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BIOL2016 - Pharmacology > Nervous Systems > Flashcards

Nervous Systems Flashcards

1
Q

What is the Autonomic Nervous System?

A

all the neural pathways that leave the brain and don’t innervate voluntary muscles

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2
Q

Sympathetic?

A

Fight or Flight

Short preganglionic and long postganglionic

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3
Q

Parasympathetic?

A

Rest and Digest

Long preganglionic and short postganglionic

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4
Q

Ganglion?

A

Point of contact between first and second efferent neurones in the pathway.
Group of nerve cell bodies that lie outside the CNS

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5
Q

Sympathetic ganglia?

A

Preganglionic neurone is located in the midbrain, medulla or lateral horn of spinal cord.
Provides diffuse innervation of target tissues (not very precise).

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6
Q

Parasympathetic ganglia?

A

Preganglionic neurone is located in the medulla or sacral segment of spinal cord.
Provides discrete innervation of target tissue.
Ganglia are in the target tissue.

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7
Q

Role of amygdala?

A

main limbic region for emotions

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8
Q

Role of hypothalamus?

A

main integration centre

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9
Q

Role of reticular formation?

A

most direct influence over autonomic function

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10
Q

Where is dopamine released in the ANS?

A

Postganglionic neurones to the smooth muscle of the renal (kidney) vascular bed release dopamine

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11
Q

Where in the ANS is there no postganglionic neurone?

A

In the paravertebral sympathetic ganglion. Directly onto the adrenal gland, releasing acetylcholine and activating nicotinic receptors on the adrenal gland. The gland releases epinephrine into system circulation.

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12
Q

Neurotransmission at the ganglia?

A

acetlycholine acting on nicotinic acetylcholine receptors

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13
Q

Neurotransmission at postganglionic sympathetic synapse?

A

noradrenaline acting on a/b- adrenoreceptors

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14
Q

Neurotransmission at postganglionic parasympathetic synapse?

A

acetylcholine acting on muscarinic receptors

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15
Q

Effects of sympathetic system?

A

Dilate pupil and bronchi, speeds up heart rate, inhibits peristalsis and urination

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16
Q

Effects of parasympathetic system?

A

Constricts pupil and bronchi, slows down heart rate, stimulates peristalsis and urination

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17
Q

Enteric Nervous System?

A

Myenteric Plexus receives the sympathetic/parasympathetic innervation. They synapse to the submucosal plexus. Sensory neurones can send local information back to local layers and CNS.

Regulates GI tract. Wide diversity of neurotransmitters. Local reflex pathways which regulate gut activity, independently of neural input from higher centres.

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18
Q

What is dysautonomia?

A

Damage to autonomic nerves.
Usually dizziness/fainting upon standing up. Inability to alter heart rate for exercise. Sweating abnormalities. Digestive problems. Urine, sex and vision problems.

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19
Q

What is the Valsalva Maneuver test?

A

tests the body’s ability to compensate for changes in the amount of blood that returns to the heart.

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20
Q

What is a receptor agonist?

A

Mimics neurotransmitters and activates receptors

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21
Q

What is a receptor antagonist?

A

Blocks neurotransmitters and stops endogenous neurotransmitters from activating the receptors

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22
Q

What did Von Euler demonstrate?

A

Noradrenaline is the main endogenous catecholamine in the sympathetic nerves

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23
Q

Another name for noradrenaline?

A

Norepinephrine

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24
Q

Another name for adrenaline?

A

Epinephrine

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25
Q

Finkleman preparation?

A

Uses intestine. NA stimulates sympathetic nerves. Catecholamine

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26
Q

When is noradrenaline not the transmitter at postganglionic sympathetic synapses?

A

in sweat glands, acetylcholine

resistance blood vessels in skeletal muscle - vasodilation

other neurotransmitters, non-adrenergic and non-cholinergic

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27
Q

How are false transmitters made?

A

If DDC is used instead of tyrosine hydroxylase, then tyramine is made.
DBH would make octopamine.
PNMT would make synephrine.

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28
Q

What is a competitive inhibitor of tyrosine hydroxylase?

A

a methyl-tyrosine

used in treatment of pheochromocytoma

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29
Q

What can interfere with noradrenaline transmission?

A

a methyl-DOPA leads to synthesis of flase transmitter a methyl-noradrenaline

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30
Q

Treatment of Parkinson’s Disease?

A

Carbidopa inhibits DDC (L-DOPA –> dopamine) and is administered with L-DOPA.
No peripheral metabolism of L-DOPA.
Carbidopa doesn’t cross the BBB. Prevents L-DOPA from being converted into dopamine prematurely in the bloodstream.

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31
Q

How is noradrenaline stored?

A

In vesicles. ATP driven proton gradient pumps the noradrenaline into the vesicles.

Stored with ATP and chromogranin.

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32
Q

Reserpine

A

Inhibitor of noradrenaline storage. Side effect of antihypertension from treating depression.

33
Q

Guanethidine?

A

Inhibitor for incorporation of noradrenaline into presynaptic vesicles. Side effect - orthostatic hypotension

34
Q

High affinity noradrenaline uptake?

A 
Low capacity. 
Noradrenaline transporter (NAT). On nerve terminal. Requires Na+ gradient and ATP. Active so high affinity. Substrate specificity.
35
Q

Low affinity noradrenaline uptake?

A

High capacity.

Present on extraneuronal tissue. Inhibited by cortisol. Passive. Cotransport with Na+

36
Q

Drugs which block noradrenaline transporter?

A

Clinically used as antidepressants.

Cocaine blocks active uptake.
Imipramine first tricyclical antidepressant. Desipramine and amitriptyline are similar.

Guanethidine also weakly blocks.

37
Q

Which drugs stimulate noradrenaline release?

A

Tyramine
Ephedrine
Amphetamine

38
Q

Important enzymes in noradrenaline metabolism?

A

MAO (monoamine oxidase)

COMT (catechol-o-methyltransferase)

39
Q

Important metabolites in noradrenaline metabolism?

A

VMA and MPHG

Plamsa levels of the metabolites can be useful biomarkers of disease

40
Q

Drugs that interfere with noradrenaline metabolism?

A

MAOIs - Monoamine oxidase inhibitors

Iproniazid

41
Q

What type of receptor are adrenoceptors?

A

G Protein Coupled Receptors

42
Q

Adrenoceptor subtypes?

A

A1, A1, B1, B2, B3

43
Q

What drives feedback inhibition of noradrenaline release at the synapse?

A

alpha 2 adrenoceptors

44
Q

where is alpha 1?

A

postsynaptic

45
Q

where is alpha 2?

A

presynaptic

46
Q

Alpha adrenoceptor agonists?

A

phenylephrine a1>a2
methoxamine a1
clonidine a2

47
Q

How do you block raised blood pressure?

A

agonise alpha 2

48
Q

Alpha adrenoceptor antagonists?

A

phentolamine a1=a2
phenoxybenzamine a1
prasozin a1>a2
yohimbine a2>a1

49
Q

Antihypertensive?

A

Block a1

50
Q

Effect of yohimbine on noradrenaline transmission?

A

low dose just blocks a1, high dose blocks both

51
Q

What do b adrenoceptors stimulate?

A

cAMP formation

52
Q

effects of b1 adrenoceptors?

A

cardiac acceleration
lipolysis
decreased gut motility & secretion
renin release

53
Q

effects of b2 adrenoceptors?

A

bronchodilation
blood vessels to skeletal muscles vasodilation
glycogen breakdown

54
Q

beta adrenoceptors agonists?

A

isoprenaline b1>b2
salbutamol b2>b1
dobutamine b1>b2

55
Q

Use of isoprenaline

A

used to treat asthma, high incidence of heart failure

56
Q

Use of salbutamol

A

effective bronchodilation by inhalation

57
Q

Use of dobutamine

A

cardiac stimulant

58
Q

beta adrenoceptor antagonists?

A

propranolol - non selective beta blocker, local anaesthetic action

atenolol - b1 antagonist. cardioselective.

59
Q

How is choline taken up to nerve terminals?

A

by choline transporter

60
Q

How is acetylcholine taken up into presynaptic vesicles?

A

Active transport process (blocked by vesamicol). Vesicle Acetylcholine Transporter

61
Q

What blocks choline transporter?

A

Hemicholinium

62
Q

How is acetylcholine inactivated?

A

Acetylcholinesterase breaks down into choline and acetic acid.

63
Q

2 actions of cholinergic transmission?

A

muscarine - paralysed by atropine

nicotine - paralysed by nicotine

64
Q

How can acetylcholine produce 2 different effects on blood pressure?

A

The same compound triggers two dose dependent opposite responses.
Low affinity receptor can only be triggered with high levels of acetylcholine.

65
Q

Muscarinic agonists?

A 
Acetylcholine (also nicotinic)
Carbachol (also nicotinic) 
Bethanechol 
Muscarine 
Pilocarpine 
Oxotremorine
66
Q

Effects of muscarinic agonists?

A

Decreased HR, CO and vasodilation
Increased GI activity
Increased sweating and salivation

67
Q

Treatment of glaucoma?

A

Failed drainage in the eye via the drainage canal. Gets blocked, increases intraocular pressure and the optic nerve gets damaged.

Pilocarpine - ciliary muscle relaxes and relieves the pressure on the drainage canal.

68
Q

M1 receptor?

A

Neural - CNS
Increases IP3 and DAG
Gastric acid secretion & Gut motility

69
Q

M2 receptor?

A

Cardiac - Atria & presynaptic terminals
Decreased cAMP
Cardiac and neural inhibition

70
Q

M3 receptor?

A

Glandular - exocrine glands, smooth muscle and vascular endothelium.
Increases IP3 and DAG
Secretion, smooth muscle contraction and vasodilation via NO.

71
Q

Muscarinic receptor structure?

A

Has a central binding site for ACh.

Can be coupled to Gq (excitatory) or G/o (inhibitory)

72
Q

Muscarinic receptor antagonists?

A

atropine

pirenzepine

73
Q

Which receptors have a higher affinity for acetylcholine?

A

muscarinic

74
Q

N1 receptor?

A

Neuromuscular junction. NN

75
Q

N2 receptor?

A

Autonomic ganglia, CNS or adrenal medulla. NM

76
Q

Nicotinic agonists?

A

acetylcholine

nicotine - stimulates autonomic ganglia

77
Q

What happens when acetylcholine binds at nicotinic receptors?

A

Binds to alpha subunits, the channel opens and allows sodium and potassium to flow through.

78
Q

What blocks ganglionic nicotinic receptors?

A

Hexamethonium
Reduces bp, dry mouth, constipation, urinary retention, blurred vision, sexual dsyfunction. Better to alter either sympathetic or parasympathetic, not entire ANS.

79
Q

What series does hexamethonium belong to?

A

polymethylene bismethonium series

shorter - ganglionic block
longer - neuromuscular block

BIOL2016 - Pharmacology (6 decks)

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