M3 L4: heart failure Flashcards
what is heart failure
inability of heart to pump sufficient quantities of blood to meet requirements of the tissues
causes of HF
cardiac
- CAD
- hypertension
- heart valve lesions
- cardiomyopathy (dilated, restrictive, obstructive)
extracardiac:
- ex: thyrotoxicosis - anemia
“Extra cardiac causes” means they still give the heart fatigue, even though the heart itself is okay.
types of HF
- left ventricular failure
- right ventricular failure
- biventricular failure
Can affect atriums or ventricles
Right side heart failure: right ventricle is focused on
Left side: left ventricle is focused on
manifestations of HF
- exertional
- dyspnea
- fatigue
- cough - dependent edema
- enlarged heart (cardiomegaly)
Decreased ADLs
Edema with gravity (dependent on position of patient - can be for the feet, legs, thigh, etc.)
Width of heart should be about 50% of ribcage, CHF causes heart to be huge!
nonpharmacologic treatment of HF
Slow down condition but won’t stop it - nonpharmacologic treatment
You need medications to get better
- modification of lifestyle
physical activity
- bed rest (during acute condition)
- gradual rehab program
dietary control
Bc can’t tolerate activity must be have bed rest
Avoid salt** when hypertension, even more strict with heart failure
Surgeries can help fix structural problems, or plaque buildup
- surgical treatment
- valve repair
- coronary revascularization
- cardiac transplantation
pharmacotherapy treatment of HF
- diuretics
- inhibitors of RAAS: ACEI, ARB, Aldosterone antagonists
- β blockers
- vasodilators
- positive inotropic agents: cardiac glycosides (digitalis)
Diuretics: used when notice edema
RAAS: ACE inhibitors, ARB, Aldosterone antagonists (these are diuretics or ass them to RAAS - very important in treatment of heart failure)
Vasodilators - not 1st thought, but good to consider
Cardiac glycosides: group of meds but only 1 is used right now they are positive inotropic agents
Inotropic - deals with the heart myocardial contractability - +’ve increases, -‘ve decreases
+‘ve chronotropic = tachycardia
-‘ve = bradycardia
Focus on digitalis
cardiac glycosides (digitalis)
derived from plant sources
Digoxin and Digitoxin: from the plants digitalis purpurea (foxglove) and digitalis lanata
Ouabain: from the plant strophanthus
Most famous digitalis plant: Foxglove - gives digoxin - digitoxin we don’t use as it is very toxic
Glycoside: molecule in which a sugar is bound to a non-carbohydrate moiety by a glycosidic bond
Steroids are made from cholesterol
chemical structure of digitalis
left side sugar, non-sugar right side (aglycone steroid nucleus)
sugar: determine solubility
aglycone steroid nucleus: determines pharmacological activity
Glycone is the sugar component
Non-sugar part is derived from a steroid part
Sugar and non sugar to make digitalis
Sugar determines the solubility, therefore it is soluble in water
Non-sugar is responsible for the effect of the drug “what it does”
mechanism of action of digitalis
- Na+-K+-ATPase
- Na+-Ca2+ exchanger
mechanism of action 1:
- decreased Na+-K+-ATPase -> decreased Na+-K+ pump -> increased intracellular [Na+], decreased Na+-Ca2+ exchange -> increased intracellular [Ca2+] -> INCREASED MYOCARDIAL CONTRACTILITY (+’ve intropy)
mech action 2:
- increased vagal effect on heart -> decreased SA node firing rate (-‘ve chronotropy) -> decreased conduction at AV node (-‘ve dromotropy) -> decreased HR
Na-K-ATPase: enzyme involved in exchange pump, sodium potassium exchange pump
When I stim a cell, sodium will rush inside cell, when sodium goes into cell and cell becomes excited and reaches energy potential
Concentration gradient - low to high concentration
If you want to send Na outside - it has to be against concentration gradient
And if u want to bring K inside it must go against concentration gradient
You have to actively do this by pumping it out with ATP energy through force, the pump is activated through Na and K
This would pump 3 sodium out and 2 K in
Brings things back to normal
Where is the main sodium concentration: outside the cell
Where is the main potassium concentration: inside
Na-Ca-exchanger: Changer, does not require energy. Brings Na inside, and sends Ca outside. Brings 3 sodium, and one calcium outside. Sometimes it will flip if needed by sending Na outside, and Ca inside. Cardiomyocytes are weak in contraction.
Calcium is important for contraction, to improve contraction of heart you need Ca and digitalis will do this.
Digoxin will inhibit (enzyme 1) sodium potassium enzyme - Na will stay inside because of this - concentration of Na inside increases - when too much Na inside cell this affects sodium calcium enzyme - Na cannot enter more, so (enzyme 2) it will flip to bring Na out and bringing Ca in because it notices there is too much Na
(SEE BOTH PICS ON PHONE of what was added) + 1 diagram not included
Stim of parasympathetic affect on the vagus of the heart
Vagus supplies atrium
Vagus inhibits SA node, SA node is activated tachycardia, SA node deactivated bradycardia
Chronotropic: heart rate
Dromotropic effect - conduction
Inotropic - contraction
Digoxin will improve hear contractively, and slow down heart rate
effect of digitalis
- increased myocardial contractility
- decreased heart size
- decreased venous congestion
- decreased edema
- increased renal perfusion - decreased HR
Improving myocardial contractivity and the heart gets smaller but in a good way
You want kidney to work well to get rid of unwanted materials so your body doesn’t go into heart failure
Also slows heart rate
pharmacokinetics of digoxin
half life: 40h
duration: 3 days
Digoxin takes so long in our body
If u take it early is starts working in 1-2 hrs
Half life eliminates 50% in 40 hours, it accumulates in the body bc it stays a while
More toxicity with this because it stays longer and builds up
Eliminated through kidney
Liver has very weak participation in breaking down digoxin
More side effects if you have renal disease
More toxic effect
therapeutic indications for digoxin
- congestive heart failure
- tachyarrhythmia: specifically atrial flutter or fibrillation (AF)
Digitalis is 2nd or 3rd line of treatment - not 1st line
Not preferred as #1 bc it can accumulate in body and adverse effects
Combo of CHF and AF then #1 choice is digitalis
AF - tachy (fast) arrhythmias
drug interactions w digitalis
- K+
- hyperkalemia: decreased digitalis activity (compete for Na+-K+-ATPase)
- hypokalemia: increased digitalis activity/toxicity (K+ losing diuretics: increased digitalis activity/toxicity) - Ca2+ IV: increases risk of dysrhythmia
- Quinidine: decreased renal clearance and Vd of digitalis -> increased level
- Verapamil: decreased renal excretion of digitalis -> increased level
- antibiotics: ex. erythromycin: inhibit intestinal flora that inactivate digoxin -> increase level
Digitalis = high rate of side effects
Potassium and digitalis don’t mix
Na and K compete - high levels of K, they tend to occupy the enzyme and make digitalis less effective - low levels of K, increase effect of digitalis and can lead to toxic effects (DDI type: called altered physiology)
Only one to decrease effect of digitalis: Hypokalemia: common reason is use of diuretics - thiazide diuretics, etc.
Give K to these patients - you want these levels just right.
Too much Ca = too much muscle contraction - leads to higher risk of dysrhythmia, you have to be careful if u r doing Ca intravenously and on digitalis
All increases digitalis effects:
Quinidine (anti arrhythmic drug for cardiac arrythmias - this would increase toxic effect of digoxin when mixed) and Verapamil (Ca channel blockers)
Erythromycin - inhibits what breaks down digoxin, by killing this will cause digoxin to not be inactivated which can lead to high levels of digoxin
adverse effects of digoxin
- GI
- anorexia, nausea, vomiting, diarrhea - CNS
- headache, fatigue, mental depression, confusion, hallucination, convulsions - visual disturbances
- gynecomastia
- CVS: sinus bradycardia, AV block, ventricular dysrhythmia (ex: VT)
Why GI symptoms important: early warning signs of digoxin
Yellow vision can occur - visual disturbances with digitalis
Gynecomastia: K+ sparing, aldosterone antagonists also cause this - gyne (female) mastia (mastectomy) males who develop enlarged breasts like females by using digoxin - Both have a steroid ring, will act in males like estrogen
Ventricular fibrillation is a toxic affect of digitalis
Atrial fibrillation can be treated by digitalis
digitalis toxcicity
- narrow therapeutic index
- accumulates in body
- more common
- old age
- renal impairment
- certain drug interactions - early sign
- GI sympt - dangerous sign
- VT and VF -> fatal - treatment
- stop digitalis
- digitalis antibody (digoxin immune fab [fragment antigen-binding]) - follow up by measuring plasma digoxin level
Narrow therapeutic index drugs have easier achieved toxicity levels and more chances of adverse effects, and tends to stay in body
Cardiac arrest - ventricular fibulation
How do u treat digitalis toxicity:
1. Stop digitalis, and take it away from body
If they are dependent you can’t stop it forever, give them smaller doses when you have to re give it to them
