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CRRAB 1 > Week 6: Adrenergic Agonists > Flashcards

Week 6: Adrenergic Agonists Flashcards

1
Q

Where are alpha 1 receptors found?

A

vascular smooth muscle of skin and splanchnic regions, GI and bladder sphincters

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2
Q

What is the effect of alpha 1 receptor stimulation?

A

Contraction/constriction

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3
Q

Which G protein is associated with alpha 1 receptors?

A

Gq

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4
Q

How do alpha 1s exert their effects?

A

Gq protein -> stim of phospholipase C -> increased IP3 -> inc intracellular [Ca]

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5
Q

Where are alpha 2 receptors found?

A

sympathetic post-gang nerve terminals (autoreceptors), platelets, fat cells, walls of GI tract

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6
Q

What is the effect of alpha 2 receptor stimulation?

A

Relaxation or dilation. Inhibition of neural NE release.

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7
Q

Which G protein is associated with alpha 2 receptors?

A

Gi

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8
Q

How do alpha 2s exert their effects

A

Gi protein -> activates Na/H antiporter OR inhibits adenylate cyclase -> dec cAMP

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9
Q

Where are beta 1 receptors found?

A

Heart: SA node, AV node, ventricular muscle, JG apparatus, adipose tissue

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10
Q

What is the effect of beta 1 stimulation

A

Increased HR (chronotropic), inc conduction velocity (dromotropic), inc contractility (inotropic)

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11
Q

Which G protein is associated with beta 1 and 2 receptors?

A

Gαs

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12
Q

How do beta 1 and 2s exert their effects?

A

Gαs -> stimulation of adenylate cyclase -> inc cAMP

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13
Q

Where are beta 2 receptors found?

A

vascular smooth muscle of skeletal muscle, bronchial smooth muscle, walls of the GI tract and bladder

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14
Q

What is the effect of beta 2 stimulation?

A

Relaxation e.g. dilation of vascular smooth muscle and bronchioles, relaxation of bladder wall.

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15
Q

Compare isoproterenol, epi, and NE sensitivity of beta 1 receptors

A

isoproterenol > epi = NE

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16
Q

Compare isoproterenol, epi, and NE sensitivity of beta 2 receptors

A

isoproterenol > epi&raquo_space; NE

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17
Q

Compare isoproterenol, epi, and NE sensitivity of alpha 1 receptors

A

epi >/= NE&raquo_space; isoproterenol

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18
Q

Compare isoproterenol, epi, and NE sensitivity of alpha 2 receptors

A

epi >/= NE&raquo_space; isoproterenol

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19
Q

alpha 1 agonists

A

NE, phenylephrine

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20
Q

Alpha 1 antagonists

A

-zosin e.g. Prazosin

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21
Q

Alpha 2 agonist

A

Clonidine

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22
Q

Beta 1 agonists

A

NE, isoproterenol, dobutamine

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23
Q

Beta 1 antagonists

A

Propranolol (non-selective), Metoprolol

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24
Q

Beta 2 agonists

A

Isoproterenol, albuterol

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25
Q

Beta 2 antagonists

A

Propranolol, butoxamine

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26
Q

-terol suffix

A

B2 agonist

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27
Q

What components of the CV system are innervated by sympathetics?

A

Atria, ventricles, arterioles, and veins

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28
Q

How are NE and Epi synthesized?

A

Tyrosine -> DOPA -> Dopamine -> NE -> Epi (in adrenal medulla)

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29
Q

What enzyme is rate limiting in sympathetic neurotransmitter synthesis?

A

Tyrosine hydroxylase

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30
Q

What does Reserpine do?

A

Irreversibly blocks vesicular monoamine transporter -> no sequestration of free NE -> NE degraded by MAO and COMT

31
Q

Where does the cholera toxin act?

A

Irreversibly activates Gsalpha -> secretion from colon -> death by dehydration

32
Q

What does Dobutamine do?

A

Selective B1 agonist. Increases HR and contractility.

33
Q

Albuterol MOA

A

B2 agonist -> relaxation of smooth muscle of bronchioles and uterine lining. Decreases BP via dec TPR.

34
Q

Phenylephrine MOA

A

Alpha 1 agonist -> inc BP.

35
Q

Isoproterenol MOA

A

Nonselective Beta agonist

36
Q

How does epinephrine reversal work?

A

Give epi -> rise in BP. Then give α-antagonist -> no α actions from epi. E.g. vasoconstriction is interrupted, but vasodilation of other vascular beds caused by stimulation of β receptors is not blocked. Therefore alpha antagonist -> dec BP in response to epi

37
Q

Where are muscarinic receptors?

A

Postganglionic parasympathetic targets (heart and vessels) + sweat glands and vessels (postganglionic sympathetic cholinergic)

38
Q

How are adrenergic amines released?

A

Stim of nicotinic receptors on postganglionic nerve

39
Q

How does NE inhibit own release?

A

Via alpha 2 autoreceptor

40
Q

Action of cocaine

A

Inhibits axoplasmic pump -> potentiates sympathetic response

41
Q

What does Guanethidine do?

A

Induces release of NE from vesicle leading to degradation by MAO -> reduced sympathetic response

42
Q

What does pargyline do? (IMPORTANT!)

A

MAO inhibitor (potentiates sympathetic responses), blocks Guanethidine effects

43
Q

What 2 enzymes degrade adrenergic amines, and where are they located?

A

COMT (catechole-O-methyl transferase) in cytoplasm, MAO in mitochondria

44
Q

Effect of dopamine?

A

Dilation of renal and mesenteric vasculature (dopaminergic) vasoconstrictor (alpha 1) at higher doses. Positive inotrope (B1), release NE from nerves

45
Q

Dobutamine therapeutic use

A

CHF, AMI with HF

46
Q

What adrenergic agonist can raise HR, SV, and TPR respectively?

A

HR and SV: B1, TPR: alpha 1

47
Q

What autonomic activity can result in decreased HR, SV, and TPR respectively?

A

HR: muscarinic, SV: none, TPR: beta 2 and muscarinic

48
Q

Therapeutic use of dopamine

A

shock (maintains renal perfusion at low dose via dopaminergic receptor), hypotension (inc BP and CO), chronic refractory HF

49
Q

What is midodrine? What is it used for?

A

Alpha 1 agonist for orthostatic hypotension

50
Q

What is phenylephrine? What is it used for?

A

Alpha 1 agonist. Treats hypotension, paroxysmal atrial tachycardia, decongestant, topical vasoconstrictor and mydriatic

51
Q

B2 selective agonists

A

Metaproterenol, Terbutaline, Albuterol, Ritodrine, Salmeterol

52
Q

Uses for B2 selective agonists

A

asthma (except Ritodrine which does not result in bronchodilation

53
Q

B2 agonists for delaying labor

A

Ritodrine, terbutaline

54
Q

Major side effects of B2 agonists

A

Tremor (skel muscle B2 stim), HA (B2 vasodilation), tachycardia, palpitations (b1)

55
Q

What is isoproterenol?

A

Synthetic catecholamine that stimulates beta receptors -> vasodilation (b2) and tachy (b1)

56
Q

NE effects

A

Vasoconstriction (alpha 1), Inc HR and force (B1)

57
Q

NE therapeutic use

A

hypotension

58
Q

Epi effects

A

vasoconstricts (a1) vasodilates (b2) - vasoconstriction generally wins therapeutically, inc HR, force (can have reflex vagal stim -> dec HR)

59
Q

Epi uses

A

Hypersensitivity reaction, low BP, bronchospasm (a1 and B2). With anesthetic -> vasoconstrict, prevent diffusion away

60
Q

How do indirectly acting sympathomimetics work? What is an example?

A

Release NE from nerves by reversing catecholamine axoplasmic uptake pump. Phenylethylamines e.g. amphetamine.

61
Q

Amphetamine therapeutic uses

A

Narcolepsy, obesity, hyperkinetic syndrome

62
Q

How does Ephedrine work?

A

releases NE -> inc BP via a1 and b1, vasodilates via B2

63
Q

Therapeutic uses of ephedrine

A

Bronchospasm. For colds: NE -> vasoconstriction -> dec mucosal congestion (a1), bronchodilates (b2)

64
Q

How does pseudoephedrine work?

A

Same as ephedrine, just a stereoisomer.

65
Q

Which drugs block accumulation of NE in nerves, potentiating sympathetic action? (2)

A

Cocaine, Imipramine

66
Q

Which drugs reverse the axoplasmic transporter, mimicking symp stim (3)?

A

Tyramine, amphetamine, ephedrine

67
Q

Which drug blocks vesicular accumulation of NE leading to its degradation?

68
Q

Which drugs release NE from vesicles -> depletion? (2)

A

Guanethidine, guanadrel

69
Q

Epi acts on what adrenergic receptor(s)?

A

a1, a2, b1, b2

70
Q

NE acts on what adrenergic receptor(s)?

A

a1, a2, b1

71
Q

Phenylephrine acts on what adrenergic receptor(s)?

72
Q

Dobutamine acts on what adrenergic receptor(s)?

73
Q

Ritodrine and Terbutaline act on what adrenergic receptor(s)?

74
Q

Albuterol and other -terols work on what adrenergic receptor(s)?

CRRAB 1 (12 decks)

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