Anxiolytics oxazepam

In the presence of cirrhosis or other liver impairment, lorazepam or oxazepam should be utilized for detoxification. These two benzodiazepines have no active hepatic metabolites and are generally considered safer choices for patients with liver damage. Once the starting point for the taper is determined, the dose is decreased by 10-20% per day. It is important to note that this rate of taper is much faster than that used for patients treated chronically with benzodiazepines who are discontinuing their anxiolytic in order to determine if it is still needed for control of symptoms. In that case, the rate of decrease is 10-20% per week. Should the patient display... 

The speciflc clinical use of the numerous available benzodiazepines depends on their individual pharmacokinetic and pharmacodynamic properties. Drugs with a high affinity for the GABAa receptor (alprazolam, clonazepam, lorazepam) have high anxiolytic efficacy drugs with a short duration of action (temazepam) are used as hypnotics to minimise daytime sedative effects. Diazepam has a long half-life and duration of action and may be favoured for long-term use or when there is a history of withdrawal problems oxazepam has a slow onset of action and may be less susceptible to abuse. 

Nevertheless, the GABAergic properties of benzodiazepines remain their most important clinical application. Over the past 30 years, the most widely used benzodiazepine drug has been diazepam (1.6). It is an anxiolytic, sedative, and muscle relaxant the anxious, depressed person becomes more outgoing and relaxed. There have been many diazepam analogs. Oxazepam (4.177) and lorazepam (4.178) have similar effects. Temazepam (4.179), flunitrazepam (4.180), and flurazepam (4.181) are useful sedative-hypnotics. Clonazepam (4.182) is a clinically useful anticonvulsant. Brotizolam (4.183), a novel benzodiazepine analog, seems to be an effective sedative-hypnotic. Midazolam (4.184) is an imidazolo-benzodiazepine that is water soluble and thus easily injectable. It is a hypnotic sedative with marked amnestic (i.e., memory loss) properties and is used in dentistry, endoscopic procedures, and induction to anesthetics in the elderly and in... 

Adumbran 8, Seresta1 (UK), Serax (USi Oxazepam 20-150 Anxiolytic, sedative... 

A simple and efficient procedure for the direct oxidation of C-3 of l,4-benzodiazepin-2-ones, applicable to the preparation of the anxiolytic agents oxazepam and lorazepam, has been developed that represents an improvement over the well-established Polonovsky rearrangement of the N-4 oxide <20060PD1192>. Iodine in AcOH at 65 °C catalyzed acetoxylation in a reaction that involved iodination at C-3 followed by a rapid nucleophilic displacement by KOAc. The liberated HI was recycled to iodine by inclusion of a stoichiometric oxidant, with K2S2O8 being the optimal compromise of cost, availability, and efficiency. 

OFFICIAL NAMES Minor tranquilizers (sedative-hyp-notics/anxiolytics)/Benzodiazepines Alprazolam (Xanax) chlordiazepoxide (Librium, Novopoxide) clonazepam (Klonopin) clorazepate (Azene, Tranxene) diazepam (Valium) estazolam (ProSom) flunitrazepam (Rohypnol/illegal in the United States) flurazepam (Dalmane) halazepam (Paxipam) lorazepam (Ativan) midazolam (Versed) oxazepam (Serax) prazepam (Centrax) quazepam (Doral) temazepam (Restoril) triazolam (Halcion)... 

Kava is most often used as a sedative-hypnotic to treat anxiety. The substance has been evaluated in Europe and in the USA for the treatment of anxiety in several placebo-controlled studies. Most of these trials have shown significant improvements in anxiety symptoms in patients with moderate to severe anxiety within 8 weeks after starting treatment. In one study, kava was compared with oxazepam, a benzodiazepine. Similar reductions in anxiolytic effects and fewer adverse effects were reported for the kava group. Kava appears to have a slow onset of action for the treatment of anxiety symptoms, most patients responding only after 4-8 weeks. Kava should not be used to treat acute symptoms of anxiety or panic attacks. 

As well as compounds specifically indicated for the short-term treatment of insomnia, some benzodiazepines used primarily as anxiolytics have found extensive usage as symptomatic remedies for insomnia in anxious individuals. Examples include oxazepam, lorazepam, and diazepam. Patterns of use vary from country to country and at different times. 

Insomnia is a common complaint in the elderly. As people age they require less sleep, and a variety of physical ailments to which the elderly are subject can cause a change in the sleep pattern (e.g. cerebral atherosclerosis, heart disease, decreased pulmonary function), as can depression. Providing sedative hypnotics are warranted, the judicious use of short half-life benzodiazepines such as temazepam, triazolam, oxazepam and alprazolam for a period not exceeding 1-2 months may be appropriate. Because of their side effects, there would appear to be little merit in using chloral hydrate or related drugs in the treatment of insomnia in the elderly. It should be noted that even benzodiazepines which have a relatively short half-life are likely to cause excessive day-time sedation. The side effects and dependence potential of the anxiolytics and sedative hypnotics have been covered elsewhere in this volume (Chapter 9). 

Additional doses of benzodiazepines in long-term users are commonly needed, but it is unknown whether these additional doses have any effect. The effects of an additional 20 mg dose of oxazepam has been assessed in a double-bhnd, balanced-order, crossover, randomized study in 16 long-term users of oxazepam and 18 benzodiazepine-naive controls (5). The effects of oxazepam 10 and 30 mg were assessed on (a) saccadic eye movements as a proxy for the sedative effect (b) the acoustic startle response as a proxy for the anxiolytic effects (c) memory (d) reaction time tasks (e) subjective measurements. There were dose-related effects on the peak velocity of saccadic eye movement and response probability and on the peak amplitude of the acoustic startle response. Comparison with the controls suggested that the sedative effects might be confounded with the suppression of sedative withdrawal symptoms, whereas the patients were as sensitive as the controls to the effects of an additional dose of oxazepam on the acoustic startle response. 

ZIDOVUDINE ANXIOLYTICS AND HYPNOTICS-BZDs t adverse effects, including t incidence of headaches when oxazepam is co-administered with zidovudine Uncertain Monitor closely... 

Halazepam, USP. Halazepam. 7-chloro-l.3-dihydro-3-phenyl- I (2.2.2-trinuoroethyl)-2W-1,4-henzodiazpin-2-one (Paxipam). is well absorbed. It is active and present in plasma, but much of its activity is due to the major metabolites nordazepam and oxazepam. The drug is marketed us an anxiolytic. 

The best-known and most-used anxiolytics are the benzodiazepines, of which those in use include alprazolam, bromazepam, chlordiazepoxide, clobazam, clonazepam, diazepam, flunitrazepam, halazepam, loprazolam, lorazepam, medazepam, midazolam, oxazepam, quazepam, temazepam and triazolam. The benzodiazepines work by acting as benzodiazepine binding-SITE AGONISTS at a site of the GABA receptors. 

Although the BZs show a robust anxiolytic effect, many of the clinical trials were conducted before the currently used divisions between specific anxiety disorders became available (4). As a result, knowledge of their efficacy in discrete anxiety disorders is incomplete. In clinical practice (48) BZs are widely used for GAD and as prophylactics in situational anxiety, with diazepam (l)historically being the most popular choice. Others in common use are chlordiazepoxide (2), clorazepate (3), lorazepam (4), alprazolam (5), oxazepam (6), bromazepam (7), and clonazepam (8) Response rates are high and the onset of therapeutic effect is immediate. This is an important contrast to the MAOIs, TCAs, and SSRIs, where an anxiolytic effect is not seen for several weeks. Although not specifically approved for this disorder. BZs are also effective in social phobia, with clonazepam (49) showing a superior response rate to that of alprazolam (50). Alprazolam and clonazepam are the only BZs approved for the treatment of panic disor-... 

Compared with diazepam, lorazepam and oxazepam are relatively less lipophilic and have a slower onset of effect. These benzodiazepines have smaller volumes of distribution and a resulting longer duration of action." Oxazepam absorption is slow, and peak levels are not obtained until 2 to 4 hours after a single dose however, like lorazepam, oxazepam s anxiolytic effects are long lasting because extensive distribution does not occur. 

In another study, Malsch and Kieser (2001) investigated the anxiolytic effects of WS 1490 compared to placebo in patients previously treated with a benzodiazepine. They evaluated the potential of the kava preparation as a replacement for the benzodiazepine, as well as the ability of the kava preparation to reduce benzodiazepine withdrawal symptoms. This was a five-week randomized, double blind placebo-controlled study in outpatients with non-psychotic anxiety (e.g., generalized anxiety disorder, social phobia, and simple phobia). Forty patients were included, and all had been on benzodiazepines (i.e., lorazepam, bromazepam, oxazepam, or alprazolam) for a mean duration of 20 months prior to entering the study. Of the 40 patients, 25 were males, and the mean age of the total sample was 40 years (range 21—75 years). 

Several clinical studies have shown buspirone (14a) to have anxiolytic efficacy equivalent to that of DZ with significantly less sedation. ° Rats trained to discriminate oxazepam or pentobarbital from vehicle did not generalize to buspirone. At doses above those which are anxiolytically relevant in man, the drug caused a dose-related elevation of plasma prolactin in male subjects, and like the BZ s also increased growth hormone levels. Buspirone elicits a dose-dependent rise in rat striatal dopamine (DA) metabolite levels and may do so by selective antagonism of presynaptic DA autoreceptors with minimal postsynaptic effects. Its catalepsy-reversal effects may occur... 

Oxazepam is an active metabolite of both chlordiazepoxide and diazepam and is marketed separately, as a shortacting anxiolytic agent. Oxazepam is rapidly inactivated to glucuronidated metabolites that are excreted in the urine (Fig. 22.18). The half-life of oxazepam is approximately 4 to 8 hours, and cumulative effects with chronic therapy are much less than with long-acting benzodiazepines, such as chlordiazepoxide and diazepam. Lorazepam is the 2 -chloro derivative of oxazepam and has a similarly short half-life (2-6 hours) and pharmacological activity. 

Anxiolytics and hypnotics Benzodiazepines Alprazolam, Bromazepam, Brotizolam, Chlordiazepoxide, Clobazam, Clonazepam, Clorazepate, Clotiazepam, Diazepam, Flunitrazepam, Flurazepam, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Midazolam, Nitrazepam, Oxazepam, Oxazolam, Quazepam, Temazepam, Triazolam... 

Metabolic breakdown of several benzodiazepine compounds commonly prescribed in the body leads to the production of several intermediate metabolites which have anxiolytic properties. Oxazepam occupies the position of a final common pathway in the metabolic breakdown process, further chemical changes producing inactive compounds. The failure of oxazepam to prevent diazepam withdrawal symptoms when it has been described as producing such symptoms on its own account (39 ) suggests another unresolved complexity in benzodiazepine dependence. 

Anti-anxiety drugs. The most used of the anxiolytics are the benzodiazepines which not only relieve anxiety, and relax skeletal muscle, but can suppress convulsions, all accomplished apparently by augmenting the inhibitory transmission effected by gamma-aminobutyric acid in the spinal cord (Choi, Farb, and Fischbach, 1977). Discovered in 1933, the benzodiazepines gained clinical acceptance about 1965 (Zbinden and Randall, 1967). The first used member was chlordiazepoxide ( Librium ) followed by the simpler, but more potent, diazepam (/J.//) ( Valium ). Some think that diazepam is a pro-drug for oxazepam ( Serax ) which is a N-demethylated and 3-hydroxylated metabolic product, and is frequently prescribed as such. Related benzodiazepines such as nitrazepam ( Mogadon ) and flurazepam are much used as hypnotics in the place of barbiturates. 

---