Heterocyclic Drug Design and Development
Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg in Promising Drug Molecules of Natural Origin, 2020
Antiemetic refers to an agent used for combating vomiting and nausea. Such drugs are used primarily for the treatment of motion sickness. Antiemetics of natural origin are given in Table 9.36.
‘In and Out of the Hole’
Ornella Corazza, Andres Roman-Urrestarazu in Handbook of Novel Psychoactive Substances, 2018
Hepatic failure and renal failure were reported among users of MXE; yet, renal failure was more prominent, as only one study stated hepatic toxicity (Wiergowski et al., 2014). Renal damage was seen among both lethal and non-lethal cases with increased levels of creatinine (2.8 mg/dL) and creatine kinase (up to 5023 U/L). CK levels also indicated muscle damage, and that agreed with findings of one study that reported massive rhabdomyolysis (Wiergowski et al., 2014). The results were confirmed by a study in mice, where significant bladder and kidney toxicity were seen after three months of exposure to MXE. In the study, significant abnormalities were seen in the kidneys of mice after they were subjected to MXE (intraperitoneally or via saline). Abnormalities included glomerular shrinkage, tubular necrosis, and inflammatory cell infiltration (Dargan, Tang, Liang, Wood, & Yew, 2014). Management of MXE toxicity depends on the clinical scenario and other drugs taken (Adamowicz & Zuba, 2015; Hydzik, Gomółka, Sulka, & Cudzich-Czop, 2012; Rosenbaum et al., 2012). Low doses of benzodiazepines are recommended along with keeping the patient under observation during recovery (Wood et al., 2012). Benzodiazepines were used intravenously for treatment of agitation and aggression induced by MXE. The benzodiazepine derivatives used were diazepam, clonazepam, chlorprothixene, and midazolam. Antiemetics can be used for nausea and vomiting. Prevention of rhabdomyolysis can be undertaken by administering body fluids. Moreover, malignant hypertension can be treated using BZDs, sodium nitroprusside, or phentolamines (Craig & Loeffler, 2014). If needed, respiratory support should be offered to the patient. Tolerance, dependence, and addiction are reported among users, as heavy consumers can escalate the dose up to ten times (Adamowicz & Zuba, 2015). A study by Botanas et al. (2015) showed that MXE increases the rewarding and reinforcement effects, thus increasing the potential for human abuse. A further study of online discussion fora analysis reported redosing among some users who lost control over drug intake (Kjellgren & Jonsson, 2013). Risk of accidental overdose is reported with MXE derivatives, as users only experience the desired effects after 30–90 minutes of snorting, and that could lead inexperienced users to re-dose in order to achieve the effects (Craig & Loeffler, 2014; Hondebrink et al., 2017). Withdrawal symptoms of MXE included decreased cognition, depressive thoughts, insomnia, low mood, and potential suicidal attempts (Corazza et al., 2012; Craig & Loeffler, 2014). Lethal effects were seen in 11 studies associated with the use of MXE derivatives; these were associated with the use of MXE on its own or MXE in conjugation with other drugs (Zawilska, 2014). Reported cases of deaths were associated with hyperthermia or drug interactions as MXE was used with other drugs of abuse (Zanda, Fadda, Chiamulera, Fratta, & Fattore, 2016; Zawilska, 2014).
Systemic care—Renal, hematologic, gastrointestinal
Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor in Essentials of Anesthesia for Neurotrauma, 2018
A low-fat diet with small frequent meals is recommended. Prokinetic drugs help promote GI motility and are widely used to improve enteral feeding in critically ill patients. Cisapride stimulates gut motility by activating 5-HT receptors, but it has been withdrawn from many countries because of cardiac toxicity. Metoclopramide is the only medication approved by the FDA and improves gut motility by inhibiting dopamine D2 receptor and presynaptic muscarinic receptors. The possible best dosage is 10 mg intravenously three times a day. However, its use is hindered by the potential CNS-related adverse effects such as extrapyramidal side effects and increasing frequency and severity of seizures. Therefore, metoclopramide should be avoided in patients with seizure disorders. Erythromycin is a macrolide antibiotic that stimulates motilin receptors on enteric nerves and intestinal smooth muscle which leads to increased gastric emptying. The prolonged use of erythromycin causes tachyphylaxis which can be managed by discontinuation for 2 weeks and then resuming. A retrospective study in TBI patients demonstrated that the efficacy of metoclopramide 10 mg, metoclopramide 20 mg, and metoclopramide 10 mg plus erythromycin 250 mg intravenously every 6 hours to treat gastric feeding intolerance were 55%, 62%, and 79%, respectively; thus, the authors suggested combination therapy (metoclopramide and erythromycin) as first line treatment of gastric feeding intolerance in head injury patients. Antiemetic medications can be used if patients experience nausea and vomiting.
Development and evaluation of a sublingual film of the antiemetic granisetron hydrochloride
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2016
Vani Kalia, Tarun Garg, Gautam Rath, Amit Kumar Goyal
The objective of this study was to develop an oral transmucosal formulation of an antiemetic drug that can not only serve in the active form but also provide a controlled release profile. In this study, sublingual films based on the biodegradable and water-soluble polymers, that is HPMCK-4M and PVPK-30, were developed by the solvent casting method, and were loaded with the antiemetic drug granisetron hydrochloride (granisetron HCl). The entrapment efficiency of the developed formulation was found to be 86%. The in vitro profile showed an instant release of the drug from the sublingual film, in a pattern following the first order kinetics array. The in vivo studies showed that granisetron HCl was delivered in its active state and showed effective results, as compared to its activity in the marketed formulation.
Ondansetron Versus Metoclopramide as Antiemetic Treatment During Cisplatin-based Chemotherapy: A prospective study with special regard to electrolyte imbalance
Published in Acta Oncologica, 1995
Nicolas Tsavaris, Gavrilos Charalambidis, Nicolas Ganas, Margarita Pagou, Athanasios Karabellis, Nicolas Mylonakis, Nikoleta Benou, Dimitris Tsikalakis, Paris Kosmidis
Cancer patients selected for cisplatin-based chemotherapy were randomly divided into two groups (42 patients in each) which received either metoclopramide or ondansetron as antiemetics. Metoclopramide was given i.v. with 5 doses of 2 mg/kg starting 30 min before the cisplatin infusion and continued with one dose every 3 h. Ondansetron was given with a first injection of 8 mg i.v. 30 min before the cisplatin infusion; the patients were given 8 mg orally 5 and 10 h after the cisplatin infusion followed by 8 mg × 3 during the next two days. In the present study ondansetron was superior to metoclopramide concerning antiemetic efficacy and gave also less side-effects as diarrhea, dizziness, extrapyramidal symptoms and electrolyte imbalance (sodium, potassium, magnesum, phosphorous) during the first 24 h following the cisplatin infusion.
Economic and clinical burden of opioid-induced nausea and vomiting
Published in Postgraduate Medicine, 2017
Opioids are the standard of care for treating moderate-to-severe pain; however, their efficacy can be limited by adverse events (AEs), including nausea and vomiting. Opioid-induced nausea and vomiting (OINV) is an inherent adverse effect of opioid treatment, exerting effects centrally and peripherally. Opioid-related AEs can impact treatment adherence and discontinuation, which can result in inadequate pain management. OINV may persist long-term, negatively affecting patient functional outcomes, physical and mental health, patient satisfaction, and overall costs of treatment. Multiple factors may contribute to OINV, including activation of opioid receptors in the chemoreceptor trigger zone, vestibular apparatus, and gastrointestinal tract. Prophylactic or early treatment with antiemetics may be appropriate for patients who are at high risk for OINV.