FRCA Notes


Sympathomimetics


  • Sympathomimetic drugs exert their effects by stimulation of the sympathetic nervous system
  • The structure of sympathomimetics is a benzene ring with an amine side chain attached at the C1 position
  • If there are also hydroxyl groups present on the C3 and C4 carbons, then the drug is a catecholamine (3,4-dihydroxybenzene is known as 'catechol')

By mode of stimulation

  • Directly acting sympathomimetics
    • Agonise receptors directly (either adrenoreceptors or dopamine receptors) to stimulate the sympathetic nervous system

  • Indirectly acting sympathomimetics
    • Trigger the release of noradrenaline from nerve endings, which then causes sympathetic nervous system activation via the above receptors
    • Examples include:
      • Release stimulants e.g. ephedrine
      • Enzyme inhibitors e.g. monoamine oxidase inhibitors, catechol-O-methyl transferase inhibitors
      • Re-uptake inhibitors e.g. amphetamine, cocaine and tyramine

By origin

  • Naturally occurring catecholamines include the endogenous neurotransmitters adrenaline, noradrenaline and dopamine
  • Of course, synthetic versions of these molecules are used in clinical practice

  • Synthetic catecholamines
    • Isoprenaline
    • Dobutamine
    • Dopexamine


Receptor Location Effect when agonised Mechanism
ɑ1 Vascular smooth muscle Vasoconstriction Gq GPCR
ɑ2 CNS Sedation, analgesia, attenuation of sympathetically mediated responses Gi GPCR
β1 Cardiac myocytes
Kidneys
Platelets
Positive inotropy and chronotropy
Activation of RAAS
Platelet aggregation
Gs GPCR
β2 Bronchi
Vascular smooth muscle
Uterus
Cardiac tissue
Relaxation of smooth muscle
Insulin secretion from pancreatic islets
Gs GPCR
β3 Adipose tissue Lioplysis Gs GPCR
D1 CNS and periphery Modulate extrapyramidal activity
Vasodilation (of renal and mesenteric vasculature)
Gs GPCR
D1 CNS and periphery Reduced pituitary hormone output
Nausea and vomiting at chemoreceptor trigger zone
Inhibit further noradrenaline release
Gi GPCR



Catecholamine synthetic pathway