(THER) Nitric Oxide

Question 1

Nitric Oxide (INOMAX) MOA and Route

Answer 1

MOA: NO interacts with the heme moiety of guanyl cyclase and then converts GTP to cyclic GMP. This leads to protein kinase G activation and vasodilation as a result

Route: Inhalation

Question 2

Nitric Oxide (INOMAX) Indications and Side Effects

Answer 2

Ind: Acute Coronary Syndrome (improves cardiopulmonary function in adults with pulmonary hypertension)

SE: Vasodilation (so is sometimes used for kids with acute respiratory distress syndrome)

Question 3

Nitroglycerine MOA and Route

Answer 3

MOA: NO donor

Route: Sublingual

Question 4

Nitroglycerine Indications and Side Effects

Answer 4

Ind: Pulmonary Artery Hypertension

SE: Hypotension

Question 5

Name the NO related drugs which have an oral route of administration (3)

Answer 5

1. Hydralazine
2. Sildenafil (Viagra)
3. L-Arginine

Question 6

Hydralazine MOA

Answer 6

NO donor/ vasodilator

Question 7

Hydralazine Indications and Side Effects

Answer 7

Ind: Hypertension

SE: Headache, nausea, vomiting, hypotension

Question 8

Sildenafil (Viagra) MOA

Answer 8

Phosphodiesterase inhibitor

Question 9

Sildenafil (Viagra) Indications and Side Effects

Answer 9

Ind: Pulmonary Hypertension; Erectile Dysfunction

SE: Hypotension, drug interactions

Question 10

L-arginine MOA

Answer 10

NO donor

Question 11

L-arginine indications and side effects

Answer 11

Ind: Acute Coronary Syndrome; Vascular disease

SE: Hypotension

Question 12

What response is the hallmark of excessive NO production?

Answer 12

Inflammation (and decreased cell adhesion)

Question 13

What synthesizes NO?

Answer 13

A family of enzymes collectively termed “nitric oxide synthase”

Question 14

Name the 3 isoforms of NO. Which is the good type? Which is pathogenic?

Answer 14

NOS-1, NOS-2, NOS-3

NOS-2 is pathogenic because it is inducible. The others are constitutive and thus have housekeeping functions.

Question 15

Name the categories of inhibitors of NO

Answer 15

1. L-arginine derivatives
2. Inhibitors of NO synthases synthesis
3. Inhibitor of binding of arginine to NOs
4. Scavengers of NO

(most are arginine analogues)

Question 16

What functions as the key substrate for NO function?

Answer 16

L-arginine

Question 17

What is the most important NO Inhibitor?

Answer 17

Hemoglobin

Question 18

Pathologic responses to NO include…

Answer 18

Free radical formation, irritation and nitrosation

Question 19

What can happen if sildenafil and nitrates are combined?

Answer 19

Sildenafil (viagra) + nitrates can lead to severe hypotension crisis.

Question 20

NO and white cell adhesion

Answer 20

NO is a potent inhibitor of white cell adhesion to the endothelial wall. It decreases the secretion of adhesion molecules such as E-selectin, on the endothelial wall

Question 21

NO has been shown to protect against _______ and ________ injury

Answer 21

Ischemic and reperfusion

Question 22

NO and platelets

Answer 22

NO is a potent inhibitor of platelet adhesion, activation, and aggregation, and regulates the release of serotonin, growth factors and thromboxane from platelets.

Question 23

NO and organ transplantation

Answer 23

IT HELPS!

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

Dietary arginine supplements are helpful in the management of transplantation patients

Question 24

NO in the nervous system

Answer 24

It plays a major role as a ne_u_rotransmitter. It is implicated in the neuromodulatory process and affects stroke/vascular dementia. Also widely distributed to the peripheral tissues

Question 25

What is the most widely used donor of NO?

Answer 25

Nitrates

Question 26

What is the relationship between route of administration and duration of action for NO donors?

Answer 26

1. Inhaled: Ultra short (3-5 minutes)
2. Sublingual: Short (10-30 minutes)
3. Oral/sustained release: Intermediary (4-8 hours)
4. Transdermal: Long (8-10 hours)