M&R Session 10 Flashcards Preview

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Flashcards in M&R Session 10 Deck (104):
1

Is the ANS efferent, afferent or both?

Entirely efferent

2

What type of input regulates the ANS?

Afferent inputs

3

Where do parasympathetic nerves originate from?

Lateral horn of medulla and sacral spinal cord

4

Describe parasympathetic pre-ganglionic neurones.

Long
Myelinated

5

Describe parasympathetic post-ganglionic neurones.

Short
Unmyelinated

6

Where are the ganglia in the parasympathetic division of the ANS?

Target tissues

7

Where do sympathetic nerves originate in the sympathetic nervous system?

Lateral horn of lumbar and thoracic spinal cord

8

Describe sympathetic preganglionic nerves.

Short
Myelinated

9

Describe sympathetic postganglionic nerves.

Long
Unmyelinated

10

Where are sympathetic ganglia found?

Paravertebral chain

11

Which neurotransmitter is used in all preganglionic neurones?

ACh

12

What type of receptors are found on postganglionic neurones in both the sympathetic and parasympathetic nervous systems?

Nicotinic AChR

13

Which neurotransmitter and corresponding receptor do postganglionic parasympathetic neurones use?

ACh
mAChR

14

Which type of neurotransmitter and corresponding receptor do postganglionic sympathetic neurones utilise?

NA
Alpha and beta adrenoceptors

15

How may genes code for adrenoceptors in the human genome?

9

16

Are all sympathetic postganglionic neurones noradrenergic?

Nope

17

Which sympathetic postganglionic neurones are cholinergic?

Sweat glands
Piloerector muscles

18

When can NANC transmitters be released?

Coreleased w/NA or ACh

19

Give four examples of NANC transmitters.

ATP
Nitric oxide
5-hydroxytryptamine
Neuropeptide

20

How is ATP used as a NANC transmitter?

Copackaged into vesicles, especially w/NA

21

What does ATP use as a NANC transmitter regulate?

BP

22

Give two examples of neuropeptides used as NANC transmitters.

Vasoactive intestinal peptide
Substance P

23

What do sympathetic postganglionic neurones in the adrenal glands differentiate to form?

Neurosecretory chromaffin cells

24

What is the function of chromaffin cells?

Release adrenaline into blood

25

What type of receptors are found in chromaffin cells?

nAChR

26

Which area/s of the heart does parasympathetic ACh release act on?

Atria - sparse if any input to ventricles

27

What two effects does activation of M2 receptors by ACh have in the heart?

SAN --> bradycardia
AVN --> decrease cardiac conduction velocity

28

Which receptor subtype is found in the lungs and GI tract and is activated by ACh?

M3

29

What is the affect of ACh release on the lungs and GI tract?

Lungs - bronchial contraction
GI - increased mobility and secretion

30

What are the effects of ACh release on the GU tract?

Bladder contraction
Sphincter relaxation
Penile erection (increased bloodflow)

31

What is the affect of ACh release on the eye?

Ciliary muscle and iris sphincter contraction

32

What causes the increase in bloodflow which causes penile erection?

Nitric oxide

33

Which receptor type is found in glandular tissue which is activated by ACh release?

M1/3

34

What is the affect of M1/3 activation by ACh in glandular tissue?

Control level and composition of secretion

35

Which component of the lungs, GI tract, GU tract and eye is affected by ACh release?

Smooth muscle

36

What does the ANS exist in parallel but separate to?

Somatic nervous system

37

What effects does NA release have on the heart?

SAN --> +ve chronotropy
Ventricle --> +ve inotropy

38

Which receptors are activated in the heart by NA?

Beta-1 (mainly)
Beta-2

39

What does the balance of beta-1 and beta-2 receptors in the heart depend on?

The individual

40

What affect does NA release have on the smooth muscle of the vasculature?

BV contract
Arteriolar relaxation in some vascular beds

41

What type of receptors constrict visceral BV upon NA release?

Alpha-1

42

What type of receptors dilate BV in exercising tissue?

Beta-2

43

What subtype/s of receptor cause smooth muscle relaxation in the lungs, GI tract and GU tract upon NA release?

Beta-2
(Beta-3)

44

What does the activation of receptors (thought to be beta-3) in the GU by NA cause the bladder sphincter to do?

Contract

45

What does alpha-1 activation by NA cause in the eye?

Radial muscle contraction

46

What increases viscous secretion in the salivary glands?

NA release

47

What causes renin release in the kidney?

NA release

48

How is the prostate gland innervated by the ANS?

Parasympathetic on epithelial cells controlling generation of secretion
Sympathetic on smooth muscle contraction --> release of secretory products

49

What additional medication were prostate cancer patients with a better prognosis noted to be taking?

Beta-blockers

50

What is seen in all prostate cancers irrespective of age of patient that affects the rate of development and metastasis?

Neurogenesis

51

What constantly modulates efferent ANS neurone activity?

Afferent/sensory ANS inputs

52

What monitors carbon dioxide, oxygen, arterial pressure, GI tract content and chemical composition?

Sensory neurones

53

What is sensed by the carotid body/ chemoreceptors at carotid artery bifurcation?

Blood oxygen, carbon dioxide and pH

54

How are the inputs to the carotid body/ chemoreceptors at carotid artery bifurcation coordinated?

Glossopharyngeal nerve --> CNS

55

What forms the nucleus tractus solitarius (nTS)?

Primary sensory neurones acting on second order sensory neurones in medulla oblongata

56

What is the function of area postrema?

Detect toxins in blood and CSF
Essential for chemical-induced vomiting
Essential for conditional taste aversion

57

What integrates all visceral afferent information?

Nucleus tractus solitarius

58

What are the 12 basic steps in neurotransmission?

Uptake of precursors
Synthesis of transmitter
Vesicular storage of transmitter
Degradation of transmitter
Depolarisation by propagated AP
Depolarisation-dependent influx of calcium ions
Exocytotic release of transmitter
Diffusion to post-synaptic membrane
Interaction w/ post-synaptic receptors
Inactivation of transmitter
Re-uptake of transmitter
Interaction w/pre-synaptic receptors

59

Which steps of neurotransmission can be targeted by drugs?

Degradation of neurotransmitter
Interaction w/post-synaptic receptors
Inactivation of transmitter
Re-uptake of transmitter
Interaction w/pre-synaptic receptors

60

Why is degradation of ACh immediate?

Abundance of AChE

61

What can be used to irreversibly inhibit AChE in terrorist attacks?

Sarin

62

How is ACh formed?

Acetyl CoA + choline --> ACh + CoA
Uses choline acetyltransferase (CAT)

63

Where can cholinergic function be manipulated in the ANS?

Ganglia
Effector - especially parasympathetic branch

64

What does interfering with the cholinergic function at the ganglia of the ANS effectively do?

Switch off ANS

65

Why can nAChR at autonomic ganglia be targeted and the nAChR at the NMJ be unaffected?

Different receptor structures

66

What is Trimethapan?

Ganglion-blocking drug used in hypertensive emergencies and when hypotension is needed during surgery

67

How many mAChR subtype specific agonists or antagonists are currently available clinically?

Only a few

68

What is Tolterodine?

mAChR antagonist used to treat an overactive bladder w/limited tissue selectivity

69

How can endogenous ACh release be enhanced?

AChE inhibitors

70

Pyridostigmine and Donepezil are AChE inhibitors. What are they used to treat?

Pyridostigmine - myasthenia gravis
Donepezil - Alzheimer's

71

What often has to be given with a mAChR agonist to prevent unwanted side effects caused by low specificity?

Antagonist

72

How can low specificity mAChR agonists and antagonists be used effectively clinically?

Administer locally not systemically

73

How are mAChR agonists pilocarpine and bethanechol used to treat glaucoma and to stimulate bladder emptying respectively?

Used w/pharmacodynamics to localise drug effects

74

What are mAChR antagonists ipratrapium and tiotropium used to treat?

Asthma
COPD

75

What are Tolterodine, clarifenacin and oxybutynin?

mAChR antagonists used to treat an overactive bladder

76

What do postganglionic sympathetic neuron axons form to allow for specialised sites of calcium-dependent NA release?

Highly branched atonal network w/numerous varicosities which are regularly arranged
(Beads on a string)

77

What do varicosities allow for?

Coordinated responses on a wide field of the effector organ

78

Give the intermediates of noradrenaline synthesis

Tyrosine --> DOPA --> dopamine --> noradrenaline

79

Which enzymes are needed for NA synthesis?

Tyrosine hydroxylase
DOPA decarboxylase
Dopamine beta-hydroxylase

80

Which stage of NA synthesis takes place in the vesicle?

Conversion of dopamine to NA

81

What type of receptor forms the auto-regulatory feedback system in NA release?

Alpha-2

82

How does alpha-2 activation prevent further NA release?

Beta-gamma subunits inhibit VOCCs

83

How can DOPA be sued to treat Parkinson's disease?

Delivered in pharmacokinetic protected dose

84

How is NA release terminated?

Rapidly by Uptake 1
Rest by Uptake 2
Small amount escapes

85

What is Uptake 1?

High affinity, sodium dependent NA transporter

86

What percentage of released NA is recaptured by Uptake 1?

90-95%

87

What is Uptake 2?

Lower affinity, non-neuronal NA transporter protein

88

Why can NA metabolism only occur after uptake?

Lack of extracellular enzymes

89

What happens to the majority of NA uptaken after release?

~90% is repackaged into vesicles

90

What happens to the NA uptake that is not repackaged into vesicles?

Metabolised by monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT)

91

What are tyramine, amphetamine and ephedrine examples of?

Indirectly acting sympathiomimetic agents

92

How do indirectly acting sympathiomimetic agents intervene in adrenergic transmission?

Taken up into vesicles --> allow NA leak from vesicles and into synaptic cleft without influx of calcium ions

93

What are tricyclic antidepressants and selective NA re-uptake inhibitors examples of?

Uptake 1 inhibitors

94

Where do Uptake 1 inhibitors exert their major therapeutic action?

CNS

95

What must be minimised by drug choice and dosage when using amitryptyline, imipramine or reboxetine for example?

Peripheral actions e.g. tachycardia and cardiac dysrhythmia

96

What are salbutamol and salmeterol?

Beta-2 selective agonists used to treat asthma

97

What are doxazosin and atenolol, drugs used for CVS disorders incl. hypertension?

Doxazosin - alpha-1 antagonist
Atenolol - beta-1 antagonist

98

What are the NICE guidelines for treatment of chronic heart failure?

Beta blocker
ACEI
Diuretic

99

What do the NICE guidelines for treatment of chronic heart failure using three classes of drugs cause?

Proven mortality and morbidity benefits

100

Give three examples of proven efficacy drugs which are better than other types of beta-blockers for treatment of chronic heart failure.

Bisoprolol
Metoprolol
Carvedilol

101

Which adrenoceptors do bisoprolol and metoprolol act on in chronic heart failure?

Beta-1

102

Why is Carvedilol which acts on beta-1, beta-2 and alpha-1 receptors very effective?

Causes uniques adaptations to receptors not seen with other drugs

103

How does the paradoxical increase in alpha-adrenoceptor subtypes seen when using Carvedilol to treat chronic heart failure present clinically?

Initially patients become very tired but a week later they are much better

104

What percentage of the population is affected by chronic heart failure, which is classified as a disease of old age?

3%