Sedative-hypnotic agents include a class of drugs called barbiturates. Barbiturates, specifically phenobarbital, offer a wide array of clinical uses that commonly include anti-seizure management.[1] It is even recommended as an agent to treat status epilepticus.[2] A study in China compared valproic acid to phenobarbital for the treatment of status epilepticus. Results showed intravenous phenobarbital to have better clinical outcomes in the study population compared to valproic acid.[3] Although proven effective for status epilepticus, phenobarbital has mostly been replaced with other drugs that offer less harmful side effects.[4][2] Phenobarbital can also be used to relieve insomnia and apprehensiveness, although addiction is a point of concern when using phenobarbital for insomnia.[5] This drug is also useful for benzodiazepine and alcohol withdrawal treatment due to its anti-seizure properties and sedative effect.[6] The syndrome resulting from alcohol withdrawal has a better clinical outcome when treated with benzodiazepines according to significant evidence-based studies.[5][6] Long-acting agents such as phenobarbital are not the preferred option for surgical induction; short-acting barbiturates are commonly used for this purpose.[7] The involvement of phenobarbital in severe brain injury management is to reduce intracranial pressure by suppressing cerebral metabolism, but phenobarbital's adverse effect of hypotension negatively impacts the brain's supply of oxygen, thus offsetting any clinical benefit.[8]

Phenobarbital's mechanism of action increases the amount of time chloride channels are open, which in turn depresses the central nervous system. This action occurs by acting on GABA-A receptor subunits. When phenobarbital binds to these receptors, the chloride ion gates open and stay open, allowing a steady flow of these ions into neuronal cells.[1] This action hyperpolarizes the cell's membrane, thereby increasing the threshold for the action potential. This increase in action potential is the reason why this drug is effective in the treatment of seizures. As per the metabolism and clearance of the drug, phenobarbital is a water-soluble agent metabolized by the liver and expelled mainly through the kidneys.[1] It is important to remember clearance rates vary with patients and their specific presentations. For instance, terminally ill cancer patients on phenobarbital may need dose adjustments due to reduced clearance of this drug.[9] Phenobarbital induces cytochrome p450, and so careful consideration is necessary when given concurrently with other medications. For instance, a woman with epilepsy who takes oral contraceptive pills and phenobarbital at the same time must be fully aware of the possible interaction between the medications. Phenobarbital, an antiepileptic drug, is known to induce the liver's cytochrome p450 enzyme. The induction of this enzyme speeds up the metabolism of estrogens and progestins. Thus, a woman taking both antiepileptic medication and oral contraceptive pills can have an unexpected pregnancy due to the decreased efficacy of her oral contraceptive pills.[10] This scenario is why it is crucial to educate the patient about potential risks.

Phenobarbital administration is via a variety of routes. These include[11]:

• Intramuscular (IM)
• Oral
• Intravenous (IV)

When phenobarbital is given intravenously, it should be for emergency cases. Other routes of administration should be accessed first and checked for any indurations. Studies have shown that an induration at a site of infusion results in a decreased bioavailability of phenobarbital.[12] Another study demonstrated the rectal administration of phenobarbital to be effective, with a relative bioavailability reaching 90%.[13]

Complications associated with phenobarbital use are coma, decreased effort to breathe, and low blood pressure.[1] The more common adverse effects include[14]:

• Incoordination
• Impaired balance
• Drowsiness

These adverse effects, stemming from phenobarbital usage, impact the geriatric patients to a greater degree, and therefore, the use of newer antiepileptics (lamotrigine, levetiracetam) are preferable as seizure treatment in this population.[14]

This drug has some correlations with Steven-Johnson syndrome, but this is a rare complication. The following adverse events also correlate with long-term use of phenobarbital: irritability, loss of appetite, achiness in the bones, joints or muscles, depression, and liver damage, although liver damage is a rare complication.[1]

Patients with underlying obstructive lung disease will have an increased risk of complications.[1] The depression of respiratory drive associated with barbiturate toxicity compounded with an already compromised respiratory system can contribute to complications.[15] Research has also found that the drug interaction from combined oral theophylline medication and phenobarbital, exerted a negative impact on theophylline blood levels compared to plain oral theophylline pills.[15] Phenobarbital has shown a capacity to decrease levels of steroids and theophylline via the cytochrome p450 liver metabolism system.[15] Therefore, patients receiving combined oral therapy for their lung condition may experience issues with subtherapeutic blood levels of corticosteroids and/or theophylline. 

It is imperative not to use alcohol while taking barbiturates because of the danger of severe respiratory depression when both drugs are in the patient's system. When taken simultaneously, both drugs' individual effects on GABA-A are additive, potneitally resulting in a life-threatening scenario.[1]

When taking barbiturates such as phenobarbital, one may go into withdrawal if they were to stop taking it suddenly. Tapering off the drug is necessary.