Drugs for heart failure Flashcards
most common reason for hospitalization
heart failure
-in those over 65
types of CHF
- diastolic (can’t relax heart)
- systolic (can’t contract, or weak contraction)
symptoms seen in both types of CHF
- dyspnea
- fatigue
- palpitations
diastolic pathology
- increased left ventricular diastolic pressure with increase interstitial collagen
- low ATP
- increased Ca (cause of trouble of cant relax)
- pulmonary HTN: left atrium enlarged and pulmonary edema
- ventricles may not be enlarged
- some cardiac remodeling
what isn’t tolerated well with diastolic pathology
tachycardia
systolic pathology
Cardiac remodeling:
- decrease number of cells, giants cells,
- decrease capillary density,
- decrease mito,
- decreased rate contraction due fetal actin and myosin
- increase fibroblast
what causes increased gene expression in systolic HF
exposure to excessive NE, angio II, aldosterone and pro-Inflammatory cytokines, possibly endothelin, vasopressin
what does digitalis glycosides do for CHF?
improve function of systolic HF
-mild positive inotropes (heart can’ handle strong ones)
what is used to increase CO in HF
-digoxin
“dobutamine holiday” (beta-1 agonist): positive inotrope, used a pressor agent. Causes increase in force without increase in HR. Very short half life, a few seconds
what is given to relieve edema
-diuretics (furosemide, strong diuretic)
-spironolactone (aldosterone antagonist)
(*wound healing inhibited and circulation is inhibited by Pulmonary edema)
what is given to decrease angio II
- improve quality of life
- ACE-I
- ARB’s if cough severe
- decrease preload and decrease afterload
what is given to decrease in PR
- isosorbide dinitrate (has tolerance)
- hydralazine (causes strong reflex tachycardia so must use with BB)
- unload stressed heart
- decrease mortality
what is given to decrease HR
- beta blockers can decrease mortality and improve life quality
- low starting dose
- carvedilol especially good
what does carvedilol do
- blocks beta1/2 and alpha 1
- has antioxidant effect
- decreases remodeling
treatments to increase survival in CHF
- spironolactone
- ACEI-I
- vasodilators
- beta-blockers
MOA of digoxin
- inhibits Na/K/ATPase in plasma membrane of myocyte and cell Na accumulates
- decrease Na gradient across membrane
- Na gradient drives ca extrusion during repolarization-> reduced Na gradient leads to less Ca- extrusion- by Na/Ca exchanger
digoxin causes
CA ACCUMULATION IN CELL
vagal effect of digitalis glycosides
- action of brain stem
- strong cardiac slowing
- also some direct slowing of conduction in heart due to partial depolarization
- glycosides may still be used in atrial tachycardias when other drugs don’t work.
digoxin usage
- oral absorption ~ 70%
- does get in brainstem to cause vagal response
- plasma half life= 36 hours
- 80% secreted unchanged in urine
toxicity of cardiac glycosides
- low TI (~2%)
- therapeutic blood level 1.5 ng/ml
three common symptoms of toxicity of cardiac glycosides
- anorexia, nausea
- arrhythmias
- neurological: headache, drowsiness, confusion
- green, yellow vision
- also gynecomastia and increase blood coagulation
factors that influence digoxin toxicity
- diuretics: increase K loss and increase toxicity
- antidiarrheals and Al-containing antacids (Rolaids) bind to glycosides and inhibit absorption
- digoxin 25% bound to plasma protein, may be displaced by other drugs (thyroid hormones)
how does loss in K lead to digoxin toxicity?
low potassium increased glycoside binding to ATPase
how is cardiac toxicity treated?
- KCL when K low
- antiarrythmic drugs
- atropine for excess vagal activity
- digoxin antibody: onset 30 min, most patients recover completely
duration of digoxin therapy
- long term for most patients
- temporary after heart attack
drugs for diastolic HF
- first line: BB, slow HR
- some CCB’s can decrease ventricular stiffness
- verapamil: decrease HR - ACE-I: prevent remodeling and lower BP (maybe)
- diuretics: hypotension can result
what is taken for dyspnea
nesiritde
- IV (not available in oral form)
- h-l: 18 mins
- causes vasodilation, natriuresis relieves edema
what does nesiritde work on?
GPCR to increase cGMP and NO
-known as BNP (made by recombinant DNA technology)
another positive inotrope for HF
milrinone
- caffeine analog
- short term use in those who don’t respond to digoxin
what does milrinone inhibit?
inhibits PDE-3: specific for heart and blood vessels
-good TI
side effects of milrinone
fever
-some hepatotoxicity
