The Autonomic Nervous System and Pharmokinetics Flashcards Preview

ESA 2- Membranes and Receptors > The Autonomic Nervous System and Pharmokinetics > Flashcards

Flashcards in The Autonomic Nervous System and Pharmokinetics Deck (76):
1

What is the ANS comprised of?

A series of two neurones, one pre-ganglionic and one post-ganglionic

2

What is the ganglion?

The collection of cell bodies in the PNS

3

Where do the neurones in the ANS have their cell bodies?

One in the CNS, one in the PNS

4

What do neurones in the ANS exert action via?

Smooth muscle
Viscera
Secretory glands

5

What is the thoraco-lumbar outflow part of?

The sympathetic nervous system

6

Where do the nerve fibres that contribute to the thoraco-lumbar outflow have their cell bodies?

In all 12 thoracic sections and the first 2 lumbar sections

7

How long are the nerve fibres in the thoraco-lumbar outflow?

Short pre-ganglionic nerve fibre
Long post-ganglionic nerve fibre

8

Where can the nerve fibres synapse in the thoraco-lumbar outflow?

May synapse at the same level as origin (paravertebral origin)
May synapse at different level to origin
May not synapse in paravertebral chain

9

What kind of neurones are the pre-ganglionic in the thoraco-lumbar outflow?

Cholinergenic (ACh)

10

What do the post-ganglionic neurones in the thoraco-lumbar outflow express?

Nicotinic receptors

11

What kind of neurones are the post-ganglionic in the thoraco-lumbar outflow?

Noradrenergic (NA)

12

What are the classes of adrenoreceptors?

Alpha (1 and 2)
Beta (1 and 2)

13

What is the exception to the rules of the thoraco-lumbar rules?

Some synapses are cholinergic- perspiration and ejaculation pathways

14

What is the cranio-sacral outflow part of?

The parasympathetic nervous system

15

How long are the nerve fibres in the cranio-sacral outflow?

Long pre-ganglionic nerve fibre
Short post-ganglionic nerve fibre

16

What kind of neurones are the pre-ganglionic in the cranio-sacral outflow?

Cholinergic

17

What do the post-ganglionic neurones in the cranio-sacral outflow express?

Nicotinic receptors

18

What kind of neurones are the post-ganglionic in the cranio-sacral outflow?

Cholinergic

19

What synthesises acetylcholine?

The enzyme choline acetyltransferase (CAT)

20

What is acetylcholine synthesised from?

Choline and the metabolic intermediate Acetyl-CoA

21

Where is acetylcholine synthesised?

In the cytoplasm of cholinergic terminals

22

What happens to acetylcholine once synthesised?

Some is degraded by cytoplasmic cholinesterase
The majority is transported into synaptic vesicles by an indirect active transport mechanism

23

What do cholinergic terminals possess?

Numerous vesicles contain high concentrations (>100mM) of ACh

24

How can ACh be released from cholinergic terminal vesicles?

By Ca mediated exocytosis

25

What happens to released ACh?

It can interact with both pre- and postsynaptic cholinoreceptors

26

What is the opportunity for ACh to interact with receptors limited by?

ACh in the synaptic cleft being acted upon by cholinesterase, which rapidly degrades ACh to choline and acetate

27

Where is the activity of cholinesterase highest?

At fast (nicotinic) cholinergic synapses

28

What is the result of cholinesterase at cholinergic synapses?

The synaptic cleft half-life of ACh is only a few milliseconds

29

What recaptures most choline?

A choline transporter present in the synaptic terminal

30

What is noradrenaline synthesised from?

Tyrosine

31

Where is noradrenaline synthesised?

Within the nerve terminal

32

What is the rate limiting enzyme in noradrenaline synthesis?

Tyrosine hydroxylase

33

Where is the enzyme dopamine ß-hydroxylase located?

Within synaptic vesicles

34

What does dopamine ß-hydroxylase do?

Transports newly synthesised dopamine into the vesicle prior to its conversion to noradrenaline

35

What does dopamine ß-hydroxylase recognise?

Dopamine and noradrenaline

36

What does dopamine ß-hydroxylase recognising dopamine and noradrenaline allow for?

It's recycling following release and reuptake

37

At what level is cytoplasmic NA concentration under most circumstances?

Low

38

At what level is intravesicular NA concentration under most circumstances?

Very high (0.5-1.0M)

39

Why is a very high intravesicular NA concentration possible?

Because the vesicular transporter exploits a H-ATPase-generated cytoplasm-vesicle H-gradient to move catecholamines against their concentration gradient

40

What is cytoplasmic NA susceptible?

Enzymatic breakdown by monoamine oxidase

41

How is tyrosine converted to noradrenaline?

Tyrosine -> dopa -> dopamine -> noradrenaline

42

How is NA released?

Ca mediated exocytosis

43

What can released noradrenaline interact with?

Both pre- and postsynaptic adrenoreceptors

44

What is the opportunity for noradrenaline to interact with adrenoreceptors limited by?

A high affinity reuptake system, Uptake 1

45

What does uptake 1 act to do?

Rapidly remove NA from the synaptic cleft, rapidly decreasing the localised concentration and terminating its actions

46

What happens to any NA escaping from the synaptic cleft?

It is removed from the extracellular space by another, widespread, lower affinity reuptake system, uptake 2

47

What is ACh and NA release triggered by?

Depolarisation of the nerve terminal membrane, Ca entry, and fusion of vesicles with the pre synaptic membrane (Ca mediated exocytosis)

48

What drugs act on cholinergic nerve terminals?

Nicotinic cholinoceptor antagonists
Muscarinic cholioceptor agonists
Muscarinic cholinoceptor antagonists
Cholinesterase inhibitors

49

How do agents that interfere with cholinergic transmission and are of therapeutic use generally act?

By interaction with cholinoceptors

50

What is the exception to agents interfering with cholinergic transmission acting by interaction with cholinoceptors?

Cholinesterase inhibitors

51

How are cholinesterase inhibitors used therapeutically?

They decrease the rate of ACh degradation, and so prolong the lifetime of ACh within the synaptic cleft

52

What drugs act on adrenergic nerve terminals?

α-methyl-tyrosine
α-methyl-DOPA
CarbiDOPA
Adrenergic blocking drugs
Indirectly-acting sympathomimetic agents (IASAs)
Uptake 1 inhibitors

53

What does α-methyl-tyrosine do?

Completely inhibits tyrosine hydroxylase, and therefore blocks de novo synthesis of noradrenaline

54

What is the clinical use of α-methyl-tyrosine?

Inhibits NA synthesis in pheochromocytoma

55

What is α-methyl-DOPA taken up by?

Adrenergic neurones

56

What happens do α-methyl-DOPA when taken up by adrenergic neurones?

It is converted to α-methyl-noradrenaline

57

How is α-methyl-DOPA differ from a true neurotransmitter?

It is poorly metabolised

58

What is the result of α-methyl-DOPA being poorly metabolised?

It accumulates in the synaptic vesicles of noradrenergic terminals

59

How is α-methyl-DOPA released from synaptic vesicles?

Ca mediated exocytosis

60

What happens when α-methyl-DOPA is released from synaptic vesicles?

It preferentially activates pre-synaptic α2 receptors

61

What happens when α-methyl-DOPA activates pre-synaptic α2 receptors?

The ßγ subunit of the α2 receptor inhibits the VOCC, reducing Ca mediated neurotransmitter release

62

What does carbiDOPA do?

Inhibits DOPA decarboxylase in the periphery, but not in the CNS

63

Why does carbiDOPA not inhibit DOPA decarboxylase in the CNS?

It does not cross the BBB

64

What is carbiDOPA used for?

In combination with L-DOPA in the treatment of Parkinson's disease

65

Where are adrenergic blocking drugs selectively concentrated?

In terminals

66

How are adrenergic blocking drugs selectively concentrated in terminals?

By uptake 1

67

How do adrenergic blocking drugs act?

Via a variety of mechanisms, including a local anaesthetic action reducing impulse conduction and Ca mediated exocytosis and repletion of NA from synaptic vesicles

68

Why are adrenergic blocking drugs rarely used therapeutically?

Because of their severe side effects, including postural hypotension

69

What are IASAs structurally related to?

NA

70

Why are IASAs though to exert their actions by additional/other methods to NA?

Because they are only weak agonists at adrenoreceptors

71

What happens to IASAs?

They are recognised and transported into the adrenergic terminal by Uptake 1 and taken up into the synaptic vesicles

72

What happens to NA displaced by IASAs?

It can leak into the synaptic cleft, by a mechanism unrelated to Ca mediated exocytosis

73

What is the extent to which NA leaks into the synaptic cleft greatly enhanced by?

The inhibition of the NA-degrading enzyme MAO

74

What do uptake 1 inhibitors comprise?

An important class of therapeutic agents, the tricyclic antidepressants

75

How do uptake 1 inhibitors exert their therapeutic action?

Centrally

76

What are the unwanted side effects of tricylic antidepressants?

Their possible peripheral actions, e.g. tachycardia and cardiac dysrhythmias