z-Pharm Antianginal I and II
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- What is Varient Angina?
- An uncommon angina resulting from a decreased myocardial O2 supply during nL O2 demand caused by focal spasms of coronary a. and can occur at rest or in sleep.
- Is relaxation from NO action endothelium dependant or independant?
- INDEPENDANT
- What are the four drugs (or types of drugs) a Px with exertional angina would be on?
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1. nitrates
2. beta blocker
3. Ca channel blocker
4. Ranolazine - What is Nitrates MOA in exertional angina?
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1. direct coronary artery vasodilation
2. reduced afterload
3. reduced LV wall tension
4. decreased venous return by dilating venouse capacitance vessels - What do Nitroglycerin and isosorbide dinitrate do for exercise-induced ischemia?
- Both prevent future episodes and nitroglycerin terminates present exercise-induced ischemia.
- Three very important side effects of nitrate theurapy (used for angina, hypertensive emergency, and CHF)
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1. orthostatic hypotension
2. reflex hypertension
3. headache - What is nitrate tolerance?
- When, with repeated use of nitrates, cysteine stores are depleted so the body no longer responds.
- Explain how smooth muscle contraction differs from cardiac muscle contraction?
- Unlike in cardiac m., myosin phosphorylation is REQUIRED for activation of smooth m. myosin ATPase needed to contract.
- How do Ca channel blockers cause vasodilation?
- Ca channel blockers reduce Ca entry and thus decrease Ca available to bind to calmondulin and help to phosphorylate myosin light chains and contract the smooth muscle. Thus they prevent smooth muscle contraction.
- What do Beta 1 and Beta 2 receptors effect?
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Beta 1 - cardiac muscle
Beta 2 - cardiac muscle, bronchial smooth muscle, and vascular smooth muscle - What four things does cAMP do in cardiac muscle?
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1. increased opening of L-type Ca channels (inotrophy)
2. increased reuptake of Ca into SR stores (inotrophy and lusitrophy)
3. increased pacemaker current (chronotrophy)
4. increased rate of conduction - What does beta 1 stimulation cause?
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1. increased HR
2. increased AV nodal conduction
3. increased force of contraction - What do beta 1 antagonists do?
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1. decrease HR
2. decrease contractility
3. decrease mean arterial blood pressure - What does a decrease in heart rate do to myocardial O2 delivery?
- Increases it which increases diastolic perfusion time.
- Eight clinical uses of Beta blockers?
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1. angina
2. hypertension
3. arrhythmias
4. dissecting aortic aneurysm
5. mitral valve prolapse
6. post-MI
7. hyperthyroidism
8. migraine - How is the double product used? What is it?
- It is a calculation of the o2 consumption of the heart vs the HR x systolic BP. This value is used to see how well medication to decrease 02 consumption of the heart is working. Beta blockers cause a smaller double product when running on the treadmill the same amount of time as someone who is not on beta blockers.
- By what mechanism do organic nitrates decrease the severity of myocardial ischemia?
- Nitrates increase nitric oxide which increase cGMP which increases the dephosphorylation of myosin light chains leading to vascular smooth muscle relaxation. This vasodilation reduces the heart's afterload as well as it's wall tension. These reduction cause a decrease in myocardial oxygen consumption which allows more 02 to be available to the pending ischemic area.
- What are the mechanisms by which Calcium channel antagonists decrease the severity of myocardial ischemia?
- Ca channel blockers decrease the influx of Ca available to contracting smooth muscle. Therefore the smooth muscle will be unable to contract. They produce vasodilatory effects which decrease 02 consumption as well as decrease the amount of Ca available to the heart causing decreased HR and contractility - both of which decrease 02 consumption!
- How can a beta blocker increase blood flow to an area of ventricular muscle supplied by a stenotic coronary artery?
- By decreasing storage of Ca in the SR, conteracting sympathetic effects of the heart, beta blockers cause a decrease in HR and contractility of the heart (and decrease in afterload). All of these slow the heart down to allow for increased 02 delivery -> increased diastolic perfusion time and decreased vascular compression. This allow oxygenated blood flow the time to reach poorly perfused areas.
- Why would nadolol be expected to cause less mental depression and fatigue than propranolol?
- Nadolol is less lipophilic and thus less of it crosses the BBB.
- What would the hemodynamic effects of the administration of a nitrate in combination with beta blocker be?
- Nitrate + Beta blocker = both would cause vasodilation!
- Why are "pure" arteriolar vasodilators such as dipyramidole not effective in treating myocardial ischemia?
- While dipyramidole does vasodilate and also inhibits platelet function by inhibiting adenosine uptake and cGMP activity it has by itself little beneficial effect. Must be used in conjunction with aspirin to benefit from it.
- What is the difference between stable and unstable angina?
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Stable:
1. precipitated by increased 02 consumption
2. a critical stenosis forms from exercise causing a 70% narrowing of coronary artery
3. chest discomfort that goes away with rest within 1-5 min
Unstable:
1. new onset chest discomfort
2. increasing frequency of discomfort
3. discomfort comes on with rest or minimal exertion
4. episodes of discomfort are prolonged
5. critical stenosis forms from a superimposed thrombosis - What drugs are useful in treating varient angina?
- Nitrates and Ca channel blockers are better than beta blockers
- What are the major side effects of nifedipine?
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reflex tachycardia
peripheral edema
hypotension - What drugs would be administered to a Px with angina AND hypertension?
- Beta blockers or Ca channel blockers are good
- What drugs can not be used on patients with COPD, asthma, and acute CHF?
- beta blockers
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VIP
What blocks the reflex tachycardia and increased contractile activity associated with nitrates? (2) - Beta blockers or verapamil