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barbiturates

barbiturates

Introduction:

  • Introduced in 1903.
  • Meprobomate was introduced in 1954 as a nonbarbiturate sedative lacking the disadvantages of the older drugs. It turned out to have more similarities than differences from barbiturates.
  • Use as sedative/hypnotic has declined since benzodiazepines were introduced in 1960.
  • Barbiturates cause decr. excitable tissues CNS »> peripheral;
  • Act by inhib. of post-synaptic neurones via incr. chloride ion entry into these cells

  *NB. this is also the mechanism by which increased GABA concentration acts;

CNS effects:

  • mild sedation → general anaesthesia, some are anticonvulsants (eg. phenobarb.)
  • more sedation than anxiolytic than benzodiazepines; euphoria; overexcitement in some if pain;
  • 3x hypnotic dose → eliminates CO2 drive, decr. hypoxic drive;
  • P/Dyn. tolerance (peak wks-mths) > P/K tolerance (peak days-wks);
  • As tolerance incr., less sed/hyp/mood effect for same anticonv. & lethal effects → decr. therapeutic index;
  • P/D toler. confers to other CNS depressant drugs - ethanol (alcohol and alcohol withdrawal)/opioids!!

P/K of barbiturates:

  • rapidly & completely absorbed orally, onset 10-60min. - delayed if food;
  • Mod. bound to plasma protein (max. 65% with thiopentone);
  • Nearly complete metab. by microsomals & conjug. → renal excretion;
  • Enzymes rapidly induced esp. by phenobarbitone.

Phenobarbitone:

  • NB. methylphenobarbitone & primidone are metab.to phenobarbitone
  • Use as anticonvulsants has declined as concerns over mental dulling;
  • Broader spectrum anticonv. than carbamazepine/phenytoin - also use for myoclonic;
  • Not as effective as valproate in generalised seizures;
  • But more effective in partial seizures - occasionally works where others have failed;
  • T1/2 = 2-4days; thus once daily dose;
  • To avoid sedation, introduce dose slowly over several wks;
  • Important to ensure mental dulling does not build up insidiously after dose increased;
  • Initial Rx range after several wks use = 60-80umol/L (15-20mg/L);
  • If slow introduction, much higher levels may be tolerated;

Thiopentone:

barbiturates.txt · Last modified: 2009/03/18 16:28 (external edit)