Pharmacotherapy of Heart Failure Notes Flashcards
What are the two types of heart failure? What pressure is associated with each?
- Systolic failure (High pressure)
- Diastolic failure (low pressure/relaxed)
2 characteristics of Systolic Heart failure
- reduced mechanical contractility
- reduced ejection fraction
2 characteristics of Diastolic Heart failure
(HFpEF)
1. stiffening and loss of relaxtion
2. reducing filling and CO
3. EF is reduce
What is the mortality rate of heart failure?
5 year 50% mortality
MC cause of heart failure
CAD
What are the overal and subsequent 2 therapy goals of pharmacotherapy of heart failure
Overall: increase perfusion
1. Reducing symptoms and slowing progression
2. Managing acute epidsode of decompensated failure output
What are the three markers for heart failure
- HTN
2.
What type of dysfunction is MC with acute heart failure?
Systolic dysfunction
w/ reduced CO and EF
What is the normal EF?
Not in HF
> 60%
what causes diastolic dysfunction?
list 2
- hypertrophy
- stiffening of the myocardium
what does the P in HFpEF stand for
“Huff puff”
Preserved
One ventricle heart failure can lead to ___
the other ventricle failiing
Main goal of heart failure pharmacology
emphasized by Dr. B
Reestablish adequate perfusion without further straining the heart
What happens to EF in diastolic dysfunction?
May be reduced or nromal
What kind of drugs does Diastolic dysfunction not respond to?
Positive inotropic drugs
Diastole is supposed to be in relaxation
What is High Output failure? What is the cause?
Rare failure
caused by demands of body being HIGH, this increases the CO (despite being insufficient)
What conditions can cause High Outpute Failure
list 4
- hyperthyroidism
- beriberi
- anemia
- arteriovenous shunts
aka- nutritional deficients, thyroid issues, lack of blood flow
Signs and symptoms of Heart failure
list 5
- tachycardia
- decreased exercise intolerance (rapid muscular fatigue)
- SOB
- Cardiomegaly
- Peripheral and pulmonary edema (may or may not be present)
What are the 4 primary factors of Cardiac performance
- preload
- afterload
- contractility
- Heart rate
What is the preload
the stretch of the heart
What happens to preload during heart failure
- stretch of the heart increases
- preload increases, contractile force _______
what is the range of pressure of preload that results in heart failure
> 20-25 mmHg
What happens to the heart during preload (of heart failure)
2 things (not including increased preload)
- increased fiber length
- increased filling pressure increases O2 demand in the myocardium2
What causes preload to increase during heart failure?
list 2
- increased blood volume
- increase venous tone
What is the goal of salt restriction and diuretic therapy in heart failure
(think preload)
reduction of high filling pressure
what can venodilator drugs do for heart failure?
reduce preload by redistributing blood away from the chest and into the systemic sx
(nitroglycerin)
what is afterload
the resistance that the heart must pump blood against
What represents the afterload?
aortic impedance and systemic vascular resistance
Think afterload
what does decreased CO in chronic failure lead to?
a reflex increase in systemic vascular resistance
-this is mediated by increase in sympathetic outflow, catecholamines and activation of RAAS and endothelin
What is increased systemic vascular resistance mediated by
- increased sympathetic outflow
- catecholamines
- Partial from activation of RAAS
- partial from activation of endothelin
aldosterone is the
“salt whisperer”
wants salt to stay in the body
what are some catecholamines
(list 3)
- dopamine
- norepinepherin
- epinepherine
They all will do the same thing in the body
what does chronic low-output failure do to intrinsic contractility
reduces intrinsic contractility
List 3 things that happen as contractility decreases?
- reduction in the velocity of muscle shortening
- reduction in the rate of intraventricular pressure development
- reduction of the stroke output
Can a heart in heart failure still increase contractility measure in response to inotropic drugs
yes
What is the carotid sinus firing refering to?
baroreceptrors in the carotids
what is the first compensatory mechanism that tries to maintain cardiac output (when dropping)
heart rate increase through sympathetic activation of B adrenoceptors
what does failure of the heart do to the heart rate?
decrease
-stroke volume also lowers
what does tachycardia do to diastolic filling and coronary flow?
Slows/limits
-this causes stress on the heart
What type of drugs can help with tachycardia due to heart failure
bradycaric drugs
What types of drugs are used first in chronic heart failure
list 4
- diuretics
- ACE inhibitors
- B-agonists
- B-blockers
When are positive inotropic agents used for heart failure? what can it result in?
not the first or only drug
-CAN result in over therapy of heart failure pts
what releases naturetic peptides?
cardiac myocytes
What tissues do cardiac glycosides
all excitable tissues (including CNS and smooth muscle)
What is the most common site of digitalis toxicity outside of the heart? what is the second mc?
GI tract
CNS
A patient presents with GI symptoms, what medicine might they have a toxicity of?
Cardiac glycosides
(digitalis)
What is the effect of K+ and digitalis?
- hyperkalemia (reduces actions of digitalis)
- Increased cardidac automaticity (from hyperkalemia), reduces toxic effect of digitalis
what does hypokalemia do to digitalis
facilitates the enzyme inhibiting action of digitalis
What does hypercalcemia do to cardiac glycosides
Increased the risk of digitalis-induced arryhthmia
what is the etiology of cardiac glycoside poisoning
-hypokalemia (bc digitalis compounds compete with K+)
-Renal failure (decrease excretion)
-drug interaction (removes digoxin from the body)
-Dehydration
What drugs can lower the renal elimination of cardiac glycoside?
list 4
1.verapamil
2.diltiazem
3.amiodarone
4.quinidine
Symptoms of cardiac glycoside poisoning
list 7
- GI tract symptoms (n/v, diarrhea, pain, anorexia)
- visual damage
- xanthopsia (yellow tinted vision)
- photophobia
- blurry vision w yellow tints and halos
- disorientation
- palpations
ECG indication of Cardiac glycoside poisoning
List 5
-PVC
-T wave flattening
-scooped ST segment
-low QT
-high PR
-atrial tachy w av block
Abnormal lab studies in cardiac glycoside poisoning
- serum digoxin concentration (6 hrs after ingestion)
- serum electrolyte levels (hyperkalemia)
- creatinine and blood urea nitrogen (renal funciton)
Treatment of Cardiac glycoside poisoning
list 6
- anti-digoxin FAB fragments
- atropine (bradycardia)
- normalize serum K+
- magnesium
- Class 1b antiarrhythmias
- temporary cardiac pacing
Types of drugs without positve inotropic effects used in heart failure
- diuretics
- ACE inhibitors (-pril)
- Angiotensin receptor antagonists (-sartans)
- Aldosteron antagonists (-one)
- B-blockers (-lol)
vasodilators impact on HF
- reduction in preload
- reduction in afterload
What 2 drugs can reduce damaging remodeling of the heart
- hydralazine
- isosorbide dinitrate
what electrolyte can be removed to manage HF? what symptom is indicative of this treatment?
sodium
-salt removal through diuretic or restriction
-EDEMA
what diuretic is typically required to treat mild heart failure?
furosemide
(thiazide diuretic occasionally)
What does sodium loss do to potassium?
loss of potassium
hazardous if given certain drugs (digoxin)
what situation is ACE inhibitor the first line tx for?
left ventricular dysfunction but no edema
what two drug classes are first-line therapy for chronic heart failure
ACE inhibitor and Diuretic
What is the impact of ACE inhibitors in pts with heart failure
reduction of preload and afterload
-slows the progress of ventricular dilation (slows heart failure)
When are ARBS used? What symptom is associated
for patients who can’t tolerate ACE inhibitors (usually a cough)
4 types of vasodilators
- selective arteriolar dilators
- venous dilators
- drugs with non-selective vasodilating effects
If a patient has high filling pressures with dyspnea (main symptom) what type of drug should be used? Name 3 specific
venous dilators
1.isosorbide dinitrate
2.hydralazine
3.prazosin
these reduce filling pressure and relieves pulmonary congestion symptoms
If a pt has fatigue from lower left ventricular output, what type of drug should be used? Name one
Arteriolar dilators
hydralazine (increases forward CO)
Name 4 Beta Blockers that reduce HF mortality
- bisoprolol
- carvedilol
- metoprolol
- nebivolol
when are B-Blocker drugs given for patients with heart failure? why?
-tachycardiac patients
reduces tachycardia which lowers the adverse effects of high catecholamine levels on the heart (worsens HF)
When is digoxin indicated in treatment of HF?
Heart failure AND artrial fibrillation
-only when diuretics and ACE inhibitors failed
What is the slow loading dose of digoxin?
when symptoms are mild
0.125 or 0.25 mg/d
What is the rapid dose of digoxin?
0.5-0.75mg every 8 hours (x3 doses)
followed by 0.125 or 0.25mg/d
what other situations can digitalis be useful in
- atrial arrhythmias
- paroxysmal atrial and atrioventricular nodal tachycardia
- WPW AND atrial fibrillation
What is the best route of administration for treatment of acute HF
IV
what drugs are used for acute treatment of heart failure
- diuretics (furosemide)
- positive inotropic drugs (for severe hypotension) (dopamine, dobutamine)
- Vasodilators (nitroprusside, nitroglycerine)
name 2 vasodilators used to treat acute heart failure
1.nitroprusside
2.nitroglycerine
reduces afterload, improves EF
What is the MOA of Nitroglycerin
- forms NO. In smooth muscle, NO activates cGMP, which leads to dephsophorylation of MLCK–leads to smooth muscle relaxation
- reduces cardiac oxygern demand by decreasing preload, slightly reduce afterload, dilates coronary arteries (increases flow to ischemic regions)
What system do vasodilators have a larger effect on?
the venous system
Onset of Nitroglycerin
sublingual: 1-3 min
Translingual spray: ~60 minutes
Topical: 15-30 min
Transdermal: ~30 min
IV: immediate
What is the half life of nitroglycerin
~1-4 min
What are indications of Nitroglycerin
- angina pectoris
- Prevention of angina petoris, acute decompensated heart fialure (esp w acute MI)
Sublingual dosage of Nitroglycerin.
How often
0.3-0.4 mg every 5 minutes up to 3 doses
What are the CI to nitroglycerin
- hypersensitivitiy
- other nitrates (any similar drug)
- use of PDE-5 inhibitors (avanafil, sildenafil, tadalafil, vardenafil)
Side effects of nitroglycerin
list 4
- CNS (headache)
- Hypotension
- syncope
- peripheral edema
MOA of Nitroprusside
-peripheral vasodilator
-results in peripheral resistance, increased CO, decreased outload, reduced aortal and L ventricular impedance
What is the impact in the body from taking Nitroprusside
reduced peripheral resistance
increase CO
Decreased afterload
reduced aortal and L ventricular impedance
Onset of action of Nitroprusside
Hypotensive effect <2 minutes
duration of Nitroprusside
1-10 minutes
How is Nitroprusside metabolized
combines w hemoglobin to produce cyanide and cyanmethomoglobin
Indications Of Nitroprusside
Acute decompensated heart failure
acute hypertension
Dose of nitroprusside for acute hypertension
Initial: 0.3-0.5 mcg/kg/min, titrated 0.5/mcg/minute every few minutes to acheive effect
max dose: 10mcg/kg/min for max of 10 min
Max dose: 2mcg/kg/min (some people do it to avoid toxicity)
Dose/administration of nitroprusside for acute decompensated heart fialure
IV
initial 5-10mcg/minute
titrated rapidly (up to q5min)
usual dose range: 5-300mcg/min
absolute MAX 400 mcg/min
CI of nitroprusside
-tx of compensatory hypertension (aortic coarctation, arteriovenous shunting), acute HF w reduced systemic vascular resistence
adverse reactions of