L 54 Flashcards
What are the 3 components of the cardiovascular function
The pump
The blood volume
The blood pressure
Heart failure because of ?
abnormality of the heart muscles
What is heart failure?
Inability of the heart to pump enough blood to meet the needs of the body, resulting in low cardiac output.
What changes may occur during HF ? (immediate)
Structural and functional changes
that impair the ability of the ventricle to fill and eject blood.
What are the Primary causes of HF
Long standing HTN, MI
Determinants of cardiac output
CO = HR x SV
How is HR controlled?
By SNS and simulation of B adrenergic receptors
How is SV regulated?
It is a function of preload, afterload and contractility
There are many compensatory mechanisms that try to maintain cardiac output in a failing heart such as: x3 + examples
- SNS (tachycardia and inc contractility, vasoconstriction)
- Neurohormonal (ventricular hypertrophy/remodelling)
- RAA system (inc preload via H2O and Na+ retention, vasoconstriction)
What are the consequences of these compensatory mechanisms?
They paradoxically lead to cardiac damage, and pathological remodelling, therefore producing symptoms experienced by patients.
What are the consequences of the following mechanisms?
- Tachycardia: increased oxygen demand - worsens ischaemia
- Ventricular hypertrophy/remodelling: structural changes increases oxygen demand, causing myocyte cell death.
- Increased preload: oedema and congestion
- Increased contractility: increased oxygen demand
- Vasoconstriction: decreased CO, activation of further compensatory mechanisms
What drug classes target the following?
- Tachycardia: B-blockers
- Ventricular hypertrophy/remodelling: ARB, ACEI, spironolactone
- Increased preload: Sacubitril, spironolactone, diuretics, ARB, ACEI
- Increased contractility: B blocker, digoxin
- Vasoconstriction: ARB, ACEI, sacubitril
Examples of 3x B blockers used in HF
Metoprolol, bisoprolol, carvedilol
… diuretics have no role in HF but a role in HTN, and … diuretics have no role in … but a role in HF.
Thiazide diuretics have no role in HF but a role in HTN
Loop diuretics have no role in HTN but have a role in HF.
In a heart attack, we use …/… to stop the heart from thickening and remodelling.
In a heart attack, we use ACEI/ARBs to stop the heart from thickening and remodelling.
Giving small doses of … is also pertinent so you don’t shut down the heart.
The purpose of this drug is to slow down the heart and protect it from itself.
Giving small doses of B blockers is also pertinent so you don’t shut down the heart. The purpose of this drug is to slow down the heart and protect it from itself.
What 2 B blockers have a greater affinity for B1?
What 2 B blockers are “non-selective”?
What is the importance of this?
Metoprolol and bisoprolol have a greater affinity for B1
Propanolol and carvedilol are non-selective for alpha receptors.
Want a selective B blocker, so that it helps to vasodilate and nothing else. Can have a non-selective alpha inhibitor.
Rank the following in terms of highest to lowest lipophilicity (and therefore CNS penetration): metoprolol, bisoprolol, propranolol
What is a notable side effect of propranolol?
Which drug doesn’t affect diabetic/lipid control? (may not be from this list)
Propranolol > metoprolol > bisoprolol (low)
Propranolol = sleep disturbances
Carvedilol = limited impact on diabeties/lipid control.
Give an example of a drug with intrinsic sympathomimetic activity.
Is this desirable in HF?
Pindolol - has partial B agonist effects
This is not desirable in HF as it causes vasoconstrictinon.
How is furosemide PRN?
So patient can decide when they are retaining fluid via weight monitoring and then take the diuretic.
Must use ARBs/ACEIs at … doses in HF
Why?
Must use ARBs/ACEI at low doses in HF as they can cause AKI in patients with low renal perfusion when first used aggressively.
Example of a loop diuretic (x1)
Furosemide
3 drug examples in HF that don’t have classes
Spironolactone, sacubitril, digoxin
NOTE: sacubitril + valsartan = Entresto aka ARNI
MoA of ARB and ACEI in HF x3
- Dampens RAAS and decreases ventricular hypertrophy and remodelling
- Decreases systemic vascular resistance, therefore diastolic and systolic BP
- Increases renal BF
Clinical notes about ACEI and ARB treatments !!!!!
- Used for…
- Notes about dosing…
Used for treatment of hypertension, CVD, HF, and diabetic nephropathy
HF patients often have low renal perfusion, so aggressive ACEI and ARB use can cause AKI. Therefore need to start at low doses and titrate up
MoA of B-blockers in HF x3
B1 blockers competitively inhibit the influence of SNS at b1-adrenergic receptors.
- Therefore they decrease HR and O2 demand, and also decrease contractility.
- They also reduce ventricular mass and improve ventricular shape.
- They slowly exhibit anti-arrhythmic effects, slow or reverse ventricular remodelling.
Benefits vs risks of B-blockers
The benefits of inhibiting the SNS outweigh any acute negative inotropic (contractility) effects.
Clinical notes about B-blocker dosing
Start with low doses and slowly titrate to target doses over weeks to months.
MoA of diuretics in HF
- Relieve acute congestion and oedema symptoms
- Used chronically to maintain euvolemia
(Increase urine flow rate and Na+ excretion (therefor water too), reduced ECF)
Euvolemia
State of normal body fluid volume
Diuretics also alter the renal handling of other ions e.g x6
K+, H+, Ca2+, Mg2+, Cl-, HCO3
Patients with CKD and HF will end up with … doses of furosemide
Large doses of furosemide
When are diuretics indicated in HF?
If a patient becomes overloaded with fluid
Loop diuretics MoA
Max effect is ….
Why?
Inhibit Na/K/2Cl cotransporter in the thick ascending loop of henle.
Max effect = 20-25% because by the time the filtrate reaches the TA loop, 75% of filtered Na+ has been reabsorbed.
There is a … … in diuretic effect with worsening renal function.
This is because …..
Therefore loop diuretics require…
There is a gradual decline in diuretic effect with worsening renal function.
This is because the amount of drug reaching the renal tubule is reduced
Therefore loop diuretics require larger doses in CKD (e.g 500mg+)
In patients with CKD, … and … can exacerbate HF
In patients with HF, … can cause renal impairment
In patients with CKD, hypertension and volume expansion can exacerbate HF.
In patients with HF, reduced renal perfusion can cause renal impairment.
MoA spironolactone
Competitively inhibits binding of aldosterone to mineralocorticoid receptor to decrease Na+ and water reabsorption
What kind of doses of spironolactone are used in HF?
What can spironolactone cause? What 2x drug classes also do this?
Low doses in HF, 25-50mg OD
Spironolactone, ACEI and ARBs can cause HYPERkalaemia
What is the point of spironolactone in heart failure?
ACEI don’t suppress chronic aldosterone release and production, therefore they are used to inhibit aldosterone.
Neprilysin inhibitor + ARB MoA
Name of product
Normally: Neprilysin beaks down the natural natriuretic peptide (NP), which stimulate the excretion of Na+ by the kidneys.
Sacubitril inhibits neprilysin, increasing the circulating NP to increase Na+ excretion by kidneys.
Name: Entresto (sacubitril + valsartan)
What is sacubirtil in combination with?
Why?
Sacubitril also increases ATII, therefore is in combination with ARB to decrease this.
What does an increase in NP do?
An increase in NP promotes natriuresis, diuresis and vasodilation.
Digoxin is derived from …
What effects does it have?
What is the therapeutic range like?
Good evidence?
Derived from the foxglove plant
Effects:
- treats oedema
- Has a positive inotropic (contractility) effect via binding to Na/K pump.
Narrow therapeutic range
Evidence base for LT use in HF is not robust.
A failing heart is unable to … resulting in low …
Compensatory mechanisms help to maintain … but actually lead to …, … and ….
A failing heart is unable to pump enough blood, resulting in low CO
Compensatory mechanisms help to maintain cardiac output but actually led to cardiac damage, pathological remodelling, and produce many symptoms experienced by patients (oedema, tachycardia etc)
Drug therapy is aimed at... The main drug targets: 1) ... (drug classes to target this: ) 2) ... (drug classes to target this: ) 3) ... (drug classes to target this: )
Drug therapy is aimed at controlling the compensatory mechanisms. The main drug targets: 1) RAAS (ACEI, ARBs, spironolactone) 2) SNS (b-blockers 3) Oedema + symptoms (diuretics)
