FRCA Notes


Enzyme Inducers


  • The rate of reaction of an enzyme is described by the Michaelis-Menten equation:
Michaelis-menton_equation
  • The rate of the reaction can therefore be increased by:
    • Changing substrate concentration
    • Changing enzyme concentration
    • Changing Vmax
    • Changing KM

  • Sometimes enzyme activity is increased directly by positive allosteric modulation
    • For example, insulin binding to its receptors increased the activity of the tyrosine kinase portion of the receptor
    • This tends to either increase KM or Vmax

  • Other enzyme activity is increased indirectly via intermediate messengers
    • For example, G-protein coupled receptors whose alpha subunit increases the activity of adenylyl cyclase e.g. β-adrenoreceptors, D1 receptors, H2 receptors
  • Enzyme induction occurs, for example, in CYP450 enzymes in response to chronic exposure to their substrate
  • It leads to increased CYP450 enzyme concentration and can reduce the available concentration of drugs metabolised by the induced enzymes
  • Examples include:
CYP1A2 CYP2B6/2C9 CYP2C19 CYP2E1 CYP3A4
Omeprazole Barbiturates Prednisolone Ethanol (chronic) Phenytoin
Tobacco Rifampicin Rifampicin Isoniazid Barbiturates
Carbamazepine Carbamazepine
Rifampicin
Glucocorticoids
  • Specific examples of relevant clinical interactions include:
    • Phenytoin and carbamazepine will reduce vecuronium (CYP3A4) duration
    • Rifampicin and carbamazepine will reduce warfarin (CYP2C9) efficacy
    • Rifampicin will reduce ciclosporin efficacy
    • Barbiturates will reduce corticosteroid efficiency