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PubMed1991

Phenothiazine-associated apnea in two siblings.

A two-month-old white girl presented to our facility with increasing lethargy and new onset apnea and bradycardia following a week of upper respiratory tract infection symptoms. The patient had been receiving a cough syrup containing promethazine hydrochloride during the previous five days, which was temporally correlated with the onset of lethargy and apneic episodes. Upon further investigation, it was discovered that the patient's older sibling also may have experienced phenothiazine-associated apnea after receiving a combination of meperidine hydrochloride, promethazine hydrochloride, and chlorpromazine as a premedication prior to an endoscopic examination. In addition to the presentation of these cases, the literature pertaining to phenothiazine-associated apnea is reviewed.

Apnea↗
PubMed1984

The effects of cimetidine and ranitidine on psychomotor function in healthy volunteers.

Single oral doses of cimetidine (400 mg), ranitidine (150 mg), promethazine (25 mg) or placebo were administered to 8 healthy volunteers in a double-blind study. Cimetidine and ranitidine did not cause any significant change in critical flicker frequency (c.f.f.), reaction time, pursuit rotor of the visual analogue scale scores for sedation. Promethazine significantly lowered c.f.f., prolonged reaction time and increased sedation when compared with placebo. It is concluded that in this study cimetidine and ranitidine had little, if any, effect on psychomotor function.

Adult↗
PubMed2002

TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243].

BACKGROUND: Agitated or violent patients constitute 10% of all emergency psychiatric treatment. Management guidelines, the preferred treatment of clinicians and clinical practice all differ. Systematic reviews show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments. Worldwide, current treatment is not based on evidence from randomised trials. In Brazil, the combination haloperidol-promethazine is frequently used, but no studies involving this mix exist. METHODS: TREC-Rio (Tranquilização Rápida-Ensaio Clínico [Translation: Rapid Tranquillisation-Clinical Trial]) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro, Brazil. TREC-Rio is a randomised, controlled, pragmatic and open study. Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed. TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible. Because the design of this trial does not substantially complicate clinical management, and in several aspects simplifies it, the study can be large, and treatments used in everyday practice can be evaluated.

Brazil↗
PubMedDate not supplied

Neonatal electroencephalographic patterns as affected by maternal drugs administered during labor and delivery.

Effects of drugs used during labor and delivery on spontaneous (resting) and evoked brain electrical activity were studied in 45 normal human newborns 48 hours after delivery. Mothers received either anesthesia (general plus local) alone (group 1), anesthesia plus meperidine (group 2), anesthesia plus meperidine and promethazine (group 3), or anesthesia plus meperidine and diazepam (group 4). Autoregressive spectral analyses and subsequent stepwise discriminant analyses showed no differences in spontaneous brain electrical activity in the infants related to the type of drugs given to the mother. However, when auditory stimuli were reduced in intensity from 80 dB to 63 dB, a significant effect was found in newborn brain electrical activity between the anesthetic-only drug pattern (group 1) and the drug patterns of anesthetics with meperidine (group 2) and anesthetics with meperidine plus diazepam (group 4). The data suggest that this effect diminishes in the presence of promethazine (group 3). Evoked responses to visual, tactile, and olfactory stimuli remained unaffected.

Anesthesia, Obstetrical↗
PubMed2002

A comparative evaluation of oral midazolam with other sedatives as premedication in pediatric dentistry.

The purpose of present study was to evaluate the safety and efficacy of orally administered midazolam in children as a sedative agent and to compare it with two other older agents, triclofos and promethazine. The study was conducted on ninety child patients requiring some short dental procedure. All the patients were with a good physical status (ASA-I). The ages ranged between 3 and 9 years. The patients were randomized into three study groups: Group 1, midazolam, Group II, triclofos and Group III, promethazine, on the basis of the drugs to be administered. After administration of drugs in each group, the effects were evaluated in terms of onset of action, sedative effect, ease of treatment completion, recovery time and postoperative amnesia. Midazolam was found to be the best drug among the three to produce conscious sedation in children.

Administration, Oral↗
PubMed2005

2-O-(2-hydroxybutyl)-beta-cyclodextrin as a chiral selector for the capillary electrophoretic separation of chiral drugs.

A new beta-cyclodextrin (beta-CD) derivative, 2-O-(2-hydroxybutyl)-beta-CD (HB-beta-CD), was successfully synthesized and used as chiral selector in capillary zone electrophoresis. Six chiral drugs, such as anisodamine, ketoconazole, propranolol, promethazine, adrenaline and chlorphenamine enantiomers, belonging to different classes of compounds of pharmaceutical interest were resolved. The chiral resolution (R(S)) was strongly influenced by the concentrations of the cyclodextrin derivative, the background electrolyte, and the pH of the background electrolyte. Under the conditions of 50 mmol/L tris-phosphate buffer at pH 2.5 containing 5 mmol/L 2-O-(2-hydroxybutyl)-beta-CD, the baseline separation of enantiomers, such as anisodamine (R(S) = 3.10), ketoconazole (R(S) = 3.01), propranolol (R(S) = 3.87), promethazine (R(S) = 3.63), adrenaline (R(S) = 3.42) and chlorphenamine (R(S) = 2.96), could be achieved.

Adrenergic alpha-Agonists↗
PubMed1985

Age-related osteopenia: evidence for an intrinsic defect of bone resorbing cells and a possible treatment.

B6D2F1 and B6AF1 mice of various ages were given sublethal or lethal doses of X radiation and injected with marrow and/or spleen cells from young, mature, or old syngeneic donors. Four to five months later they were killed and ash weights were determined on femurs, sacrum, and ilium. It was found that large numbers of marrow cells (i.e., greater than 25 X 10(6] and/or spleen cells (greater than 50 X 10(6] from old mice retarded the growth of bone in young hosts and induce loss of bone mass in mature recipients, spleen cells from young donors consistently prevented the loss of bone mass normally seen in aging mice, and the thymus and T cells did not appear to play a significant role in bone resorption and remodeling. These observations suggested that in aging mice loss of bone mass is caused by an intrinsic defect in a hematopoietic cell population, perhaps the macrophage/osteoclast or their common precursor, which results directly or indirectly in increased bone resorption. On this basis, promethazine HCl, an inhibitor of macrophage metabolism and phagocytosis, was added to the drinking water (1.0 to 4.0 mg/dl) of aging mice. Four to five months later it was found that bone mass was significantly greater in the groups given promethazine than in the age and weight matched controls.

Aging↗
PubMed2000

Antihistamines and aircrew: usefulness of fexofenadine.

INTRODUCTION: The aim of this study was to establish whether fexofenadine hydrochloride, an antihistamine, modulates daytime sleepiness or performance. METHODS: The effects of fexofenadine (120, 180, and 240 mg) on digit symbol substitution, tracking, and vigilance tasks, and on objective (multiple sleep latency test) and subjective sleepiness, were studied in six healthy volunteers (two males, four females, aged 20-34 [mean 26.5] yr) from 1 h pre-ingestion to 8 h post-ingestion. The study was placebo-controlled and double-blind with a six-way cross-over design. The centrally acting antihistamine, promethazine (10 mg), was used as an active control to confirm the sensitivity of the experimental procedures. RESULTS: There were no changes in performance or sleepiness with any dose of fexofenadine at any time, compared with placebo. Promethazine, compared with both placebo and fexofenadine, impaired performance on the digit symbol substitution task (2.5 h post-ingestion), vigilance task (2.5-5h post-ingestion) and tracking task (2.5-3.5 h post-ingestion), increased objective sleepiness (1.5-2.5 h post-ingestion) and subjective sleepiness (1.5-8h post-ingestion). CONCLUSION: Consideration may be given to the clinical use of currently licensed doses of fexofenadine (120-180 mg) by individuals involved in skilled activity. Fexofenadine may be potentially useful for aircrew.

Adult↗
PubMed2002

Central effects of cinnarizine: restricted use in aircrew.

HYPOTHESIS: Our aim was to establish the effects of cinnarizine, a drug used for the treatment of motion sickness, on daytime sleepiness and performance. METHODS: The effects of cinnarizine (15, 30, and 45 mg) were assessed on digit symbol substitution, tracking, vigilance, and on subjective and objective (daytime sleep latencies) sleepiness in six healthy volunteers between the ages of 20 and 34 yr (mean 27 yr) from 1.0 h prior to ingestion to 8.0 h after ingestion. The study was placebo-controlled and double-blind in a six-way, cross-over design. Promethazine (10 mg) was used as an active control. RESULTS: No effects of 15 mg cinnarizine were observed on performance. Sleep latencies were reduced at 3.5 and 5.0 h after ingestion, and the subjects as a group reported increased sleepiness at 5.0 and 6.5 h after ingestion. With 30 mg cinnarizine there was evidence of impaired performance at 5.0, 6.5, and 8.0 h after ingestion. Sleep latencies were not reduced, but the subjects as a group reported increased sleepiness 5.0 h after ingestion. With 45 mg cinnarizine there was evidence of impaired performance 5.0 h after ingestion. Sleep latencies were reduced at 5.0 and 6.5 h after ingestion, and the subjects as a group reported increased sleepiness 6.5 h after ingestion. Promethazine (10 mg) shortened sleep latencies from 2.5 to 5.0 h after ingestion, and the subjects as a group reported increased sleepiness overthis period. CONCLUSION: Cinnarizine is not free of central activity over the usual therapeutic dose range of 15 to 30 mg. It is contraindicated for motion sickness in aircrew involved in the control of aircraft. Caution should be exercised in the use of the drug by other aircrew who may be involved in tasks which demand continued attention.

Adult↗
PubMed1992

Effect of H1 receptor blockade on the early and late response to cutaneous allergen challenge.

We investigated whether cutaneous antigen-induced inflammatory cell infiltration and mediator release were modified by H1 receptor antagonists. Three chemically unrelated antihistamines (cetirizine, promethazine and chlorpheniramine) were tested in three groups of allergic subjects in a double-blind, crossover design. Chamber fluids were collected for 12 hr and histamine release, prostaglandin D2 production and cellular infiltration were quantified. Cetirizine significantly decreased late leukocyte migration into antigen-challenged chambers: eosinophils by 68% (P less than .04), basophils by 64% (P less than .04) and neutrophils by 72% (P less than .04), whereas mononuclear cells were not significantly affected. No alteration in the numbers of peripheral blood leukocytes or eosinophils occurred while on cetirizine treatment, suggesting that the decrease in inflammatory cells during the late phase reaction in the skin is not secondary to alterations in the peripheral leukocyte pool. In contrast, neither promethazine nor chlorpheniramine induced any significant alteration in inflammatory cell infiltration. All three antihistamines caused significant inhibition of the immediate reaction to antigen without any significant alteration in late phase reaction cutaneous reactivity. None of the three antihistamines caused any significant alteration in histamine or prostaglandin D2 levels. Thus, cetirizine may be an antihistamine uniquely capable of downregulating the late phase reaction inflammatory cell milieu without altering either early or late mediator production. The mechanisms involved and the clinical relevance of these findings remain to be explored.

Allergens↗
PubMedDate not supplied

An assessment of cadmium toxicity on cytochrome P-450 and flavin monooxygenase-mediated metabolic pathways of dimethylaniline in male rabbits.

Cadmium is an environmental pollutant and its effect on the in vitro metabolism of N,N-dimethylaniline (DMA) using male rabbits was investigated. Activities of cytochrome P-450 and FMO-dependent monooxygenases were studied using hepatic microsomes. Following CdCl2 (i.p.) administration (6 mg/kg/day for 6 days), both DMA-N-oxidation and DMA-N-demethylation decreased by 86%. The effects of CdCl2 on the phenobarbitone (PB)-induced form of P-450 were also studied. Intraperitoneal pretreatment of rabbits with PB (5 mg/kg/day for 5 days) increased N-demethylation by 82%, while N-oxidation decreased by 49%. Both reactions decreased significantly on additional treatment with CdCl2. Promethazine (5 mg/kg/day for 5 days) did not produce any change in the activities of either enzyme. The enzymes remained unaffected by CdCl2 treatment in promethazine-pretreated animals thus confirming its role as a hepatoprotective agent.

Aniline Compounds↗
PubMedDate not supplied

Action of stobadine on respiratory and vascular smooth muscle in vivo: evidence for histamine receptor antagonist activity.

The effect of stobadine on respiratory smooth muscles, blood pressure, heart rate and gastric acid secretion was studied and compared with the action of other antihistamines in vivo. Stobadine, as diphenhydramine, dithiadene and promethazine, but in contrast to cimetidine and ranitidine, prevented histamine from producing bronchospasm both after i.v. and oral administration. Based on the potency of its pharmacological action, diphenhydramine had a lower bioavailability after oral administration than the other antihistamines. Both cimetidine and ranitidine reduced the gastric acid secretion while stobadine was ineffective in this respect. None of the drugs studied antagonized histamine in reducing blood pressure, but all of them, with exception of promethazine and diphenhydramine, reduced mean arterial blood pressure. The results suggest that the action of stobadine on the respiratory and vascular smooth muscle effects is intermediate between that of diphenhydramine and dithiadene. In view of the minimal effect of stobadine on gastric acid secretion and its marked activity on airways, it is concluded that this drug predominantly acts on H1-receptors.

Airway Resistance↗
PubMed1989

[Premedication in ENT operations under local anesthesia].

Midazolam 15 mg orally, was compared with the combination of pentobarbital, promethazine, opial and scopolamine as premedication for ear surgery under local anaesthesia in the first of a series of three double blind clinical trials. Sedation, pain sensation and appreciation by patient and surgeon alike were in favour of the pentobarbital regime. Anxiolysis was the same for both regimes. The number of actions needed to administer the medication was basically lower for midazolam. Comparing in a similar, second study midazolam 15 mg with higher doses of 20 mg and 25 mg, the results were satisfactory with the highest dose. Pain during the administration of the local anaesthesia was felt in 16% of the patients. Adding 10 mg morphine intramuscularly in a third study did not prove to diminish the percentage of patients with pain complaints. It is concluded that 25 mg midazolam taken orally 45 minutes pre-operatively is a satisfactory premedication for ear surgery and less troublesome than the pentobarbital, promethazine, opial, scopolamine we used before. In day-care surgery this short acting premedication in our opinion is quite useful.

Adolescent↗
PubMed1986

Some behavioral effects of histamine H1 antagonists in squirrel monkeys.

Graded dose of the histamine H1 antagonists tripelennamine (0.1-3.0 mg/kg), promethazine (0.1-3.0 mg/kg), diphenhydramine (0.3-10.0 mg/kg) and chlorpheniramine (0.3-1.7 mg/kg) increased rates of nonsuppressed responding under a second-order schedule of food presentation to a maximum beyond which responding was increased less or decreased. In contrast, the H2 antagonist, cimetidine, had no effect or decreased responding at the highest doses studied (56.0-100.0 mg/kg). Intermediate doses of tripelennamine, diphenhydramine and promethazine also increased rates of food-maintained responding that were suppressed by electric shock. Maximal increases in rates of suppressed responding were comparable to those produced by effective doses of chlordiazepoxide (3.0-10.0 mg/kg). Under identical conditions, clozapine (0.1-1.0 mg/kg) increased responding to a lesser extent, and d-amphetamine (0.01-0.3 mg/kg) and cimetidine (3.0-100.0 mg/kg) either did not increase or, at the highest doses, only decreased rates of suppressed responding. Doses of tripelennamine and diphenhydramine that increased rates of nonsuppressed and suppressed responding also maintained self-administration in cocaine-trained squirrel monkeys under a second-order schedule of i.v. injection. Rates and patterns of responding maintained by tripelennamine and diphenhydramine were comparable to those maintained by cocaine and d-amphetamine under identical conditions. The results show that histamine H1 antagonists can have pronounced rate-increasing effects on nonsuppressed and suppressed behavior, and that they can serve as reinforcers in monkeys. These effects occur at doses that probably are greater than those required to saturate H1 sites of action in central nervous system and may not be mediated solely through histaminic mechanisms.

Animals↗
PubMed1988

[The effect of neuroleptics and neuroleptic/analgesic combinations on the sensitivity to seizures in mice].

UNLABELLED: Combinations of neuroleptic and morphine-like analgesic drugs are used alone for minor surgery or as anesthetic premedication. While morphine-like analgesics given in the therapeutic dose range show anticonvulsant properties, there is evidence indicating that neuroleptics are rather proconvulsant. This study was performed to investigate the influence of the most widely used combinations pethidine/promethazine and fentanyl/droperidol on seizure susceptibility. METHODS: Thresholds for convulsions induced by electroshock and pentetrazole infusion were used as models for seizure susceptibility. The drugs tested were injected s.c. 20-30 min before determination of the seizure threshold. RESULTS: Pethidine/promethazine and fentanyl/droperidol reduced the susceptibility to seizures induced by electroshock. Promethazine and droperidol alone elevated the threshold only at the highest doses used (2 mg/kg and 2.5 mg/kg respectively). Promethazine, whether given alone or in combination with pethidine, showed no effect on the threshold for pentetrazole-induced convulsions. Droperidol alone lowered the threshold for pentetrazole-induced clonic convulsions only at the lowest dose used (0.625 mg/kg), but lowered that for tonic convulsions at all doses studied (0.625, 1.25 and 2.5 mg/kg). The combination of fentanyl and droperidol lowered the threshold for both clonic and tonic convulsions at the two lower doses (12.5 micrograms/kg fentanyl + 0.625 mg/kg droperidol and 25 micrograms/kg fentanyl + 1.25 mg/kg droperidol). Only the highest dose studied (50 micrograms/kg fentanyl + 2.5 mg/kg droperidol) showed no significant effect. CONCLUSION: Pethidine and fentanyl show anticonvulsant properties in mice, but it is evident from our results that there is some interaction between their combinations with neuroleptics and seizure susceptibility. This is more pronounced with the combination fentanyl/droperidol in the model of pentetrazole-induced convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1987

Noninvasive measurement of gastric emptying in obstetric patients.

An epigastric impedance technique was used to measure gastric emptying in nonpregnant women, women in the third trimester of pregnancy, and women within 60 min of delivery. The basis of the technique is the increase in epigastric impedance after the ingestion of a nonionic fluid. The subsequent decline in impedance is used as a measure of gastric emptying. The impedance epigastrograph used consisted of a four-electrode array (two source, two detector) that was applied over the epigastrium. The method was sufficiently sensitive to measure the effects of pregnancy, labor, and narcotics on gastric emptying. There was no difference in the rate of gastric emptying between pregnant and nonpregnant females. Labor appeared to cause a significant delay in gastric emptying; the mean +/- SEM time taken for the gastric volume to decrease to 50% (T0.5) was 7.2 +/- 0.6 min during pregnancy and 13.0 +/- 1.9 min in the immediate postpartum period. However, the principal factor associated with the delay in gastric emptying in the group studied within 60 min of delivery was probably the use of meperidine and promethazine, because there was a significant difference (P less than 0.05) between subjects who received meperidine and promethazine during labor and those in another group who had received either no analgesia or extradural analgesia, the T0.5 values for the two groups being 18.2 +/- 4.0 and 10.3 +/- 1.4 min, respectively.

Drinking↗
PubMed1986

Turpentine-induced acute inflammatory response in Gallus gallus: oedema, vascular permeability and effects of non-steroidal anti-inflammatory drugs.

Turpentine-induced acute inflammatory responses in chicks were studied experimentally. Foot pad oedema was measured using a plethysmograph. Skin vascular permeability was evaluated using the Evans blue technique. Turpentine injury induced a typical biphasic response when the two parameters of the inflammatory reaction were studied. Some unexpected alterations of the turpentine-induced inflammatory response were seen when chicks received non-steroidal anti-inflammatory drugs. Pretreatment with promethazine, phenylbutazone, methysergide and indomethacin resulted in a decrease in foot oedema. An inhibitory effect upon vascular permeability was found when promethazine, phenylbutazone and indomethacin were used. Methysergide did not inhibit the increase in vascular permeability of the skin. Possible mechanisms are discussed.

Animals↗
PubMed1986

Memory facilitation by histamine.

The immediate posttraining intracerebroventricular administration of histamine (1 or 10, but not 0.1 or 100, ng/rat) facilitated retention test performance of step-down inhibitory avoidance behavior measured 24 hr later, in rats. The effect was antagonized by the simultaneous administration of both promethazine (1000 ng/rat) and cimetidine (1000 ng/rat), but not by either promethazine or cimetidine given alone. The antagonists had no effect of their own on behavior. The findings show that histamine has an extraordinarily powerful effect on memory processes, but do not necessarily suggest that this substance has a physiological role in memory modulation.

Animals↗