Nitrates

Question 1

MOA

Answer 1

organic nitrate ester reductase
–>NO–>GC–>cGMP–>PKG–>SM relaxation

Decreases demand and increases supply!

increase NO
–vasodilates–>
decreases afterload

–venodilates–>
decreases preload
(so decreases contractility via Frank-Starling)

Question 2

CV effects

Answer 2

decreased preload
coronary vasodilation
(prevents or reverses vasospasm)

BP: unchanged/slight decrease
HR: unchanged or slight increase
Pulmonary vascular resistance: decreased
CO: reduced (slightly)

Question 3

Preparations

Answer 3

mucosal

• -sublingual
• -nasal sprays

oral

transdermal

paste

IV

Question 4

adverse effects

Answer 4

High doses...
--extreme vasodilation
....hypotension
....reflexive increase in HR and contractility
(worsens angina!!!)

transient headache
(meningeal arteries dilated until tolerance)

rash

Drug interaction
–Sildenafil (Viagra) [Type 5 PDE inhibitors]
(increases cGMP by decreasing metabolism)

Question 5

pharmacokinetics

Answer 5

Rapidly metabolized (short-lived)

ok and beneficial for exertional angina
–can take it when they need it

challenge for others

Question 6

Problem w/ continuous Nitrate exposure

Answer 6

tolerance

avoided by “nitrate free” interval each day… i.e. remove patch at night

Question 7

Anginal rebound

Answer 7

Do Not suddenly interrupt IV nitroglycerin in unstable angina…overlap w/ oral or patch form

(coronary vasospasm has been observed after abrupt stop)