Med Chem Spring Lec 4

Front 1

Why is congestive heart failure or CHF termed like this?

Back 1

because the body becomes congested with fluid

Front 2

A group of drugs known as the __ ____ were found to reverse most of these CHF symptoms?

Back 2

cardiac glycosides

Front 3

Cardiac glycosides are what kind of agents?

Back 3

positive inotropic

Front 4

Both positive and negative inotropes are used in the management of various ___conditions

Back 4

cardiovascular

Front 5

. One of the most important factors affecting inotropic state is what?

Back 5

state is the level of calcium in the cytoplasm of the muscle cell

Front 6

Positive inotropes usually do what?

Back 6

increase the level of calcium in the cytoplasm of the muscle cell

Front 7

negative inotropes usually do what?

Back 7

decrease the level of calcium in the cytoplasm of the muscle cell

Front 8

Positive inotropic agents increase what?

Back 8

myocardial contractility

Front 9

Positive inotropic agents are used to support what?

Back 9

to support cardiac function in conditions such as decompensated congestive heart failure, cardiogenic shock, septic shock, myocardial infarction, cardiomyopathy, etc.

Front 10

Negative inotropic agents decrease what? What are they used to decrease?

Back 10

decrease myocardial contractility, and are used to decrease cardiac workload in conditions such as angina.

Front 11

Cardiac glycosides are composed of two portions? What are they?

Back 11

a sugar, and an aglycone segment

Front 12

The aglycone portion of the cardiac glycosides is what?

Back 12

is a steroid nucleus with a unique set of fused rings, easily distinguished from the other steroids

Front 13

In hydroxyl groups Hydroxyl groups: the ___ ____ is normally unsubstituted

Back 13

C-14 hydroxyl

Front 14

Hydroxyl groups: the C-14 hydroxyl is normally unsubstituted; however, additional hydroxyl groups may be found at ___ and ___

Back 14

C-12 and C-16

Front 15

Lactone ring: the size and degree of unsaturation of the lactone ring at C17 varies with what?

Back 15

the source of the glycoside

Front 16

. In most cases, the cardiac glycosides of plant origin, _____?

Back 16

cardenolide

Front 17

How do Cardenolides differ from bufadienolides?

Back 17

possess a 5-membered, α,β-unsaturated lactone ring, whereas those derived from animal origin, the bufadienolides, possess a 6-membered lactone ring with two conjugated doublebonds (referred to as α-pyrone).

Front 18

Digoxigenin and Gitoxogenin have one more hydroxyl than what?

Back 18

Digitoxigenin.

Front 19

Ouabagenin has additional hydroxyl groups and Strophanthidin has what functional group?

Back 19

aldehyde

Front 20

The hydroxyl group at C3 of the aglycone portion usually is conjugated to a ____ or ____ with what kind of linkage?

Back 20

monosaccharide or a polysaccharide with β-1,4-glycosidic linkages.

Front 21

most commonly found sugars in the cardiac glycosides are what 4?

Back 21

D-glucose, D-digitoxose, L-rhamnose, and D-cymarose.

Front 22

D-glucose, D-digitoxose, L-rhamnose, and D-cymarose. These sugars predominately exist in the ___ conformation?

Back 22

β-conformation

Front 23

Lanatoside A is composed of what? ITs connected to what?

Back 23

Lanatoside A is composed of the aglyconedigitoxigenin connected to three digitoxose sugar molecules, the third of which carries a 3-acetyl group, and a terminal glucose molecule.

Front 24

Lanotoside B and C have have what portions in common and what portions differ?

Back 24

identical sugars portions, but differ in their aglycone portions

Front 25

Partial hydrolysis of the glucose sugar and the acetyl group of Lanotoside A and C give us, what 2 cardiac agents?

Back 25

Digitoxin and Digoxin

Front 26

The medicinally used preparations of the cardiac glycosides are mainly obtained from what plants?

Back 26

from Digitalis purpurea and Digitalis lanata plants.

Front 27

Currently, _____ is the only cardiac glycoside commercially available for therapeutic use in the United States

Back 27

digoxin

Front 28

To arrive at an effective plasma concentration what is given?

Back 28

a large initial dose (i.e., digitalizing or loading dose) often is given

Front 29

The purpose of this large initial dose is to achieve what?

Back 29

achieve a therapeutic blood and tissue level in the shortest possible time.

Front 30

Once the desired effect is obtained, the amount of drug lost from the body per day is replaced with what?

Back 30

with a maintenance dose.

Front 31

It generally is accepted that the toxicity of the cardiac glycosides results from inhibition of what?

Back 31

the Na+/K+ATPase pump

Front 32

It generally is accepted that the toxicity of the cardiac glycosides results from inhibition of the Na+/K+ATPase pump, which results in what?

Back 32

which results in increased intracellular levels of Ca2+.

Front 33

Hypokalemia(decreased potassium) can be an important factor in initiating what?

Back 33

toxic response

Front 34

It has been shown that low levels of extracellular K+ partially inhibit what?

Back 34

Na+/K+ATPase pump.

Front 35

A common procedure used in treating cardiac glycoside toxicity is to administer what?

Back 35

potassium salts to increase extracellular potassium level

Front 36

A common procedure used in treating cardiac glycoside toxicity is to administer potassium salts to increase extracellular potassium level, which stimulates what?

Back 36

Na+/K+ATPase pump

Front 37

A common procedure used in treating cardiac glycoside toxicity is to administer potassium salts to increase extracellular potassium level, which stimulates the Na+/K+ATPase pump, resulting in decreased what?

Back 37

intracellular sodium levels and, thus, decreased intracellular calcium.

Front 38

Concurrent use of compounds that are substrates for P-gp may affect what?

Back 38

the therapeutic control of arrhythmias.

Front 39

Digoxin is actively secreted into where? By what cell? Via what?

Back 39

urine by the renal tubular cell via a P-gp efflux pump.

Front 40

Quinidine competes for binding in the ___ ___ and reduces what? By raising what concentration?

Back 40

renal tubule and reduces renal secretion of digoxin by P-gp, raising digoxin plasma conentration to toxic levels.

Front 41

Verapamil inhibits what?

Back 41

intestinal efflux of P-gp,

Front 42

Verapamil inhibits intestinal efflux of P-gp, competing with digoxin secretion into where?

Back 42

secretion into the lumen of the intestine

Front 43

Verapamil inhibits intestinal efflux of P-gp, competing with digoxin secretion into the lumen of the intestine, raising what to toxic levels?

Back 43

raising digoxin plasma conentration to toxic levels.

Front 44

Rifampin, on the other hand, is an inducer of what?

Back 44

inducer of intestinal P-gp expression,

Front 45

Rifampin, on the other hand, is an inducer of intestinal P-gp expression, thereby increasing the __-__-___ ___ of digoxin

Back 45

P-gp–mediated transport of digoxin.

Front 46

Rifampin, on the other hand, is an inducer of intestinal P-gp expression, thereby increasing the P-gp–mediated transport of digoxin. This results in the lowering of what?

Back 46

This results in the lowering of digoxin blood levels to subtherapeutic concentrations.

Front 47

Absorption of digoxin after oral administrationalso can be significantly altered by other drugs concur-rently present in what?

Back 47

gi tract

Front 48

laxatives may interfere with the absorption of digoxin because of increased what?

Back 48

increased intestinal motility.

Front 49

Antacids, especially magnesium trisilicate, and antidiarrheal adsorbent suspensions also may inhibit the absorption of what?

Back 49

of the digoxin.

Front 50

Potassium-depleting diuretics, such as thiazides, may increase the possibility of what? because of what?

Back 50

digitalis toxicity because of the additive hypokalemia.

Front 51

Rifampin, on the other hand, is an inducer of intestinal P-gp expression, thereby increasing the P-gp–mediated transport of digoxin. This results in the lowering of what?

Back 51

This results in the lowering of digoxin blood levels to subtherapeutic concentrations.

Front 52

Absorption of digoxin after oral administrationalso can be significantly altered by other drugs concur-rently present in what?

Back 52

gi tract

Front 53

laxatives may interfere with the absorption of digoxin because of increased what?

Back 53

increased intestinal motility.

Front 54

Antacids, especially magnesium trisilicate, and antidiarrheal adsorbent suspensions also may inhibit the absorption of what?

Back 54

of the digoxin.

Front 55

Potassium-depleting diuretics, such as thiazides, may increase the possibility of what? because of what?

Back 55

digitalis toxicity because of the additive hypokalemia.

Front 56

Several other drugs that are known to bind to plasma proteins, such as what?

Back 56

thyroid hormones

Front 57

Several other drugs that are known to bind to plasma proteins, such as thyroid hormones, have the potential to displace digoxin from where?

Back 57

from its plasma-binding sites,

Front 58

Several other drugs that are known to bind to plasma proteins, such as thyroid hormones, have the potential to displace digoxin from its plasma-binding sites, thereby increasing its __ ___ ___ to a toxic level

Back 58

free drug concentration to a toxic level.