Antiepileptic Drugs
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
Clonazepam is used for the treatment of myoclonic seizures and absence of seizures in children. Intranasal spray of clonazepam is used as an orphan drug for recurrent acute repetitive seizures. Lorazepam and diazepam are efficacious in the treatment of status epilepticus. The latter is more frequently used because of less lipid solubility, more effectively confined to the vascular compartment, and has a longer effective half-life after a single dose (Porter et al., 2018). Clorazepate is effective in the treatment of focal seizures in combination with other antiepileptics. Clorazepate should be avoided in children less than 9 years of age (Porter et al., 2018). Clobazam is used in a variety of seizure phenotypes and is FDA approved for the treatment of Lennox–Gastaut syndrome in patients of age 2 years or more (Misty et al., 2018). Midazolam is used as an orphan drug for intermittent treatment of episodes of increased seizure activity in refractory epilepsy patients who are otherwise stable on other AEDs. More recently, midazolam was granted orphan drug designation in 2009 as a rescue agent for patients with intermittent bouts of increased seizure activity (i.e., acute repetitive seizure clusters), in 2012 for the treatment of nerve agent-induced seizures, and in 2016 for the treatment of status epilepticus and seizures induced by organophosphorus poisoning (Misty et al., 2018).
Saliva Drug Analysis
Steven H. Y. Wong, Iraving Sunshine in Handbook of Analytical Therapeutic Drug Monitoring and Toxicology, 2017
Clorazepate is converted to N-desmethyldiazepam in the acidic conditions of the stomach.57 After an acute 15-mg oral dose of clorazepate, Hallstrom et al.52 reported detection of approximately 5 to 20 ng/ml of N-desmethyldiazepam in saliva. S/P (total) ratios averaged 5.78 (range = 2.33 to 6.65). Another benzodiazepine, chlordiazepoxide, was reported to be detectable by radioimmunoassay in saliva after acute and multiple dosing.58 Saliva and plasma concentrations were highly correlated and were detectable for 30 to 60 hr. The S/P (total) had a mean value of approximately 0.03. Drug half-lives determined from plasma and saliva were equivalent.
Overview of the Biotransformation of Antiepileptic Drugs
Carl L. Faingold, Gerhard H. Fromm in Drugs for Control of Epilepsy:, 2019
Some other benzodiazepines should be mentioned because of somewhat different aspects of their biotransformation. Clorazepate is a prodrug which is rapidly decarboxylated in the acid milieu of the stomach to form N-desmethyldiazepam.42 This active metabolite is eventually eliminated from the body as described above. Lorazepam is the only anticonvulsant benzodiazepine which is biotransformed almost completely by glucuronidation without undergoing some phase I reactions first.43 This is because the drug has a hydroxyl group attached to carbon 3 whereas other benzodiazepines must add the 3-hydroxyl group in vivo.
Pharmacotherapy of adjustment disorder: A review
Published in The World Journal of Biological Psychiatry, 2018
Dan J. Stein
Razavi et al. (1999) compared trazodone (mean dose 111.5 mg/day) and clorazepate (mean dose 17.5 mg/day) in a small study of DSM-III-R adjustment disorder in patients undergoing treatment for breast cancer. Eighteen patients were enrolled in a 4-week study, with efficacy assessed by the Hospital Anxiety and Depression Scale and a number of other scales. A successful response to treatment was seen in 91% of those receiving trazodone and 57% of those receiving clorazepate, although in this small sample this difference did not reach statistical significance. There were also no group differences in adverse events. The authors concluded that trazodone is not associated with dependence and is therefore a valuable option in the treatment of adjustment disorders in cancer patients.
What are the pharmacotherapeutic options for adjustment disorder?
Published in Expert Opinion on Pharmacotherapy, 2022
Jacob Hoffman, Dan J. Stein
Two studies compared trazodone (a sedative with serotonin antagonist and reuptake inhibitor effects) with clorazepate (a benzodiazepine with GABAergic effects) for the treatment of adjustment disorder [13,14]. One study (n = 18) showed potential benefit for trazodone (91% response rate) compared to clorazepate (57% response rate) at 4 weeks, however the difference was not statistically significant [13]. In a similarly small study (n = 21) conducted in patients living with HIV, trazodone showed similar efficacy compared to clorazepate (80% vs 64% response rate respectively), with fewer concerns of adverse effects [14].
The pharmacological interactions between direct-acting antivirals for the treatment of chronic hepatitis c and psychotropic drugs
Published in Expert Review of Clinical Pharmacology, 2018
Carlos Roncero, Jose Luis Villegas, Maria Martínez-Rebollar, Maria Buti
It should also be administered with caution with alfentanil, codeine, dihydrocodeine, fentanyl, hydrocodone, oxycodone, tramadol, alprazolam bromperidol, buspirone, clobazam, clorazepate, clotiapine, diazepam, estazolam, oral midazolam, quazepam, triazolam, zaleplon, zolpidem, zopiclone, imipramine, mirtazapine, nefazodone, trazodone, GHB and phencyclidine (see Table 1).
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