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An unusual multiple drug intoxication case involving citalopram.

A 47-year-old male with a history of drug abuse and suicide attempts was found dead at home. The death scene investigation showed evidence of cocaine abuse and multiple drug ingestion. Citralopram, a new selective serotonin reuptake inhibitor, cocaine, oxycodone, promethazine, propoxyphene, and norpropoxyphene were identified and quantitated in the postmortem samples by gas chromatography-mass spectrometry. The concentration of citalopram in the femoral blood was 0.88 mg/L. The heart blood concentration was 1.16 mg/L. Femoral blood concentrations of the other drugs were as follows: cocaine, 0.03 mg/L; oxycodone, 0.06 mg/L; promethazine, 0.02 mg/L; propoxyphene, 0.02 mg/L; and norpropoxyphene, 0.07 mg/L. Other tissue samples were also analyzed. The concentrations of cocaine, oxycodone, promethazine, and propoxyphene in the blood, liver, brain, and gastric contents did not suggest an intentional overdose. However, the possibility of multiple drug interactions including citalopram was evident. In this case, the citalopram concentrations were consistent with those reported in fatal cases involving multiple drug use. Citalopram was present in urine at a concentration of 0.9 mg/L.

Antidepressive Agents, Second-Generation↗

The efficacy low dose of prednisolone in the treatment of hyperemesis gravidarum.

BACKGROUND: To determine whether low dosages of prednisolone are effective in the treatment of outpatients with hyperemesis gravidarum. METHODS: Eighty pregnant women with gestational ages of 6 to 12 weeks and persistent nausea and vomiting participated. The women were assigned by simple randomization to receive prednisolone 5 mg daily or promethazine 75 mg daily by oral route for 10 days. The severity of nausea, frequency of vomiting per day, sickness and the drugs' side-effects were compared (Fisher's exact test, Mann-Whitney U-test, Odds Ratio test). RESULTS: The women who received promethazine responded better in the first 48 h (p = 0.02). With continuation of the treatment, the difference decreased, and one week after completion of the treatment, the subjects who had received prednisolone had less symptoms. CONCLUSION: Promethazine reduces the symptoms of hyperemesis gravidarum faster than prednisolone, but during prolonged treatment, prednisolone has at least the same effects on the symptoms and less drug side-effects.

Administration, Oral↗

Melanotropic drugs and retinal functions. II. Effects of phenothiazine and rifampicin on the sheep ERG.

The acute effects of chlorpromazine, promethazine and rifampicin on the a-, b- and c-waves of the conventional electroretinogram (ERG) were studied in sheep. Iv administration of chlorpromazine and promethazine resulted in a b-wave amplitude decrease and an initial c-wave amplitude decrease, followed by cyclic amplitude changes resembling damped oscillations. Iv injections of rifampicin, however, resulted in cyclic changes of the c-wave amplitude without initial concomitant b-wave changes. The results of the present study indicate that rifampicin has a selective influence on the pigment epithelial cells, while chlorpromazine and promethazine seem to have more generalized retinal effects on both the neuroretina and the pigment epithelial cells.

Animals↗

Studies on role of calmodulin in Ca2+ regulation of rabbit ileal Na and Cl transport.

To study the role of calmodulin in regulation of rabbit ileal active electrolyte transport by Ca2+, the effects of the Ca2+-calmodulin antagonist naphthalenesulfonamides W12 and W13 and the weak Ca2+-calmodulin antagonist promethazine, a phenothiazine, were studied on basal ileal Na and Cl transport and on secretion stimulated by Ca2+ and by cAMP. The naphthalenesulfonamides and promethazine all stimulated basal ileal Na and Cl absorption. The stimulation of Na absorption was dependent on Cl in the bathing solutions, and the stimulation of Cl absorption was Na dependent. This suggests that the transport process stimulated was the neutral, linked NaCl absorptive process. W13, which is a better Ca2+-calmodulin antagonist but has similar hydrophobic properties to W12, stimulated active ileal absorption at a lower concentration than W12, suggesting that the naphthalenesulfonamide-induced stimulation of active ileal absorption was not due to the hydrophobic properties of these drugs but could be due to their effects on the calcium-binding protein calmodulin. W12, W13, and promethazine did not alter paracellular transport, not affecting dilution potentials or structural features of the paracellular pathway. W12 and W13 did not decrease the changes in active ileal Na and Cl transport caused by increasing ileal cAMP content or intracellular Ca2+. This suggests that calmodulin is not directly involved in the active electrolyte secretion caused by increased intestinal Ca2+ or cAMP.

Animals↗

Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study.

BACKGROUND: The medical management of aggressive and violent behaviour is a critical situation for which there is little evidence. In order to prepare for a randomised trial, due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001, a survey of current practice was necessary. METHODS: A seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro, Brazil. RESULTS: In one hospital data were not available. Of the 764 people with psychosis attending these ERs, 74 were given IM medication for rapid tranquillisation (9.7%, 2.1/week/100,000). A haloperidol-promethazine mix (with or without other drugs) was used for the majority of patients (83%). CONCLUSION: The haloperidol-promethazine mix, given intramuscularly for rapid tranquilization, is prevalent in Rio, where it is considered both safe and efficient. However, scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a randomized trial of IM haloperidol-promethazine is overdue.

Aggression↗

Purification of histamine receptor (VI). An improved double labeling method with "double protection".

Studies were done on the specific labeling of the histaminergic H1-receptor of the longitudinal smooth muscle of cat small intestine. A procedure involving 'double protection' combined with the double labeling technique was developed. The first protection was the usual with a protective antihistamine, promethazine, and the second was cross protection of non-specific sites with non-hitaminergic drugs, thioriazine and atropine. Muscle tissue protected with promethazine against non-radioactive dibenamine was treated with 3H-dibenamine in the presence of these second protectors. The second protectors covered non-receptor sites which had been protected from non-radioactive dibenamine with promethazine. The dose-response curves were carefully checked in each experiment to confirm that the second protectors did not interfere with the specific coverage provided by the first protector. Finally 14C-dibenamine was applied to measure non-specific binding after which the labeled muscles were fractionated and the radioactivity was counted. The specificity of labeling achieved in the receptor-rich fraction by this method is discussed.

Animals↗

Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines).

This article reviews clinical pharmacokinetic data on the H1-receptor antagonists, commonly referred to as the antihistamines. Despite their widespread use over an extended period, relatively little pharmacokinetic data are available for many of these drugs. A number of H1-receptor antagonists have been assayed mainly using radioimmunoassay methods. These have also generally measured metabolites to greater or lesser extents. Thus, the interpretation of such data is complex. After oral administration of H1-receptor antagonists as syrup or tablet formulations, peak plasma concentrations are usually observed after 2 to 3 hours. Bioavailability has not been extensively studied, but is about 0.34 for chlorpheniramine, 0.40 to 0.60 for diphenhydramine, and about 0.25 for promethazine. Most of these drugs are metabolised in the liver, this being very extensive in some instances (e.g. cyproheptadine and terfenadine). Total body clearance in adults is generally in the range of 5 to 12 ml/min/kg (for astemizole, brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, promethazine and triprolidine), while their elimination half-lives range from about 3 hours to about 18 days [cinnarizine about 3 hours; diphenhydramine about 4 hours; promethazine 10 to 14 hours; chlorpheniramine 14 to 25 hours; hydroxyzine about 20 hours; brompheniramine about 25 hours; astemizole and its active metabolites about 7 to 20 days (after long term administration); flunarizine about 18 to 20 days]. They also have relatively large apparent volumes of distribution in excess of 4 L/kg. In children, the elimination half-lives of chlorpheniramine and hydroxyzine are shorter than in adults. In patients with alcohol-related liver disease, the elimination half-life of diphenhydramine was increased from 9 to 15 hours, while in patients with chronic renal disease that of chlorpheniramine was very greatly prolonged. Little, if any, published information is available on the pharmacokinetics of these drugs in neonates, pregnancy or during lactation. The relatively long half-lives of a number of the older H1-receptor antagonists such as brompheniramine, chlorpheniramine and hydroxyzine suggest that they can be administered to adults once daily.

Astemizole↗

Studies on antituberculotic action of some phenothiazine derivatives in vitro.

Five phenothiazine derivatives (chlorpromazine, levomepromazine, diethazine, promethazine and chlorpromazine) sulphoxyde were tested for antimycobacterial activity. The growth of Mycobacterium tuberculosis, M. bovis and M. butyricum was inhibited by chlorpromazine practically at identical concentrations. The minimum inhibitory concentrations for M. tuberculosis were: chlorpromazine and levomepromazine, 10 microgram/ml; diethazine and promethazine 20 microgram/ml, whilst chlorpromazine sulphoxyde was ineffective even at a concentration of 100 microgram/ml. Chlorpromazine and promethazine exerted a measurable bactericidal activity on M. tuberculosis at 50 microgram/ml; total destruction of the organism and loss of acid fastness in part of the cells were shown at 300 microgram/ml. Preliminary studies, in mouse experiments phenothiazine derivatives were ineffective.

Antipsychotic Agents↗

Instrument flight performance under the influence of certain combinations of antiemetic drugs.

Two different combinations of antiemetic drugs were evaluated using a digital flight simulator. Drug treatments consisted of a lactose placebo, a combination of thiethylperazine (10 mg) and cimetidine (300 mg), and a combination which added promethazine (25 mg) to the two-drug combination. The performance effects of these combinations were evaluated on both a dual task (instrument flight task with the Sternberg Memory Scanning task) and a single task condition (Sternberg task only) for 3 h post drug ingestion. Analysis indicated a significant treatment effect on three of the six flight performance variables and that the three-drug combination, containing promethazine, was primarily responsible for the decrease in performance. Implications for operation in a radiation environment are that thiethylperazine and cimetidine will not cause significant performance decrements, but the addition of promethazine to those two drugs will significantly impair performance. The Sternberg task was sensitive to changes in workload.

Adult↗

Types of interaction of amphiphilic drugs with phospholipid vesicles.

Binding characteristics of nine amphiphilic drugs, which induce pulmonary phospholipidosis, to L-alpha-dipalmitoyl phosphatidylcholine (DPPC) vesicles were studied using fluorescence probes, 1,6-diphenyl-1,3,5-hexatriene and 1-anilino-8-naphthalene sulfonate (ANS) for hydrophobic and hydrophilic interactions, respectively. Drug binding to DPPC was quantitated using Scatchard analysis. The tested drugs bound to DPPC with different capacities. The order of binding capacity to hydrophobic site of DPPC using 1,6-diphenyl-1,3,5-hexatriene as fluorescence probe was promethazine greater than amiodarone greater than chlorpromazine greater than chloramphenicol greater than imipramine greater than trimipramine greater than propranolol much greater than chloroquine and chlorphentermine. Two binding affinities were evident for amiodarone, chlorpromazine, imipramine, trimipramine and promethazine. The order of binding strength at high affinity site was amiodarone greater than trimipramine greater than chlorpromazine greater than promethazine greater than imipramine. The order of drug binding capacity using ANS as fluorescence probe was chlorphentermine greater than trimipramine greater than propranolol much greater than amiodarone, chloroquine and chloramphenicol. Each of these drugs displayed a single binding affinity. Imipramine and chlorpromazine at 1 mM and higher concentrations showed intense fluorescence with ANS (5-20 microM) in the absence of DPPC indicating an interaction of these drugs with ANS. Chloroquine did not bind to either sites on DPPC. The binding of these drugs and their interactions with hydrophobic or hydrophilic sites of DPPC were correlated with their capacity to induce pulmonary phospholipidosis. These results indicate that not all the drugs which bind to DPPC in vitro induce phospholipidosis in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗

Treatment of severe motion sickness with antimotion sickness drug injections.

This report concerns the use of intramuscular injections of scopolamine, promethazine, and dramamine to treat severely motion sick individuals participating in parabolic flight experiments. The findings indicate that a majority of individuals received benefit from 50-mg injections of promethazine or 0.5mg-injections of scopolamine. By contrast, 50-mg injections of dramamine and 25-mg injections of promethazine were nonbeneficial. The use of antimotion drug injections for treating space motion sickness is discussed.

Dimenhydrinate↗

Temperature dependence of the binding of [3H]mepyramine and related compounds to the histamine H1 receptor.

The extent of the promethazine-sensitive binding of [3H]mepyramine to a washed fraction from guinea pig cerebellum was little altered between 4 degrees and 30 degrees. The dissociation of [3H]mepyramine from the H1 receptor was markedly temperature-sensitive. An Arrhenius plot of the variation of the dissociation rate constant, k-1, with temperature was linear over the range 37 degrees -15 degrees (E alpha = 160 kJ mole-1). The association rate constant, k1, was also temperature-dependent, and an Arrhenius plot approximated well to a straight line between 30 degrees and 15 degrees (E alpha = 112 kJ mole-1). The linear relationship may hold down to 4 degrees. A consequence of the slow dissociation at 4 degrees is that the IC50 for mepyramine inhibition of promethazine-sensitive [3H]mepyramine binding at 4 degrees is independent of the concentration of [3H]mepyramine if the cerebellar homogenate is first incubated with the nonradioactive antagonist before addition of the 3H-ligand. Promethazine binding showed a temperature dependence similar to that of mepyramine, and for both antagonists and for chlorpromazine the affinity constant was not greatly increased (equal to or less than a factor of 2) at 4 degrees compared with 30 degrees. Tripelennamine showed a more rapid dissociation at 4 degrees than the other antagonists. Mequitazine dissociated slowly at 4 degrees, but the affinity constant was lower at 4 degrees than at 30 degrees.

Aminopyridines↗

A comparison of some effects of three antimotion sickness drugs on nystagmic responses to angular accelerations and to optokinetic stimuli.

While the basic efficacy of antimotion sickness drugs is rooted in the reduction of motion sickness symptoms, adverse side effects are important practical considerations of their usage in aviation. This study examined the influence of three established antimotion sickness drugs on nystagmic eye movement responses to angular acceleration (whole-body movement) with vision either permitted or denied, and to optokinetic stimulation (visual field movement). Dimenhydrinate and promethazine hydrochloride, particularly at higher dose levels, reduced optokinetic nystagmus, thereby making less accurate the following ability of the eye. During whole-body motion in darkness, there was little placebo-drug difference in the vestibular response under alert conditions; under relaxed conditions, dimenhydrinate and promethazine hydrochloride produced significant declines in the vestibular eye movements. These same drugs also interfered with the ability of the individual to fixate adequately on a visual task during motion. Subjects who received a combination of promethazine plus d-amphetamine were able to suppress vestibular eye movements and maintain good visual fixation under the task condition. Thus, the effect of a drug on nystagmus may be a poor indicator of its value in preventing motion sickness. Moreover, assessments of antimotion sickness drugs for many practical situations should include, as a possible adverse side effect, the inability to maintain visual fixation during motion.

Acceleration↗

Stability of five liquid drug products after unit dose repackaging.

The room temperature stabilities of repackaged pentazocine hydrochloride injection, promethazine hydrochloride injection, haloperidol oral concentrate, phenytoin oral suspension, and isoetharine inhalation solution were determined. After being repackaged as unit doses in a Hy-Pod Hypodermic Syringe, Ped-Pod Oral Dispenser, or NebuJect Nebulizer Injector (all made by MPL, Inc., SoloPak Division), several containers of each drug were stored at room temperature. Isoetharine samples were assayed after 15 and 30 days, while samples of the other drugs were assayed after 90, 180, and 360 days. Also, separate samples of pentazocine and promethazine were stored at 40, 50, and 60 degrees C and were assayed after 15, 30, and 90 days. The long-range stabilities of the drugs stored at elevated temperatures were predicted using the Arrhenius technique. The results indicate that, under the conditions tested, isoetharine can be stored for at least 30 days at room temperature and promethazine, pentazocine, haloperidol, and phenytoin can be stored for at least a year, all with less than 10% loss in potency. Arrhenius data indicate that pentazocine injection probably would be stable at room temperature for much longer than the 360 days for which it was tested.

Drug Packaging↗

Prevention of experimental motion sickness by scopolamine absorbed through the skin.

A double-blind placebo-controlled study compared the efficacy of the antimotion sickness drug scopolamine when administered by oral or transdermal routes. A secondary purpose was to extend our bioassay involving fixed-dose combinations of the homergic drugs promethazine and ephedrine. After receiving 12 apparently identical drug-placebo treatments, eight normal male students were exposed to a slow rotation room to stressful accelerations generated by their execution of 40 head movements out of the plane of the room's rotation of 1 rpm and at 1-rpm increments until either symptoms were experienced (just short of frank motion sickness) or the 27-rpm ceiling on the test was reached. Efficacy of a drug was defined in terms of the placeborange and categorized as beneficial, inconsequential, or detrimental. The rank order of drugs with beneficial effects was: 1) promethazine 25 mg plus ephedrine 12.5 mg (86%); 2) scopolamine by mouth (75%); 3) scopolamine transdermally (63%); and 4) promethazine 12.5 mg plus ephedrine 25 mg (29%). The only detrimental effect was with scopolamine given orally. It is concluded that the advantages of the transdermal scopolamine, which include minimal side effects and prolonged effectiveness, deserve full exploitation.

Administration, Topical↗

Evaluation of two antiemetic agents during outpatient gynaecological surgery.

Thirty-two adult female ASA I patients (American Society of Anesthesiologists' grading) undergoing voluntary termination of pregnancy (VTP) under general anaesthesia were randomly divided into three groups. Patients received 0.6 mg/kg pentazocine intravenously five minutes prior to induction of anaesthesia along with either isotonic saline, or promethazine 0.5 mg/kg or metoclopramide 0.2 mg/kg. Anaesthesia was induced with intravenous thiopentone and maintained with nitrous oxide in oxygen and boluses of thiopentone. Vomiting and sedation were scored at the end of anaesthesia, one hour later and at the time of discharge. The mean vomiting score was comparable in the three groups. Though the mean dose of thiopentone used was significantly less in the promethazine group, the sedation scores and the duration of stay in the clinic were comparable in all the groups. It is concluded that promethazine and metoclopramide in the doses used are ineffective as antiemetic agents in outpatient gynaecological patients.

Abortion, Induced↗

[Microbiological assay of some phenothiazine derivatives using different strains of Bacillus subtilis].

This paper deals with the microbiological assay of chloropromazine, levomepromazine and promethazine, whose bacteriostatic power was measured in the diffusion test against four different strains of Bacillus subtilis. The four strains proved to be equally sensitive to solutions of phenothiazine derivatives containing more than 0.5 mg/ml. There was no difference between the four strains as referred to the median percentual error in the chlorpromazine determination. The median percentual error has been very high (around 20%) in the levomepromazine determination using Bacillus subtilis ATCC 9945. When promethazine was used against the four strains of Bacillus subtilis a very high percentual error (around 20%) has been obtained, therefore, they are not recommended for the promethazine determination.

Bacillus subtilis↗

[A case of life-threatening ventricular arrhythmias probably due to psychotropic drugs].

We present a case provoked life-threatening ventricular arrhythmias probably due to psychotropic drugs. The patient was a 55-year-old man who had previously twice operations of aortic valve replacement (AVR). The signs of cardiac failure were recurrently appeared from the end of 1991, and he had received promethazine and sulpiride for his depressive state. From cardiac catheterization, we planned his third AVR. The electrocardiographic (ECG) QTc interval was prolonged to 0.48 seconds on this admission. In March 1992 syncopal attack appeared suddenly, and his monitor ECG revealed frequent polymorphous ventricular tachycardia (VT) and Torsade de Pointes (Tdp). These arrhythmias stopped by emergent cardiac pacing. After discontinuing these psychotropic drugs, no ventricular arrhythmias appeared. Since the patient complained severe insomnia one month before operation, the diminished dose of psychotropic drugs (promethazine and levomepromazine) was readministered. Ten days after the operation, syncopal attack reappeared and his ECG recorded frequent VT and Tdp. During both syncopal attacks his serum potassium and magnesium were within normal limits. Two days later, he died from multi-organ failure. We concluded that life-threatening arrhythmias such as VT and Tdp might develop under the administration of mild psychotropic drugs (promethazine or levomepromazine), therefore, must better take a care of ECG changes in cases of using any psychotropic drugs.

Electrocardiography, Ambulatory↗