Adrenaline

[PHW2:p190-103]

 

Structure

Naturally occurring catecholamines

 

[WG:???

Synthesized from norepinephrine

Catalysed by Phenylethanolamine-N-Methyl-transferase (PNMT)
* Present in appreciable quantity in brain and adrenal medulla only

 

 

Pharmacodynamics

Mechanism of action

Agonism at alpha and beta adrenoceptors

• Alpha 1 activation (coupled to Gq)
  --> Stimulation of phospholipase C
  --> Increased IP3 and DAG
• Alpha 2 receptor activation (coupled to Gi)
  --> Inhibition of adenylate cyclase
  --> Reduce cAMP concentration
• Beta adrenoceptors (coupled to Gs)
  --> Stimulation of adenylate cyclase
  --> Increased cAMP

Effects

CNS

• Increases MAC
• Increases peripheral pain threshold

CVS

Effects vary according to dose.

• At low dose infusion --> beta effects predominate
  * Increased CO
  * Increased myocardial oxygen consumption
  * Coronary artery dilatation
  * Reduced threshold for arrhythmia
  * (Peripheral beta effect) Reduced peripheral vascular resistance and reduced diastolic blood pressure
• At high dose infusion or as 1mg bolus during cardiac arrest --> Alpha1 effects predominate
  * Increased systemic vascular resistance

Other CVS effects

• When used with halothane
  --> Limit dose to 100mcg per 10 minutes to avoid arrhythmia
• Extravasation --> Tissue necrosis
• Do not use in areas supplied by end arteries
  --> Vascular supply may become compromised

Respiratory

• Small increase in minute volume
• Potent bronchodilators
  * But secretion may become more tenacious
• Increased pulmonary vascular resistance

Metabolic

• Increases basal metabolic rate
• Increase plasma glucose
  * Stimulation of glycogenolysis (in liver and skeletal muscle)
  * Stimulation of gluconeogenesis
• Stimulation of lipolysis
  * Increased lipase activity --> Increased free fatty acid
  --> Increased fatty acid oxidation in liver and ketogenesis
• Insulin secretion
  * Initially increased (beta2 effect)
  * Later becomes inhibited (alpha effect)
• Hypokalaemia
  * Due to increased transport of K+ into cells
  * Potassium may initially rise instead due to release from liver

Renal

• Increased sodium reabsorption
  * Direct stimulation of tubular Na+ transport
  * Stimulation of renin release --> Increased aldosterone
• Renal blood flow moderately decreased
• Increased bladder sphincter tone
  --> Difficulty in micturition

Pharmacokinetics

Absorption

Not given orally due to inactivation

S/C absorption is slower than IM

Tracheal absorption is erratic
--> But may be used in emergency where there is no IV access

Metabolism

Metabolised by mitochondrial monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) within liver, kidney, and blood

Metabolites
* Inactive vanillylmandelic acid (VMA, or 3-methoxy-4-hydroxymandelic acid)
* Metadrenaline

Elimination

Metabolites are excreted in urine

Elimination T1/2 = 2 min
* Due to rapid metabolism

Pharmaceutics

Clear solution

0.1 - 1mg/mL

 

 

 

Clinical

Use

• Resuscitation in asystole
• In circulatory failure (as an infusion)
• Reduce swelling in upper airway (as nebulisation)
• Open-angle glaucoma (1% ophthalmic solution)
• Anaphylaxis
• Vasoconstrictor (with local anaesthetics)
  * 1:80,000 to 1:200,000

 

Administration