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Old 08-04-2012
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Drug Mechanism of a drug used to help maintaining sobriety

A 46-year-old woman with chronic alcoholism has recently undergone detoxification and has abstained from alcoholic beverages for several weeks. She has joined a “twelve-step” program and seeks assistance from her physician in helping maintain sobriety. Her physician prescribes an agent that is a structural analogue of γ-aminobutyric acid (GABA). By which mechanism does this agent help maintain abstinence from alcohol?

a) Accelerating ethanol catabolism
b) Augmenting dopaminergic activity in the nucleus accumbens
c) Blocking the effects of endorphins that reinforce the use of ethanol
d) Producing distressing symptoms when ethanol is ingested
e) Restoring the balance between excitatory and inhibitory neurotransmission
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e) Restoring the balance between excitatory and inhibitory neurotransmission
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Ya E

The phenomenon of alcohol dependence can be explained on a molecular basis. When GABA binds to the GABAA receptor, it opens a chloride channel, which permits extracellular chloride to move into the intracellular compartment. Because the chloride ion is negatively charged, it hyperpolarizes the neuron, which makes it refractory to excitatory postsynaptic potentials. Several compounds, such as neurosteroids, benzodiazepines, ethanol, and barbiturates, potentiate the activity of GABA. When an individual ingests alcohol, it facilitates the ability of GABA to open chloride ion channels, so that greater amounts of chloride ion move from the extracellular to the intracellular space. With chronic use of alcohol, the GABA system is down-regulated and the neuron may eventually become dependent on alcohol to enable GABA to function.
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The answer is e) Restoring the balance between excitatory and inhibitory neurotransmission

The patient was prescribed acamprosate, which is a structural analogue of the neurotransmitter GABA and the neuromodulator taurine. Acamprosate is believed to restore the balance between inhibitory GABA and excitatory glutamate neurotransmission in the brain, and so reduce the craving for ethanol. Acamprosate does not alter ethanol metabolism or the physiological and subjective effects of ethanol.
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