barbiturates

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!!

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;