What are examples of barbiturates?

Examples of Barbiturates

Barbiturates are derivatives of barbituric acid and include both long-acting agents (phenobarbital) and short-acting agents (pentobarbital, secobarbital, amobarbital, butalbital, and thiopental). 1

Long-Acting Barbiturates

• Phenobarbital is the primary long-acting barbiturate, with an elimination half-life of 80-120 hours and duration of action of 6-12 hours. 1
• It has a molecular weight of 232 Da, pKa of 7.2, and approximately 20-25% is excreted unchanged in urine. 1
• Phenobarbital is used clinically as an anticonvulsant for partial, complex partial, and secondarily generalized seizures, though it is no longer first-line for all seizure types. 2

Short-Acting Barbiturates

Pentobarbital

• Pentobarbital is a short-acting barbiturate with an elimination half-life of 15-48 hours and duration of action of 3-4 hours. 1
• It has a molecular weight of 226 Da, pKa of 7.9, and less than 5% is excreted unchanged in urine. 1
• Pentobarbital is used clinically for anesthesia and in veterinary practice, making it accessible for intentional poisoning. 1, 3
• The FDA describes pentobarbital sodium (NEMBUTAL) as containing 50 mg/mL in a vehicle of propylene glycol (40%), alcohol (10%), and water for injection. 4

Secobarbital

• Secobarbital is an intermediate-acting barbiturate that is no longer licensed for use in the United States, United Kingdom, and most developed countries, and can only be prescribed to patients already taking it for intractable insomnia. 1
• Adverse reactions include CNS depression, respiratory depression, apnea, and circulatory collapse. 5

Amobarbital

• Amobarbital is an intermediate-acting barbiturate that is also no longer licensed for general use in most developed countries. 1
• It is used diagnostically in the evaluation of patients with medically intractable seizure disorders for possible surgical therapy. 2

Butalbital

• Butalbital is an intermediate-acting barbiturate that is no longer licensed as a standalone agent but remains available in combination products. 1
• Butalbital-acetaminophen-caffeine is classified as a Schedule III controlled substance due to its barbiturate content. 6
• It is primarily metabolized in the liver through the cytochrome P450 system and can induce the CYP enzyme system. 6

Thiopental

• Thiopental is an ultrashort-acting thiobarbiturate used for intravenous anesthesia induction. 7

Clinical Classification Framework

Barbiturates are classified according to their pharmacokinetic properties into long-acting and short-acting agents (consisting of ultrashort-, short-, and intermediate-acting agents). 1

• Short-acting barbiturates are more protein bound (35-70%) and lipid soluble than long-acting counterparts, have more rapid onset, higher pKa, shorter duration of action, and are metabolized nearly exclusively in the liver. 1
• Long-acting barbiturates accumulate less extensively in tissue (smaller volume of distribution of 0.25-1.2 L/kg), are less lipid soluble, and are excreted as active drugs by the kidneys more readily. 1

Common Pitfalls

• Do not assume that all barbiturates listed in historical literature are currently available—intermediate-acting agents like butobarbital, secobarbital, and amobarbital are no longer licensed for general use in most developed countries. 1
• Recognize that barbiturates are potent inducers of the hepatic CYP450 enzyme system, increasing metabolic clearance of other medications that are CYP substrates. 1, 6
• When combined with other CNS depressants (alcohol, opiates, benzodiazepines), barbiturates have additive depressant effects on the CNS and respiratory system, making overdose significantly more dangerous. 1, 6