Barbiturates are a class of medications that are used as anticonvulsants to manage seizure disorders; to induce anesthesia in surgical procedures; as anxiolytics to relieve anxiety; and to manage insomnia.
Barbiturates enhance the effect of gamma-aminobutyric acid, or GABA, which is the major inhibitory neurotransmitter in the brain, by binding to its receptor.
It’s pretty well-established that your brain’s really important. It controls your feelings, your movements, your sleep, your memory… It controls everything, whether you’re aware of it or not.
The cells that make up our brain are called neurons.
Neurons communicate with each other through neurotransmitters.
When one neuron is stimulated, it’ll release excitatory neurotransmitters like glutamate, which bind to receptors on the next neuron. This causes the next neuron to depolarize and release its own excitatory neurotransmitters, propagating the signal throughout the brain.
Now, we also have inhibitory neurons that will shut down this chain of events.
These neurons release the main inhibitory neurotransmitter in the nervous system, gamma-aminobutyric acid, or GABA, which binds to GABA receptors on other neurons. These receptors are large multi-unit complexes that form ligand-gated ion channels, which open up to let Cl- ions into the cell.
The influx of negatively charged ions causes hyperpolarization, where the cell’s membrane potential becomes more negative, which means it’s much more difficult for it to depolarize and fire off an action potential, and that means it’s less responsive to stimuli.
Now, there are cases where neurons in the brain start sending out more excitatory signals than normal. This can occur due to either too much excitation by the excitatory neurotransmitters, or too little inhibition by the inhibitory neurotransmitters like GABA.
Excessive excitatory signals can cause psychiatric disorders like anxiety, and neurological disorders like seizures and epilepsy.
Okay, so one way we can decrease the excitatory signals is by enhancing the effect of inhibitory neurons through medication like barbiturates.
Common medications in this class include pentobarbital, phenobarbital, secobarbital, and thiopental. These medications target the GABAA receptors but they bind at a different site than GABA.
At a lower dose, barbiturates keep the Cl- channels open for longer periods of time and increase the intracellular Cl- level, thus enhancing the effects of GABA.
At higher doses, barbiturates can trigger the opening of these channels even without GABA.
This differentiates them from benzodiazepines which also work by binding to GABAA receptors, except they cause the ion channels to open more frequently.
Now at a higher dose, barbiturates also inhibit the electron transport chain, which is a process that occurs within the inner mitochondrial membrane and results in the synthesis of adenosine triphosphate, or ATP.
ATP is the main form of energy that keeps all of our body cells going. So when the electron transport chain gets interrupted, the ATP synthesis doesn’t happen and that can eventually lead to the death of the cell.
Barbiturates also induce a class of enzymes called cytochrome P450. These enzymes are involved in the metabolism of various medications like benzodiazepines, phenytoin, quinidine, warfarin, and others.
Increased cytochrome P450 activity can cause these medications to break down too rapidly, so larger doses are needed to achieve a therapeutic effect.
Alright, now barbiturates are indicated when the neurons get “super excited” and we want to calm them down, like during an epileptic seizure where clusters of neurons in the brain become temporarily impaired and start firing off a ton of excitatory signals. This is also useful for treating acute anxiety states like a panic attack.
Also, barbiturates are used in general anesthesia and as a hypnotic to induce sleep, since we basically want to depress the function of the patient’s nervous system.
Moving on to side effects, barbiturates can have severe adverse effects even when used at therapeutic levels.
And when it’s combined with alcohol or other medications that depress the nervous system like antihistamines, the depressive effects are additive and can get severe to the point of coma.
Barbiturates cause drowsiness, as well as a decrease in concentration, problem solving ability, and reaction time, so it’s important not to drive while taking these medications.
Despite being a central nervous system depressant, barbiturates can cause paradoxical stimulation in certain parts of the brain, leading to symptoms like fast speech, excitement, and restlessness.