Lecture 16 and 17 Flashcards Preview

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Flashcards in Lecture 16 and 17 Deck (20):
1

How is noradrenaline produced at a noradrenergic synapse?

Tyrosine is converted to DOPA by tyrosine hydroxylase
DOPA is converted to Dopamine by Dopamine decraboxylase
Dopamine is converted to noradrenaline by dopamine beta hydroxylase
This noradrenaline is then taken up by VMAT into vesicles where it is stored with ATP

2

What is the rate limiting step for production of noradrenaline?

The conversion of tyrosine to DOPA by tyrosine hydroxylase

3

What occurs during an action potential at a noradrenergic synapse?

Action potential travels down the axon activating calcium channels these activate the fusion of the vesicle and nerve membranes releasing ATP and noradrenaline into the synapse,
noradrenaline acts on postsynaptic alpha/beta receptors and presynaptic alpha 2 receptors to form an autoinhibitory feedback loop
ATP acts at P2 Purinergic receptors

4

How is noradrenaline action at the synapse terminated?

There is no synaptically localised enzyme instead action is terminated through the use of two reuptake systems
NET which takes NA up into the presynaptic where it is recycled into vesicles or if there is excess it is metabolised by monoamine oxidase
EMT where 1/4 of the NA is taken up by non neural cells

5

What are the different adrenoreceptors and what are there functions?

alpha 1 acts through phospholipase C to activate PIP, IP3 and DAG to facilitate Ca2+ channel opening and smooth muscle contraction
Alpha 2 inhibits the opening of Ca2+ channels preventing further release of neurotransmitter and inhibits adenylate cyclase lowering cAMP levels and inhibiting smooth muscle contraction
Beta receptors which activate adenylate kinase which increases cAMP and leads to heart muscle contraction, glycogenolysis and smooth muscle relaxation

6

What is different about NA metabolism in the skin and in the brain?

In the skin NA is metabolised by aldehyde dehydrogenase to give NM and then VMA as the major excretion product in the urine
In the brain Aldehyde reductase is used to give MHPEG as the excretion product for the urine

7

Where does gluanethidine act?

Prevents NA release from vesicle into synaptic space

8

Where do methanphedamies act?

Block NET inhibiting the reuptake of NA

9

Where does reserpine act?

Prevents the storage of NA into vesicles

10

What are the non-selective agonists for adrenoreceptors?

Adrenaline and noradrenaline

11

What are the non-selective antagonists for adrenoreceptors?

Phentolamine

12

What are the selective agonists for adrenoreceptors?

Alpha1 : Phenylephrine
Alpha 2: Clonidine
Beta 1: Dobutamine
Beta 2: Salbutamol

13

What are the selective antagonists for adrenoreceptors?

Alpha 1: Prazosin
Alpha 2: Yohimbine
Beta 1: atenolol and propranolol
beta 2: Butoxamine

14

What are the uses of non selective agonists and antagonists at a noradrenergic synapse?

Agonists can be used to help in situations of cardiac arrest and anaphylactic shock
Antagonists can be used in pheochromocytoma where there is a tumour which when removed would cause a surge in NA levels

15

What are the effects of adrenergic agonists on vascular smooth muscle?

Alpha 1: Phenylephrine stimulates smooth muscle contraction except in the GI tract
Alpha 2: Clonidine activates presynaptic receptors in the cardiovascular control centre reducing sympathetic nerve activity and decreased blood pressure

16

What are the effects of adrenergic antagonists on smooth muscle?

Alpha 1: Prazocin which causes smooth muscle relaxation (e.g. vasodilation)
Alpha 2: Complex responses increase the release of NA but also block post synaptic NA receptors

17

What are the effects of adrenergic agonists on the heart?

Beta 1: Act as positive inotropes and chronotropes to increase heart rate and and force of contraction
e.g. Dobutamine

18

What are the effects of adrenergic antagonists on the heart?

Beta 1: Atenolol, these have an effect dependant on the level of sympathetic activity, very little effect at rest but are used to treat cardiac dysrhythmias

19

What are the effects of adrenergic agonists on bronchial smooth muscle?

Beta 2: Relax smooth muscle e.g. Salbutamol for asthma treatment (can also be used to relax uterine muscle in premature labour)

20

What are the effects of antagonist on bronchial smooth muscle?

Would trigger bronchial constriction therefore there is no clinical relevance