01/26-27/16 Flashcards
Congestive Heart Failure: Background
- slow/progressive decline in cardiac output
- heart unable to perfuse organs
- acute decompensated heart failure
- immediate treatment
- ~5 million with CHF in USA
- chronic disease: years to develop
Compensatory mechanisms in CHF
- Increase SNS output
- Increase RAAS activity
- Increase plasma volume
- Increase heart rate
- Increase blood pressure
- Increase cardiovascular remodeling
Frank-Starling curve in CHF patients
Spiral into CHF
- Example of body making the situation worse
- Release transmitters to increase BP, enothelin, angiotensin II
- Increase afterload because constricts blood vessels. Makes heart have to work harder
- Decreased ejection fraction. Less blood out of heart because hard to push blood out
- Lots of other bad things happen from chronic NE and AT II release
Symptoms of CHF
- shortness of breath
- coughing/wheezing
- edema
- fatigue
- lack of appetite, nausea
- confusion
- tachycardia/arrhythmia
CHF patient classification
- Class I
- no symptoms
- Class II
- mild symptoms
- comfortable at rest
- Class III
- marked limitation in activity
- only comfortable at rest
- Class IV
- severe activity limitations
Stages of Heart Failure and recommended intervention
Cardiac Glycosides
- Digitoxin (Crystodigin)
- Digoxin (Lanoxin)
- isolated from digitalis species of herbaceous perennials
Cardiac Glycosides: MOA
- inhibit Na+/K+ ATPase
- Increase [Na+]i
- Decrease Ca2+/Na+ exchange
- Increase [Ca2+]i
- Increase Ca2+ uptake into ER/SR by SERCA2 transporter
- NCX activity depands upon Na+/K+ ATPase; because can’t go out of the NCX, more calcium intracellular. At the next heart beat, there is more calcium, makes a stronger contraction.
- Increase inotropy (force of contraction)
- Increase stroke volume
- Increase PSNS activity
- Decrease HR
Cardiac Glycosides: Electrical Effects
- Increase intracellular Na+ and Ca2+
- Increase resting membrane potential
- oscillatory depolarizing afterpotentials
Cardiac Glycosides: Arrhythmias
- Afterpotentials elicit action potentials in Purkinje fibers
- bigeminy: one abnormal beat per cardiac cycle
- Self-sustaining tachycardia
- ventricular fibrillation
Cardiac Glycosides: Pharmacokinetics
- 1 week for steady state levels to be reached
- serum levels: TI=2
- <0.9 ng/mL=safe
- >2 ng/mL=toxic
- use Digoxin antibody (Digibind) to find levels
- duration 36-40 h
- numerous DDI
- excreted unmetabolized in urine, unless…
- Eubacterium lentum: 10% of population
Symptoms of Cardiac Glycoside toxicity
- CNS:
- delirium, malaise, dizziness, abnormal dreams
- Visual:
- blurred vision, yellow halos
- Cardiac:
- atrial and ventricular arrhythmias, SA/AV node block
- GI:
- anorexia, nausea, vomiting, abdominal pain
- Respiratory:
- enhanced ventilatory response to hypoxia
Cardiac Glycoside: Clinical Use
- Only oral ionotropic agent recommended for CHF
- Increase quality of life/exercise tolerance
- does not treat underlying disease progression
- recommended for CHF with AFib
- DIG trial:
- 1997, ~6800 patients with Stage II-III CHF
- ACE inhibitor + placebo or digoxin
- Decrease risk of CHF mortality
- Increase risk of arrhythmia mortality
- net effect: no difference in mortalitly rates!
Beta-adrenergic receptor antagonists
- Cardioselective (Beta1-ARs)
- Metoprolol (Lopressor)
- Bisoprolol (Zebeta)
- Mixed selectivity (alpha1/beta1-ARs)
- Carvedilol (Coreg)
Beta-adrenergic receptor antagonists: MOA
- Antagonise cardiac beta1-ARs
- decrease HR, decrease CO
- decrease arrhythmias
- decrease cardiac remodeling
- Angatonize renal beta1-ARs
- decrease renin release, decrease AT II/aldosteronse
- decrease afterload, TPR
- Carvedilol: antagonize vascular alpha1-ARs
- decrease afterload, TPR
Beta-adrenergic receptor antagonists: Clinical Use in CHF
- recommended for CHF II-III
- use with ACE-inhibitor, diuretic
- increase lifespan (probably because decrease odds of arrhythmia)
Beta-adrenergic receptor antagonists: toxicity
- bradycardia
- nausea
ACE-Inhibitors
- Captopril (Capoten)
- Enalapril (Vasotec)
- Ramipril (Altace)
ACE-Inhibitors: MOA
- Inhibit ACE
- Decrease ATII production
- Decrease aldosterone/VP→decrease plasma volume
- Decrease afterload/total peripheral resistance
- Decrease CVS remodeling
ACE-Inhibitors: Clinical Use in CHF
- 1st line therapy for CHF
- Decrease CHF mortalilty and morbidity
- use with diuretics
ACE-Inhibitors: Toxicity
- severe hypotension
- cough reflex
- angioedema
- hyperkalemia
- teratogenic
Angiotensin II receptor antagonists
- Losartan (Cozaar)
- Olmesartan (Benicar)
- Telmisartan (Micardis)
Angiotensin II receptor antagonists: MOA
- inhibit ATII type 1 receptor
- type 2 work on endothelium; stimulating type 2, NO production and vasodilation; type 1 effects will win over type 2. These drugs are selective to type 1. AT-II still floating around body, but now can work on the type 2 receptors
- No effect on ATII production
- Decrease aldosterone/VP→decrease plasma volume
- Decrease afterload/total peripheral resistance
- Decrease CVS remodeling
Angiotensin II receptor antagonists: Clnical Use in CHF
- 1st line therapy for CHF
- less data available than ACE-I on CHF morbidity and mortality
- use with diuretics