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Semester 2 - Membranes and Receptors > Session 6+7 - Noradrenaline > Flashcards

Session 6+7 - Noradrenaline Flashcards

1
Q

Where is Noradrenaline released in the body?

A

In the post ganglionic neurones of the sympathetic nervous system

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2
Q

Are there any post ganglionic synapses in which noradrenaline is not the transmitter?

A

Sweat glands
- ACh (nicotinic receptors)
Ejaculation

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3
Q

What are the “biogenic amines”? What is the synthetic pathway?

A

Biological compounds containing NH2 synthesized from tyrosine
Tryosine –> (tryosine hydroxylase) DOPA –> (DOPA decarboxylase) Dopamine –> (dopamine b-hydroxylase) Noradrenaline

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4
Q

Where does the synthetic production of biogenic amines take place?

A

The sympathetic nerve axon
Tryosine –> DOPA –> Dopamine in cytoplasm
Dopamine - Noradrenaline in synaptic vesicle

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5
Q

What determines whether a nerve terminal is dopaminergic or noadrenergic?

A

The presence of DBH, which converts dopamine to noradrenaline

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6
Q

How is noradrenaline packaged for release?

A

Packaged into synaptic vesicles, which actively take up noradrenaline via vesicular catecholamine pump

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7
Q

Outline the key events of post-ganglionic sympathetic innervation of target tissues

A
  • Actions potential travels down axon and reaches pre-synaptic knob
  • Voltage gates calcium ion channels open and Calcium flows in
  • Calcium binds to synaptotagmin
  • Vesicle containing noradrenaline brought close to membrane
  • Snare complex makes a fusion pore
  • Noradrenaline is released into synaptic cleft
  • Binds to adrenergic receptors
  • Causes influx of Na+ ions into effector organ
  • Action potential generated in effector organ
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8
Q

List five sites of sympathetic innervation

A 
The heart
Skeletal muscle
Smooth muscles
Adipose tissue
Glands (not sweat glands)
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9
Q

What is positive chronotrophy in heart rate?

A

Increase in HR

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10
Q

What is positive intropy in the heart?

A

Increase in force of contraction

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11
Q

Explain the anatomical basis for positive chronotrophy due to NA

A
  • Right sympathetic nerve acts on the B1 adrenoreceptors of the SA node
  • B1 adreno receptors activate adenylyl cylcase
  • Causes increase in rate of AP generation
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12
Q

Explain the anatomical basis for positive inotrophy due to NA

A

NA acts on B1 receptors, increase in Ca2+ influx in ventricular cardiomyocyte.

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13
Q

For each receptor subtype, give the G protein, effector and whether in activates or inhibits
a1

A

Gq
Activates phospholipase C, producing secondary messenger IP3. IP3 interacts with IP3 sensitive calcium channels in sarcoplasmic reticulum

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14
Q

For each receptor subtype, give the G protein, effector and whether in activates or inhibits
a2

A

Gi
Inhibits adenylyl cyclase
Inhibits calcium channels, activates potassium channels

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15
Q

For each receptor subtype, give the G protein, effector and whether in activates or inhibits
B1 + B2

A

Gs
Stimulate adenylyl cyclase causing increase cAMP
Causes opening of calcium channels
B1 - in heart increase in force and rate of contraction
B2 In smooth muscle, causes relaxation

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16
Q

How are extracellular noradrenaline levells decreased?

A
  • Noradrenaline can be taken up by noradrenaline transporter and repackaged into vesicles in presynaptic neuron
  • Norepinephrine transporter
    Na+ Cl- dependent reuptake
    Uses Na+ gradient to move into cells
  • Vesicular Monoamine Transporter
    Repackage into vesicles
    Uses proton gradient
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17
Q

Name two enzymes which degrade noradrenaline

A

Monoamine oxidase

Catechol-O-methyltransferase

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18
Q

What do enzymes degrade NA into?

A

Its aldehyde derivative by O-methylation which can be excreted in the urine

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19
Q

Which products of metabolism can be measured in the blood or urine as an indirect index of sympathetic activity?

A

VMA and MHPG are metabolites of noradrenaline
Can be measured in urin
High levels indicative of adrean or sympathetic nervous system tumour

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20
Q

What are the adrenoreceptors and physiological response of liver cells?

A

A1, B2

Increased glycogenolysis, increased gluconeogenesis

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21
Q

What are the adrenoreceptors and physiological response of vascular smooth muscles?

A

a1 - constrict
a2 - constrict/dilate
b2 - dilate

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22
Q

What are the adrenoreceptors and physiological response of airways (bronchi)

A

a1 - constrict

b2 - dilate

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23
Q

What are the adrenoreceptors and physiological response of GI tract

A

a1 - relax
a2 - relax
b3 - relax

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24
Q

What are the adrenoreceptors and physiological response of the SA node of the heart

A

B1 - increased heart rate

25
Q

What are the adrenoreceptors and physiological response of ventricle of the heart

A

B1 - force of contraction increased

26
Q

What are the adrenoreceptors and physiological response of skeletal muscle

A

B2 - Tremor, increased muscle mass and speed of contraction and glycogenolysis

B3 - thermogenesis

27
Q

What are the adrenoreceptors and physiological response of adipose tissue

A

B1, B3 - Increased lipolysis

28
Q

What are the adrenoreceptors and physiological response of the iris?

A

A1 - Radial muscle contracts

B2 - cillary muscle relax

29
Q

Does adrenaline contribute to or exert the predominant effects of any of the receptors we have so far talked about?

A

Smooth muscle relaxation in airways
Smooth muscle contraction in most arteries
Major bronchiodilatory used to treat asthma
Skeletal muscle affected buy far less than the heart

30
Q

What is an adrenoreceptor agonist?

A

Agents which mimic the actions of noradrenaline/adrenaline

31
Q

What would the advantage be of synthesizing an adrenoreceptor agonist which only interacts with particular receptor subtypes?

A
  • Increase specificity
  • Pevents additional side effect
  • Greater efficacy, so lower dose required
  • Can clearly predict clinical effects
32
Q

Outline the type of adrenoreceptor agonist used to reverse bronchoconstriction in asthmatics

A

Salbutamol, B2 agonist

33
Q

Outline the type of adrenoreceptor agonist used to aid decongestion o nasal passages

A

Oxymetazoline

A1 and partial a2 agonist

34
Q

Outline the type of adrenoreceptor agonist used to prolong the action of local anaesthetic

A

A2 agonist

Clonidine

35
Q

What is an adrenoreceptor antagonist?

A

One which prevents the actions of catecholamins

36
Q

Give an example of the clinical use of an a adrenoreceptor antagonist

A

Prazosin

Treats high blood pressure, anxiety and panic disorder

37
Q

Give an example of the clinical use of a b adrenoreceptor antagonist

A

Beta blockers

Used for management of cardiac arrythmias, preventing the heart from hypertension MI

38
Q

What unwanted side effects limit the usefulness of prazosin?

A

Syncope, hallucination, vivid dreams

39
Q

What unwanted side effects limit the usefulness of beta blockers?

A

Nausea, insomnia, bronchospasm

40
Q

Which enzyme is specifically inhibited by a methyltyrosine? Why is this important with respect to noradrenaline synthesis? What particular cancer is treated by this drug?

A

Tyrosine hydroxylase
Inhibits the first step of noradrenaline synthesis.
Important in treating pheochromocytoma (a neuroendocrine tumour of the adrenal medulla.

41
Q

What is an adrenoreceptor agonist?

A

Agents which mimic the actions of noradrenaline/adrenaline

42
Q

What would the advantage be of synthesizing an adrenoreceptor agonist which only interacts with particular receptor subtypes?

A
  • Increase specificity
  • Pevents additional side effect
  • Greater efficacy, so lower dose required
  • Can clearly predict clinical effects
43
Q

Outline the type of adrenoreceptor agonist used to reverse bronchoconstriction in asthmatics

A

Salbutamol, B2 agonist

44
Q

Outline the type of adrenoreceptor agonist used to aid decongestion o nasal passages

A

Oxymetazoline

A1 and partial a2 agonist

45
Q

Outline the type of adrenoreceptor agonist used to prolong the action of local anaesthetic

A

A2 agonist

Clonidine

46
Q

What is an adrenoreceptor antagonist?

A

One which prevents the actions of catecholamins

47
Q

Give an example of the clinical use of an a adrenoreceptor antagonist

A

Prazosin

Treats high blood pressure, anxiety and panic disorder

48
Q

Give an example of the clinical use of a b adrenoreceptor antagonist

A

Beta blockers

Used for management of cardiac arrythmias, preventing the heart from hypertension MI

49
Q

What unwanted side effects limit the usefulness of prazosin?

A

Syncope, hallucination, vivid dreams

50
Q

What unwanted side effects limit the usefulness of beta blockers?

A

Nausea, insomnia, bronchospasm

51
Q

Alpha-methyl DOPA acts as a competitive inhibtor for which enzyme?

A

DOPA decarboxylase

52
Q

What product of alpha-methyl DOPA metabolism accumulates in noradrenergic terminals?

A

It is converted to alpha-methylnoadrenaline by dopame beta-hydroxylase

53
Q

If released, what is the major action of alpha-methyl DOPA?

A

Agonist for adrenergic terminals

54
Q

How is alpha-methyl DOPA used to treat hypertension?

A

alpha-methylnoadrenaline causes inhibition of sympathetic nervous system and decreases blood pressure. This is achieved by activating alpha-2-adrenergic receptors in the brainstem

55
Q

How does guanethidine inhibit noradrenaline release?

A

Competes with NA for uptake into presynaptic terminal.
Becomes concentrated in NA transmitter vesicles, causing gradual depletion.
Blocks release NA

56
Q

What is guanethidine used as?

A

An anti-hypertensive

57
Q

What side effects does guanethidine cause?

A

Causes postural hypotension, failure of ejaculation, fluid retention and diarrhoea

58
Q

Why are adrenoreceptor agonists and antagonists the drugs of choice?

A

Mimic, block or reduce effects

Focused response

Semester 2 - Membranes and Receptors (14 decks)

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