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PubMed2005

The utility of antiemetics in the prevention and treatment of postoperative nausea and vomiting in patients scheduled for laparoscopic cholecystectomy.

Postoperative nausea and vomiting (PONV) are distressing and frequent adverse events of anesthesia and surgery, with a relatively high incidence after laparoscopic cholecystectomy. Numerous antiemetics have been studied for the prevention and treatment of PONV in patients scheduled for laparoscopic cholecystectomy. Traditional antiemetics, including anticholinergics (e.g., scopolamine), antihistamines (e.g., dimenhydrinate), phenothiazines (e.g., promethazine), butyrophenones (e.g., droperidol), and benzamide (e.g., metoclopramide), are used for the control of PONV. The available nontraditional antiemetics for the prophylaxis against PONV are dexamethasone and propofol. Serotonin receptor antagonists (ondansetron, granisetron, tropisetron, dolasetron, and ramosetron), compared with traditional antiemetics, are highly efficacious for PONV. The prophylactic ondansetron, granisetron, tropisetron, and dolasetron in antiemetic efficacy are comparable. Ramosetron is effective for the long-term prevention of PONV. None of the available antiemetics is entirely effective, perhaps because most of them act through the blockade on one type of receptor. There is a possibility that combined antiemetics with different sites of activity would be more effective than one drug alone for the prophylaxis against PONV. Combination antiemetic therapy is often effective for the prevention of PONV following laparoscopic cholecystectomy. The efficacy of a combination of serotonin receptor antagonists (ondansetron and granisetron) and droperidol is superior to monotherapy with a serotonin receptor antagonist or droperidol. Similarly, adding dexamethasone to ondansetron or granisetron improves antiemetic efficacy in PONV. Knowledge regarding antiemetics is necessary to completely prevent and treatment of PONV in patients scheduled for laparoscopic cholecystectomy.

Antiemetics↗
PubMed2003

Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view.

The so-called "classic" histamine H(1) receptor antagonists are highly lipophilic compounds associated with significant biotransformation and tissue distribution. They are categorized according to their chemical structure into ethanolamines, alkylamines, ethylenediamines, piperazines, phenothiazines and piperidines, all of which have characteristic metabolic fates. The former four categories undergo primarily cytochrome P450-mediated oxidative N-desalkylations and deamination whereas the aromatic rings of the latter two undergo P450-mediated oxidative hydroxylation and/or epoxide formation. The common tertiary amino group is susceptible to oxidative metabolism by flavin containing monooxygenases forming N-oxides, and the alicyclic tertiary amines produce small amounts (up to 7%) of N-glucuronides in humans. Species, sex and racial differences in the metabolism and pharmacokinetics of antihistamines are known. Specific P450-isozymes implicated in the metabolism were identified in a few cases, such as CYP2D6 that contributes to the metabolism of promethazine, diphenhydramine and chlorpheniramine. Low circulating plasma concentrations of antihistamines are in part explained by significant first-pass effect and tissue distribution. Antihistaminic effects last up to 6 hours though some compounds exhibit a longer duration of action due to circulating active metabolites. Importantly, diphenhydramine inhibited CYP2D6 leading to a clinically significant drug-drug interaction with metoprolol. Other classic antihistamines were shown to be potent in vitro inhibitors of CYP2D6 and CYP3A4. The prescription-free access to most classic antihistamines can easily lead to their co-administration with other drugs metabolized by the same enzyme system thereby leading to drug accumulation and adverse effects. In depth knowledge of the metabolic pathways of classic antihistamines and the enzymes involved is crucial to prevent the high incidence of drug interactions in humans, which are predictable based on pre-clinical data but unexpected when such data is unavailable.

Animals↗
PubMed1996

[Drug induced hemolytic anemia associated with agranulocytosis].

A 27-year-old female was admitted to a hospital because of severe anemia (hemoglobin 4.9 g/dl) after taking PL (a drug for common cold consisted of Salicylamide, Acetaminophen, Caffeine and Promethazine methylene di-salicylate) and Cefadroxil (an oral antibiotic) for ten days. History and laboratory data leaded to a diagnosis of drug induced hemolytic anemia. 6 units of concentrated red blood cells were transfused and the suspected drugs were discontinued immediately. Though resolution of anemia and no further hemolysis were observed, progressive leukocytopenia developed since four days after the admission. Bone marrow aspiration revealed marked decrease of granulocytic series. The patient was transferred to our hospital and was isolated under laminar air-flow to prevent her from bacterial and fungal infections. She was treated with prednisolone and granulocyte-colony stimulating factor. She recovered from leukocytopenia in two weeks without suffering from any life-threatening infection. We extensively analyzed the suspected drugs and mechanism of hemolysis and granulocytopenia. Cefadroxil is turned out to be contributed to hemolysis by an immune complex mechanism. Cefadroxil and Salicylamide were suggested to be involved in granulocytopenia by the induction of antibodies against the leukocytes to which these drugs were bound. Thus Cefadroxil was regarded as a causative drug of both hemolysis and granulocytopenia. This case is of interest for analyzing drug-induced blood abnormality because it is very rare that two lineage of blood were injured by one drug at the same time as far as we know.

Adult↗
PubMed1985

Nitrous oxide: effective analgesic for vascular and interventional procedures.

During a 2 year period nitrous oxide was used as a sole or supplementary analgesic during 173 vascular or interventional procedures including peripheral angiography and endourologic and endobiliary procedures. The decision to administer nitrous oxide to a given patient was a matter of physician preference. Patients with bowel obstruction, pneumothorax, or chronic obstructive pulmonary disease were excluded from this method of analgesia. The nitrous oxide was administered by a radiology nurse under the supervision of an attending radiologist. Nitrous oxide was used without premedication for 39 procedures and with premedication (usually meperidine 1 mg/kg, promethazine 0.3 mg/kg, or atropine 0.01 mg/kg) in 134 procedures. In 74% of nonpremedicated individuals analgesia was adequate with nitrous oxide alone; 26% required supplemental intravenous medication. In 61% of premedicated individuals pain relief was adequate with nitrous oxide; 39% required supplemental intravenous medication. Complications, including nausea, vomiting, and agitation, occurred in eight patients, but were minor and easily reversed by decreasing the concentration of nitrous oxide. Nasally administered nitrous oxide is a safe, easily used, and effective analgesic.

Analgesics↗
PubMed1976

A prospective study of drugs and pregnancy. II. Anti-emetic drugs.

In a prospective study of anti-emetic drug use during 6 376 pregnancies, the previously demonstrated negative correlation between the use of such drugs and miscarriage was confirmed. It is probably completely due to less frequent and possibly less severe morning sickness complaints in pregnancies ending with a miscarriage. A slight positive correlation is found between the use of anti-emetics and infant malformation. A detailed analysis showed that this was mainly due to a high incidence of drug use (mainly promethazine) among women giving birth to infants with congenital dislocation of the hip. The probable indirect relationship is discussed.

Abnormalities, Drug-Induced↗
PubMed1997

Histamine-induced calcium released from cultured human mucosal microvascular endothelial cells from nasal inferior turbinate.

Changes in cytosolic Ca2+ concentration ([Ca2+]i) in cultured human mucosal microvascular endothelial cells (HMMECs) from nasal inferior turbinate were measured using a fluorescent Ca(2+)-sensitive dye, fura-2, and photometric fluorescence microscopy. Histamine caused a transient increase in intracellular free Ca2+ in cell populations and in individual cells, followed by a decrease to a sustained elevation. Histamine (100 microM) elevated [Ca2+]i in HMMECs up to 563 +/- 20 nM from a resting level of 60 +/- 45 nM (means +/- SD, n = 31). Promethazine (a histamine H1 receptor antagonist) inhibited [Ca2+]i increase during histamine stimulation, whereas cimetidine (a H2 receptor antagonist) and thioperamide (a H3 receptor antagonist) showed no inhibition. These results suggest that the histamine increase [Ca2+]i in HMMECs induces both a Ca2+ release from stores and a Ca2+ influx through activation of the H1 receptor.

Calcium↗
PubMed1993

Effects of H1-receptor antagonists on 14C-aminopyrine accumulated in histamine-stimulated rabbit gastric glands.

After stimulation of gastric acid production there is a considerable delay before the acid starts to appear in the gastric lumen. The present study was carried out on isolated gastric glands to test the hypothesis that there may be a mechanism in the parietal cell that contributes to this delay by preventing emptying of the secretory canaliculi. Glands were incubated with 14C-aminopyrine and stimulated with histamine. After accumulation of 14C-aminopyrine various concentrations of H1-receptor antagonists were added. Clemastine, promethazine, and hydroxyzine effectively and cetirizine and tripelennamine less effectively decreased the accumulated 14C-aminopyrine content in a dose-dependent manner without significantly reducing the oxygen consumption. The H1-receptor antagonists influenced the 14C-aminopyrine content in another manner than H2-receptor antagonists. No effects were obtained by atropine or lidocaine, indicating that the elimination of 14C-aminopyrine is not an anticholinergic effect or due to membrane effects as exerted by local anesthetics. Stimulation of glands by further addition of histamine did not significantly stimulate the uptake of 14C-aminopyrine in the glands, whereas stimulation with db-cAMP produced an increase that was most pronounced when low concentrations of hydroxyzine had been used. It is suggested that H1-receptor antagonists do not inhibit stimulation of acid production in the secretory canaliculi. They may, however, interfere with a mechanism preventing acid from leaving the parietal cell. Such a mechanism may contribute to the delay in appearance of acid in the gastric lumen after stimulation of gastric acid production.

Aminopyrine↗
PubMed1991

Physostigmine (alone and together with adjunct) pretreatment against soman, sarin, tabun and VX intoxication.

A pretreatment for organophosphorus (OP) anticholinesterase (e.g., soman) intoxication should prevent lethality and convulsions (CNV) at 2 LD50s and be behavioral-decrement-free when given alone. Behavioral-deficit-free pretreatment regimens (PRGs) for guinea pigs consisted of Physostigmine (0.15 mg/kg, im) and adjunct. Adjuncts [mg/kg, im] tested were akineton [0.25], aprophen [8], trihexyphenidyl [2], atropine [16], azaprophen [5], benactyzine [1.25], cogentin [4], dextromethorphan [7.5], ethopropazine [12], kemadrin [1], memantine [5], promethazine [5], scopolamine [0.08] and vontrol [2]. PRGs were given 30 min before soman (60 micrograms/kg, sc; 2 LD50s) or other OP agents. Animals were then observed and graded for signs of intoxication, including CNV at 7 time points and at 24 hr. Physostigmine alone reduced the incidence of CNV and lethality induced by 2 LD50s of soman by 42 and 60%, respectively. All of the PRGs tested abolished lethality and 12 shortened recovery time to 2 hr or less. Also, PRGs including azaprophen or atropine prevented CNV. When selected PRGs were tested against intoxication by sarin, tabun or VX, the efficacy was generally superior to that for soman. The data show that several PRGs are effective against soman intoxication in guinea pigs.

Animals↗
PubMed1996

Protein phosphorylation in Golgi, endosomal, and endoplasmic reticulum membrane fractions of lacrimal gland.

Ca2+/calmodulin- and cAMP-dependent protein kinase activities were characterized in two subcellular membrane samples. Membranes from rat lacrimal gland were isolated by differential and density gradient centrifugation into six density windows. The present study focused on membranes from density windows III and V which contain mixtures of apical, Golgi, endosomal, and endoplasmic reticulum membranes in different proportions. Phosphorylation of membrane proteins was measured by incubating the samples in [g-32P]ATP and separating the proteins by discontinuous SDS-PAGE followed by autoradiography. The amount of phosphate incorporated into specific peptide bands was quantified by densitometry. Ca2+/calmodulin-dependent protein kinase phosphorylated a 52,000 MW peptide in membranes from both density windows with a maximal increase from 0.3 to 66 microM free Ca2+. Trifluoperazine and promethazine, two inhibitors of Ca2+/calmodulin-dependent protein kinases, inhibited this phosphorylation. cAMP-dependent protein kinase phosphorylated a 22,000 MW peptide and a 91,000 MW peptide which were present in membranes from density window III only. We conclude that a Ca2+/calmodulin-dependent protein kinase activity is present in membranes from both density window III and V whereas a cAMP-dependent protein kinase activity is present only in membranes from density window III.

Animals↗
PubMed1989

The effects of protein kinase inhibitors on lymphocyte blastogenesis and GVHD-induced splenomegaly.

The activation of the protein kinase C (PKC) pathway plays an integral part in the proliferation of many cell types including lymphocytes. We report that the PKC inhibitor H-7 caused inhibition of three commonly studied blastogenic responses (Con A, LPS, and MLR) with the strongest suppression being detected in the MLR. In contrast, HA1004, a potent inhibitor of cyclic nucleotide-dependent protein kinases, did not alter the blastogenic response but occasionally caused augmentation. The phenothiazine compounds studied inhibited the Con A and, to a lesser extent, the LPS responses. One of the compounds, promethazine-HCl, was effective in vivo in inhibiting splenomegaly resulting from the induction of graft vs. host disease. Our studies support the involvement of PKC in lymphoid blastogenesis. They also suggest that agents that can inhibit PKC activity may be useful in inducing immunosuppression in vivo.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1983

[The participation of platelets in anaphylactic shock in the rat].

In the IgE-sensitized Brown Norway rats, the intravenous antigen challenge resulted in systemic anaphylactic shock without thrombocytopenia. In the IgG-sensitized Wistar rats, thrombocytopenia occurred during the anaphylactic shock. It is linked with circulating immun-complexes. Treatment of IgG-sensitized Wistar rats by antiplatelet serum, by promethazine (anti-H1), cyproheptadine (anti-5-HT1) or phenidone, a cyclo-oxygenase and lipoxygenase inhibitor, did not protect against the anaphylactic shock. In the rat, platelets did not play a significant rôle in the pathogenesis of the various forms of the anaphylactic shock.

Anaphylaxis↗
PubMed1991

Characterization and pharmacological studies of an octopamine-sensitive adenylate cyclase from nerve cord of Locusta migratoria.

An octopamine-sensitive adenylate cyclase that is insensitive to stimulation by dopamine (DA) and 5-hydroxytryptamine (5-HT), was studied in a homogenized nerve cord preparation of the migratory locust, Locusta migratoria. The enzyme complex is similar to catecholamine-sensitive cyclases from mammals with respect to pH-optimum, requirement for Mg++ and GTP, and sensitivity to forskolin. The octopamine-mediated elevation of adenylate cyclase activity is antagonized by a variety of drugs with the following order of potency: mianserin greater than phentolamine greater than promethazine greater than gramine greater than cyproheptadine greater than cis-flupenthixol greater than chlorpromazine greater than metoclopramide.

Adenylyl Cyclases↗
PubMedDate not supplied

Carvedilol suppresses intractable hiccups.

Carvedilol (6.25 mg, 4 times daily) relieved 2 years of constant hiccupping, marked tardive dyskinesia, compulsive self-induced vomiting, and feelings of hopelessness and low mood in a 59-year-old African-American man. He previously failed trials of ranitidine, chlorpromazine, promethazine, tegaserod, ondansetron, metoclopramide, pantoprazole, pyloric injections of botulinum toxin A, and a vagal nerve stimulator. At a 5-month follow-up, improvement was maintained; there had been several instances of rapid relapse on carvedilol discontinuation.

Carbazoles↗
PubMedDate not supplied

Neodymium:YAG pupilloplasty in pediatric aphakia.

An adequate pupillary aperture is required for accurate ophthalmoscopy and retinoscopy in pediatric aphakia. When pupillary miosis does not respond to pharmacologic dilation, optical iridectomy performed with a vitreous suction-cutting instrument under general anesthesia may be required. We report a 27-month-old aphakic child whose pupillary aperture was enlarged from 1 mm to 3.5 mm with neodymium (Nd):YAG pupilloplasty, following intramuscular sedation with meperidine, promethazine, and chlorpromazine. Removal of the laser chin rest and positioning of the patient on a table with adjustable height facilitated delivery of 140 applications at 2.5 to 4.3 mJ to the pupillary border. Levobunolol 0.5% controlled the transient posttreatment rise in intraocular pressure. We suggest that Nd:YAG pupilloplasty performed with sedation be considered as an alternative to intraocular surgery when pupillary miosis in pediatric aphakia does not respond to dilating agents.

Aphakia↗
PubMed1998

Cocaine as a risk factor for neuroleptic-induced acute dystonia.

BACKGROUND: A prospective study was conducted to test the hypothesis that cocaine use is a risk factor for neuroleptic-induced acute dystonia (NIAD). METHOD: The study sample consisted of a high-risk group for NIAD, males aged 17-45 years who had received high-potency neuroleptics within 24 hours of admission and had not used neuroleptics in the month prior to admission. Patients were excluded if they suffered from a neurodegenerative disorder or were exposed to anticholinergics, benzodiazepines, promethazine, carbamazepine, phenytoin, or levodopa during the study. Twenty-nine patients--9 cocaine users and 20 nonusers--entered the study, which lasted 2 years. Patients were followed for 7 days. RESULTS: Cocaine-using psychiatric patients developed significantly more NIAD than did nonusers (relative risk = 4.4, 95% CI = 1.4 to 13.9). CONCLUSION: Cocaine use is a major risk factor for NIAD and should be added to the list of well-known risk factors. The authors strongly suggest that cocaine-using psychiatric patients who are started on a regimen of neuroleptics should also be administered an anticholinergic for at least 7 days to prevent NIAD.

Adolescent↗
PubMedDate not supplied

A comparative study of the haemodynamic effects of atropine and glycopyrrolate at induction of anaesthesia in children.

BACKGROUND: Bradycardia following administration of halothane and suxamethonium in children leads to reduced cardiac output, which can be prevented with prophylactic anticholinergics. Anticholinergics may result in tachycardia and arrhythmias. This study was designed to compare haemodynamic changes and incidence of cardiac arrhythmias following intravenous atropine and glycopyrrolate. STUDY DESIGN: Ninety ASA I and II children between one month and twelve years were studied. Premedication was with oral promethazine 1mg/kg. Anaesthesia was achieved with 3 % halothane in 33 % oxygen and nitrous oxide. Patients were randomly allocated to receive atropine 0.01mg/kg (Group I) or glycopyrrolate 0.005mg/kg (Group II). Tracheal intubation was facilitated with suxamethonium 1.5mg/kg. RESULTS: Patients in Group I had a 35.7% rise in heart rate from baseline, compared to 22.5 % in Group II two minutes after anticholinergic administration (p=0.001). Following intubation, heart rate rose by 9.7 % and 13.2 % (p<0.05) in Groups I and II respectively. MAP rose similarly in both groups. Arrhythmia occurred in 44.4 % of patients in Group I and 11.1% in Group II (p=0.001) and were mainly sinus tachycardia. 2.2% of patients in Group I exhibited bigemini. No patient experienced bradycardia. Hypoxia occurred in 2.2 %, hypotension in 13.3% and mild laryngeal spasm in 0% of Group I and 11.1%, 4.4% and 4.4% of Group II respectively. CONCLUSION: The use of glycopyrrolate compared to atropine, offered better cardiovascular stability in Nigerian children. Arrhythmias occurred more in patients who had atropine and occurred most frequently after tracheal intubation.

Anesthesia, Inhalation↗
PubMed1977

An unusual snake bite story.

The case is reported of a seven-year-old girl who was bitten by a tiger snake and sustained severe liver, skeletal muscle and myocardial muscle damage as a result of envenomation. She recovered after treatment with polyvalent snake bite antivenom preceded by promethazine.

Antivenins↗
PubMed1982

Single-agent versus combination antiemetic treatments in patients receiving cytotoxic chemotherapy.

We report the results of two clinical trials in which patients receiving either doxorubicin (Adriamycin)/cyclophosphamide or cis-platinum cytotoxic chemotherapy were assigned at random either a single or a combination antiemetic treatment. The aim of each trial was to assess whether combination antiemetic therapy would result in improved efficacy. Sixty patients commencing doxorubicin/cyclophosphamide therapy were divided in two random groups to receive either haloperidol or haloperidol plus amitriptyline, and 80 patients commencing cis-platinum therapy were divided at random to receive either metoclopramide or metoclopramide plus promethazine. No statistically significant differences were apparent between single and combination antiemetic regimens in either of the two treatment groups. Antiemetic agents were generally well-tolerated, but minor side effects were common. The failure of our combination antiemetic regimens to intensify the proven antiemetic efficacy of single agents emphasises the need for re-evaluation of currently used antiemetic agents and their dosage schedules.

Amitriptyline↗