Heart Failure Drugs Flashcards
Heart Failure Defined and symptoms
HF:
- when CO is inadequate to provide O2 needed by the body
Symptoms:
- Tachycardia, decreased exercise tolerance, peripheral/pulmonary edema, cardiomegaly
Risk factors for HF
Hypertension CAD MI Diabetes Family History Use of Cardiotoxins Obesity
HFrEF vs HFpEF
Systolic HF (contraction problem)
Diastolic HF (filling problem) - more difficult to treat
Pathophysiology of HF
CHF:
abnormal increases in blood volume and interstitial fluid.
- LHF = dyspnea from pulmonary congestion
- RHF = peripheral edema
Role of Physiological Compensation in HF
The decrease in CO causes the SNS and RAAS to activate which increases all factors that will exacerbate heart failure
- by increasing force, preload, after load, and remodeling
Preload
force of contraction depends on how far the myocardial cells are stretched. (increasing preload will increase contractility)
** this has a limit
HF- preload is beyond stretching limits and thus increase in preload causes a decrease in contractility
Afterload
Force against which ventricles must act
- based on vascular resistance
Contractility
Force of cardiac muscle contraction is directly related to calcium levels
Sources: Voltage sensitive calcium channels, Na+/Ca2+ exchanger, and SR
Removal: Na+/Ca2+ exchanger, Reuptake into the SR
Therapeutic Strategies for HF
HF is a progressive disease - only cure is transplant
- treatment is directed towards:
1) reducing symptoms and slowing progression
2) managing acute episodes
Chronic HF therapeutic Strategies
Light aerobic exercise Low dietary sodium Smoking cessation Decreasing weight Fluid restriction Treat comorbid conditions Use: ACEI, diuretics, beta blockers, and Inotropic agents ** DO NOT USE: NSAIDS, Ca2+ channel blockers, and alcohol
Drugs to Treat HFrEF (systolic)
Diuretics Spironolactone (K-sparring: aldosterone antagonist) ACEI/ARBs Direct vasodilators Beta blockers Inotropic agents
Drugs to Treat HFpEF (diastolic)
Diuretics (be careful with reducing SV to much)
ACEI/ARBs
beta-blockers
Calcium channel Antagonist
AHA classification of HF
Stage 1: high risk for developing HF
- HTN, DM, CAD, Family history
Stage 2: Asymptomatic HF
- previous MI, LV dysfunction, Valvular heart disease
Stage 3: Symptomatic HF
- Structural heart disease. dyspnea and fatigue, impaired exercise tolerance
Stage 4: Refractory End Stage HF
- Marked symptoms at rest despite maximal medical therapy
NYHA classification of HF
Class I: No symptoms with ordinary physical activity
Class II: Ordinary physical activity somewhat limited by dyspnea (e.g climbing 2 flights of stairs)
Class III: Exercise is limited by dyspnea with moderate workload (e.g climbing 1 flight of stairs)
Class IV: Dyspnea at rest with little exertion
Recommended therapy for CHF
Diuretics. beta blocker, ACEI
Diuretics
Relieve pulmonary congestion and peripheral edema
reduces symptoms of volume overload
decrease plasma volume –> decreases VR –> decreases cardiac workload and O2 demand
Also decreases after load (reducing plasma volume and decreasing BP)
Clinical App. Diuretics
No evidence of mortality benefit alone
Thiazide infective with congestive symptoms
Loop: more effective (if edema is present)
ACEI
Agents of choice for HF
- Decrease vascular resistance and BP –> Increase CO by decreasing afterload
- decrease in Na+ and H2O retention (dec. preload)
- decrease in long term remodeling of the heart
Clinical App. ACEI
Recommended:
- Symptomatic HF
- Asymptomatic patients with Decrease LFEF or history of MI
Suggested:
- patients at high risk of HF
AE of ACEI
Hypotension Dry cough hyperkalemia angioedema acute renal failure (bilateral renal artery stenosis) Teratpgenic
ARBS
Potent competitive antagonist of angiotensin II type I receptor (AT1 receptor)
do not produce dry cough
substitute for patients that can not take ACEI
AE: similar to ACEI and also teratogenic
Direct Vasodilators
Hydralazine + Isosrbide dinitrate
- vasodilation –> decrease preload
- arterial dilation –> decreases PVR and afterload
(hydralazine - arterioles and nitrates- venules)
Clinical app. Direct Vasoldilators
Patients who can not take ACEI or ARB
or
In African Americans with advanced stage HF (as adjunct)
Direct vasodilators AE
Headache, dizziness. tachycardia. peripheral neuritis, and lupus like syndrome
Contraindicated: Sildenafil (severe hypotension)
Beta Blockers
studies shown some reverse of Cardiac remodeling
- Decrease HR and contractility and inhibit renin release
- prevent deleterious effects of NE on cardiac muscle fibers (decrease remodeling)
- can get initial exacerbation of symptoms (titrate the dose up)
Clinical App. Beta blockers
recommended in addition with ACEI/ARB in patients with:
- symptomatic HF
- asymptomatic HF with decrease LVEF
- use cautiously in decompensated HF or cardiogenic shock (can not take the initial exacerbated symptoms)
Spironolactone
Patients with advanced Heart Disease have elevated aldosterone levels
MOA: aldosterone antagonism - prevents Na+ retention, myocardial hypertrophy, and hypokalemia
Clinical App. and AE of spironolactone
CA:
- Plus ACEI are shown to decrease morbidity and mortality
AE:
- Hyperkalemia
- GI disturbances
- CNS effects
- Endocrine abnormalities
Inotropic Agents
digoxin
- cardiac glycoside
- derivative from foxglove plant
- widely used treatment in HF
- Digoxin can decrease the symptoms of heart failure, increase exercise tolerance and decrease rate of hospitalization, but DOES NOT increase survival
Digoxin disadvantages
Narrow therapeutic margin
unfavorable and complicated PK
Drug sensitivity varies between patients and with in therapy
sever and lethal side effects
Digoxin MOA
Positive Iontropic:
increases cytosolic calcium by blocking Na+/K+ ATPase
** if extensively inhibited –> dysrhythmias
Negative Chronotropic: (dec HR)
- enhances vagal tone
Digoxin PK
Very potent (narrow TW) Widely distributed (including CNS) half life: 36-40 hours Large Vd (loading dose required)
digoxin AE
cardiac: arrhythmias, (slowing of AV conduction)
GI: anorexia and N/V
CNS: headache, fatigue, confusion, blurred vision, yellow-green color perception, and halos on dark objects
Precipitating factors of digoxin toxicity
- Hypokalemia
- Overdose
- hypomagnesemia or hypercalemia
- hyperthyreosis
- abnormal renal function
- respiratory disease
- acid-base imbalance
- drugs causing digoxin displacement from tissue:
- Quinidine, verapamil, and amiodarone
Treatment of digoxin toxicity
withdraw drug
monitor plasma levels of digoxin and K+
adjust electrolytes
if Ventricular tachyarrhythmia: lidocaine or magnesium
Sever digoxin toxicity:
- bradyarrthythmias, suppressed automaticity –> temp cardiac pacemaker
- treat with digitalis antibodies (digoxine immune fab, digibind)
Digoxin Contraindications
patients Right side HF
presence of uncontrolled HTN
presence of bradyarrhythmias
non-responders or intolerant patients
Treatment of HFpEF (diastolic)
Diuretics: treat pulmonary edema, but caution because of reduction in SV (not wanted in diastolic HF)
ACEI/ARB: same benefits with systolic HF
Calcium Channel blockers: Decrease inotropic which increase relaxation time and increase filling
Beta-blockers: Similar to Calcium channel blockers
Inotropic Agents used in treatment if Acute HF
PDE III inhibitors
Dopamine
Dobutamine
Glucagon
PDE III inhibitors
Inamrinone
Milrinone
inhibits myocardial cAMP PDE activity thus increases cAMP levels (positive inotropic effect and increase CO)
possess systemic and pulmonary vasodilator effects (reduces preload and after load)
shown slightly to increase AV conduction
Short term therapy
Dopamine
Stimulates both adrenergic and dopaminergic receptors
(dose dependent)
- Higher doses: affects both dopaminergic and b1 (produces cardiac stimulation- b1 as well as renal vasodilation- d1)
Dobutamine
administered as a racemic mixture
- (-) isomer is a1 receptor agonist and weak b1 agonist
- (+) isomer is an a2 antagonist and a potent b1 agonist and a mild b2 agonist
- therapeutic levels stimulates b1 receptors most
- used to increase CO in acute management
Glucagon
Stimulates Adenylyl cyclase to produce cAMP (binds to GPCR) leading to potent inotropic and chronotropic effects
- produces similar effects of beta agonist but without using beta receptors
- Used for cardiac stimulation in beta blocker overdose
