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1st Year - Principles > Pharmacology 6 and 7 - Autonomic Pharmacology > Flashcards

Pharmacology 6 and 7 - Autonomic Pharmacology Flashcards

1
Q

Afferent?

A

Towards the CNS

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2
Q

Efferent?

A

Away from the CNS

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3
Q

4 branches of the PNS?

A

Somatic effent Autonomic (ANS)EntericSomatic and visceral afferent

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4
Q

What are the 2 division of the ANS?

A

SympatheticParasympathetic

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5
Q

What is the purpose of the ANS?

A

To carry output from the CNS to the whole body with the exception of skeletal muscle

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6
Q

What allows a degree of copious control of some ANS functions?

A

Training e.g. urination, defecation

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7
Q

What does the parasympathetic ANS coordinate?

A

the bodies basic homeostatic functions

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8
Q

What does the sympathetic ANS coordinate?

A

The body’s response to stress, associated with fight, flight and fright reactions

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9
Q

What 2 neurones is a sympathetic/ parasympathetic branch made up of?

A

Preganglionic neuronePostganglionic neurone

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10
Q

What is the transmitter in the preganglionc neurone of the sympathetic ANS?

A

Acetylcholine (ACh)

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11
Q

What is the transmitter in the preganglionic neurone in the parasympathetic ANS?

A

Acetylcholine (ACh)

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12
Q

What is the transmitter in the post-ganglionic neurone in the parasympathetic division?

A

Acetylcholine (ACh)

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13
Q

What is the transmitter in the postganglionic neurone in the sympathetic division?

A

Usually Noradrenaline (NA)

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14
Q

What is the word used to describe neurones that use ACh?

A

Cholinergic

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15
Q

What is the word used to describe neurones that use NA?

A

Adrenergic

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16
Q

Where can sympathetic signals synapse?

A

In the sympathetic chainIn the prevertebral ganglia

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17
Q

What organs sympathetic supply tends to synapse in the sympathetic chain?

A

signals going to the eye, heart and lungs (above diaphragm)

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18
Q

What organs sympathetic supply tends to synapse in pre-vertebral ganglia?

A

Signals going to the liver, gallbladder, stomach, pancreas, spleen, kidney, intestines and genitourinary tract (below diaphragm)

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19
Q

What tissues sympathetic supply doesn’t synapse?

A

Adrenal gland (nerve supply only consists of a preganglionic neurone - transmitter released is ACh)

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20
Q

What branch of the ANS has thoracolumbar outflow?

A

Sympathetic

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21
Q

What branch of the ANS has craniosacral outflow?

A

Parasympathetic

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22
Q

Where does the parasympathetic axons leave the CNS?

A

Via cranial nerves III, VII, IX, and XVia sacral spinal nerves

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23
Q

What organs does the parasympathetic outflow supply?

A

Parasympathetic ganglia in head = Lacrimal gland and salivary glandsVagus nerve = organs of the neck, chest and abdomen as far as the midgutSacral spinal nerves “carry” parasympathetic axons to the hind-gut, pelvis and perineum

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24
Q

Where are parasympathetic ganglia?

A

Usually in the target organs (discrete ganglia exist in the head and beck)

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25
Q

What does sympathetic stimulation at heart cause? (2)

A

Increases heart rateIncreases force of contraction

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26
Q

What does parasympathetic stimulation of the heart cause?(1)

A

Decreases heart rate

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27
Q

What does sympathetic stimulation of the lungs cause? (2)

A

Relaxes bronchi Decreases mucus production (decreasing airway resistance)

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28
Q

What does parasympathetic stimulation of the lungs cause? (2)

A

Constricts bronchiStimulates mucus production

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29
Q

How does sympathetic nervous system cause the relaxation of bronchi?

A

Via release of adrenaline

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30
Q

Effect of sympathetic stimulation on the GI tract? (2)

A

Reduces motilityConstricts sphincters

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31
Q

Effect of parasympathetic stimulation on the GI tract? (2)

A

Increases motilityRelaxes sphoncters

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32
Q

Effect of sympathetic stimulation on the arterioles?

A

Constricts in most locations although relaxes at muscles

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33
Q

Effect of parasympathetic stimulation on arterioles?

A

Largely no effect

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34
Q

Effect of sympathetic stimulation on adrenal gland?

A

Release of adrenaline

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35
Q

Effect of parasympathetic stimulation on adrenal gland?

A

No effect

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36
Q

Effect of sympathetic stimulation on penis?

A

Ejaculation

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37
Q

Effect of parasympathetic stimulation on penis?

A

Erection

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38
Q

What are the steps of neurochemical transmission?

A

1) Uptake of precursor2) Synthesis of transmitter3) storage of transmitter4) depolarisation by action potential5) Ca2+ influx through voltage-activated Ca2+ channels6) Ca2+ induced release of transmitter (exocytosis)7) receptor activation8) enzyme mediated inactivation of transmitter OR9) reuptake of transmitter

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39
Q

What are ligand-gated ion channels?

A

Ion channels that are gated by chemicals

40
Q

What is the name of the ligand-gated ion channel on the post-ganglionic neurone opened by ACh?

A

Nicotinic ACh receptors

41
Q

What happens when an action potential arising from the CNS arrives at the presynaptic terminal of the preganglionic neurone? (either sympathetic or parasympathetic)

A

Ca2+ entry is triggered causing the release of AChACh opens nicotonic ACh receptors (a ligand gated ion channel) in the postganglionic neurone causing depolarisation and the generation of action potentials

42
Q

What happens when an action potential arrives at the pre-synaptic terminal of the post-ganglionic neurone in the sympathetic division?

A

Ca2+ entry is triggered causing the release of noradrenalineNoradrenaline activated G-protein-coupled adrenoceptors in the target cell membrane causing a cellular response

43
Q

What type of receptor in the target cell is activated by noradrenaline?

A

G-protein-coupled adrenoceptors

44
Q

What type of receptor on the target cell is activated by ACh?

A

G-protein-coupled muscarinic acetylcholine receptors

45
Q

What happens when an action potential arises at the pre-synaptic terminal of the post-synaptic neurone (parasympathetic)?

A

ACh is always the transmitter usedCa2+ entry is triggered causing the release of AChAt activated G-protein-coupled muscarinic acetylcholine receptors in the target cell membrane to cause a cellular response

46
Q

What are other names for ligand-gated ion channels? (2)

A

Transmitter-gated ion channelsIonotropic receptors

47
Q

What are ligand-gated ion channels made up from?

A

Separate glycoprotein subunits that form a central, ion conducting, channel

48
Q

What does ligand-gated ion channels allow? (2)

A

Allow rapid changes in the permeability of the membrane to certain ionsRapidly alter membrane potential

49
Q

What does the binding of a transmitter to a ligand-gated ion channel cause?

A

The gate to be opened (stays closed for a small period of time before opening)Increases the membrane permeability to the selected ion

50
Q

What are 2 types of receptors on neurones?

A

Ligand-gated ion channels (on post-ganglionic neurones)G-protein-coupled receptors (on target cell membrane)

51
Q

What does the G-protein couple in G-protein-coupled receptors?

A

Receptor activation to effector modulation

52
Q

What is the speed of signalling via G-proteins like in comparison to transmitter-gated ion channels

A

Relatively slow

53
Q

What are the 3 separate parts of a G-protein-coupled receptor?

A

ReceptorG-proteinEffector (enzyme or ion channel)

54
Q

What is the basic structure of the receptor in in G-protein coupled receptors? (3)

A

Integral membrane protein formed from a single polypeptide with extracellular NH2 and intracellular COOH terminiContains seven transmembrane spans joined by 3 extracellular and 3 intracellular connecting loops

55
Q

What is the full title for a G-protein?

A

Guanine nucleotide binding portein

56
Q

What are the 3 polypeptide subunits of a g-protein?

A

AlphaBetaGamma

57
Q

What is the structure of a g-protein?

A

3 polypeptide chains (alpha, beta and gamma) with a guanine nucleotide binding site in the alpha subunit that can hold guanosine triphosphte (GTP) or guanosine diphosphate (GDP)

58
Q

What can the effector in G-protein-coupled receptors be?

A

Enzyme or ion channel

59
Q

What is the appearance of a G-protein coupled receptor that has no signalling?

A

The receptor is unoccupiedThe G protein alpha subunit binds GDPThe effector is not modulated

60
Q

What happens to a G-protein coupled receptor when signalling is turned on?

A

Agonist activates receptorG-protein couples with receptorGDP dissociated from, and GTP binds to, the alpha subunitThe G-protein dissociated into separate alpha and beta-gamma subunitsThe G-protein alpha subunit combines with and modifies activity of effectorThe agonist may dissociate from the receptor but the signalling can persist

61
Q

How is the G-protein-coupled receptor signal turned off?

A

The alpha subunit acts as an enzyme (a GTPase) to hydrolyse GTP to GDP and PiThe signal is turned offThe Gprotein alpha subunit recombined with the Geta-gamma subunit completing the G-protein cycle

62
Q

Structure of Nicotinic Acetylcholine receptors?

A

Consist of 5 glycoprotein subunits that form a central, cation conducting, channel (Na+, K+ and Ca2+)

63
Q

What are the possible subunits that nicotinic Ach receptors can be formed from?

A

Alpha 1-10Beta 1-4GammaDeltaEpsilon

64
Q

What are the parts skeletal muscle (alpha 1)2 beta gamma epsilon is made up of?

A

2 X alpha 11 X gamma1 X beta 11 X delta/ epsilon

65
Q

What are the parts that “ganglionic” alpha3 beta4 is made up from?

A

2 X alpha 33 X beta 4

66
Q

What are the parts that alpha 4 beta 2 is made up from?

A

2 X alpha 43 X beta 2

67
Q

What are the parts that Alpha7 is made up from?

A

5 X alpha 7

68
Q

What are the 2 reactant in the formation of acetylcholine?What is the enzyme in the formation of acetylcholine?

A

Choline (uptake via transporter)Acetyl CoACholine acetyltransferase

69
Q

What type of receptors can AcH activate?

A

NicotinicMuscarinic (G-protein coupled)

70
Q

What happens after AcH activates a receptor?

A

It is degraded to choline and acetate by acetylcholinesterasenReuptake and reuse of choline

71
Q

What does an activated nicotinic ACh receptor (alpha3 beta4) transport into the cell?What does this create?

A

Na+A graded depolarisation (excitatory post-synaptic potential) - more likely to reach action potential

72
Q

What is a clinically significant drug that affects cholinergic transmission at ganglia?

A

Nicotine - most drugs that affect cholinergic transmission at ganglia have little clinical significance (often used experimentally)

73
Q

What is an agent that selectively blocked ganglionic transmission at cholinergic receptors?What was this previously used for?How does this work?

A

HexamethoniumFirst effective antihypertensive agent (no longer used)Open channel blocker (a form of non-competitive antagonism)

74
Q

How many muscarinic ACh receptor subtypes are there?

A

M1-3

75
Q

What is the name of the junction between a neurone and effector cell?

A

Neuroeffector junction

76
Q

What alpha subunit of G protein is associated with M1?what does activation of this G-protein-coupled muscarinic ACh receptor cause?What effect does this have?

A

GqSimulation of phospholipase CIncreased acid secretion

77
Q

What alpha subunit of G protein is associated with M2?what does activation of this G-protein-coupled muscarinic ACh receptor cause?What effect does this have?

A

GiInhibition of adenyly cyclase; opening of K+ channelsDecreased heart rate

78
Q

What alpha subunit of G protein is associated with M3?what does activation of this G-protein-coupled muscarinic ACh receptor cause?What effect does this have?

A

GqStimulation of phospholipase CContraction of airway smooth muscle (vascular smooth muscle indirectly replaces by M3 receptor activation

79
Q

What are the 2 broad categories of adernoceptors?

A

alpha Beta

80
Q

What is noradrenaline synthesised from?

A

L-Tyrosine

81
Q

How is NA removed from the synapse?

A

Repute by transporters uptake 1 (U1 - neurone) and uptake 2 (U2 - effector/ surrounding cell) and reutilised or metabolised by monoamine oxidase (MAO - neurone) and catechol-O-methyltransferase (COMT - effector/ surrounding cell)

82
Q

What alpha subunit of G protein is associated with B1?what does activation of this G-protein-coupled adrenoceptor receptor cause?What effect does this have?

A

Gsstimulation of adenylyl cyclaseIncreased rate and force of heart contraction

83
Q

What alpha subunit of G protein is associated with B2?what does activation of this G-protein-coupled adrenoceptor receptor cause?What effect does this have?

A

GsStimulation of adenylyl cyclase Relaxation of bronchial and vascular smooth muscle

84
Q

What alpha subunit of G protein is associated with a1?what does activation of this G-protein-coupled adrenoceptor receptor cause?What effect does this have?

A

GqStimulation of phospholipase CContraction of vascular smooth muscle

85
Q

What alpha subunit of G protein is associated with a2?what does activation of this G-protein-coupled adrenoceptor receptor cause?What effect does this have?

A

GiInhibition of adenylyl cyclaseInhibition of NA release

86
Q

What is an autoreceptor?

A

An autoreceptor is a type of receptor located in the membranes of presynaptic nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the autoreceptor sits.

87
Q

Example of auto receptor on post-ganglionic parasympathetic neurone?

A

M2

88
Q

Example of auto receptor on post-ganglionic sympathetic neurone?

A

a2

89
Q

What is the purpose of auto receptors?

A

To mediate negative feedback inhibition of transmitter release (neurotransmitter released by the neurone binds to auto receptor which inhibits the calcium channel preventing more neurotransmitter being released)

90
Q

What effect does cocaine have on the autonomic nervous system?What symptoms does this cause?

A

It blocks U1 increasing the concentration of NA in the synaptic cleft resulting in increased adrenoceptor stimulation (3, 4)Peripheral actions cause vasocontriction (alpha1 stimulation) and cardiac arrhythmias (B1 stimulation)

91
Q

What effect does amphetamine have on the autonomic nervous system?What symptoms does this called?

A

It is a substrate for U1 and enters the noradrenergic terminal where it inhibits MAO, enters the synaptic vehicle (where NA is stored) and displaces NA into the cytoplasmNA exits the terminal on U1 running backwards and accumulates in the synaptic cleft causing increased adrenoceptor stimulationPeripheral actions cause vasocontriction (alpha1 stimulation) and cardiac arrhythmias (B1 stimulation)

92
Q

Do agonists of presynaptic auto receptors increase or decrease release of transmitter?

A

Decrease release

93
Q

Do antagonists of presynaptic auto receptors increase or decrease release of transmitter?

A

Increase release

94
Q

What does Prazosin do in the ANS?Use?

A

Selective, competitive, antagonist of alpha 1Vasodilator used an anti-hypertensive agent

95
Q

What does Atenolol do in the ANS?Use?

A

Selective, competitive, antagonist of B1 (beta blocker)Does not block B2, alpha 1 or alpha 2Used as an anti-anginas and anti-hypertensive agent

96
Q

What does salbutamol do in the ANS?Use?

A

Selective agonist at B2Does not activate B1, alpha 1 or alpha 2Used as a bronchodilator in asthma

97
Q

What does atropine do in the ANS?Use?

A

Competitive antagonist of muscarinic ACh receptors, does not block nicotinic ACh receptorsBlocks all muscarinic ACh receptors with equal affinity (1, 2, 3)Exerts widespread effects by blockade of the parasympathetic division of the ANSUsed to reverse bradycardia following MI and in anti cholinesterase poisoning

1st Year - Principles (37 decks)

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