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PubMed1996

Compatibility of cefmetazole sodium with commonly used drugs during Y-site delivery.

The compatibility of cefmetazole sodium and selected other drugs during Y-site delivery was evaluated. Cefmetazole 100 mg/mL (as the sodium salt) in sterile water for injection and each of 34 drugs or solutions commonly used with it were mixed together by Y-site injection. Secondary drugs were administered at selected concentrations and rates and delivered by the method (i.v. push, i.v. infusion, or syringe pump) commonly used for the drug at the institution where the study was done. Each injection set included a filter system with a 0.8-micron filter disk. Tests were done in triplicate. After each test, the Y injection site and the tubing after it were visually inspected for precipitate and color change. If no particles or color change was detected, the filter disk was observed under a microscope. Drugs were deemed compatible with cefmetazole if unaided observation detected no color change or particles and the number of particles detected by microscopic examination was below that specified in USP guidelines. A precipitate formed when cefmetazole sodium mixed with diphenhydramine hydrochloride, droperidol, erythromycin (50 mg/mL, as the lactobionate), haloperidol lactate, prochlorperazine edisylate, promethazine hydrochloride, or vancomycin (50 mg/mL, as the hydrochloride salt). No particles or color change was detected by unaided observation of mixtures containing dobutamine or erythromycin 10 mg/mL, but the number of particles detected by microscopic examination exceeded USP limits. All other drugs tested were compatible with cefmetazole. Cefmetazole 100 mg/mL (as the sodium salt) in sterile water for injection was shown to be compatible with 25 of 34 tested drug solutions during Y-site delivery.

Cefmetazole↗

PubMed2005

Prevention and treatment of postoperative nausea and vomiting.

PURPOSE: The physiology, risk factors, and prevention and treatment of postoperative nausea and vomiting (PONV) are discussed. SUMMARY: Factors to consider when determining a patient's risk for PONV include sex, history of PONV, history of motion sickness, smoking status, duration of anesthesia, use of opioids, and type of surgery. Receptors that, when activated, can cause nausea or vomiting or both include dopamine type 2, serotonin type 3, histamine type 1, and muscarinic cholinergic type 1 receptors. Patients at moderate to high risk for PONV benefit from the administration of a prophylactic antiemetic agent that blocks one or more of these receptors. Effective agents include transdermal scopolamine, prochlorperazine, promethazine, droperidol, ondansetron, dolasetron, granisetron, and dexamethasone. In high-risk patients, combining two or more antiemetics with different mechanisms of action has been shown to be more effective than using a single agent. In addition to administering a prophylactic antiemetic, it is important to reduce the patient's risk by considering regional anesthesia, considering inducing and maintaining general anesthesia with propofol, ensuring good intravenous hydration, avoiding hypotension, and providing effective analgesia. If PONV occurs in the immediate postoperative period, it is best treated with an antiemetic agent from a pharmacologic class different from that of the prophylactic agent. CONCLUSION: Prophylactic antiemetic therapy for PONV is effective, but combinations of agents may be necessary for high-risk patients. Nonpharmacologic strategies are also important.

Antiemetics↗

PubMed2025

Integrating explainable artificial intelligence with multiomics systems biology and electronic health record data mining for personalized drug repurposing in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by region- and patient-specific molecular heterogeneity, which hinders therapeutic design. In this study, we introduce PRISM-ML (PRecision-medicine using Interpretable Systems and Multiomics with Machine Learning), an open-source integrated analysis pipeline that combines interpretable machine learning with systems biology and electronic health records data mining to elucidate the molecular diversity of AD and predict promising drug repurposing opportunities. First, we integrated and harmonized transcriptomic (bulk RNA-seq) and genomic (genome-wide association study) data from 2105 brain samples, each with matched data from the same individual (1363 AD patients, 742 controls; 9 tissues), sourced from three independent studies. Random forest classifiers with SHapley Additive exPlanations identified patient-specific biomarkers; unsupervised clustering resolved 36 molecularly distinct subtissues (defined as clusters of samples within a brain tissue that share a specific expression pattern); and gene-gene coexpression networks prioritized 262 high-centrality bottleneck genes as putative regulators of dysregulated pathways. Next, knowledge graph-based drug repurposing predicted six Food and Drug Administration (FDA)-approved drugs that simultaneously target multiple bottleneck genes and multiple AD-relevant pathways. Notably, in a large US de-identified insurance-claims database (n = 364 733), exposure to promethazine, one of the candidate drugs, was associated with a 57%-62% lower incidence of AD versus an active antihistamine comparator (adjusted hazard ratio 0.38; inverse-probability weighted 0.43; both P < .001), providing real-world support for its repurposing potential. In summary, PRISM-ML, as an explainable multiomics analysis pipeline, is readily transferable to other complex diseases, advancing precision medicine.

Alzheimer Disease↗

PubMed1978

The action of commonly used antiemetics on the lower oesophageal sphincter.

The effects of five antiemetic drugs on the lower oesophageal sphincter (LOS) were studied in five groups, each comprising eight healthy volunteers. Cyclizine, prochlorperazine and metoclopramide have a desirable functional effect on LOS, while promethazine and droperidol were associated with evidence of increased gastro-oesophageal reflux.

Adult↗

PubMed1983

Possible role for calmodulin in calcium paradox-induced heart failure.

Several phenothiazines were found to provide significant protection against loss of tissue creatine phosphokinase caused by the calcium paradox. The concentration of phenothiazine required for protection lies within the range generally attributable to their calmodulin inhibition properties. Moreover, the order of effectiveness in protecting the calcium overloaded myocardium is consistent with their potency as calmodulin inhibitors (trifluoperazine greater than chloropromazine greater than promethazine). The most potent calmodulin inhibitor was shown to dramatically reduce the amount of creatine phosphokinase loss from calcium depleted hearts exposed to buffer containing calcium under anoxic conditions. On the other hand, the drug failed to alter the oxygen-dependent component of the calcium paradox. It also failed to prevent the proteolytic conversion of xanthine dehydrogenase to xanthine oxidase. The possibility that calmodulin activation promotes cellular damage by activating either directly or indirectly specific membrane cellular phospholipases is discussed. Also discussed is the hypothesis that oxygen-dependent damage may be linked to the generation of superoxide anion by the enzyme xanthine oxidase.

Animals↗

PubMed1998

Prolonged inhibition of presynaptic catecholamine synthesis does not alter leptin secretion in normal-weight men and women.

Leptin has been called a hormone of reproduction, and seems to link fat and fertility. It has been speculated that the neurotransmitter norepinephrine (NE) (noradrenaline), possibly via the sympathetic nervous system, may represent the afferent signal which modulates leptin release from adipocytes. The purpose of this study was to produce a state of decreased sympathetic output by using the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine (AMPT), in order to study the effect of this compound on the secretion of leptin from fat cells. Ten subjects (five women and five men) received a total of 5 x 1 g doses of AMPT or 5 x 50 mg promethazine (active placebo) over a 26 h period, separated by 4-6 weeks using a randomized, double-blind, placebo-controlled, cross-over design. Blood samples for hormone measurements were obtained over 24 h (18 time points) on day 2 of each experiment. Urinary measurement of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) on study day 2 served as a marker of the effectiveness of AMPT as an inhibitor of NE synthesis. The daily excretion of this metabolite decreased from 1.56 +/- 0.22 mg in the placebo experiment to 0.53 +/- 0.1 mg in the active experiment (P < 0.05). Plasma leptin concentrations measured in the control group in women and men were similar to those reported previously in lean subjects with a body mass index < 27.5 kg/m2. Leptin concentrations in women were 3-fold higher than in men. Leptin is secreted in a circadian rhythm in both sexes with an increase of nocturnal concentrations by approximately 50%. Two-way analysis of variance reveals no significant difference in leptin secretion between the control and active groups in women and men. In summary, preliminary results do not support the hypothesis that NE represents the afferent signal from the central nervous system which modulates leptin release from adipocytes in the human. Further studies are needed to define the role of the sympathetic nervous system as well as NE in the regulation of leptin secretion and its involvement in obesity and reproduction.

Adult↗

PubMed1984

Chlorpromazine inhibits neutrophil chemotaxis beyond the chemotactic receptor-ligand interaction.

Phenothiazines depress Ca++-dependent neutrophil functions, perhaps by binding to calmodulin or perturbing membrane structure through hydrophobic interactions. We examined effects of chlorpromazine (CPZ) on the human polymorphonuclear neutrophil (PMN) chemotactic-oligopeptide receptor and PMN membrane fluidity. CPZ had a reversible, biphasic effect on PMN motility in the Boyden chamber (slight depression at 5 microM, enhancement at 10 microM, and dose-dependent inhibition at higher concentrations). Order of potency for inhibition of motility (trifluoperazine greater than CPZ greater than promethazine) was identical to that for both inhibition of superoxide (O-2) release and binding to calmodulin. CPZ nonspecifically altered the binding affinity of chemotactic fMet-Leu-[3H]Phe. As assessed with two spin-probes, PMN membrane fluidity was unaltered at CPZ concentrations that depressed PMN receptor-mediated chemotaxis and O-2 release. The data suggest that CPZ nonspecifically alters receptor affinity and depresses chemotaxis and O-2 release independently, without altering bulk membrane fluidity. We speculate that unidentified "post-receptor changes" at a common translocation step for functions tested account for the observed inhibition.

Chemotaxis, Leukocyte↗

PubMedDate not supplied

Use of corrected retention indices based on 1-nitroalkane and alkyl arylketone scales for HPLC identification of basic drugs.

Sixteen basic drugs were examined by HPLC (gradient elution in acetonitrile/phosphate buffer, pH 3.2, containing 0.05% nonylamine) with six different ODS-silica columns. The retention indices (RI) were calculated with alkyl arylketone and 1-nitroalkane scales and were subjected to correction, which enabled comparison of results from commercially different column packing materials. The correction procedure was successful for the 1-nitroalkane scale. The scale based on alkyl arylketones was of less use for basic drugs, because some of them eluted earlier than the first reference homologue. This made impossible the proper calculation and correction of RI values for drugs such as cocaine, diphenhydramine, doxepin, and promethazine. The correction procedure of RI values calculated against the series of 1-nitroalkanes is recommended as a method of standardization of HPLC data.

Alkanes↗

PubMedDate not supplied

Study of the metabolism of phenothiazines: determination of N-demethylated phenothiazines in urine.

When phenothiazine drugs (chlorpromazine, promazine, promethazine, propiomazine, propionylpromazine, trifluoperazine and trimeprazine) were reacted with m-chloroperbenzoic acid, N-demethylated phenothiazines were obtained in moderate yield. The mass spectra of the N-demethylated phenothiazines showed either m/z 44 and 72 or m/z 58 as characteristic ions depending on their side chain. The N-demethylated propiomazine was identified as a metabolite of propiomazine from the urine of a rat which was given propiomazine orally.

Animals↗

PubMed2002

Immunoassay screening of lysergic acid diethylamide (LSD) and its confirmation by HPLC and fluorescence detection following LSD ImmunElute extraction.

In all, 3872 urine specimens were screened for lysergic acid diethylamide (LSD) using the CEDIA DAU LSD assay. Forty-eight samples, mainly from psychiatric patients or drug abusers, were found to be LSD positive, but only 13 (27%) of these could be confirmed by high-performance liquid chromatography with fluorescence detection (HPLC-FLD) following immunoaffinity extraction (IAE). Additional analysis for LSD using the DPC Coat-a-Count RIA was performed to compare the two immunoassay screening methods. Complete agreement between the DPC RIA assay and HPLC-FLD results was observed at concentrations below a cutoff concentration of 500 pg/mL. Samples that were LSD positive in the CEDIA DAU assay but not confirmed by HPLC-FLD were also investigated for interfering compounds using REMEDI HS drug-profiling system. REMEDI HS analysis identified 15 compounds (parent drugs and metabolites) that are believed to cross-react in the CEDIA DAU LSD assay: ambroxol, prilocaine, pipamperone, diphenhydramine, metoclopramide, amitriptyline, doxepine, atracurium, bupivacaine, doxylamine, lidocaine, mepivacaine, promethazine, ranitidine, and tramadole. The IAE/HPLC-FLD combination is rapid, easy to perform and reliable. It can reduce costs when standard, rather than more advanced, HPLC equipment is used, especially for labs that perform analyses for LSD infrequently. The chromatographic analysis of LSD, nor-LSD, and iso-LSD is not influenced by any of the tested cross-reacting compounds even at a concentration of 100 ng/mL.

Chromatography, High Pressure Liquid↗

PubMed1993

Measurement of cremophor EL following taxol: plasma levels sufficient to reverse drug exclusion mediated by the multidrug-resistant phenotype.

BACKGROUND: Paclitaxel (Taxol) is the first of a new class of cytotoxic agents with activity against tumors resistant to other drugs. For clinical use, paclitaxel is currently formulated in a vehicle of 50% ethanol and 50% polyethoxylated surfactant Cremophor EL (Cremophor). We have previously shown that Cremophor will block the P-glycoprotein drug efflux pump responsible for the multidrug-resistant phenotype. Overexpression of P-glycoprotein is one mechanism of in vitro resistance to a number of currently used cytotoxic agents including paclitaxel. PURPOSE: Our aim was to develop a bioassay to measure plasma levels of Cremophor and to determine whether or not plasma levels of Cremophor achieved during paclitaxel therapy are sufficient to inhibit the activity of the P-glycoprotein. METHODS: All patients studied had histologically proven, advanced ovarian carcinoma with measurable or evaluable disease and had received at least one prior platinum-containing regimen. The bioassay used flow cytometry to measure the increase in equilibrium intracellular daunorubicin levels in multidrug-resistant human T-cell leukemia cells (CEM/VLB100) in the presence of a series of concentrations of Cremophor. Levels of Cremophor were measured in plasma from 21 patients after a 3-hour infusion of 135 or 175 mg/m2 paclitaxel. Both dose levels were given following premedication with oral dexamethasone, intravenous promethazine hydrochloride, and intravenous cimetidine. The Cremophor bioassay involved incubation of CEM/VLB100 cells (5 x 10(5)) for 1 hour with 2 micrograms/mL daunorubicin in 0.5 mL HL-1 medium plus 0.5 mL plasma prior to flow cytometric analysis. Pretreatment plasma was used to derive a standard curve for the effect of Cremophor on equilibrium daunorubicin levels. All measurements were done in triplicate. RESULTS: In vitro experiments indicated that, for maximal inhibition of P-glycoprotein activity, concentrations of Cremophor of 0.1% (vol/vol) were required. At the end of a 3-hour infusion of paclitaxel, plasma levels of Cremophor in 19 of 21 patients were 0.1% or higher and 0.09% in the remaining two. Concentrations of 5-20 microM paclitaxel dissolved in ethanol without Cremophor did not inhibit P-glycoprotein in this assay. CONCLUSION: The concentrations of Cremophor measured in plasma drawn from patients after a 3-hour infusion of paclitaxel at 135 or 175 mg/m2 were found to be sufficient to inhibit P-glycoprotein activity in vitro. IMPLICATIONS: The efficacy of paclitaxel against some tumors may be aided by its administration in a vehicle solution containing Cremophor in quantities that reach concentrations in the plasma sufficient to reverse multidrug resistance of neoplastic cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1990

A prospective toxicity evaluation (COMPACT) on 40 chemicals currently being tested by the National Toxicology Program.

The computer-optimized molecular parametric analysis of chemical toxicity (COMPACT) procedure has been used to determine the molecular conformation and electronic structure of a series of 40 chemicals (out of a total of 44). The procedure can evaluate whether they interact with the active site of cytochrome P450 I or to the binding site of the Ah receptor, and hence to manifest carcinogenicity/toxicity. This is in response to the recent publication by Tennant et al. and their invitation to participate in a prospective identification of potential mutagenicity/carcinogenicity of these 44 chemicals. Correlation of COMPACT with potential genotoxicity was 25/40 (63%); COMPACT also predicted toxicity/carcinogenicity in 10 chemicals (25%) considered to be potentially non-genotoxic (naphthalene, promethazine, resorcinol, p-nitrophenol, tricresyl phosphate, bis(bromoethyl) propanediol, 3,4-dihydrocoumarin, theophylline, triamterene and chloramine), and predicted the absence of toxicity in four chemicals (10%) considered to be potentially genotoxic (methyl bromide, hydrazoic acid, 2,3-dibromo-1-propanol and 1,2,3-trichloropropane).

Binding Sites↗

PubMed2000

Lethal combination of tramadol and multiple drugs affecting serotonin.

The death of a 36-year-old alcoholic man who died after developing seizure activity while being treated with tramadol, as well as with venlafaxine, trazodone, and quetiapine, all of which interact with the neurotransmitter serotonin, is reported. The decedent, who had a history of chronic back pain, alcoholism, depression, mild hypertensive cardiovascular disease, and gastritis, had just been discharged from the hospital after 4 days of alcohol detoxification treatment. During the admission, no withdrawal seizures were noted. The morning after discharge, a witness observed the decedent exhibiting seizure activity and then collapsing. An autopsy was performed approximately 6 hours after death, and the anatomic findings were consistent with seizure activity and collapse, which included biting injuries of the tongue and soft-tissue injuries of the face. Toxicologic analysis identified tramadol, venlafaxine, promethazine, and acetaminophen in the urine; tramadol (0.70 mg/L) and venlafaxine (0.30 mg/L) in the heart blood, and 0.10 mg of tramadol in 40 ml of submitted stomach contents. No metabolites, such as acetate, acetone, lactate, and pyruvate, were found in the specimens that would be characteristically found in a person with alcohol withdrawal syndrome. The threshold for seizures is lowered by tramadol. In addition, the risk for seizure is enhanced by the concomitant use of tramadol with selective serotonin reuptake inhibitors or neuroleptics, and its use in patients with a recognized risk for seizures, i.e., alcohol withdrawal. The cause of death in this individual was seizure activity complicating therapy for back pain, depression, and alcohol withdrawal syndrome. The data in Adverse Event Reporting System of the Food and Drug Administration from November 1, 1997 to September 8, 1999 was reviewed along with a MEDLINE search from 1966 to the present. This case appears to be the first reported death caused by seizure activity in a patient taking tramadol in combination with drugs that affect serotonin.

Adult↗

PubMed1999

Efficacy and adverse effects of prophylactic antiemetics during patient-controlled analgesia therapy: a quantitative systematic review.

UNLABELLED: Nausea and vomiting are frequent adverse effects of patient-controlled analgesia (PCA) with opioids. To identify the optimal prophylactic antiemetic intervention in this setting, we performed a systematic search for randomized trials (MEDLINE, EMBASE, Cochrane library, reference lists, hand-searching, no language restriction) published up to May 1998 that compared prophylactic antiemetic interventions with placebo or no treatment in the postoperative PCA-setting with opioids. Fourteen placebo-controlled trials (1117 patients) with different regimens of droperidol, ondansetron, hyoscine TTS, tropisetron, metoclopramide, propofol, and promethazine were analyzed. One PCA was with tramadol, all others were with morphine. At 24 h, the cumulative incidence of nausea and vomiting without antiemetics was approximately 50%. Droperidol 0.017-0.17 mg/mg of morphine (0.5-11 mg/d droperidol) was statistically significantly more effective than placebo without evidence of dose-responsiveness; the number needed to treat to prevent nausea compared with placebo was 2.7 (95% confidence interval 1.8-5.2), and that to prevent vomiting was 3.1 (2.3-4.8). Compared with placebo, the incidence of minor adverse effects with droperidol was increased with doses >4 mg/d. IMPLICATIONS: Of 100 patients treated with droperidol added in a patient-controlled analgesia pump with morphine, 30 who would have vomited or been nauseated had they not received droperidol will not suffer these effects. There is no evidence of dose-responsiveness for efficacy with droperidol, but the risk of adverse effects is dose-dependent. There is a lack of evidence for other antiemetics.

Analgesia, Patient-Controlled↗

PubMed2002

Cesarean delivery: a randomized trial of epidural analgesia versus intravenous meperidine analgesia during labor in nulliparous women.

BACKGROUND: Controversy concerning increased cesarean births as a result of epidural analgesia for relief of labor pain has been attributed, in large part, to difficulties interpreting published studies because of design flaws. In this study, the authors compared epidural analgesia to intravenous meperidine analgesia using patient-controlled devices during labor to evaluate the effects of labor epidural analgesia, primarily on the rate of cesarean deliveries while minimizing limitations attributable to study design. METHODS: Four hundred fifty-nine nulliparous women in spontaneous labor at term were randomly assigned to receive either epidural analgesia or intravenous meperidine analgesia. Epidural analgesia was initiated with 0.25% bupivacaine and was maintained with 0.0625% bupivacaine and fentanyl 2 microg/ml at 6 ml/h with 5-ml bolus doses every 15 min as needed using a patient-controlled pump. Women in the intravenous analgesia group received 50 mg meperidine with 25 mg promethazine hydrochloride as an initial bolus, followed by 15 mg meperidine every 10 min as needed, using a patient-controlled pump. A written procedural manual that prescribed the intrapartum obstetric management was followed for each woman randomized in the study. RESULTS: A total of 226 women were randomized to receive epidural analgesia, and 233 women were randomized to receive intravenous meperidine analgesia. Protocol violations occurred in 8% (38 of 459) of women. There was no difference in the rate of cesarean deliveries between the two analgesia groups (epidural analgesia, 7% [16 of 226; 95% confidence interval, 4-11%] vs. intravenous meperidine analgesia, 9% [20 of 233; 95% confidence interval, 5-13%]; P = 0.61). Significantly more women randomized to epidural analgesia had forceps deliveries compared with those randomized to meperidine analgesia (12% [26 of 226] vs. 3% [7 of 233]; P < 0.001). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received intravenous meperidine analgesia. CONCLUSIONS: Epidural analgesia compared with intravenous meperidine analgesia during labor does not increase cesarean deliveries in nulliparous women.

Adult↗

PubMed2004

Labor analgesia and cesarean delivery: an individual patient meta-analysis of nulliparous women.

BACKGROUND: The authors performed an individual patient meta-analysis of 2,703 nulliparous women who were randomized to either epidural analgesia or intravenous opioids for pain relief during labor from five trials conducted at their hospital. The primary purpose in this meta-analysis was to evaluate the effects of epidural analgesia during labor on the rate of cesarean delivery. METHODS: Between November 1, 1993, and November 3, 2000, 2,703 nulliparous women (2,188 healthy parturients and 515 women with pregnancy-induced hypertension) in spontaneous labor at term were randomized to receive either epidural analgesia or intravenous opioid analgesia in the five studies. Epidural analgesia was initiated with either epidural bupivacaine or intrathecal sufentanil and was maintained with a low-dose (0.0625% or 0.125%) mixture of bupivacaine with fentanyl. Intravenous opioid analgesia was initiated with 50 mg meperidine and 25 mg promethazine hydrochloride and was maintained with intravenous boluses of meperidine as needed. RESULTS: A total of 1,339 nulliparous women were randomized to receive epidural analgesia, and 1,364 women were randomized to receive intravenous meperidine analgesia. There was no difference in the rate of cesarean deliveries between the two analgesia groups (epidural analgesia, 10.5% [140 of 1,339] vs. intravenous meperidine analgesia, 10.3% [141 of 1,364]; adjusted odds ratio, 1.04; 95% confidence interval, 0.81-1.34; P = 0.920). Significantly more women randomized to epidural analgesia had forceps deliveries compared to meperidine analgesia (13% [172 of 1,339] vs. 7% [101 of 1,364]; adjusted odds ratio, 1.86; 95% confidence interval, 1.43-2.40; P < 0.001). Epidural women had longer first and second stages of labor. Women who received epidural analgesia reported lower pain scores during labor and delivery compared to women who received intravenous meperidine analgesia. CONCLUSION: Epidural analgesia compared to intravenous meperidine analgesia during labor does not increase the number of cesarean deliveries.

Adult↗

PubMedDate not supplied

Hiccups associated with lateral medullary syndrome. A case report.

We present a case of persistent hiccups (singultus) after a lateral medullary cerebrovascular accident. The patient presented with a two-day history of nausea and vomiting. Clinically, the patient had a loss of pain and temperature on the left side of the face, a loss of pain and temperature on the right side of the trunk, a mild left hemiparesis, and a left-sided ataxia. Nystagmus, diplopia, and hiccups were also evident. A left lateral medullary syndrome in the vascular distribution of the posterior inferior cerebellar artery was diagnosed. Work-up included a magnetic resonance imaging angiogram, which revealed an occlusion v high-grade stenosis of the basilar artery. The patient reported that the most distressing symptom was the chronic hiccups (25/min), which interfered with nutrition, sleep, and activity. While in the acute care hospital, the patient was treated with prochlorperazine, promethazine, and chlorpromazine. Each of these medications was unsuccessful in stopping the hiccups. After a search of the European literature revealed that baclofen was recommended as the drug of choice for stopping persistent hiccups, the patient was given 5 mg of baclofen by mouth three times per day, and the hiccups abated within 48 hours. The baclofen was discontinued after one week of therapy, and the hiccups did not return. We recommend consideration of baclofen for the treatment of persistent hiccups after lateral medullary syndrome because of its desirable side effects and reported success rate compared with other drugs used to treat chronic hiccups.

Aged↗

PubMed1986

Medical treatment of nystagmus and ocular motor disorders.

An increased compendium of drugs useful in ocular motor system dysfunction has expanded our capacity to treat selected ocular motility disorders. Adjunctive therapeutic modes (e.g., Fresnel prisms and orthoptic exercises) can also be beneficial. PAN and see-saw nystagmus can be treated with baclofen. Downbeat nystagmus may respond to clonazepam therapy, and prisms may help if the nystagmus can be modified with convergence. Congenital nystagmus may respond minimally to drugs (e.g., baclofen), but prisms or surgical procedures, or both, are still the primary treatment modalities. Innovar may be helpful in patients with severe, incapacitating vestibular disorders, and scopolamine alone or in combination with promethazine may be beneficial in patients with milder ambulatory acute peripheral vestibular disorders. Benign positional vertigo is best treated initially with positional exercises before drug therapy is instituted. Opsoclonus and ocular flutter have been treated successfully with corticosteroids, propranolol, and clonazepam, while microflutter, an extremely rare disorder, can resolve with baclofen. Although therapy with carbamazepine, 5-hydroxtryptophan, and scopolamine has been useful in selected patients with ocular palatal myoclonus, most do not respond to drug treatment. It is not usually necessary to treat voluntary nystagmus, but Fresnel prism lenses should be remembered in refractory patients. Potentially reversible and pseudointernuclear ophthalmoplegias also were discussed. Orthoptic exercises can be beneficial in posttraumatic internuclear ophthalmoplegia. Selected supranuclear palsies can be improved completely with the proper drug regimen. Lastly, superior oblique myokymia can be treated successfully with carbamazepine, with tight surveillance for possible adverse side effects. Descriptive phenomenology and pathophysiological localization must be correlated with brain stem neurochemistry and neuropharmacology to medically treat additional ocular motor system disorders.

Adolescent↗