MI drugs Flashcards
what causes stable angine
due to coronary atherosclerotic occlusion
what causes Vasospastic/variant/Prinzmetal angina
due to reversible reduction in coronary blood flow
anginal pain is usually due to release of what?
release of bradykinin and adenosine onto nociceptive afferents
duration for acute MI
sudden onset, last >/=30 min
duration of rest or unstable angina
<20 min
duration of angina
2-10 min
organic nitrates for MI
Nitroglycerin (GTN), Isosorbide Dinitrate (ISDN), Isosorbide Mononitrate (ISMN)
MOA of organic nitrates
Organic nitrates are prodrugs that must undergo denitrification by mitochondrial aldehyde reductase to yield NO
NO activates soluble GC, increasing cGMP –> cGK-1 activation:
- increase mitochondrial Ca2+ uptake
- decrease Ca2+ influx
- Phosphorylates MLCK
–> vasorelaxation
explain nitrate tolerance
When given acutely, nitrates have potent hemodynamic and therapeutic effects. However, these effects were lost rapidly during sustained therapy, almost completely when significant plasma concentrations are present throughout the 24-hr period. Tolerance develops early, and cannot be overcome with higher doses
how can nitrate effects be maintained (avoiding tolerance)
Nitrate effects could be maintained using dosing regimens that allow for a nitrate-free or low-nitrate concentration for several hours each day.
what nitrate undergoes hepatic and intravascular metabolism
Nitroglycerin
- fast acting
Nitroglycerin is very effective when given via what route
sublingual or transdermal
what forms of isosorbide dinitrate are available
Available in phasic, sustained release form –> QD dosing –> avoid tolerance
which nitrate does not undergo first pass hepatic metabolism – completely available
isosorbide mononitrate
what forms of isosorbide mononitrate are available
Available in sustained, phasic release form –> QD dosing –> avoid tolerance
Pharmacodynamic effects of nitrates:
Potent vasodilation in veins –> decrease ventricular volume and 1
No effect on 2.
Little or no effect on the 3 vessels –> avoid 4
- preload
- peripheral vascular resistance
- coronary resistance
- coronary steal
form of nitration that is used for classic therapy for the treatment of acute attacks of angina
Sublingual nitrates
what nitrates can be prescribed as a prophylactic therapy, taken before activity that would generally lead to angina
Nitroglycerin
Isosorbide dinatrate (ISDN)
what are long-acting nitrates effective in?
angina,
increase exercise duration,
decrease anginal frequency
how should dosing be done for long-acting nitrates?
Due to nitrate tolerance, dosing must allow for a low or nitrate-free period during the day
In acute HF and active ischemia, _____ can be the therapy of choice.
organic nitrates
good in African-Americans with CHF, especially CHF that results from systolic dysfunction.
Isosorbide dinitrate and hydralazine combo
what nitrate is often used for Unstable angina and acute myocardial infarction (MI)
Sublingual GTN is often used, but intravenous (IV) and transdermal formulations also have a role.
SE of nitrates
Headaches - most pronounced early aftern initiation
Hypotension - more common with rapid onset
what nitrate should be up-titrated over several days to avoid hypotension)
Isosorbide dinatrate
therapeutic use of ranolazine
angina
SE of ranolazine
Prolongs the QT interval in patients with coronary artery disease (but shortens it in patients with long QT syndrome, LQT3).
***Has not been associated with torsades de pointes
MOA of ranolazine
Inhibits late sodium current (INaL) that facilitates Ca2+ entry via the NCX –> decrease intracellular Ca2+ –> decrease diastolic tension, cardiac contractility.
funny current blocker for MI
Ivabradine
MOA of ivabradine
- **specific inhibition of If channel –> prolongs phase 4 AP.
- -> decrease spontaneous firing rate of SA pacemaker cells
***NO negative inotropic effects
No effect on ventilation in COPD patients
clinical use of ivabradine
Chronic stable angina in pts who cannot take beta blockers
SE of ivabradine
Luminous phenomenon
- sensation of enhanced brightness
- due to Ih blockade in retina
