Antianginals Flashcards
Treatment for the immediate relief of angina, prophylaxis of angina and increase in exercise tolerance includes:
organic nitrates
calcium channel blockers
beta blockers
(via reducing myocardial O2 demand)
What is the prototype for organic nitrate?
Nitroglycerin
Nitroglycerin is a ___drug
Pro
Nitroglycerin releases __ when ….
NO; when metabolized by ALDH-2
At therapeutic doses, NTG mainly causes dilation of the ____
veins
(some arterial dilation can happen)
NTG effect on the heart is direct/indirect?
indirect; NTG decreases venous return which reduces cardiac preload which reduces oxygen demand
NTG also has a modest effect on coronary ….
blood flow
What is the MOA of NTG on coronary blood flow?
modest dilation of large epicardial arteries to promote flow of blood to regions os ischemia in the endocardium
What are the effects of NTG on small resistance vessels?
effects are minimal; small resistance vessels may already be maximally dilated due to autoregulation
NTG also has a direct vasodilation effect on ..
VASOSPASTIC coronary arteries
NTG is effective in prophylaxis and termination of
acute anginal attacks (abloshes ST segment depression)
improves exercise tolerance
does NTG have a survival benefit or prevention of MI?
NO
what are the CV effects of NTG at usual doses?
what are the CV effects of NTG as higher doses
arterioles in face/neck and meningeal arteries are sensitive/insensitive to vasodilation from NTG?
sensitive
ALDH-2 polymorphism, which has a high prevalence in patients of Asian origin, have LOW-ACTIVITY of ______. Why is this important?
ALDH2*2 allele and therefore have possible diminished clinical efficacy due to decreased metabolism of the prodrug
the route of administration of organic nitrates determines …
time to onset and DOA
What are the 3 forms of NTG?
sublingual
oral
transdermal
forms of sublingual NTG include ____ and _____
tablets and sprays
tablets and sprays (forms of sublingual NTG) bypass _____ and therefore attain therapeutic levels within in ______. This provides ____ relief but has a short ____.
bypasses first pass metabolism
attains therapeutic levels in 1-2 minutes
RAPID relief
DOA (< 1 hr)
Active NTG tablets cause a ______ sensation when placed under the tongue
tingling
tablets are unstable to ….
heat/light, moisture
Patients should contact EMS if ______ does not terminate angina within _ minutes
1st dose
5 minutes
oral or transdermal forms are available for acute relief and prophylaxis; onset is _____ (compared to sublingual) and DOA is _____ (compared to sublingual)
slower onset (30-60 min)
DOA is longer (4-24 hr)
tolerance to organic nitrates occurs
with too frequent or sustained use and can happen within 24 hours
“Monday morning headaches”
MOA of tolerance to organic nitrates
NTG-mediated inactivation of ALDH-2 (i.e. mechanism based enzyme inhibition)
tolerance to organic nitrates are most common with what kinds of formulations?
oral, transdermal
how is tolerance to organic nitrates minimized?
minimized using eccentric dosing that provides nitrate-free intervals of 10-12 hr
adverse effects of nitrates:
headache, facial flushing
orthostatic hypotension
reflex tachycardia
one adverse effect of nitrates includes orthostatic hypotension. This is because …
nitrates effect on veins
another adverse effect of nitrates is reflex tachycardia. This is because ….
nitrates increases O2 demand… This can negate the drugs beneficial effect. Use in combo with beta blockers or calcium channel blockers to suppress this.
drug interactions of nitrates include:
-vasodilators (severe refractory hypotension and possible MI if taken within 24 hr of a PDE 5 inhibitor or alpha blocker)
-alcohol (complex interaction due to inhibition of ALDH-2, acutely worsens NTG-induced orthostatic hypotension)
the two subclasses of ca channel blockers are
dihydropyridines
and
HR lowering
an example of dihydropyridine ca channel blocker is
nifedipine
an example of a HR lowering ca channel blocker is
verapamil
