pharm: 10-1 Nitric Oxide

Question 1

A: In what Physical state (solid vs liquid vs gas) does Nitric Oxide typically work?

B: Molecularly, From What and how is NO created?

C: Name the 2 Ways NO is generated in the body

D: NO is also known as ____

Answer 1

A: Gaseous (NO is a gaseous signaling molecule)

B: Oxidation of an [Arginine guanidine group] by [Nitric Oxide Synthase]

C:

1) Exposure to [bacterial LPS-B] / [bacterial endotoxin] —> Macrophage upregulation of iNOS2 –> Nitric Oxide Secretion
2) [ACh and Carbochol] can stimulate vasulcar endothelium to secrete NO

D: AKA EDRF [Endothelin Derived Growth Factor]

Question 2

There are 3 Isoforms of [Nitric Oxide Synthase - NOS]

Describe NOS 1

A: Other Name

B: Tissue

C: Expression

D: Ca+ requirement?

E: Chromosome

Answer 2

(nNOS1)

A: [Neuronal NOS - 1]

B: Enables Neuronal epithelium to produce NO

C: [Constitutive Housekeeper]

D: YES, DOES REQUIRE Ca+

E: Chromo 12

Question 3

There are 3 Isoforms of [Nitric Oxide Synthase - NOS]

Describe NOS 2

A: Other Name

B: Tissue

C: Expression (2)

D: Ca+ requirement?

E: Chromosome

F: Relation to Bacteria

Answer 3

(iNOS2)

A: [Inducible NOS - 2]

B: [Macrophage and Smooth Muscle cells]

C: [Transcriptional Induction]

D: No

E: Chromo 17

F: iNOS2 is bad because it is induced by [Bacterial LPS-B]

Question 4

There are 3 Isoforms of [Nitric Oxide Synthase - NOS]

Describe NOS 3

A: Other Name

B: Tissue

C: Expression

D: Ca+ requirement?

E: Chromosome

F: How does eNOS3 contribute pathologically? (2)

Answer 4

(eNOS3)

A: [Endothelial NOS - 3]

B: Peripheral Endothelial Cells

C: [Constitutive Housekeeper]

D: No

E: Chromo 7

F: Involved in vasodilation during [acute inflammation] AND [Inflammation Diseases]–> allows NO to promote edema

Question 5

A: How do you inhibit NO synthesis (5)?

B: [Nitric Oxide Synthase] isoforms are _____that contain ____ and require what to function?

C: Describe NO [Mechanism of Action]

D: Most NOS inhibitors are ______ analogues

Answer 5

“Use a [Free HAND] to inactivate NO”

A:

1. Arginine analogues inhibit conversion of [L-arginine] to [L-citrulline].
2. Heme (NO scavenger)
3. [Free Radical Superoxides] (which can also combine with NO to form [peroxynitrite ONOO]. [peroxynitrite ONOO​] IS TOXIC and regulated by [glutathione which DEC in DM and CVD].
4. NO Scavengers
5. Direct Inhibitors of NOS or [NOS-to-arginine binding]

B: [Nitric Oxide Synthase] isoforms are Flavoproteins that contain HEME and require Co-FActors to function

C: NO interacts with [Heme moiety of soluble guanyl cylclase] –>causes it to convert GTP into cGMP. cGMP removes phosphate from [Myosin light chain]–> VasoRelaxation

D: Most NO inhibitors are [Arginine SUBSTRATE] analogues

Question 6

A: NO undergoes oxidation AND reductive rxns —> ________

B: What is the Function of Nitrous Oxide?

C: Function of NiTrite?

D: Function of [Nitric Oxide] (4)?

Answer 6

A: NO undergoes oxidation AND reductive rxns —> Variety of Oxides of Nitrogen

B: Anesthetic

C: Stable Oxidation product of NO that decomposes to NO at an acidic pH

D: NO: Vasodilator / Platelet inhibitor / Immune regulator / neurotransmitter

Question 7

A: Most NO inhibitors are ______ analogues

B: Name the 5 NO inhbiitors- ______ analogues

C: Which one inhibits iNOS2 dimerization? How does it work with the other 2 isomers?

D: Which is a [NO scavenger]?

Answer 7

A: Most NO inhibitors are [Arginine SUBSTRATE] analogues

B: L-NMMA / L-NAME / [7-Nitroindazole] / BBS2 / Hgb

C: BBS2 - and weakly works on [nNOS1 and eNOS3]

D: Hgb

Question 8

A: NO can generate several reactive nitrogen derivatives by interacting with ______ and ______

B: How are these compounds bad for the body?

Answer 8

NO can generate [reactive nitrogen derivatives] by interacting with [molecular oxygen] and [Free superoxide radicals]

B: These RND oxides of nitrogen are highly reactive / unstable, interact with numerous proteins, lipids, [nucleic acids] and metabolize. They alter physiology of cells and tissues and mediate pathologic effects

Question 9

A: 5 PROS/Indications of Nitric Oxide

B: 3 Cons of Nitric Oxide

Answer 9

PROS: “ PAPA’S D is a PRO with Nitric Oxide”

1. [Broncho / VasoDilation] via smooth m. relaxation
2. Immune Regulation (inhibits [WBC E-selectin] from adhesing to endothelium–>reduces ischemic/reperfusion injury)
3. Anesthetic
4. [Atherosclerosis Prevention and Tx]
5. Pulmonary HTN
6. Pediatric Acute Respiratory Distress Syndrome - PARDS
7. [Stroke and Vascular Dementia] as a NTS and receptor neuromodulator

CONS:

1. [Free Radical Formation]
2. Nitrosation
3. Irritant Effects

Question 10

A: How does NO prevent Atherosclerosis (3)

B: How is NO related to [Graft Atherosclerosis]

B2: What’s the Catch 22 with this

Answer 10

1. potent inhibitor of platelet [adhesion, activation, aggregation]
2. regulates release of [serotonin, (Platelet Derived growth factors), thromboxane] from platelets
3. Indircectly enhances Fibrinolysis by inhibiting antiplasmin release from platelets

B: [Graft Atherosclerosis] occurs after organ transplant and is a major cause of graft failure. [NO AND (Dietary L-Arginine) prevents Platelet activation–> Reduce [Graft Atherosclerosis].

B2: Catch 22 = EXCESSIVE NO–>Actually Promotes [Graft Atherosclerosis]

Question 11

A: What does NANC neurons stand for?

B: Where are they and what are they used for?

Answer 11

A:[NANC neurons] = [Nonadrenergic, noncholinergic neurons].

B: Found in peripheral tissues and mediate Erectile response by releasing NO

Question 12

A: Which Nitrate Drug is Ultra Short acting and rarely prescribed?

B: Duration of Action for Sublingual NTG

C: How is NO administered for [Primary Pulmonary HTN]

C2: Name 4 other indications for this type of NO administration

Answer 12

A: [Inhaled Amyl Nitrate]: DOA= 3-5 min

B: Sublingual NTG: DOA= 10-30 min

C: Administered in a Close Fitted Mask and then gradually tapered off to avoid rebound

C2:

• [INC Oxygenation in Newborn pulmonary hypOtension]
• Lung Transplant / Sickle Cell Crisis / [Cardiopulmonary bypass]

Question 13

A: What is INOMAX and what’s it’s indication?

B: NTG is _____ (route of administration) and used for _______

C: MOA / Route of Admin / Indication / Side Effects(4) for Hydralazine

Answer 13

A: INOMAX = Inhaled Nitric Oxide for Acute Coronary Syndrome

B: NTG is sublingual and used for [Pulmonary Arterial HTN]

C: Hydralazine: [NO donor] administered orally for HTN. Side Effects= HA / N/V / hypOtension

Question 14

[Dietary L-Arginine]

A: MOA

B: Route of Administration

C: Indications (2)

D: Side Effects

Answer 14

A: NO Donor

B: Oral

C: ACS / Vascular Dz

D: hypOtension