Barbiturates behave similarly to benzodiazepines. Phenobarbital binds to an allosteric site on the GABAA receptor and potentiates the effects of the endogenous ligand, gamma-aminobutyric acid. When barbiturates bind to the GABAA receptor, it causes the ion pore to open for extended periods of time, causing an increase of intracellular chlorine ion concentrations. As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of barbiturates on the nervous system. Phenobarbital's biological half life is 53-118 hours. It is metabolized by the liver and excreted by the kidneys and intestines.
Phenobarbital has an oral bioavailability of about 90%. Peak plasma concentrations (Cmax) are reached eight to 12 hours after oral administration. It is one of the longest-acting barbiturates available – it remains in the body for a very long time (half-life of two to seven days) and has very low protein binding (20 to 45%). Phenobarbital is metabolized by the liver, mainly through hydroxylation and glucuronidation, and induces many isozymes of the cytochrome P450 system. Cytochrome P450 2B6 (CYP2B6) is specifically induced by phenobarbital via the CAR/RXR nuclear receptor heterodimer. It is excreted primarily by the kidneys.
moderate toxicity relative to dose. However, phenobarbital is lethal when mixed with depressants like alcohol or opioids]]. Phenobarbital has a higher risk of death or serious adverse effects associated with concurrent depressant use than other drugs such as benzodiazepines. There have been studies linking the use of barbiturates, particularly phenobarbital, with the development of cancer .
It is strongly recommended that one use harm reduction practices when using this drug.
-extremely physically and psychologically addictive. Barbiturate withdrawal is medically serious and can potentially cause a life-threatening withdrawal syndrome that can cause seizures, psychosis, and death. Drugs which lower the seizure threshold such as tramadol and amphetamine should be avoided during withdrawal.
Tolerance will develop to the sedative-hypnotic effects of phenobarbital after prolonged use. It is unknown exactly how long it takes for tolerance to reach baseline. Phenobarbital presents cross-tolerance with all barbiturates, meaning that after its consumption all barbiturates will have a reduced effect.
Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be harmless in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
- Depressants** (1,4-Butanediol, 2-methyl-2-butanol, alcohol, barbiturates, GHB/GBL, methaqualone, opioids) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should try to fall asleep in the recovery position or have a friend move them into it.
- Dissociatives** - This combination can lead to an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
- Stimulants** - It is unsafe to combine barbiturates with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of barbiturates, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of barbiturates will be considerably increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of barbiturates per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.
- Overdose
Barbiturate overdose may occur when a barbiturate is taken in extremely heavy quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as benzodiazepines and alcohol since they work in a similar fashion, but bind to distinct allosteric sites on the GABAA receptor, thus their effects potentiate one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABAA receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer. Barbiturate overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and properly. Barbiturate overdose has an increased frequency of serious adverse effects when compared to other depressants.
Symptoms of a barbiturate overdose may include severe thought deceleration, slurred speech, confusion, delusions, respiratory depression, coma or death.
Internationally, phenobarbital is listed in Schedule IV of the UN Convention on Psychotropic Substances.
Australia: Phenobarbitone is listed in Schedule 4, making it a prescription only medicine.
Canada: Phenobarbital is a Schedule IV controlled substance.
Germany: Phenobarbital is controlled under Anlage III BtMG (Narcotics Act, Schedule III). It can only be prescribed on a narcotic prescription form, except preparations which contain up to 10% or up to 300 mg phenobarbital in each dosage form.
Russia: Phenobarbital is a Schedule III controlled substance since 2013. but phenobarbital is also found in the medicines Corvalol or Valocordin, which is dispensed without a doctor’s prescription.
Switzerland: Phenobarbital is a controlled substance specifically named under Verzeichnis B. Medicinal use is permitted.
United Kingdom: Phenobarbitone is a Class B controlled substance.
United States: Phenobarbital is a Schedule IV controlled substance.
Depressants
Benzodiazepines
GABA
Phenobarbital (Wikipedia)
Phenobarbital (Isomer Design)
Phenobarbital (DrugBank)
Phenobarbital can be administered via oral. The route of administration can influence both the onset and intensity of seizure suppression.