Table of Contents
- 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/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.
- 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;
barbiturates.txt · Last modified: 2009/03/18 05:28 by 127.0.0.1