Download Therapy for Chronic and Acute Heart Failure

Therapy for Chronic and Acute Heart Failure
Acute and Decompensated Chronic Heart Failure
Aim
Immediate ↑ in Cardiac Output
Immediate ↓ in Cardiac Workload
1. Loop diuretic
a. Furosemide
2. Nitrovasodilator
a. Glyceryl trinitrate
3. Non – cardiac glycoside
a. B1 agonist
i. Dobutamine
b. Calcium sensitizer
i. Levosimendan
c. Bypiridine (Phosphodiaesterase Inibitor)
i. Milrinone
4. Anti-Angiotensin II Drugs
a. ACE inhibitor
i. Captopril
b. ARB
i. Losartan
5. Morphine
Chronic Heart Failure
Aim
↑ in Cardiac Output (Sustainable)
↓ in Cardiac Workload (Sustainable)
1. Anti-Angiotensin II Drugs
a. ACE inhibitor
i. Captopril
b. ARB
i. Losartan
2. Diuretics
a. All types
3. Aldosterone antagonist
a. Spironolactone
4. Cardiac glycosides
a. Digoxin
5. Beta blockers
a. Atenolol
6. If inhibitor
a. Ivabradine
Therapy for Acute and Decompensated Chronic Heart Failue
Loop Diuretics
Drug Name/ Infos
Furosemide
1.
2.
3.
Drug interaction
1. Warfarin
a. Replace warfarin from
protein binding
2. Ototoxicity
a. ↑ incidence if given
together with
4.
Aminoglycosides
3. Increase toxicity
a. Given with Probenecid
– organic acid
tansporter inhibitor
Mechanism of Action
Acts on Thick Ascending Limb of Henle
Inhibit the Na+/K+/2Cl- cotransporter
Therefore will lead to ↑ urinary excretion of
a. Na
b. Cl
c. K
d. Mg
e. Ca
Immediately reduce the preload, therefore less
burden exerted to the failing heart  improve
cardiac efficiency
1.
2.
3.
4.
5.
6.
7.
8.
Adverse Effects
Ototoxicity
Hyperuriceamia
Acute hypovolumia
Nephritis
Hypokaleamia
Hyperglycaemia
Gouty arthritis
Allergic reaction
Nitrovasodilator
Drug Name/ Infos
Glyceryl Trinitrate (Prodrug)
Infos
1. Fast tolerance
Mechanism of Action
1. Undergoes denitration immediately upon
entering into the body
2. Producing Nitric Oxide which is a very potent
vasodilator
a. Activate Guanylyl Cyclase
b. ↑cGMP
c. ↓Ca release
d. ↑ smooth muscle relaxation
3. Immediately reduce afterload, therefore
reducing workload  improve cardiac efficiency
Adverse Effects
1. Severe headache
a. Due to immediate response
of vasodilation
2. Severe hypotension
3. Reflex tachycardia
Non-cardiac Glycosides
Drug Name/ Infos
B1 Agonist
1. Dobutamine (the most
preferable)
2. Dopamine
3. Epinephrine
Pharmacokinetic
1. Given IV
2. Immediate response
3. Only use in emergency
cases, cause long term
use can lead to
a. Cardiac arrhythmia
b. Cardiac arrest
c. Mortality
Drug Name/ Infos
Calcium Sensitizer
1. Levosimendan
1.
2.
3.
4.
5.
Mechanism of Action
Binds Beta 1 receptor
Activates Adenylyl Cyclase
Converts ATP to cAMP
This will therefore
a. + chronotropic
i. ↑heart rate
b. + inotropic
i. ↑ cardiac contractility
c. + dormotrophic
i. ↑impulse conduction
All of these will lead to ↑ cardiac output 
improve efficiency of the failing heart
Mechanism of Action
1. Binds to cardiac troponin C thus ↑ its sensitivity to
Ca
2. This will then lead to more powerful contraction
of cardiac muscle  improve cardiac output
3. Opens K+ ATPase, efflux of K+ outside the
peripheral smooth muscle cells  relaxation of
arterial and venous smooth muscle cells
a. ↓afterload and preload leads to
improvement of cardiac efficiency
1.
2.
3.
4.
Adverse Effects
Tachycardia
Hypertension
Atrial fibrillation
Cardiac arrest
Adverse Effects
1. Headache
2. Hypotension
3. Arrhythmias
Drug Name/ Infos
Bypiridine
(Phosphodiaesterase
Inhibitor)
1. Milrinone
Info
1. Phosphodiaesterase
Type III is an enzyme use
in conversion of cAMP
into AMP
Mechanism of Action
1. Inhibits the Phosphodiaesterase type III leads to ↑
level of cAMP
a. ↑cAMP will lead to activation of Protein
Kinase A in which will further
i. ↑ Ca level in the cytoplasm by
1. ↑Ca entry through Ca channel
2. ↓Ca sequestration (taking up) into the
Sarcoplasmic Reticulum
2. This will then ↑ cardiac output and improve
cardiac efficiency
Adverse Effects
1. Cardiac arrhythmias
Never been used for long time
Anti-angiotensin II Drugs
Drug Name/ Infos
Anti-angiotensin II Drugs
1. ACE inhibitor
a. Captopril
2. ARB
a. Losartan
Both drug should never be
given to pregnant women
For ARB, it is C/I in pts with
1. Angioedema due to
ACEI
These agents are very useful
cause it will inhibit the
inappropriate cardiac
remodelling  ↑pts survival
Mechanism of Action
ACE inhibitor
1. Inhibit the activity of ACE, therefore inhibit the
conversion of Angiotensin I to Angiotensin II
a. Leads to vasodilation
b. ↓TPR  ↓afterload
c. ↓aldosterone release
i. ↑water and Na excretion
ii. ↓preload
ARB
1. Blocks AT1 receptor, leads to
d. Leads to vasodilation
e. ↓TPR  ↓afterload
f. ↓aldosterone release
i. ↑water and Na excretion
ii. ↓preload
All of these will ↓ cardiac workload thus improving
cardiac
1.
2.
3.
4.
Adverse Effects
Dry cough (ACEI only)
Angioedema
Hyperkaleamia
Acute renal failure
a. Pts with renal artery stenosis
Therapy for Chronic Heart Failure
Anti-angiotensin II Drugs
Drug Name/ Infos
Anti-angiotensin II Drugs
3. ACE inhibitor
a. Captopril
4. ARB
a. Losartan
Both drug should never be
given to pregnant women
For ARB, it is C/I in pts with
2. Angioedema due to
ACEI
These agents are very useful
cause it will inhibit the
inappropriate cardiac
remodelling  ↑pts survival
Mechanism of Action
ACE inhibitor
1. Inhibit the activity of ACE, therefore inhibit the
conversion of Angiotensin I to Angiotensin II
a. Leads to vasodilation
b. ↓TPR  ↓afterload
c. ↓aldosterone release
i. ↑water and Na excretion
ii. ↓preload
ARB
1. Blocks AT1 receptor, leads to
d. Leads to vasodilation
e. ↓TPR  ↓afterload
f. ↓aldosterone release
i. ↑water and Na excretion
ii. ↓preload
All of these will ↓ cardiac workload thus improving
cardiac
5.
6.
7.
8.
Adverse Effects
Dry cough (ACEI only)
Angioedema
Hyperkaleamia
Acute renal failure
a. Pts with renal artery stenosis
Diuretics
1.
2.
3.
4.
Drug Name/ Infos
Loop diuretics
a. Furosemide
Thiazide diuretics
a. Hydrochlorothiazide
Potassium Sparing
Diuretic
a. Spironolactone
Carbonic Anhydrase
Inhibitor
a. Acetozolamide
Mechanism of Action
1. Reducing cardiac preload by
a. ↑diuresis  water and Na excretion from urine
2. After several periods of usage, diuretic will start to
mobilize accumulated fluid in the interstitium
(edema) into the blood vessel, this will then lead
to improve Cardiac Output
Adverse Effects
Numerous side effects of diuretics
Aldosterone Receptor Antagonist
Drug Name/ Infos
Spironolactone
Infos
Aldosterone roles in cardiac
failure
1. ↑ Na and water retention
a. ↑preload (↑cardiac
burden)
2. ↑formation of fibrous
tissue in heart
a. Cardiac remodelling
(↓efficiency)
3. Hypokaleamia and
hypomagnesimia
a. Cardiac arrest
Mechanism of Action
1. This weak diuretic exerts its important role not thru
diuretic but thru the inhibition of aldosterone
receptor
2. Inhibition of aldosterone effect is very important
as it will inhibit inappropriate cardiac remodelling
3. This will improve pts survival
Adverse Effects
1. Gyneacomastia
2. Hyperkaleamia
Cardiac Glycosides (Digitalis)
Drug Name/ Infos
Digoxin
Mechanism of Action
Direct effect
1. Irreversible blocks the Na+/K+ ATPase pump
Pharmacokinetics
a. ↑intracellular Na
1. Oral absorption 65% b. ↓transmembrane potential
80%
c. Activate Na+/Ca2+ exchanger
2. Plasma protein binding
d. ↑Ca level in the cell
e. ↑cardiac contractility  increase cardiac
25%
3. Large volume of
output
distribution
Indirect effect
a. 400L
1. ↓catecholamine release
b. Stored in skeletal
2. ↑parasympathetic activity
muscle
3. ↓RAAS activity
4. 2/3 excreted unchanged In which all these will ↓ preload and afterload
thru urine
(↓cardiac workload)
5. Half life 36 hours
6. Late onset
Major effects of Digoxin
a. 4-5 days
1. + inotropic
b. Not preferable for
a. ↑ cardiac contractility
acute attack
2. + tonotropic
7. Narrow therapeutic
a. ↓size of the heart
index
3. + bathmotropic
a. Major limitation
a. ↑cardiac excitability
4. – chronotropic
a. ↓ heart rate
5. – dromotropic
a. ↓impulse conduction
1.
2.
3.
4.
Adverse Effects
Arrhythmias
Headache
Fatigue
Electrolyte imbalances
a. Hypokalemia
b. Hypomagnesimia
c. Hypercalceamia
Beta Adrenergic Blocker
Drug Name/ Infos
Atenolol
Beta blocker is the standard
therapy for chronic heart
failure for pts
1. Heamodynamically
stable
2. No dyspnea during
resting
3. Not C/I to use this agent
Mechanism of Action
1. Cardiovascular system
a. (-) in :
i. Inotropic
ii. Chronotropic
b. Causing in:
i. ↓cardiac output
ii. ↓cardiac work
iii. ↓oxygen consumption
2. Improve cardiac efficiency
Adverse Effects
1. Rebound hypertension
If Inhibitor
Drug Name/ Infos
Ivabradine
Mechanism of Action
1. Block the HCN channel/ Funny channel
a. ↓pacemaking activity of SA node
b. ↓heart rate
c. ↓cardiac workload
d. ↓cardiac oxygen demand
2. There is no effect on cardiac contractility
Adverse Effects
1. Luminous phenomena
2. Headache
3. Bradycardia