3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.1. Scrap
                  3.1.1.1. Sympathomimetics
 3.1.1.1.1. Adrenaline 

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