Norepinephrine (NE)

Question 1

What is the trade name for NE?

Answer 1

Levophed

Question 2

What is the formal drug classification of NE?

Answer 2

NE is a direct acting catecholamine and adrenergic agonist

Question 3

What receptors does NE work on? Does NE have a preference for receptors?

Answer 3

Alpha and Beta-1»»Beta-2 (technically we believe it does NOT work at beta-2!!!!!)

Question 4

What are the clinical uses of NE?

Answer 4

• NE is a potent vasoconstrictor generally used for patients with adequate cardiac output but low SVR in acute hypotensive episodes
• Preserves cerebral and coronary blood flow during hypotensive emergencies and is an adjunct in the treatment of cardiac arrest and profound hypotension
• one of the most useful drugs when intense activity is needed with reduced vascular tone states with or without cardiogenic shock, including separation from cardiopulmonary bypass or situations when other vasopressors fail to maintain a steady hemodynamic state
• also been shown to improve renal and splanchnic blood flow by increasing pressure provided the patient is volume resuscitated

Question 5

What is the MOA of NE?

Answer 5

NE binds to alpha and Beta-1 receptors and has DIRECT acting effects in a dose related manner;

Question 6

In general, what are the effects of NE in low doses?

Answer 6

• NE produces increased CO (inotropy and chronotropy) and BP
• once bound to a receptor, NE activates a specific class of G proteins. The G protein activates an effector protein such as the enzyme adenylate cyclase. Stimulation of thie enzyme causes increased production of cAMP.

Question 7

What are the effects of NE in higher doses? What happens to coronary artery perfusion, and why?

Answer 7

• NE reduces flow because of alpha arteriolar constriction superseding the Beta-1 effects; the end result is unopposed alpha receptor stimulation and a decrease in vital organ flow
• coronary artery perfusion may be increased due to the increase in diastolic pressure!

Question 8

Is NE a peripheral or central vasoconstrictor? What does this cause?

Answer 8

NE is a PERIPHERAL vasoconstrictor and causes a marked increase in peripheral vascular resistance and MAP

Question 9

What does an increase in cAMP cause if the alpha-1 receptor is stimulated?

Answer 9

In alpha-1 receptors, cAMP will stimulate inward flux of calcium and facilitate the release of bound intracellular calcium causing vasoconstriction

Question 10

What does an increase in cAMP cause if the Beta-1 receptor is stimulated?

Answer 10

In Beta-1 receptors, cAMP stimulates an influx of calcium, increasing cytoplasmic calcium concentrations. this enhances the intensity of actin and myosin interaction increasing myocardial contractility

Question 11

What is the onset of IV NE?

Answer 11

RAPID

Question 12

What is the DOA of NE?

Answer 12

limited

Question 13

How is NE metabolized?

Answer 13

• It is inactivated by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) or both in the Blood, Liver, and Kidneys.
• NE that has undergone uptake will be metabolized in the cytoplasm by MAO and the excess NE that escapes uptake is metabolized by COMT

Question 14

Where is monoamine oxidase (MAO) present, and how does it work?

Answer 14

present in the Liver, Kidneys, and GI tract, which catalyzes oxidative deamination

Question 15

How does catechol-O-methyltransferase (COMT) work?

Answer 15

methylates the hydroxyl groups of catecholamines. Once methylated, the resulting metabolites are conjugated with glucuronic acid and normetanephrine

Question 16

What is the urine metabolite of NE, and how much is normally excreted in a 24hr period?

Answer 16

Vanillylmandelic acid; 2-4mg in a 24hr period

Question 17

What is the elimination route of NE?

Answer 17

25% of circulating NE is extracted during a single passage through lungs in normal resting ppl

Question 18

What is the e 1/2 life for NE?

Answer 18

2.5 minutes

Question 19

What are the side effects of NE usually the result of?

Answer 19

intense vasoconstriction; ischemic injury results from potent vasoconstrictor action and tissue hypoxia

Question 20

What can happen/signs and symptoms from overdose of NE?

Answer 20

Severe HTN with violent headache, photophobia, stabbing retrosternal chest pain, pallor, intense sweating, and vomiting

Question 21

What are the CV side effects of NE?

Answer 21

-sudden increase in SVR causes reflex baroreceptor mediated bradycardia despite active Beta stimulation

Question 22

When should NE be used cautiously?

Answer 22

• in the management of cardiogenic shock due to vasoconstriction that increases the pressure work of the LV and has an adverse effect of the oxygen economy of the ischemic pump
• also further vasoconstriction and end organ ischemia in a syndrome in which intense constriction may already have occurred

Question 23

What are the contraindications to NE?

Answer 23

• should not be given to patients who are Hypotensive from blood volume deficits except in emergency situations where cardiac and cerebral perfusion is necessary until blood volume has been replaced
• should not be used in patients with mesenteric or peripheral vascular thrombosis due to risk of increasing ischemia and extending area of infarction

Question 24

When NE is given with either ____________ or ____________, it can significantly induce cardiac arrhythmias such as Vtach or Vfib

Answer 24

Cyclopropane and Halothane anesthetics

Question 25

What drugs if taken with NE can produce severe, prolonged HTN or HTN crisis?

Answer 25

MAOIs or | Antidepressants of the triptyline or imipramine types

Question 26

What can happen if NE and beta-blockers are administered together?

Answer 26

Beta-blockers can increase the hypertensive effect, thus avoid concurrent use

Question 27

What can happen if NE and cocaine are administered together?

Answer 27

Cocaine can induce malignant arrhythmias

Question 28

What drugs if given with NE can increase pressor response? (hint: 4)

Answer 28

Methyldopa Guanethidine TCAs Reserpine

Question 29

What is the standard concentration of NE?

Answer 29

4mg/250mL; 16mcg/mL

Question 30

What is the dosage of NE?

Answer 30

0.01-0.1 mcg/kg/min OR | 4-16 mcg/min IV

Question 31

What is something to consider when administering Intravascular NE?

Answer 31

Should be given through a CENTRALLY placed IV to avoid tissue necrosis from extravasation

Question 32

If extravasation of NE occurs, what should you do?

Answer 32

infiltrate the area immediately with 10-15mL of saline solution containing 5mg-10mg of PHENTOLAMINE (an adrenergic blocking agent) with a hypodermic needle. This will prevent sloughing and necrosis of the area