Nitric Oxide Flashcards
Why may nitric oxide inhibitors be helpful in treating sepsis-related disorders?
excess production of NO (as with sepsis) results in generation of peroxynitrite, which is toxic to cells
NO’s major effects are mediated by:
activation of guanylyl cyclase, resulting in the generation of cGMP (which causes vasodilation)
List the physiological vs. pathological effects of NO.
- physiological: smooth muscle relaxation, vasodilation, immune regulation, anesthetic responses, anti-atherosclerotic responses
- pathological: free radical formation, nitrosation, irritant effects
How does a decreased level of NO in blood vessels affect blood pressure?
it may increase BP
Which drug has a strong interaction with the nitrates?
Sildenafil (Viagra); if a patient is on a nitrate for cardiac reasons, taking Viagra may lead to hypotension
Does phosphorylation or dephosphorylation of myosin light chain cause relaxation?
dephosphorylation! (this effect is mediated by cGMP)
What is helpful in the management of transplant patients and why?
dietary arginine supplements; graft atherosclerosis is a major cause of graft failure, and NO acts as a cytoprotective agent to prevent platelet adhesion (and NO is synthesized from Arg)
How does NO affect fibrinolysis?
It indirectly enhances it by inhibiting the release of antiplasmin from platelets.
How does NO affect the CNS?
It acts as a neurotransmitter and has a neuromodulatory impact on stroke and vascular dementia.
Describe the basic MOA of Sildenafil (Viagra).
It is a phosphodiesterase (PDE5) inhibitor, thus inhibiting degradation of cGMP and enhancing smooth muscle relaxation as well as vasodilation.
What are the most widely used donors of NO?
nitrates! (denitration of such drugs, including nitroglycerin, results in formation of NO)
Which formulation of NO donor drugs exhibits the shortest and longest duration of action, respectively?
- inhaled amyl nitrate=shortest (3-5 mins)
- transdermal nitroglycerine=longest (8-10 hrs)
What are the NO donors we should be aware of?
nitroglycerine, hydralazine, and L-arginine
What is the main clinical indication of INOmax?
pulmonary hypertension
