Lecture 10 - The Autonomic Nervous System; Pharmacokinetics

Question 1

what comprises the autonomic nervous system?

Answer 1

series of 2 neurones - pre and post ganglionic

Question 2

where do cell bodies lie in the ans?

Answer 2

one in the cns, one in the pns

Question 3

how do neurones exert actions?

Answer 3

via smooth muscle, viscera and secretory glands

Question 4

describe the thoraco-lumbar outflow

Answer 4

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

short pre ganglionic, long post ganglionic

Question 5

where can thoraco-lumbar outflow synapse?

Answer 5

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

Question 6

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

Answer 6

cholinergic

Question 7

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

Answer 7

noradrenergic

Question 8

describe the cranio-sacral outflow

Answer 8

long pre ganglionic

short post ganglionic

Question 9

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

Answer 9

cholinergic

Question 10

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

Answer 10

cholinergic

Question 11

how is acetylcholine synthesised?

Answer 11

from choline and acetyl CoA with choline acetyltransferase

Question 12

how is ACh tranported into synaptic vesicles?

Answer 12

indirect active transport mechanism

Question 13

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

Answer 13

activity is higher

Question 14

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

Answer 14

from tyrosine within the nerve terminal

tyrosine hydroxylase

Question 15

what is the role of dopamine beta-hydroxylase?

Answer 15

transports newly synthesised dopamine into vesicle prior to conversion to noradrenaline

Question 16

what breaks down cytoplasmic noradrenaline?

Answer 16

monoamine oxidase

Question 17

what is the pathway from tyrosine to noradrenaline?

Answer 17

tyrosine -> dopa -> dopamine -> noradrenaline

Question 18

how is noradrenaline released?

Answer 18

calcium mediated exocytosis

Question 19

what is the ‘uptake 1’ system?

Answer 19

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

Question 20

what is the ‘uptake 2’ system?

Answer 20

widespread, low affinity reuptake

extra na is removed from the extracellular space

Question 21

how is ACh and na release regulated?

Answer 21

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

Question 22

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

Answer 22

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

Question 23

how do cholinoceptor ant/agonists interfere with cholinergic transmission?

Answer 23

interact with cholinoceptors

Question 24

how do cholinesterases interfere with cholinergic transmission?

Answer 24

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

Question 25

what is an example of a nicotinic cholinoceptor antagonist?

Answer 25

tubocurarine

Question 26

what is the action of tubocurarine?

Answer 26

muscle paralysis during anasthesia

Question 27

what is an example of a muscarinic cholinoceptor agonist?

Answer 27

pilocarpine

Question 28

what are 4 actions of a pilocarpine?

Answer 28

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

Question 29

what are 4 examples of a muscarinic cholinoceptor antagonist?

Answer 29

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

Question 30

what is the action of hyoscine?

Answer 30

anaesthetic premedication

Question 31

what is the action of ipratropium bromide?

Answer 31

treat bronchoconstriction in asthmatics

Question 32

what is the action of homatropine and tropicamide?

Answer 32

pupillary dilation and paralysis

Question 33

what are 5 examples of cholinesterase inhibitors?

Answer 33

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

Question 34

what is the action of edrophonium, physostigimine and dyflos?

Answer 34

treatment of glaucome and myasthenia gravis

Question 35

what is the action of tacrine and donepezil?

Answer 35

treatment of alzheimers

Question 36

what is an example of a selective beta1 agonist?

Answer 36

dobutamine

Question 37

what is the action of dobutamine?

Answer 37

positive inotropic/chonotropic effects

Question 38

what is an example of a selective beta2 agonist?

Answer 38

salbutamol

Question 39

what is the action of salbutamol?

Answer 39

bronchodilation

Question 40

what are 2 examples of selective alpha1 agonists?

Answer 40

1) phenylephrine | 2) adrenaline

Question 41

what is the action of phenylephrine?

Answer 41

nasal decongestant

Question 42

what is the action of adrenaline?

Answer 42

local vasoconstriction to retard dissipation of anaesthetic

Question 43

what is an example of a selective alpha2 agonist?

Answer 43

clonidine

Question 44

what is the action of clonidine?

Answer 44

antihypertension | acts on presynaptic receptors to reduce na release

Question 45

what is an example of an alpha antagonist?

Answer 45

phentolamine

Question 46

what is the action of phentolamine?

Answer 46

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

Question 47

what is an example of a selective alpha1 antagonist?

Answer 47

prazosin

Question 48

what is the action of prazosin?

Answer 48

treat hypertension

Question 49

what is an example of a beta-antagonist?

Answer 49

propanolol

Question 50

what is the action of propanolol?

Answer 50

treats hypertension, mi and angina

Question 51

what is a side effect of propanolol?

Answer 51

bronchoconstriction

Question 52

what is the action of alpha-methyl-tyrosine?

Answer 52

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

Question 53

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

Answer 53

converted to alpha-methyl-noradrenaline

Question 54

what happens to alpha-methyl-noradrenaline?

Answer 54

poorly metabolised | accumulates in synaptic vesicles of noradrenergic terminals

Question 55

what does alpha-methyl-noradrenaline activate?

Answer 55

pre synaptic alpha2-receptors

Question 56

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

Answer 56

inhibit vocc, reducing Ca mediated neurotransmitter release

Question 57

what is the action of carbiDOPA?

Answer 57

inhibits dopa decarboxylase in periphery but not cns

Question 58

what is carbiDOPA used for?

Answer 58

in combination with l-dopa in treatment of parkinsons

Question 59

what is the action of adrenergic blocking drugs?

Answer 59

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

Question 60

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

Answer 60

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

Question 61

how can na leakage into synaptic cleft be enhanced?

Answer 61

inhibition of na degrading enzyme mao

Question 62

how do uptake 1 inhibitors exert their therapeutic action?

Answer 62

centrally

Question 63

what do uptake 1 inhibitors comprise?

Answer 63

important class of therapeutic agents - tricyclic antidepressants