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[Advances in the pharmacotherapy of osteoporosis].

In the pharmacotherapy of osteoporosis administration of calcium, small amounts of vitamin D and fluorides still is the basic treatment. Thyrocalcitonin can be also administered, recently also in the form of a nasal spray. It does not only prevent reabsorption of bone but has also an analgetic effect. In the treatment of postmenopausal osteoporosis we use conjugated oestrogens in cyclic preparations with gestagens. Biphosphonates prevent bone resorption but also apposition of the mineral. As to new preparations, Ipriflavone and TGF-beta seem most promising, moreover, there is the perspective of the use of other preparations: small doses of PTH, tamoxifen and raloxifen, promethazine and vitamin K. The author emphasizes the comprehensive character of therapy and the urgent necessity to initiate it early.

Animals↗

Allergy skin testing of children.

Skin tests are important aids in the management of patients with inhalant allergy. Their usefulness will be increased if these basic principles are kept in mind: (1) Scratch test should be sufficiently deep, (2) Antigen extracts used for intradermal tests should be fresh enough to insure their activity, (3) Two control tests should be used each time tests are done, (4) Hydroxyzine and promethazine may diminish skin reactivity; therefore, negative skin tests should not be relied upon until repeated in the absence of such medication, and (5) Skin tests for food allergy are quite unreliable, whether positive or negative. Food allergy is best studied by means of elimination trial diets.

Age Factors↗

[Histamine-liberating effect of antihistaminics on the isolated rat mast cells].

Research Allergological Laboratory of the USSR Academy of Medical Sciences and Laboratory of Pharmacology, S. Ordzhonikidze Research Chemico-Pharmaceutical Institute, Moscow. Among the tested new antihistaminic drugs (quinuclidine derivatives) quinuclidyl-3-(O-tolyl) carbinol possessed histamine releasing action (HRA) on the isolated rat mast cells. In used concentrations (up to 0.4 mmol) all phenothiazines (promethazine, phenethazine, chlorpromazine, methylene blue) had HRA. There was no correlation between the HRA and the antihistaminic activity of the tested drugs. Histamine release induced by antihistaminic drugs and a steep dose-response curve, was produced at low temperature and was not inhibited under conditions of inhibition of energy-dependent stage of 48/80-induced histamine release. It was concluded that the tested antihistaminic drugs which had HRA were non-selective histamine releasers.

Animals↗

Effects of routine premedication for cardiac catheterization on sedation, level of anxiety and arterial oxygen saturation.

OBJECTIVE: To assess the efficacy and side effects of routine premedication in patients undergoing cardiac catheterization procedures in a tertiary cardiac care institute. The criteria used included: arterial hemoglobin oxygen saturation (%SaO2), level of sedation and level of anxiety before and after the procedure. Overall patient satisfaction was also quantified. DESIGN: Sixty-two adult patients scheduled for cardiac catheterization procedures were recruited for the study. They were premedicated with one of several premedication regimens: oral diazepam 5 to 10 mg; oral lorazepam 1 mg; oral diazepam 10 mg+oral promethazine 25 mg; or oral diazepam 10 mg+oral diphenhydramine 25 mg. No attempt was made to control the premedication the patients received; it was ordered by each patient's cardiologist according to personal preference. Patients underwent pulse oximetry and evaluation of sedation, anxiety and level of satisfaction before and after cardiac catheterization. RESULTS: All patients tested had values for mean precatheterization %SaO2 above 92%. No patient had postcatheterization %SaO2 readings below that defined as indicating clinically significant hypoxemia (%SaO2 less than 90%). Patients were awake or lightly sedated before and after cardiac catheterization. Thirteen per cent of patients suffered from high levels of anxiety before, and 16% during, cardiac catheterization. Twenty-three per cent of patients reported being dissatisfied with the premedication before, and 10% of patients reported being dissatisfied during, cardiac catheterization. CONCLUSIONS: Clinically significant hypoxemia and oversedation are not problems for most patients given the types and doses of precatheterization medication used in the study population. The premedication schedules followed in the study failed to provide satisfaction and anxiolysis in a significant number of those studied.

Aged↗

Inhibitory effect of epinastine on bronchoconstriction induced by histamine, platelet activating factor and serotonin in guinea pigs and rats.

Effects of epinastine ((+/-)-3-amino-9,13b-dihydro-1H-dibenz[c,f]imidazo[1,5-a]azepine hydrochloride, WAL 801 CL, CAS 80012-43-7) and reference drugs on bronchoconstriction induced by histamine, platelet activating factor (PAF) and serotonin were studied in guinea pigs and rats. Oral administration of epinastine resulted in a potent inhibition on bronchoconstriction induced by all three bronchoconstrictor agents, and especially, an inhibitory effect on histamine-induced response was remarkable. The effect of epinastine was stronger than that of ketotifen in inhibiting the responses induced by both PAF and serotonin. However, the extent of inhibition in the latter was less remarkable than that seen after histamine. Azelastine was 1.36-4.57 times less potent than epinastine in inhibiting the bronchoconstriction induced by either bronchospasmogen. Although promethazine displayed inhibitory effects on the responses induced by histamine, PAF and serotonin, the inhibiting potency was distinctly inferior to that of epinastine.

Airway Resistance↗

[Which sedation for minor trauma surgery in children?].

Children under 6 often show marked anxiety and physical pain during laceration repair. If locally infiltrated anesthetics usually give a good control of physical pain, they have no effect on anxiety and restlessness for which several medications are available for conscious sedation. Continuous nitrous oxide, intramuscular sedative "cocktail" with meperidine-promethazine-chlorpromazine or intravenous fentanyl have various inconveniences and therefore are not ideal for this purpose. By contrast, Midazolam, a short acting watersoluble benzodiazepine with anxiolitic, hypnotic and anterograde amnestic effect, appears to be a safe and effective treatment when given orally or intranasally for alleviating anxiety in under 6 year-old out-patient in emergency department; its rectal administration appears less effective and needs further studies before to be routinely used.

Benzodiazepines↗

[Intravenous midazolam for sedation in epidural anesthesia].

30 cases receiving epidural anesthesia for lower extremities and abdominal surgery were selected in this study. Their physical status and average age were ASA I or II and 41 +/- 10.0 years old. Premedication included intramuscular injection of pethidine, atropine and promethazine. Epidural anesthesia was accomplished with 15 ml 2% lidocaine with epinephrine (1:80,000). After the stabilization of vital signs, the patients were put asleep by 0.1 mg/kg of midazolam intravenously. They were then evaluated by the sedative, cardiovascular, respiratory and recovery effects of intravenous midazolam in epidural anesthesia. The results were as follows: The patients receiving IV midazolam averagely fell asleep in 61.6 +/- 20.5 seconds and maintained asleep for 55.4 +/- 12.7 minutes. Pain on injection was not noted in these cases. Cardiovascular parameters revealed midazolam with general depression on systolic pressure (17.4 +/- 7.3%), diastolic pressure (13.4 +/- 8.4%), mean arterial pressure (12.7 +/- 7.0%), heart rate (10.9 +/- 7.2%), stroke volume (13.7 +/- 8.9%) and cardiac output (18.4 +/- 7.0%) respectively. The peak depression reached around 10 minutes after drug administration. Respiratory parameters dropped with SaO2 (1.1 +/- 1.6%) and respiratory rate (9.7 +/- 5.7%) and fell into trough after 5 minutes of drug administration. Although all the above parameters measured were statistically significant, they were of no clinical importance that required further management. No case had delirium, anxiety and vomiting in the recovery period. Conclusively, patients receiving epidural anesthesia with supplement of intravenous midazolam provides a good sedative effect. Clinically, there was less severe untowards reaction either in cardiovascular or respiratory systems. Smooth and stable recovery was also noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mild pregnancy-induced hypertension at term.

It was elected to induce labor in Mrs AB after excluding any evidence of severe preeclampsia. Both the fetus and Mrs AB were evaluated. The history, physical examination, and laboratory results were all within normal limits for Mrs AB. Her fetus was appropriately grown for gestational age with an estimated fetal weight of 3,200 g. There was ample but not excessive amniotic fluid noted clinically and by sonography. An amniocentesis to document fetal lung maturation was not done. Two hours after commencing parenteral magnesium sulfate therapy, an oxytocin induction of labor was begun. Fetal well-being was assessed using continuous external electronic monitoring of the fetal heart rate and uterine contractions. Three hours after the induction was started, the cervix was completely effaced and 3 cm dilated. The fetal head was at O station. At this time, the fetal membranes were ruptured and clear amniotic fluid was noted. An internal uterine pressure catheter was inserted, and a fetal scalp electrode applied. The patient received 75 mg of meperidine and 25 mg of promethazine intramuscularly at this time. Five hours after commencing the induction of labor, both mother and fetus were tolerating the labor well. The cervix was 7 cm dilated, and the fetal head was at +2/+5 station. The oxytocin induction was discontinued and another 75 mg dose of meperidine was administered. Blood pressure readings between 150/100 mm Hg and 140/98 mm Hg were recorded throughout labor. Urine output exceeded 150 mL/h. The patient delivered a 3,070-g male infant approximately 9 hours after the start of the induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pharmacological activities of chlorpromazine involved in the inhibition of tumour necrosis factor production in vivo in mice.

Chlorpromazine (CPZ) was shown to inhibit tumour necrosis factor (TNF) production in vivo. Several drugs sharing one of the various pharmacological activities of CPZ were tested in endotoxin-treated mice. It was found that alpha-blockers (prazosin, idazoxan, phenoxybenzamine), antiserotoninergics (methysergide, methergoline) and antihistamine (chlorpheniramine, promethazine) also inhibited TNF production indicating that the effectiveness of CPZ in protecting from endotoxin shock is due to its multiple pharmacological activities.

Adrenergic alpha-Antagonists↗

Treatment of nausea and vomiting in pregnancy.

The nausea and vomiting that often accompany early pregnancy may be ameliorated if the patient eats small portions of food at frequent intervals, increases the amount of carbohydrates and decreases the amount of fat, and avoids bothersome food odors. When these strategies fail, antiemetic drugs such as pyridoxine and phosphorated carbohydrate solution may help, as well as doxylamine, promethazine or trimethobenzamide. When drugs are considered for use in pregnant patients, the safety of the patient and the fetus must always come first.

Decision Trees↗

Intravenous regional anesthesia in the treatment of forearm and wrist fractures and dislocations in children.

OBJECTIVE: To evaluate the efficacy and safety of intravenous regional anesthesia in the treatment of unilateral closed fractures and dislocations of forearm or wrist in children. DESIGN: A prospective study over 6 years. SETTING: The study was undertaken in the well-equipped emergency department of a community general hospital for ambulatory patients. PATIENTS: One hundred and thirty-nine children between the ages of 4 and 18 years with unilateral closed fractures and dislocations of forearm or wrist. INTERVENTION: All children received premedication with a combination of meperidine and promethazine (0.5 mg/kg intramuscularly) and regional upper limb anesthesia with 0.5% lidocaine solution (3 mg/kg intravenously) after inflation of an arm tourniquet. MAIN OUTCOME MEASURES: The relief of pain, allowing closed reduction with intravenous regional anesthesia, and the incidence of complications. RESULTS: All patients had complete relief of pain allowing successful closed reduction in 133 patients (96%); tourniquet pain occurred in 10 patients (7%). There were no symptoms of lidocaine toxicity. There were no neurovascular or compartment syndrome complications. CONCLUSIONS: Intravenous regional anesthesia for the treatment of fractures and dislocations of forearm and wrist in children was found to be simple, safe and effective.

Adolescent↗

Functional endoscopic sinus surgery under local anaesthesia: possibilities and limitations.

Functional endoscopic sinus surgery under local anaesthesia with one single intramuscular injection of systemic premedication (pethidine and promethazine) and careful local preparation (decongestive nose drops, cocaïne application and lidocaine infiltration). It is well tolerated and accepted in 95% of the patients. Blood loss is minimal and pain during the operation is rare. Major and minor orbital and intracranial complications were not seen. Local anaesthesia with this kind of surgery offers many advantages and is preferable to general anaesthesia when possible.

Adjuvants, Anesthesia↗

Comparative analysis of the cardiotoxicity proclivities of second generation antihistamines in an experimental model predictive of adverse clinical ECG effects.

Terfenadine and astemizole belong to the second generation histamine H1 antagonists and are widely prescribed for allergic and upper respiratory diseases. The popularity of the newer H1 antihistamines is due to their ability to provide relief from allergic symptoms without the undesirable side effect of sedation commonly associated with first generation H1 receptor antagonists such as diphenhydramine and promethazine. Recent clinical evidence that the second generation histamine H1 antagonists terfenadine and astemizole have the potential for inducing life threatening ventricular arrhythmias has raised questions as to whether other drugs in this class have similar cardiotoxic potential. The objective of this study was to evaluate and compare the arrhythmogenic potential of a series of second generation antihistamines in a quantitative experimental model predictive of adverse ECG effects in man. Antihistamines were given intravenously and electrocardiographic (ECG) and cardiovascular parameters (blood pressure and heart rate) were measured. The ECG wave form was analyzed to determine QTc interval, PR interval, QRS interval and heart rate. To determine the relative cardiotoxic potential of the antihistamines, the lowest dose producing significant prolongation of the QTc interval was compared with the dose required to inhibit by 50% the peripheral bronchospasm elicited by histamine at 10 micrograms/kg i.v. (antihistamine ED50). The second generation antihistamines studied were astemizole (CAS 68844-77-9), carebastine (CAS 90729-42-3), cetirizine hydrochloride (CAS 83881-52-1), ebastine (CAS 90729-43-4), norastemizole (CAS 75970-99-9), terfenadine (CAS 50679-08-8) and terfenadine carboxylate (CAS 83799-24-0). The second generation antihistamines astemizole, ebastine and terfenadine produced pronounced dose-dependent QTc interval prolongation effects. These arrhythmogenic effects occurred at doses that were between 1 and 4 times their respective peripheral antihistamine doses. These drugs produced significant disruption of the ECG wave form including large amplitude, morphologically aberrant T-waves and, in some cases, torsades de pointes-type arrhythmias. In contrast, terfenadine carboxylate (100 mg/kg i.v.), norastemizole (20 mg/kg, i.v.) and carebastine (50 mg/kg, i.v.), the major metabolites of terfenadine, astemizole and ebastine, were largely devoid of adverse ECG effects. Similarly, cetirizine (20 mg/kg, i.v.) was also found to not alter ECG or cardiovascular function. These findings demonstrate that terfenadine, astemizole and ebastine exhibit significant arrhythmogenic effects including QTc interval prolongation, bradycardia and distortion of the ECG morphology in the guinea pig. The relative cardiotoxicity of these antihistamines based on the separation of antihistamine activity and adverse ECG effects was similar for terfenadine and astemizole, but slightly less for ebastine. In this model carebastine, cetirizine, loratadine, norastemizole and terfenadine carboxylate are devoid of QTc prolongation effects. Given the structural similarity of terfenadine and ebastine it is not surprising that these drugs produce significant cardiotoxicity in this animal model. Taken together, these results indicate that the ability to cause QTc interval prolongation and the proclivity for producing arrhythmias is not a class effect and is seen only with some second generation nonsedating antihistamines.

Animals↗

Biochemical and clinical assessment of histamine blockade.

The effects of antihistamines on biochemical stress indicators and on psychomotor and physiological functions were studied in 60 healthy patients receiving in a randomized, double-blind study either 25 mg promethazine, 150 mg ranitidine, both drugs or placebo (n = 15 in each group). Different aspects of the premedications were evaluated by determining various hormone, neurotransmitter and neurotransmitter metabolite levels in blood and cerebrospinal fluid, and subjectively using questionnaires concerning the quality of the preoperative night's sleep and visual analogue scales, and objectively by measuring changes in blood pressure and heart rate, impairment of vigilance with the Maddox wing apparatus and the critical flicker fusion threshold test. The relationships between the subjective assessments and the biochemical stress indicators were also investigated. There were no differences between the study groups in the quality of the preoperative night's sleep, estimated fear, apprehension or dizziness, or in the various physiological stress indicators. Only few statistically significant correlations were found between the subjective and biochemical assessments. It is concluded that histamine receptor antagonists used in clinical doses do not interfere with the biochemical, clinical preoperative, and physiological responses.

Adult↗

Esmolol for hypotensive anesthesia in middle ear surgery.

This study was performed to investigate the efficacy of esmolol, an agent used in hypotensive anesthesia for middle ear surgery. We compared 20 ASA I-II patients to 20 controls in whom we administered routine anesthesia. All patients were premedicated with intramuscular 0.05 mg/kg atropine, 1 mg/kg pethidine and 25 mg promethazine. Anesthesia was induced with 0.004 mg/kg fentanyl and 5 mg/kg thiopental sodium. Succinylcholine 1.5 mg/kg was administered to facilitate intubation. Isoflurane, nitrous oxide, oxygen, 0.08 mg/kg vecuronium bromide and controlled ventilation were used for anesthetic maintenance. Before the controlled hypotensive period, nitrous oxide was discontinued and an esmolol infusion started. We registered hemodynamic values (via noninvasive and invasive radial artery cannulation), central venous pressure, electrocardiography, body temperature, end-tidal carbon dioxide levels, periferal oxygen saturation, and arterial blood gas analysis. Mean infusion rate of esmolol was 330 +/- 10 micrograms/kg/min. We found significant decreases in systolic blood pressure (28.7%), mean blood pressure (26.5%) and diastolic blood pressure (33.4%). The operative field was virtually bloodless. Hemodynamic values recovered to normal or to within -12.45% of normal at the end of intravenous esmolol infusion. During the postoperative period, no side effects were observed. In conclusion, esmolol is an appropriate hypotensive agent for patients undergoing middle ear surgery under hypotensive anesthesia because it yields no side effects, it is easy to control administration and it provides the desired degree of hypotension without complications.

Adrenergic beta-Antagonists↗

Augmenting sedation with hypnosis in drug-dependent patients.

The successful use of conscious sedation in patients physically dependent on centrally acting drugs is problematic for the dental anesthesiologist because of the concomitant development of tolerance to standard sedative agents. Dosage requirements necessary to adequately sedate these patients are often higher than recommended and carry an increased risk of drug overdose. The following report summarizes our experience with 18 drug-dependent patients in whom hypnosis was employed in conjunction with a standard sedation regimen. Attempts to complete various dental procedures while employing sedation alone on these patients had previously failed. All patients exhibited highly fearful or phobic behavior toward dental treatment as assessed by the Corah Dental Anxiety Scale. If an intravenous sedative regimen (midazolam or diazepam plus methohexital) was employed, hypnotic induction preceded the administration of the sedative drugs. If an intramuscular sedative regimen was employed (meperidine plus promethazine), the hypnotic induction took place after drug administration. With the combined hypno-sedative approach, treatment outcomes were judged to be good or excellent in 11 of 18 patients. Interestingly, in five of seven patients for whom the treatment outcome was rated poor or fair, the possibility of tolerance or cross-tolerance existed between a drug being abused and the sedative regimen. In contrast, this possibility existed in only 1 of 11 patients with good or excellent treatment outcomes. We conclude that hypnosis can augment the effects of sedation in this patient population. However, it is also important to choose a sedative regimen where tolerance is unlikely to exist.

Adolescent↗

Gruppo Italiano Ricerca Dermatiti da Contatto ed Ambientali Italian Multicenter Study of Allergic Contact Photodermatitis: epidemiological aspects.

A total of 1,050 patients with histories and clinical pictures suggestive of photoallergic contact dermatitis were seen. All the patients underwent photopatch tests with haptens proposed by the Gruppo Italiano Ricerca Dermatiti da Contatto plus other substances suggested by each patient's history. Two hundred fifty-nine patients (24.6%) were positive to at least one test substance of the standard series or to substances added. Typical photoallergic reactions were seen in 198 subjects (259 minus 40 toxic photodermatitis to chlorpromazine and 21 to promethazine), which represents 18.8% of the total population. Topical drugs represent the most involved substances in photodermatitis. The incidence in our population was about equal for antimicrobial agents, additives to fragrances, and fragrances themselves. Other allergens found were salicylanilides, whereas sun-screening agents were the fifth group of haptens but with clear-cut relevance. This study is a first attempt to organize the data about results of photopatch tests applied to Italian patients.

Adult↗

Effect of hexavalent chromium on drug-metabolizing enzymes in male domesticated rabbits.

We studied the effect of chromium on the drug-metabolizing enzymes (DME) in male New Zealand white rabbits, Oryctolagus cuniculus, with and without pretreatment with phenobarbitone (PB) and promethazine (PM). The activities of cytochrome P-450 (183%), aniline hydroxylase (ANH, 265%), acetanilide hydroxylase (ACH, 160%), benzphetamine demethylase (BD, 112%), aminopyrine demethylase (AD, 97%), N,N,-dimethyl aniline demethylase (DAD, 72%), and cytochrome-c-reductase (100%) were increased after PB treatment. The activities of cytochrome b5 and N,N,-dimethyl aniline N-oxide (DAO) were, however, decreased 79% and 47%, respectively. Most of the DME remained unaffected after PM treatment except for the increase in ANH (55%), ACH (56%), and BD (16%). Potassium dichromate administered to rabbits at a dose of 8 mg/kg body weight/day for 5 days resulted in an increase in the activities of ANH (108%), BD (76%), AD (25%), and DAD (49%), while that of cytochrome b5 and DAO were inhibited 81 and 77%, respectively. There was no effect on the activities of cytochrome P-450, ACH, and cytochrome-c-reductase. Chromium, administered to PB-pretreated animals decreased the activities of ANH (41%), ACH (35%), BD (34%), AD (30%), DAD (51%), cytochrome-c-reductase (72%), and DAO (62%). Other enzymes remained unaffected. When administered to PM-pretreated animals, the activities of ANH, BD, AD, and DAD increased 34, 69, 24 and 54%, respectively, whereas activities of cytochrome b5 and DAO were decreased 96 and 68%, respectively. All other DME remained unaffected.

Animals↗