Med Chem CHF Part 1

Question 1

define heart failure

Answer 1

inability of the heart to pump blood effectively at a rate that meets the needs of the tissues

Question 2

heart failure is a direct result of what

Answer 2

reduced contractility of the heart muscle (esp left ventricle)

Question 3

heart failure leads to what 2 things

Answer 3

-increase blood volume in the heart (congestion)

-edema in the lower extremities

Question 4

4 major stages of heart failure and explain what they are

for which 2 stages do you actually have heart failure and pharmacologic therapies are used to treat it?

Answer 4

A-D

A - RISK. no symptoms or structural disease

B - structural disease but NO symptoms

C - structural disease WITH symptoms

D - persistent heart failure

stages C and D

A and B are just at risk

Question 5

what kind of drugs are used in stages A and B heart failure

Answer 5

these patients are just AT RISK for heart failure

their HTN, hyperlipidemia, obesity, diabetes, etc are treated to SLOW THE PROGRESSION

heart failure itself is not treated because the patient doesnt have it yet

Question 6

name 6 classes of drugs used to treat heart failure

Answer 6

thiazides
ACE inhibitors
ARBS

+ inotropes
sympathomimetics
ARNI (ARB + neprlyisin inhibitor combo)

Question 7

name 3 positive (+) inotropes that can be used for heart failure

Answer 7

cardioactive glycosides
amrinone
milrinone

Question 8

name 2 sympathomimetics that can be used for heart failure

Answer 8

dopamine and dobutamine

Question 9

explain how dopamine and dobutamine work to treat heart failure

(they are both + inotropes and sympathomimetics)

Answer 9

they are beta adrenergic agonists

thus, they stimulate the heart via B1 receptors. this increases cAMP which leads to increased calcium, and myocardial contraction

Question 10

chemically, dobutamine and dopamine are both…..

Answer 10

catecholamines

Question 11

true or false

cardioactive glycosides are naturally derived

Answer 11

true

Question 12

*briefly state the structure of cardiac glycosides

Answer 12

“glycoside” — sugar + an aglycone

an aglycone is a steroid nucleus. A/B and C/D must be CIS FUSED**** and B/C are TRANS FUSED***

Question 13

What is the name of the most important sugar in cardioactive glycosides (inotropes)

Answer 13

digitoxose

Question 14

where on the steroid structure are the sugars attached for the structure of cardioactive glycosides?

Answer 14

at the C3 hydroxy

Question 15

true or false

for the structure of cardioactive glycosides, it is absolutely necessary for activity for A/B to be cis fused

Answer 15

FALSE

trans will decrease activity, but it will still be somewhat active

Question 16

true or fasle***

the B/C rings of cardioactive glycosides MUST be trans fused for activity

Answer 16

true

Question 17

true or false

the C/D rings of cardioactive glycosides MUST be cis fused for activity

Answer 17

true

Question 18

**MOA of cardioactive glycosides

Answer 18

inhibits the Na/K ATPase in the myocardium membrane

Question 19

**name the 3 major drug interactions for cardioactive glycosides

Answer 19

-increased or decreased P-glycoprotein activity

-absorption inhibition

-CYP3A4 inducer (only affects digitoxin)

Question 20

if a drug INDUCES P-glycoprotein, what does this do to the levels of the cardioactive glycosides?

Answer 20

decreased levels

if inhibit - increased levels bc drug not being pumped out

Question 21

name 3 NON glycosidic positive inotropes

Answer 21

amrinone
milrinone
inamrinone

Question 22

MOA of the non glycosidic (+) inotropes

Answer 22

PDE3 inhibitors

thus inhibit cAMP breakdown. increased cAMP leads to increased calcium and causes muscle contraction

Question 23

how are the non-glycose inotropes administered

Answer 23

all are via IV

Question 24

**pharmacophore of the nonglycosidic inotropic agents

Answer 24

dihydro-bypyridines

Question 25

inhibiting neprilysin increases the bioavailability of what 3 things and what does this result in

Answer 25

natriuretic peptides
bradykinin
substance P

natriuresis and vasodilation

Question 26

***true or false

sacubitril is a prodrug

Answer 26

TRUE

Question 27

oldest class for treating acute angina

Answer 27

nitro vasodilators

Question 28

***metabolism of nitro vasodilators

Answer 28

by glutathione-nitrate reductase in the liver (reduces nitrate to an OH)

Question 29

MOA of nitro vasodilators

Answer 29

they are organic nitrates. they release NO

this activates guanylyl cyclase which causes an INCREASE in cGMP.

this increase in cGMP activates kinase —– results in relaxation

Question 30

**key piece of hydralazine that gives it its activity

Answer 30

hydrazine

H2N-NH2

Question 31

is sodium nitroprusside used a lot?
why or why not?

Answer 31

NO

neurotoxic – has cyano group which gets metabolized in the liver to cyanide which becomes thiocyanate

Question 32

*name of the non-nitro vasodilator that is structurally related to the thiazides

**does it have a similar MOA?

Answer 32

diazoxide

NOT same MOA at all - causes sodium and water retention and decreased UO - not used for long time

**MOA diazoxide – potassium channel opener. activates ATP potassium channels – causing decrease in intracellular calcium, and REDUCING THE EXCITABILITY of smooth muscle – vasodilation

Question 33

true or false

to get vasodilatio, we want increased calcium

Answer 33

FALSE - decreased

this is what diazoxide does

Question 34

ADR diazoxide

Answer 34

hyperglycemia

Question 35

**true or false

minoxidil is not a prodrug

Answer 35

FALSE - it is

active form is MINOXIDIL SULFATE**8

Question 36

*MOA minoxidil

Answer 36

SAME AS DIAZOXIDE – potassium channel opener

Question 37

*pharmacophore minoxidil

Answer 37

piperidine-pyrimidine

Question 38

issue with using minoxidil for heart failure

Answer 38

causes a reflex response - increase in heart rate and cardiac output, increased renin activity and sodium and water retention :(

Question 39

*name the 2 different chemical classes of beta blockers and if they prefer to be R or S

Answer 39

arylethanolamines - prefer to be R

aryloxypropanolamines - prefer to be S