Antianginals

Question 1

Treatment for the immediate relief of angina, prophylaxis of angina and increase in exercise tolerance includes:

Answer 1

organic nitrates
calcium channel blockers
beta blockers
(via reducing myocardial O2 demand)

Question 2

What is the prototype for organic nitrate?

Answer 2

Nitroglycerin

Question 3

Nitroglycerin is a ___drug

Answer 3

Pro

Question 4

Nitroglycerin releases __ when ….

Answer 4

NO; when metabolized by ALDH-2

Question 5

At therapeutic doses, NTG mainly causes dilation of the ____

Answer 5

veins
(some arterial dilation can happen)

Question 6

NTG effect on the heart is direct/indirect?

Answer 6

indirect; NTG decreases venous return which reduces cardiac preload which reduces oxygen demand

Question 7

NTG also has a modest effect on coronary ….

Answer 7

blood flow

Question 8

What is the MOA of NTG on coronary blood flow?

Answer 8

modest dilation of large epicardial arteries to promote flow of blood to regions os ischemia in the endocardium

Question 9

What are the effects of NTG on small resistance vessels?

Answer 9

effects are minimal; small resistance vessels may already be maximally dilated due to autoregulation

Question 10

NTG also has a direct vasodilation effect on ..

Answer 10

VASOSPASTIC coronary arteries

Question 11

NTG is effective in prophylaxis and termination of

Answer 11

acute anginal attacks (abloshes ST segment depression)
improves exercise tolerance

Question 12

does NTG have a survival benefit or prevention of MI?

Answer 12

NO

Question 13

what are the CV effects of NTG at usual doses?

Question 14

what are the CV effects of NTG as higher doses

Question 15

arterioles in face/neck and meningeal arteries are sensitive/insensitive to vasodilation from NTG?

Answer 15

sensitive

Question 16

ALDH-2 polymorphism, which has a high prevalence in patients of Asian origin, have LOW-ACTIVITY of ______. Why is this important?

Answer 16

ALDH2*2 allele and therefore have possible diminished clinical efficacy due to decreased metabolism of the prodrug

Question 17

the route of administration of organic nitrates determines …

Answer 17

time to onset and DOA

Question 18

What are the 3 forms of NTG?

Answer 18

sublingual
oral
transdermal

Question 19

forms of sublingual NTG include ____ and _____

Answer 19

tablets and sprays

Question 20

tablets and sprays (forms of sublingual NTG) bypass _____ and therefore attain therapeutic levels within in ______. This provides ____ relief but has a short ____.

Answer 20

bypasses first pass metabolism
attains therapeutic levels in 1-2 minutes
RAPID relief
DOA (< 1 hr)

Question 21

Active NTG tablets cause a ______ sensation when placed under the tongue

Answer 21

tingling

Question 22

tablets are unstable to ….

Answer 22

heat/light, moisture

Question 23

Patients should contact EMS if ______ does not terminate angina within _ minutes

Answer 23

1st dose
5 minutes

Question 24

oral or transdermal forms are available for acute relief and prophylaxis; onset is _____ (compared to sublingual) and DOA is _____ (compared to sublingual)

Answer 24

slower onset (30-60 min)
DOA is longer (4-24 hr)

Question 25

tolerance to organic nitrates occurs

Answer 25

with too frequent or sustained use and can happen within 24 hours

Question 26

"Monday morning headaches"

Question 27

MOA of tolerance to organic nitrates

Answer 27

NTG-mediated inactivation of ALDH-2 (i.e. mechanism based enzyme inhibition)

Question 28

tolerance to organic nitrates are most common with what kinds of formulations?

Answer 28

oral, transdermal

Question 29

how is tolerance to organic nitrates minimized?

Answer 29

minimized using eccentric dosing that provides nitrate-free intervals of 10-12 hr

Question 30

adverse effects of nitrates:

Answer 30

headache, facial flushing orthostatic hypotension reflex tachycardia

Question 31

one adverse effect of nitrates includes orthostatic hypotension. This is because ...

Answer 31

nitrates effect on veins

Question 32

another adverse effect of nitrates is reflex tachycardia. This is because ....

Answer 32

nitrates increases O2 demand... This can negate the drugs beneficial effect. Use in combo with beta blockers or calcium channel blockers to suppress this.

Question 33

drug interactions of nitrates include:

Answer 33

-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)

Question 34

the two subclasses of ca channel blockers are

Answer 34

dihydropyridines and HR lowering

Question 35

an example of dihydropyridine ca channel blocker is

Answer 35

nifedipine

Question 36

an example of a HR lowering ca channel blocker is

Answer 36

verapamil