Exam 1: Lecture 10, Medical Chemistry Flashcards
three major disorders making up heart disease?
Cardiac failure or contractile dysfunction
ischemia
cardiac arrhythmia
Cardiac Glycoside formation to be active?
Cis-Trans-Cis
A/B = cis fused B/C = trans fused C/D = cis fused
any other combo is inactive
Will cardiac glycosides have positive or negative inotropic effect?
positive
work on SA node, AV node, and His-Purkinje system
most widely accepted MOA of cardiac glycosides?
inhibition of Na/H ATPase pump
increasing intracellular ca, more ca released by SR, more available to bind troponin-C = increase contractility
origin source of glycosides causes variation in?
size and degree of unsaturation of lactone ring
5-member a/b unsaturated = plant derived
6 membered, 2 double bond = animal derived
Animal vs plant glycosides?
animal way more rare, less medicinal importance due to their high toxicity
Where are two angular methyl groups located usually on cardiac glycoside?
C-10 and C-13
Where are hydroxyl groups located on cardiac glycoside?
C-3 and C-14
C-3 = site of sugar
C-14 usually unsubstituted
-genin represents…
lack of sugar, just steroid part
Most commonly found sugars in cardiac glycosides are…
D-glucseo, D-digitoxose, L- rhamnose, and D-cymarose
Where do cardiac glycosides have indirect action?
on cardiovascular system mediated by increased vagal nerve activity.
What confirmation do the four sugars predominately exist in cardiac glycosides?
B-conformation
What does the presence of an O-acetyl group on sugar do?
affects the lipophilic character and pharmacokinetics of entire glycoside
Hydroxy group 16 position?
Gitoxin
Hydroxy group at 12 position?
Digoxin
No hydroxy group on 12?
Digitoxin
Digoxin vs digitoxin
digoxin is more polar, digitoxin is more lipophilic so absorbed faster/exhibit longer duration of action.
only differ by an extra hydroxyl group on the aglycone part.
Digoxin info
oral bioavailability exhibits inter individual variability ranging form 70-85%
P-gp
ABC-transporter, extensively distributed and epodes in normal cells
“throws drug out”
Digoxin and Quinidine interaction
quinidine binds to P-gp, reducing secretion of digoxin by 60%, raising its plasma conc to toxic levels
other drugs include verapamil (inhibit P-gp efflux) and rifampin (induces P-gp expression, increasing mediated secretion = more thrown out)
antianginal drugs act by mainly…
by dilating the coronary artery
5 nitrates in use today?
Amyl nitrite nitroglycerin isosorbide dinitrate erythritol tetra nitrate pentaerythrivol tetranitrate
nitrate group potency
increasing # of groups = increase potency
why is long term efficacy of nitrates limited?
due to development of tolerance.
