Pharmacological treatment of cardiac failure Flashcards
What are the aims of treatment of Left Ventricular Systolic Dysfunction (LVSD) (=
Heart failure with reduced ejection fraction (HFrEF))
- Relieve symptoms
- Improve exercise tolerance
- Reduce incidence of acute exacerbations
- Reduce mortality
Discuss strategies for treatment of heart failure
- ↑ cardiac contractility
- ↓ preload and/or afterload 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
Discuss non pharmaceutical methods of treating heart failure
- Lifestyle factors – as per all CVD conditions, remember mental health factors
- “Device therapy”
• Pacing
• Cardiac Resynchronisation Therapy
• Implantable Cardiac Defibrillators
• Coronary revascularisation
• Heart transplant
What are the main drugs used in chronic heart failure (HFrEF)
Loop diuretics • e.g furosemide, bumetanide ACE inhibitors • e.g.ramipril, Lisinopril Angiotensin II receptor blockers • e.g candesartan, losartan Beta-blockers • bisoprolol, carvedilol Aldosterone receptor antagonists • e.g. spironolactone
These approaches can prolong life in heart failure and counteract some of the symptoms of heart failure…But they don’t correct the underlying fault
What is the basic drug use pathway in heart failure
ABBA Waterloo:
ACEI or ARB
Beta Blocker
Aldosterone antagonist
(diuretics sometimes)
Overview of treatment of chronic heart failure
Step 1 = “DAB”
(D = Diuretic if fluid retention) A = ACE Inhibitor or ARB
B = Beta-Blocker
A&B shown to reduce mortality (i.e. prolong life!)and improve quality of life.
Discuss kidney function modifiers in HF
Increase excretion of sodium and water
Loop diuretics (step 1) - furosemide, bumetanide Aldosterone receptor antagonists (step 2) - spironolactone
Further along this system you go, less diuretic effect: PCT = Proximal convoluted tubule TAL = Thick ascending loop DT = Distal tubule CT = Collecting tubule
So loop diuretics most effective, then thiazides, then spironolactone
Discuss flexible loop diuretic regimes
Use if clinical signs/symptoms of fluid overload/congestion
Aim to achieve a “dry” weight using the lowest diuretic dose possible.
Patient self-management with education:
• daily weights – if varies in either direction, alter dose
• Symptom review – breathlessness, peripheral oedema • Thirst level, dizziness, “washed out”
GP – blood chemistry checks within a week of any dose change
Discuss loop diuretics common side effects
(e.g. furosemide, bumetanide)
- 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
Discuss 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)
Discuss 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.
Discuss side effects/cautions of Renin-Angiotensin system inhibitors
Common to both
• Dizziness
• headache
• Riskofhyperkalaemia (care with drug which also raise K+)
• Renal impairment - can be reno-protective also
• Avoid in bilateral renal artery stenosis
• teratogenic
Angiotensin converting enzyme (ACE) inhibitors
• Persistentdrycough, tiredness, rare but serious – angioedema
Angiotensin AT1 receptor antagonists (ARBs)
• back/legpain
Why use beta blockers in HF?
?Bad news - may slow HR, which could decrease CO…
Good news
• allows ventricle to fill more completely during diastole
• Some Beta-blockers (e.g. carvedilol) cause vasodilation through blockage of alpha-receptors, therefore ↓ afterload
• Reduce renin release by kidney
Discuss beta blockers for HF
e.g. 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 – risk of bradycardia/AV block with: digoxin, amiodarone, verapamil, diltiazem
Discuss examples of beta blocker side effects
- Bradycardia /Heart Block (contra-indicated)
- Fatigue
- Shortness of breath (Contra-indicated in Asthma)
- Dizziness, cold peripheries, impotence/reduced libido, insomnia (more with older versions)
Discuss step 2 in the pathway: adding aldosterone antagonists
(Mineralocorticoid receptor 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
Discuss common side effects of aldosterone receptor antagonists
- Hyperkalaemia
- hyponatraemia
- Nausea
- Hypotension
- gynaecomastia with spironolactone •renal impairment
Discuss 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
What is step 3 or 4
- A 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)
What other options for treatment should you consider if concurrent
Persistent sodium/water retention
– Additional diuretics (e.g. thiazides like metolazone)
Co-existing angina
– Oral nitrates
– Amlodipine (care!)
Atrial fibrillation
– Digoxin
Discuss digoxin
– cardiac glycoside
• option if other treatment strategies failing
• shows no reduction in mortality rate
• narrow therapeutic window
Mechanisms of action:
• (In AF : ↑ vagal efferent ac$vity to the heart therefore ↓ SAN firing rate (↓ HR) and ↓ conduction velocity in the AV node)
• In Heart Failure: Increases force of myocardial contraction
– Inhibits Na/K ATP-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
What are the side effects/toxicity of digoxin
- GIupset
- dizziness
- Conduction abnormalities
- Blurred or yellow vision
Discuss 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
Causes: MI, infection, anaemia, thyroid dysfunction, arrhythmia, uncontrolled hypertension, poor concordance
Aims:
• Normalise ventricular filling pressures
• Restore adequate tissue perfusion
First Line Drug Treatments:
IV loop diuretics
• Cause venodilation and diuresis
• Reduces pre-load
IV opiates (eg morphine) • Reduce anxiety • Vasodilates, reducing preload • Reduces sympathetic drive • Not routinely offered
IV buccal or sublingual nitrates (Glyceryl trinitrate GTN)
• Reduce preload and afterload
• vasodilates
Oxygen maintains O2 sats
Positioning - keep patient upright
REMEMBER AS LMNOP - LOOP MORPHINE NITRATES OXYGEN POSITIONING
Second
Discuss first and second line treatments for acute heart failure
First Line Drug Treatments:
IV loop diuretics
• Cause venodilation and diuresis
• Reduces pre-load
IV opiates (eg morphine) • Reduce anxiety • Vasodilates, reducing preload • Reduces sympathetic drive • Not routinely offered
IV buccal or sublingual nitrates (Glyceryl trinitrate GTN)
• Reduce preload and afterload
• vasodilates
Oxygen maintains O2 sats
Positioning - keep patient upright
REMEMBER AS LMNOP - LOOP MORPHINE NITRATES OXYGEN POSITIONING
Second line - increasing contractility
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 ↓ sympathetic drive and so ↓ HR and ↓ TPR
Discuss second line drug treatments for acute HF (Only used in coronary care units and ICUs)
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
Learning outcomes
- To understand the strategies for treatment of chronic heart failure
- To understand the strategies for treatment of acute heart failure
- To recognise how the apparently paradoxical use of beta blockers is of benefit
- To understand the mechanism of action and uses of drugs which inhibit the renin- angiotensin-aldosterone system
- To know the mechanism of action of digoxin and how it increases myocardial contractility
- To know the mechanism of action and uses of inotropes
