Term
| When B1 interacts with its receptor on a muscle fiber what cascade events follow? |
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Definition
1)increase in cAMP
2)activation of cAMP dependent protein kinase
3)kinase phosphorylates L-type Ca channel for Ca uptake
4)kinase phosphorylates phospholamban
5)phospholamban stimulates activity of SERCA2A increasing rate of uptake of Ca even more into SR |
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Term
| the increase in SR Ca load increases ___________ |
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Definition
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Term
| The increase in SR Ca reuptake increases __________ |
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Definition
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Term
| B adrenergic agonists increase ____________ and they also enhance ____________. |
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Definition
| contractility, relaxation |
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Term
| you get a down-regulation of your _________ in the failing heart. |
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Definition
| B-receptor (so diminished effect of B-1 adrenergic agonist) |
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Term
| Na/Ca exchanger does what to Ca in muscle fiber? |
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Definition
It may extrude Ca or cause influx according to voltage.
1)polarized:extrudes
2)depolarized:influx |
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Term
| Digitalis & Digoxin inhibit the ____________ |
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Definition
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Term
| Na/K ATPase in muscle does what? |
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Definition
| extrudes 3 Na for the influx of 2K, this helps to repolarize the cell after contraction. (this happens during relaxation) |
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Term
| What mechanism is independent from the L-type Ca2+ channel for bringing Ca2+ into the cell? |
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Definition
| Inhibition of Na/K ATPase by Digitalis or Digoxin causing accumulation of Na in cell which is then extruded in exchange for Ca influx. |
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Term
| what drug reduces the sensitivity of these muscle proteins to Ca2+? |
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Definition
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Term
| 3 subunits of troponin complex? |
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Definition
1)troponin T : which interacts with tropomyosin
2)troponin C : which binds Ca2+
3)troponin I: which can be phosphorylated. |
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Term
| Phosphorylation of troponin I aids in ___________ |
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Definition
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Term
| B-adrenergic agonists aid in relaxation by? |
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Definition
| phosphorylation of troponin I |
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Term
| B-adrenergic agonists aid in contractility by? |
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Definition
| phosphorylation of L-type Ca channels |
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Term
| Dobutamine is a ______________ |
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Definition
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Term
| Milrinone is a _____________ |
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Definition
| PDE inhibitor (this increases cAMP causing the same effective cascade as B-agonists) |
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Term
| According to Frank-Starling relationship increased LV filling pressure should increase LV ____________ |
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Definition
| stroke work (this is depressed in heart failure patients) |
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Term
| Impaired relaxation in heart failure pts may cause an increase in ___________________ due to a failure of Ca to return to basal levels during diastole |
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Definition
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Term
| pathophys of heart failure |
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Definition
1)pump failur eleads to either diastolic or systolic dysfunction
2)Baroreceptor reflex activated to increase sympathetic activity
3)Symps increase vasoconstriction
4)symps activate renin release
5)renin further increases peripheral resistance
6)angiotensin II increases aldosterone production = increase H2O absorption
7)symps reduce renal blood flow leading to Na and water retention
All of this will increase the work of the heart and contribute to further failure, think of these things when discussing drugs for heart failure! |
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Term
| Treatment of heart failure depends on the __________ |
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Definition
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Term
| Aim of therapy vs. heart failure (3) |
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Definition
1)improve contractile function
2)promote water and salt excretion
3)prevent ventricular remodeling |
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Term
| What your ionotropic agent does directly is merely to increase your stroke volume. It doesn’t directly affect ______________________ |
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Definition
| ventricular filling pressure |
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Term
| Digoxin increases ____________ activity along with extruding Na for the influx of Ca. |
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Definition
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Term
| enhanced vagal activity from Digoxin is associated with? |
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Definition
1)decreased atrial beating
2)Reduced conduction and prolongation of refractory through the AV node (can lead to AV block) |
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Term
| 3 main electrophysiologic actions of digoxin? |
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Definition
1)extra systoles in atria
2)AV block
3)ventricular tachycardia |
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Term
| Ouabain blocks __________ |
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Definition
| Na/K ATPase (like digoxin) |
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Term
| The vagal effect of digoxin may be blocked by ____________ |
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Definition
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Term
| treat atrial tachycardia due to digoxin by ________________ |
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Definition
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Term
| Ventricular arrhythmias caused by digoxin may be treat with _________ and ________ |
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Definition
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Term
| treat AV junctional tachycardia caused by digoxin w/ ___________ |
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Definition
| K administration (the increased K levels work vs the actions of digoxin at the Na/K ATPase) |
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Term
| Signs of digoxin toxicity? (3) |
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Definition
1)G.I. symptoms (anorexia, nausea, vomiting)
2)blurred vision
3)CNS toxicity (headache, fatigue, confusion) |
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Term
| Why is digoxin useful for treating supraventricular tachycardia? |
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Definition
| b/c it slows conduction through the AV node |
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Term
| Digoxin has a ___________ therapeutic window and is excreted __________ in most pts. |
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Definition
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Term
| Digoxin may be administered how? |
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Definition
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Term
| Digoxin gel caps or tablets have a better bioavailability? |
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Definition
| gel caps (important since such a small therapeutic window) |
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Term
clicker question:
Digoxin increases cardiac contractility by directly:
A. Activating L-type Ca2+ channels
B. Inhibiting cardiac phosphodiesterase
C. Inhibiting myocardial Na+/Ca2+ ATPase
D. Inhibiting myocardial Na+/K+ ATPase |
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Definition
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Term
clicker question:
Which of the following is the most accurate statement regarding digoxin?
A. Decreases mortality in patients with congestive heart failure exhibiting normal sinus rhythm
B. Increases vagal tone and decreases AV nodal conduction
C. Lengthens the action potential and increases the refractoriness of the heart
D. Useful in the treatment of Wolff-Parkinson-White Syndrome |
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Definition
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Term
| Pharmacologic actions of dobutamine: (3) |
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Definition
1) Enhances contractility but causes only a slight increase in heart rate.
2) Beta 1 agonist but also exhibits beta 2 activity, the latter which accounts for its ability to serve as a weak vasodilator.
3) Thus, it causes a slight reduction in afterload pressure. It also improves renal function. |
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Term
| Dobutamine increase _____________ and decreases _________________ |
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Definition
| cardiac fxn; systemic resistance |
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Term
| High doses of dobutamine can cause: (3) |
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Definition
1)tachycardia
2)hypoglycemia
3)ischemia |
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Term
| Mechanism of action of milrinone: |
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Definition
1)inhibits PDE preventing the breakdown of cAMP
2)this increases contractility and promotes relaxation
3)reduces systemic vascular resistance |
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Term
| Does milrinone or dobutamine cause a greater change in systemic vascular resistance? |
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Definition
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Term
| What drug actually increases mortality in patients with ischemic tissue? (inotropic agent) |
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Definition
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Term
| Milrinone is used strictly for pts with ________________ |
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Definition
| refractory heart failure; (short-term treatment can increase exercise capacity and stroke volume) |
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Term
| A reduction in outflow resistance will ___________ stroke volume |
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Definition
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Term
|
Definition
1)captopril
2)enalapril and
3)lisinopril |
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Term
| ACE inhibitors reduce __________ & __________ |
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Definition
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Term
| 2 main angiotensin receptor blockers: |
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Definition
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Term
| angiotensin receptor blockers reduce ___________ & ___________ |
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Definition
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Term
| Angiotensin II interacts with what 2 receptors? |
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Definition
AT1 and AT2
(AT1 is responsible for all the major effects we think of, AT2 effects are not completely established) |
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Term
| Pharmacologic actions of ACE inhibitors and AT1 receptor blockers: (6) |
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Definition
| 1)decrease afterload and preload 2)decrease HR (secondary to drop in symps) 3)increase renal blood flow decreasing blood volume 4)Reduce salt and water retention (attenuate aldosterone secretion) 5)Decrease ventricular remodeling 6)Reduce systolic wall stress |
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Term
| what grade of heart failure pts should receive ACE inhibitors and AT1 antagonists? |
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Definition
| All of them, they significantly decrease mortality, hospital time, complications, etc. |
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Term
| Does digoxin decrease mortality? |
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Definition
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Term
| What drug causes a characteristic cough? |
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Definition
| ACE inhibitors due to bradykinin increase (bradykinin is usually degraded by ACE) |
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Term
| Is there a difference in mortality rates b/w heart failure pts on Losartan (AT1 receptor blocker) vs. captopril (ACE inhibitor)? |
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Definition
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Term
| ACE inhibtors and AT1 receptor blockers can cause what in pts with bilateral renal artery stenosis or stenosis of a single remaining renal srtery? |
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Definition
| renal insufficiency (since AngII can maintain glomerular filtration during low pressure) |
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Term
| _________ is a nitric oxide donor that reduces preload and afterload |
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Definition
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Term
| Name 2 orgnanic nitrates that reduce preload: |
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Definition
1)nitroglycerin
2)isosorbide dinitrate |
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Term
| Pharmacologic actions of nitroprusside: (4) |
|
Definition
1) Elevates NO
2) Reduces both preload and afterload
3) In severe heart failure, reduction in vascular resistance dominates and cardiac output rises as afterload falls.
4) Increases venous compliance, resulting in redistribution of blood to peripheral veins. |
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Term
| This vasodilator is very potent so is regularly used in emergency situations: |
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Definition
Nitroprusside
(It’s also effective in patients with CHF due to mitral regurgitation or vascular resistance) |
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Term
| This vasodilator can be metabolized to cyanide then thiocyanate (CNS toxin). |
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Definition
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Term
| Nitroprusside can cause coronary steal which is what? |
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Definition
| Arterioles are dilated, causing diversion of blood from coronary vessels |
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Term
| Hydralazine reduces ___________ |
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Definition
| afterload (so would be good to use with a drug like isosorbide dinitrate) |
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Term
| Pharmacologic actions of hydralazine: (3) |
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Definition
1)It reduces afterload by decreasing systemic vascular resistance
2)It evokes a moderate positive inotropic effect
3)It reduces renal vascular resistance, increasing renal blood flow |
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Term
| vasodilator of choice if the patient cannot tolerate the ACE inhibitor or AT1 antagonist |
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Definition
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Term
| Hydralazine is often combined with a venodilator, such as ___________ |
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Definition
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Term
| Does hydralazine decrease mortality? |
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Definition
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Term
| What vasodilator is rapidly acetylated in plasma and deactivated? |
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Definition
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Term
| Toxicity of hydralazine : (3) |
|
Definition
1)Hypotension
2)Coronary steal
3)Lupus like syndrome |
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Term
| important function of B-blockers for fighting heart failure: |
|
Definition
| disrupting the effects of sympathetic stimulation on renin release and the Ang II system |
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Term
| This drug class reduces the incidence of malignant ventricular arrhythmias: |
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Definition
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|
Term
This drug class:
1)Enhances ventricular function.
2)Reduces incidence of malignant ventricular arrhythmias,
3)reduces the degree of ventricular remodeling. |
|
Definition
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Term
| When a heart failure pt is treated with metoprolol what is the initial effect? |
|
Definition
| A decrease in ejection fraction due to decreased contractility. After an extended time of treatment, you get improvement! |
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Term
| Do B-blockers decrease mortality? |
|
Definition
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|
Term
| Adverse side effects of B-blockers: (2) |
|
Definition
1)can suppress contractile fxn
2)slow HR |
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Term
| Spironolactone is what type of drug? |
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Definition
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|
Term
| 2 main actions of spironolactone: |
|
Definition
1) interfere with sodium and water retention
2) prevent myocardial fibrosis and fibroblast proliferation (a form of remodeling) |
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Term
| Therapeutic uses of spironolactone: |
|
Definition
1)Reduces mortality by ~30%
2)Reduces hospitalization for heart failure.
3)Effects additive to those of ACE inhibitors
4)Reduces remodeling, therefore, progression of heart failure. |
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Term
| Side effects of spironolactone? |
|
Definition
| can elevate K levels, (but may also be associated with reduction in mortality) |
|
|
Term
| Stages of Heart Failure slide, I just posted it on here because it gives you a good idea of when drugs start to be used. I'd take a look at it just to get big picture! |
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Definition
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|
Term
| Use _______________ early in heart failure because they affect remodeling, and you want to get to that as soon as possible |
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Definition
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