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LF261: Neuropharmacology > Lecture 7. Noradrenergic Transmission and the Monoamines > Flashcards

Lecture 7. Noradrenergic Transmission and the Monoamines Flashcards

1
Q

What are examples of catecholamines?

A

Noradrenaline
Adrenaline
Dopamine

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2
Q

What is an example of a tryptamine?

A

Serotonin

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3
Q

What enzyme converts L-tyrosine into dihydroxyphenylalanine (DOPA)?

A

Tyrosine hydroxylase (rate-limiting enzyme)

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4
Q

Where is tyrosine hydroxylase located?

A

Within noradrenergic and dopaminergic neurones and adrenal chromaffin cells of the adrenal medulla

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5
Q

What are adrenal chromaffin cells?

A

The cells that produce adrenaline and noradrenaline

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6
Q

What can tyrosine hydroxylase be used for?

A

Marker for the NA and DA terminals

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7
Q

What enzyme converts DOPA into dopamine?

A

DOPA decarboxylase

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8
Q

What enzyme converts dopamine into noradrenaline?

A

Dopamine-β-hydroxylase

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9
Q

Where is dopamine-β-hydroxylase found?

A

Noradrenergic vesicles

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10
Q

What enzyme converts noradrenaline into adrenaline?

A

Phenylethanolamine N-methyl transferase

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11
Q

Where is Phenylethanolamine N-methyl transferase found?

A

Adrenal chromaffin cells of adrenal medulla

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12
Q

What does chromagranin A do?

A

Binds to noradrenaline and adrenaline within the chromaffin cells and prevents the leakage from the vesicles into the cytosol

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13
Q

What drug interferes with the conversion of L-tyrosine to DOPA and why is it important?

A

α-methylparatyrosine, used for treating tumour cells of the chromaffin cells)

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14
Q

What drugs interfere with the conversion of DOPA into dopamine?

A

Carbidopa and benserazide, inhibits DOPA decarboxylase so Parkinson’s patients can be treated with L-DOPA and cannot cross the blood brain barrier (allows selective inhibition)

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15
Q

What drugs interfere with the conversion of of dopamine into noradrenaline?

A

Disulfiram, used to treat alcohol abuse disorder

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16
Q

What does reserpine do?

A

Inhibits noradrenaline uptake, resulting in depletion
General decrease in sympathetic function
Decreases heart rate and blood pressure

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17
Q

What side effects are caused by taking reserpine?

A

Postural hypotension
Hypothermia
Sedation, depression (suicidal at high dose)

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18
Q

What does α-methyl DOPA do?

A

Converts into α-methyl noradrenaline which replaces/displaces and is released instead of noradrenaline
Less potent than noradrenaline at α₁ adrenoceptor and activates α₂ adrenoceptor, resulting in less noradrenaline release
Decreases heart rate and blood pressure

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19
Q

What is α-methyl DOPA used to treat?

A

Hypertension (during pregnency)

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20
Q

What is clonidine?

A

α₂ agonist, reduces noradrenaline release

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21
Q

What is clonidine used to treat?

A

Hypertension
Migraines
Tourette’s syndrome
Menopausal flushing

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22
Q

What is used as a drug target for inactivating noradrenergic transmission and why?

A

Norepinephrine transporter (NET), it has a high affinity and is presynaptic

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23
Q

What is monamine oxidase (MAO) and what is it used for?

A

Inhibitors used to treat depression

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24
Q

What is catechol-o-methyl transferase (COMT) and what is it used for?

A

Inhibitors used to treat Parkinson’s disease

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25
Q

How were α-adrenoceptors and β-adrenoceptors distinguished?

A

Noradrenaline was more effective in tissue that predominantly contained α-adrenoceptors whilst isoprenaline was more effective in tissues which predominantly contained β-adrenoceptors

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26
Q

What is the representative tissue of α₁?

A

Vascular smooth muscle
Vas deferens smooth muscle

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27
Q

What is the physiological response of α₁?

A

Contraction

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28
Q

What is the representative tissue of α₂?

A

Adrenergic nerve terminals

29
Q

What is the physiological response of α₂?

A

Decrease in noradrenaline release

30
Q

What is the representative tissue of β₁?

A

Cardiac muscle

31
Q

What is the physiological response of β₁?

A

Increase in heart rate
Increase in force of contractions

32
Q

What is the representative tissue of β₂?

A

Cardiac blood vessels
Skeletal muscle blood vessels
Bronchial smooth muscle

33
Q

What is the physiological response of β₂?

A

Dilation
Relaxation

34
Q

What is the representative tissue of β₃?

A

Adipose tissue (not found in the brain)

35
Q

What is the physiological response of β₃?

36
Q

What are all adrenoceptors?

A

G-protein coupled receptors

37
Q

What is the G protein subtype coupled to α₁?

A

Gαq (queer)

38
Q

What are the typical second messengers released by α₁?

A

Protein kinase C (PKC)
Ca²⁺

39
Q

What is the physiological response caused by the second messengers of α₁?

A

Contraction of vascular smooth muscle

40
Q

What is the G protein subtype coupled to α₂?

A

Gαi (inhibitory)

41
Q

What are the typical second messengers released by α₂?

A

Reduced cAMP & PKA activity
Gβγ, decrease in voltage-gated Ca²⁺ channels

42
Q

What is the physiological response caused by the second messengers of α₂?

A

Decrease in insulin release
Decrease in noradrenaline release

43
Q

What is the G protein subtype coupled to β₁, β₂, β₃?

A

Gαs (stimulatory)

44
Q

What are the typical second messengers released by β₁, β₂, β₃?

A

Increased cAMP & PKA activity

45
Q

What is the physiological response caused by the second messengers of β₁, β₂, β₃?

A

Increase in cardiac output
Dilation/relaxation
Lipolysis

46
Q

What receptors do noradrenaline act upon?

47
Q

What is the physiological response caused by noradrenaline?

A

Increase in blood pressure due to α₁ vasoconstriction

48
Q

What are the clinical uses of noradrenaline?

A

To treat shock and cardiac arrests

49
Q

What receptors do adrenaline act upon?

50
Q

What is the physiological response caused by adrenaline?

A

Increase in heart rate (chronotropic)
Increase in force (ionotropic)
Bronchodilation

51
Q

What are the clinical uses of adrenaline?

A

Used to treat cardiac arrest, anaphylactic shock and used for local anaesthetics

52
Q

What receptor does salbutamol act upon?

53
Q

What is the physiological response caused by salbutamol?

A

Smooth muscle relaxation (eg bronhodilation)

54
Q

What are the clinical uses of salbutamol?

A

To treat asthma and inhibit premature labour

55
Q

What does tyramine stimulate?

A

Noradrenaline release

56
Q

What is the cheese reaction?

A

When tyramine in food (red wine, cheese, yogurt) is metabolised by MAO whilst MAO is being inhibited by an antidepressant (eg Phenelzine) resulting in a hypertensive crisis

57
Q

What adrenoceptor does prazosin antagonise?

58
Q

What adrenoceptor does labetalol antagonise?

59
Q

What is the physiological response caused by prazosin and labetalol?

A

Decreases in BP via α₁

60
Q

What are prazosin and labetalol used to treat?

A

Hypertension (increases heart rate), prazosin has fewer side effects

61
Q

What receptors does propanolol antagonise?

A

β (non-selective)

62
Q

What is the physiological response caused by propanlol?

A

Decrease in HR, BP and cardiac output via β₁

63
Q

What are the side effects of taking propanolol?

A

Bronchoconstriction (β₂)
Sleep disturbance
Hypoglycaemia
Cardiac failure
Cold extremities

64
Q

What is propanolol used to treat?

A

Angina
Heart dysrhythmias

65
Q

What receptor does propanolol antagonise?

A

β₁ (cardioselective)

66
Q

What is the physiological response caused by atenolol?

A

Decrease in HR, BP and cardiac output via β₁

67
Q

What is atenolol and pindolol used to treat?

A

Hypertension

68
Q

What are the physiological responses caused by pindolol?

A

Partial agonists
Don’t give maximum response
Inhibit action of full agonists

LF261: Neuropharmacology (15 decks)

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