Sedative Hypnotics flurazepam

Like the barbiturates, the benzodiazepines make it easier to fall asleep and to stay asleep through the night. However, they also suppress REM sleep, which can lead to REM rebound when they are discontinued. Tolerance to their sleep-promoting effects often develops after chronic use. Some long-acting benzodiazepines, such as flurazepam (Dalmane), are associated with pronounced hangover effects in the morning and are therefore problematic as sedative-hypnotics. Others, with a short-to-intermediate dnration of action, are more desirable as hypnotics. 

The benzodiazepines that have been most commonly marketed as sedative-hypnotics include temazepam (Restoril), estazolam (ProSom), flurazepam (Dalmane), quazepam (Doral), and triazolam (Halcion). Of these five, temazepam is the most easily metabolized and eliminated. Therefore, temazepam is preferred for elderly and medically ill patients to minimize the risk of drug accumulation. 

Flurazepam (Dalmane) [C-IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia Action Benzodiazepine Dose Adults Beds >15 y. 15-30 mg PO qhs PRN X in elderly Caution [X, /-] Elderly, low albumin, hepatic impair Contra NAG PRG Disp Caps SE Hangover d/t accumulation of metabolites, apnea, anaphylaxis, angioedema, amnesia Interactions T CNS depression W/ antidepressants, antihistamines, opioids, EtOH T effects OF digoxin, phenytoin T effects W/ cimetidine, disulfiram, fluoxetine, iso-niazid, ketoconazole, metoprolol, OCPs, propranolol, SSRIs, valproic acid. 

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... 

The principal disadvantages of barbiturates as hypnotics include the development of physical dependence, a relatively low therapeutic index (and the potential of poisoning, as in suicide), suppression of REM sleep, and possible hangover effects. As mentioned above, benzodiazepines (e.g., flurazepam or brotizolam) are hypnotics as effective as barbiturates and are much safer in terms of their therapeutic index, addiction potential, and REM sleep-deprivation effects. Thus benzodiazepines have displaced barbiturates as sedative hypnotics. 

Zopiclone was the first of the new sedative-hypnotics to be launched in the late 1970s and has been shown to be equi-effective with the standard sedative-hypnotic benzodiazepines such as flurazepam and temazepam. There is evidence that zopiclone may cause less "hang-over effects than the conventional benzodiazepines but some studies have shown that this drug does produce performance decrement when this is tested shortly after treatment. A similar profile has been reported for zolpidem while abercarnil... 

Flurazepam has a longer half-life than some other sedative hypnotics, so it may be less likely to cause rebound Insomnia on discontinuation... 

Lorazepam (la) in 2 or 4 mg doses showed hypnotic activity in insomniacs and good sedation in surgical premedication.41 Flurazepam (2h) is useful in the long term treatment of insomnia42 and shows no rebound effect after withdrawal.43 Flunitrazepam (2 ) has hypnotic activity in man at 2.5 mg, but does not induce physiological sleep.44 Fosazepam (2j) at 60-80 mg decreased sleep onset and awakening in healthy subjects.45 Quazepam (Sch 16134 2k) has been entered in the USAN listing as a sedative, hypnotic.46 Clobazam (9a) at 10—20 mg, but not triflubazam (9b) was useful for limited sleep difficulties in healthy males.47... 

Flurazepam (15 to 30 mg p.o. at bedtime) is a benzodiazepine derivative sedative-hypnotic that is used in the management of insomnia. Flurazepam depresses the CNS at the limbic and subcortical levels of the brain. It produces a sedative effect by potentiating the effect of the neurotransmitter gamma-amino-butyric acid on its receptor in the ascending reticular activating system, which increases inhibition and blocks both cortical and limbic arousal (see also Figure 50). 

Psychomotor dysfunction This includes cognitive impairment, decreased psychomotor skills, and unwanted daytime sedation. These adverse effects are more common with benzodiazepines that have active metabolites with long half-lives (eg, diazepam, flurazepam). The dosage of a sedative-hypnotic should be reduced in elderly patients to avoid excessive... 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Many benzodiazepines have potent hypnotic activity and are useful in the treatment of insomnia. Examples include flurazepam (Dalmane, A.93), midazolam (Versed, A.94), temazepam (Restoril, A.95), and triazolam (Halcion, A.96) (Figure A.28). Flunitrazepam (Rohypnol, A.97) is a particularly notorious sedative. Often called roofie or the date rape drug, flunitrazepam causes sedation and amnesia. Because of flunitrazepam s tendency to be abused, almost all nations tightly regulate the drug s availability. 

The antianxiety effects of chlordiazepoxide (165) were described in 1960 and this compound was followed by diazepam (135). These two drugs have captured 75% of the market for sedatives in the USA. Other benzodiazepines used as antianxiety agents include oxazepam (166 R = H), a metabolite of diazepam that is better tolerated, lorazepam (166 R = Cl) and potassium clorazepate (167). Prazepam is the iV-cyclopropylmethyl analogue of diazepam. The benzodiazepines have other therapeutic applications, many being used for inducing sleep, diazepam and nitrazepam are anticonvulsants and flurazepam (168) is both an antianxiety agent and a potent hypnotic. Thieno- and pyrazolo-1,4-diazepinones isosteric with diazepam have similar pharmacological properties (B-81 Ml 10604). 

Clinically important, potentially hazardous interactions with alcohol, anticholinergics, barbiturates, benzodiazepines, butabarbital, chloral hydrate, chlordiazepoxide, chlorpromazine, clonazepam, clorazepate, diazepam, ethchlorvynol, fluphenazine, flurazepam, hypnotics, lorazepam, MAO inhibitors, mephobarbital, mesoridazine, midazolam, narcotics, oxazepam, pentobarbital, phenobarbital, phenothiazines, phenylbutazone, primidone, prochlorperazine, promethazine, quazepam, secobarbital, sedatives, temazepam, thioridazine, tranquilizers, trifluoperazine, zolpidem... 

Brotizolam is a hypnotic/sedative approximately 60-100 times more potent than flurazepam. As with other short-acting, annu-lated benzodiazepines (e.g., triazolam), cited advantages include lack of adverse effects on sleep and performance after arousal. 

Loprazolam mesylate is a potent hypnotic/sedative belonging to the second generation of annulated-1,4-benzodiazepines. The of loprazolam ( 6 hr.) is longer than those of triazolam and midazolam, but shorter than the "effective" TJs of flurazepam. 

Many benzodiazepine derivatives have been reported to possess sedative and hypnotic activity in both animals and man. Flurazepam (l) has been found to possess useful hypnotic activity in man without producing significant "hangover" effects the following morning . In animals flurazepam was found to possess activity, in many tests systems, similar in potency and profile to diazepam . 

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