Heart Failure Flashcards
Primary Cause of Heart Failure
Decreased cardiac output
Decreased Heart Rate
Decreased Force of Contraction of Heart
and Decreased Volume of Blood in Heart which decreases volume of blood ejected from the heart with each heart beat
Types of Heart Failure
Acute Heart Failure
-develops rapidly (hours/
- life threatening
- successful management by pharmacological or surgical interventions
Chronic Heart Failure
- long term condition (months/
- associated with adaptive changes in the heart
Compensatory Mechanisms to Restore Cardiac Output
In Chronic Heart Failure
Increased Sympathetic Activity
- increased heart rate
- increased force of contraction
Increased Renin Angiotensin Aldosterone System
lead to retention of water and salt ( in kidney lead to increased volume of blood returning to the heart
both lead to constriction of blood vessel
increased arterial blood pressure
increased resistance to blood flow
decreased cardiac output !
Characteristics of Chronic Heart Failure
Increased Sympathetic Activity -lead to heart rate and force of contraction of heart \+ constriction of blood vessels which lead to increased cardiac workload then lead to myocardial hypertrophy
Increased Renin Angiotensin Aldosterone System
lead to increased water and salt retention + constriction of blood vessels
which lead to
- myocardial hypertrophy
-oedema of peripheral tissues
eg swelling of legs and ankles
fluid in lungs increased shortness of breath)
Type and effect of Positive Inotropic Drugs
Positive Inotropic Drugs
- Force of Contraction of the Heart
-Cardiac Glycosides
eg digoxin
-b-Adrenoceptor Stimulants
e g dobutamine, dopamine
-Phosphodiesterase Inhibitors
e g amrinone milrinone
which three of them increased intracellular calcium concentration
-Calcium Sensitizer e g levosimendan
Name of Cardiac Glycosides and mechanism of actions
e.g. digoxin
Inhibit Na ++/K ATPase (sodium pump)
-which increased intracellular sodium concentration
- which lead to decreased Ca2 expulsion by Na +/Ca2+ exchanger
- then lead to increased intracellular calcium concentration
-facilitate parasympathetic activation
Characteristics of Digoxin
Advantages
-Anti-Arrhythmic drug
Adverse Effects Pro-Arrhythmic GI Disturbances CNS Disturbances Narrow Safety Margin
Applications NOT 1st Line Therapy Effect Opposed by increased K Effect Opposed by increased Mg 2+
Name and mechanism of actions β-Adrenoceptor Stimulants
e.g. dobutamine , dopamine
Activate b1-Adrenoceptor in the Heart
lead to the increased intracellular concentration of cyclic adenosine monophosphate (cAMP)
then lead to activate protein kinase A (PKA)
-which lead to increased calcium entry in cardiac cells
-then lead to increased intracellular calcium concentration
Characteristics of
β Adrenoceptor Stimulants
Advantages
- Fast Onset
- Short Duration of Action
Adverse Effects
- Tachyphylaxis
- Pro-Arrhythmic
- Pro-Angina
Applications
Used For
Acute Heart Failure
Names and mechanism of actions of Phosphodiesterase Inhibitors
e.g. inamrinone , milrinone
- decreased breakdown of cAMP
- which lead to increased PKA activation
- then lead to increased intracellular calcium concentration
Characteristics of Phosphodiesterase Inhibitors
Advantages
-Vasodilator Action
Adverse Effects
- GI Disturbances
- Pro-Arrhythmic
Applications
-Used For Acute Heart Failure
Choices of Positive Inotropic Drugs (Common properties)
All three has Pro-arrhythmic effects
B-adrenergic receptor stimulants and phosphodiesterase inhibitors are used for acute heart failure
Name and mechanism of actions of Calcium Sensitizers
e.g. levosimendan
Stabilize the Binding between Troponin C and Calcium
- increased the affinity of troponin C for calcium
increased sensitivity to calcium contractility WITHOUT increasing intracellular calcium concentration
Characteristics of
Levosimendan
Advantages
-Coronary and
systemic vasodilator
Available Formulations
-Intravenous
Adverse Effects
Headache
Hypotension
Name, Effect and Adverse efffect Inhibitors of
Renin
Angiotensin System
Inhibitors of
Renin Angiotensin System
Angiotensin Converting Enzyme Inhibitors
-eg captopril enalapril quinapril
Angiotensin Receptor Blockers eg losartan
Pharmacological Effects
- reduces fluid retention
lead to decreased blood volume (slightly diuretic)
which reduces oedema
- reduces vasoconstriction
which lowers peripheral vascular resistance
and then decreased cardiac workload
Adverse Effects
severe hypotension (e g in patients with fluid loss)
hyperkalemia therefore caution with K sparing diuretics
Name, effect and adverse effect of Diuretics
Increased Fluid Excretion
-decreased oedema especially in lungs
- which decreases pulmonary vascular congestion
- which increases oxygenation of blood
- lead to improve myocardial function
Loop Diuretics
eg furosemide bumetanide
Thiazide Diuretics
-eg hydrochlorothiazide, indapamide
Potassium Sparing Diuretics
-eg amiloride, spironolactone, eplerenone
Name, effect and adverse effect of Vasodilators (I)
Vasodilators (I)
Nitrovasodilators eg isosorbide dinitrate
-dilation of veins
-lead to decreased volume of blood returning to the heart
lead to decreased cardiac workload
-then lead to decreased pulmonary congestion
Hydralazine
- dilation of arterioles
- lead to decreased resistance to blood flowing from the heart
- lead to decreased cardiac workload
Isosorbide Dinitrate Hydralazine
-synergistic vascular actions which decreases myocardial hypertrophy
Name, effect and adverse effect of Vasodilators (II)
Synthetic Brain Natriuretic Peptide e g nesiritide
- activates natriuretic peptide receptors
- which activates particulate guanylyl cyclase
- then increases cyclic guanosine monophosphate (cGMP) level
- in vascular smooth muscle
lead to arteriolar and venous dilation - which decreases systemic and pulmonary vascular resistance
- in kidney collecting duct
lead to inhibit cyclic nucleotide gated non-selective cation channel
which decreases sodium reabsorption then lead to diuresis
-administered intravenously [very short half life]
therefore only used for acute heart failure
-adverse effects hypotension and risk of renal damage
Name, effect and adverse effect of B- Blockers
bisoprolol , carvedilol and metoprolol
-Reversal of Potentially Harmful increased Sympathetic Activity in Chronic Heart Failure
Decreased Force of Contraction of Heart
-further decreases cardiac output
- lead to increased risk of arrhythmia
- therefore initiated with low doses
Hence, Improve Survival in Chronic Heart Failure
Name, effect, adverse effect, and precautions of Ivabradine
Mechanism of Action
- inhibit hyperpolarization activated cyclic nucleotide gated ( channels
- lead to selectively inhibit If current in the sinoatrial node
- therefore decreases heart rate and hence decrease cardiac workload
Adverse Effects
- bradycardia, phosphenes atrial fibrillation
Precautions
contraindicated in patients with low heart rate 60 bpm) low blood pressure
90 50 mmHg) unstable/acute heart failure, severe hepatic impairment, or
concomitant use of strong cytochrome P 450 3 A 4 inhibitors
- not for women who are pregnant or breast feeding
- cautions in patients with arrhythmia or risk of arrhythmia
Effect of Sacubitril
in combination with ARB
- selectively inhibit the enzyme neprilysin (a neutral endopeptidase)
→ decreases the breakdown of vasoactive peptides
[which are upregulated in heart failure and
serve as counter-regulatory mechanisms (as opposed to the compensatory mechanisms)]
Effect Adverse effect and Precautions of Valsartan/
Sacubitril (LCZ696)
A combination of valsartan and sacubitril in a 1 1 ratio by molecule count
→a dual angiotensin receptor neprilysin inhibitor (ARNI)
→→ inhibit the actions of angiotensin II and neprilysin
Adverse Effects
- hypotension
- angioedema [due to accumulation of bradykinin and substance P]
- hyperkalemia, renal dysfunction, harm to fetus
[adverse effects of angiotensin receptor blockers]
Precautions for the Use of LCZ 696
- not to use in combination of an angiotensin-converting enzyme inhibitor
discontinue angiotensin-converting enzyme inhibitor for at least 36 hours before
valsartan/sacubitril treatment [to reduce risk of angioedema]
- Check and correct sodium and volume depletion states before valsartan/sacubitril
treatment [to minimize hypotensive effects]
