L10 & L11 - drugs affecting the SNS Flashcards

1
Q

what are ganglia

A

clusters of cell bodies

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2
Q

what does SNS stimulate

A
increased HR 
vasoconstriction
bronchodilation 
pupils dilate 
decrease smooth muscle contraction
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3
Q

where is SNS ganglia

A

close to spinal cord

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4
Q

what does disynaptic mean?

A

there are 2 synapses along the pathway (pre and post ganglionic ) compared to one synapse in somatic motor neurons

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5
Q

describe adrenal medulla (what is it)

A

modified post ganglionic neuron

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6
Q

is there ganglia in the pathway from CNS to adrenal medulla?

A

no, the adrenal medulla is modified ganglia

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7
Q

what cells release NA and A

A

chromaffin cells

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8
Q

describe the entire process of adrenaline synthesis

A

phenylalanine — tyrosine — L DOPA — Dopamine — Noradrenaline — adrenaline

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9
Q

what enzyme converts phenylalanine to tyrosine

A

phenylalanine hydroxylase

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10
Q

what enzyme converts tyrosine to L-DOPA

A

tyrosine hydroxylase

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11
Q

what enzyme converts L-DOPA to dopamine

A

DDC

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12
Q

what enzyme converts dopamine to noradrenaline

A

dopamine B hydroxylase

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13
Q

what enzyme converts noradrenaline to adrenaline

A

PNMT

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14
Q

where does synthesis of the catecholamines (dopamine/NA/A) occur?

A

adrenal medulla

postganglionic SNS neurons

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15
Q

where can drugs act in the synthesis of catecholamines and give examples

A

inhibit tyrosine hydroxylase
by a-methyl-P-tyrosine

carbidopa inhibit DDC (L-DOPA - dopamine)

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16
Q

where is dopamine converted to NA/A

A

in vesicles

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17
Q

what is VMAT and what does it do

A

vesicular monoamine transporter

packages free NA/dopamine in presynaptic membrane into vesicles

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18
Q

what does reserpine do?

A

blocks VMAT
leads NT being broken down
leads to block of SNS transmission

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19
Q

what does guanethidine do

A

prevents catecholamine exocytosis

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20
Q

what does carbidopa do

A

blocks DDC preventing L-DOPA to dopamine

21
Q

what is uptake 1

A

uptake back into presynaptic neuron

main transmission terminator (80% re uptake)

22
Q

what is uptake 2

A

breakdown of NT by enzymes in cleft / diffusion of NT away from cleft

23
Q

what is the effect of uptake 1 blockers

A

enhance transmission

24
Q

give example of uptake 1 blocker

A

cocaine

25
Q

what degrades NA/A in the presynaptic nerve terminal

A

monoamine oxidase

26
Q

what uptake mechanism is adrenaline most likely to be taken up by

A

uptake 2

27
Q

how can SNS transmission be stopped by negative feedback and what receptors are involved

A

a2 adrenoreceptors on the presynaptic membrane

  1. when [NA] in cleft is high it will bind to a adrenoreceptors on the presynaptic membrane
  2. these inhibit NA release
28
Q

list the drugs that inhibit SNS transmission presynapticly

A
  1. a-methyl-P-tyrosine
  2. carbidopa
  3. reserpine
  4. guanethidine
29
Q

define indirect sympathomimetics

A

drugs that provoke SNS effect by causing release of NA/A but dont act on adrenoreceptors

30
Q

what are the 2 mechanisms of indirect sympathomimetics?

A
  1. enter sym nerve and displace NT from vesicles

2. inhibit NT reuptake (uptake 1)

31
Q

what is the name of the transporter for NA uptake 1

A

NET

32
Q

describe the primary actions of amphetamine

indirect sympathomimetics

A

primary mechanism

  1. ‘hijacks’ uptake 1 then displaces NA from vesicles
  2. NA will be broken by MAO / leak into cleft
  3. increase in neurotransmission
33
Q

describe the secondary actions of amphetamine (indirect sympathomimetics)

A

can inhibit MAO when concs high enough

34
Q

side effects of imipramine

A

anti histamine
sodium channel blocker
anti muscarinic

35
Q

put these in order of their effectiveness on smooth muscle
adrenaline
noradrenaline
isoprenaline

A

noradrenaline > adrenaline > isoprenaline

36
Q

put these in order of their effectiveness on cardiac muscle
adrenaline
noradrenaline
isoprenaline

A

isoprenaline > adrenaline > noradrenaline

37
Q

what type of receptors are adrenoreceptors

A

G protein coupled

38
Q

where are B1 receptors found

A

post synaptic - mainly heart

39
Q

where are B2 receptors found

A

non synaptic sites eg airways

40
Q

where are a1 receptors found

A

post synaptic - most tissues except heart

41
Q

where are a2 receptors found

A

pre synaptic - everywhere

42
Q

does NA have a greater effect on a or B receptors

A

a

43
Q

does NA have a greater effect on B1 or B2

A

B1

44
Q

what receptors does isoprenaline act on

A

B only

45
Q

does adrenaline have greater effect on a or B

A

B

46
Q

effect of α1 agonist?

A
  1. contracts vascular smooth muscle

2. increase in TPR and MABP - reflex decrease in HR

47
Q

effect of B agonist

A
  1. increase HR & contractility
  2. relax vascular smooth muscle
  3. decrease TPR (increase CO to balance)
48
Q

side effects of B blockers?

A
  1. fatigue
  2. reduced B.P to extremities
  3. bronchoconstriction
  4. risk of cardiac failure