Administration Of Prochlorperazine Research Articles

The Effect of Spontaneous Neuromuscular Activity on the Development of Atrophy of the Functionally Unloaded <i>m. soleus</i>

It is well known that the inactivity of mammalian skeletal muscles leads to the cessation of their electrical activity and is accompanied by atrophic changes in muscle fibers. However, it has been repeatedly noted that starting from the 3rd day of functional unloading, spontaneous rhythmic neuromuscular activity appears, which is the result of a decrease in the expression of the potassium chloride co-transporter KCC-2 in neurons of the lumbar spinal cord. A decrease in the expression of KCC-2 and the onset of autonomous electrical activity of the unloaded muscle can be prevented by the administration of the neuroleptic prochlorperazine. Thus, the aim of this study was to evaluate the structural and signaling effects of the reduced spontaneous activity of the unloaded m.soleus. It was found that daily administration of prochlorperazine to rats under conditions of 7-day simulated gravitational unloading prevented a decrease in the content of the main markers of ribosome biogenesis (c-Myc, 18S rRNA and 28S rRNA), and also partially prevented a decrease in the cross-sectional area of fast and slow muscle fibers in the m.soleus. Morphofunctional changes caused by a decrease of spontaneous activity of the unloaded muscle were accompanied by complete or partial prevention of activation of key proteolytic markers expression (MuRF-1, MAFbx/atrogin-1, ubiquitin). Thus, we assume that spontaneous neuromuscular activity may be a factor that augments muscle atrophy during the first week of functional unloading.

Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study.

A gradual increase in rat soleus muscle electromyographic (EMG) activity is known to occur after 3–4 days of hindlimb suspension/unloading (HS). The physiological significance and mechanisms of such activity of motoneurons under unloading conditions are currently unclear. Since hyperactivity of motoneurons and muscle spasticity after spinal cord injury are associated with KCC2 downregulation, we hypothesized that a decrease in potassium (K+)/chloride (Cl−) co-transporter 2 (KCC2) in motoneurons would be responsible for an increase in soleus muscle EMG activity during HS. We aimed to investigate the effect of prochlorperazine (KCC2 activator) on the electrical activity of rat soleus muscle under HS. Wistar rats were divided into the following groups: (1) vivarium control (C), (2) 7-day HS group (7HS) and (3) 7-day HS group plus intraperitoneal injections of prochlorperazine (10 mg/kg, daily) (7HS + P). Expression of proteins in the motoneurons of the lumbar spinal cord was determined by Western blotting. An electromyogram of the rat soleus muscle was recorded using intramuscular electrodes. KCC2 content after 7-day HS significantly decreased by 34% relative to the control group. HS-induced decrease in KCC2 protein content was prevented by prochlorperazine administration. HS also induced a significant 80% decrease in KCC2 Ser940 phosphorylation; however prochlorperazine did not affect KCC2 phosphorylation. The treatment of the rats with prochlorperazine prevented a HS-induced increase in Na(+)/K(+)/(Cl−) co-transporter 1 (KCC2 antagonist) protein content. In parallel with the restoration of KCC2 content, prochlorperazine administration during HS partially prevented an increase in the soleus muscle tonic EMG activity. Thus, prochlorperazine administration during 7-day HS prevents a decrease in KCC2 protein expression in motoneurons and significantly reduces the level of HS-induced soleus muscle electrical activity.

RETCHING IN PNEUMONIA: AN UNCOMMON PRESENTATION OF A COMMON PROBLEM

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Retching is defined as periodic, forceful, spasmodic contraction of the muscles of the diaphragm, abdomen and chest wall without the expulsion of the contents of the stomach. It often occurs as a precursor to vomiting. Here we present the case of a patient presenting with retching as his only symptom, the cause was deemed to be community acquired pneumonia. CASE PRESENTATION: A 60-year-old man with a 40-pack-year smoking history presented with 4 days of severe retching. He described this as dry heaving, the sensation of vomiting with nothing coming up. He denied any cough, fever, chest pain or vomiting. Labs were significant for a WBC of 19,700/mL, and a serum sodium of 126mEq/L. Remaining serum electrolytes were normal. Urine sodium was 24mEq/L and urine osmolality was 307mOsm/kg. CT chest showed a 7.5 x 3.6cm focal opacification in the right upper lobe (fig 1). The patient was started on Piperacillin/Tazobactam with a plan to biopsy the lesion if there was no improvement. He was given Prochlorperazine which led to immediate improvement, with complete resolution of retching by day 4. A Repeat CT done after completion of a 10 day course of antibiotics (fig 2) showed some improvement. Follow up CT at 6 months (fig 3) showed complete resolution. DISCUSSION: Retching is a prelude to vomiting and involves contraction of the diaphragm and intercostal muscles with a closed glottis to reduce intrathoracic pressure while abdominal wall muscles contract to increase intra-abdominal pressure. The lower esophageal sphincter remains closed preventing ejection of gastric contents. The physiologic pathway of the emetic reflex is not completely understood, but it involves afferent input to the brainstem centers like solitary tract nucleus and the chemoreceptor trigger zone (CTZ) via the vagus, glossopharyngeal, trigeminal and phrenic nerves. This leads to stimulation of the vomiting center. Impulse then travels to the nucleus ambiguus, dorsal motor nucleus of the vagal nerve, and the ventral respiratory group leading to the aforementioned muscular action associated with retching. In the index patient we hypothesize that the inflammatory response associated with pneumonia led to irritation of the vagus and phrenic nerves causing persistent retching. This is supported by the improvement of symptoms after administration of prochlorperazine, which works via suppression of the CTZ. Further, there was complete resolution of retching after treatment with antibiotics. The patient’s smoking history, hyponatremia due to SIADH, and the presence of a large mass raised concerns for malignancy, as such biopsy was planned if lesion did not improve after antibiotic treatment. CONCLUSIONS: Evaluation of the thorax with imaging is prudent in patients presenting with retching as inflammatory, infectious or malignant lesions can cause this symptom via stimulation of the afferent limbs of the vagus or phrenic nerves. Reference #1: Quigley EM, Hasler WL, Parkman HP. AGA technical review on nausea and vomiting. Gastroenterology. 2001;120(1):263-86. Reference #2: Nair J, Streeter KA, Turner SMF, et al. Anatomy and physiology of phrenic afferent neurons. J Neurophysiol. 2017;118(6):2975-2990 Reference #3: Babic T, Browning KN. The role of vagal neurocircuits in the regulation of nausea and vomiting. Eur J Pharmacol. 2014;722:38-47 DISCLOSURES: No relevant relationships by Muhammad Faiz, source=Web Response No relevant relationships by Jovan Gayle, source=Web Response No relevant relationships by Somshukla Ghosh, source=Web Response No relevant relationships by Moises Matos, source=Web Response No relevant relationships by Jose Urdaneta Jaimes, source=Web Response

Acute Dystonic Reactions in Children Treated for Headache With Prochlorperazine or Metoclopramide

BackgroundThe incidences of dystonic reactions to metoclopramide and prochlorperazine have not been well characterized in children. MethodsMedical record data were reviewed for patients at a tertiary care pediatric hospital who received metoclopramide or prochlorperazine for treatment of headache. ResultsA total of 4588 clinical encounters were identified, 2542 with prochlorperazine and 2046 with metoclopramide. One patient had a dystonic reaction with metoclopramide (0.049%). Eleven patients had a dystonic reaction with prochlorperazine (0.43%). The relative risk of a dystonic reaction with prochlorperazine over metoclopramide is 8.85 (95% confidence interval 1.15 to 68.5). There were differences between groups of patients who received metoclopramide versus prochlorperazine in terms of age, number of doses, and coadministration of diphenhydramine. In a logistic regression, administration of prochlorperazine over metoclopramide (P = 0.019) and greater number of doses (P < 0.001) remained associated with acute dystonic reactions. ConclusionsDystonic reactions are rare events among pediatric patients treated for acute headache, but are more common with prochlorperazine than metoclopramide.

Impact of genetic and non-genetic factors on clinical responses to prochlorperazine in oxycodone-treated cancer patients

BackgroundThe contributions of DRD2 and OPRM1 genetic variants to clinical responses to prochlorperazine remain to be clarified in opioid-treated patients. We evaluated the clinical responses to prochlorperazine based on non-genetic and genetic factors in oxycodone-treated patients. MethodsSeventy Japanese cancer patients starting oral prochlorperazine together with oxycodone were enrolled. Predose plasma prochlorperazine concentrations and serum prolactin concentrations were determined. The incidences of oxycodone-induced nausea and vomiting were monitored for 2weeks. ResultsPlasma prochlorperazine concentration and oxycodone daily dose were not associated with the incidences of nausea and vomiting. The incidence of nausea was significantly higher in the DRD2 TaqIA A1A2+A1A1 group than in the A2A2 group. The incidence of vomiting was significantly higher in females than in males. Before and after the prochlorperazine administration, the serum prolactin concentration was significantly higher in female patients than in male patients. The serum prolactin concentration was weakly correlated with prochlorperazine concentration and was significantly higher in the OPRM1 118AA group than in the AG+GG group. ConclusionsDRD2 TaqIA and female gender altered the prophylactic antiemetic efficacy of prochlorperazine. OPRM1 A118G together with plasma exposure of prochlorperazine and gender affected prolactin secretion in oxycodone-treated patients.

Rescuing Ferster and DeMyer’s behavioral pharmacology research in autism from oblivion

In 1961, Charles B. Ferster and Marian K. DeMyer published a one-page report in the Journal of the Experimental Analysis of Behavior titled, “Increased Performances of an Autistic Child with Prochlorperazine Administration.” It may be the first and only report of basic behavioral pharmacology research using both operant apparatus and measures and a within-individual replication design to analyze the behavior of a child with autism. However, it is now lost in history. In this article, we rescue the report by providing historical context (e.g., a literature review, the setting), describing and elaborating on the report (e.g., the participant, method), and relating the report to the research of its day and afterward. We also discuss the grounds on which the report warrants being rescued and, in a postscript, summarize Ferster’s later work in autism.

Clinical Outcomes of Children Treated with Intravenous Prochlorperazine for Migraine in a Pediatric Emergency Department

Prochlorperazine is the only treatment that has been studied so far in a randomized controlled trial and found to reduce pain at 1 h in children with migraine who presented to an emergency department (ED). To evaluate the rate of treatment failure associated with prochlorperazine used in children with severe migraine in a pediatric ED. This study was a retrospective chart review of patients < 18 years of age who visited the ED of a tertiary care pediatric hospital between November 2005 and June 2007. All patients diagnosed with migraine by the emergency physicians were included in the study. Charts were evaluated by a data abstractor blinded to the study hypothesis using a standardized datasheet. Inter-rater agreement was measured. Prochlorperazine treatment failure was defined as either administration of further rescue therapy, a hospitalization, or a return visit to the ED within 48 h for symptom recurrence or side effects from the medication. Prochlorperazine was administered in 92 episodes of migraine, including 43 confirmed by a pediatric neurologist; all received diphenhydramine to prevent akathisia. A total of 13 (14%) of these patients had a treatment failure: 8 patients received one or more further rescue therapies after the administration of prochlorperazine; 5 patients were hospitalized, including 3 who had received further rescue therapy; and 3 patients returned to the ED within 48 h due to symptom recurrence. There was a treatment failure rate of 14% with the use of prochlorperazine in association with diphenhydramine for severe migraine in children seen in a pediatric ED.

The Pharmacokinetics and Bioavailability of Prochlorperazine Delivered as a Thermally Generated Aerosol in a Single Breath to Volunteers

A thermally generated aerosol (TGA) system can effect reliable delivery of excipient-free drug to alveoli, resulting in rapid systemic drug absorption. We developed a pharmacokinetic model of prochlorperazine, administered by inhalation and as a rapid intravenous infusion, and we determined absolute TGA bioavailability in eight healthy volunteers in this institutional review board-approved, two-period crossover study. After the drug was administered as either a 5-s intravenous infusion or a TGA single-breath inhalation, blood was collected at various times for up to 24 h. Plasma prochlorperazine concentrations were measured using liquid chromatography-tandem mass spectrometry. Inhalation and rapid intravenous administration produced similar plasma prochlorperazine concentration profiles. Intravenous and inhalation pharmacokinetics were well characterized by a simultaneous two-compartment model with multiple absorption delays. Prochlorperazine pharmacokinetic parameters were similar to those reported for single intravenous doses. The geometric mean bioavailability after TGA delivery was 1.10. The administration of prochlorperazine by inhalation resulted in pharmacokinetics similar to that seen after intravenous administration, in terms of speed, extent, and consistency of absorption.

111: Safety and Effectiveness of Intravenous Prochlorperazine for Intractable Vomiting in Children With Gastroenteritis

Intravenous (IV) administration of prochlorperazine (PCZ) in treating child and adolescent vomiting has not been established. In this study, we will report our results on the effectiveness and tolerability of IV PCZ in consecutive children seen in the emergency department (ED) for severe, intractable vomiting.

Bioavailability and Metabolism of Prochlorperazine Administered via the Buccal and Oral Delivery Route

Prochlorperazine has been accepted as an effective antiemetic for more than 50 years; however, its therapeutic success has been limited by its low and variable absorption and high first-pass metabolism. A buccal dosage form of prochlorperazine has been developed. This article discusses 2 clinical studies conducted to characterize the single-dose and multiple-dose pharmacokinetics of prochlorperazine and its metabolites after buccal administration. The results of these studies demonstrate that buccal administration of prochlorperazine produces plasma concentrations more than twice as high as an oral tablet, with less than half the variability. In addition to the metabolites, N-desmethyl prochlorperazine and prochlorperazine sulfoxide, 2 new metabolites, prochlorperazine 7-hydroxide and prochlorperazine sulfoxide 4'-N-oxide, were identified and quantitated. Exposure to metabolites after the buccal prochlorperazine formulation was approximately half that observed after the oral tablet. Buccal administration of prochlorperazine, twice daily, should enhance the therapeutic role of prochlorperazine in preventing and treating nausea and vomiting.

Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: A prospective, randomized, controlled trial

Study Objective: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. Methods: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. Results: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Δ=–6.7%; 95% confidence interval [CI] –24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI –9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI –4.6% to 29.8%). Conclusion: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made. [Collins RW, Jones JB, Walthall JDH, Chisholm CD, Giles BK, Brizendine EJ, Cordell WH. Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, controlled trial. Ann Emerg Med. November 2001;38:491-496.]

Recent clinical experience with dronabinol

Dronabinol, Δ-9-tetrahydrocannabinol in sesame oil, has been used for several years as an antiemetic for patients receiving cancer chemotherapy. In combination studies with prochlorperazine, enhancement of efficacy, as measured by duration of episodes of nausea and vomiting and by severity of nausea, has been found. The incidence of psychotropic effects from dronabinol appears to be decreased by concomitant administration of prochlorperazine. In open pilot studies, dronabinol caused weight gain in seven of ten patients with symptomatic HIV infection. In both HIV and cancer patients, dronabinol improved appetite at a dose which was well tolerated for chronic administration.

Acute Oculogyric Crisis After Administration of Prochlorperazine

We report a case of acute oculogyric crisis due to prochlorperazine administration in a young black woman with a concomitant viral infection. Neuroleptic medications are the most common cause of drug-induced acute dystonic reactions such as oculogyric crisis. Prochlorperazine is an antiemetic agent with a phenothiazine-type chemical structure and is known to cause dystonic reactions. Drug-induced acute dystonic reactions are most common in young adults and in men. Viral infections may also predispose patients to these adverse reactions. Caution is warranted when this drug is used in patients who have other risk factors for an acute dystonic reaction.

A comparison of the availability of prochlorperazine following i.m. buccal and oral administration

The administration of prochlorperazine by the i.m. p.o. and buccal routes has been evaluated in a series of single and multi-dose pharmacokinetic studies in non-patient volunteers. Studies have indicated that the drug has an elimination half-life of 8.1 h following single i.m. injection and 9.0 and 8.6 h following multi-dose administration by the buccal and oral routes, respectively. Plasma levels following single-dose (10 mg) oral administration are too low to obtain meaningful pharmacokinetic parameters but steady-state data indicates 3 mg b.d. buccal delivery (Buccastem - trademark of Reckitt & Colman Products Ltd.) to be equivalent to 5 mg t.i.d. oral (Stemetil - trademark of May & Baker Ltd.). This observation has been confirmed in clinical evaluation in patients suffering vertigo disorders.

Akathisia From Prochlorperazine

To the Editor.—Report of a Case.— A 26-year-old man with multiple hospitalizations for chemotherapy of stage IV lymphoma experienced a severe subjective sense of restlessness and anxiety. feel like jumping out of my skin.... I can't stand this hospital anymore. These complaints were considered to be secondary to his anxiety about his illness and prognosis. However, the restlessness was a distinct change from his behavior during previous hospitalizations and coincided with administration of prochlorperazine (Compazine), 10 mg intravenously every six hours, for nausea. A tentative diagnosis of drug-induced akathisia was made, prochlorperazine treatment was discontinued, and the restlessness completely abated within three days. Comment.— Extrapyramidal reactions can occur from dopamine blocking agents such as prochlorperazine or metoclopramide, which are commonly used as antiemetics.1However, it has been my experience as well as others'2that akathisia, an intense and highly distressing subjective sense of restlessness, is the side

Breathing during sleep: the responses to asphyxia and prochlorperazine in normal subjects and patients with obstructive sleep apnea.

The effects of sleep and prochlorperazine (12.5 mg intravenous bolus) on the ventilatory and arousal responses to asphyxia were studied in normal subjects and patients with obstructive sleep apnea (OSA). The ventilatory response to asphyxia was reduced during non-rapid eye movement sleep in the six normal subjects studied (1.93 +/- 0.18 l min-1.% SaO2 awake vs. 1.01 +/- 0.10 l min-1.% SaO2 asleep; mean +/- SEM; p less than 0.01) (SaO2 = arterial oxygen saturation). In the two normal subjects studied during sleep following prochlorperazine administration, ventilatory responsiveness was increased (p less than 0.05) but arousal response to asphyxia was depressed (p less than 0.025). Although prochlorperazine increased waking ventilatory responsiveness to asphyxia in five of six patients with OSA (2.26 +/- 0.44 l min-1.% SaO2 vs. 4.77 +/- 1.39 l min-1.% SaO2; mean +/- SEM; p less than 0.01), the drug had no clinically significant effect on upper airway obstruction during sleep; in three patients, apnea frequency was slightly reduced but in four of six patients severity of hypoxemia during apnea was increased with drug administration. We conclude that prochlorperazine administration is unlikely to benefit patients with obstructive sleep apnea despite its ventilatory effects during wakefulness and sleep. This lack of effect may be explained by separate effects of the drug on ventilatory and arousal responses to asphyxia.

Development of Mucoadhesive Patches for Buccal Administration of Prochlorperazine: Evaluation of In Vitro Release and Mechanical Properties

The aim of this investigation was to develop and evaluate mucoadhesive buccal patches of prochlorperazine (PCPZ). Permeation of PCPZ was calculated in vitro using porcine buccal membrane. Buccal formulations were developed by solvent-casting technique using hydroxy propylmethyl cellulose (HPMC) as mucoadhesive polymer. The patches were evaluated for in vitro release, moisture absorption and mechanical properties. The optimized formulation, based on in vitro release and moisture absorption studies, was subjected for bioadhesion studies using porcine buccal membrane. In vitro flux of PCPZ was calculated to be 2.14 ± 0.01 µg. h–1.cm–2 and buccal absorption was also demonstrated in vivo in human volunteers. In vitro drug release and moisture absorbed was governed by HPMC content. Increasing concentration of HPMC delayed the drug release. All formulations followed Zero order release kinetics whereas the release pattern was non-Fickian. The mechanical properties, tensile strength (10.28 ± 2.27 kg mm–2 for formulation P3) and elongation at break reveal that the formulations were found to be strong but not brittle. The peak detachment force and work of adhesion for formulation P3 were 0.68 ± 0.15 N and 0.14 ± 0.08 mJ, respectively. The results indicate that suitable bioadhesive buccal patches of PCPZ with desired permeability and suitable mechanical properties could be prepared

Enhanced Mortality of Selected Central Nervous System Depressants in Hypoexcretory Mice

The mortality of nine central nervous system depressant drugs was compared in normal and hypoexcretory mice. Anuria was produced in mice by penile ligation; cholestasis was produced by bile duct ligation. The intraperitoneal administration of prochlorperazine, trifluoperazine, perphenazine, meprobamate, and chloral hydrate produced significantly elevated mortality rates in anuric mice whereas promazine, perphenazine, and meprobamate showed elevated mortality rates in cholestatic mice. The mortality of chlorpromazine and phenobarbital was not altered in hypoexcretory mice.

PITUITARY-ADRENAL FUNCTION DURING ACUTE PROCHLORPERAZINE ADMINISTRATION IN THE DOG.

Increased plasma 17-OH corticosteroid concentrations, as compared to controls, were observed after 4, 6, and 8 hr of prochlorperazine infusions into normal anesthetized dogs. ACTH-like activity was detectable in plasmas obtained at the 8th hr in the prochlorperazine-treated animals, by a bio-assay procedure involving corticosteroid secretion rates by the isolated adrenal of hypophysectomized dogs. Methopyrapone infusions resulted in increased plasma 17-OH corticosteroid concentrations at the 6th and 8th hr. However, the combination of methopyrapone and prochlorperazine resulted in greater loss of the adrenal stimulatory effect than seen with either agent alone. Prompt increases in plasma 17-OH corticosteroid concentrations upon addition of ACTH to these combined infusions reflected normal secretory capacity of these adrenals. Prochlorperazine alone perfused into the isolated adrenal preparation was neither stimulatory nor inhibitory. The evidence suggests a complex action of prochlorperazine. First, intravenous administration of prochlorperazine results in ACTH release, readily detectable after 8 hr. Second, partial inhibition of ACTH production, as evoked by methopyrapone in the intact animal, possibly may occur at the hypothalamic level.

PROBABLE HEPATIC ALLERGY TO CHLORPROMAZINE AND DELIBERATE DESENSITIZATION

Excerpt This report issues from studies concerning the pathogenesis of hepatic dysfunction due to chlorpromazine, the prophylactic and therapeutic influence thereon of synthetic adrenocortical horm...