OzEMedicine - Wiki for Australian Emergency Medicine Doctors

see also sedatives, hypnotics and anxiolytics, anticonvulsants, induction agents for anaesthesia, pharmacology main index

• 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;

• 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!!

• 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.

• 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;

• see thiopentone
• IV use as anticonvulsant or induction agents for anaesthesia;
• Redistrib. after IV thio. terminates action (brain → muscle → fat) in 5-15min;