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Renin + Angiotensinogen
Salt & Water Retention
Vasoconstric on: ↑’s the resistance against which
heart has to pump (i.e., ↑’s a erload), and may
therefore ↓ CO
Na and water reten on: ↑’s ﬂuid volume, which ↑’s
preload. If too much “stretch” (d/t too much ﬂuid) →
↓ strength of contrac on and ↓’s CO
Excessive tachycardia → ↓’d diastolic ﬁlling me → ↓’d
ventricular ﬁlling → ↓’d SV and CO
ACC/AHA HF Stage NYHA Functional Class
A At high risk for heart failure but without
structural heart disease or symptoms
of heart failure (eg, patients with
hypertension or coronary artery disease)
B Structural heart disease but without
symptoms of heart failure
C Structural heart disease with prior or
current symptoms of heart failure
D Refractory heart failure requiring
II Symptomatic with moderate exertion
IV Symptomatic at rest
III Symptomatic with minimal exertion
D ig ita lis p u rp u re a (F o x g lo v e ) W . W ith e rin g (1 7 8 5 )
F ra n c e , U K N a tiv e lle
(1 8 6 9 )
•D ig ito x in
Inhibits NaK/ATPase pump
Contractility increases as intracellular Ca, Na increases and
loss of intracellular K+
• Positive inotropic effect- increases force of contraction
without increasing of oxygen consumption
• Positive bathmotropic effect-Modifying degree of
• Negative chronotropic effect-rate of heart is decreased
• Negative dromotropic effect-conduction speed of AV
• CGs are effective in CHF, occurring with normal or
accelerated heart rhythm, especially in cases of atrial
ARs: bradycardia, AV block,
accumulation and intoxication.
Digoxin toxicity- renal insufficiency, ischemia, hypokalemia
calcium channel blockers, beta blockers, cyclosporine and
Normal levels- 0.5-2ng/ml
Treatment of toxicity-charcoal. Correct potassium, calcium
IV, DIGIBIND antibodies
Preparations of Digitalis (foxglove)
Digitoxin (t1/2 168 h)
Digoxin (t1/2 40 h): p.o. or i.v.
Semisynthetic derivatives of Digoxin
– Acetyldigoxin (Lanatilin): p.o.
– Methyldigoxin (Lanitop): p.o.
Preparations of Strophanthus gratus
– Strophanthin G (Ouabain) – i.v.
AC PDE III
Amrinone, Enoximone, Milrinone
These agents are indicated in severe congestive
AHF, resistant to other drugs; usually for short
i.v. treatment. They have positive inotropic effect,
but they increase oxygen consumption.
ARs: ventricular and SV arrhythmias, angina,
hypotension, headache, hypokalemia.
In AHF with cardiogenic shock Dobutamine (β1-agonist)
and Dopamine are administered by i.v. infusion.
In high doses dopamine may increase peripheral vascular
resistance, while dobutamine does not influence it.
Dopamine in low doses activates D2-receptors in renal and
mesenterial vessels and in coronaries. It causes arterial
vasodilation, activates D5-receptors in myocardium and
increases myocardial contractility.
Used in low doses (2 to 5 mcg/kg/min i.v.) dopamine
does not increase blood pressure.
In high doses (> 5 mcg/kg/min i.v.) its α- and β-effects
They increase salt and water loss,
reduce blood volume
and lower excessive venous filling pressure,
reduce circulating blood volume and preload.
The congestive features of oedema, in the lungs
and periphery, are alleviated,
cardiac output is also increased.
Diuretics are administered together with
ACE inhibitors and other drugs.
Spironolactone is a weak diuretic.
In cases of severe heart failure low doses of
Spironolactone are added to the therapy while regularly
checking creatinine and electrolyte levels.
It blocks aldosterone receptors in the distal renal tubules
and reduces increased aldosterone levels in CHF.
In low doses (25 mg/24 h) Spironolactone
potentiates the effects of ACE inhibitors.
It also saves K+ and Mg2+ and has antiarrhythmic activity.
Spironolactone prevents myocardial fibrosis, caused by
aldosterone, and in this way increases myocardial
Similar to spironolactone is another aldosterone
antagonist – Eplerenone.
ACE inhibitors reduce pre- and afterload.
They are administered in lower doses alone
or together with diuretics, cardiac glycoside,
antiischemic agents in all stages of CHF,
due to systolic dysfunction.
In preparations with t1/2 ≥ 24 h (Perindopril,
Ramipril) the risk of lowering blood pressure after
the first dose is avoided.
Na+ & water
Rise in BP
Competitive antagonist and inverse agonist of AT1
receptor Complete inhibition of AT1 – alternative
remains with ACEs
Result in indirect activation of AT2 – vasodilatation
Does not interfere with other receptors except TXA2
Blocks all the actions of A-II - vasoconstriction,
sympathetic stimulation, aldosterone release and renal
actions of salt and water reabsorption
No inhibition of ACE
Organic nitrates dilate capacity vessels, reduce preload
and myocardium oxygen needs.
They connect with thiol groups (-SH) and release nitric
oxide (NO). NO combines with new thiol groups in vascular
endothelium to form nitrosothiol (R-SNO).
Nitrosothiols activates guanylate cyclase which raises the
concentration of cyclic GMP.
This reduces the bioavailability of intracellular calcium and
Glyceryl trinitrate is prescribed sublingually at 18–20 min
intervals in acute left-ventricular heart failure
Trimetazidine has prolonged concentration plateau lasting
up to 11 h.
It increases ATP synthesis and decreases acidosis in
It supplies energy for Na+/K+ transmembrane pump,
but can cause parkinsonism.
Carvedilol is a blocker of β- and α-receptors. It also has
antioxidant, vasodilating and cardioprotective effects.
It decreases cardiac output, peripheral vascular resistance
Carvedilol lowers mortality with 25–67%, but it is
contraindicated in CHF, occuring with cor pulmonale. The
treatment begins with low doses (3.125 mg/12 h).
Cardioselective beta-blockers Bisoprolol and
Metoprolol decrease with 31% mortality in
patients with CHF, if used in combination with
diuretics, ACE inhibitors and Digoxin.
Levocarnitine is a N-containing amino
acid in muscle, which has antioxidant activity.
It is indicated in cardiomyopathy and muscle
dystrophy caused by carnitine deficiency.
Preparations containing Coenzyme Q10
(a part of the mitochondrial redox system),
stimulate ATP synthesis and improve
myocardial contractility in CHF.
Levosimendan increases sensitivity of troponin in the
heart to calcium.
This results in increased myocardial contractility.
It is infused i.v. for short treatment of severe heart
ACE inhibitor (angiotensin-
ARB (angiotensin receptor
Type What it does
Expands blood vessels which lowers blood
pressure, neurohormonal blockade
Similar to ACE inhibitor—lowers
Reduces the action of stress hormones
and slows the heart rate
Slows the heart rate and improves the heart’s
pumping function (EF)
Filters sodium and excess fluid from the blood
to reduce the heart’s workload
Blocks neurohormal activation and controls