Therapy of Heart Failure Flashcards
What symptoms, clinical presentation, and treatment are associated with NYHA class I?
Symptoms:
• None
Presentation:
• Low EF below 50%
Treatment:
• Ace I or ARB, ß-blocker
What symptoms, clinical presentation, and treatment are associated with NYHA class II?
Symptoms:
•on Moderate exertion
Clinical Presentation:
• Dyspnea on exertion, edema
Treatment:
• DIURETIC, Ace I or ARB, ß-blocker
What symptoms, clinical presentation, and treatment are associated with NYHA class III?
Symptoms:
• on Minimal Exertion
Clinical Presentation:
•Dyspnea, ORTHOPNEA, PND, edema
Treatment:
• DIGOXIN, diuretic, ACE I or ARB, ß-blocker, Spironolactone
What symptoms, clinical presentation, and treatment are associated with NYHA class IV?
Symptoms:
• At rest
Clinical Presentation:
• Refractory Edema
Treatment:
• Digoxin, diuretic, ACE I or ART, ß-blocker, Spironolacter + COMBINATION DIURETICS, IV VASODILATORS, TRASPLANTATION/ASSIST DEVICES
What preventative measures should be taken at all stages of heart failure?
prevent: HTN, Lipids, Smoking, Diabetes, EtOH
Which of the ACE inhibitors are NOT prodrugs?
- Captopril
* Lisinopril
What drug directly inhibits the protease activity of renin?
• Aliskiren
What general effect do the ACE inhibitors, ARBs, and renin blockers have?
Decreased Aldosterone => Natriuresis = Loss of Na+ in Urine
**Reduction in Total Peripheral Resistance (vasodilation)
What substrate besides angiotensin in acted on by ACE?
• Potential Implications?
Bradykinin - normally broken down by ACE, but it builds up with ACE I’s
• Bradykinin increases Prostaglandin Production and may contribute to Vasorelaxation
This is a good effect unless it induces angioedema
African Americans are less likely to benefit from ACE therapy. What modifications can be made to make therapy with ACE I drugs effective?
• Administer them with an ACE-I with a THIAZIDE
What are some major advantages of ACE I therapy over other HF therapies?
• Contraindications?
Benefits:
• Little Effects on Lipids and Sexual Function
Disadvantage:
• FETOTOXICITY - don’t give to pregnant or breastfeeding women or those that are expecting to conceive
What are some of the MOST common adverse effects of ACE Inibitors?
MOST COMMMON:
• 1st Dose Hypotension
• Na+ depletion
NEXT MOST COMMON: • Dry Irritating Cough • HyperKalemia • Angioedema • RENAL INSUFFICIENCY
others: proteinuria, rashes, fever, bone marrow depression, hepatotoxicity pancreatitis
If someone develops a Cough what drug could you give that acts on the same pathway to prevent this?
Angiotensin Receptor Antagonists because they don’t act on Bradykinin
What side effects are associated with ARBs?
- 1st Dose Hypotension
- Hyperkalemia
- Hepatic Dysfunction
- FETOTOXICITY
**Olmesartan - can cause spruelike enteropathy (chronic nausea and diarrhea)
What are the side effects of the Renin Inhibitors?
•Drug Interactions?
- 1st dose Hypotension
- Hyperkalemia
- Angioedema
- Fetotoxicity
Drug-Drug Interactions:
• p-glycoprotein inhibitor so don’t give with Erythromcin or Amiodarone (or other p-gp inhibitors)
What adverse effect is common to Renin inhibitors are ACE inhibitors, but not to ARBs?
ANGIOEDEMA: this is because both ultimately prevent ACE from breaking down bradykinin
What adverse effects are seen with ARBs, ACE I, and Renin Inhibitors?
- 1st Dose Hypotension
- Hyperkaleia
- Fetotoxicity
What 3 things happen with Angiotensin II is allowed to bind its receptor?
- Vasoconstriction => inc. BP
- Aldosterone Production => Na+/H2O retention => inc. BP
- Cell Growth => Left Ventricular Hypertrophy, Vascular Remodeling
T or F: Angiotensin II causes Cardiac and Vascular Fibrosis and Atheroslcerosis.
True
In the treatment of heart failure are ARBs or ACE I’s better?
- ACE I’s are considered better
- possible because of Bradykinin buildup causing Vasodilation
Note: there is no added benefit of combining ACE I’s with ARBs
T or F: Beta blockers used to be contraindicated in CHF because we didn’t want to DECREASE inotropy of an already defective heart.
True
Why are Beta Blockers now inidicated in CHF management?
Blocking NE and E from binding is advantageous b/c these cause:
•Arrhythmias
• Myocardial O2 consumption => ischemia
• Myocyte apoptosis => Fibrosis of heart
Why is it so important that Beta blockers prevent arrhythmias?
• Arrhythmias are the leading cause of death in class II and III heart failure
Differentiate the short term and long term effects of beta blockers in CHF patients?
Short Term:
• Lower CO and BP
Long Term:
• Increased CO and Decreased Left Ventricular End Diastolic Pressure
This means patients may experience worsening symptoms before things get better
What 3 general effects do beta blockers have on the receptor pathways in myocytes?
- Reversed Desensitization (caused by persistent NE/E signaling)
- Increases Receptor Number
- Restores Fast Signaling Modes (contractility) over slow signaling modes (gene expression)
What contraindications are there for giving a beta blocker in heart failure?
- Heart Block
- Bradycardia
- DECOMPENSATED CHF (i.e. if they need IV inotropes like dobutamine to stay alive)
- Volume overload
What Beta blockers are used in CHF?
• Metoprolol
• Carvedilol
• Bisoprolol
*Nebivolol - used in CHF in Europe
*****What are the guidelines for CHF managment by stage in ACC/AHA? What NYHA classes do these fit into?
Stage A - At Risk (NO SYMPTOMS):
• Eat Better, Stop Smoking, Manage Diabetes/HTN
• ACE I, ARBs
Stage B - NYHA I (NO SYMPTOMS - Low E.F.):
• Stage A + Beta Blockers
Stage C - NYHA II/III (SYMPTOMS w/ EXERTION):
• Stage B + Diuretic/Digoxin/Spironolactone
Stage D - NYHA IV (SYMPTOMS at REST):
• IV Inotropes/Transplant
T or F: Measuring serum levels of digoxin is useful for meeting a set dose for all CHF patients
False, there is no set dose - serum measurements are useful only for meeting the dose that has been adjust for a particular CHF patient
What is the MOA of DIGOXIN?
DIGOXIN
• Blocks the Na+/K+ pump causing INCREASED INTRACELLULAR sodium. This triggers increased Ca2+ influx during the depolarized state and decreased Ca2+ efflux during the
What is the effect of Digoxin on the pressure volume curve?
• Shifts the Curve up and to the left
Digoxin
• administration
• % absorption (per method)
• Half-life
Administration/Absorption:
• Tablet (55-60% abs.) or Capsule (100% abs.)
Half-life = 36 hours
T or F: Digoxin plasma concentrations correlate to therapeutic effect
Truish - might contribute to therapeutic effect in a particular patient but not across patients
What Adverse effects are seen with Digoxin toxicity?
•why is it so hard to manage these effects?
DIGOXIN has a VERY narrow therapeutic window so seeing effects of drug toxicity probably aren’t uncommon.
- Atrial and Ventricular Arrhythmias
- BLURRING/YELLOW-GREEN HALO IN VISION
- headach, fatigue, drowsiness, confusion, seizures
In the case of SEVERE digoxin toxicity what drug can you use? MOA?
Digibind = antibody used to neutralize digoxin
***Really only used in life-threatening Situations
Mutiple drug-drug interactions is a major drawback of digoxin. Name a few drugs that are likely to cause adverse effects?
- NON-K+ sparing Diuretics - may increase potential for arrhythmias
- Verapamil cause cause Slowing of HR and digoxin tox.
- Amiodarone - inc. digoxin by decreasing elmination
- Quinidine - Decreases Digoxin Elimination
Who benefits the most from digoxin therapy?
Patients with:
• Ejection Fraction below 0.25
• Cardiac Enlargement
• NYHA class III, IV
What effect do Diuretics have on the survival and prognosis of CHF patients?
• what are they given for?
• possible exceptions?
- NO effect on survival or prognosis in CHF patients on ACE I’s and Beta Blockers changes these factors
- DIURETICS are ONLY given to manage the CONGESTIVE EFFECTS (like pulmonary congestion)
Exceptions would be Spironolactone/eplerenone because they have effects on Aldosterone too, but these effects are not linked to the diuretic actions of these drugs
What are the effects of diuretics on preload and cardiac output?
• Diuretics - Decrease Preload (overall less fluid volume), but have NO effect on Afterload (this is because Afterload is affected by pressure in the arterial end which has more to do with vasodilation?)
What are the 4 potassium sparing diuretics?
• which are used in CHF?
• What are some loop diuretics?
Used in CHF = the aldosterone antagonists:
•Spironolactone
• Eplerenone
since aldosterone is toxic to the heart this effect is important
Loop Diuretics:
• Furosemide
• Bumetanide
T or F: combination of diuretics is not a good medical practice.
False, combination of diuretics is commonly used in treatment of CHF
What combinations are typically used?
- Loop Diuretic plus Meolozone (not K+ sparing) or
* Loop Diuretic plus Spironolactone
What are some adverse effects and possible drug-drug interactions that may result from diuretics?
- Problems associated with XS fluid and Electrolyte loss including hypotension
- OTOTOXICITY - tinnitus, hearing loss (loop diuretics)
What do ACE I’s, ARB’s and Spironolactone have in common?
• what does this mean about ACE I’s and ARB’s?
- They inhibit the release of Aldosterone**
- Aldosterone has a mitogenic and fibrinogenic effect on the heart*
- aldosterone is important in both Na+ and H2O retention, this means ACE I’s have somewhat of a Diuretic Effect
What is the benefit of vasodilation in CHF?
•Main Vasodilator used in CHF?
• Venous or Arterial action?
• Reduced AFTERLOAD => increased ventricular emptying
- HYDRALAZINE - acts on arterial side of things
- Nitrates - act both on veins and arteries but are usually given IV
To have effects on preload and afterload the vasodilator must dilate both veins and arteries
T or F: decreasing preload is a good thing in CHF
True, we don’t want to the heart to work harder so decreasing preload will decrease frank starling mechanism so that heart won’t try to overwork
***Nitrates - main vasodilator useful in reducing preload
Hyralazine:
• Adverse Effects
• Toxicity
Adverse Effects:
• Stimulate RAAS (so give with ACE I) - can stimulate peripheral edema, circulatory congestion
Toxicity:
• NAUSEA, ANOREXIA = frequent
• Drug-Induced Lupus
• Exacerabate Angina (by reflex tachycardia - so give witha Beta blocker)
What nitrate is commonly given IV in CHF?
• Nitroprusside (reduces preload and afterload)
What drugs are only given as short-term therapy in CHF? MOA?
• Administration?
Dobutamine, Milrinone, Nitrates, Nseritide
Nitrates - Veno/Arterio dilation
Dobutamine - acts to to agonize BETA-1 primarily and Alpha-1 (racemic angonist/antagonist) to VASODILATE and increase IONOTROPY
Milrinone - INHIBITS phosphodiesterase so that cAMP stays active and you get increased effects of Beta Stimulation
Nesiritide - B-type natriuretic peptide
BOTH drugs are given IV and are only given in an EMERGENCY situations
What phosphodiesterase inhibitor would you give to someone with Stage IV CHF?
Milrinone
What are the effects of giving the 4 end-stage drugs?
•specify by drug.
Nitrates - Decreased preload (red. venous pressure) Decrease Afterload (red. arteriole pressure)
Dobutamine - Stimuation of Inotropy, Chronotropy => increased CARDIAC OUTPUT (shorterm)
Milrinone - increased cAMP enhances Sympathetic stimulation (inc. CO)
Nesiritide - Reduced blood volume and vasodilation- Decreased PRELOAD and AFTERLOAD
What are the general effects of (A and B) Natriuretic Peptides? MOA?
• when is Nesiritide used?
Induce Peeing out of Sodium (as the name implies)
• binds to BNP receptor in smooth muscle and causes vasodilation via cGMP
- Increased GFR and reduced Na+ reabsorption
- Suppressed RAAS
SAME EFFECTS AS NITROGLYCERINE BUT LONGER ACTINGONLY GIVE AFTER NITROGLYCERINE HAS FAILED***
