Cardiovascular Drugs

and Diuretics

Heart
Failure
Pharmacology 2 Lecture
I. Definition
- Heart failure is a chronic, progressive
condition in which the heart muscle is
unable to pump enough blood to meet the
body’s needs for blood and oxygen
- Significant reduction in cardiac contractility
- May arise from left side, right side, or
biventricular
II. Terminologies
- CARDIAC OUTPUT
- total volume of blood pumped through the heart

- Stroke Volume : blood that passes through the

heart per beating
- Heart Rate : number of heart beats measured per
minute
II. Terminologies
- PRELOAD
- Tension that exists in the walls of the heart as a
result of diastolic filling
- Measure of the volume that stretches the left
ventricle at the end of diastole

- AFTERLOAD
- Force that the heart must generate to eject the
blood from left ventricle
II. Terminologies
- CARDIAC CONTRACTILITY
- Contraction and relaxation of the heart is
dependent on:

A. Ca++
B. stimulation of SANS
C. Amount of O2 available
D. Diameter of blood vessels
II. Terminologies
- CARDIAC RESERVE
- Ability of the heart to increase cardiac output
during increased activity

- If the heart is unable to maintain sufficient cardiac

output to meet tissue metabolic needs, HF may arise
III. Etiology
A. CAD J. Renal disease
B. MI K. Infection
C. Cardiomyopathy
D. HTN
E. Vascular Heart Disease
F. Arrhythmia
G. Pregnancy
H. Drugs
I. Pulmonary embolism
IV. Classifications
Class Patient Symptoms
I No limitation of physical activity.
Ordinary physical activity does not
cause undue fatigue, palpitation,
dyspnea (shortness of breath).

II Slight limitation of physical activity.

Comfortable at rest. Ordinary
physical activity results in fatigue,
palpitation, dyspnea (shortness of
breath).
IV. Classifications
Class Patient Symptoms
III Marked limitation of physical activity.
Comfortable at rest. Less than
ordinary activity causes fatigue,
palpitation, or dyspnea.

IV Unable to carry on any physical

activity without discomfort.
Symptoms of heart failure at rest. If
any physical activity is undertaken,
discomfort increases.
IV. Classifications
FORMS
- LOW OUTPUT HF
- Metabolic demands are within normal
limits but the heart is unable to meet them

HIGH OUTPUT HF
- Increased metabolic demands and heart is
unable to meet them
 V. Pathophysiology
FRANK-STARLING MECHANISM - Stroke volume is dependent on the
- A relationship characterizing following:
stroke volume with preload
i. Preload: Changes in preload affect the
end-diastolic volume which in turn alter
stroke volume
ii. Contractility: influenced by SANS and
PANS. Decrease in contractility result in
increased end-systolic volumes
iii. Afterload: altered by changes in
vascular resistance or damage to valves
of the heart
V. Pathophysiology
When HF occurs, increases
in preload do not result in
a stroke volume sufficient
to meet the demands of
the body’s peripheral
tissues. As a result:
- RAAS is activated
- Activation of SANS
 V. Pathophysiology
As the disease progresses,
the CO does not increase
appropriately despite
increased preload.
Eventually, the increased in
left ventricle end diastolic
volume/pressure transmits
pressure back to the
pulmonary veins leading to
the symptoms of pulmonary
congestion.
 V. Pathophysiology
CARDIAC REMODELLING
- Dilation and other
structural changes that
occur in stressed
myocardium
- Myocardial hypertrophy :
increase in heart muscle mass
(results to reduced diastolic filling,
ischemia, abnormal heart
geometry)
 V. Pathophysiology
- Myocardial hypertrophy : increase in heart muscle mass (results to reduced
diastolic filling, ischemia, abnormal heart geometry)
 V. Pathophysiology
- Myocardial hypertrophy : increase in heart muscle mass (results to reduced
diastolic filling, ischemia, abnormal heart geometry)
 V. Pathophysiology
CARDIAC DECOMPENSATION
- Exhaustion of
compensatory responses
and mechanisms
- Dilated pupils, dyspnea,
falling O2 saturation,
dependent pitting edema,
cough, elevated BP, anxiety
and confusion
 VI. Signs and Symptoms
- LEFT-SIDED HF
- Blood is not adequately pumped from left ventricle going to peripheral circulation
- Left Ventricle is unable to accept blood from Left Atrium and LUNGS
- Results to PULMONARY EDEMA

- RIGHT-SIDED HF
- Blood is not adequately pumped from right ventricle going to the lungs
- Right Ventricle is unable to accept blood from Right Atrium; blood backs up
throughout the body (veins, liver, legs, bowel) → Cor Pulmonale
- Results to SYSTEMIC EDEMA
VI. Signs and Symptoms
VI. Signs and Symptoms
 VII. Pharmacologic Therapy
I. Diuretics
a) LOOP DIURETICS
b) THIAZIDES

- Disadvantages:
- Electrolyte imbalances → hypokalemia
- PE: increase intake of potassium-rich foods, maintain fluid intake, monitor
edema by weighing daily
 VII. Pharmacologic Therapy
II. ACE Inhibitors – mainstay agents IV. Beta Blockers : reduces
a) Captopril inotropic activity to improve filling
efficiency
b) Enalapril

III. ARB Agents V. Vasodilators : secondary

a) Candesartan c) Valsartan agents for patients who do not
b) Losartan respond to ACEIs; sometimes used
in combination
- Disadvantages of ACEI & ARB :
- May induce hyperkalemia, dry &
non-productive cough, renal
impairment
 VII. Pharmacologic Therapy
VI. Inotropic Agents
a) DIGITALIS GLYCOSIDES
- increases CO, reduces cardiac filling pressure,
decreased venous return; reverses S/Sx but no net
effect on mortality
- (+) inotropy, (-) chronotropy, (-) dromotropy
MOA: inhibition of Na/K ATPase pump in myocardial
cell results in a transient increase of intracellular
sodium, which in turn promotes Ca influx
 VII. Pharmacologic Therapy
VI. Inotropic Agents
a) DIGITALIS GLYCOSIDES
DIGOXIN DIGITOXIN
IV/PO PO
30% protein bound 97% protein bound
t ½ : 36hrs t ½ : 5 to 7 days
Kidneys Liver
 VII. Pharmacologic Therapy
VI. Inotropic Agents
a) DIGITALIS GLYCOSIDES

Digitalization
Loading Dose : 500mcg to 750mcg q8h for 3 doses
Maintenance : 125mcg to 250mcg tab OD

Target : 1ng/ml or less plasma conc.

Toxic : >1.5ng/ml plasma conc.
 VII. Pharmacologic Therapy
VI. Inotropic Agents
a) DIGITALIS GLYCOSIDES

Toxicity
a. Cardiac – dysrhythmia, AV block
b. GI disturbances, anorexia
c. HA
d. Alterations in visual perception
e. Gynecomastia
f. Disorientation
 VII. Pharmacologic Therapy
VI. Inotropic Agents
a) DIGITALIS GLYCOSIDES

Toxicity Management
a. Discontinuation
b. Potassium supplementation
c. Activated charcoal, cholestyramine, or lavage
d. Lidocaine (for arrhythmia)
e. Cardioversion
f. Purified digoxin specific Fab fragment antibody
 VII. Pharmacologic Therapy
VI. Inotropic Agents
b) PHOSPHODIESTERASE INHIBITORS
- increases CO by improving contractility
while reducing preload and afterload

- MOA: inhibits the enzyme PDE-III which

degrades cAMP in cardiac muscles

- cAMP in the heart → mycocardial contraction

- cAMP in blood vessels→ vasodilation
 VII. Pharmacologic Therapy
VI. Inotropic Agents
b) PHOSPHODIESTERASE INHIBITORS

1. Amrinone
- given IV, for short-term mgt of acute CHF; associated
with reversible thrombocytopenia

2. Milrinone
- showed increase mortality and no beneficial effects
 VII. Pharmacologic Therapy
VI. Inotropic Agents
c) BETA-1 AGONISTS
- used for emergency cases such as in cardiogenic shock
- produces (+)inotropy but can cause refractory arrhythmia and increased
workload of heart
1. Dopamine : CHF with hypotension
2. Dobutamine : preferred in HF with normal BP; minimum chronotropic and
peripheral vasoconstrictive effects
 VII. Pharmacologic Therapy
VI. Inotropic Agents
c) BETA-1 AGONISTS
DOPAMINE DOBUTAMINE
Source Natural catecholamine Synthetic
(NT, neurohormone) (sympathomimetic drug)
Mechanism D, β, α, β1 > β2 > α
inotropic action less more
PVR increase reduction
 VII. Pharmacologic Therapy
VI. Inotropic Agents
d) LEVOSIMENDAN
- short-term treatment of acutely decompensated CHF
- calcium sensitizer - increases the sensitivity of the heart to Ca++, thus
increasing cardiac contractility without a rise in intracellular Ca++ (lesser O2
demand)
MOA: increasing calcium sensitivity of myocytes by binding to cardiac
troponin C in a calcium-dependent manner allowing normal or improved diastolic
relaxation
 VII. Pharmacologic Therapy
VII. Newer Agents
a) SACUBITRIL
- a neprilysin inhibitor

MOA : a prodrug that inhibits neprilysin which degrades atrial and brain
natriuretic peptide

EFFECT: Increased concentrations of natriuretic peptides which promote Na+

excretion in the urine
 VII. Pharmacologic Therapy
VII. Newer Agents
b) AQUARETICS
1. Tolvaptan
2. Conivaptan
- used to treat low blood Na+ levels associated with various conditions like CHF
MOA : a selective and competitive vasopressin receptor antagonist. By
blockade of V2 receptors in the renal collecting ducts ultimately results in an
increase in urine volume and increase electrolyte-free water clearance.

EFFECT: reduction of blood volume and an increase serum sodium levels.

End