Pentobarbital elimination

Pentobarbital is biotransformed by oxidation of the penultimate carbon of the methyl butyl side-chain to produce a mixture of alcohols, and by iV -hydroxylation. The alcoholic metabolites of pentobarbital are pharmacologically inactive. Approximately 86% of a radioactive dose is excreted in the urine in 6 days, about 1% as unchanged drug and up to 73% as the L- and D-diastereoisomers of 3 -hydroxypentobarbital in a 5.4 1 ratio, and up to 15% as JV-hydroxypentobarbital.9 None of these metabolites is eliminated as a conjugate. 

All three barbiturates are primarily eliminated by hepatic metabolism and renal excretion of inactive metabolites a small fraction of thiopental undergoes desulfuration to the longer-acting hypnotic pentobarbital. Each drug is highly protein bound (Table 13-2). Hepatic disease or other conditions that reduce serum protein concentration will decrease the volume of distribution and thereby increase the initial free concentration and hypnotic effect of an induction dose. 

In the first step the diethyl ester of malonic acid is treated with ethyl bromide in the presence of sodium ethoxide when one of the active hydrogen atoms in the former gets eliminated with bromine atom in the later as a molecule of hydrobromic acid resulting into the formation of the corresponding diethyl ester of ethyl malonic acid. This on subsequent addition of 2-monobromopentane and in the presence of sodium ethoxide gives rise to diethyl ether of ethyl-(l-methyl butyl) malonate with the elimination of one molecule of hydrobromic acid. Urea is made to condense with the product obtained from the previous step when pentobarbital is formed with the elimination of two moles of ethanol. Finally, the pentobarbital is treated with a calculated amoimt of sodium hydroxide when the required official compoimd is formed. 

I. Pharmacology. Pentobarbital is a short-acting barbiturate with anticonvulsant as well as sedative-hypnotic properties. It is used as a third-line drug in the treatment of status epilepticus. It may also reduce intracranial pressure in patients with cerebral edema by inducing vasoconstriction. After intravenous administration of a single dose, the onset of effect occurs within about 1 minute and lasts about 15 minutes. Pentobarbital demonstrates a biphasic elimination pattern the half-life of the initial phase is 4 hours, and the terminal phase half-life is 35-50 hours. Effects are prolonged after termination of a continuous infusion. 

Heinemeyer G, Roots I, Schulz H, DennhardtR Hemmung der Pentobarbital-Elimination du-rch Miconazol bei Intesivdierapie des erhohten intracraniellen Druckes. Intensivmed (1985) 22,164-7. 

Fig. 41. Opioid peptide (D.ALA) blocks spontaneous ipsp s in hippocampal pyramidal cell. The responses were recorded on running film with a 3 M KCl-filled microelectrode in the absence of pentobarbital. To block spontaneous action potentials the membrane was hyper-polarized to - 69 mV while the film records were obtained. Switching to a solution containing 5 pM D.ALA for 6 min eliminates the spontaneous depolarizing potentials. Addition of 2 xM naloxone to the D.ALA-containing solution reverses the depressant action of D.ALA. The resting membrane potential was - 53 mV in control, - 56 mV in D.ALA, and - 50 mV in D.ALA + NAL. The faster decay of the potentials in D.ALA + NAL was due to a fall in membrane resistance resulting from imperfect sealing of the electrode when these records were obtained. (From Nicoll et al., 1980.)...

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