Alcohol and Barbiturates
Acute alcohol intoxication causes increased sensitivity of an individual to the general
depressant effects of barbiturates.
Barbiturates and alcohol both interact with the gaminobutyrate (GABA)activated chloride channel.
Activation of the chloride channel inhibits neuronal firing, which may explain the depressant effects of both compounds.
This drug combination is very dangerous and normal prescription doses of barbiturates have
potentially lethal consequences in the presence of ethanol.
In addition to the depressant effects of both ethanol and barbiturates on the central nervous system (CNS), ethanol
inhibits the metabolism of barbiturates, thereby prolonging the time barbiturates remain
effective in the body.
Hydroxylation of barbiturates by the endoplasmic reticulum of the liver is inhibited by ethanol.
This reaction, catalyzed by the NADPH dependent
cytochrome system, forms watersoluble derivatives of the barbiturates that are eliminated readily from the circulation by the kidneys.
Blood levels of barbiturates remain high when ethanol is present, causing increased CNS depression.
Surprisingly, the alcoholic when sober is less sensitive to barbiturates.
Chronic ethanol consumption apparently causes adaptive changes in the sensitivity of the CNS to barbiturates (crosstolerance).
It also results in the induction of the enzymes of liver endoplasmic reticulum involved in drug hydroxylation reactions.
Consequently, the sober
alcoholic is able to metabolize barbiturates more rapidly.
This sets up the following
scenario. A sober alcoholic has trouble falling asleep, even after taking several sleeping
pills, because his/her liver has increased capacity to hydroxylate the barbiturate contained in the pills. In frustration he/she consumes more pills and then alcohol. Sleep results, but may be followed by respiratory depression and death because the alcoholic, although less
sensitive to barbiturates when sober, remains sensitive to the synergistic effect of alcohol