Psychotropics in Your Medicine Cabinet: A Case Study of Dimenhydrinate Use.

: Reporting of intoxication and withdrawal from aberrant use of over-the-counter medication has been sparse and inconsistent in literature. Attributed to their anticholinergic properties, medications such as dimenhydrinate (Gravol) taken in supratherapeutic doses have been associated with euphoria, anxiolysis, and hallucinations. We present a case of a woman in her forties, with a psychiatric history of bipolar disorder, and complex concurrent medical history including familial Mediterranean fever (FMF), and fibromyalgia, admitted for withdrawal management of her intravenous dimenhydrinate use. As a result of her FMF, there were numerous hospital admissions and treatment which required intravenous access. Hence, a physician-inserted intravenous access port was placed on her chest. The port was maintained monthly with the help of a community agency. In this port, she was injecting 100 to 200 mg of dimenhydrinate hourly for its euphoric and calming effects, consuming upwards of 2400 mg/d. Comprehensive laboratory work-up and urine drug screening were unremarkable. Vital signs were stable. Her mental status at time of admission was lethargic, unfocused, but calm. Her withdrawal symptoms included severe nausea, vomiting, sedation, headaches, dizziness, anxiety, and muscle stiffness. Her detoxification was managed with benztropine and lorazepam, and was well tolerated. The patient was discharged to a community inpatient rehabilitation center. Urine drug testing before discharge was negative. This case draws attention to the addictive potential of dimenhydrinate and offers a regime for its medical withdrawal management. Additionally, this case highlights that screening and management of over-the-counter medications warrants further clinical consideration and investigation.

Comparison of Dexamethasone-Dimenhydrinate and Dexamethasone-Ondansetron in Prevention of Nausea and Vomiting in Postoperative Patients.

INTRODUCTION: Postoperative Nausea and Vomiting is one of the most common problems after implementation of general anesthesia. The incidence can reach 80% in high-risk patients, depending on the type of surgery. In our study, we aimed to compare dexamethasone-dimenhydrinate and dexamethasone-ondansetron combinations in prevention of nausea and vomiting in postoperative patients. METHOD: Sixty 18-65-year-olds ASAI-II females who underwent rhinoplasty were included in the study. Patients were randomly included in two groups: Dexamethasone-dimenhydrinate group (group DD) and dexamethasone-ondansetron group (group DO). All patients received dexamethasone 8 mg iv after endotracheal intubation. Anesthesia continuation was established with sevoflurane, air-oxygen mixture and remifentanil infusion. At the 30th minute of the operation, group DO received ondansetron 4 mg iv and group DD received dimenhydrinate 1 mg/kg iv. For postoperative analgesia tramadol (1.5 mg/kg) iv, tenoksikam (20 mg) and afterward for postoperative patient-controlled tramadol was used. In the postoperative recovery room, nausea and vomiting were evaluated at the 30th, 60th, 120th minutes and at the end of 24 h. Total amount of tramadol was recorded. All results were statistically evaluated. OBSERVATIONS: Demographics and Apfel risk scores of both groups were similar. Surgical operation duration (p = 0.038) and total preoperative remifentanil consumption were higher in group DD (p = 0.006). In group DO, nausea at 30 and 60 min (p = 0.001, p = 0.007), retching at 30 and 60 min (p = 0.002, p = 0.006) were higher than group DD. The additional antiemetic need in group DO was significantly higher at 30 min (p = 0.001). Postoperative analgesic consumption was similar in both groups. RESULT: Our study revealed that dexamethasone-dimenhydrinate combination was more effective than dexamethasone-ondansetron in prevention of nausea and vomiting after rhinoplasty operations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of running training on DMH-induced aberrant crypt foci in rat colon.

PURPOSE: We examined the effects of treadmill-running training on the induction of aberrant crypt foci (ACF), which is the first step of colon cancer induction, in the colonic mucosa of rats injected with 1,2-dimethylhydrazine (DMH). METHODS: Four-week-old F344 rats (N = 38) were randomly assigned to training (19 rats) and control (19 rats) groups. After a week, all rats were given DMH (20 mg.kg(-1) body weight) once a week for 2 wk. Running training was started at age 7 wk (speed: 10 m.min(-1), 0% grade, 120 min.d(-1), 5 d.wk(-1)). After 4 wk of training, the rats were sacrificed and the colon was removed, opened, and counted for ACF with 0.2% methylene blue staining. RESULTS: Running training resulted in lower body- (P < 0.01) and adipose fat weight (P < 0.05). The numbers of ACF and total AC were significantly lower in the running training group than in the control group (P < 0.05). The occurrences of one, three, and five aberrant crypts per focus were also significantly lower in the running training group than in the control group (P < 0.05). The ratios of total AC/ACF did not significantly differ between the running training and control groups. CONCLUSIONS: The results of the present investigation suggest that low-intensity running training inhibits the DMH-induced initiation of colon ACF development.

Contribution to the treatment of nausea and emesis induced by chemotherapy in children and adolescents with osteosarcoma.

CONTEXT AND OBJECTIVE: Chemotherapy-induced emesis is a limiting factor in treating children with malignancies. Intensive chemotherapy regimens along with emetogenic drug administration have increased the frequency and severity of emesis and nausea. Our study was designed to consider the importance of this problem and the need for improvement in emesis treatment for patients receiving chemotherapy. Our objective was to compare the efficacy and safety of the antiemetic drug granisetron and a regimen of metoclopramide plus dimenhydrinate. DESIGN AND SETTING: Open, prospective and randomized study at Instituto de Oncologia Pediátrica, Department of Pediatrics, Universidade Federal de São Paulo. METHODS: From February to August 1994, 26 patients (mean age: 14 years) with osteosarcoma received 80 chemotherapy cycles of iphosphamide (2,500 mg/m2) plus epirubicin (75 mg/m2) or carboplatin (600 mg/m2), or epirubicin (75 mg/m2) plus carboplatin (600 mg/m2). Eighty chemotherapy treatments were analyzed regarding nausea and vomiting control. Patients were randomized to receive either a single dose of granisetron (50 microg/kg) or metoclopramide (2 mg/kg) plus dimenhydrinate (5 mg/kg infused over eight hours). Emesis and nausea were monitored for 24 hours by means of the modified Morrow Assessment of Nausea and Emesis. Statistical analysis utilized the chi-squared, Student t and Mann-Whitney tests, plus data exploration techniques. RESULTS: 62.5% of the patients undergoing chemotherapy responded completely to granisetron, whereas 10% responded to metoclopramide plus dimenhydrinate (p < 0.0001). No severe adverse reactions were found in either of the treatments given. CONCLUSION: In children and adolescents with osteosarcoma, granisetron was safe and more efficient than metoclopramide plus dimenhydrinate for controlling chemotherapy-induced emesis and nausea.

Contribution to the treatment of nausea and emesis induced by chemotherapy in children and adolescents with osteosarcoma

CONTEXTO E OBJETIVO: A êmese induzida por quimioterapia é fator limitante no tratamento de crianças com câncer. O uso de quimioterapia com drogas emetogênicas tem aumentado a freqüência desse efeito colateral. O objetivo é comparar a eficácia e a toxicidade do granisetron às da combinação de altas doses de metoclopramida e dimenidrato em crianças com osteossarcoma utilizando a mesma quimioterapia. TIPO DE ESTUDO E LOCAL: Aberto, prospectivo, randomizado, realizado no Instituto de Oncologia Pediátrica, Departamento de Pediatria, Universidade Federal de São Paulo, Brasil. MÉTODOS: Entre fevereiro e agosto de 1994, 26 crianças com idade de 7 a 18 anos (média de 14 anos), recebendo quimioterapia para osteossarcoma, entraram no estudo. A quimioterapia consistiu de ciclos repetidos de: A) ifosfamida 2.500 mg/m² + epirrubicina 75 mg/m²; B) ifosfamida 2.500 mg/m² + carboplatina 600 mg/m²; C) carboplatina 600 mg/m² + epirrubicina 75 mg/m². 80 tratamentos quimioterápicos foram avaliados para o controle de náuse e vômito. Os pacientes foram randomizados para receber dose única de granisetron (50 µ/kg) ou metoclopramida (2 mg/kg) mais dimenidrato (5 mg/kg) infundidos por oito horas. Êmese e náusea foram monitoradas por 24 horas por meio de escore de MANE (Morrow Assessment of Nausea and Emesis). Foram utilizados testes de Qui-quadrado, t e Mann Whitney, além da técnica de análise exploratória de dados. RESULTADOS: O granisetron induziu resposta completa em 62,5% dos pacientes submetidos aos tratamentos quimioterápicos comparado a apenas 10% obtidos com a combinação de metoclopramida associado ao dimenidrato (p < 0,0001). CONCLUSÕES: Concluímos que o granisetron é droga segura e eficiente em crianças com osteossarcoma superior à associação de metoclopramida e dimenidrato no controle de náuseas e vômitos induzidos por quimioterapia para osteossarcoma em crianças.

Prophylaxis of postoperative nausea and vomiting with oral, long-acting dimenhydrinate in gynecologic outpatient laparoscopy.

UNLABELLED: Dimenhydrinate is an inexpensive antiemetic with few side effects available as an oral, long-acting (LA) formulation (Gravol L/A) containing 25 mg of immediate and 50 mg of sustained release drug. We designed this double-blind comparison trial to assess the efficacy of dimenhydrinate LA versus droperidol alone and the combination for prophylaxis of nausea, vomiting, and retching in outpatient gynecologic laparoscopy. One-hundred-forty-one women were randomized into 3 groups: 1) droperidol (placebo capsule preoperatively and IV droperidol 0.625 mg before induction), 2) dimenhydrinate LA preoperatively and IV placebo before induction, or 3) combination. Information regarding nausea, vomiting, retching, pain, and sedation was recorded in the postanesthesia care unit (PACU) and collected by telephone for the presence of symptoms: on arrival home; at bedtime; upon arising, and at lunchtime the following day. The overall incidence of complete treatment failure (rescue medication in PACU or nausea, vomiting, or retching at any time point) was 28 of 46 (61%), 28 of 48 (58%), and 22 of 47 (47%); and for treatment failure vomiting (rescue medication in PACU or vomiting or retching at any time point) was 16 of 46 (35%), 11 of 48 (23%), and 5 of 47 (11%), for the droperidol, dimenhydrinate, and combination groups, respectively (P = 0.007 for droperidol versus combination). There were no differences in sedation or pain. Preoperative administration of an oral dose of LA dimenhydrinate in combination with droperidol when compared with droperidol alone effectively reduced the incidence of vomiting but not nausea in women undergoing elective outpatient gynecologic laparoscopy. IMPLICATIONS: Dimenhydrinate is an inexpensive antiemetic with few side effects available as a long-acting oral formulation. Women undergoing outpatient gynecologic laparoscopy were given droperidol, an effective antiemetic, dimenhydrinate alone, or the combination of the two drugs. Dimenhydrinate plus droperidol significantly reduced the overall incidence of vomiting, but not nausea, when compared with droperidol alone.

[Droperidol and dimenhydrinate alone or in combination for prevention of postoperative nausea and vomiting]. / Droperidol und Dimenhydrinat alleine und in Kombination zur Prophylaxe von Ubelkeit und Erbrechen in der postoperativen Phase.

BACKGROUND: Droperidol and dimenhydrinate are inexpensive antiemetic drugs. Droperidol, especially, has been studied extensively in the past, but there are no studies that used the combination of both drugs for prevention of postoperative nausea and vomiting (PONV). Thus, the aim of this randomised controlled and double-blinded study was to evaluate the antiemetic efficacy and the side effects of such a combination therapy. METHODS: 240 inpatients undergoing ENT surgery under general anaesthesia were randomised to receive one of four antiemetic regimes: placebo, dimenhydrinate (1 mg x kg-1), droperidol (15 micrograms x kg-1), or the combination of both drugs (droperidol 15 micrograms x kg-1 + dimenhydrinate 1 mg x kg-1) was administered after induction of anaesthesia and repeated 6 hours after the first administration. For general anaesthesia a standardised technique including benzodiazepine premedication, propofol, desflurane in N2O/O2, vecuronium, and a continuous infusion of remifentanil was used. Postoperative analgesia and antiemetic rescue medication were standardised. Episodes of vomiting, retching, nausea, and the need for additional antiemetics were recorded for 24 hours. The main goal of the study was to increase the number of patients who were completely free from PONV (chi 2-test with Fisher-Yates' correction). Furthermore, the severity of PONV was analysed using a standardised scoring algorithm. RESULTS: Data of 227 patients could be analysed. The incidence of patients who suffered from PONV was 41.3% (95%-confidence interval: 29-55%) in the placebo-group. Dimenhydrinate alone reduced PONV to 34.5% (95%-CI: 22-48%). This marginal effect and the effect of droperidol (PONV: 26.4% (95%-CI: 15-40%)) could not be proven statistically, since the power of the study was too small. The combination of both drugs decreased PONV to 19.6% (95%-CI: 10-32%) and also reduced the severity of the symptoms to a clinically acceptable level. CONCLUSION: Dimenhydrinate failed to reduce the incidence and severity of PONV. The efficiency of droperidol given alone was within the ranges previously known from metaanalytic data. The combination of both drugs showed a moderate synergistic effect.

[Anticholinergic syndrome after postoperative dimenhydrinate administration]. / Anticholinerges Syndrom nach postoperativer Dimenhydrinatgabe.

Appearance of an anticholinergic syndrome after treatment with drugs in therapeutic dosages is seldom reported in the literature. Based on a case report, the development and course of an anticholinergic syndrome after treatment with dimenhydrinate are described. The drug was given due to different symptoms such as vertigo and vomiting after surgery. The anticholinergic syndrome could successfully be treated with physostigmine.

Dimenhydrinate and metoclopramide alone or in combination for prophylaxis of PONV.

PURPOSE: Dimenhydrinate and metoclopramide are inexpensive antiemetic drugs. Metoclopramide, especially, has been studied extensively in the past, but there are no studies on the combination of both drugs for prevention of postoperative nausea and vomiting (PONV). METHODS: One hundred and sixty male inpatients undergoing endonasal surgery were randomized to receive one of four antiemetic regimens in a double-blind manner: placebo, 1 mg x kg(-1) dimenhydrinate, 0.3 mg x kg(-1) metoclopramide, or the combination of both drugs was administered after induction of anesthesia. Patients received a second dose of these drugs six hours after the first administration to mitigate their short half-life. Standardized general anesthesia included benzodiazepine premedication, propofol, desflurane in N2O/O2 vecuronium, and a continuous infusion of remifentanil. Postoperative analgesia and antiemetic rescue medication were standardized. Episodes of vomiting, retching, nausea, and the need for additional antiemetics were recorded for 24 hr. The incidences of PONV were analyzed with Fisher's Exact test and the severity of PONV (rated by a standardized scoring algorithm) with the Jonckheere-Terpestra-test. RESULTS: The incidence of patients free from PONV was 62.5% in the placebo-group and increased to 72.5% in the metoclopramide-group (P = 0.54), 75.0% in the dimenhydrinate-group (P = 0.34), and 85.0% in the combination- group (P = 0.025). In the latter group, the severity of PONV was reduced compared with placebo treatment (P = 0.017; Jonckheere-Terpestra-test). CONCLUSION: Dimenhydrinate and metoclopramide were ineffective in reducing the incidence and the severity of PONV. Their combination reduced the incidence of PONV compared with placebo.

Rectally administered dimenhydrinate reduces postoperative vomiting in children after strabismus surgery.

We have investigated the effectiveness of rectally administered dimenhydrinate on postoperative vomiting in children undergoing strabismus surgery, in a double-blind, randomized, placebo-controlled study. In one group, dimenhydrinate 50 mg was administered rectally 30 min before starting anaesthesia, whereas in the control group, placebo suppositories were given. Children who received dimenhydrinate showed a significantly (P < 0.001) lower incidence of vomiting (15%) than those in the control group (75%). We conclude that rectal administration of dimenhydrinate is an effective means of reducing postoperative vomiting in children undergoing strabismus surgery.

Equipment for drug release testing of medicated chewing gums.

An apparatus was specially designed and constructed for release testing of medicated chewing gums. The adjustable instrumental settings such as temperature, chewing frequency, chewing time, volume of test medium, distance between the jaws and twisting angle increased the versatility of the apparatus. Selection of the test medium was also an important parameter. Each sample was kneaded mechanically in separate test chambers and the drug release was followed by sampling and HPLC analysis. Different gum formulations were tested and the obtained results demonstrated satisfactory release curves for a variety of formulations and active ingredients. The tested gum formulations comprised nicotine, meclizine, dimenhydrinate and xylitol. The apparatus proved to be suitable in product control of commercial batches but also a useful tool in the research and development of medicated gum formulations.

Postoperative nausea and vomiting after Faden operation.

OBJECTIVE: The purpose of this study was to evaluate the antiemetic effect of prophylactic dimenhydrinate application prior to Faden operation and to compare the incidence of PONV between bimedial Faden operation (BMF) and horizontal recess-resect procedure (R&R). METHODS: Ninety-nine children (4-10 years) scheduled for BMF were included in this prospective double-blind study. Midazolam (0.5 mg/kg body weight, BW) was administered orally for premedication 30 min before induction of anesthesia. Additionally, children weighing >/=23 kg received either dimenhydrinate suppositories or placebo. The placebo group was compared with 148 children who underwent R&R surgery without antiemetic prophylaxis during the same period. Anesthesia was induced with thiopentone (5-10 mg/kg BW) and vecuronium (0.1 mg/kg BW) bromide and maintained with halothane (1-2 vol%) in N(2)O/O(2) (65/35 vol%). Age, height, weight, and incidence of oculocardiac reflex were documented. PONV was classified into "no vomiting", "vomiting without therapy", and "vomiting requiring rescue medication". In the latter case dimenhydrinate was given again. The chi-square test was used for statistical analysis. RESULTS: Forty-eight patients received placebo, while 51 received dimenhydrinate. No differences between any groups were observed concerning age, height, weight, and incidence of oculocardiac reflex. Compared to R&R surgery, PONV requiring rescue medication occurred significantly more frequently after BMF (45% vs 23% after R&R). PONV after BMF was significantly less severe in the dimenhydrinate group than in the placebo group. The total incidence of PONV after BMF, however, was not significantly reduced. CONCLUSION: The high incidence of PONV after BMF can be explained by the greater invasiveness of BMF than R&R surgery. PONV requiring antiemetic rescue medication can be reduced by preoperative administration of dimenhydrinate suppositories.

Reduction of postoperative nausea and vomiting by dimenhydrinate suppositories after strabismus surgery in children.

UNLABELLED: Although dimenhydrinate has been used for treatment and prevention of postoperative nausea and vomiting (PONV) since the fifties, there have been few controlled studies about its efficacy. We performed a double-blinded study of 301 children aged 4 to 10 yr who underwent strabismus surgery. Preanesthetic medication with midazolam (0.5 mg/kg) as well as application of either dimenhydrinate suppositories or a placebo preparation was performed 30 min before the induction of anesthesia. Anesthesia was induced with thiopentone (5-10 mg/kg) and vecuronium (0.1 mg/kg) and maintained with halothane (1%-2%) in N(2)O/O(2) (65%/35%). The incidence of PONV, requirements for rescue dimenhydrinate, and time to recovery were recorded. The overall incidence of PONV was 60.1% in the placebo group and 30.7% in the dimenhydrinate group. In the dimenhydrinate group, children had to be observed in the recovery room significantly longer than those in the placebo group. Children having received dimenhydrinate were discharged from the recovery room with lower arousal scores. We conclude that the rectal administration of dimenhydrinate is effective for the prevention of PONV, although the sedative effect may require longer postoperative monitoring. IMPLICATIONS: We performed a double-blinded, randomized study to investigate the effects of prophylactic rectal dimenhydrinate application on postoperative nausea and vomiting in children undergoing strabismus surgery. In comparison with placebo, dimenhydrinate reduced the incidence of postoperative vomiting from 60.1% to 30.7%.

Novos avanços no controle da náusea pós-quimioterapia antineoplásica / New advances in controlling nausea and vomiting related to anticancer chemotherapy

A náusea é um dos efeitos colaterais mais temidos pelos pacientes que se submetem à quimioterapia (QT) antineoplásica. O controle inadequado desta complicaçäo confere significativa morbidade aos pacientes tratados com QT. Com o advento dos antagonistas dos receptores 5-HT, a incidência de náusea e vômito relacionados à quimioterapia (NVQT) diminuiu significativamente. Isso permitiu a administraçäo de regimes altamente emetizantes em nível ambulatorial para a maioria dos pacientes com câncer, melhorando sua qualidade de vida. O uso dessas drogas, entretanto, aumentou sobremaneira os custos do tratamento. Nesta revisäo, abordaremos sumariamente os mecanismos fisiopatológicos da emese, para entäo podermos compreender como atuam as drogas antieméticas atualmente utilizadas na prática oncológica. Discutiremos também os novos rumos da pesquisa clínica nesta área, incluindo estratégias para minimizar o custo desse tratamento

Oral ondansetron decreases vomiting after tonsillectomy in children.

Vomiting is a common, unpleasant aftermath of tonsillectomy in children. Intraoperative intravenous ondansetron (OND) reduces vomiting after this operation. Our double-blind, placebo-controlled, randomized investigation studied the effect of the oral form of OND on vomiting after outpatient tonsillectomy in children. We studied 233 healthy children age 2-14 yr undergoing elective tonsillectomy. Subjects were given placebo (PLAC) or OND 0.1 mg.kg-1 rounded off to the nearest 2 mg one hr before surgery. Anaesthesia was induced with either propofol or halothane/N2O. Vecuronium 0.1 mg.kg-1 was administered at the discretion of the anaesthetist. Anaesthesia was maintained with halothane/N2O, 50 micrograms.kg-1 midazolam iv and 1-1.5 mg.kg-1 codeine im. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine and atropine. All episodes of in-hospital emesis were recorded by nursing staff. Rescue antiemetics in the hospital were 1 mg.kg-1 dimenhydrinate iv for vomiting x 2 and 50 micrograms.kg-1 droperidol iv for vomiting x 4. Parents kept a diary of emesis after discharge. Postoperative pain was treated with morphine, codeine and/or acetaminophen. The two groups were similar with respect to demographic data, induction technique and anaesthesia time. Oral OND (n = 109) reduced postoperative emesis from 54% to 39%, P < 0.05. This effect was most dramatic in-hospital, where 10% of the OND-patients and 30% of the PLAC-group vomited, P < 0.05. The OND-subjects required fewer rescue antiemetics, 7% vs 17%, P < 0.05. In conclusion, oral ondansetron decreased the incidence of vomiting after outpatient tonsillectomy in children.

Mallory-Weiss tear. A complication of cancer chemotherapy.

Since the original report by Mallory and Weiss of tears in the lower esophagus or cardia of the stomach following alcoholic debauch, there have been many other cases, associated with sundry other causes, described in the literature. Recently, a Mallory-Weiss tear was reported in a patient as a complication of cancer chemotherapy. This article describes two similar cases and suggests that the Mallory-Weiss syndrome should be included in the differential diagnosis of any patient with epigastric pain, hematemesis, or melena after chemotherapy-induced retching or vomiting.