Non barbiturates

Hypnotics. Common hypnotics are thiopental, propofol, midazolam, etomidate, ketamine and inhaled anesthetics. The incidence of hypersensitivity reactions with thiopental is rare. Recently, thiopental was involved in less than 1% of allergic reactions in France [9]. Ever since Cremophor EL, used as a solvent for some non-barbiturate hypnotics, has been avoided, many previously reported hypersensitivity reactions have disappeared. In the last French surveys, reactions to propofol accounted for less than 2.5% of allergic reactions, and reactions to midazolam, etomidate or ketamine appear to be really rare [9]. Finally, no immune-mediated immediate hypersensitivity reaction involving isoflurane, desflurane or sevoflurane has been reported despite their wide use. 

Reves JG, Glass PSA, and Lubarsky DA. Non-barbiturate Intravenous Anesthetics. In Miller RD (ed.). Anesthesia (5 th ed.). Philadelphia Churchill Livingstone, 2000. 

Mechanism of Action Although its exact mechanism of action is unknown, this non-barbiturate is thought to bind to serotonin and dopamine receptors in the CNS. The drug may also increase norepinephrine metabolism in the locus ceruleus. Therapeutic Effect Decreased anxiety... 

It is a new non-barbiturate anaesthetic agent and pharmacologically related to phencyclidine, a hallucinogen. Intravenous ketamine produces unconsciousness and analgesia within 30 seconds. It can be given by intramuscular route also. It acts on the cerebral cortex and subcortical areas. 

Non-barbiturate sedatives like chloral hydrate, paraldehyde and glutethimide may be used. 

The ideal intravenous anaesthetic agent Mechanism(s) of intravenous anaesthesia Pharmacokinetics and metabolism Rapidly acting intravenous anaesthetics Non-barbiturate intravenous anaesthetics Slower-acting intravenous anaesthetics Other drugs INTRODUCTION... 

Glenn JB (1980) Animal studies of the anesthetic activity of ICI 35868. Br J Anaesth 52 731-742 Goldenthal El (1971) A compilation of LD50 values in newborn and adult animals. Toxicol Appl Pharmacol 18 185-207 Janssen PAJ, Niemegeers CJE, Marsboom RPH (1975) Etomidate, a potent non-barbiturate hypnotic. Intravenous etomidate in mice, rats, guinea pigs, rabbits and dogs. Arch Int Pharmacodyn 214 92-132... 

Etomidate, a non-barbiturate anesthetic, is considered to be safe, especially in patients with hemodynamic instability. The most common complications of using etomidate are venous sequelae, pain on injection (1), and involuntary muscle movements (SED-11, 211) (2). 

Propofol is a non-barbiturate, i.v. anesthetic that provides rapid-onset, short-duration anesthesia. It is widely used in human and small animal anesthesia. Propofol has not yet reached widespread use in equine anesthesia but a number of investigations into its clinical use have now been reported. 

Sigg, E. B., Sigg, T. D., Brinling, J. C. Autonomic actions of the diethylamide of 2-methoxy-4-allyl-phenoxyacetic acid (G 29505). A Non-Barbiturate Anesthetic. 

Barbiturates. Based on the finding that some compounds containing a quaternary carbon (sulfonal and amylene) displayed hypnotic properties, in 1903, Emil Fischer and J. von Mehring synthesized 5,5-diethylbarbi-turic acid. This was marketed by Bayer as Veronal in the early 1900s. Since 1903, hundreds of barbiturates have been synthesized, but only a few turned out to be useful. In addition, because of their side effects, the synthesis of non-barbiturate hypnotics has been undertaken. 

Barbiturates. QSAR studies by Hansch presented evidence that the hypnotic activity of barbiturates depends largely on their relative lipophilic character as determined by octanol-water partition coefficients (102-104). Employing Equation 5.6, a QSAR analysis was conducted on over 100 barbiturates as well as a number of non-barbiturates having hypnotic activity. 

Because thiopental causes myocardial and respiratory depression and has a very narrow margin of safety, it has been largely superseded by non-barbiturates. 

In this section the mechanism of action of certain drugs already discussed in this chapter shall be explained in two categories, namely (a) Barbiturates and b) Non-barbiturates. 

B] Non-Barbiturates The five non-barbiturates discussed are as stated below ... 

Methyprylon. Interestingly, the two piperidinediones viz., glutethimide and methyprylon and the quinazolone viz., methaqualone, are of vital importance within the context of non-barbiturate sedatives and hypnotics. However, glutethimide and methyl prylon possess a striking resem-blanee to barbiturates as given below ... 

Give the structure, chemical name and uses of a potent non-barbiturate drug having a benzodiazepin nucleus. 

Chloral hydrate, paraldehyde, meprobamate and glutethimide cause sedation, but are neither benzodiazepines or barbiturates. Chloral hydrate is used most often for the sedation of children. It is reduced in the body to trichloroethanol, a potent ethanol. Like ethyl alcohol, the side effects of chloral hydrate include mucosal irritation, light-headedness, malaise and ataxia. Paraldehyde, meprobamate and glutethimide are seldom used and their mechanism of action is unknown. The non-barbiturate/non-benzodiazepine sedatives are not listed in a table. 

A barbiturate with a hydroxy group in the side chain (XXXV) (ipronal) was reported to have tranquiilising activity in a clinical study when given orally for a 2 to 3 week period [182]. Its short-term hypnotic effect was found to be very weak, and it was reported not to be an anticonvulsant. However, it markedly potentiates the hypnotic effect of phenobarbitone and barbitone. This effect is not produced with non-barbiturate hypnotics, such as chloral hydrate or ether. 

The Identification of Non-Barbiturate Hypnotics from Biological Specimens J. Chromatogr. Sci. 12(5) 237-245 (1974) CA 81 115339g... 

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