Norepinephrine

From Anvita Health Wiki

Contents 1 Function 2 Pharmacology 3 Indications 4 Contraindications 5 Dosage 6 Pharmacokinetics 7 Adverse-effects 8 Drug-interactions 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Function

• inhibitory neurotransmitter of the central nervous system & the sympathetic nervous system

• the most prominent nucleus in the CNS containing noradrenergic neurons is the locus ceruleus
• most of the remaining noradrenergic neurons are clustered in the lateral tegmental area

• also released by chromaffin cells of the adrenal medulla in response to stress.
• effects are mediated via adrenergic receptors

Pharmacology

• Tradenames: Levarterenol, Levophed. Norepinephrine bitartrate.

Indications

• septic shock
• hypotension persistent after adequate fluid volume replacement

Contraindications

• Caution: in patients with hyperthyroidism
  

• pregnancy category = ?
• safety in lactation = ?

Dosage

• 4 mg in 500 mL D5W (8 ug/mL):
• initiate at 2-4 ug/min (adults), 0.05-0.1 ug/kg/min (children)*
• 20 mL/hr = 3 ug/min
• titrate to desired response
• adults: 2-20 ug/min

*              dose ug/kg/min x weight kg x 60 min/hr 
* * Rate mL/hr = -------------------------------------- 
*                     concentration ug/mL

Pharmacokinetics

• onset of action 1-2 minutes
• duration of action: 1-2 minutes
• metabolized by:

• adrenergic nerve uptake
• catechol-O-methyl transferase ( COMT)
• monoamine oxidase ( MAO)

• 1/2life is 2.5 minutes
  

• elimination via plasma

Adverse-effects

• most common (1-10%)

• dizziness, headache, trembling, insomnia, thyroid gland enlargement

• uncommon (<1%)

• hypertension, gangrene of extremities, cardiac arrhythmias, palpitations, tachycardia, bradycardia (treat with atropine)

• other [3]

• lactic acidosis
• extravasation:

• treated with 5-10 mg of phentolamine in 10-15 mL of NS
• infiltrate involved area
  

• drug adverse effects of adrenergic receptor agonists
• drug adverse effects of beta-adrenergic receptor agonists
• drug adverse effects of alpha-adrenergic receptor agonists

Drug-interactions

• beta-blockers antagonize the effects of norepinephrine
• general anesthetics in combination increase cardiac irritability
• MAO inhibitors potentiate the direct pressor response

Mechanism-of-action

• directly stimulates

• alpha-1 adrenergic receptors
• alpha-2 adrenergic receptors
• beta-1 adrenergic receptors

• no direct action on beta-2 adrenergic receptors
• positive inotropic effects
• increases systolic & diastolic blood pressure
• increases myocardial oxygen consumption
• positive chronotrope overcome by vagal activity with resultant bradycardia
• increases in coronary blood flow
• decreases renal, skin, cerebral & muscle blood flow
• increases glycogenolysis & inhibits insulin release, resulting in hyperglycemia
• increases lipolysis

More General Terms

• catecholamine
• alpha adrenergic receptor agonist
• beta-1 adrenergic receptor agonist
• vasoconstrictor agent or vasopressor
• antiasthmatic agent

Additional Terms

• adrenergic receptor
• Na+ dependent noradrenaline transporter; norepinephrine transporter; NET; solute carrier family 6 member 2 (SLC6A2, NAT1, NET1, SLC6A5)
• norepinephrine in plasma
• norepinephrine metabolism

Internet Database

PubChem: 951
PubChem: 5814
PubChem: 439260
PubChem: 297812
PubChem: 5813
PubChem: 168929
PubChem: 9488
PubChem: 3047796

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 221

norepinephrine; noradrenaline (Levophed)