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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
Beta 2 antagonists
Propranolol, butoxamine
26
-terol suffix
B2 agonist
27
What components of the CV system are innervated by sympathetics?
Atria, ventricles, arterioles, and veins
28
How are NE and Epi synthesized?
Tyrosine -> DOPA -> Dopamine -> NE -> Epi (in adrenal medulla)
29
What enzyme is rate limiting in sympathetic neurotransmitter synthesis?
Tyrosine hydroxylase
30
What does Reserpine do?
Irreversibly blocks vesicular monoamine transporter -> no sequestration of free NE -> NE degraded by MAO and COMT
31
Where does the cholera toxin act?
Irreversibly activates Gsalpha -> secretion from colon -> death by dehydration
32
What does Dobutamine do?
Selective B1 agonist. Increases HR and contractility.
33
Albuterol MOA
B2 agonist -> relaxation of smooth muscle of bronchioles and uterine lining. Decreases BP via dec TPR.
34
Phenylephrine MOA
Alpha 1 agonist -> inc BP.
35
Isoproterenol MOA
Nonselective Beta agonist
36
How does epinephrine reversal work?
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
Where are muscarinic receptors?
Postganglionic parasympathetic targets (heart and vessels) + sweat glands and vessels (postganglionic sympathetic cholinergic)
38
How are adrenergic amines released?
Stim of nicotinic receptors on postganglionic nerve
39
How does NE inhibit own release?
Via alpha 2 autoreceptor
40
Action of cocaine
Inhibits axoplasmic pump -> potentiates sympathetic response
41
What does Guanethidine do?
Induces release of NE from vesicle leading to degradation by MAO -> reduced sympathetic response
42
What does pargyline do? (IMPORTANT!)
MAO inhibitor (potentiates sympathetic responses), blocks Guanethidine effects
43
What 2 enzymes degrade adrenergic amines, and where are they located?
COMT (catechole-O-methyl transferase) in cytoplasm, MAO in mitochondria
44
Effect of dopamine?
Dilation of renal and mesenteric vasculature (dopaminergic) vasoconstrictor (alpha 1) at higher doses. Positive inotrope (B1), release NE from nerves
45
Dobutamine therapeutic use
CHF, AMI with HF
46
What adrenergic agonist can raise HR, SV, and TPR respectively?
HR and SV: B1, TPR: alpha 1
47
What autonomic activity can result in decreased HR, SV, and TPR respectively?
HR: muscarinic, SV: none, TPR: beta 2 and muscarinic
48
Therapeutic use of dopamine
shock (maintains renal perfusion at low dose via dopaminergic receptor), hypotension (inc BP and CO), chronic refractory HF
49
What is midodrine? What is it used for?
Alpha 1 agonist for orthostatic hypotension
50
What is phenylephrine? What is it used for?
Alpha 1 agonist. Treats hypotension, paroxysmal atrial tachycardia, decongestant, topical vasoconstrictor and mydriatic
51
B2 selective agonists
Metaproterenol, Terbutaline, Albuterol, Ritodrine, Salmeterol
52
Uses for B2 selective agonists
asthma (except Ritodrine which does not result in bronchodilation
53
B2 agonists for delaying labor
Ritodrine, terbutaline
54
Major side effects of B2 agonists
Tremor (skel muscle B2 stim), HA (B2 vasodilation), tachycardia, palpitations (b1)
55
What is isoproterenol?
Synthetic catecholamine that stimulates beta receptors -> vasodilation (b2) and tachy (b1)
56
NE effects
Vasoconstriction (alpha 1), Inc HR and force (B1)
57
NE therapeutic use
hypotension
58
Epi effects
vasoconstricts (a1) vasodilates (b2) - vasoconstriction generally wins therapeutically, inc HR, force (can have reflex vagal stim -> dec HR)
59
Epi uses
Hypersensitivity reaction, low BP, bronchospasm (a1 and B2). With anesthetic -> vasoconstrict, prevent diffusion away
60
How do indirectly acting sympathomimetics work? What is an example?
Release NE from nerves by reversing catecholamine axoplasmic uptake pump. Phenylethylamines e.g. amphetamine.
61
Amphetamine therapeutic uses
Narcolepsy, obesity, hyperkinetic syndrome
62
How does Ephedrine work?
releases NE -> inc BP via a1 and b1, vasodilates via B2
63
Therapeutic uses of ephedrine
Bronchospasm. For colds: NE -> vasoconstriction -> dec mucosal congestion (a1), bronchodilates (b2)
64
How does pseudoephedrine work?
Same as ephedrine, just a stereoisomer.
65
Which drugs block accumulation of NE in nerves, potentiating sympathetic action? (2)
Cocaine, Imipramine
66
Which drugs reverse the axoplasmic transporter, mimicking symp stim (3)?
Tyramine, amphetamine, ephedrine
67
Which drug blocks vesicular accumulation of NE leading to its degradation?
Reserpine
68
Which drugs release NE from vesicles -> depletion? (2)
Guanethidine, guanadrel
69
Epi acts on what adrenergic receptor(s)?
a1, a2, b1, b2
70
NE acts on what adrenergic receptor(s)?
a1, a2, b1
71
Phenylephrine acts on what adrenergic receptor(s)?
alpha 1
72
Dobutamine acts on what adrenergic receptor(s)?
B1
73
Ritodrine and Terbutaline act on what adrenergic receptor(s)?
B2
74
Albuterol and other -terols work on what adrenergic receptor(s)?
B2

CRRAB 1 (12 decks)

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