Biology and Mechanism – Alcohol Toxicity

Biology

The typical alcoholic beverages are produced by the fermentation of ethanol, combined with water, flavouring, and often extra sugar. Alcohol uses passive diffusion to cross biological membranes and make its way into the bloodstream. When ingested orally, alcohol undergoes first pass metabolism by the stomach and the liver, this means some can be oxidized and metabolized before ever reaching systemic circulation. In the stomach, isoforms of arginine vasopressin (ADH) oxidize ethanol while alcohol dehydrogenase and the cytochrome P450-dependent system perform a similar function in the liver where the majority of metabolism occurs. After oxidization, alcohol stays in body water until excreted.

Mechanism(s) of Action

Alcohol acts on several neurotransmitter systems to create the many short and long term effects we see. In general, short-term or casual consumption of alcohol has inhibitory effects on neurotransmission, leading to a depressant effect. This is responsible for the behaviours associated with intoxication (i.e., mood changes, memory loss, etc.).

An infographic that says "Under normal conditions, a balance exists between excitatory and inhibitory neurotransmission in the brain. Short-term alcohol exposure tilts the balance towards inhibition by both enhancing the function of inhibitory neurotransmitters and neuromodulators (i.e., GABA, glycine, and adenosine) and decreasing the function of excitatory neurotransmitters (i.e., glutamate and aspartate). Research suggests that after long term alcohol exposure, the brain attempts to restore equilibrium by compensating for the depressant effects of alcohol; thus, the brain decreases inhibitory neurotransmission and enhances excitatory neurotransmission. During alcohol withdrawal, these compensatory changes are no longer opposed by the presence of alcohol and the balance shifts towards a state of excessive excitation. This state of hyperexcitation is characterized by seizures, delirium, and anxiety." — Credit

The brain acts as a system, not just individual components, which means there are many proposed mechanisms behind the various effects of alcohol:

Short Term Exposure

It can act as a gamma-aminobutyric acid (GABA)_A receptor agonist which means it increases that receptor’s natural inhibitory effects, similar to the effects of sedatives.
It can aid in the function of glycine receptor’s inhibitory effects.
It can increase inhibitory neuromodulators such as adenosine.
It can inhibit NMDA receptors, which are involved in excitatory neurotransmission. This would prevent the effects of excitatory neurotransmitters such as aspartate and glutamate.

Long Term Exposure/Withdrawal

The brain is like a thermostat, it strives to maintain balance and restore proper equilibrium states.
Excitatory receptors can try to adapt by increasing their activity, and it is possible to achieve balance during long term exposure.
When long term alcohol consumption ceases it may take time for the receptors adaption to overcompensate to stop and return to a normal level of activity.