1 - Intro to ANS

Question 1

Pharmacodynamics

Answer 1

What drugs do to body

Question 2

Pharmacokinetics

Answer 2

What body does to drug

Question 3

What are the three branches of the peripheral nervous system (and what do they control)

Answer 3

Autonomic [automatic], somatic and (neuroendocrine)

exocrine glands, smooth muscle, cardiac muscle, metabolism, host defence

skeletal muscle, respiratory muscle

growth, metabolism, reproduction, development, salt/water balance, host defence

Question 4

Is vagus sympathetic or parasympathetic

Answer 4

Parasympathetic

Question 5

Parasympathetic

Answer 5

Rest and digest, thoracic lumbar

Question 6

Sympathetic

Answer 6

Fight or flight, cranial/sacral

Question 7

Describe the relative lengths of the pre- and post-ganglionic fibres and neurotransmitter(s) in the parasympathetic nervous system

Answer 7

(Only 1 type) Long pre-ganglionic, short post-

Acetylcholine (ACh)

Discrete, localised 1:1

Question 8

Describe the relative lengths of the pre- and post-ganglionic fibres and neurotransmitter(s) in the sympathetic nervous system

Answer 8

(1 type w/ exceptions) Short pre-ganglionic, long post-

ACh then NorA (90%)

• Same but no post ganglionic, adrenal medulla secretes A/NorA (80:20)
• Same but ACh for both (e.g. sweat gland)

Coordinated, divergent 1:20 (formation of trunk)

Question 9

Why does sweat use ACh as post-ganglionic neurotransmitter

Answer 9

ACh is also used by parasympathetic nervous system
Parasympathetic often controls secretions (rest and digest)
Sweat (though sympathetic) is also a secretion
Thus may be a relic

Question 10

Summarise the layout of the enteric nervous system

Answer 10

Chemo and stretch receptors (mucosal)

Sensory neurones

via Interneurones

Submucosal (Meissner)/Mesenteric (Auerbach) plexus

Motor neurones [ACh or substance P to contract smooth muscle, vasoactive intestinal peptide or nitric oxide to relax smooth muscle)

Question 11

What does the somatic nervous system use as its neurotransmitter

Answer 11

The only similarity is that the somatic nervous system also uses ACh as its neurotransmitters

Direct

Question 12

What are the types of cholinoceptor

Answer 12

Nicotinic and Muscarinic

Question 13

Briefly outline the structure and location of nicotinic receptors

Answer 13

Type 1 - ionotropic

In nervous system, therefore all pre-ganglions

Question 14

Briefly outline the structure and location of muscarinic receptors

Answer 14

Type 2 - g protein coupled

In effector organ, therefore all post-ganglion where ACh is used

Question 15

Manipulation of which receptor would allow you to control all aspects of the autonomic nervous system

Answer 15

Nicotinic receptors

Question 16

Which of the following effects would be observed after blockade of nicotinic receptors in an individual at rest?

1. Bronchoconstriction
2. Increased sweat
3. Constipation
4. Increased urine
5. Short-sightedness

Answer 16

At rest = parasympathetic function
Therefore observation must equate to opposite of parasympathetic function.

3. Constipation

Question 17

What effect would blockade of nicotinic acetylcholine receptors have on heart rate;

1. At rest
2. During exercise

Answer 17

1. At rest parasympathetic (vagus) keeps HR down so inhibition would cause an increase in HR
2. During exercise the sympathetic system is in control and causes an increase in HR so inhibition will decrease the rate of increase

Question 18

Draw out the diagram of target organs and the effect of either sympathetic or parasympathetic stimulation

Answer 18

See diagram (6,5)
*exception, 1 only one function, 2 one pathway for both

Eyes, Salivary Glands
*Trachea and Bronchioles, 2*Skin
2Liver, Heart
1Adipose, GI
1Kidneys, 2BVs
Ureter and Bladder

Pupil, Ciliary Muscle
Detrusor, trigones, sphincter
Rate and contractility
Tone, contractility and sphincter

Question 19

How many subtypes of muscarinic receptor are there and where are they found

Answer 19

5 subtypes
M1 Neural {forebrain, learning and memory}
M2 Cardiac {brain, inhibitory autoreceptors}
M3 Exocrine and Smooth Muscle {hypothalamus, food intake}

M4 Periphery; prejunctional nerve endings
M5 Striatal dopamine release

Question 20

What are the types of adrenoceptor

Answer 20

a1, a2, b1, b2

Question 21

Where are adrenoceptors located

Answer 21

Only in the sympathetic nervous system

In the effector organs where NorA or A are the neurotransmitters

Question 22

Where are the cholinoceptors located

Answer 22

Both in the parasympathetic and sympathetic nervous systems
Nicotinic is in all between pre and post
Muscarinic only in effector organs where ACh is used

Question 23

Draw diagram which shows location of all the receptors

Answer 23

See diagram

Question 24

What are 3 important questions to consider for all drugs

Answer 24

1. What is the drug target? (nicotinic/muscarinic, adrenoceptor)
2. Where is the drug target? (side effects due to different targets)
3. What is the end result [of the interaction]?

Question 25

Using the 3 q structure, how does the autonomic nervous system control gut function

Answer 25

Gut function is parasympathetic

M3 muscarinic receptors, exocrine (endocrine) and smooth muscle cells in the stomach, increased secretion of pepsin and HCL (gastrin) + increased tone and motility

Question 26

Using the 3 q structure, how does the autonomic nervous system increase heart rate

Answer 26

Increase in HR is sympathetic via NorA

beta adrenoceptors, nodal tissue, HR increases

Question 27

Blockade of which of the following targets would cause the most significant increase in NorA concentrations?
1. Tyrosine hydroxylase
2. DOPA decarboxylase
3. Uptake 1 transport protein
4, Monoamine oxidase
5. Cathecol-O-methyl transferase

Answer 27

3. Uptake 1 transport protein

Question 28

What is the 7 step general pathway for neurotransmitter synthesis, release and metabolism

Answer 28

1. Precursor
2. Formation of neurotransmitter (T)
3. Packaging T into vesicles
4. Exocytosis
5. Receptor binding
6. Metabolism into degradation products
7. Reuptake

Question 29

Draw out the 7 step general pathway for neurotransmitter synthesis, release and metabolism

Answer 29

See diagram

Question 30

What is the 7 step pathway for ACh synthesis, release and metabolism

Answer 30

1. Acetyl CoA + Choline
2. ACh + CoA (choline acetyltransferase)
   3.
   4.
   5.
3. Acetate + Choline (acetylcholinesterase)
   7.

Question 31

What is the 7 step pathway for NorA synthesis, release and metabolism

Answer 31

1. Tyrosine
2. DOPA (tyrosine hydroxylase), Dopamine (DOPA decarboxylase)
3. NorA (dopamine b hydroxylase in vesicle)
   4.
   5.
4. Uptake 1 [close], Uptake 2 [far]
5. MOA-A (Monoamine Oxidase), COMT (Catechol-O-methyl-transferase)

Question 32

What enzymes are involved in ACh synthesis, release and metabolism

Answer 32

Choline acetyltransferase

Acetylcholinesterase

Question 33

What enzymes are involved in NorA synthesis, release and metabolism

Answer 33

Tyrosine hydroxylase
DOPA decarboxylase
Dopamine b hydroxylase

MOA-A, COMT

Question 34

What does COMT stand for

Answer 34

Catechol-O-methyl-transferase

Question 35

Which receptors do we have a lot/do not have specific drugs for

Answer 35

Not many specific drugs for muscarinic receptors

Many specific ones for adrenoceptors

Question 36

In which of the following tissues are muscarinic ACh receptors not found?

1. the pancreas
2. ciliary muscle
3. cardiac muscle
4. sweat glands
5. adrenal medulla

Answer 36

5. adrenal medulla