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
Propanolol and timolol are examples of
non-selective B blockers
metoprolol and atenolol are examples of
selective B1 antagonists
when are B blockers ineffecient at tx angina?
when its dt vasospasm (use nitroglycerin!)
How do Beta blockers decrease oxygen demand in an ischemic heart?
Decreases HR, decreases contractility, decreases BP (afterload)
Do Beta blockers help increase oxygen to ischemic areas?
a little– they slow the HR so that heart spends more time in diastole thus longer time in coronary perfusion
When we have decreased CO we can have ______ prelaod that can lead to _______ wall tension
increased
increased
Can we use B blockers in patients with COPD?
NOPE
Pt comes in with IHD and you recommend he be treated with a Beta Blocker. Pt has:
elevated LDL
family hx of HTN
heart block
insulin-tx diabetes
Which of these prevents you from tx with beta blockers?
Insulin dependent diabetes and heart block (as well as bradycardia) are contraindicated for Beta Blocker
Nifedipine and Amlodipine are examples of:
Dihydropyridine Ca+ channel blockers
Verapamil and Diltiazem are examples of:
Non-dihydropyridine Ca+channel blockers
Which are more potent vasoD; non-dihydropyridine or dihydropyridine
dihydropyridine: such as nifedipine and amlodipine
How do dihydropyridine (nifedipine and amlodipine) relieve ischemia?
Decrease O demand via vasoD which will decrease Afterload thereby reducing wall stress
What channel blockers are potent agents for relief of vasospasm?
Nifedipine or amlodipine
Nondihydropyridine; verapamil or diltiazem relieve ischemia by:
decreasing O demand by reducing force of contraction and heart rate
Which drug works by decreasing O demand by reducing force of contraction and heart rate
Nondihydropyridine; verapamil or diltiazem
What negative effects are seen in all Ca+channel blockers?
headache and flushing
Constipation is a side effect seen in which Ca+ blocker
Verapamil
Which Ca+ blockers cause Edema the worse
Nifedipine and diltiazem
Which Ca+ blocker cause bradycardia and decrease contractility?
verapamil and diltazem
What benefits do we see from combinding a nitrate with a Beta Blocker?
Beta blocker prevents potential reflex increase in HR and contractility produced by nitrates
Nitrates prevent the potential increase in wall tension from beta blockers
What do we need to be worried about when combinding a Beta blocker with Verapamil or Diltiazem Ca+ channel blocker?
additive negative inotropic effect can cause excessive cardiodepression
How does RANOLAZINE work?
anti-ischemic tx; decreases frequency of anginal episodes and increases exercise capacity: but no effect on HR via vasodialation
Its works to inhibit late Na current in cardiac myocytes
Which anti-ischemic tx works to inhibit late sodium current in cardiac myocytes
Ranolazine
