Pharm - Lec#4 - Nitric Oxide Flashcards Preview

PHARM/MHD - Exam #4 > Pharm - Lec#4 - Nitric Oxide > Flashcards

Flashcards in Pharm - Lec#4 - Nitric Oxide Deck (34):
1

Nitric Oxide (INOMAX)

- MOA
- route

Covalent modification of proteins

- inhalation

2

Nitric Oxide (INOMAX)

- indications
- side effects

- Pulmonary Hypertension

- Vasodilation

3

Nitroglycerine

- MOA
- route

NO donor

- sublingual

4

Nitroglycerine
- indications
- side effects

ACUTE CORONARY SYNDROME

- hypotension

5

Hydralazine

- MOA
- route

NO donor, vasodilator

- ORAL route

6

Hydralazine

- indications
- side effects

- hypertension

SE:
- headache
-nausea
-vomiting
-hypotension

7

Sildenafil (viagra)

- MOA
- route

MOA: phosphodiesterase inhibitor

Route - oral

8

Sildenafil (viagra)

- indications
- side effects

Indications: hypertension

SE:
- hypotension
- drug interactions (if given with NITRATE)

9

L- Arganine

- MOA
- Route

MOA: NO donor

Route: Oral

10

L- Arganine

- Indications (2)

- Side effects

Indications:
ACS
Vascular Disease

SE: hypotension

11

What causes the generation of NO in the macrophage?

What is it generated from?

exposure to bacterial LPS

- oxidation of the guanidine group of arginine

12

Acetylcholine & Carbachol causes the endothelium to release _____

EDRF (NO)

13

State the following for Nos1, Nos2, and Nos3:

1. other name
2. Tissue expression
3. Constitutive/inducible

NOS1:
- neuronal NOS (nNOS)
- NEURONAL epithelium
- constitutive

NOS2****
- iNOS
-macrophage, smooth muscle cells
- INDUCIBLE
(bad! associated with pathologic conditions)

NOS3:
- endothelial nos (eNOS)
- endothelial cells
- constitutive

14

What NOS is only activated in pathologic states?

What causes this activation?

iNOS

- induced by LPS

15

What is L- Arginine converted to generate NOS

What does it require as cofactors

L- Arginine to L - CITRULLINE

1. NADPH
2. FAD
3. THF

16

Some nitric oxide donors such as oxygenated nitroprusside, spontaneously generates NO,

whereas others such as the _____ and organic ____ and _____ such as nitroglycerin require the presence of a THIOL compound such as cysteine.

furoxan
nitrates
nitrites

17

What nitric oxide derivative is conveniently measured in SEPSIS?

NITRATE
(NO3-)

- MOST STABLE

- CONVENIENTLY MEASURED IN PATIENTS WITH SEPSIS!!!!
- iNOS --> due to lipopolysaccharide of bacteria

18

Why are low levels of GLUTATHIONE related to increased vascular pathology in CV disease and diabetes?

low glutathione = HIGH NO

- increased NO results in greater hypotensive effects and INFLAMMATION

- contributes to vascular pathology

19

What are the 4 inhibitors of NO?

1. L-arginine Derivatives (L-NMMA, L-NAME)

2. Inhibitors of nitric oxide synthase synthesis

3. Inhibitor of binding of arginine to NOs

4. Scavengers of NO

20

Excess production of NO results in the generation of _____ which is toxic to cells

peroxynitrite

21

State the 5 inhibitors of NO

1. L- NMMA
2. L- NAME
3. 7 - Nitroindazole
4. BBS-2
5. Hemoglobin!!

22

What is a scavenger of NO that inhibits it?

HEMOGLOBIN!!!

23

What are the beneficial and pathologic effects of NO?

The beneficial effects include smooth muscle relaxation, vasodilation, immune regulation, anesthetic and anti-athlerosclerotic responses.

The pathologic responses include free radical formation, nitrosylation of protein and irritant effects.

24

What is particularly dangerous of taking Nitrates w/ sildenifil (viagra)

many patients are taking NITRATES & phosphodiesterase inhibitors like VIAGRA (sildenifil)

can generate severe hypotension AND SHOCK!!!!

(nitrates already lower BP, sildenifil increases this effect)

25

How does NO generate smooth muscle relaxation?

NO -> bind GC by heme moiety--> convert GTP to cGMP --> DEPHOSPHORYLATION OF MYOSIN LIGHT CHAIN
= relaxation!

26

State the vascular effects of NP

NO is also a potent inhibitor of the white cells adhesion to the endothelial surface.

It decreases the release of adhesion molecules such as the E-selectin on the endothelial surface.

NO has been shown to protect against ischemic and reperfusion injury. (TEST)


27

State pulmonoary effects of NO

How is it administered

- bronchodilator
(used in kids for ARDS)

- used for PULMONARY HTN!!!

INHALATION

28

What reduces the shock & hypotension caused by iNOS activated by bacterial LPS?

L-NMMA

- High levels of NO and dysoxia result in severe ischemia and perfusion defects

29

How does NO inhibit platelet function?1

1. inhibit adhesion, activation, aggregation
- regulates the release of serotonin, growth factors and thromboxane from platelets

2. NO also indirectly enhances fibrinolysis by inhibiting the release of antiplasmin from the platelets.

30

How does NO affect organ transplants?

Nitric oxide acts as a cytoprotective agent and prevents cellular and platelet adhesion

- Dietary arginine supplements are helpful in the management of transplantation patients

31

Which NOS (1,2,3) is responsible of the inflammatory affects experienced in diseases like IBD, arthritis, etc?

NOS 3
- mediates ACUTE inflammation

32

What is the most long acting NO donor?

Transdermal nitroglycerine 8-10 hours

33

What is the MOA of NO?

Primarily produce smooth muscle relaxation by releasing endogenous NO which produces the following effects.

A.Stimulates guanyl cyclase
B.Increased production of cGMP
C.Dephosphorylation of myosin

34

What are the indications of NO?

Selective pulmonary vasodilation

Treatment of newborn with persistent pulmonary hypotension (improves oxygenation)

Beneficial effects in cardiopulmonary bypass in adults, congestive heart disease, primary pulmonary hypertension, pulmonary edema , lung transplantation and sickle cell crisis.