General Anesthetics
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
Dexmedetomidine, an imidazole derivative stimulates α2A adrenergic receptor (Kamibayashi and Maze, 2000) and produces sedation, analgesia but does not dependably provide general anesthesia (Aho et al., 1992). Dexmedetomidine has distribution as well as terminal half-life is 6 min and 2 h, highly protein bound drug, metabolize primarily by hepatic glucuronide and methyl conjugates, and excreted via kidney (Khan et al., 1999). The drug shows reduced blood pressure and bradycardia which might be due to the activation of α2A adrenergic receptor. At higher concentration, it also stimulates α2B-subtype receptor which results in hypertension followed by reduced heart rate and cardiac output (Lakhlani et al., 1997). Dexmedetomidine has good property to induce sedation and analgesic effect along with minimum respiratory problems (Belleville et al., 1992). The drug is available in the form of hydrochloride salt which has to be diluted with normal saline solution before administration. The suggested dose of the drug is 1 mg/kg, the infusion is not recommended for more than 24 h as it produces rebound hypertension (Khan et al., 1999).
Information on level of drugs into breastmilk
Wendy Jones in Breastfeeding and Medication, 2013
Nystatin is used vaginally to treat candidiasis and orally to treat intestinal infection. It is poorly absorbed from the gastro-intestinal tract. It is not absorbed through the skin or mucous membranes when applied topically. It is also used to treat oral lesions using suspension or pastilles. Avoidance of food or drink for one hour after administration is advised to maintain contact with the oral mucosa for as long as possible. It has poor bio-availability and so passage into breastmilk is unlikely. The BNF states that absorption from the gastro-intestinal tract is negligible although no levels have been measured in breastmilk. Compatible with use during breastfeeding. Terbinafine Brand name: Lamisil US brands: Lamisil Australian brands: Lamisil Terbinafine is used to treat dermatophyte infection of the nails and ringworm infections. The most frequent adverse effects after oral use of terbinafine hydrochloride are gastro-intestinal disturbances such as nausea, diarrhoea and mild abdominal pain. Loss or disturbance of taste may occur and occasionally may be severe enough to lead to anorexia and weight loss. Terbinafine hydrochloride is well absorbed from the GI tract. The bio-availability is about 40% because of first-pass hepatic metabolism. Treatment generally lasts for a maximum of 3 months although this may be longer in toenail infections. 241
Principles of Radioiodination and Iodine-Labeled Tracers in Biomedical Investigation †
Garimella V. S. Rayudu, Lelio G. Colombetti in Radiotracers for Medical Applications, 2019
In a typical protein radioiodination, 5 to 10 μg of protein in 0.1 M borate or phosphate buffer (pH 8.4) are reacted with 3 to 5 μmol of labeled ester per micromole of protein. The reaction mixture in a very small volume (10 to 50 μℓ) is kept in an ice bath for 15 to 30 min and the excess ester is then inactivated by conjugation of a large excess of an amino acid. The radioiodinated protein is mixed with a carrier protein, and free iodine is separated by conventional procedure. The disadvantage of this technique is that it is time-consuming. The first step has a labeling efficiency of 50 to 80%, and the second step has a labeling efficiency of 20 to 40%, leading to an overall labeling efficiency of 10 to 30%. Presently 125I-labeled N-SHPP in dry benzene is commercially available as a kit form from several manufacturers (New England Nuclear Co., Boston, Mass.; Amersham, Inc., Arlington Heights, Ill.; Calbiochem, San Diego, Calif.). The solvent benzene is removed under a stream of dry nitrogen prior to protein acylation. Iodinated methyl-p-hydroxybenzemidate hydrochloride also has been used as a conjugating agent.102 Under refrigeration, the radiolytic degradation is ⋍5%/ week.
Acetaminophen and tramadol hydrochloride-loaded soft gelatin capsule: preparation, dissolution and pharmacokinetics in beagle dogs
Published in Pharmaceutical Development and Technology, 2021
Tramadol is a centrally acting synthetic opioid medication with monoaminergic actions similar to serotonin-norepinephrine reuptake inhibitors (Miotto et al. 2017). It is considered as an first member of the ‘atypical opioids’ group with the pharmacodynamics drug effect district to those of the more classic opioids (Bravo et al. 2017). It has been marketed as a hydrochloride salt; moreover, it is available in injectable, oral, and rectally administered preparations. With an onset time of 1 h and Tmax of 2 h, it is well-absorbed in the gastrointestinal tract and then metabolized in the liver with the participation of cytochrome P450 (Siepsiak et al. 2019). Tramadol is used as a pain reliever for various acute or chronic diseases. However, for some diseases, other analgesics are being used due to the slow onset time of tramadol (Shipton 2000). For the treatment of cancer pain, in the initial treatment, morphine has been more effective for severe cancer pain which may reflect tramadol’s slower onset (Bamigbade and Langford 1998).
Comparing the dopaminergic neurotoxic effects of benzylpiperazine and benzoylpiperazine
Published in Toxicology Mechanisms and Methods, 2018
Daniel P. Katz, Mohammed Majrashi, Sindhu Ramesh, Manoj Govindarajulu, Dwipayan Bhattacharya, Subhrajit Bhattacharya, Aimen Shlghom, Chastity Bradford, Vishnu Suppiramaniam, Jack Deruiter, C. Randall Clark, Muralikrishnan Dhanasekaran
Synthesis of Benzylpiperazine and Benzoylpiperazine: A mixture of benzaldehyde (1 g, 0.01 mol) and piperazine (1.43 g, 0.0165 mol) in methanol was stirred for half an hour. Then sodium cyanoborohydride (2.1 g, 0.033 mol) was added and the mixture was allowed to stir for half an hour. The reaction was quenched by adding ice/water mixture and stirring the mixture for 20 min followed by extracting the final product using dichloromethane (3 × 30 ml). The combined organic extract was dried with anhydrous magnesium sulfate, filtered and evaporated to yield yellow oil. The oil was dissolved in anhydrous diethyl ether, and hydrochloric acid was added to form the hydrochloride salt. Benzoyl chloride (1.4 g, 0.01 mol) was dissolved in dichloromethane and the solution was dripped slowly over the piperazine solution over 10 min. The mixture was allowed to stir for 15 min. The solution was evaporated under reduced pressure to yield light yellow oil. The oil was dissolved in anhydrous diethyl ether, and hydrochloric acid gas was added to form the hydrochloride salt (Figure 1).
Novel and emerging therapeutics for genetic epilepsies
Published in Expert Review of Neurotherapeutics, 2021
Ana Pejčić, Slobodan M. Janković, Miralem Đešević, Refet Gojak, Snežana Lukić, Nenad Marković, Miloš Milosavljević
Clemizole hydrochloride (EPX-100) is a first-generation antihistamine that was used in the therapy of itchiness [88]. The anticonvulsant effect of clemizole and its derivates were discovered in experimental in vivo studies on scn1Lab mutant zebrafish models of Dravet syndrome [95,122,123]. The mechanism of action by which clemizole reduces the frequency of seizures is similar to fenfluramine and is most likely the result of modulation of 5-HT2B receptors and stimulation of serotoninergic transmission in the brain [123]. The pharmacokinetics and safety of clemizole hydrochloride were tested in a phase I, placebo-controlled, double-blind, 2-period study (NCT04069689) in three sequential groups of eight healthy subjects each [124]. Six participants in each group received clemizole hydrochloride at three different doses (20, 40, or 80 mg), while the other two participants received a placebo [124,125]. The study was completed in January 2020 and the results showed that it was well-tolerated by both male and female participants [88,125]. After the completion of the first phase of the clinical trial, a phase II multicenter, randomized, double-blind, placebo-controlled study (NCT04462770) began in late 2020 [126]. The efficacy of clemizole hydrochloride as adjunctive therapy will be assessed in 24 patients with Dravet syndrome, 2–17 years old with documented genetic mutations of SCN1A gene [126]. The study will have a 4-week observational period, 4-week titration period, and 12-week maintenance period [126].
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