congestive heart failure (CHF) Flashcards
what are drugs for CHF - 8 Classes
- ACE Inhibitor (Enalapril, Lisinopril)use1or 3
- ß1- Blocker (Atenolol, Metoprolol) use 2 or 4
- Ang II Receptor Blocker (ARB, Losartan)
- a/ß Adrenerg. Blocker (Carvedilol, Labetolol)
- Tailored Diuretics decrease Edema (Loop Diuretic
Furosemide + K+ Sparing: Spironolactone)
Digoxin (inhibits Na+ Pump - Na+-K+ ATPase) Narrow Therapeutic Window. - Vasodilators: Hydralazine and Nitrates.
- Dobutamine (DA agonist), Milrinone (PDEI)
what is the definition and prevalence of CHF? (cardiac heart failure)
Reduced C.O. relative to body’s needs
or at the expense of cardiac dilatation
Systolic (EF<45% normal 60%); emptying
Diastolic (preserved EF); filling (30-50%)
2% of population (10% at 80)
Common(est) cause for admission to medical wards
what are the symptoms; signs, for CHF?
Dyspnea on exertion, then at rest, orthopnea,
PND (paroxysmal nocturnal dyspnea difficulty in breathing – shortness of breath when lying flat)
Fatigue
Edema Reduced Renal function
Heart - Big on chest x-ray in systolic HF
Echocardiogram (Reduced EF; diastolic function).
what are the antecedents for CHF?
Increased Workload
- HTN (Hypertension)
- Valve (aortic stenosis, mitral regurgitation)
- Pregnancy, hyperthyroid, beri-beriDecreased Muscle
- Coronary artery disease (infarction)
- Myocarditis
- Cardiomyopathy
what is the compensatory mechanism in CHF?
To meet the demands, Heart Muscle Stretches to contract - Dilated heart increase LVEDP, increase O2 demand CO = SV x HR [SV is decrease CHF] BP = CO x TPR. In CHF very large decrease CO X increase TPR
(look at this diagram in the notes!!!!!!!)
decrease CO, decrease BP, increase SNS Act.
increase Sweating, decrease RBF,
increase Renin Release,
increase ANG II, increase ALDOST
increase TPR, increase Na+ Retention
increase Blood Volume,
Edema, increase Venous Pressure increase Work Load
increase Demand on heart increase
Preload, increase Afterload Decreased CO – Hall Mark.
how do you calculate cardiac output?
CO= Heart Rate (HR) X Stroke Volume (SV)
Normal about 5L/min
SV proportional to Preload
afterload
contractility
LVDEP – Left Ventricular End Diastolic
Pressure is a measure of Venous Return
Increase preload=increase SV
Note: Despite increase Preload, increase LVEDP, SV Elevation is Lower in Heart Failure !
what is afterload and contractility like in heart failure?
There is increased Preload, increase Afterload [increased Systemic Vascular Resistance or increased TPR with decreased SV / decreased CO in CHF. To compensate, heart muscle stretches to enhance contractility. Unable to compensate, heart quits – systemic & pulmonary congestion sets in resulting in Decreased blood supply to all organs – resulting in EDEMA & Congestive Heart Failure.
Goal: Use Drugs to decrease greatly both Preload & Afterload. We can also enhance Contractility without increasing Cardiac Energy Consumption & workload – DIGOXIN does this.
what is a good nutshell for preload and afterload and CO?
√ Heart failure can be defined as the failure of the heart to provide adequate CO in accordance with the metabolic demands of the body. Heart failure often leads to Congestion in the pulmonary circulation (left heart failure) and/or the systemic circulation (right heart failure)- called CHF.
√ The three most common precipitating causes of heart failure are: Hypertension, Coronary Artery Disease & Diabetes.
√ The determinants of CO are: HR , and Stroke Volume (SV). The determinants of SV include the Preload (proportional to end-diastolic pressure), Afterload (proportional to resistance to flow), and cardiac contractility. In CHF, the Stroke Volume is
decreased with increased preload (venous pressure) or increased afterload (arterial resistance - increased TPR).
√ The Goal of Therapy: greatly increase CO by greatly decreasing Preload, decreased Afterload, greatly increased Cardiac Contractility without Increasing Work Load.
what are the two compensatory mechanisms in heart failure and why is the preload increased in heart failure?
√ Two compensatory mechanisms in heart failure include the sympathetic nervous system (extrinsic control system) and the Frank-Starling Law of the Heart (local control system). Both increase contractile force. Sympathetic activity also accounts for some of the symptoms of heart failure including tachycardia, poor peripheral perfusion, sweating, increased renin levels. The edema associated with heart failure is due both to an increase in venous pressure and to activation of the renin-angiotensin-aldosterone system (RAAS).
√ In heart failure, the preload is increased because of incomplete emptying of the heart and afterload is increased because of elevated SNS activity and activation of the RAAS.
So goal is to REDUCE - Preload, Afterload Edema, Congestion Enlarged Heart and restore/enhance Cardiac output (CO) without increased work load on the heart.
what is the role of diuretics in CHF?
Role of Diuretics XX Rationale for combining Furosdemide-Spironolactone
Relieve Congestion – Edema First decrease Preload
Thiazides used more as Antihypertensives
Loop Diuretics: Furosemide mainly for CHF (Problem, AE: Hypovolemia, Hypokalemia)
Add Spironolactone, a K+ Sparing Diuretic, a steroid, aldosterone antagonist, Overcomes hypokalemia, blocks aldosterone action on heart remodeling & cardiac fibrosis. As an androgen antagonist, it can cause gynecomastia.
what are the drugs decreasing afterload?
ACEI, ARBs, Hydralazine, Nitrates
These are the biggies:
ACEi, ARB–> decrease Ang II effect, decrease TPR, decrease BP*
* may be limiting if SBP <80 mmHg.
Vasodilatoes: Hydralazine, Nitrates**
Hydralzine is only an arteriolar dilator
** Nitrats are Veno- and Arteriolar Dilators.
Note: ACEi, b blockers: decrease afterload, decreased preload, decrease aldosterone secretion, decrease blood volume, Na+ Retention, decrease symapathetic discharge. If ACE-I are not well tolerated, then switch to an ARB.
what increases contractility?
Digoxin, Milrinone, beta agonists
Digoxin Inhibits Na-K ATPase (Na+ pump)
- Increases [Na+]i –> increases Na-Ca exchange Increase [Ca2+]i Contractility – No O2 Consumption – No Work Load on Heart.
Causes depolarization, reduced Phase 0 slope, reduced conduction velocity, causes A-V block
Increases BP, increased Vagal tone
Drawback: Low Therapeutic Index (~2)
Nausea, Visual changes, hyperkalemia, vomiting, vagal effect A-V block Proarrhythmic.
what is cardiac contractility intiated by?
Cardiac Contractility is initiated by β1 and β2 receptor-linked adenylate cyclase activation and increased
cAMP generation that promotes L-type Ca2+ Channel opening and rapid influx of [Ca2+]e.
Influx of Ca2+ triggers more Ca2+ Release from the Sarcoplasmic Reticulum (SR) called Ca2+-
Induced Ca2+ Release (CICR). increased [Ca2+]i then goes back into the SR, pumped out, Muscle Relaxes.
Beat to beat Contraction-Relaxation is thus maintained by energy Utilization, ATP is Utilized.
While in a normal heart rapid beat to beat Contraction-Relaxation is maintained by β receptor
mediated, energy driven (ATP is utilized) Ca2+ Transient [rapid cyclical increase & fall in cytosolic
Free Ca2+ - [Ca2+]i level, Digoxin increase cardiac contractility without any Energy Utilization
by inhibiting the Na+ pump (blocks of Na+-K+ ATPase). When this Na+ Pump is inhibited,
Na+ remaining inside the cell is extruded via the Na+-Ca2+ Exchanger. [Ca2+]i level is greatly increased.
Na+ always tries to move out of the cell in exchange for K+ coming in and this Na+ Pump
enzyme is active in cardiomyocyte and it utilizes energy. When this enzyme is inhibited,
Na+ level increases in cardiomyocyte and elevated Na+ is pushed out via the bi-directional Na+-
Ca2+ exchanger so cardiomyocyte [Ca2+]i level is elevated. With increased [Ca2+]i level, CICR-induced
Contractility is enhanced at the myofibrils without any energy (ATP) Utilization. Thus,
Digoxin increases cardiac contractility without increased O2 Consumption-without increased Work Load on the Heart.
what’s the weird graph that I didn’t really understand about digoxin?
Digoxin – increases – HR, BP, SV, CO
decrease Phase 0 slope–> decreased Conduction Velocity
Shortens Refractory Period (Phase 2 and 3)
increased Phase 4 slope–> increased Automaticity, Excitability
It produces A-V block - VAGAL EFFECT- greatly decrease PAT Paroxysmal Atrial Tachycardia (PAT) - Supraventricular Tachycardia.
what else is about digoxin?
Plasma K+ and digoxin compete for Na+ Pump. So, hypokalemia aggravates Digoxin toxicity.
Verapamil, Amiodarone increase Plasma Level of digoxin by displacing its tissue binding (Drug Interaction)
Effective in overcoming reduced EF in Systolic HF. Overcomes increase Symp, RAAS TPR. Digoxin is also the 2nd choicedrug for overcoming Atrial Flutter, Atrial Fibrillation 1st choice being - b1 blocker or Verapamil.
Contraindicated: In hypokalemia, patients with A-V block or on verapamil, amiodarone Do not give digoxin in diastolic HF patients with normal EF.
Eliminated through kidney, Caution in Renal Failure.
Effective plasma Conc. 0.7 ng/ml; Toxic >1.2 ng/ml.
