nitrates Flashcards
what is the function of endothelial produced NO
vasodilation, anti-thrombotic, and anti-inflammatory function by inhibiting endothelial cell and leukocyte interaction
how is endothelial NO produced
produced by endothelial nitric oxide synthase, eNOS. the NO produced by this is then released
how do the endogenous vasodilators work
things such as ACh or bradykinin and so on will bind to a receptor on an endothelial cell. this receptor is bound to a ligand-gated calcium channel. activating the channel allows calcium into the endothelial cells. increased calcium triggers eNOS activity. eNOS then breaks down L-argenine into NO and citrulline NO is then released to smooth muscle cells
how does NO cause vasodilation
NO gets into the smooth muscle increasing guanylate cyclase activity, this helps form cGMP. the cGMP activates protein kinases. these protein kinases then act to promote smooth muscle relaxation by causing increased Ca2+ efflux and SERCA Ca2+ uptake.
what breaks down cGMP
posphodiesterase activity.
how do GTN and other nitrates work
they mimic the effects of endogenous NO. they either cause NO release from endothelia or they form NO within cells
what are the nitrate drugs
sodium nitroprusside or GTN (nitrate)
how does GTN work
it gets into the cell and is broken down by an enzyme to release the NO and then the NO does its thang
what is the primary action of nitrodilators
they cause venous vasodilation. this reduces preload which reduces diastolic wall stress and work
reduction of diastolic wall stress improves subendothelial blood flow in coronary artery disease as the diastolic time is increased. remember that coronary perfusion is mainly occurring during diastole.
also reduces systemic resistance
so less afterload and cardiac work
why do we give it sublingual spray
fast acting as buccal veins take it straight to venous plexus so its fast acting. and avoids first pass metabolism.
main use of nitrates
angina pain.
doesnt necessarily dilate the coronary arteries. just reduces diastolic wall stress and cardiac work by reducing preload through venous dilation.
other uses of nitrates
Reduction in afterload
* improvement in ejection fraction and stroke volume all this during chronic heart failure
also the reduction in venous pressure can decrease oedema. also antiplatelet effect
also can be given in an acute hypertensive emergency .
PKs of GTN
completely destroyed by first pass metabolism
bypass this sublingual spray for quick effect.
can also be transdermal patch - depends on how fast we want the effect to be.
we can tolerate tolerance for nitrates
so we can put them on patches that we take off some times. or we do the spray on a per need base too prevent tolerance.
nitrate adverse effects
these are due to vasodilation and exacerbating hypotension, flushing, headache, reflex tachycardia, palpitations, nausea, postural dizziness
