14. Chronic ischemia Drugs Flashcards
Nitrates IG are vasodialator but have most effect on:
venous blood vessels
Mech of action of nitrates
Become denitrated in Smooth muscle–> free nitrate converts to NO
NO–> activate GC which increases cGMP
cGMP–> activates cGMP protein kinase (PKG)
PKG phosphoylates stuff leading to decreased Ca and dephosphorylation of myosin
How do nitrates affect preload
Increase venous capacitance to DECREASE preload
this reduces diastolic wall tension thus Oxygen deman
Decreased preload has small increase in subendo blood flow
What effect do nitrates have on afterload?
SMALL REDUCTION to afterload or small reduciton in systemic atrial pressure
see reduction in systolic wall tension
slight reflex tachycardia
When are nitrates valuble as a coronary dialator?
if ischemia is dt vasospasm… not so much is pt has angina with maximal dilation d/t accumulation of local metabolites
How are nitrates activated?
by organic nitrate reductase in the liver: low bioavailability d/t 1st pass effect
What form of nitrate is biologically active?
Mononitrate: doesn’t need to be metabolized while isosorbide dinitrate gets metabolized in liver–> mono form
How can we acheive high conc of nitrates rapidly?
sublingual to avoid 1st pass affect; last 30 mins or so
Can we use nitrates for chronic angina?
yes, provides prophylaxsis against angina episodes
Nitrate with no first pass metabolism and 1/2 life of 5 hours
mononitrate
has 25% bioavailability with longer DOA (4-6hrs) and metabolized to be active
dinitrate
Nitrate that is orally controlled release tabs/capsules and available as patch and ointment/paste applied to skin
Nitroglycerin
Do pts devo tolerance to nitrates?
yes; if used constantly w/in in a few hours, but rapid reversal…. limits how effective slow release forms are so use small dose and schedule nitrate free period
Adverse effects of nitrates
headache, hypotension, reflex tachycardia, flushing
Why are beta blockers recommended for IHD?
have anti-anginal effect by reducing oxygen demand dt decrease force of ventricular cnx and HR; because blocks effects of catecholamines on B1 receptors