Organic nitrates and phosphodiesterase inhibitors Flashcards
What is the clinical use of organic nitrates?
Relief of angina pain - used prophylactically
Nitrovasodilators are prodrugs. What are they converted into?
Nitric oxide
What is the mechanism of action of organic nitrates?
Nitrovasodilator is a prodrug that is converted to NO
NO activates soluble guanylyl cyclase which converts GTP to cGMP
cGMP then activates PKG which leads to phosphorylation of target protein
This leads to reduction in conc of calcium and vasodilation
Angina is a crushing pain under the sternum that radiates to towards left shoulder and arm. True or false?
True
What are the three kinds of angina?
Stable
Unstable
Variant
Stable angina occurs on exertion whereas unstable occurs at rest. True or false?
True
Nitrovasodilators relieve an angina attack by decreasing oxygen demand by reducing cardiac output. True or false?
True
The more stretched the cardiac muscle is at the end of diastole, the harder the heart has to work. True or false?
True - because the higher the SV and so higher CO. So by reducing the stretch, EDV is reduced and hence SV is reduced
Nitrovasodilators cause vasodilation in veins. True or false?
True - this reduces central venous pressure, venous return and hence preload
Why is GTN ineffective if given orally?
Inactivated by the liver
Isosorbide mono-nitrate is effective orally. True or false?
True
What is riociguat used for?
CTEPH - chronic thromboembolic pulmonary hypertension - causes increases in BP
How does riociguat work?
Activates secondary guanylyl cyclase - by either direct activation or enhancement of NO effects
cGMP and cAMP are broken down by what?
cyclic nucleotide phosphodiesterases?
How do phosphodiesterase inhibitors work in leading to vasodilation?
PDE is inhibited and so doesn’t break down cGMP and cAMP which allows the pathway to vasodilation to take place
PDE3 prefer to hydrolyse cGMP over cAMP. True or false?
False - hydrolyse cAMP over cGMP
PDE4 are cAMP specific. True or false?
True
PDE5 are cGMP specific. True or false?
True
caffeine and theophylline are non-selective alpha receptor antagonists. True or false?
True
What affects do theophylline and caffeine have on the heart?
Increase HR and force of contraction
How do caffeine and theophylline cause smooth muscle relaxation?
Because they are PDE inhibitors as lead to accumulation of cAMP - leading to vasodilation
A low dose of caffeine reduces reaction time. True or false?
True
Which PDE inhibitor is used in neonatal intensive care?
Caffeine
Theophylline is used in asthma treatment. True or false?
True
How is theophylline administered in acute asthma?
Orally
PDE4 is the only PDE present in inflammatory cells. True or false?
True
Enoximone and milrinone are selective inhibitors of which PDE isoform?
PDE3
Cilostazol is a PDE3 inhibitor. True or false?
True
Sildenifil inhibits which PDE isoform?
5
Why may males that take high doses of sildenifil experience visual disturbances?
Because although sildenifil is more selective for PDE5 than other PDEs, it’s not much more selective to PDE5 than it is for PDE6, which is found in the retina
Sildenifil can be used to treat pulmonary arterial hypertension. True or false?
True
Why should patients receiving nitrates such as riociguat not take PDE5 inhibitors?
Because nitrates increase cGMP and PDE5 inhibitors prevent its removal so excessive build up of cGMP leads to dangerous drop in BP
