Promethazine Group Research Articles

Transcutaneous electrical nerve stimulation with the injection of pethidine and promethazine in the labor pain reduction: A randomized controlled trial.

The use of transcutaneous electrical nerve stimulation (TENS) to relieve labor pain remains controversial and existing evidence is neither strong nor consistent. This research was designed to compare TENS' effectwith the injection of pethidine and promethazine in labor pain reduction. In this trial, for 45 pregnant women in the active phase of labor, TENS electrodes were placed (two on both arms, and two over the participants' low back) continuously for 120 minutes; and for another group 45 pregnant women, 100 milligrams of pethidine and 250 micrograms of promethazine were injected intramuscularly which could be repeated once at least one hour later. Labor pain and duration, need for labor induction/augmentation/other pain control methods/ instrumental delivery, delivery type, and maternal and newborn complications were measured in both groups. The baseline mean visual analog scale (VAS) score, in the TENS group was 8.51±0.62 and in the pethidine and promethazine groups was 8.37±0.61 (P=0.31). While in a 120min post-intervention, it was 6.29±1.50 and 5.73±1.46 in the TENS group and the pethidine and promethazine group, respectively with no statistically significant difference (P=0.07). The labor duration in the TENS group was 6.61±1.71 hours and in the pethidine and promethazine group was 6.17±2.07 hours, with no statistically significant difference (P=0.33). In addition, no complication was recorded neither in the mothers nor newborns. This study showed that applying TENS in the active labor phase can reduce at least two scores in patient labor pain with no significant complications.

Transcutaneous electrical nerve stimulation with the injection of pethidine and promethazine in the labor pain reduction: A randomized controlled trial.

The use of transcutaneous electrical nerve stimulation (TENS) to relieve labor pain remains controversial and existing evidence is neither strong nor consistent. This research was designed to compare TENS' effectwith the injection of pethidine and promethazine in labor pain reduction. In this trial, for 45 pregnant women in the active phase of labor, TENS electrodes were placed (two on both arms, and two over the participants' low back) continuously for 120 minutes; and for another group 45 pregnant women, 100 milligrams of pethidine and 250 micrograms of promethazine were injected intramuscularly which could be repeated once at least one hour later. Labor pain and duration, need for labor induction/augmentation/other pain control methods/ instrumental delivery, delivery type, and maternal and newborn complications were measured in both groups. The baseline mean visual analog scale (VAS) score, in the TENS group was 8.51±0.62 and in the pethidine and promethazine groups was 8.37±0.61 (P=0.31). While in a 120min post-intervention, it was 6.29±1.50 and 5.73±1.46 in the TENS group and the pethidine and promethazine group, respectively with no statistically significant difference (P=0.07). The labor duration in the TENS group was 6.61±1.71 hours and in the pethidine and promethazine group was 6.17±2.07 hours, with no statistically significant difference (P=0.33). In addition, no complication was recorded neither in the mothers nor newborns. This study showed that applying TENS in the active labor phase can reduce at least two scores in patient labor pain with no significant complications.

Intravenous promethazine vs. diazepam to reduce symptoms of peripheral vertigo in emergency section: a double blind clinical trial

The present research aimed to compare the effectiveness of promethazine and diazepam in patients suffering from acute peripheral vertigo. This is a double blind clinical trial with a sample of 154 patients visiting the emergency section of Shahid Mohammadi Hospital in Bandar Abbas in 2017-18. The participants were randomly divided into two groups of 77, one treated with intravenous promethazine (50 mg) and the other with intravenous Diazepam (10 mg). The severity of vertigo was measured qualitatively and quantitatively 20 minutes later in both groups. Participants were 46 (29.9%) male and 108 (70.1%) female visiting the emergency section of hospital. The mean score of vertigo severity in Promethazine group was 44.44±17.94 and that of Diazepam group was 2.49±+3.87. The severity scores before and after the treatment in promethazine group were respectively 7.75±1.59 and 2.72±1.93. The mean scores of vertigo severity before and after the treatment in promethazine group was -5.04+2.10 and in the diazepam group it was -3.83+3.09. The intergroup difference was statistically significant (p=.013). The results revealed that intravenous promethazine and diazepam applied 20 minutes after prescription are both effective in controlling the severity of vertigo. Considering the probability of occurrence of extrapyramidal side-effects it can be suggested that the infusion of this medication be done slowly and take longer time. Meanwhile, vital signs should be precisely controlled.

Comparing the effects of transcutaneous electrical nerve stimulation and pharmaceutical hyoscine – promethazine compound on duration of the first phase of labor

Background: Delivery is an experience with full of stress, with pain, fatigue and fear. The fear of labor pain causes their tendency to cesarean section. It is believed that labor pain is the most painful pain experienced by human beings. This pain occurs at different stages of delivery. Labor duration is a factor affecting pregnancy outcomes and contributing to damages inflicted on mothers and their fetus. Present study was performed with aim of comparing effects of transcutaneous electrical nerve stimulation (TENS) with those of pharmaceutical hyoscine – promethazine compound on duration of the first phase of labor in 2015. Methods: This research was done by clinical ergometric method on 84 eligible pregnant women (42 in TENS group; 42 in hyoscine – promethazine group) referring to the Martyr Chamran Hospital of Kangavar division. At the onset of active phase, medication group were injected once with 20 mg of hyoscine and 25 mg of promethazine intramuscularly simultaneously. For non – medication group, TENS device was employed, with a pair of upper electrodes being placed between L1-T10 and a pair of lower ones being placed between S2-S4 on both sides of spinal column. Two groups were tested for duration of the first phase of labor. Results: Variables of age, body mass index(BMI), pregnancy age, dilatation of the second phase of labor and infant weight were tasted in both groups showing no significant differences in this regard (p>0.05). In the first phase of labor, no statistically significant difference was observed between 2 groups in terms of the means of contraction number means (p=0.23). But during of the first phase of labor exhibited some significant difference between 2 groups (p=0.002); in TENS group, mean duration of the first phase was shorter than hyoscine-promethazine group. Conclusion: compared to pharmaceutical hyoscine-promethazine compound, TENS further shortened duration of the first phase of labor; therefore, it is recommended that TENS be used to shorten labor duration.

Promethazine inhibits neuronal apoptosis via PI3K/Akt signaling pathway in rats with cerebral infarction.

To study the effect of promethazine on neuronal apoptosis in rats with cerebral infarction (CI) through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/Akt) signaling pathway. A total of 36 Sprague-Dawley rats were randomly divided into the sham group (n=12), model group (n=12), and promethazine group (n=12). The external carotid artery was only exposed in the model group, and the ischemia-reperfusion model after CI was established using the suture method in the other two groups. After modeling, the normal saline was intraperitoneally injected in the sham group and model group, while promethazine was intraperitoneally injected in the promethazine group. The rats were sampled after 1 week of intervention. The neurological deficits of rats were evaluated using the Zea-Longa score, and the cognitive function, the spatial learning, and memory of rats were detected via the water maze test. Moreover, the expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in brain tissues were detected via immunohistochemistry, and the relative protein expressions of PI3K p85, PI3K p110, and p-Akt were detected via Western blotting. The mRNA expressions of Bax and Bcl-2 were detected via quantitative Polymerase Chain Reaction (qPCR), and the apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The Zea-Longa score was significantly increased in the model group and promethazine group compared with that in the sham group (p<0.05), while it significantly declined in the promethazine group compared with that in the model group (p<0.05). The escape latency was significantly prolonged and the times of crossing platform were significantly reduced in the model group and promethazine group compared with those in the sham group (p<0.05), while the escape latency was significantly shortened and the times of crossing platform were significantly increased in the promethazine group compared with those in the model group (p<0.05). Compared with those in the sham group, the positive expression of Bax was significantly increased, while the positive expression of Bcl-2 was remarkably decreased in the model group and promethazine group (p<0.05). Compared with those in the model group, the positive expression of Bax was significantly decreased, while the positive expression of Bcl-2 was remarkably increased in the promethazine group (p<0.05). Besides, the model group and promethazine group had evidently higher relative protein expressions of PI3K p85, PI3K p110, and p-Akt than the sham group (p<0.05), while the promethazine group also had evidently higher relative protein expressions of PI3K p85, PI3K p110, and p-Akt than the model group (p<0.05). Compared with the sham group, model group, and promethazine group had remarkably increased relative mRNA expression of Bax, and remarkably decreased relative mRNA expression of Bcl-2 (p<0.05). Compared with those in the model group, the relative mRNA expression of Bax was remarkably decreased, while the relative mRNA expression of Bcl-2 was remarkably increased in the promethazine group (p<0.05). Finally, the apoptosis rate was significantly higher in the model group and promethazine group than that in the sham group (p<0.05), while it was significantly lower in the promethazine group than that in the model group (p<0.05). Promethazine inhibits neuronal apoptosis in CI rats by upregulating the PI3K/Akt signaling pathway, thereby exerting a protective effect.

Comparison Effect of Promethazine/Dexamethasone and Metoclopramide /Dexamethasone on Postoperative Nausea and Vomiting after Laparascopic Gastric Placation: A Randomized Clinical Trial.

BackgroundLaparoscopic gastric plication (LGP) is a technique in the restrictive category of bariatric procedures that reduces the gastric volume and increases intragastric pressure. Nausea and vomiting are the most common complications after this procedure. The goal of this research is to compare the combined effect of promethazine/dexamethasone versus Metoclopramide/ dexamethasone on the prevention of nausea and vomiting after LGP.MethodsIn recovery, the patients were divided into two groups, the Metoclopramide group which was given Metoclopramide 10 mg plus dexamethasone 4 mg/8 hours intravenous for 48 hours, and the promethazine group which was given promethazine 50 mg /12 hours, intramuscular for the first 24 hours and then promethazine 25 mg/12 hours for the next 24 hours plus dexamethasone 4 mg/8 hours intravenous for 48 hours. The frequency of nausea and vomiting, number of reflux episodes, frequency of epigastric fullness, and the duration of walking around q12 hours were recorded in the first 48 hours post-operation.ResultsEighty patients were enrolled into the study. Promethazine group were found to significantly reduce the incidence of PONV in the first 24 hours compared with the other group (41% vs. 97.5%), relative risk = 0.042 [95% CI = 0.006, 0.299]. The mean numbers of epigastric fullness and severity of epigastria pain were lower in the promethazine group (P = 0.01) and the total opioid requirement was also reduced in promethazine group (32.1 ± 2.6 VS .68.5 ± 4.6 mg). However, the patients in the promethazine group were more sedated, which caused the duration of walking q12 hours in this group to decrease.ConclusionsIn morbidly obese patients undergoing laparoscopic gastric plication, promethazine/dexametasone was more effective than Metoclopramide/dexametasone in preventing and reducing the incidence of nausea, epigastric fullness, and reflux. That combination was also more effective than Metoclopramide in reducing the severity of epigastric pain.

(119) A Comparative Study on the Sedative Effect of Oral Midazolam and oral Promethazine Medication in lumbar puncture

Lumbar puncture (LP) essentially is a painful and stressful procedure that indicated for diagnosis and therapeutic purposes. One way to reduce the anxiety is oral premedication. The aim of this study is to compare clinical effects of oral Midazolam and oral Promethazine. This prospective randomized controlled clinical trial study was performed on 80 children 2-7 years old were candidate for LP. They were divided into two randomized equal groups. First group received oral Midazolam syrp 0.5 mg/kg and the other group received oral Promethazine syrp 1 mg/kg. Level of sedation, hemodynamic changes and any other complications monitored every 5 minutes from 30 minutes before the start of the procedure. Midazolam group and Promethazine group were similar in age, gender and weight. Oral Midazolam significantly had shorter onset of sedation (P<0.001) and also shorter duration to maximal sedation (P<0.022). The two groups were similar with respect to sedative effect at all time. The only complication that was significantly more in Midazolam group, nausea and vomiting (P<0.012). Midazolam syrp and Promethazine syrp have same sedative effect in children. Both of these medications are easy to use in preschool children and none of them appeared to be superior to another.

Intravenous promethazine versus lorazepam for the treatment of peripheral vertigo in the emergency department: A double blind, randomized clinical trial of efficacy and safety

Vertigo imposes considerable health restrictions with significant impact on the patient's quality of life. The most effective antivertigo agent is undetermined thus far. This study was performed to assess whether promethazine has superior vertigo reduction compared with lorazepam in ED patients. In this randomized, double-blind, parallel group trial 184 patients were assigned (1:1 ratio) to receive either promethazine, 25 mg intravenously, or lorazepam, 2 mg intravenously. Primary endpoint was mean change in vertigo intensity at 2 hours measured using visual analog scale (VAS). Secondary endpoints were mean change in nausea score, need for second dose of study medications, and adverse events (AEs). Promethazine was associated with significantly more reduction (46.5 mm) in vertigo than lorazepam (25.7 mm, p< 0.001). Mean change in nausea score 2 hours after drug injection on the VAS was 28.7 mm for promethazine and 22.8 for lorazepam (p=0.002). The most frequently reported AEs were lethargy (14.1% in lorazepam group, 4.3% in promethazine group, p=0.013) and drowsiness (10.8% for promethazine, 2.1% for lorazepam, p=0.017). Our study demonstrated the evidence that promethazine is superior to lorazepam in management of peripheral vertigo and vertigo-related nausea in ED adults.

Effects of promethazine or dexamethasone pretreatment on mivacurium‐induced histamine release in children

To determine the effects of pretreatment with either promethazine or dexamethasone on mivacurium-induced histamine release in children. Eighty ASA I-II children (4-10years of age) scheduled for tonsillectomy and/or adenoidectomy were randomly divided into 4 groups (n=20 per group) designated as either the rocuronium, mivacurium, dexamethasone (DXM), or promethazine group. Children in the DXM and promethazine groups were treated separately with intramuscular DXM 0.2mg·kg(-1) or promethazine 0.5mg·kg(-1) injections 60min before operation. Radial artery blood samples were collected to quantify plasma histamine concentrations 1min before and 1, 3, and 5min after administration of the relaxant. Mean arterial pressure (MAP), heart rate (HR), and skin flushing were recorded at the same time. No significant decreases in plasma histamine concentrations were observed between groups; however, more stable MAP and HR and less skin flushing were observed in DXM group participants compared with individuals in the mivacurium group (P<0.05). By contrast, children in the promethazine group had significantly decreased plasma histamine concentrations and stable MAP and HR (without a significant increase in HR) compared with patients in mivacurium group. In addition, skin flushing was significantly decreased compared with that observed in the rocuronium group (P<0.05). Pretreatment with promethazine significantly decreased mivacurium-induced histamine release in children and provided stable hemodynamics during administration of anesthesia.

To Compare the Effect of Dextromethorphan, Promethazine and Placebo on Nocturnal Cough in Children Aged 1–12 y with Upper Respiratory Infections: A Randomized Controlled Trial

To evaluate whether promethazine and dextromethorphan reduce nocturnal cough and improve sleep quality in children aged 1-12 y with upper respiratory tract infection (URI). This randomised double-blinded placebo-controlled trial was conducted in Pediatric outpatient department of Lok Nayak Hospital, Delhi. After randomization into promethazine, dextromethorphan and placebo groups, parental assessment of 120 children with URI for nocturnal cough severity (child), post-tussive vomiting (child) and sleep quality (child and parent) on the night before enrolment and after 3 d of assigned medication was measured using an internally validated indigenously prepared ordinal scale. Entire cohort improved in all the study parameters after 3 d. However, no superior benefit was noted when individual parameters were compared in the promethazine and dextromethorphan groups with the placebo group. Adverse effects were more frequent in the dextromethorphan and promethazine groups although the difference was not statistically significant. Nocturnal cough in URI is self-resolving and dextromethorphan and promethazine prescribed for the same are not superior to placebo.

A comparative study of the sedative effect of oral midazolam and oral promethazine medication in lumbar puncture.

Lumbar puncture (LP) essentially is a painful and stressful procedure, however indicated for diagnosis and therapeutic purposes. One way to reduce the anxiety is to administer an oral premedication. The aim of this study is to compare clinical effects of oral midazolam and oral promethazine in LP. This prospective randomized controlled clinical trial study was performed on 80 children aged 2-7 years that were candidate for LP. They were divided into two randomized equal groups. First group received oral midazolam syrup 0.5 mg/kg and the other group received oral promethazine syrup 1mg/kg. Level of sedation, hemodynamic changes and any other complications were monitored every 5 minutes from 30 minutes before the start of the procedure. Midazolam group and promethazine group were similar in age, gender and weight. Midazolam had significantly shorter onset of sedation and also shorter duration to maximal sedation. The two groups were similar with respect to sedative effect at all time. The only complication that was significantly more in midazolam group was nausea and vomiting. Midazolam syrup and promethazine syrup have same sedative effect in children. Both of these medications are easy to use in preschool children and none of them appeared to be superior to another.

In vivoadministration of acepromazine or promethazine to horse decreases the reactive oxygen species production response of subsequently isolated neutrophils to stimulation with phorbol myristate acetate

The previous experiments have shown that some phenothiazines have antioxidant and anti-inflammatory properties in vitro. In this study the inhibition of the production of reactive oxygen species (ROS) by neutrophils was studied in two groups of horses, which received a dose of 0.1 mg/kg of either acepromazine or promethazine intravenously. Blood samples were collected before (T0) and 0.5, 1, 3 and 5 h after drug administration. The chemiluminescence (CML) response of neutrophils was measured ex vivo in the presence of luminol for a period of 10 min and the maximum CML value (peak value) recorded. There was a significant inhibition of the ROS production in the acepromazine treated group (49% inhibition) at 5 h after administration and in the promethazine group (24% inhibition) at 3 h after administration (P < 0.05 vs. T0). These findings are of therapeutic relevance in the use of phenothiazines in equine patients with inflammatory diseases where neutrophil activation and ROS production are implicated.

Antiemetic prophylaxis with promethazine or ondansetron in major gynaecological surgery

Background: Postoperative nausea and vomiting remain a significant cause of morbidity among patients undergoing general anaesthesia. The optimal strategy for prevention, however, remains controversial. This study evaluated the efficacy of ondansetron 8 mg compared with promethazine 25 mg or placebo for the prevention of nausea and vomiting in patients undergoing elective major gynaecological surgery. Methods: Seventy-five patients received intravenous injection of the study medication (ondansetron-25, promethazine-25 or placebo-25) immediately before the induction of anaesthesia. Nausea and vomiting were assessed over a 24-hour postoperative period. Results: Nausea occurred in 20%, 40% and 72% of the promethazine, ondansetron and placebo groups respectively (p = 0.001). The overall incidence of vomiting was 12%, 16%, and 60% (p = 0.000) for promethazine, ondansetron and the placebo respectively. Postoperative drowsiness was prominent in the promethazine group. There was no significant difference in effectiveness between promethazine and ondansetron. Conclusions: Promethazine 25 mg was significantly more effective than ondansetron 8 mg in the prevention of postoperative nausea and vomiting. Promethazine is inexpensive and the cost of drugs is of importance in developing African countries. Drowsiness was a significant side-effect with promethazine, and this will be a disadvantage in ambulatory surgery.

The effectiveness of buprenorphine in combination with scopolamine and promethazine on conditioned place preference in SD rats

Objective To study the potentiality of psychological dependence of the so-called 1+1 compound (the elements are buprenorphine, scopolamine and promethazine). Methods One hundred and sixty-one male Sprague-Dawley rats were randomly assigned to 9 groups: buprenorphine, scopolamine, promethazine, buprenorphine plus scopolamine, buprenorphine plus promethazine, buprenorphine plus scopolamine and promethazine, scopolamine plus promethazine, morphine and saline groups respectively. All the 9 groups were trained by using the conditioned place preference(CPP) paradigm for 10 days. Results The rats in the five groups treated with buprenorphine alone or in combination with scopolamine/promethazine and morphine developed CPP. The time change spent by the rats in the buprenorphine plus scopolamine and promethazine group are (378.6±120.8)s , apparently longer than that by the rats in the buprenorphine group (302.2±133.9)s,but compared with that by rats in the morpine group(419.8±146.4)s, there is no significant difference(F=14.3,P=0.63). Conclusion The combination use of buprenorphine plus scopolamine and promethazine may act synergistically, and scopolamine and promethazine may enhance psychological dependence of buprenorphine. Key words: Buprenorphine; Scopolamine; Promethazine; Conditioned place preference; Craving

Ondansetron versus Promethazine to Treat Acute Undifferentiated Nausea in the Emergency Department: A Randomized, Double‐blind, Noninferiority Trial

The authors sought to compare ondansetron and promethazine among emergency department (ED) patients with undifferentiated nausea. The hypothesis was that ondansetron was not inferior to promethazine and that rates of adverse effects were similar. This was a randomized double-blind noninferiority clinical trial conducted in an urban academic ED. A convenience sample of nonpregnant adults with at least 40 mm of self-reported nausea measured on a 100-mm visual analog scale (VAS) were enrolled. Patients who had already received more than 1 L of intravenous fluid or an antiemetic agent were excluded. Subjects were block-randomized in groups of 10 to either 4 mg of ondansetron or 25 mg of promethazine delivered intravenously. The primary outcome was change in nausea over 30 minutes. The authors used a 15-mm margin of noninferiority. Secondary endpoints included changes in anxiety, sedation, and other adverse effects. Analyses included t-tests, tests for proportions, and 95% confidence intervals (CIs). A total of 120 subjects completed the study, 60 in each arm. Baseline nausea, anxiety, and sedation scores were similar. Ondansetron and promethazine reduced nausea similarly (ondansetron -34 mm, promethazine -36 mm; difference -2 mm; 95% CI = -13 to 8 mm). The reduction in anxiety was similar (ondansetron -13 mm, promethazine -14 mm; difference -1 mm; 95% CI = -10 to 10 mm). Promethazine was associated with significantly more sedation than ondansetron (ondansetron 5 mm, promethazine 19 mm; difference 14 mm; 95% CI = 5 to 24 mm). There were no cases of akathisia in the ondansetron group and 2 cases in the promethazine group. Promethazine and ondansetron have similar efficacy in reducing nausea among ED patients. Change in anxiety was similar, but promethazine was associated with greater sedation.

Study of the prophylactic effect of droperidol, alizapride, propofol and promethazine on spinal morphine-induced pruritus

We have compared the use of alizapride, propofol, droperidol and promethazine for the prevention of spinal morphine-induced pruritus. Three hundred ASA I or II women undergoing Caesarean section under spinal anaesthesia, in which morphine 0.2 mg was added to a local anaesthetic, were assigned randomly to receive i.v., in the operating room, just after delivery of the baby, alizapride 100 mg, propofol 20 mg, droperidol 1.25 mg, promethazine 50 mg or saline 2 ml (control group). In the postoperative period, the women were assessed for pruritus (absent, mild, moderate or severe) or other untoward symptoms by blinded observers. We used 95% confidence limits (95% CI) for the cumulative incidence of moderate and severe pruritus to compare the groups, and the NNT and 95% CI to compare droperidol, propofol and alizapride as for their effectiveness in preventing pruritus. For other untoward effects, the chi(2)-test was used, results being considered significant when P<0.05. The droperidol, propofol and alizapride groups had significantly lower incidences of pruritus compared with the control and promethazine groups, while the incidence of pruritus was similar among the patients assigned to the promethazine and control groups. As for the prevention of moderate and severe pruritus, droperidol had the lowest NNT (3.52; 95% CI: 3.37-3.67), followed by propofol (4.61; 95% CI: 4.45-4.77) and alizapride (5.43; 95% CI: 5.27-5.59). As for untoward effects, droperidol and promethazine increased the incidence of somnolence, which seemed more severe with promethazine. Otherwise, there were no differences between the groups. Droperidol, propofol and alizapride, in a decreasing order of effectiveness in the doses used in this study, reduced the incidence of pruritus induced by the use of morphine 0.2 mg intrathecally. On the other hand, promethazine 50 mg was shown to be ineffective.

Promethazine counteracts the positive effects of midodrine on orthostatic intolerance

Astronauts experience not only orthostatic hypotension but also motion sickness during reentry. Midodrine (Mido), α1-adrenergic agonist, is a countermeasure for orthostatic hypotension. Promethazine (PMZ) is used as a countermeasure for nausea and vomiting. Many astronauts experience both symptoms and may need to use both Mido and PMZ at the same time. The purpose of this study was to determine if the depressive effects of PMZ counteract the ability of Mido to increase venous return and arterial pressure. Subjects (n=8; M=5, F=3) were studies 4 times, in random order: no drug; Mido alone (10 mg, PO); PMZ alone (25 mg, IV); or Mido+PMZ. Arterial pressure and heart rate were measured before and during a 20-minute head-up 80° tilt test. Standing subjects in the PMZ group are lower than control (P<0.001) and Mido+PMZ lower than Mido (P<0.01). ΔSBP in PMZ is significantly lower than control and ΔDBP in Mido+PMZ markedly lower than Mido. In conclusion, PMZ significantly decreased the orthostatic tolerance provide by Mido alone. These two should not be used in combination. NASA grant: NAS9-97005

Endogenous opioids, µ‐opiate receptors and chloroquine‐induced pruritus: A double‐blind comparison of naltrexone and promethazine in patients with malaria fever who have an established history of generalized chloroquine‐induced itching

Chloroquine induces a severe generalized pruritus, in predisposed Black African patients, during treatment of malaria fever, and also in some Caucasian patients treated for rheumatological diseases. We have previously shown that chloroquine may release endogenous opioids and/or interact with micro-opiate receptors in rats, and that both histamine and malaria parasite blood density, contribute to the itching severity in malaria fever in humans. The aim of our present study was to assess and compare the antipruritic efficacy of the micro-opiate receptor antagonist, naltrexone, and the antihistamine, promethazine, in chloroquine treated patients with malaria fever. A double-blind, randomized, parallel group comparison of the chloroquine-induced pruritus intensity and time profile in patients with parasitologically proven malaria fever, who were pretreated with a single dose of either naltrexone 50 mg or promethazine 25 mg orally (six patients each). All patients had an established history of severe pruritus following chloroquine treatment of malaria fever. A self-assessed itching severity score was undertaken at 0, 6, 12, 24, 48 and 72 h after initial chloroquine dosing, and the areas under the pruritus-intensity time curve AUCP0-72 h was determined in each patient and correlated to the malaria parasite density in blood. Both naltrexone and promethazine subjectively reduced itching severity compared with prior historical experience. One patient on naltrexone and two on promethazine never experienced any itching. There was no statistically significant treatment effect, but a significant time effect (P = 0.001, F = 4.77 d.f. 5) by two-way repeated measures ANOVA. The AUCP for naltrexone was 82 +/- 25 units/h, and 57 +/- 34 units/h for promethazine [95% confidence interval for the difference being -73 to 123]. However, the malaria parasite density in the naltrexone group (740 +/- 178 microl(-1)) tended to be higher than in the promethazine group 314 +/- 69 microl(-1) (P = 0.056, 95% confidence interval for the difference being -15 to 866 microl(-1)). Correction of the AUCP for malaria parasite density (parasite pruritogenic index, AUCP. units/h/parasites/microl blood) tended to be lower with naltrexone 9.1 +/- 2.6 than with promethazine 12.2 +/- 7.0 There was a highly significant and positive correlation between the malaria parasite density and the AUCP0-72 h, on naltrexone (r2 = 0.78, P = 0.040) and promethazine (r2 = 0.93, P = 0.008). However, comparison of regressions revealed that the slope of the regression was significantly steeper with promethazine 0.48 than naltrexone 0.12 (P = 0.006, t = 4.2), with the intercepts showing a trend to a difference (P = 0.086). Naltrexone exerted an antipruritic action, at least to a similar extent to promethazine in patients with chloroquine-induced itching in malaria fever. However, the relationship between parasite density and resultant pruritus was significantly different between naltrexone and promethazine. Thus, micro-opiate receptors/and or endogenous opioids may contribute to chloroquine itching in malaria fever, in humans, in accord with animal experimental findings. Malaria parasite density in blood is a strong determinant of itching severity in patients predisposed to chloroquine-induced pruritus.

Autogenic‐Feedback Training Exercise Is Superior to Promethazine for Control of Motion Sickness Symptoms

Motion sickness symptoms affect approximately 50% of the crew during space travel and are commonly treated with intramuscular injections of promethazine. The purpose of this paper is to compare the effectiveness of three treatments for motion sickness: intramuscular injections (i.m.) of promethazine, a physiological training method (autogenic-feedback training exercise [AFTE]), and a no-treatment control. An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair. For the present paper, motion sickness tolerance, symptom reports, and physiological responses of these subjects were compared to matched subjects selected from an existing database who received either AFTE or no treatment. Three groups of 11 men, between the ages of 33 and 40 years, were matched on the number of rotations tolerated during their initial rotating-chair motion sickness test. The motion sickness test procedures and the 7-day interval between tests were the same for all subjects. The drug group was tested under four treatment conditions: baseline (no injections), a 25 mg dose of promethazine, a 50 mg dose of promethazine, and a placebo of sterile saline. AFTE subjects were given four 30-minute AFTE sessions before their second, third, and fourth motion sickness tests (6 hours total). The no-treatment control subjects were only given the four rotating-chair tests. Motion sickness tolerance was significantly increased after 4 hours of AFTE when compared to either 25 mg (p < 0.00003) or 50 mg (p < 0.00001) of promethazine. The control and promethazine groups did not differ. AFTE subjects reported fewer or no symptoms at higher rotational velocities than subjects in the control or promethazine groups. The primary physiological effect of promethazine was an inhibition of skin conductance level. The AFTE group showed significantly less heart rate and skin conductance variability during motion sickness tests administered after training.

Peripheral nerve injection injury with antiemetic agents.

Antiemetics are widely used drugs, frequently administered to alleviate postoperative and postchemotherapeutic nausea and vomiting. While antiemetics do not induce peripheral neurotoxicity when administered systemically, it is not known whether peripheral nerve injury can occur as a result of inadvertent intraneural injection during intramuscular administration. The purpose of this study was to characterize the neurotoxic effect of three commonly used antiemetic agents (promethazine, dimenhydrinate, and prochlorperazine) as compared to saline in the rat sciatic nerve model. Intrafascicular and extrafascicular injection as well as direct application of the antiemetic drugs were performed. Nerves were harvested at 2 weeks postoperatively for histology and morphometry, with an additional sacrifice point at 8 weeks for the intrafascicular injection group. Injection injuries caused by antiemetic drugs differed depending on the agent injected and the location of injection. Extrafascicular injection and direct application caused no damage. Intrafascicular injection caused diffuse axonal injury in the promethazine and dimenhydrinate groups, while prochlorperazine caused only focal injury. Regeneration was prominent at 8 weeks in all intrafascicular injection groups in this rat model. Prochlorperazine thus appears to be less neurotoxic when injected intraneurally and should preferentially be used for intramuscular injections.