Phenobarbital sedative-hypnotic

Long-acting barbiturates used as sedative-hypnotics and also for their anticonvulsant effects include phenobarbital (Luminal) and mephobarbital (Mebaral). 

Table 3-5. Sedative-hypnotic dose equivalency (equal to 30 mg of phenobarbital) ...

The third protocol is to determine the level of drug use and calculate equivalent doses of phenobarbital (Table 3-5). The patient is stabilized on this dose (divided into administration every 8 hours) for a few days, and then the dose is tapered by 10% daily. Although this method has its proponents, the determination of equivalency is an approximation, drug histories are unreliable, and mixed sedative-hypnotic dependence will complicate the procedure. 

Detoxiflcation may be accomplished with phenobarbital (60 mg of phe-nobarbital for 500 mg of glutethimide). If concomitant codeine dependence is present (and this codependence should be strongly suspected), then methadone can be used adjunctively (10 mg of methadone for 120 mg of codeine) (Khajawall et al. 1982). Approximate sedative-hypnotic dosage equivalencies are listed in Table 3-5. 

Phenobarbital. Is a sedative, hypnotic, and somewhat analgesic. It is addictive. 

The sedative hypnotic ethchlorvynol has approximately the same activity and toxicity as phenobarbital however, its hypnotic effect develops and dissipates qnicker. It is nsed mnch less than benzodiazepines in treating insomnia for a nnmber of reasons. 

Forced diuresis is occasionally useful. It may cause volume overload or electrolyte disturbances. Forced diuresis is useful for phenobarbital, bromides, lithium, salicylate, or amphetamines overdoses. Do not use for tricyclic antidepressants, sedative-hypnotics, or highly protein-bound medications. The most common agents employed are furosemide and osmotic diuretics with mannitol. 

Zaleplon (Sonata) [C IV] [Sedotive/Hypnotic] Uses Insomnia Action A nonbenzodiazepine sedative/hypnotic, a pyrazolopyrimidine Dose 5-20 mg hs PRN -1- w/ renal/hepatic insuff, elderly Caution [C, /-] w/ mental/ psychological conditions Contra Component allergy Disp Caps SE HA, edema, amnesia, somnolence, photosens Interactions t CNS depression W/ CNS d es-sants, imipramine, thioridazine, EtOH X effects W/ carbamazepine, phenobarbital, phenytoin, rifampin EMS Concurrent EtOH can t adverse CNS effects OD May cause profound CNS depression symptomatic and supportive Zanamivir (Relenza) [Antiviral/Neuramidase Inhibitor] Uses Influenza A (including HlNl swine flu) B Action X Viral neuraminidase Dose Adults Feds > 7 y.2 inhal (10 mg) bid for 5 d initiate w/in 48 h of Sxs Caution [C, M] Contra Pulm Dz Disp Powder for inhal SE Bron-chospasm, HA, GI upset EMS Does not reduce risk of transmitting virus monitor for bronchospasm or other severe resp events OD May cause resp problems s5rmptomatic and supportive... 

The water-soluble metabolites of sedative-hypnotics, mostly formed via the conjugation of phase I metabolites, are excreted mainly via the kidney. In most cases, changes in renal function do not have a marked effect on the elimination of parent drugs. Phenobarbital is excreted unchanged in the urine to a certain extent (20-30% in humans), and its elimination rate can be increased significantly by alkalinization of the urine. This is partly due to increased ionization at alkaline pH, since phenobarbital is a weak acid with a pKa of 7.4. 

Long-acting drugs such as chlordiazepoxide and diazepam and, to a lesser extent, phenobarbital are administered in progressively decreasing doses to patients during withdrawal from physiologic dependence on ethanol or other sedative-hypnotics. Parenteral lorazepam is used to suppress the symptoms of delirium tremens. 

When utilized as sedative hypnotics, barbiturates are administered orally. They are rapidly and completely absorbed by this route with nearly 100% bioavailability and an onset of action ranging from 10 to 60 min.3 Sodium salts are more rapidly absorbed than free acids. Intramuscular injections of sodium salts should be made deep into the muscle to prevent pain and tissue damage. Some barbiturates are also administered rectally barbiturates utilized for the induction and maintenance of anesthesia (thiopental) or for treating status epilepticus (phenobarbital) are administered intravenously. 

Barbiturates -barbital Phenobarbital, secobarbital Sedative-hypnotic (6), antiseizure [9], anesthetic (11]... 

Most of the sedative-hypnotics are capable of inhibiting the development and spread of epileptiform activity in the central nervous system. Some selectivity exists in that some members of the group can exert anticonvulsant effects without marked central nervous system depression (although psychomotor function may be impaired). Several benzodiazepines—including clonazepam, nitrazepam, lorazepam, and diazepam—are sufficiently selective to be clinically useful in the management of seizure states (see Chapter 24 Antiseizure Drugs). Of the barbiturates, phenobarbital and metharbital (converted to phenobarbital in the body) are effective in the treatment of generalized tonic-clonic seizures. 

Sedative-hypnotic drugs and anxiolytic drugs are CNS depressants that are used medically to reduce anxiety and/or induce sleep. They may also be used as anticonvulsants. Phenobarbital, for example, is often the maintenance drug of choice for seizure-prone individuals. In general, the sedative-hypnotic family of drugs includes alcohol, barbiturates, benzodiazepines, and such barbiturate-like drugs as chloral hydrate, glutethi-mide, meprobamate, and methaqualone. 

S.2.2.2 Barbiturates. A major event in the field was the launching of barbital (6,5-dieth-ylbarbituric acid) in 1903 and phenobarbital (5-ethyl-5-phenylbarbituricacid)in 1912. The barbiturates dominated the field for nearly 50 years, until the launch of Librium (chlordiaz-epoxide) in 1960, the first of the benzodiazepine class drugs. Benzodiazepines completely overtook the barbiturates and had become The dominant class of sedative hypnotic drugs until the launch of retrocyclic sedative-hypnotics. 

The barbiturates have a low therapeutic index and a relatively high abuse potential. Because of their rapid onset and short duration of action, the short- to intermediate-acting barbiturates are used as sedative-hypnotics (amobarbitai, butabarbital, butalbital, pentobarbital, and secobarbital) and are those most commonly abused. The longer acting barbiturates (mephobarbital and phenobarbital), used primarily for their anticonvulsant properties, are rarely abused. 

Phenobarbital has selective antiseizure activity at low doses and has a long half-life suitable for maintenance treatment in seizure disorders (for characteristics of barbiturates, see sedative-hypnotics). Clonazepam is usually a backup drug in absence and myoclonic seizures it causes marked sedation at anticonvulsant doses. IV lorazepam and diazepam are both used in status epilepticus. 

ABSORPTION, FATE, AND EXCRETION For sedative-hypnotic use, the barbiturates usually are administered orally (Table 16-3) absorption is rapid and nearly complete. The onset of action varies from 10-60 minutes, depending on the agent and the formulation, and is delayed by the presence of food in the stomach. When necessary, intramuscular injections of solutions of the sodium salts should be placed deeply into large muscles to avoid the pain and possible necrosis that can result at more superficial sites. The intravenous route usually is reserved for the management of status epilepticus (phenobarbital sodium) or for the induction and/or maintenance of general anesthesia (e.g., thiopental or methohexital). 

Other uses Thiopental is commonly used for the induction of anesthesia, and certain benzodiazepines (eg, diazepam, midazolam) are used as components of anesthesia protocols. Special uses include the management of seizure disorders (eg, clonazepam, phenobarbital) and muscle spasticity (diazepam). Longer-acting dmgs (eg, chlordiazepoxide, diazepam) are used in the management of withdrawal states in persons physiologically dependent on ethanol and other sedative-hypnotics. 

The barbiturates are substituted pyrimidine derivatives with an ureide configuration (Fig. 20.4). They are lipophilic weak acids (pKa 7-8) that are weii distributed into brain (see Appendix A for the respective pKa values). Although many barbiturates dispiay sedative-hypnotic activity (see Chapter 19), oniy a few have antiseizure properties. Paradoxically, many barbiturates cause convulsions at larger doses. The barbiturates clinically useful as AEDs are phenobarbital, mephobarbital, and primidone (Fig. 20.8). In laboratory animals, phenobarbital is effective by several tests in nontoxic doses. It is active against electrically induced seizures (MES), and it elevates the threshold for pentylenetetrazole stimulation. The mechanism of antiseizure action for the barbiturates... 

Name and draw structural formulas for the products of the complete hydrolysis of meprobamate and phenobarbital in hot aqueous acid. Meprobamate is a tranquilizer prescribed under 58 different trade names. Phenobarbital is a long-acting sedative, hypnotic, and anticonvulsant. [Hint. Remember that, when heated, jS-dicarboxylic acids and /3-ketoacids undergo decarboxylation (Section 13.8B).]... 

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