Drugs for ACS and Stable Angina (Konorev) Flashcards
What are the 3 nitrates (nitrovasodilators) used in chronic IHD?
- Nitroglycerin
- Isosorbide dinitrate
- Isosorbide mononitrate
Increasing coronary blood flow using vasodilators is useful in treating what kind of angina?
Vasospastic (Prinzmetal) angina
Why is Dipyridamole not useful in atherosclerotic (classic) angina?
- “Coronary steal” phenomenon = redistribution of blood to non-ischemic areas
- No substantial increase in coronary blood flow into the ischemic area
Which nitrate is a poor substrate of nitrate reductase in the liver and therefore has higher bioavailability?
Isosorbide mononitrate
Describe the rationale behind using sublingual, buccal, and transdermal routes of administration of nitrates, as opposed to oral administration of these drugs
Undergo significant first-pass metabolism - high nitrate reductase activity in liver = oral bioavailability is LOW
What is the crucial for the activation of nitrates to release nitric oxide?
Reduced thiols (ADH2) –> release NO from nitrates
Describe the role of nitric oxide in maintaining vascular tone?
- Open K+ channel = hyperpolarization and reduced Ca2+ entry
- NO activates guanylate cyclase –> ↑ cGMP –> ↑PKG –> Myosin-LC dephosphorylation –> smooth m. relaxation
Describe sensitivity of different types of vessels towards vasodilatory activity of nitrates, from greatest effect to least
Veins > Large arteries > Small arteries and arterioles
Nitrates used in the treatment of angina have a major effect of causing dilation of veins, which leads to what 2 therapeutic effects?
- Increased venous capacitance
- Reduced ventricular preload –> ↓O2 demand
`Higher concentratins of nitrates are needed to dilate arteries, which will have what 2 effects?
``- May reduce afterload
- May dilate large epicardial coronary arteries
Nitrous oxide has effects beyond just vasodilation, describe some of the inhibitory effects.
- Inhibits platelet aggregation
- Inhibits monocyte adhesion
- Inhibits smooth m. proliferation
- Inhibits free radical formation
- Inhibits LDL oxidation
Variant (Prinzmetal) angina is characterized by episodes of what (i.e., leading mechanism of injury)?
Episodes of vasoconstriction of coronary ateries
Major overall effect of nitrates is a decrease in?
Myocardial O2 demand
The development of tolerance to Nitrates is associated with what 4 events?
- Depletion of thiol compounds
- ↑ generation of superoxide radicals
- Reflex activation of sympathetic NS –> Tachycardia, ↓ coronary blood supply
- Retention of Na+ and H2O
Increased generation of superoxide radical depletes tissues of what?
NO
What are short-acting formulations of nitrates used for clinically?
Via which route of administration?
- Used to relieve the angina attacks
- Sublingual spray
What are long-acting formulations of nitrates used for clinically?
Via which route of administration?
- Used to prevent attacks
- Oral, ointment, or patch
Nitroglycerin comes in 3 long-acting formulations, which can be administered via which routes?
- Oral
- Ointment
- Patch
What are 4 adverse effects associated with Nitrates?
- Headache
- Orthostatic hypotension
- Increased sympathetic discharge –> Tachycardia + ↑ contractility
- Increased renal Na+ and H2O reabsorption
Why are nitrates contraindicated if ICP is elevated?
Due to meningeal vasodilation
Which drug should nitrates not be used in combination with due to drug-drug interactions?
ED drugs –> Sildenafil, Vardenafil, Tadalafil