PNS:

Fibre type
- PNS:

Answer 5

Preganglionic fibre
- PNS: long

Postganglionic fibre
- PNS: short

Neurotransmitters released from preganglionic fibre
- PNS: ACh

Neurotransmitters released from postganglionic fibre
- PNS: ACh

Fibre type
- PNS: cholinergic

Question 6

Discuss the autonomic nerve origin for the PSN.

Answer 6

PNS

• Preganglionic fibres arise from the brain or lower spinal cord
• Preganglionic fibres = long and end in ganglia (terminal ganglia) near the effector organ
• Postganglionic fibres = very short

Question 7

What are the neurotransmitters in the PNS?

Answer 7

• Preganglionic fibres: long; ACh

- Postganglionic fibres: short; ACh

Question 8

How do drugs act on the PNS?

Answer 8

Drugs can activate the PNS (muscarinic receptor agonists)

OR

Drugs can inhibit the PNS (muscarinic receptor antagonists)

Question 9

Which function is mediated by the parasympathetic nervous system?

a) Stimulation of the digestive system
b) Increased heart rate
c) Bronchodilation
d) Increased cell metabolism

Answer 9

a) Stimulation of the digestive system

Question 10

True or false: all parasympathetic nerves release acetylcholine.

Answer 10

True

Synapses and receptors that release and bind acetylcholine are described as cholinergic.

Question 11

What can ACh bind to in the PNS?

Answer 11

Acetylcholine can bind to two receptors: muscarinic (M) and nicotinic (NN) receptors.

Question 12

What is the difference between muscarinic and nicotinic receptors?

Answer 12

Muscarinic receptors are typical G-protein coupled receptors, while nicotinic receptors are ligand-gated ion channels.

Muscarinic (M)
- Primary locations: heart
• Responses: decreased heart rate and force of contraction
- Primary locations: smooth muscle, glands
• Responses: smooth muscle contraction and gland secretion

Nicotinic (NN)
- Primary locations: ganglia
• Responses: impulse conducted to postganglionic neuron

Question 13

How are ACh-mediated responses terminated?

Answer 13

To terminate the acetylcholine-mediated response within the parasympathetic nervous system, acetylcholinesterase (AchE) breaks down acetylcholine in the synaptic cleft into acetate and choline.

Question 14

Drugs can be classified into five groups (agonist, partial agonist, allosteric activator, competitive antagonist, and non-competitive antagonist) based on their interaction with the receptor. Of these five groups, which are activators and which are inhibitors?

Answer 14

Activators:

• Agonist
• Partial agonist
• Allosteric activator

Inhibitors:

• Competitive antagonists
• Non-competitive antagonist

Question 15

What are the 3 main actions that drugs can stimulate/activate the PNS?

Answer 15

1) Drugs can bind to and activate nicotinic receptors
2) Drugs can bind to and activate muscarinic receptors
3) Drugs can block the metabolism of acetylcholine (by inhibiting AchE), thereby increasing the concentration of acetylcholine in the synaptic cleft.

Question 16

True or false: drugs that block the metabolism of acetylcholine are called indirect acting agents.

Answer 16

True

Also called parasympathomimetic or cholinomimetic agents.

Question 17

True or false: drugs that bind receptors are called direct acting agents.

Answer 17

True

Also called parasympathomimetic or cholinomimetic agents.

Question 18

What do drugs that stimulate the PNS do?

Answer 18

Drugs that stimulate the parasympathetic nervous system produce characteristics of rest and relaxation.

Direct and indirect acting agents can be referred to as cholinomimetics drugs, since they mimic the action of acetylcholine (at NN or M receptors).
- The activation of the NN receptors activates the postganglionic neurons of both the parasympathetic and sympathetic nervous systems. Therefore, to activate specifically the parasympathetic nervous system, the drug must bind to and activate just M receptors.

Question 19

Why aren’t cholinergic drugs widely used?

Answer 19

Clinically, cholinergic drugs are not widely used as they can adversely slow the heart rate and constrict the respiratory passages.

Question 20

What are some clinical indications for cholinergic drugs?

Answer 20

1) Glaucoma
2) Poor muscle tone in the bladder
3) Asthma

Question 21

How do cholinergic drugs treat glaucoma?

Answer 21

Glaucoma is a condition where the patient experiences an increase in intraocular pressure (can lead to optic nerve damage, which will affect vision and eventually lead to blindness) due to poor drainage of the fluid of the eye.

One treatment for glaucoma is muscarinic receptor agonists, such as pilocarpine. Administration of a muscarinic receptor agonist increases PNS activation in the eye, leading to contraction of the ciliary body of the eye.
- This facilitates drainage of the fluid and decreases the pressure in the eye.

While muscarinic agonists can be used to treat glaucoma, often beta antagonists are preferred.

Question 22

How do cholinergic drugs treat poor muscle tone in the bladder?

Answer 22

Patients who’re postop or postpartum sometimes experience poor muscle tone in the bladder. It can be due secondary to spinal cord injury or disease.

The administration of a muscarinic agonist will cause the bladder to contract, allowing the patient to urinate.

Question 23

How do cholinergic drugs diagnose asthma?

Answer 23

The diagnostic test for asthma is called the methacholine challenge. Methacholine is a muscarinic agonist, and when inhaled it causes the bronchioles to constrict, inhibiting breathing.

• Patients are given increasing doses of methacholine, with each dose being followed by a pulmonary function test.
• Patients who have asthma will be hypersensitive to methacholine, meaning that their breathing will become restricted due to the methacholine at a lower dose than will occur for patients who do not have asthma.

Once the methacholine challenge is completed, patients are given a beta 2 (β2) agonist to relax the bronchioles and return the lungs to normal functioning.

Question 24

What drugs that inhibit the PNS?

Answer 24

• Anticholinergic drugs
• Ganglion-blocking drugs
• Muscarinic receptor blockers

Question 25

What is the most common drug used to inhibit the PNS? Why do they have limited clinical use?

Answer 25

The most common drugs that inhibit the PNS are anticholinergic drugs – drugs that antagonize or block M or NN receptors and are more common than cholinergic drugs.
- By inhibiting the parasympathetic nervous system, anticholinergic drugs cause effects of “fight or flight.”

These drugs are associated with high incidences of adverse effects, which has limited their clinical use. In particular, anticholinergic drugs can cause tachycardia (i.e. a fast heart rate), which can be dangerous.

Question 26

What are ganglion-blocking drugs? Why do they have limited clinical use?

Answer 26

Ganglion-blocking drugs (e.g. hexamethonium), which are drugs that specifically inhibit the NN receptors found in all autonomic ganglia, are important for physiological and pharmacological research, as they block all autonomic outflow.

However, ganglion-blocking drugs have limited clinical use because of the broad range of adverse effects associated with them.

Question 27

What are muscarinic receptor blockers?

Answer 27

Muscarinic receptor blockers are used more commonly. The prototypical muscarinic receptor antagonist is atropine, which is a competitive antagonist of all muscarinic receptors, and when administered as a liquid drop to the eyes, will dilate pupils for a week or more! Thus, shorter-acting muscarinic antagonists are now used to dilate pupils.

Question 28

What are the other clinical indications for drugs that ibhibit the PNS?

Answer 28

Respiratory disorders: people who have asthma or chronic obstructive pulmonary disease can sometimes be prescribed muscarinic antagonists. - When inhaled, these drugs have a good safety profile and will produce moderate bronchodilation and decreased airway secretion.

Gastrointestinal (GI) disorders: gastrointestinal cramps, hypermotility, and diarrhea can be treated with muscarinic antagonists, which will decrease intestinal motility.

Urinary disorders: some patients experience urgency to urinate due to conditions such as minor bladder inflammation and incontinence. A muscarinic antagonist will inhibit the contraction of the bladder

Question 29

Cholinergic poisoning, meaning poisoning due to excess acetylcholine, can occur due to toxic nerve gas. In August 2013, toxic nerve gas was released in Syria. Specifically, this toxic nerve gas was Sarin, which is a colourless, odourless gas that is a potent acetylcholinesterase inhibitor. Acetylcholinesterase is responsible for breaking down acetylcholine in the synaptic cleft into acetate and choline, thereby terminating the response to acetylcholine. Using your previous knowledge, discuss the role of acetylcholine in the parasympathetic nervous system.

Answer 29

Acetylcholine is a neurotransmitter released by pre-and post-ganglionic neurons in the PNS.

Acetylcholine can bind to nicotinic or muscarinic receptors to activate the parasympathetic nervous system and induce the ‘rest-and-digest’ response

Question 30

Sarin blocks acetylcholinesterase, thereby inhibiting the breakdown of acetylcholine. The result is an exaggerated parasympathetic response, including constriction of pupils, tightness in the chest, nausea, drooling, defecation, and urination. Death is due to asphyxiation, and in this incidence in Syria, hundreds of people died due to cholinergic poisoning. Now that you have learned about the parasympathetic nervous system, if you were asked how to treat people with toxic nerve gas poisoning, what type of drug would you suggest?

Answer 30

People suffering with cholinergic poisoning have too much ACh in their system, producing exaggerated PNS responses.

One good drug to use would be a muscarinic receptor antagonist.

• This would inhibit some of the exaggerated parasympathetic effects observed.
• A good choice would be atropine, since it blocks all muscarinic receptors and is long-acting. It would help delay the symptoms, however the major problem of acetylcholine not being broken down still remains.

We need to somehow regenerate acetylcholinesterase. The drug pralidoxime will bind to the Sarin gas and remove it from the acetylcholinesterase, thereby regenerating enzyme activity.

Question 31

True or false: the antidote for cholinergic poisoning is atropine and pralidoxime.

Answer 31

True

However pralidoxime has to be administered within five hours of poisoning for the acetylcholinesterase to be regenerated

Question 32

An indirect activator of the parasympathetic nervous system initiates a response or alters a response by:

a) Directly binding to muscarinic receptors
b) Directly binding to alpha receptors
c) Directly binding to beta receptors
d) Directly binding to acetylcholinesteras

Answer 32

d) Directly binding to acetylcholinesteras

Question 33

Which one of the items is an appropriate therapeutic use of an antagonist of the parasympathetic nervous system?

a) To dilate pupils
b) To diagnose asthma
c) To treat poor muscle tone in the bladder
d) To treat gastrointestinal paralysis

Answer 33

a) To dilate pupils