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Flashcards in deck_762610 Deck (58):
1

Where is Noradrenaline released in the body?

In the post ganglionic neurones of the sympathetic nervous system

2

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

Sweat glands- ACh (nicotinic receptors)Ejaculation

3

What are the "biogenic amines"? What is the synthetic pathway?

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

4

Where does the synthetic production of biogenic amines take place?

The sympathetic nerve axonTryosine --> DOPA --> Dopamine in cytoplasmDopamine - Noradrenaline in synaptic vesicle

5

What determines whether a nerve terminal is dopaminergic or noadrenergic?

The presence of DBH, which converts dopamine to noradrenaline

6

How is noradrenaline packaged for release?

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

7

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

- 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

8

List five sites of sympathetic innervation

The heartSkeletal muscleSmooth musclesAdipose tissueGlands (not sweat glands)

9

What is positive chronotrophy in heart rate?

Increase in HR

10

What is positive intropy in the heart?

Increase in force of contraction

11

Explain the anatomical basis for positive chronotrophy due to NA

- 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

12

Explain the anatomical basis for positive inotrophy due to NA

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

13

For each receptor subtype, give the G protein, effector and whether in activates or inhibitsa1

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

14

For each receptor subtype, give the G protein, effector and whether in activates or inhibitsa2

GiInhibits adenylyl cyclase Inhibits calcium channels, activates potassium channels

15

For each receptor subtype, give the G protein, effector and whether in activates or inhibitsB1 + B2

GsStimulate adenylyl cyclase causing increase cAMPCauses opening of calcium channelsB1 - in heart increase in force and rate of contractionB2 In smooth muscle, causes relaxation

16

How are extracellular noradrenaline levells decreased?

- Noradrenaline can be taken up by noradrenaline transporter and repackaged into vesicles in presynaptic neuron- Norepinephrine transporter Na+ Cl- dependent reuptakeUses Na+ gradient to move into cells- Vesicular Monoamine TransporterRepackage into vesiclesUses proton gradient

17

Name two enzymes which degrade noradrenaline

Monoamine oxidase Catechol-O-methyltransferase

18

What do enzymes degrade NA into?

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

19

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

VMA and MHPG are metabolites of noradrenalineCan be measured in urinHigh levels indicative of adrean or sympathetic nervous system tumour

20

What are the adrenoreceptors and physiological response of liver cells?

A1, B2Increased glycogenolysis, increased gluconeogenesis

21

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

a1 - constricta2 - constrict/dilateb2 - dilate

22

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

a1 - constrictb2 - dilate

23

What are the adrenoreceptors and physiological response of GI tract

a1 - relax a2 - relaxb3 - relax

24

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

B1 - increased heart rate

25

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

B1 - force of contraction increased

26

What are the adrenoreceptors and physiological response of skeletal muscle

B2 - Tremor, increased muscle mass and speed of contraction and glycogenolysisB3 - thermogenesis

27

What are the adrenoreceptors and physiological response of adipose tissue

B1, B3 - Increased lipolysis

28

What are the adrenoreceptors and physiological response of the iris?

A1 - Radial muscle contractsB2 - cillary muscle relax

29

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

Smooth muscle relaxation in airways Smooth muscle contraction in most arteriesMajor bronchiodilatory used to treat asthmaSkeletal muscle affected buy far less than the heart

30

What is an adrenoreceptor agonist?

Agents which mimic the actions of noradrenaline/adrenaline

31

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

- Increase specificity - Pevents additional side effect- Greater efficacy, so lower dose required- Can clearly predict clinical effects

32

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

Salbutamol, B2 agonist

33

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

OxymetazolineA1 and partial a2 agonist

34

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

A2 agonistClonidine

35

What is an adrenoreceptor antagonist?

One which prevents the actions of catecholamins

36

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

PrazosinTreats high blood pressure, anxiety and panic disorder

37

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

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

38

What unwanted side effects limit the usefulness of prazosin?

Syncope, hallucination, vivid dreams

39

What unwanted side effects limit the usefulness of beta blockers?

Nausea, insomnia, bronchospasm

40

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?

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

41

What is an adrenoreceptor agonist?

Agents which mimic the actions of noradrenaline/adrenaline

42

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

- Increase specificity - Pevents additional side effect- Greater efficacy, so lower dose required- Can clearly predict clinical effects

43

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

Salbutamol, B2 agonist

44

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

OxymetazolineA1 and partial a2 agonist

45

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

A2 agonistClonidine

46

What is an adrenoreceptor antagonist?

One which prevents the actions of catecholamins

47

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

PrazosinTreats high blood pressure, anxiety and panic disorder

48

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

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

49

What unwanted side effects limit the usefulness of prazosin?

Syncope, hallucination, vivid dreams

50

What unwanted side effects limit the usefulness of beta blockers?

Nausea, insomnia, bronchospasm

51

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

DOPA decarboxylase

52

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

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

53

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

Agonist for adrenergic terminals

54

How is alpha-methyl DOPA used to treat hypertension?

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

How does guanethidine inhibit noradrenaline release?

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

56

What is guanethidine used as?

An anti-hypertensive

57

What side effects does guanethidine cause?

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

58

Why are adrenoreceptor agonists and antagonists the drugs of choice?

Mimic, block or reduce effectsFocused response