1-10 (Anti-Anginals) Flashcards
____: Imbalance in myocardial oxygen demand and supply
Ischemia
What three factors affect myocardial oxygen demand?
1) HR
2) Cardiac Contractility
3) Wall Tension
The ____ is determine by coronary blood flow and regional/tissue specific blood flow
oxygen supply
CK-MB and Troponin T and Troponin I are common markers for what medical condition?
MI
True or False: Angina is a disease
False - angina is NOT a disease. Rather, it is a symptom of hidden cardiovascular complication (e.g CAD/Ischemic Heart Disease)
What are the four type of angina?
1) Stable Angina
2) Unstable Angina
3) Variant/Prinzmetal Angina
4) Microvascular Angina
Which type of angina is associated with no overt plaques, but intense vasospasm?
Variant/Prinzmetal Angina
What causes symptoms associated with Variant/Prinzmetal Angina?
Malfunctioning of NO mediated vasodilation
What type of angina is associated with plaque rupture, platelet aggregation, and thrombus formation?
Unstable Angina
Which type of angina is associated with inappropriate vasoconstriction and lumen narrowed by plaque?
Stable Angina
What are the four causes of impaired microvessels, as is seen in Microvascular Angina?
1) Imbalance in neural factors
2) Endothelial factors
3) Myogenic contribution
4) Metabolic stress
In general, how do anti-anginal medications work?
1) Decrease myocardial O2 demand
2) Increase myocardial O2 supply
True or False: Beta blockers and calcium channel blockers can be used to treat anginas
True
What type of drug class does Ranolazine belong to?
Inward sodium channel inhibitor
What type of drug class does Ivabradine belong to?
Hyperpolarization activated cyclin nucleotide gated channel inhibitor
What are 3 high potency nitrates?
1) GTN/Nitroglycerin
2) Pentaerythritol tetranitrate (PETN)
What are 2 low potency nitrates?
1) ISMN (Isosorbide mononitrate)
2) ISDN (isosorbide dintrate)
When administered at a low dose, GTN and PETN undergo bioactivation to form nitrite. Which enzyme allows for this conversion?
Mitochondrial aldehyde dehydrogenases (ALDH2)
When GTN/PETN are given in low dose, they are are converted to nitrite then to NO. What enzymes allow for conversion to NO?
Xanthine Oxidase or Mitochondrial Cytochrome
When GTN/PETN are given in high doses, they are activated via: ____ , ____, and by ER residing ___ system, allow for NO production
ALDH2 (mitochondrial aldehyde dehydrogenases), mitochondrial cytochrome oxidase, and P450
What type of nitrates are known to utilize ER residing CYP 450 system to get bioactivated and release NO, irrespective of dose?
Low potency nitrates (ISDN, ISMN)
When NO is released ___ is produced, leading to production of ___ and ___ = relaxation of VSM
sGC (soluble guanylate cyclase) -> cGMP -> cGK-1
What are two systemic positive effects of nitrates?
1) VSM - increase venous capacitance, reduce pre-load (decrease change of getting MI or HF)
2) Increase cGMP inside platelets, prevents aggravation (THIS PROPERTY IS MADE USE OF IN UNSTABLE ANGINA!!)
What is the most common AE associated with nitrates and is due to the fact that nitrites associate with Hb to form methemoglobin (molecule w low O2 affinity)?
Pseudocyanosis
Overdose of Nitrovasodilators may lead to generation of ____
ROS
How does excess levels of Reactive Oxidative Species affect NO and peroxynitrite levels?
Excess ROS can down regulate NO by converting NO to Peroxynitrite
DDI with nitrites?
PDE-5 Inhibitors
True or False: Nitroglycerin is known to prevent first pass metabolism of Ergotamine.
True
True or False: Excess ergot alkaloids can precipitate angina, should be avoided in patients on nitrites
True
What drug is an inward sodium current/channel inhibitor?
*Ranexa/Ranolazine
Myocardial Ischemia is accompanied by an increase in inward ____and ____in myocardial tissues
sodium current; sodium overload
How does increase inward sodium current and sodium overload in myocardial tissues, as seen in Myocardial Ischemia, affect calcium entry?
Increase Na causes increase Ca entry via Na/Ca2+ Exchanger
True or False: Enhanced calcium overload may increase contractility followed by a DECREASE myocardial oxygen demand
False - Enhanced calcium overload may increase contractility followed by a INCREASE myocardial oxygen demand
How does Ranolazine affect:
- myocardial O2 demand?
- ca2+ overload?
- sodium load?
- REDUCED myocardial O2 demand
- indirectly PREVENTS excess ca2+ overload
- DECREASES excess sodium load
What drugs can Ranolazine be co-administered with?
Other anti-anginal drugs
Which anti-anginal drug is contraindicated in patients with QT prolongations? Why is it contraindicated?
Ranolazine
- can lead to torsade de pointes and ventricular tachycardia
How does increase SA Nodal Activity affect contractility and myocardial O2 demand?
Increased SA Nodal Activity increases contractility and enhances myocardial O2 demand
True or False: Ivabradine is a HCN channel blocker
True
___ inhibits sodium entry (inward funny current_ through HCN in the SA Node with reduction in HR, leading to reduced myocardial ___ demand
Ivabradine; HCN
Bradycardia, A-Fib, and Visual disturbances are associated with which anti-anginal?
Ivabradine
In angina, calcium channel blockers bind to which subunit of the L-Type Calcium Channel?
How does this affect HR, force of contraction, and vasodilation?
Alpha 1 subunit
(this is the MAIN pore-forming unit of the calcium channel)
- HR/force of contraction: decreases
-Increased vasodilation
Which anti-anginal is associated with the AE of: bradycardia, asystole, and WORSENING of heart failure?
Calcium channel blockers
True or False: Taking anti-retroviral drugs or grapefruit with CCB’s can enhance CCB toxicity
True
What three beta-1 blockers that are most commonly prescribed for exertional angina, prior MI, or stable/unstable angina?
1) Atenolol
2) Metoprolol
3) Bisoprolol
AE associated with beta-1 blockers used to treat angina?
1) Left Ventricular Dysfunction
True or False: Cholestyramine and Colestipol decrease absorption of beta blockers, resulting in reduced bioavailability of beta blockers
True
By specifically blocking beta-1 receptors in CV tissue, beta blockers lead to ____ chronotropic and inotropic effects. As a result, myocardial O2 demand and use is ____
negative; decreased
True or False: B1 receptors are known to regulate HCN channel activity in SA Node, along with their direct stimulatory effects on cardiac muscle
True
Which drugs decrease oxygen demands?
A. Vasodilators
B. Ranolazine
C. Ivabradine
B. Ranolazine
C. Ivabradine (decreases myocardial sodium levels)
