Organic Nitrates and Vasodilators Flashcards

1
Q

Minoxidil activated in vivo by ______________ 1A1

A

sulfotransferase

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2
Q

adenosine binds to _______ which is a _______

A

A1 receptor; GPCR

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3
Q

With sildenafil, there is lack of _____________

A

systemic vasodilation

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4
Q

Where is PDE5 expressed?

A

VSM of the lungs

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5
Q

What are viagra and cialis indicated for?

A

TREATMENT OF PULMONARY ARTERIAL HTN

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6
Q

hypertrichosis definition

A

excessive hair growth

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7
Q

Hyperpolarization of vascular smooth muscle:

A1 (adenosine receptor) and the ______

A

GIRK (G-protein activated inwardly rectifying K+ channel)

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8
Q

Mechanisms for controlling smooth muscle tone: contraction

A
  • Ca2+ channels (L-type)
  • intracellular Ca2+ stores
  • increases Ca2+ in combination with calmodulin
  • impacts myosin light kinase
  • impacts myosin light chain
  • myosin light chain is phosphorylated with actin
  • CONTRACTION
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9
Q

diazoxide is a ________ vasodilator. Effective in _______, drug resistant forms of ______

A

potent; severe; HTN

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10
Q

Prostacyclin (PGI2) - Epoprostenol given _______

A

IV (produced in the endothelium)

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11
Q

Vasoconstrictor antagonists: ambrisentan

A
  • blocks only ETa receptors
  • approved for pulmonary arterial hypertension***
  • contraindicated in pregnancy (class); hepatotoxicity (Bosentan)
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12
Q

Treprostinil (Remodulin) given _______

A

orally ; IV

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13
Q

The _____ allele accounts for alcohol __________ intolerance, as ___________ metabolism is also reduced

A

Lys 504 ; intolerance ; acetaldehyde

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14
Q

hydralazine is an ____________

A

organic nitrate

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15
Q

adenosine given ____ for ________

A

IV; coronary stress test (and supraventricular arrhythmias)

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16
Q

For minoxidil, _________ may contribute to its efficacy

A

cAMP PDE inhibition

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17
Q

Natrecor binds to and activates _______________ in vascular smooth muscle and endothelial cells

A

membrane-bound guanylate cyclase

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18
Q

Cyclic GMP modulators

A
  • organic nitrates/nitrites
  • PDE inhibitors
  • natriuretic peptide
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19
Q

vasodilators

A

beta 2 agonists, CGRP, VIP

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20
Q

Prostacyclin analogs

A
  • PGIs
  • Treprostinil
  • Iloprost
  • Selexipag
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21
Q

Pharmacogenetics of Glycerol Trinitrate:

Likely accounts for the lack of efficacy of ____ in a large percentage of the ______ population

A

GTN ; Asian

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22
Q

sodium nitroprusside is metabolized in ____________ to ____, ____ and cyanomethemoglobin (limits duration of treatment)

A

erythrocytes ; NO, 4 CN

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23
Q

NOS stands for

A

nitric oxide synthase

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24
Q

sodium nitroprusside _________ veins and arteries

A

dilates

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25
Q

For sildenafil, the PDE 5 inhibitor is predominant in the ________________

A

corpus cavernosum

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26
Q

Natrecor (nesiritide) is a ______________

A

vasodilator (human type B natriuretic peptide)

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27
Q

Organic nitrate facts

A

non-selective vasodilators

breakdown to nitric oxide (bioactivation)

don’t require functional endothelium

acute or chronic administration

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28
Q

What is the most potent and specific inhibitor of cGMP PDE5?

A

sildenafil (viagra)

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29
Q

Organic nitrate/nitrite examples

A

amylnitrite

glyceryl trinitrate (GTN)

pentaerythritol tetranitrate (PETN)

isosorbide dinitrate

isosorbide mononitrate

nitroprusside

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30
Q

Pharmacokinetics of organic nitrates:

Given _________ in tx of acute attacks of ________

Given _______ or _______ for prolonged _________

Tolerance occurs with _________ administration

A

sublingually; angina

orally; transdermally; prophylaxis

continuous

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31
Q

hydralazine combined with ISDN in BiDil. Antioxidant activity potentiates ___________ activity of ISDN. BiDil _________ mortality in ___________ with CHF

A

vasodilatory ; decreases ; African-Americans

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32
Q

Ambrisentan is contraindicated in _________ patients

A

pregnant

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33
Q

How does protein kinase G relax smooth muscle?

Inhibition of L-type Ca2+ channels with

A

Cav1.2

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34
Q

Vasodilators that regulate membrane potential

A

reduce voltage-gated Ca2+ channel activity

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35
Q

diazoxide is used _________ to treat _________

A

intravenously; acute HTN

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36
Q

What to know about amrinone/milrinone?

A
  • given IV
  • direct positive inotropic effect on myocardium
  • minimal chronotropic effect
  • direct vasodilatory effect on vascular smooth muscle
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37
Q

riociguat (adempas) is a ________________

A

SMALL MOLECULE

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38
Q

prostacyclin analogs used to treat _____________

A

pulmonary arterial HTN

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39
Q

Examples of phosphodiesterase III inhibitors

A
  • inamrinone

- milrinone

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40
Q

CN is converted to less toxic ____ by ___________, excreted via kidney

A

SCN- ; rhodanase

41
Q

What drugs inhibit the break down of cGMP/AMP?

A

Phosphodiesterase inhibitors

42
Q

eNOS is found in the ________ of the ________

A

endothelial cells; vasculature

43
Q

diazoxide used _______ for ________ secondary to________

A

orally; hypoglycemia; hyperinsulinemia

44
Q

Minoxidil can give a ______ vasodilation. Used in ______, drug resistant forms of ____

A

rapid/effective ; severe ; HTN

45
Q

The isoform of NO, ______, in the vascular endothelium is activated by _______

A

eNOS; Ca2+ - CAM

46
Q

diazoxide inhibits _________ from _________

A

release of insulin; pancreatic beta cells

47
Q

What is the alternative mechanism of action for NO?

A
  • covalent modification of PRTs by nitrosyl transfer from glutathione
  • inhibition of Cav1.2 by GSNO***
  • May also contribute to tolerance and endothelial dysfunction
48
Q

What are viagra and cialis thought to enhance?

A

THE VASODILATORY EFFECT OF NO

49
Q

Minoxidil used with ________ and _________

A

diuretics; beta blockers

50
Q

Phosphodiesterase V inhibitor impacts

A

cGMP

51
Q

Iloprost (Ventavis) given _______

A

inhalation

52
Q

Minoxidil and diazoxide

A

K+ channel agonist/opener

53
Q

riociguat (adempas) used for ________________

A

pulmonary arterial HTN

54
Q

cGMP and cAMP stimulate ________ via distinct mechanisms

A

vasodilation

55
Q

Gbetagamma binds and activates ______ to ______ & _____

A

GIRK; conduct K+ efflux; membrane hyperpolarization

56
Q

Why does increasing K+ channel opening relax vascular smooth muscle?

A

K+ sets the membrane potential

the longer the K+ channels are open, the closer the membrane potential is to the K+ equilibrium potential

the closer the membrane potential is to the K+ equilibrium potential, the harder it is to depolarize the membrane enough to open voltage-gated Ca2+ channels

57
Q

Examples of selective PDE 5 inhibitors (3)

A
  • tadalafil (cialis)
  • vardenafil (levitra)
  • sildenafil (viagra)
58
Q

Types of Vasodilators

A
  • cGMP modulators
  • K+ channel agonists
  • Endothelin antagonists
  • PGI2 analogs
59
Q

Natrecor given ___ in ___________

A

IV ; acutely decompensated HF

60
Q

PDE5 inhibitors are contraindicated with _______ because

A

nitrates ; drop in BP (both drugs increase cGMP)

besides agonizing guanylyl cyclase, cGMP inhibits PDE3 which potentially increases cAMP levels in VSM cells

cGMP and cAMP stimulate vasodilation via distinct mechanisms

61
Q

hydralazine _________ arterioles preferentially. Mechanism not clear. Appears to interfere with release of Ca2+ from _____

A

dilates ; ER

62
Q

Vasoconstrictor antagonists: Bosentan and Macitentan facts

A
  • specific, low MW
  • endothelin receptor antagonists***
  • block ETb (VSM + endothel) receptors
63
Q

riociguat (adempas) potentiates the effect of _______ NO. This stimulates ____ activity allosterically and increases cGMP concentration in ______________

A

NO ; sGC ; vascular smooth muscle

64
Q

NO used to be referred to as _____

A

EDRF (endothelial derived relaxing factor)

65
Q

Mechanisms for controlling smooth muscle tone: relaxation

A
  • G-protein coupled receptor (beta-2,IPR)
  • increases cAMP (this can be blocked by PDE3 which causes increase in AMP)
  • impacts myosin light chain phosphorylation
  • causes relaxtion
66
Q

sildenafil has __-fold selectivity over inhibition of _______

A

10 ; PDE 6 (retina)

67
Q

CN can inhibit _______________

A

oxidative metabolism - lactic acid accumulation

68
Q

vasoconstrictors

A

angiotensin, alpha-1 agonists, endothelin

69
Q

hydralazine can induce _______-like syndrome

A

lupus

70
Q

What is increased in pulmonary arterial HTN?

A

endothelin signaling

71
Q

Ambrisentan is approved for____________

A

pulmonary arterial HTN

72
Q

Compared to viagra, cialis:

A
  • more selective for PDE 5

- longer duration of action than either viagra or levitra

73
Q

Prostacyclin analogs are ____________. They ___________

A

vasodilators ; relax pulmonary smooth muscle

74
Q

examples of vasoconstrictor antagonists

A
  • bosentan (tracleer)
  • macitentan (opsumit)

-ambrisentan (letairis)

75
Q

How does protein kinase G relax smooth muscle?

Enhanced Ca2+ uptake in to ER with

A

phospholamban

76
Q

How does protein kinase G relax smooth muscle?

Decreased MLC phosphorylation with

A

myosin phosphatase 1

77
Q

Minoxidil generally given ________ or _______

A

orally; topically to promote hair growth

78
Q

cGMP inhibitors, such as ________, can cause______ vision

A

sildenafil ; blueish

79
Q

Examples of phosphodiesterase V inhibitors

A
  • dipyridamole

- sildenafil

80
Q

nitric oxide binds to the ______ group in ______, stimulating production of cGMP and activating ______

A

heme iron prosthetic; guanylate cyclase; protein kinase G (cGKI)

81
Q

guanylate cyclase is found in the ________

A

vascular smooth muscle

82
Q

Nitric oxide production occurs in the

A

endothelial layer of the muscle

83
Q

Amrinone/milrinone is a ______ PDE inhibitor

A

cAMP

84
Q

How does protein kinase G relax smooth muscle?

Stimulation of Ca2+ activated K+ channels with

A

BKca

85
Q

hydralazine is given ______ or IV

A

orally

86
Q

Differences in activation of GTN and ISMN/ISDN:

Bioactivation is _________

A

ALDH-2-independent

87
Q

exogenously applied NO can directly __________

A

relax smooth muscle

88
Q

Selexipag (Uptravi) given _______

A

orally

89
Q

adenosine increases _________ of a K+ channel

A

conductance

-causes hyperpolarization and relaxation

90
Q

Sodium nitroprusside (SNP) is a __________

A

vasodilator

91
Q

Amrinone/milrinone used mainly in

A

CHF (acute treatment)

92
Q

nitric oxide synthase is in the _________ and ___ diffuses to the _________

A

vascular endothelium; NO; vascular smooth muscle

93
Q

Allosteric activator of sGC

A

riociguat (adempas)

94
Q

Compared to viagra, levitra:

A
  • shorter time to onset

- more selective for PDE5

95
Q

Phosphodiesterase III inhibitor impact

A

cAMP

96
Q

Sodium nitroprusside is given ___ for acute management of _______ and severe decompensated ____________

A

IV ; hypertensive crisis ; heart failure

97
Q

ET receptors between ______ and ______

A

GPCR ; Calcium. Blocking the ET receptor blocks the increase in calcium and causes relaxation

98
Q

Natrecor synthesized and secreted from ___________ in response to ________ blood volume

A

heart muscle ; increased

99
Q

riociguat (adempas) is not combined with _______ or _____ inhibitors. It is ____________. There is risk of hemorrhage. It is a substrate for P-gp, CYP1A1, 3A

A

nitrates ; PDE5 ; contraindicated in pregnancy