Professional Documents
Culture Documents
1. Diuretics
Mainstay of heart failure management
No direct effect on cardiac contractility
Reduce venous pressure and ventricular preload
Results in reduction of salt and water retention and edema and its symptome
COMPOUNDS
Furosemide (generic, Lasix)
Loop Diuretic
Possesses a free carboxyl group making it a strong acid
Furan ring
Aromatic amino
MOA – Decreases NaCl and KCl reabsorption in thick ascending limb of the loop
of Henle in the nephron
Weakly acidic
An electron withdrawing group is necessary at position 6 for diuretic activity (Cl
or CF3 highly active
CH3 diuretics are more lipid-soluble and have a longer duration of action vs Cl
analogs
Electron donating groups (-CH3, -OCH3) decreases diuretic activity
Replacement or removal of sulfonamide group in position 7 leads to little or
diminished diuretic activity
Saturation of the double bond to give a 3,4-dihydro derivative 10x more active
than unsaturated analog
Other SAR will be discussed when diuretics are covered
MOA - Decreases NaCl reabsorption in the distal convoluted tubule
2. Aldosterone receptor angagonists
Also diuretics
Additional benefit of decreasing morbidity and mortality in patients with severe
heart failure who are also receiving ACE inhibitors and other standard therapy.
Aldosterone promotes salt and water retention and potassium and hydrogen ion
excretion. An aldosterone antagonists will promote diuresis.
COMPOUNDS
Spironolactone (generic, Aldactone)
O O
O O
S
O CH3 O Canrenone
O
Spironolactone
COO-
OH
COMPOUNDS
ACE inhibitors can be subclassified into three groups based on their chemical
composition.
A. Sulfhydryl-containing inhibitors
C. Dicarboxylate-containing inhibitors
Perindopril (Aceon)
Trandolapril (Mavik)
HN
N
N B
N
R N
C HOOC
Acidic group
SAR
1. The acidic group amino acids of angiotensin II. Groups capable include (A)
carboxylic acid, (B) phenyl tetrazole, (C) phenyl carboxylate
2. In the biphenyl series, the tetrazole and carboxylate groups must be in the ortho
position for optimal activity (tetrazole is superior in terms of stability, lipophilicity and
oral bioavailability)
3. The n-butyl group of the model compound provides hydrophobic binding (can be
replaced with an ethyl ether or an n-propyl group)
4. The imidiazole ring or an isosteric equivalent is required.
5. Substitution can vary at the “R” position
COMPOUNDS
Losartan (Cozarr)
Candesartan (Atacand)
Eprosartan (Teveten)
Irbesartan (Avapro)
Olmesartan (Benicar)
Telmisartan (Micardis)
Valsartan (Diovan)
5. Beta blockers
Competitively blocks B1 receptors
COMPOUNDS
Bisiprolol (generic, Zebeta)
Carvedilol (Coreg)
Racemic mixture
Racemic mixture
6. Cardiac glycosides
Digitalis is the genus name for the famil of plants that provide most of the
medically useful cardiac glycosides
All of the cardiac glycosides of which digoxin is the prototype combine a steroid
nucleus linked to a lactone ring at the 17 position and a series of sugars at carbon
3 of the nucleus.
MOA – Na+, K+ATPase inhibition results in reduced Ca2+ expulsion and
increased Ca2+ stored in sarcoplasmic reticulum.
COMPOUNDS
Digoxin (generic, Lanoxicaps, Lanoxin)
Sugar – digitoxose Aglycone – digoxigenin
7. Vasodilators
Effective in acute heart failure or
Provides reduction in preload or reduction in afterload or both
COMPOUNDS
Venodilators
Releases nitric oxide (NO)
Activates guanyl cyclase
Arteriolar dilators
Probably increases NO synthesis in endothelium
Hydralazine (generic, Apresoline)
Combination
Releases NO spontaneously
Activates guanyl cyclase
Nitroprusside (generic, Nitropress)
COMPOUNDS
Catecholamines
Dobutamine (generic) – most widely used B1 agonist
Produces an increase in cardiac output with a decrease in ventricular
filling pressure.
COMPOUNDS
Inamrinone (generic)
Bosentan (Tracleer)