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iopental is an ultra short acting barbiturate that is marketed under the name sodium pentothal it is often mistaken for truth serum or sodium amytal an intermediate acting barbiturate that is used for sedation and to treat insomnia but was also used in so called sodium amytal interviews where the person being questioned would incorrectly be thought to be more likely to provide the truth whilst under the influence of the drug 10 when dissolved in water sodium amytal can be swallowed or it can be administered by intravenous injection the drug does not itself force people to tell the truth but is thought to decrease inhibitions and slow creative thinking making subjects more likely to be caught off guard when questioned and increasing the possibility of the subject revealing information through emotional outbursts lying is somewhat more complex than telling the truth especially under the influence of a sedative hypnotic drug 11 the memory impairing effects and cognitive impairments induced by sodium thiopental are thought to reduce a subject s ability to invent and remember lies this practice is no longer considered legally admissible in court owing to findings that subjects undergoing such interrogations may form false memories putting the reliability of all information obtained through such methods into question nonetheless it is still employed in certain circumstances by defense and law enforcement agencies as a humane alternative to torture interrogation when the subject is believed to have information critical to the security of the state or agency employing the tactic 12 chemistry edit in 1988 the synthesis and binding studies of an artificial receptor binding barbiturates by six complementary hydrogen bonds was published 13 since this first article different kind of receptors were designed as well as different barbiturates and cyanurates not for their efficiencies as drugs but for applications in supramolecular chemistry in the conception of materials and molecular devices the preferred iupac name of the base compound barbituric acid is 1 3 diazinane 2 4 6 trione different barbiturates have different substituents in the basic structure mainly in position 5 on the ring 14 sodium barbital and barbital have also been used as ph buffers for biological research e g in immuno electrophoresis or in fixative solutions 15 16 classification edit barbiturates are classified based on the duration of action examples of each class include 17 ultra short acting 30 minutes thiopentone methohexitone short acting 2 hours hexobarbitone cyclobarbitone pentobarbitone secobarbitone intermediate acting 3 6 hours amobarbitone butabarbitone long acting 6 hours phenobarbitone indications edit indications for the use of barbiturates include 18 seizure neonatal withdrawal syndrome insomnia anxiety inducing anesthesia side effects edit addiction experts in psychiatry chemistry pharmacology forensic science epidemiology and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs barbiturates were ranked third in physical harm fourth in social harm and fifth in dependence 19 there are special risks to consider for older adults and women who are pregnant when a person ages the body becomes less able to rid itself of barbiturates as a result people over the age of 65 are at higher risk of experiencing the harmful effects of barbiturates including drug dependence and accidental overdose 20 when barbiturates are taken during pregnancy the drug passes through the placenta to the fetus after the baby is born it may experience withdrawal symptoms and have trouble breathing in addition nursing mothers who take barbiturates may transmit the drug to their babies through breast milk 21 a rare adverse reaction to barbiturates is stevens johnson syndrome which primarily affects the mucous membranes this article is in list format but may read better as prose you can help by converting this article if appropriate editing help is available july 2022 common side effects edit nausea hypotension headache drowsiness skin rash serious side effects edit confusion coma hallucination fainting slow breathing 22 rare side effects edit agranulocytosis stevens johnson syndrome liver injury megaloblastic anemia 22 tolerance and dependence edit main article barbiturate dependence with regular use tolerance to the effects of barbiturates develops research shows tolerance can develop with even one administration of a barbiturate as with all gabaergic drugs barbiturate withdrawal produces potentially fatal effects such as seizures in a manner reminiscent of delirium tremens and benzodiazepine withdrawal although its more direct mechanism of gaba agonism makes barbiturate withdrawal even more severe than that of alcohol or benzodiazepines it is considered one of the most dangerous withdrawals of any known addictive substance similarly to benzodiazepines the longer acting barbiturates produce a less severe withdrawal syndrome than short acting and ultra short acting barbiturates withdrawal symptoms are dose dependent with heavier users being more affected than lower dose addicts the pharmacological treatment of barbiturate withdrawal is an extended process often consisting of converting the patient to a long acting benzodiazepine i e valium followed by slowly tapering off the benzodiazepine mental cravings for barbiturates can last for months or years in some cases and counselling support groups are highly encouraged by addiction specialists patients should never try to tackle the task of discontinuing barbiturates without consulting a doctor owing to the high lethality and relatively sudden onset of the withdrawal attempting to quit cold turkey may result in neurological damage due to excitotoxicity severe physical injuries received during convulsions and even death resulting from arrhythmias during grande mal seizures paralleling death caused by delirium tremens citation needed overdose edit main article barbiturate overdose some symptoms of an overdose typically include sluggishness incoordination difficulty in thinking slowness of speech faulty judgement drowsiness shallow breathing staggering and in severe cases coma or death the lethal dosage of barbiturates varies greatly with tolerance and from one individual to another the lethal dose is highly variable among different members of the class with superpotent barbiturates such as pentobarbital being potentially fatal in considerably lower doses than the low potency barbiturates such as butalbital even in inpatient settings the development of tolerance is still a problem as dangerous and unpleasant withdrawal symptoms can result when the drug is stopped after dependence has developed tolerance to the anxiolytic and sedative effects of barbiturates tends to develop faster than tolerance to their effects on smooth muscle respiration and heart rate making them generally unsuitable for a long time psychiatric use tolerance to the anticonvulsant effects tends to correlate more with tolerance to physiological effects however meaning that they are still a viable option for long term epilepsy treatment barbiturates in overdose with other cns central nervous system depressants e g alcohol opiates benzodiazepines are even more dangerous owing to additive cns and respiratory depressant effects in the case of benzodiazepines not only do they have additive effects barbiturates also increase the binding affinity of the benzodiazepine binding site leading to exaggerated benzodiazepine effects ex if a benzodiazepine increases the frequency of channel opening by 300 and a barbiturate increases the duration of their opening by 300 then the combined effects of the drugs increases the channels overall function by 900 not 600 the longest acting barbiturates have half lives of a day or more and subsequently result in bioaccumulation of the drug in the system the therapeutic and recreational effects of long acting barbiturates wear off significantly faster than the drug can be eliminated allowing the drug to reach toxic concentrations in the blood following repeated administration even when taken at the therapeutic or prescribed dose despite the user feeling little or no effects from the plasma bound concentrations of the drug users who consume alcohol or other sedatives after the drug s effects have worn off but before it has cleared the system may experience a greatly exaggerated effect from the other sedatives which can be incapacitating or even fatal barbiturates induce a number of hepatic cyp enzymes most notably cyp2c9 cyp2c19 and cyp3a4 23 leading to exaggerated effects from many prodrugs and decreased effects from drugs which are metabolized by these enzymes to inactive metabolites this can result in fatal overdoses from drugs such as codeine tramadol and carisoprodol which become considerably more potent after being metabolized by cyp enzymes although all known members of the class possess relevant enzyme induction capabilities the degree of induction overall as well as the impact on each specific enzyme span a broad range with phenobarbital and secobarbital being the most potent enzyme inducers and butalbital and talbutal being among the weakest enzyme inducers in the class people who are known to have killed themselves by barbiturate overdose include stefan zweig charles boyer ruan lingyu dalida jeannine deckers felix hausdorff abbie hoffman phyllis hyman carole landis c p ramanujam george sanders jean seberg lupe vélez and the members of heaven s gate cult others who have died as a result of barbiturate overdose include pier angeli brian epstein judy garland jimi hendrix inger stevens dinah washington ellen wilkinson and alan wilson in some cases these have been speculated to be suicides as well those who died of a combination of barbiturates and other drugs include rainer werner fassbinder dorothy kilgallen malcolm lowry edie sedgwick marilyn monroe and kenneth williams dorothy dandridge died of either an overdose or an unrelated embolism ingeborg bachmann may have died of the consequences of barbiturate withdrawal she was hospitalized with burns the doctors treating her were not aware of her barbiturate addiction contraindications edit the use of barbiturates is contraindicated in the following conditions variegate porphyria because of induction of enzymes needed for porphyria synthesis by barbiturates status asthmaticus because of respiratory depression caused by the barbiturates 18 mechanism of action edit barbiturates act as positive allosteric modulators and at higher doses as agonists of gaba a receptors 24 gaba is the principal inhibitory neurotransmitter in the mammalian central nervous system cns barbiturates bind to the gaba a receptor at multiple homologous transmembrane pockets located at subunit interfaces 25 which are binding sites distinct from gaba itself and also distinct from the benzodiazepine binding site like benzodiazepines barbiturates potentiate the effect of gaba at this receptor in addition to this gabaergic effect barbiturates also block ampa and kainate receptors subtypes of ionotropic glutamate receptor glutamate is the principal excitatory neurotransmitter in the mammalian cns taken together the findings that barbiturates potentiate inhibitory gaba a receptors and inhibit excitatory ampa receptors can explain the superior cns depressant effects of these agents to alternative gaba potentiating agents such as benzodiazepines and quinazolinones at higher concentration they inhibit the ca 2 dependent release of neurotransmitters such as glutamate via an effect on p q type voltage dependent calcium channels 26 barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the gaba a receptor pharmacodynamics this increases the efficacy of gaba whereas benzodiazepines increase the frequency of the chloride ion channel opening at the gaba a receptor pharmacodynamics this increases the potency of gaba the direct gating or opening of the chloride ion channel is the reason for the increased toxicity of barbiturates compared to benzodiazepines in overdose 27 28 further barbiturates are relatively non selective compounds that bind to an entire superfamily of ligand gated ion channels of which the gaba a receptor channel is only one of several representatives this cys loop receptor superfamily of ion channels includes the neuronal nach receptor channel the 5 ht 3 receptor channel and the glycine receptor channel however while gaba a receptor currents are increased by barbiturates and other general anesthetics ligand gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds for example neuronal nachr channels are blocked by clinically relevant anesthetic concentrations of both thiopental and pentobarbital 29 such findings implicate non gaba ergic ligand gated ion channels e g the neuronal nachr channel in mediating some of the side effects of barbiturates 30 this is the mechanism responsible for the mild to moderate anesthetic effect of barbiturates in high doses when used in anesthetic concentration interactions edit drug interactions with barbiturates are 22 alcohol opioids benzodiazepines anticoagulants antihistamines atazanavir birth control boceprevir caution edit caution is needed in people using 22 medications such as opioids or benzodiazepines alcohol caution is also required in patients with asthma kidney or liver problems heart disease substance use disorder depression history of suicidal thoughts history edit barbituric acid was first synthesized 27 november 1864 by german chemist adolf von baeyer and later perfected in 1879 by the french chemist edouard grimaux who developed and improved the synthesis 31 this was done by condensing urea with diethyl malonate there are several stories about how the substance got its name the most likely story is that baeyer and his colleagues went to celebrate their discovery in a tavern where the town s artillery garrison were also celebrating the feast of saint barbara the patron saint of artillerymen an artillery officer is said to have christened the new substance by amalgamating barbara with urea 32 another story holds that baeyer synthesized the substance from the collected urine of a munich waitress named barbara 33 no substance of medical value was discovered however until 1902 when two german scientists working at bayer emil fischer and joseph von mering discovered that barbital was very effective in putting dogs to sleep barbital was then marketed by bayer under the trade name veronal it is said that mering proposed this name because the most peaceful place he knew was the italian city of verona 32 in 1912 bayer introduced another barbituric acid derivative phenobarbital under the trade name luminal as a sedative hypnotic 34 it was not until the 1950s that the behavioral disturbances and physical dependence potential of barb...
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