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Membranes and Receptors > Lecture 10 - The Autonomic Nervous System; Pharmacokinetics > Flashcards

Lecture 10 - The Autonomic Nervous System; Pharmacokinetics Flashcards

1
Q

what comprises the autonomic nervous system?

A

series of 2 neurones - pre and post ganglionic

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2
Q

where do cell bodies lie in the ans?

A

one in the cns, one in the pns

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3
Q

how do neurones exert actions?

A

via smooth muscle, viscera and secretory glands

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4
Q

describe the thoraco-lumbar outflow

A

nerve fibres have cell bodies in T1-L2 (14 sections)

short pre ganglionic, long post ganglionic

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5
Q

where can thoraco-lumbar outflow synapse?

A

same level to origin
different level to origin
not in paravertebral chain

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6
Q

what is the neurotransmission of pre ganglionic neurones in thoraco-lumbar outflow?

A

cholinergic

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7
Q

what is the neurotransmission of post ganglionic neurones in thoraco-lumbar outflow?

A

noradrenergic

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8
Q

describe the cranio-sacral outflow

A

long pre ganglionic

short post ganglionic

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9
Q

what is the neurotransmission of pre ganglionic neurones in cranio-sacral outflow?

A

cholinergic

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10
Q

what is the neurotransmission of post ganglionic neurones in cranio-sacral outflow?

A

cholinergic

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11
Q

how is acetylcholine synthesised?

A

from choline and acetyl CoA with choline acetyltransferase

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12
Q

how is ACh tranported into synaptic vesicles?

A

indirect active transport mechanism

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13
Q

how does the activity of acetylcholinesterase change at fast cholinergic synapses?

A

activity is higher

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14
Q

how is noradrenaline synthesised and what is the rate limiting enzyme?

A

from tyrosine within the nerve terminal

tyrosine hydroxylase

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15
Q

what is the role of dopamine beta-hydroxylase?

A

transports newly synthesised dopamine into vesicle prior to conversion to noradrenaline

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16
Q

what breaks down cytoplasmic noradrenaline?

A

monoamine oxidase

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17
Q

what is the pathway from tyrosine to noradrenaline?

A

tyrosine -> dopa -> dopamine -> noradrenaline

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18
Q

how is noradrenaline released?

A

calcium mediated exocytosis

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19
Q

what is the ‘uptake 1’ system?

A

high affinity reuptake
rapidly removes na from synaptic cleft
rapidly decreases localised concentration and terminating actions

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20
Q

what is the ‘uptake 2’ system?

A

widespread, low affinity reuptake

extra na is removed from the extracellular space

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21
Q

how is ACh and na release regulated?

A

triggered by depolarisation of nerve terminal membrane, Ca entry and fusion of vesicles with presynaptic membrane

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22
Q

what are the major drug classes that affect autonomic nervous system function?

A

nicotinic cholinoceptor antagonists
muscarinic cholinoceptor agonists
muscarinic cholinoceptor antagonists
8cholinesterase inhibitors

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23
Q

how do cholinoceptor ant/agonists interfere with cholinergic transmission?

A

interact with cholinoceptors

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24
Q

how do cholinesterases interfere with cholinergic transmission?

A

decrease rate of degradation of ACh so prolong lifetime in the cleft

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25
Q

what is an example of a nicotinic cholinoceptor antagonist?

A

tubocurarine

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26
Q

what is the action of tubocurarine?

A

muscle paralysis during anasthesia

27
Q

what is an example of a muscarinic cholinoceptor agonist?

A

pilocarpine

28
Q

what are 4 actions of a pilocarpine?

A

1) treatment of glaucoma
2) GI motility after surgery
3) suppression of atrial tachycardia
4) stimulates bladder emptying

29
Q

what are 4 examples of a muscarinic cholinoceptor antagonist?

A

1) hyoscine
2) ipratropium bromide
3) homatropine
4) tropicamide

30
Q

what is the action of hyoscine?

A

anaesthetic premedication

31
Q

what is the action of ipratropium bromide?

A

treat bronchoconstriction in asthmatics

32
Q

what is the action of homatropine and tropicamide?

A

pupillary dilation and paralysis

33
Q

what are 5 examples of cholinesterase inhibitors?

A

1) edrophonium
2) physostigimine
3) dyflos
4) tacrine
5) donepezil

34
Q

what is the action of edrophonium, physostigimine and dyflos?

A

treatment of glaucome and myasthenia gravis

35
Q

what is the action of tacrine and donepezil?

A

treatment of alzheimers

36
Q

what is an example of a selective beta1 agonist?

A

dobutamine

37
Q

what is the action of dobutamine?

A

positive inotropic/chonotropic effects

38
Q

what is an example of a selective beta2 agonist?

A

salbutamol

39
Q

what is the action of salbutamol?

A

bronchodilation

40
Q

what are 2 examples of selective alpha1 agonists?

A

1) phenylephrine

2) adrenaline

41
Q

what is the action of phenylephrine?

A

nasal decongestant

42
Q

what is the action of adrenaline?

A

local vasoconstriction to retard dissipation of anaesthetic

43
Q

what is an example of a selective alpha2 agonist?

44
Q

what is the action of clonidine?

A

antihypertension

acts on presynaptic receptors to reduce na release

45
Q

what is an example of an alpha antagonist?

A

phentolamine

46
Q

what is the action of phentolamine?

A

peripheral vasodilation
treat peripheral vascular disease
not used to treat hypertension as cause postural hypotension

47
Q

what is an example of a selective alpha1 antagonist?

48
Q

what is the action of prazosin?

A

treat hypertension

49
Q

what is an example of a beta-antagonist?

A

propanolol

50
Q

what is the action of propanolol?

A

treats hypertension, mi and angina

51
Q

what is a side effect of propanolol?

A

bronchoconstriction

52
Q

what is the action of alpha-methyl-tyrosine?

A

competitively inhibits tyrosine hydroxylase
blocks de novo synthesis of na
used to inhibit na synthesis in pheochromocytoma

53
Q

what happens when alpha-methyl-dopa is taken up by adrenergic neurones?

A

converted to alpha-methyl-noradrenaline

54
Q

what happens to alpha-methyl-noradrenaline?

A

poorly metabolised

accumulates in synaptic vesicles of noradrenergic terminals

55
Q

what does alpha-methyl-noradrenaline activate?

A

pre synaptic alpha2-receptors

56
Q

what does the beta-gamma subunit of the alpha2 receptor do?

A

inhibit vocc, reducing Ca mediated neurotransmitter release

57
Q

what is the action of carbiDOPA?

A

inhibits dopa decarboxylase in periphery but not cns

58
Q

what is carbiDOPA used for?

A

in combination with l-dopa in treatment of parkinsons

59
Q

what is the action of adrenergic blocking drugs?

A

local anaesthetic action reducing impulse conduction and Ca mediated exocytosis
repletion of na from synaptic vesicles

60
Q

what is the action of indirectly-acting sympathetic agents (IASAs)?

A

weak agonists at adrenoceptors
recognised and transported into adrenergic terminal by uptake 1 and taken up into synaptic vesicles
displaced na leaks into synaptic cleft

61
Q

how can na leakage into synaptic cleft be enhanced?

A

inhibition of na degrading enzyme mao

62
Q

how do uptake 1 inhibitors exert their therapeutic action?

63
Q

what do uptake 1 inhibitors comprise?

A

important class of therapeutic agents - tricyclic antidepressants

Membranes and Receptors (10 decks)

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