Term
| what new drug (nitrate) has benefit of being effective in treating CHRONIC angina? |
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Definition
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Term
| The major acute adverse effects of nitrates are due to _______________ |
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Definition
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Term
| Angina pectoris is a symptom of an imbalance b/w _____________ and ___________ |
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Definition
| Myocardial oxygen demand; oxygen delivery |
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Term
| Ventricular wall stress is determined by ___________ and __________ |
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Definition
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Term
| 3 determinants of ventricular wall stress: |
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Definition
1)ventricular wall stress
2)Heart rate
3)contractility (inotropic state) |
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Term
| 4 major determinants of myocardial O2 delivery: |
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Definition
1)coronary srterial blood flow during diastole
2)aortic diastolic pressure
3)duration of diastole
4)coronary vascular resistance |
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Term
| ATP breaks down into __________ during an ischemic episode to mediate vasodilation |
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Definition
| adenosine (local vasoactive mediator) |
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Term
| Name a neural autonomic signal which causes an increase in coronary vascular resistance by constriction. |
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Definition
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Term
| 5 regulators of coronary vascular resistance: |
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Definition
1)local vasoactive mediators (adenosine)
2)neural autonomic signals
3)atherosclerosis
4)thrombi
5)extravascular compression |
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Term
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Definition
1)stable
2)unstable
3)vasospastic |
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Term
| Stable angina is due to __________________ |
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Definition
| coronary artery atherosclerosis |
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Term
| Coronary artery atherosclerosis causes stable angina by? |
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Definition
| limiting blood flow (O2 delivery)when work of the heart increases (O2 demand) |
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Term
| Stable anginal episodes may be precipitated by : |
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Definition
1)exercise
2)cold
3)stress
4)emotion
5)eating |
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Term
| Therapeutic goals for stable angina? (3) |
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Definition
1)increase myocardial blood flow by dilating coronary arteries
2)decrease cardiac work by decreasing preload/afterload (decrease O2 demand)
3)decrease heart rate (decrease O2 demand) |
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Term
| ___________ angina is associated with increased severity, frequency and duration. (also occurs at rest) |
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Definition
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Term
| Unstable angina is caused by: |
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Definition
| Caused by recurrent platelet clumping and embolization of coronary artery at site of a ruptured atherosclerotic plaque, which can also precipitate local vasospasm (can precipitate an MI) |
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Term
| Therapeutic goals in unstable angina: |
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Definition
1)increase coronary blood flow (dilate coronary arteries; inhibit platelet formation and thrombus formation)
2)decrease work (O2 demand; same as stable angina) |
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Term
| Vasospastic angina is often associated with ________________ |
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Definition
| underlying atherosclerosis |
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Term
| vasospastic angina is caused by _______________ |
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Definition
| transient, intense constriction of coronary artery |
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Term
| What 2 types of angina can occur at rest? |
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Definition
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Term
| Therapeutic goal of vasospastic angina: |
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Definition
| relaxation of smooth muscle |
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Term
| 3 major classes of antianginal drugs: |
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Definition
1)organic nitrates
2)Ca channel blockers
3)B-adrenergic receptor antagonist |
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Term
| How do vasoconstrictor agonists act to cause constriction in underlying smooth muscle? |
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Definition
| They activate a G protein which activates PLC causing an increase IP3 leading to an increase in Ca contributing to contraction |
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Term
| How does calcium cause contraction? |
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Definition
1)Ca binds to calmodulin
2)this activates MLCK
3)MLCK phosphorylates MLC
4)MLC mediates contraction |
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Term
| 2 main actions of nitric oxide (NO) |
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Definition
1)vasodilator
2)inhibitor of platelet activation |
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Term
| All drug forms of organic nitrates/nitrovasodilators are converted into _______________ |
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Definition
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Term
| 4 examples of organic nitrates/nitrovasodilators that schaffer gave us: |
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Definition
1)nitroglycerin
2)amyl nitrite
3)isosorbide-5-mononitrate
4)isosorbide dinitrate |
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Term
| Endothelial cells produce ___________ in response to Ach |
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Definition
| NO (he demonstrated this by the study that showed no vasodilation when Ach was introduced to a denuded artery, but showed rapid dilation when Ach was introduced to an intact artery) |
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Term
| How do nitrates cause smooth muscle cell relaxation? |
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Definition
1)nitrates are converted to NO
2)NO activate guanylate cyclase
3)Guanylate cyclase converts GTP to cGMP
4)cGMP activates cGMP dependent kinase
5)cGMP dep protein kinase phosphorylates proteins that reduce Ca and Ca sensitivity |
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Term
| 1 major problem with nitrates |
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Definition
| They lose their effectiveness |
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Term
| NO reduces myocardial work and O2 demand by _________________ |
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Definition
| reducing preload/afterload (mainly preload, by dilating venous circulation) |
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Term
| NO can increase coronary blood flow and O2 delivery through _____________ |
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Definition
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Term
| which nitrate is not subject to first-pass metabolism and is 100% available after oral administration ? |
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Definition
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Term
| Continuous or frequent exposure to nitrovasodilators can lead to the development of _________________ |
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Definition
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Term
| hepatic first-pass metabolsim is high and oral bioavailability is low for ___________ and _____________ (nitrates) |
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Definition
| nitroglycerin; isosorbide dinitrate |
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Term
| First pass metabolism of nitrates may be avoided by what kind of administration? |
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Definition
1)sublingual
2)transdermal |
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Term
| 4 main beneficial effects of NO: |
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Definition
1)decreases ventricular volume, arterial pressure and ejection time (decreasing O2 requirement)
2)Vasodilates coronary arteries relieving vasospasm
3)increases collateral flow improving O2 delivery
4)decreases left ventricular diastolic pressure (improves ischemic zone) |
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Term
| The major acute adverse effects of nitrates are due to ______________ |
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Definition
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Term
______________________ can potentiate
the systemic vasodilation and hypotension induced by nitrates |
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Definition
| PDE-5 inhibitors (i.e. viagra) |
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Term
| Adverse effects of nitrates: |
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Definition
Orthostatic hypotension
Tachycardia
Headache
Dizziness
Flushing
Syncope |
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Term
| 3 Ca channel blockers (schaffer said to know): |
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Definition
1)Verapamil
2)Nifedipine (dihydropyridine)
3)diltiazem |
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Term
| mechanism of vasodilation by Ca channel blockers: |
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Definition
inhibits Ca influx through voltage gated L-type and/or T-type Ca channels
(Have little or no effect on Ca2+ influx through receptor- or store-operated Ca2+ channels, or on Ca2+ release from intracellular stores) |
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Term
| T/F: Verapamil has both venodilatory and vasodilatory effects |
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Definition
| F; verapamil (Ca channel blocker) has very little effect on veins but relaxes arterial smooth muscle |
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Term
| Name 2 Ca channel blockers that depress SA node and AV node conduction. |
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Definition
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Term
| ___________________ have minimal direct effects on SA node and AV conduction,but they can cause systemic hypotension and reflex tachycardia |
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Definition
| dihydropyridines (i.e. nifedipine) |
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Term
| Dihydropyridine elicits __________________ that results in baroreceptor mediated increase in sympathetic tone. |
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Definition
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Term
| antianginal mechanisms of Ca channel blockers: (3) |
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Definition
1)increasing blood flow through dilation of coronary arteries and arterioles
2)decreasing O2 demand by silation of systemic arteries and reducing afterload
3)decrease of heart rate/contractility by verapamil and diltiazem. |
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Term
| Major adverse effects of verapamil and diltiazem: |
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Definition
1)depression of contractility and exacerbation of heart failure
2)AV block
3)bradycardia
4)cardiac arrest |
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Term
| minor effects of Ca channel antagonists (i.e. nifedipine) |
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Definition
| Hypotension, dizziness, edema, flushing |
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Term
In pts with myocardial ischemia, immediate release forms of _______________
may increase mortality. |
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Definition
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Term
| What pts should not be put on verapamil or diltiazem? |
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Definition
those with:
1)ventricular dysfunction
2)SA node/AV node conduction probs
3)WPW syndrome
4)systolic BP below 90 mmHg |
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Term
| 3 (2 primary, 1 secondary) anti-anginal mechanisms of B-blockers |
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Definition
1)decrease HR/contractility reducing O2 demand
2)decrease systemic pressure and afterload
3)(secondarily) improves coronary blood flow due to decrease in heart rate |
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Term
| 4 adverse effects of B-blockers: |
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Definition
1)contraindicated in pts with asthma due to bronchoconstriction
2)may exacerbate heart failure
3)may mask the tachycardia induced by hypoglycemic diabetic pt
4)contribute to AV block in pts receiving verapamil or diltiazem |
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Term
| _____________ are the most effective for reducing risk of recurrent ischemia in unstable angina. |
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Definition
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Term
| In unstable angina pts the risk of MI is diminished by _____________ and ______________ drugs. |
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Definition
| antiplatelet; antithrombotic |
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Term
| Hospitalized moderate- to high-risk ACS (acute coronary syndrome; unstable angina) patients should be treated with: |
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Definition
| aspirin (ASA), clopidogrel, antithrombin therapy, a b-blocker, statin, and, in selected individuals, a GPIIb/IIIa inhibitor. |
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Term
| this Ca channel blocker can cause a reflexive increase in heart rate |
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Definition
| Nefidipine (dihydropyridine) |
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Term
| Nitrates plus B-blockers or Ca channel blockers ____________ contractility and ____________ heart rate |
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Definition
| doesn't effect contractility ; decrease heart rate |
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Term
| B-blockers or CCBs used alone _____________ preload and _________ afterload |
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Definition
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Term
| B-blockers or CCBs alone __________ ejection time |
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Definition
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Term
| Nitrates alone _________ heart rate and _________ contractility |
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Definition
| increase; increase (through reflex due to baroreceptors detecting drop in BP from vasodilation) |
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Term
| 4 good antianginal combos: (courtesy of schaffer) |
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Definition
1)dihydropyridine + B-blocker (B-blocker prevents reflexive rise in HR)
2)Nitrate + B-blocker (B-blocker prevents reflexive rise in HR)
3)Nitrate + verapamil or diltiazem (V or D prevents reflexive rise in HR)
4)Nitrate + CCB + B-blocker (you've got the idea) |
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Term
| a bad antianginal combo: (courtesy of schaffer) |
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Definition
| B-blocker + CCB = bradycardia, AV block, depressed left ventriculr function |
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