L16 Flashcards
What does the P wave represent?
Atrial depol
What does the QRS represent?
Ventricular depol
What does the T wave represent?
Ventricular repol
What does the QT interval represent?
Length of ventricular cycle
How does the sympathetic NS respond to heart failure (↓CO)?
Sympathetic
- Vasoconstriction = ↑afterload
- Na/H2O retention = ↑BV
- LV remodeling
Which substances naturally oppose vasoconstriction and Na retention to counter regulate maladaptive processes?
Natriuretic peptides
PGs
What is the difference between short and long term adaptations/compensation for ↓CO?
Short = adaptive changes Long = maladaptive
Which vasoactive peptides are released due to heart failure?
RAAS
Natiuretic peptides
ADH
Endothelins
What inflammatory mediators are released due to heart failure?
PGs
What type of HF are RAS inhibitors and BB really beneficial for?
HR w/ ↓EF
What are the 3 triggers that ↑renin release during HF?
↓Pre-glomerular BP
↓NaCl @ macula densa
↑NE from sympa at B1 receptors
What is ACE2? Same as ACE?
ACE = Angiotensin converting enzyme, AGT1 –> AGT2
ACE2 = counters adverse cardiac effects of excess AGT2
- Vasodilation
- Antiproliferative
3 ACE inhibitors
Captopril
Enalapril
Linospril
2 angiotensin receptor blockers
Losartan
Valsartan
Renin inhibitor
Aliskiren
How does AGT 2 change TPR when binding AT1 receptors? Net response?
↑vasoconstriction
↑Sympa
Net = rapid ↑BP
How does AGT2 change renal fxn when binding AT1 receptors? Net response?
↑Na reabsorption
- Directly
- Indirectly via ↑aldosterone
Net = slow ↑BP (volume expansion)
How does AGT2 change CV structure when binding AGT1 receptors? Net response?
↑proto-oncogenes ↑GF ↑Afterload ↑Wall tension Net = LV hypertrophy/remodeling
What explains part of ↓BP of ACE inhibitors?
↑Bradykinin & PGs
Turning off ACE also turns off the enzymes that inactivates bradykinin
Bradykinin fxn
Vasodilator
↑PG synthesis
Adverse effects of ↑bradykinin/PGs due to ACE inhibitors
Dry cough
Angioedema
Captopril
- Excretion
- Dosing
Renal excretion - impt for pts w/ HF
Low doses to avoid SEs
Captopril SE (usually seen at high doses)
Disrupt taste
Skin rashes
Nephropathy
Neutropenia
Enalapril & fosinopril
- Excretion
Both = longer t1/2 than captopril Enalapril = renal excretion Fosinopril = renal and bile excretion
Changes in plasma levels due to ACE inhibitors
- Renin
- AGT1
- AGT2
- Aldosterone
↓AGT2 & aldosterone
- Both downstream of ACE action
↑renin –> ↑AGT1 b/c no - FB
- Doesn’t matter b/c ↑AGT1 can’t be converted
Aldosterone fxn
↑Na & H2O reabsorption in collecting duct
K wasting
2 mineralcorticoid receptor antagonists
X aldosterone binding
Spironolactone
Eplerenone
Effects of binding AT2 receptors (not AT1)
Counter reg to AT1: Vasodilation Antiprolif Differentiation Plaque rupture
When do you see AT2 receptors ↑regulated?
Failing heart!
Natural counter reg against AGT1
Which drug is AT1 selective?
Angiotensin receptor blockers
Big deal b/c the AGT2 produced by feedback acts selectively on AT2 receptors = beneficial!
Which drug changes AT1 & AT2 receptor activity?
ACE inhibitors
↓total AGT2 so can’t work on either receptor
Plasma levels of these on ARBs
- Renin
- AGT1
- AGT2
- Aldosterone
↓Aldosterone
↑renin, AGT 1 & 2
Plasma level on renin inhibitors of Renin AGT1 AGT2 Aldosterone
↓all
What is one of the biggest shared benefits of ACE, renin inhibitors, and ARBs?
INHIBIT vascular hyperplasia
Regress existing LVH!!!
Preserve renal fxn
Shared adverse effects of ACE inhib, renin inhib, ARBs?
Hyperkalemia –> arrhythmia
Renal failure if you have renal artery stenosis
Teratogenic - don’t give to women of childbearing age
What change is significant to pts with renal artery stenosis?
Any ↓AGT2
That is what is constricting the efferent arteriole of the glomerulus to maintain GFR
What is measure to determine natriuretic peptide levels?
Cleavage product in plasma that has longer t1/2
= BNP
↑BNP = ↑HF level
Effects of natiuretic peptide
- Renal
- Vasc
- Cardiac
- SNS
Renal: ↓Na resorption
Vasc: vasodilation
Cardiac: ↑rate relaxation, antiproliferative
SNS: ↓SNS & renin release
