Organic Nitrates and Vasodilators Flashcards
Minoxidil activated in vivo by ______________ 1A1
sulfotransferase
adenosine binds to _______ which is a _______
A1 receptor; GPCR
With sildenafil, there is lack of _____________
systemic vasodilation
Where is PDE5 expressed?
VSM of the lungs
What are viagra and cialis indicated for?
TREATMENT OF PULMONARY ARTERIAL HTN
hypertrichosis definition
excessive hair growth
Hyperpolarization of vascular smooth muscle:
A1 (adenosine receptor) and the ______
GIRK (G-protein activated inwardly rectifying K+ channel)
Mechanisms for controlling smooth muscle tone: contraction
- 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
diazoxide is a ________ vasodilator. Effective in _______, drug resistant forms of ______
potent; severe; HTN
Prostacyclin (PGI2) - Epoprostenol given _______
IV (produced in the endothelium)
Vasoconstrictor antagonists: ambrisentan
- blocks only ETa receptors
- approved for pulmonary arterial hypertension***
- contraindicated in pregnancy (class); hepatotoxicity (Bosentan)
Treprostinil (Remodulin) given _______
orally ; IV
The _____ allele accounts for alcohol __________ intolerance, as ___________ metabolism is also reduced
Lys 504 ; intolerance ; acetaldehyde
hydralazine is an ____________
organic nitrate
adenosine given ____ for ________
IV; coronary stress test (and supraventricular arrhythmias)
For minoxidil, _________ may contribute to its efficacy
cAMP PDE inhibition
Natrecor binds to and activates _______________ in vascular smooth muscle and endothelial cells
membrane-bound guanylate cyclase
Cyclic GMP modulators
- organic nitrates/nitrites
- PDE inhibitors
- natriuretic peptide
vasodilators
beta 2 agonists, CGRP, VIP
Prostacyclin analogs
- PGIs
- Treprostinil
- Iloprost
- Selexipag
Pharmacogenetics of Glycerol Trinitrate:
Likely accounts for the lack of efficacy of ____ in a large percentage of the ______ population
GTN ; Asian
sodium nitroprusside is metabolized in ____________ to ____, ____ and cyanomethemoglobin (limits duration of treatment)
erythrocytes ; NO, 4 CN
NOS stands for
nitric oxide synthase
sodium nitroprusside _________ veins and arteries
dilates
For sildenafil, the PDE 5 inhibitor is predominant in the ________________
corpus cavernosum
Natrecor (nesiritide) is a ______________
vasodilator (human type B natriuretic peptide)
Organic nitrate facts
non-selective vasodilators
breakdown to nitric oxide (bioactivation)
don’t require functional endothelium
acute or chronic administration
What is the most potent and specific inhibitor of cGMP PDE5?
sildenafil (viagra)
Organic nitrate/nitrite examples
amylnitrite
glyceryl trinitrate (GTN)
pentaerythritol tetranitrate (PETN)
isosorbide dinitrate
isosorbide mononitrate
nitroprusside
Pharmacokinetics of organic nitrates:
Given _________ in tx of acute attacks of ________
Given _______ or _______ for prolonged _________
Tolerance occurs with _________ administration
sublingually; angina
orally; transdermally; prophylaxis
continuous
hydralazine combined with ISDN in BiDil. Antioxidant activity potentiates ___________ activity of ISDN. BiDil _________ mortality in ___________ with CHF
vasodilatory ; decreases ; African-Americans
Ambrisentan is contraindicated in _________ patients
pregnant
How does protein kinase G relax smooth muscle?
Inhibition of L-type Ca2+ channels with
Cav1.2
Vasodilators that regulate membrane potential
reduce voltage-gated Ca2+ channel activity
diazoxide is used _________ to treat _________
intravenously; acute HTN
What to know about amrinone/milrinone?
- given IV
- direct positive inotropic effect on myocardium
- minimal chronotropic effect
- direct vasodilatory effect on vascular smooth muscle
riociguat (adempas) is a ________________
SMALL MOLECULE
prostacyclin analogs used to treat _____________
pulmonary arterial HTN
Examples of phosphodiesterase III inhibitors
- inamrinone
- milrinone