Pharmacological Treatment of Cardiac Failure Flashcards
Left Ventricular Systolic Dysfunction (LVSD) =
Heart failure with reduced ejection fraction (HFrEF)
Aims for treatment
- Relieve symptoms
- Improve exercise tolerance
- Reduce incidence of acute exacerbations
- Reduce mortality
LVSD strategies fro treatment
- ↑ cardiac contrac$lity
- ↓ preload and/or a’erload in order to ↓ cardiac work demand
- By relaxing vascular smooth muscle
- By reducing blood volume
- Inhibit the Renin-Angiotensin-Aldosterone-System (RAAS)
- Prevent inappropriate ↑ in heart rate
- Mobilise the oedematous fluids
non-pharmalogical treatment of LVSD
- Lifestyle factors – as per all CVD conditions, remember mental health factors
- “Device therapy”
• Pacing
• Cardiac Resynchronisation Therapy
• Implantable Cardiac Defibrillators
• Coronary revascularisation
• Heart transplant
Main Drugs Used in chronic Heart Failure (HFrEF)
THINK ABBA Waterloo
- loop diuretics
- ACE inhibitors
- angiotensin II receptor blockers
- beta-blockers
- aldosterone receptor antagonists
step 1 in treatment of chronic heart failure
THINK DAB
(Diuretics if they are experiencing fluid retention)
A = ace inhibitors or ARB)
B = Beta Blocker
Waterloo = diuretics sometimes
Kidney function modifiers in HF
Increase excretion of sodium and water
two steps in the process which increases the excretion of sodium and water in HF
Loop diuretics (step 1) - furosemide, bumetanide Aldosterone receptor antagonists (step 2) - spironolactone
PCT = Proximal convoluted tubule TAL = Thick ascending loop DT = Distal tubule CT = Collecting tubule
Patient self-management with education
- daily weights – if varies in either direction, alter dose
- Symptom review – breathlessness, peripheral oedema
- Thirst level, dizziness, “washed out”
Loop Diuretics (e.g. furosemide, bumetanide) common side-effects
- Electrolyte disturbances –low K, Na, Mg, Ca • Hypotension
- Renal impairment – measure eGFR
- Hypovolaemia!
- Nocturia if taken too late in day (troublesome)
- Acute gout common with high doses
Renin Angiotensin System Inhibitors
- Use in HF with reduced EF of all NYHA classes
* Reduces morbidity/mortality
Angiotensin converting enzyme inhibitors
- ramipril, lisinopril
Angiotensin AT1 receptor antagonists
- candesartan, valsartan, (losartan)
Using the ACEI and ARBs in HF
- Reduce salt and water retention
- Reduce vasoconstriction
- Reduce vascular resistance
- Reduce afterload
- Improve tissue perfusion
- Reduces ventricular remodelling and hypertrophy
- Less effective in African or Caribbean ethnicity (try hydralazine+nitrate)
- Start low dose, monitoring BP & blood chemistry and symptoms and uptitrating to maximum tolerated or target doses.
renin-Angiotensin system inhibitors : Side effects/cautions
• Dizziness
• headache
• Persistentdrycough, tiredness, rare but serious – angioedema
•Risk of hyperkalaemia (care with drug which also raise K+)
• Renal impairment - can be reno-protective also
Angiotensin AT1 receptor antagonists (ARBs)
• Avoid in bilateral renal artery stenosis
• back/legpain
• teratogenic
angiotensin coveting enzyme inhibitors side effects
• Persistent dry cough, tiredness, rare but serious – angioedema
Angiotensin AT1 receptor antagonists (ARBs) side effects
back/leg pain
Why Use Beta-Blockers in HF?
may slow HR, which could decrease CO
- allows ventricle to fill more completely during diastole
- Some Beta-blockers (e.g. carvedilol) cause vasodilation through blockage of alpha-receptors, ↓ afterload
- Reduce renin release by kidney
Beta-blockers for HF
Carvedilol, Bisoprolol
- Start if reduced ejection fraction but stable NYHA class II-IV
- Start low, go slow
- reduces mortality
- Seek specialist advice if severe HF, current exacerbation of HF, heart block or bradycardia, persisting signs of fluid overload, low BP (SBP<90mmHg)
- drug interactions of beta blockers
– risk of bradycardia/AV block with: digoxin, amiodarone, verapamil, diltiazem
Beta-blockers side-effect examples
- Bradycardia /Heart Block (contra-indicated)
- Fatigue
- Shortness of breath (Contra-indicated in Asthma)
- Dizziness, cold peripheries, impotence/reduced libido, insomnia (more with older versions)
adding aldosterone antagonists
- spironolactone, eplerenone
- Add in if on ACEI or ARB + Beta-blocker + diuretic (“DAB”) and still symptoms
- In NYHA class II-IV failure (effective in severe heart failure )
- low doses used
- Reduces symptoms and mortality
Aldosterone Receptor Antagonists - Common side effects
- Hyperkalaemia
- hyponatraemia
- Nausea
- Hypotension
- gynaecomastia with spironolactone •renal impairment
Management of HF drug adverse effects
- Flexible dosing for DABs, may need to up and down titrate.
- Review BP – may be low but is patient symptomatic?
- Bradycardia – if symptomatic may need to stop beta-blocker or review any other rate controlling drugs patient on . If HR<45 BPM – stop beta-blocker, call specialist
Step3or4 in treatment of HF
- Sacubitril (Neprilysin inhibitor)– Valsartan (ARB) combination
- Ivabradine, specialist use only – reduces heart rate but not contractility, acts on sinus node. Use only if heart rate > 75 (in SR)
Persistent sodium/water retention
– Additional diuretics (e.g. thiazides like metolazone)
Co-existing angina
– Oral nitrates
– Amlodipine (care!)
Atrial fibrillation
– Digoxin
• shows no reduction in mortality rate
• narrow therapeutic window
mechanism of action in digoxin in AF
↑ vagal efferent activity to the heart ↓ SAN firing rate (↓ HR) and ↓ conduction velocity in the AV node
mechanism of action in digoxin in heart failure
Increases force of myocardial contraction
– Inhibits Na/KATP-ase pump, thus affecting Na/Ca exchanger, elevating intracellular calcium levels in Sarcoplasmic Reticulum then when Calcium released results in strengthened contractility
• i.e. indirectly increases calcium levels and subsequent storage in the SR
Digoxin side-
effects/toxicity
- GIupset
- dizziness
- Conduction abnormalities
- Blurred or yellow vision
Treatment of Acute (decompensated) Heart Failure
Sudden worsening of signs and symptoms of heart failure as a result of severe congestion of multiple organs.
Increased dyspnoea, oedema
Acute (decompensated) Heart Failure causes
MI, infection, anaemia, thyroid dysfunction, arrhythmia, uncontrolled hypertension, poor concordance
Acute (decompensated) Heart Failure aims of the treatment
- Normalise ventricular filling pressures
* Restore adequate tissue perfusion
Treatment of Acute Heart Failure: First Line Drug Treatments:
LMNOP
Treatment of Acute Heart Failure: second line
By use of inotropic agents (examples later)
↑ contractility will ↑ stroke volume, which ↑ Cardiac output
(CO) so ↑ clearance of pooled blood in the ventricles
As CO increases, baroreceptors sense change in MABP and ↓ sympathe$c drive and so ↓ HR and ↓ TPR
Inotropes - beta-agonists - increase myocardial contractility
– Dobutamine (beta 1&2) - in patients with cardiogenic shock to maintain
blood pressure
– Dopamine (DA > Beta > alpha) - Increases renal perfusion at low doses, can increase BP at high doses
– Isoprenaline – in bradycardia/heart block emergencies - Adrenaline (beta>alpha)
Vasopressors
– Noradrenaline (alpha>beta) – cause vasoconstriction, raise BP, used in severe septic shock
