Noradrenaline

[PHW2:p193-p194]

=== Unfinished ===

(Quick note only)

=====

 

NE = norepinephrine = noradrenaline

Pharmacodynamics

Mechanism of action

[PHW2:p193]

Actions are mainly via stimulation of alpha-1 adrenergic receptors

Also some stimulation of beta adrenergic receptors

Effects

[PHW2:p194]

CVS

Slightly different from endogenous NE
* Endogenous NE causes increased CO and tachycardia

 

Peripheral vasoconstriction

Increased systolic and diastolic BP

Possible reflex bradycardia

CO may fall

Increased venous return (due to venoconstriction)

Increased MVO2

Pulmonary vascular resistance may be increased

Reduced renal and hepatic blood flow

Reduced uterine perfusion
--> May result in foetal bradycardia

 

?? effect on lower oesophageal sphincter

 

NB:

Ischaemia and gangrene of extremities

Extravasation can cause tissue necrosis

[Chris Flynn] gut infarct

 

Use with caution in people taking monoamine oxidase inhibitors (MAOi)
--> Effect may be increased and prolonged

 

Pharmacokinetics

[PHW2:p194]

Metabolism

For endogenous NE, active uptake into nerve terminal (postganglionic sympathetic nerves)
--> Metabolised by MAO
* COMT is absent in sympathetic nerves

In circulation, NE is metabolised by COMT

Metabolites
* 3-methoxy-4-hydroxymandelic acid (vanillylmandelic acid or VMA) (inactive)
* Normetadrenaline (later conjugates with glucuronic acid or sulphates)

 

Rapid metabolism (T1/2 < 2 min)

 

Up to 25% is taken up by lung
* Unlike adrenaline and dopamine

Pharmaceutics

[PHW2:p193]

0.1-1 mg/mL

Preservative = sodium metabisulphite

 

Dose range = 0.05-0.5 microgram/kg/min