Medical Management of Coronary Artery Disease Flashcards
To review, what is the most important contributor of electrophysiologic changes of ischemia? What are injury currents? Describe the diastolic and systolic injury currents.
Increased K+ lead out of cells. Injury currents occur due to gradients that exist between ischemic cells and normal cells. The diastolic injury current occurs during phase 4 when intracellular positive currents flow from less negative ischemic cells to more negative normal cells. The sysolic injury current occurs during phases 2 & 3 when intracellular positive currents flow from normal cells to more negative ischemic cells.
How do we diagnose ischemia & CAD?
Noninvasive: Stress test – HR should reach 85% of maximum HR; compare EKG to baseline – positive if 1 mm ST depression; image if abnormal baseline EKG – echocardiograph or perfusion imaging. Stress testing reveals presence of hemodynamically significant lesions but will not directly image vessels. Direct imaging can be achieved with CT angiogram or e-beam CT scan (identifies calcium). Use dobutamine (sympathomimetic B1 agonist) if the patient cannot exercise. Or, use adenosine or dipyridamole (coronary vasodilators) – stenotic arteries will not respond and the result will be “coronary steal syndrome” – It is caused when there is narrowing of the coronary arteries and a coronary vasodilator is used - “stealing” blood away from those parts of the heart. This happens as a result of the narrowed coronary arteries being always maximally dilated to compensate for the decreased upstream blood supply. Thus, dilating the resistance vessels in the coronary circulation causes blood to be shunted away from the coronary vessels supplying the ischemic zones, creating more ischemia.
What should the first intervention in managing CAD be?
Treat modifiable risk factors – lipid abnormalities (use lipid-lowering agents!), hypertension (use anti-HTN agents!), diabetes (control diabetes!), smoking (stop!).
Antiplatelet agents? Which are thienopyridine derivatives?
Aspirin, Ticlopidine, Clopidogrel, Prasugrel, Ticagrelor, Dipyridamole, Cilostazol. Thienopyridine derivatives: Ticlopidine, Clopidogrel, Prasugrel.
Aspirin class? MOA? Uses?
NSAID: irreversible inhibition of platelet COX, thereby decreasing prostaglandin synthesis and thrombaxane A2 formation, which is needed for platelet aggregation. Uses: stable angina, unstable angina, acute MI, primary prevention.
Ticlopidine class? MOA? Use? Side effects? What’s the bottom line?
Thienopyridine derivitive: Inhibits platelet aggregation by ADP; reduces blood viscosity by decreasing
plasma fibrinogen; increasing RBC deformability. Use: Aspirin alternative. Side effects: neutropenia, TTP — Not really used anymore, hasn’t been shown to decrease adverse events in those with stable angina.
Clopidogrel class? MOA? Use? Side effects?
Thienopyridine derivitive: Selectively and irreversibly inhibits ADP binding to P2Y12 (blocks ADP-dependent activation of glycoprotein IIb/IIIa complex). Use: Excellent antiplatelet + antithrombotic. Side effect:Bleeding — And for this reason, this is not used in place of aspirin for daily prophylaxis or for chronic therapy. No surgical or dental procedures if patient taking this.
Prasugrel class? MOA? Use? Side effects? Use is limited to?
Thienopyridine derivitive: Irreversibly binds P2Y12 receptor (G protein-coupled chemoreceptor for ADP). Use: Reduce thrombotic events in those w/percutaneous coronary intervention(e.g., stent). Side effect: Massive bleeding risk – so much so that despite increased potency versus clopidogrel, comparion of mortality in those suffering an ACS event does not differ because of the added risk with prasugrel of serious bleeding. Limited to use in those 60kg, no history of TIA, stroke.
Ticagrelor MOA? What other antiplatelet decreases the effectiveness of ticagrelor? What is the benefit of this drug?
Similar to adenosine in structure and blocks ADP receptors reversibly. Aspirin reduces effective (FDA black box warning states aspirin > 100 mg decreases effectiveness). Benefits: Does not require hepatic activtion, fast onset, eliminated fast.
Dipyridamole class? MOA? Use? Use is limited why?
Pyrimido-pyrimidine derivitive: Increases platelet intracellular cAMP (inhibits phosphodiesterase 5, activates adenylate cyclase, inhibits uptake of adenosine from vascular endothelium and RBCs). Use: Adjunct therapy for peripheral vascular disease, stress test. Use is limited due to vasodilation of coronary arteries, which will enhance exercise-induced ischemia due to elevation of extracellular adenosine levels.
Cilostazol class? MOA? Use? Why is this dangerous in heart failure patients?
Quinoline derivative: Inhibits PDE, increasing cAMP, inhibiting platelet aggregation. Use: Treatment for claudication in those with peripheral vascular disease. Vasodilation also occurs and is thought to be the mechanism for increased morbidity and mortality seen in heart failure patients.
Class of antihypertensives that can also be used for angina? Which two are most common? Is the anti-CAD effect solely due to decreased BP?
ACEinhibitors: Lisinopril and Ramipril are two of the most common. The anti-CAD effect (reduction of recurrent MI) is not attributed to decreased BP alone – it may be due to decreased levels of renin.
Drugs more likely to be used to lower HR and treat CHF that also have anti-anginal effects? For use in CAD, these drugs are usually…? Name 3. What is the MOA in helping CAD? What else can these drugs do? Side effects? Contraindications?
Beta Blockers. In CAD, these drugs are usually B1 selective (metoprolol, atenolol, bisoprolol) – decrease contractility & HR, thereby decreaseing myocardial oxygen demand: prevent MIs, prevent sudden cardiac death, increase survival post-MI (if patients suddenly stop, really bad!). Side effects: fatigue, worsening claudication, impotence (so men don’t take), decreased exercise tolerance, lethargy, insomnia. Contraindicated in severe bradycardia, high degree AV block, sick sinus syndrome, unstable LV failure; relative contraindication is asthma, severe depression, peripheral vascular disease.
Nitrates MOA? Use? What is the standard dose? How can this be administered? Side effects? Contraindications?
Vasodilator: Facilitate formation of NO, which activates guanylyl cyclase to form cGMP, which inhibits Ca entry into cells, which allows for smooth muscle relaxation and vasodilation – vasodilate epicardial coronary arteries, relieve coronary vasospasm, reduce preload via venour dilation. Inhibit platelet aggregation, anti-inflammatory effects. Dose is 0.4mg. Immediate dose can be sublingual or spray. Long-acting can be oral or transdermal. Uses: For acute episodes; long-acting formulations are for those already on other drugs and still can’t control angina. Side effects: Tolerance w/chronic use (need nitrate free periods of 8-12 hours), headaches, hypotension, activation of Bezold-Jarisch reflex (causes bradycardia). Contraindicated in hypertrophic cardiomyopathy, severe aortic stenosis, significant hypotension, use of phosphodiestera for ED. ALSO: Should NOT be used in RV ischemia or MI.
(This should be a [very important] review!!) Are calcium channel blockers used to treat angina? Why or why not? What are the two types? Which tend to be vasoselective? How do these help angina? Which are 1st generation? 2nd generation? Which are true negative inortopes? What are the two types of these?
YES! – Reduce calcium influx, reduce smooth muscle contraction, cause vasodilation, & if in the heart, cause decreased contractility (negative inotrope). 2 types: Dihydropyridines & Non-dihydropyridines. Dihydropyridines are vasoselective: Dilate epicardial coronaries, arteriolar resistance vessels. 1st gen: Nifedipine. 2nd gen: Amlodipine, Felodipine, Isradipine. Non-dihydropyridines are true negative inotropes (also decrease HR). Verapamil is selective for the myocardium. Diltiazem is an intermediate between verapamil and dihydropyridines.
