Barbiturates have been used as hypnotic and sedative agents, for the induction of anesthesia, and for the treatment of epilepsy and status epilepticus. They have been largely replaced by newer drugs and calls to poison control centers have decreased significantly. They often are divided into four major groups according to their pharmacologic activity and clinical use: ultra–short-acting, short-acting, intermediate-acting, and long-acting (Table II–13); and combination products containing barbiturates include Fiorinal (50 mg butalbital) and Donnatal (16 mg phenobarbital). Veterinary euthanasia products often contain barbiturates such as pentobarbital.
TABLE II–13.BARBITURATES ||Download (.pdf) TABLE II–13. BARBITURATES
|Drug ||Normal Terminal Elimination Half-life (h) ||Usual Duration of Effect (h) ||Usual Hypnotic Dose, Adult (mg) ||Minimum Toxic Level (mg/L) |
| Methohexital ||3–5 ||<0.5 ||50–120 ||>5 |
| Thiopental ||8–10 ||<0.5 ||50–75 ||>5 |
| Pentobarbital ||15–50 ||>3–4 ||50–200 ||>10 |
| Secobarbital ||15–40 ||>3–4 ||100–200 ||>10 |
| Amobarbital ||10–40 ||>4–6 ||65–200 ||>10 |
| Aprobarbital ||14–34 ||>4–6 ||40–160 ||>10 |
| Butabarbital ||35–50 ||>4–6 ||100–200 ||>10 |
| Butalbital ||35 || ||100–200 ||>7 |
| Mephobarbital ||10–70 ||>6–12 ||50–100 ||>30 |
| Phenobarbital ||80–120 ||>6–12 ||100–320 ||>30 |
All barbiturates cause generalized depression of neuronal activity in the brain. Interaction with a barbiturate receptor leads to enhanced gamma-aminobutyric acid (GABA)–mediated chloride currents and results in synaptic inhibition. Hypotension that occurs with large doses is caused by depression of central sympathetic tone as well as by direct depression of cardiac contractility.
Pharmacokinetics vary by agent and group (see Table II–13 and Table II–66).
Ultra–short-acting barbiturates are highly lipid soluble and rapidly penetrate the brain to induce anesthesia, then are quickly redistributed to other tissues. For this reason, the clinical duration of effect is much shorter than the elimination half-life for these compounds.
Long-acting barbiturates like phenobarbital are distributed more evenly and have long elimination half-lives, making them useful for once-daily treatment of epilepsy. Primidone (Mysoline) is metabolized to phenobarbital and phenylethylmalonamide (PEMA); although the longer-acting phenobarbital accounts for only about 25% of the metabolites, it has the greatest anticonvulsant activity.
The toxic dose of barbiturates varies widely and depends on the drug, the route and rate of administration, and individual patient tolerance. In general, toxicity is likely when the dose exceeds 5–10 times the hypnotic dose. Chronic users or abusers may have striking tolerance to depressant effects.
The potentially fatal oral dose of the shorter-acting agents such as pentobarbital is 2–3 g, compared with 6–10 g for phenobarbital.
Several deaths were reported in young women undergoing therapeutic abortion after they received rapid IV injections of as little as 1–3 mg of methohexital per kilogram.
The onset of symptoms depends on the drug and the route of administration.
Lethargy, slurred speech, nystagmus, and ataxia are common with mild-to-moderate intoxication. With higher doses, ...