Lecture 9 Nitrates and Vasodilators Flashcards
enodthelial Nitric oxide synthase (eNOS) helps convert the amino acid _____ to ____, which releases NO
arginine, citrulline
NO made by eNOS diffuses into the _____ ____ _____, where it stimulates ___ ____
vascular smooth muscle;
guanylate cylase
stimulation of guanylate cyclase causes production of ____ and activation of ______
cGMP, protein kinase G (PKG)
PKG relaxes smooth muscle in 4 ways:
- inhibits __ ___ channels
- stimulates ___ ____ channels
- decreases ____ ____ _____ ____
- enhances ____ uptake to the _____
L-type calcium (CaV1.2)
2. Ca-activated K+ channels (BKca)
3 . Myosin Light chain phosphorylation
4. Ca, ER (phospholamban)
Organic nitrates are broken down into ____ ____, causing vasodilation
they (do/do not) require functional endothelium
nitric oxide; do not (directly stimulate guanalyl cyclase
Of the nitrates, _____ has basically 0 oral bioavailability. It is given _____ in treatment of acute anginal attacks.
_____ and _____ have better oral bioavailability and longer half life and are used for _____ _____
glyceryl trinitrate (nitroglycerin), sublingually
isosorbide mononitrate (ISMN) and dinitrate (ISDN); prolonged prophylaxis
describe “monday disease”
workers who are exposed to nitrates at work build up tolerance during the week (so no symptoms tuesday-sunday). after not being at work on the weekend, tolerance is loss–> tachycardia and dizziness on monday
nitroglycerin is metabolized by ____. This explains its lack of efficacy in a large percentage of the asian population. _____ is also metabolized by this same enzyme
Aldehyde dehydrogenase 2 (ALDH2);
alcohol
Nitroprusside is given for acute management of ______ and heart failure. It dilates _____. It is metabolized to ____, which limits duration of treatment
HTN crisis;
veins and arterioles;
cyanide
hydralazine preferentially dilates ____. It appears to interfere with release of ____ from the _____. It can cause what important side effect?
arterioles, calcium, ER;
lupus like syndrome
BiDil is a combination of ____ and _____. It decreases mortality in ____ _____ with CHF
hydralazine, ISDN;
african americans
_____ is a recombinant B natriuretic peptide. It binds to and activates _______ in vascular smooth muscle and endothelial cells and is used for ______
Natrector (nesiritide); membrane bound guanylate cyclase;
acute decompensated HF
NO may also be involved in covalent modification of proteins by nitrosyl transfer from _____. In other words, it may inhibit ___ ____ channels
glutathione;
L-type calcium (CaV1.2)
milrininone and amrinone are selective inhibitors of ____
phosphodiesterase (PDE) 3
PDE3 normally causes a conversion of ____ to ____.
cAMP to AMP
When PDE3 is inhibited, cAMP ______. This causes phosphorylation of ________, inactivating it and causing smooth muscle _____
increases;
myosin light chain kinase;
relaxation
amrinone and milrinone have a direct positive _____ effect on myocardium and a direct _____ effect on vascular smooth muscle;
mainly used in CHF
inotropic;
vasodilatory
Sildenafil, vardenafil, and tadalafil are potent inhibitors of ____ , causing an increase in _____
PDE 5; cGMP
the -afils are used for _____ and ______
erectile dysfunction; pulmonary HTN (esp arterial type)
the -afils can cause _____ vision due to some inhibition of ____ located in the retina
bluish; PDE6
Sildenafil (viagra)/other -afils cause increased relaxation of the ____ _____ in the ____ ____
helicine artery; corupus cavernosum
who should not receive -afils due to a risk of severe ____?
patients taking nitrates;
severe hypotension
which of the -afils has the longest duration of action? Which has the longest time to onset?
cialis (tadalafil) ie the weekend pill;
levitra (vardenafil)
effect on potassium channel: general
vasoconstrictors ____ the K channel, causing _____;
vasodilators ____ the K channel, causing ____
inhibit, depolarization;
increase conductance; hyperpolarization
