Benzodiazepine triazolam

Limited results from clinical laboratory evaluations suggested that the GABAj l agonists zaleplon (Rush et al. 1999b) and Zolpidem (Rush et al. 1999a) produce effects that are consistent with abuse potential comparable to that of the benzodiazepine triazolam. The reported incidence of dependence on Zolpidem in the medical literature is low, compared with that for benzodiazepines, and is characterized by use of high doses, often in individuals with a history of substance abuse (Hajak et al. 2003 Vartzopoulos et al. 2000). 

Weingartner, H.J. et al., Specific memory and sedative effects of the benzodiazepine triazolam, J. 

In a controlled study in healthy patients with a history of drug abuse, zaleplon was shown to have a comparable abuse potential to that of the benzodiazepine, triazolam [28]. 

Of all the benzodiazepines, triazolam has been most consistently assessed for rebound potential. Most studies have detected rebound (e.g., [10]). The higher dose of 0.5 mg shows very consistent rebound even after single night administration [15], Even at the lower and most used dose of 0.25 mg rebound can be found. Other shortacting benzodiazepines, for which rebound has been reported, include brotizolam and midazolam [8, 16, 17], The severity of rebound was dose related. 

Benzodiazepines (triazolam, temazepam, midazolam, lorazepam, estazolam). 

Despite common actions upon GABA, no pharmacodynamic or pharmacokinetic interations have been shown when tiagabine is combined with the benzodiazepine triazolam or with alcohol... 

A summary of the features of the pharmacophore model is shown in Figure 4.3. The jV-5-benzylated PBI parent compound is shown in white with the benzodiazepine triazolam superimposed on it in orange. The minimal requirements for tight binding are denoted as FI-bond acceptors 1 and 2 as well as lipophilic site 1. These requirements are fulfilled by the two carbonyl oxygens on the PBI and the two nitrogens on the benzodiazepines, and there... 

Annelating the 1,2-bond of ring B with an additionai eiectron-rich (i.e., proton acceptor) ring, such as s-triazoie or imidazole, also results in pharmacologically active benzodiazepine derivatives with high affinity for the BZR (Fig. 22.17). For example, the s-triazolo-benzodiazepines triazolam, alprazolam, and estazolam and the imidazo-benzodiazepine midazolam are popularly prescribed, clinically effective anxiolytic agents (Fig. 22.16). 

Fusion of an additional heterocyclic ring onto that already present in the benzodiazepines has led to some medicinal agents with considerable activity. Treatment of an intermediate like 15 with phosphorus pentasulfide affords the corresponding thio-amide (37). Condensation of this intermediate with acetyl hydra-zide affords triazolam )37). The same agent can be prepared by reaction of the amidine, 38, ° with acetylhydrazide. ... 

A rebound sleep disturbance has been found after only 7—10 days of treatment with therapeutic doses of triazolam (Greenblatt et al. 1987). Others have described a withdrawal syndrome after substitution of a short-acting benzodiazepine for a long-acting benzodiazepine (Conell and Berhn 1983). Rebound insomnia may occur with zolpidem. 

Williams H, Oyefeso A, Ghodse AH Benzodiazepine misuse and dependence among opiate addicts in treatment. It J Psychol Med 13 62-64, 1996 Wiseman SM, Spencer-Peet J Prescribing for alcoholics a survey of drugs taken prior to admission to an alcoholism unit. Practitioner 229 88—89, 1985 Wolf B, Grohmann R, Biber D, et al Benzodiazepine abuse and dependence in psychiatric inpatients. Pharmacopsychiatry 22 54—60, 1989 Wood MR, Kim JJ, Han W, et al Benzodiazepines as potent and selective bradykinin B1 antagonists. J Med Chem 46 1803—1806, 2003 Zawertailo LA, Busto UE, Kaplan HL, et al Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital. J Clin Psycho-pharmacol 23 269-280, 2003... 

Table 32.1 describes 30 persons who have been observed to use one of four available therapeutic compounds for the treatment of one of three possible disorders. The four compounds in this measurement table are the benzodiazepine tranquillizers Clonazepam (C), Diazepam (D), Lorazepam (L) and Triazolam (T). The three disorders are anxiety (A), epilepsy (E) and sleep disturbance (S). In this example, both measurements (compounds and disorders) are defined on nominal scales. Measurements can also be defined on ordinal scales, or on interval and ratio scales in which case they need to be subdivided in discrete and non-overlapping categories. 

Benzodiazepines (including alprazolam, chlordiazepoxide, diazepam, flurazepam, halzepam, prazepam, triazolam)... 

For testing sedative hypnotic drugs of the triazolam type the preparation was undertaken of 8-chloro-6-(o-chlorophenyl)-4ff-.y-triazolo[4,3-a][l,4]benzodiazepin-1 -valeric acid methyl ester as an intermediate, with subsequent cyclization and amida-... 

Bakti G, Fisch HU, Karlaganis G, Bircher J Mechanism of the excessive sedative response of cirrhotics to benzodiazepine Model experiments with triazolam. Hepatology 1987,7 629-638. 

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. 

Hypnotics fall into different categories, including the benzodiazepines (e.g., triazolam, temazepam, clotiaze-pam, nitrazepam), barbiturates (e.g., hexobarbital, pentobarbital), chloral hydrate, and Hi-antihistamines with sedative activity (p. 114). Benzodiazepines act at specific receptors (p. 226). The site and mechanism of action of barbiturates, antihistamines, and chloral hydrate are incompletely understood. 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

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