Organic nitrates and phosphodiesterase inhibitors

Question 1

What is the clinical use of organic nitrates?

Answer 1

Relief of angina pain - used prophylactically

Question 2

Nitrovasodilators are prodrugs. What are they converted into?

Answer 2

Nitric oxide

Question 3

What is the mechanism of action of organic nitrates?

Answer 3

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

Question 4

Angina is a crushing pain under the sternum that radiates to towards left shoulder and arm. True or false?

Answer 4

True

Question 5

What are the three kinds of angina?

Answer 5

Stable
Unstable
Variant

Question 6

Stable angina occurs on exertion whereas unstable occurs at rest. True or false?

Answer 6

True

Question 7

Nitrovasodilators relieve an angina attack by decreasing oxygen demand by reducing cardiac output. True or false?

Answer 7

True

Question 8

The more stretched the cardiac muscle is at the end of diastole, the harder the heart has to work. True or false?

Answer 8

True - because the higher the SV and so higher CO. So by reducing the stretch, EDV is reduced and hence SV is reduced

Question 9

Nitrovasodilators cause vasodilation in veins. True or false?

Answer 9

True - this reduces central venous pressure, venous return and hence preload

Question 10

Why is GTN ineffective if given orally?

Answer 10

Inactivated by the liver

Question 11

Isosorbide mono-nitrate is effective orally. True or false?

Answer 11

True

Question 12

What is riociguat used for?

Answer 12

CTEPH - chronic thromboembolic pulmonary hypertension - causes increases in BP

Question 13

How does riociguat work?

Answer 13

Activates secondary guanylyl cyclase - by either direct activation or enhancement of NO effects

Question 14

cGMP and cAMP are broken down by what?

Answer 14

cyclic nucleotide phosphodiesterases?

Question 15

How do phosphodiesterase inhibitors work in leading to vasodilation?

Answer 15

PDE is inhibited and so doesn’t break down cGMP and cAMP which allows the pathway to vasodilation to take place

Question 16

PDE3 prefer to hydrolyse cGMP over cAMP. True or false?

Answer 16

False - hydrolyse cAMP over cGMP

Question 17

PDE4 are cAMP specific. True or false?

Answer 17

True

Question 18

PDE5 are cGMP specific. True or false?

Answer 18

True

Question 19

caffeine and theophylline are non-selective alpha receptor antagonists. True or false?

Answer 19

True

Question 20

What affects do theophylline and caffeine have on the heart?

Answer 20

Increase HR and force of contraction

Question 21

How do caffeine and theophylline cause smooth muscle relaxation?

Answer 21

Because they are PDE inhibitors as lead to accumulation of cAMP - leading to vasodilation

Question 22

A low dose of caffeine reduces reaction time. True or false?

Answer 22

True

Question 23

Which PDE inhibitor is used in neonatal intensive care?

Answer 23

Caffeine

Question 24

Theophylline is used in asthma treatment. True or false?

Answer 24

True

Question 25

How is theophylline administered in acute asthma?

Answer 25

Orally

Question 26

PDE4 is the only PDE present in inflammatory cells. True or false?

Answer 26

True

Question 27

Enoximone and milrinone are selective inhibitors of which PDE isoform?

Answer 27

PDE3

Question 28

Cilostazol is a PDE3 inhibitor. True or false?

Answer 28

True

Question 29

Sildenifil inhibits which PDE isoform?

Answer 29

5

Question 30

Why may males that take high doses of sildenifil experience visual disturbances?

Answer 30

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

Question 31

Sildenifil can be used to treat pulmonary arterial hypertension. True or false?

Answer 31

True

Question 32

Why should patients receiving nitrates such as riociguat not take PDE5 inhibitors?

Answer 32

Because nitrates increase cGMP and PDE5 inhibitors prevent its removal so excessive build up of cGMP leads to dangerous drop in BP