Vasodilators

Question 1

What are drugs that regulate cGMP

Answer 1

Organic nitrates
PDE inhibitors
Natriuretic peptide

Question 2

What effect does elevated cGMP have on vascular smooth muscle

Answer 2

relaxes it

Question 3

Why are K channel openers vasidilatory

Answer 3

-K sets the membrane potential. The longer the K -channel is open the closer the membrane potential is to the K equilibrium
-The closer the membrane potential is to the K equilibrium potential, the harder it is to depolarize the membrane enough top open voltage gated Ca channels.
-Ca channels not open, no constriction

Question 4

Name the K channel agonists/openers

Answer 4

Minoxidil
Diazoxide
Adenosine

Question 5

Minoxidil MOA, side effects, cAMO or cGMP?,

Answer 5

Minoxidil is a prodrug that binds and opens k channels and inhibits ca influx through voltage gated ca channel.

side effects- hypertrichosis
cAMP

Question 6

Diazoxide indication?

Answer 6

used iv for htn binds to K channel, also used for hyperinsulinemia to inhibit release of insulin from pancrease

Question 7

Adenosine MOA

Answer 7

Does not directly bind to k channel like minoxidil and diazoxide, it binds to a GPCR called A1, which is coupled to a K channel. Causes relaxaton.

G(beta gamma) binds and activates
GIRK- conducts K+
efflux & membrane
hyperpolarization

Question 8

know structure of minoxidil, diazoxide and adenosine

Question 9

where and how is nitric oxide generated

Answer 9

Nitric oxide is produced in vascular endothelium.

arginine converted to citruline and NO

Question 10

What is the name of the enzyme used to create nitric oxide in vascular endothelium

Answer 10

eNOS

Question 11

how is enos activated

Answer 11

by calcium calmodulin

Question 12

is NO cAMP or cGMP

Answer 12

cGMP

Question 13

whole process of how NO is made and causes vasodilation

Answer 13

-arginie is converted to citruline and NO in endothelium by eNOS
-NO diffuses into vascular SM
-NO activates and binds guanylyl cyclase (contains heme center) and converts GTP to cGMP
-cGMP inhibits activation of contraction by activating cGKI (protein kinase G)

Question 14

What is cGKI

Answer 14

protein kinase G

Question 15

what does cGKI do?

Answer 15

relaxes smooth muscle

Question 16

How does cGKI cause relaxation of smooth muscle

Answer 16

-Inhibits Cav1.2 and inhibits Ca influx
-activates myosin phosphatase I
-Enhanced Ca uptake into ER by phosphalamban
-stimulation of ca activated K channels

Question 17

Are organic nitrates selective or non-selective

Answer 17

non-selective

Question 18

Know structure for organic nitrates

Question 19

organic nitrate drug names

Answer 19

Amylnitrate
GTN
PETN
ISDN
ISMN
Nitroprusside

Question 20

Which organic nitrate has the shortest half life

Answer 20

GTN

Question 21

which organic nitrate has the largest t1/2 and best oral bioavailability

Answer 21

ISMD

Question 22

how is GTN activated inn vivo

Answer 22

enzyme called ALDH 2 (aldehyde dehydrogenase2 ) in mirochondria activates NO

Question 23

How is tolerance to organic nitrate generated

Answer 23

• once NO is generated, we develop a disulfide on dehydrigenase
  -Lipoic acid reduces disulfide on ALDH-2 to active form
• With persistent or chronic administration of organic nitrate, we run out of reducing enzymes , so we can not generate active form.

-once we take a break from the nitrate to regenerate the enzymes, it can be efficacious again

Question 24

Why is GTN not as efficacious in Asians

Answer 24

Most asians have LYS 504 instead of glutamate.
Glutamate is 10X more efficient at metabolizing GTN

Question 25

What is the nitrous oxide with iron in the middle called

Answer 25

Sodium nitroprusside

Question 26

dangers of sodium nitroprusside

Answer 26

May have cyanide after bioactivation