Drugs And The ANS

Question 1

What does the ANS do?

Answer 1

Controls all involuntary functions (e.g. Heart rate, blood pressure etc)

Entirely efferent but regulated by afferent inputs

Question 2

What are the two divisions of the ANS?

Answer 2

Sympathetic and parasympathetic

Question 3

What is the vagus nerve important for?

Answer 3

Regulating the heart

Question 4

Where do parasympathetic nerves originate from?

Answer 4

Lateral horn of the medulla and sacral spinal cord

Question 5

What fibres do parasympathetic nerves have?

Answer 5

Long myelinated preganglionic fibres, short unmyelinated postganglionic fibres

Question 6

Where do sympathetic nerves originate?

Answer 6

Lateral horn of the lumbar and thoracic spinal cord

Question 7

What fibres do sympathetic nerves have?

Answer 7

Short myelinated preganglionic fibres, long unmyelinated postganglionic fibres

Question 8

Where are the ganglia located in sympathetic nerves?

Answer 8

Paravertebral chain close to the spinal cord

Question 9

Where are the ganglia located in parasympathetic nerves?

Answer 9

Within the innervated tissues

Question 10

What are the principal neurotransmitters in the ANS?

Answer 10

Acetylcholine and noradrenaline

Question 11

What are all pre ganglionic neurons?

Answer 11

Cholinergic - use ACh as their neurotransmitter

Question 12

What does parasympathetic and sympathetic pre ganglionic release of ACh result in?

Answer 12

Activation of post ganglionic nicotinic ACh receptors

Question 13

What are parasympathetic post ganglionic neurons?

Answer 13

Cholinergic - release ACh which acts on muscarinic ACh receptors in the target effector tissue

Question 14

What are the 5 mACh receptor subtypes?

Answer 14

M1, M2, M3, M4 and M5

Question 15

What are muscarinic ACh receptors?

Answer 15

GPCRs

Question 16

What are most sympathetic post ganglionic neurons?

Answer 16

Noradrenergic - used noradrenaline as principal neurotransmitter

Question 17

What does noradrenaline interact with?

Answer 17

a-adrenoceptors and b-adrenoceptors

Question 18

Are all adrenoceptors GPCRs?

Answer 18

Yes

Question 19

What are some examples of specialised sympathetic post ganglionic neurons that are cholinergic as opposed to noradrenergic?

Answer 19

Those innervating sweat glands and hair follicles

Question 20

What are other transmitters found in the ANS called?

Answer 20

Non Adrenergic, Non Cholinergic transmitters
NANC transmitters

(May be coreleased with NA or ACh)

Question 21

What are some examples of NANC transmitters?

Answer 21

ATP
Nitric Oxide
5-hydroxytryptamine (5HT; serotonin)
Neuropeptides (eg VIP - vasoactive intestinal peptide and substance P)

Question 22

What does the adrenal medulla release?

Answer 22

Adrenaline

Question 23

Where are chromaffin cells present?

Answer 23

Adrenal medulla

Question 24

Why are sympathetic postganglionic neurons in the adrenal glands different?

Answer 24

They differentiate to form neurosecretory chromatin cells which can be considered as postganglionic sympathetic neurons that do not project to a target tissue. Instead, on sympathetic stimulation, these cells release adrenaline into the bloodstream

Question 25

What does parasympathetic release of ACh cause in the heart?

Answer 25

Bradycardia and reduced cardiac conduction velocity - M2 receptors

Question 26

What does parasympathetic release of ACh cause in smooth muscle?

Answer 26

Bronchial contraction Increased intestinal mobility and secretion *these act on M3 receptors* ``` Bladder contraction (detrusor) and relaxation (trigone/sphincter)Emile erection Ciliary muscle and iris sphincter contraction ``` *Nitric Oxide generation*

Question 27

What does parasympathetic release of ACh cause in glands?

Answer 27

Increased sweat/salivary/lacrimal secretion M1/M3 receptors

Question 28

What does sympathetic release of noradrenaline cause in the heart?

Answer 28

Tachycardia and positive inotropy (b1 receptors)

Question 29

What does sympathetic release of noradrenaline cause in smooth muscle?

Answer 29

Arteriolar/venous contraction (a1, b2) Bronchioles/intestine/uterine relaxation (b2) Bladder sphincter contraction (b2) Radial muscle contraction in eye (a1)

Question 30

What does sympathetic release of noradrenaline cause in the kidneys?

Answer 30

Renin release

Question 31

How is acetylcholine synthesised?

Answer 31

AcetylcoA + choline --> acetylcholine + coenzyme A Choline acetyltransferase Acetyl coA produced from pyruvate by pyruvate dehydrogenase Choline obtained from diet

Question 32

How is acetylcholine degraded?

Answer 32

Acetyl choline ---> acetate + choline By acetylcholinesterase

Question 33

What is trimethaphan used for?

Answer 33

Hypertensive emergencies and to produce controlled hypotension during surgery (Ganglion blocking drug)

Question 34

What is tolterodine and what is it used to treat?

Answer 34

mAChR antagonist (M3 receptors in this case) Used to treat overactive bladder Side effects include dry mouth

Question 35

What is pyridostigime used to treat?

Answer 35

Myasthenia graves - AChE inhibitor so actions of endogenously released ACh can be enhanced

Question 36

What can donepezil be used to treat?

Answer 36

Alzheimer's disease AChE inhibitor so enhances endogenous release of ACh

Question 37

What often limits the usage of cholinergic drugs?

Answer 37

Unwanted side effects - relative lack of selectivity Eg non selective muscarinic ACh receptor agonist would decrease HR, lead to bronchoconstriction, increase sweating and salivation etc

Question 38

What is the SLUDGE mnemonic?

Answer 38

Pathological effects indicative of massive discharge of the parasympathetic nervous system ``` Salivation Lacrimation Urination Defecation Gastrointestinal upset Emesis (vomiting) ```

Question 39

When is SLUDGE usually encountered?

Answer 39

Drug overdose Ingestion of magic mushrooms Exposure to organophosphorous insecticides eg parathion Exposure to nerve gases eg sarin

Question 40

What do parathion and sarin do?

Answer 40

Covalently modify acetylcholinesterase to irreversibly deactivate the enzyme and raise acetyl choline levels

Question 41

What are the symptoms of SLUDGE primarily due to?

Answer 41

Chronic stimulation of mAChR in organs and muscles innervated by the parasympathetic nervous system

Question 42

How can SLUDGE be treated?

Answer 42

Atropine, pralidoxime or other anti cholinergic agents

Question 43

What are some examples of mAChR agonists?

Answer 43

Pilocarpine and bethanechol

Question 44

What is pilocarpine used to treat?

Answer 44

Glaucoma

Question 45

What is bethanechol used to treat?

Answer 45

Urinary retention, stimulates bladder emptying

Question 46

What are some examples of mAChR antagonists?

Answer 46

Ipratropium, tiotropium, tolterodine, darifenacin and oxybutynin

Question 47

What are ipratropium and tiotropium used to treat?

Answer 47

Asthma and COPD

Question 48

What mAChR antagonists are used to treat overactive bladder?

Answer 48

Tolterodine, darifenacin and oxybutynin

Question 49

What do post ganglionic sympathetic neurons generally possess?

Answer 49

Highly breaching atonal network with numerous varicosities, each of which is a specialised site for Ca2+ dependent noradrenaline release

Question 50

What enzyme converts noradrenaline to adrenaline in the adrenal medulla?

Answer 50

Phenylethanolamine N-methyltransferase

Question 51

Why does noradrenaline only have a limited time in which to influence pre and post synaptic adrenoceptors?

Answer 51

It is rapidly removed from the synaptic cleft by noradrenaline transporter proteins

Question 52

How are noradrenaline actions terminated?

Answer 52

Uptake 1 - re uptake into pre synaptic terminal by Na+ dependent, high affinity transporter Uptake 2 - NA not re captured by uptake 1 is taken up by a lower affinity, non neuronal mechanism

Question 53

Which two enzymes is noradrenaline susceptible to metabolism by?

Answer 53

Monoamine oxidase (MAO) Catechol-O-methyltransferase (COMT)

Question 54

What is an example of a b2 selective agonist?

Answer 54

Salbutamol, important that it is selective as it limits possible CV side effects

Question 55

What are two examples of adrenoceptor antagonists used in treating hypertension?

Answer 55

Doxazosin (a1 adrenoceptor selective antagonist) Atenolol (b1 adrenoceptor selective antagonist)