MnR S10 - Autonomic Nervous system

Question 1

Outline the general structure of how neurones are arranged in the ANS

Answer 1

Myelinated pre-ganglionic neurone in the CNS and unmylinated post-ganglionic neurone in the PNS

Question 2

Where does the parasympathetic outflow originate from?

Answer 2

Lateral horn of the medulla and sacral regions

Question 3

Where does the sympathetic outflow originate?

Answer 3

Lateral horn of the thoracic and lumbar regions

Question 4

Name two exceptions in the sympathetic nervous system where post-ganglionic neurones release ACh opposed to NA and act on muscarinic receptors

Answer 4

Sweat glands and hair follicles

Question 5

What are the other transmitters of the ANS and when would they be released?

Answer 5

Non-adrenergic, non-cholinergic transmitter (NANC)

Often co-released with NA or ACh

Question 6

Give some examples of NANC transmitters

Answer 6

ATP, Serotonin, Neuropeptides and nitric oxide

Question 7

How do sensory receptors in the carotid body and carotid artery, such as chemoreceptors, relay information to the CNS?

Answer 7

Via the glossopharyngeal nerve

Question 8

The primary sensory nerves project onto second order sensory nerves located in the medulla oblongata, what structure does this system form?

Answer 8

Nucleus tractus solitarius (nTS)

Question 9

Where else does the nucleus tractus solitarius nTS receive information from, other than primary sensory neurones?

Answer 9

The area postrema which is responsible for detecting toxins present in the blood and cerebrospinal fluid

Question 10

How are chromaffin cells stimulated and what do they behave as?

Answer 10

Stimulated by sympathetic input from pre-ganglionic neurones and then behave as specialised post-ganglionic neurones of the sympathetic NS by secreting adrenaline into the bloodstream

Question 11

How does the parasympathetic nervous system stimulate erection?

Answer 11

Release of Ach causes the release of NO which causes dilation of the trabecular arteries of the penis and subsequently the filling of the corpora cavernosa with blood

Question 12

What effect does the parasympathetic nervous system have on glands?

Answer 12

Stimulates secretion from sweat, salivary and lacrimal glands via M1 and M3 receptors

Question 13

What effect does the sympathetic nervous system have on the kidneys?

Answer 13

Stimulates renin secretion

Question 14

What is the autonomic input to the prostate gland and outline the effects

Answer 14

Parasympathetic- generation of secretions in epithelial cells

Sympathetic- contraction and secretion of the smooth muscle cells

Question 15

What are the most common targets for drug action in the neurotransmission pathway?

Answer 15

• Degradation of transmitter in the pre-synaptic neurone before release
• Interaction with post-synaptic receptors
• Inactivation of the transmitter
• Re-uptake of the transmitter
• Interaction with pre-synaptic receptors

Question 16

Which enzyme is involved in synthesis of Ach?

Answer 16

Choline acteyltransferase

Question 17

Describe the structure of sympathetic post-ganglionic neurones

Answer 17

Highly branching axonal network with numerous varicosities which are specialised sites for Ca2+ dependent noradrenaline release

Question 18

What is the function of pre-synaptic adrenoreceptors on the nerve terminal in the sympathetic NS?

Answer 18

Regulate NA release by acting as a feedback system

NA is release from the post-ganglionic nerve terminal and most binds to post-synaptic receptors whereas some binds to pre-synaptic receptors

Question 19

Which adrenoreceptors is involved in modulating the release of NA?

Answer 19

Alpha 2

• NA binding to receptors activates Gi which stimulates the beta-gamma sub-unit to block VOCC
• This decreases Ca2+ influx into the nerve terminal which decreases the release of NA via Ca2+ mediated exocytosis

Question 20

Which receptors do ganglion-blocking drugs act at and give an example of a drug of this class

Answer 20

Nicotinic Ach Receptors

Trimethaphan- used in hypertensive emergencies or to create controlled hypotension in surgery

Question 21

Which class of drugs would be used to treat overactive bladder?

Answer 21

Muscarinic antagonists e.g. tolterodine/ oxybutynin

Question 22

Give two examples of diseases treated with acteylcholinesterase inhibitors

Answer 22

Myasenthia gravis, Alzheimer’s

Question 23

List the common unwanted side effects of muscarinic agonists

Answer 23

Heart- decrease heart rate and cardiac output

Smooth muscle - increase bronchoconstriction and GI peristalsis

Exocrine glands- increase sweating and salivation

Question 24

What are the two methods of noradrenaline uptake?

Answer 24

Uptake 1- taken up into pre-synaptic terminal through the Na+ dependent high affinity transporter. Located on a neuronal membrane.

Uptake 2- takes up escaped NA, low affinity system that uses a non-neuronal mechanism. Located on non-neuronal membrane (smooth muscle cell, cardiac muscle, endothelium)

Question 25

What drugs can be used to inhibit uptake 1?

Answer 25

• Cocaine
• ## Tricyclic antidepressants

Question 26

What drugs can be used to inhibit uptake 2?

Answer 26

Steroids

Question 27

What are indirectly acting sympathiomimetic agents?

Answer 27

Drugs that are taken up into noradrenergic synaptic vesicles and displace NA causing it to leak out into the synaptic cleft independent of Ca2+ mediated exocytosis e.g. amphetamine

Question 28

What are the most commonly used beta adrenoreceptor antagonists in the treatment of heart failure?

Answer 28

Bisoprolol, metoprolol, carvedilol

Question 29

What are the different types of response brought about by ligand binding to a receptor?

Answer 29

Change in membrane permeability to ions

Generation of second messengers

Question 30

Define tachyphylaxis

Answer 30

Excessive exposure to an agonist leads to reduced sensitivity meaning more agonist is needed for the same response

Question 31

What leads to suprasensitivity?

Answer 31

Agonist deprivation

Excessive exposure to an antagonist

Question 32

List the possible causes of a change in tissue responsiveness

Answer 32

• Change in receptor number
• Change in receptor coupling to second messengers
• Change in availability of second messengers
• Change in cell responsiveness

Question 33

Where do opioids act?

Answer 33

Opioid receptors in the CNS and PNS

Question 34

What changes occur in the process of opioid withdrawel with an addict?

Answer 34

• Opiod levels fall
• As the opioid leaves the receptor it is less likely to be replaced
• Second messenger activity falls
• Patient begins to perceive pain

Question 35

How does angina treatment affect the number of beta adrenoreceptors?

Answer 35

Beta blockers cause an up-regulation of beta adrenoreceptors

Question 36

Give two possible causes of bronchoconstriction in asthmatics

Answer 36

Increased parasympathetic stimulation

Decreased sympathetic stimulations

Question 37

List four possible treatments for asthma

Answer 37

• Muscarinic antagonists
• Beta 2 adrenoreceptor agonists
• Glucocorticosteroids
• Leukotriene modifiers
• Xanthine

Question 38

What is the advantage of patient controlled analgesia?

Answer 38

Decrease chances of tachyphylaxis as patient administers the drug intermittently opposed to regularly as a doctor would so less likely to become opioid dependent

Question 39

Why are adrenoreceptors not up regulated in phaeochromocytoma?

Answer 39

Intermittent release of noradrenaline means there is no tachyphylaxis

Question 40

How does increasing age, so elderly patients compared to young, affect catecholamine sensitivity?

Answer 40

Decreased sensitivity to endogenous catecholamines

Reduced heart rate responsiveness to exogenous catecholamines

Potential excess pharmacological efficacy of administered drugs