(THER) Nitric Oxide Flashcards
Nitric Oxide (INOMAX) MOA and Route
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
Nitric Oxide (INOMAX) Indications and Side Effects
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)
Nitroglycerine MOA and Route
MOA: NO donor
Route: Sublingual
Nitroglycerine Indications and Side Effects
Ind: Pulmonary Artery Hypertension
SE: Hypotension
Name the NO related drugs which have an oral route of administration (3)
- Hydralazine
- Sildenafil (Viagra)
- L-Arginine
Hydralazine MOA
NO donor/ vasodilator
Hydralazine Indications and Side Effects
Ind: Hypertension
SE: Headache, nausea, vomiting, hypotension
Sildenafil (Viagra) MOA
Phosphodiesterase inhibitor
Sildenafil (Viagra) Indications and Side Effects
Ind: Pulmonary Hypertension; Erectile Dysfunction
SE: Hypotension, drug interactions
L-arginine MOA
NO donor
L-arginine indications and side effects
Ind: Acute Coronary Syndrome; Vascular disease
SE: Hypotension
What response is the hallmark of excessive NO production?
Inflammation (and decreased cell adhesion)
What synthesizes NO?
A family of enzymes collectively termed “nitric oxide synthase”
Name the 3 isoforms of NO. Which is the good type? Which is pathogenic?
NOS-1, NOS-2, NOS-3
NOS-2 is pathogenic because it is inducible. The others are constitutive and thus have housekeeping functions.
Name the categories of inhibitors of NO
- L-arginine derivatives
- Inhibitors of NO synthases synthesis
- Inhibitor of binding of arginine to NOs
- Scavengers of NO
(most are arginine analogues)
What functions as the key substrate for NO function?
L-arginine
What is the most important NO Inhibitor?
Hemoglobin
Pathologic responses to NO include…
Free radical formation, irritation and nitrosation
What can happen if sildenafil and nitrates are combined?
Sildenafil (viagra) + nitrates can lead to severe hypotension crisis.
NO and white cell adhesion
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
NO has been shown to protect against _______ and ________ injury
Ischemic and reperfusion
NO and platelets
NO is a potent inhibitor of platelet adhesion, activation, and aggregation, and regulates the release of serotonin, growth factors and thromboxane from platelets.
NO and organ transplantation
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
NO in the nervous system
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
What is the most widely used donor of NO?
Nitrates
What is the relationship between route of administration and duration of action for NO donors?
- Inhaled: Ultra short (3-5 minutes)
- Sublingual: Short (10-30 minutes)
- Oral/sustained release: Intermediary (4-8 hours)
- Transdermal: Long (8-10 hours)
