Exam 1: Lecture 10, Medical Chemistry

Question 1

three major disorders making up heart disease?

Answer 1

Cardiac failure or contractile dysfunction

ischemia

cardiac arrhythmia

Question 2

Cardiac Glycoside formation to be active?

Answer 2

Cis-Trans-Cis

A/B = cis fused
B/C = trans fused
C/D = cis fused

any other combo is inactive

Question 3

Will cardiac glycosides have positive or negative inotropic effect?

Answer 3

positive

work on SA node, AV node, and His-Purkinje system

Question 4

most widely accepted MOA of cardiac glycosides?

Answer 4

inhibition of Na/H ATPase pump

increasing intracellular ca, more ca released by SR, more available to bind troponin-C = increase contractility

Question 5

origin source of glycosides causes variation in?

Answer 5

size and degree of unsaturation of lactone ring

5-member a/b unsaturated = plant derived
6 membered, 2 double bond = animal derived

Question 6

Animal vs plant glycosides?

Answer 6

animal way more rare, less medicinal importance due to their high toxicity

Question 7

Where are two angular methyl groups located usually on cardiac glycoside?

Answer 7

C-10 and C-13

Question 8

Where are hydroxyl groups located on cardiac glycoside?

Answer 8

C-3 and C-14

C-3 = site of sugar
C-14 usually unsubstituted

Question 9

-genin represents…

Answer 9

lack of sugar, just steroid part

Question 10

Most commonly found sugars in cardiac glycosides are…

Answer 10

D-glucseo, D-digitoxose, L- rhamnose, and D-cymarose

Question 11

Where do cardiac glycosides have indirect action?

Answer 11

on cardiovascular system mediated by increased vagal nerve activity.

Question 12

What confirmation do the four sugars predominately exist in cardiac glycosides?

Answer 12

B-conformation

Question 13

What does the presence of an O-acetyl group on sugar do?

Answer 13

affects the lipophilic character and pharmacokinetics of entire glycoside

Question 14

Hydroxy group 16 position?

Answer 14

Gitoxin

Question 15

Hydroxy group at 12 position?

Answer 15

Digoxin

Question 16

No hydroxy group on 12?

Answer 16

Digitoxin

Question 17

Digoxin vs digitoxin

Answer 17

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.

Question 18

Digoxin info

Answer 18

oral bioavailability exhibits inter individual variability ranging form 70-85%

Question 19

P-gp

Answer 19

ABC-transporter, extensively distributed and epodes in normal cells

“throws drug out”

Question 20

Digoxin and Quinidine interaction

Answer 20

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)

Question 21

antianginal drugs act by mainly…

Answer 21

by dilating the coronary artery

Question 22

5 nitrates in use today?

Answer 22

Amyl nitrite
nitroglycerin
isosorbide dinitrate
erythritol tetra nitrate
pentaerythrivol tetranitrate

Question 23

nitrate group potency

Answer 23

increasing # of groups = increase potency

Question 24

why is long term efficacy of nitrates limited?

Answer 24

due to development of tolerance.

Question 25

structural properties of organic nitrates

Answer 25

small non-polar ester = volatile

moisture should be avoided during storage

explosive properties in conc form (ie when making at factor in big batch)

Question 26

nitrate MOA

Answer 26

nitrates undergo intracellular metabolism to produce vasodilation “bioactivation:

ALDH-2 only responsible for bioactivation of nitrates with highest vasodilator potency, not involved in lower potency ones

low potency nitrates + high dose high potency seem to have CYP450 involved

Question 27

Lanatosides A

Answer 27

makes Digitoxin = no OH

Question 28

Lanatoside B

Answer 28

Make Gitoxin = OH at C16

Question 29

Lanatoside C

Answer 29

makes Digoxin = Oh at C12