Term
| I am a tissue protease that converts ANGI to ANg II. I am not induced in HF. Who am I? |
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Definition
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Term
I am expressed in:
cardiac myocytes
fibroblasts
vascular smooth muscle cells
endothelial cells
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Definition
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Term
I am expressed in:
mast cells
other interstitial cells |
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Definition
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Term
| What are the four therapeutic effects of ACEi in HF? |
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Definition
1. inhibit formation of ANG II
12. arterial and venous dilation, decreasing both afterload and preload
3. decrease aldosterone release
4. decrease LV hypertrophy (growth mediated effect) |
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Term
| What role does the AT1 receptor play? (What effects does it have?) |
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Definition
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Term
| What effects does the AT2 receptor have? |
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Definition
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Term
| ACEi have been porven in clinical trials to improve what fourthings in HF? |
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Definition
1. hemodynamics
2. clinical status
3. lessen symtpoms of HF
4. decrease mortality |
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Term
| What stages of HF may you use ACEi? |
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Definition
| Used in all stages/classes, slow progression of the disease |
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Term
What is bradykinin?
What degrades bradykinin? |
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Definition
potent vasodilator
ACE also degrades bradykinin |
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Term
| When you give an ACEi, you block the degradation of bradykinin. ...What effects are caused by the increased bradykinin levels? |
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Definition
edema of the skin (wheals)
increased coughing |
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Term
| What are the adverse effects of ACEi in the treatment of HF? |
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Definition
1. hypotension (dizziness, syncope)
2. renal insufficiency, renal perfusion pressur in people with reduced CO is maintained by the effect of ANG II to contrict the efferent arteriole
3. elimination of ANG II in maintaing the GFR |
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Term
What receptor is responsible for the adverse effects of increased ANG II?
what are the effects? |
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Definition
AT 1
vasoconstriction
myocyte apoptosis
cardiac myocyte growth
NE release
aldosterone release
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Term
| What is the predominant Ang II receptor in the vasculature? |
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Definition
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Term
| What two ARBs are approved for heart failure when an ACEi is not well tolerated? |
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Definition
| Valsartan and candesartan |
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Term
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Definition
| losartan superior to ACEi in elderly with HF |
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Term
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Definition
| ACE i was equal to or superior to AT1 receptor antagonist in all endpoints measured |
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Term
| VALIANT was the first trial to show what result? |
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Definition
| comparable efficacy of AT1 receptor antagonist and ACe i |
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Term
| What happens to aldosterone levels after long term use of ACEi? |
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Definition
They increase back to normal or elevated levels.
This is called aldosterone escape. |
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Term
I cause:
sodium retention, increasing preload
myocardial fibrosis by stimulating collagen production
inhibit uptake of NE (elevates NE in heart)
cause baroreceptor dysfunction
who am I? |
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Definition
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Term
| T/F: there is normally no adrenergic stimulation in left ventricle during restiing state. |
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Definition
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Term
| The chronic increases in sympathetic activity are caused by what four reasons? |
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Definition
1. reduction in CO
2. increased HR
3. excessive vasoconstriction
4. excessive retention of salt and water |
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Term
| Long term sympathetic stimulation... |
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Definition
further depresses ventricular function and increases the heart's demand for energy
not goooood |
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Term
| What is the normal expression of beta 1 and beta 2 in the ventricles? |
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Definition
80/20
during HF beta 2 can increase up to 40% |
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Term
| Why are second and third generation BBs effective? |
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Definition
1. reverses downregulation of beta 1
2. produces more normal cardiac performance
- increases reserve capacity
3. restores normal coupling of receptor to adenylate cyclase
4. reduces cardiac remodeling and myocardial death resulting from apoptosis
5. reverses hyper-phosphorylation of the calcium release channel in the ER (ryanodine receptor) |
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Term
| You may not use class 1 bb in HF. |
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Definition
You may not use class 1 bb in HF.
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Term
| Further description of the beneficial effects: |
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Definition
| Beta blockers reduce the adverse effects of excessive NE by blocking the receptor from NE. BB bind the receptor but do not trigger signal transduction. BB also stabilize cardiac rhythm and reduce HR. |
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Term
Name the single, third gen BB approved for HF:
it is a non-selective BB and has potent vasodilator effects due to alpha 1 antagonism...must titrate up slowly.
also reduces afterload |
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Definition
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Term
| Etanercept has recently entered phase III trials for HF treatment....how does this drug work in HF? |
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Definition
| It is a TNF- alpha receptor fusion protein, which would block the pro-inflammatory TNF-alpha (which produces a negative ionotropic effect). |
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Term
| I am a small molecule TNF-alpha inhibitor that is used to treat other disorders, but I recently show that I can increase left ventricular funtion in a controlled trial. Who am I? |
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Definition
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