This document discusses heart failure, including its causes, pathophysiology, stages, symptoms, and treatments. It provides details on several classes of medications used to treat heart failure, including how they work and examples of common drugs. Evidence-based medications are shown to significantly reduce mortality rates within two years, with ACE inhibitors reducing risk by 23% and beta-blockers by 35%. Other effective treatments include aldosterone antagonists, implantable cardioverter-defibrillators, and diuretics.
Unit I herbs as raw materials, biodynamic agriculture.ppt
Class ccf
1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1
2. Impaired cardiac pumping such that heart is
unable to pump adequate amount of blood to
meet metabolic needs
Not a disease but a “syndrome” associated with
long-standing HTN and CAD
3. Pulmonary edema
Agitation
Pale or cyanotic
Cold, clammy skin
Severe dyspnea
Tachypnea
Pink, frothy sputum
Fatigue
Dyspnea
Paroxysmal nocturnal dyspnea (PND)
Tachycardia
Edema – (lung, liver, abdomen, legs)
Nocturia
9. Renin + Angiotensinogen
Angiotensin I
Angiotensin II
Peripheral
Vasoconstriction
Afterload
Cardiac Output
Heart Failure
Cardiac Workload
Preload
Plasma Volume
Salt & Water Retention
Edema
Aldosterone Secretion
ACE
Kaliuresis
Beta
Stimulation
• CO
• Na+
Fibrosis
10. 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
12. 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
specialized interventions
I Asymptomatic
II Symptomatic with moderate exertion
IV Symptomatic at rest
III Symptomatic with minimal exertion
None
15. 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
16. 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
excitability
• Negative chronotropic effect-rate of heart is decreased
• Negative dromotropic effect-conduction speed of AV
node
• CGs are effective in CHF, occurring with normal or
accelerated heart rhythm, especially in cases of atrial
fibrillation
17. ARs: bradycardia, AV block,
Extra-systoles arrhythmias,
accumulation and intoxication.
Digoxin toxicity- renal insufficiency, ischemia, hypokalemia
calcium channel blockers, beta blockers, cyclosporine and
furosemide
Normal levels- 0.5-2ng/ml
Treatment of toxicity-charcoal. Correct potassium, calcium
IV, DIGIBIND antibodies
18. 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.
19. ATP 3’,5’-AMP
AC PDE III
Amrinone
Enoximone
Milrinone
(–)
cAMP
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.
20. 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
dominate.
21. 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.
24. Early DCT
Late DCT
Na+
Cl-
LUMEN
K+
Na+
Cl-
THIAZIDES
25. 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.
26. 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
contractility.
Similar to spironolactone is another aldosterone
antagonist – Eplerenone.
27. 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.
30. Competitive antagonist and inverse agonist of AT1
receptor Complete inhibition of AT1 – alternative
remains with ACEs
Result in indirect activation of AT2 – vasodilatation
(additional benefit)
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
31. 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
produces vasodilation
Glyceryl trinitrate is prescribed sublingually at 18–20 min
intervals in acute left-ventricular heart failure
32. Trimetazidine has prolonged concentration plateau lasting
up to 11 h.
It increases ATP synthesis and decreases acidosis in
ischemic tissues.
It supplies energy for Na+/K+ transmembrane pump,
but can cause parkinsonism.
33. Carvedilol is a blocker of β- and α-receptors. It also has
antioxidant, vasodilating and cardioprotective effects.
It decreases cardiac output, peripheral vascular resistance
and afterload.
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).
34. Cardioselective beta-blockers Bisoprolol and
Metoprolol decrease with 31% mortality in
patients with CHF, if used in combination with
diuretics, ACE inhibitors and Digoxin.
35. 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.
36. 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
failure.
37. ACE inhibitor (angiotensin-
converting enzyme)
ARB (angiotensin receptor
blockers)
Beta-blocker
Digoxin
Diuretic
Aldosterone blockade
Type What it does
Expands blood vessels which lowers blood
pressure, neurohormonal blockade
Similar to ACE inhibitor—lowers
blood pressure
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
volume