The cardiorespiratory effects of a fentanyl infusion following acepromazine and glycopyrrolate in dogs.

We investigated whether the analgesic mu-opioid fentanyl can be used safely in dogs in everyday clinical veterinary practice, with limited and non-invasive monitoring. To this end, the cardiorespiratory effects of fentanyl, administered in doses reported to be adequate for inducing opiate analgesia in spontaneously breathing canine patients, were evaluated by measuring the respiration rate, oxygen saturation (SpO2), heart rate, respiratory sinus arrhythmia (RSA), and rectal body temperature. Ten Beagle dogs, all spontaneously breathing room air, underwent three separate sessions in which they received in random order either saline, fentanyl 5 microg/kg/h or fentanyl 10 microg/kg/h. Each session started with a non-medication period, followed by acepromazine with glycopyrrolate, followed by a loading dose and infusion of saline or fentanyl, and ended with the administration of the antagonist naloxone. At the doses studied, fentanyl did not significantly change the respiration rate or have a clinically relevant effect on SpO2 or RSA, whereas it significantly decreased the heart rate and core body temperature. In the dose range tested and under the conditions described in this protocol, we conclude that fentanyl can be safely administered to healthy dogs spontaneously breathing room air.

Stability of the tranquilizer drug propionylpromazine hydrochloride in formulated products.

An analytical method to evaluate propionylpromazine hydrochloride (PPZHCl) in tranquilizer formulations was developed using high-performance liquid chromatography (HPLC). During analysis of aged quality-control samples, a previously unreported chromatographic response was observed at a shorter retention time than PPZHCl. Further investigation of formulations stored in trap tap devices at temperatures ranging from 5 to 40 degrees C during field trials at four different locations confirmed the degradation of the active ingredient. Further investigation using HPLC/tandem mass spectrometry revealed two to five degradates, with the major degradates being oxidation products of the active ingredient, PPZHCl. As PPZHCl formulations must be stable when stored at 5 to 40 degrees C for 6 to 12 months, reformulation with the anti-oxidant ascorbic acid was utilized to achieve the required PPZHCl stability.

Acute brain syndrome as a consequence of the Cronkhite-Canada syndrome.

BACKGROUND: Cronkhite-Canada syndrome is a very rare illness and psychical disturbances developed as a consequence of this illness are very rarely described. That is the case because majority of the symptoms of this syndrome are associated with the polyposis of the gastrointestinal tract. AIM: The aim of this case report is to link the development of acute brain syndrome with this rare syndrome. PATIENT: The patient was two times treated under the diagnosis of Cronkhite-Canada syndrome in the clinics of internal medicine in Rijeka and Zagreb, and then in the Psychiatric Clinic in Rijeka under the diagnosis of acute brain syndrome (F05.0). RESULT: Therapy with a typical antipsychotic (haloperidol) and corresponding internistic treatment gave results very fast and calmed acute delirium. CONCLUSION: Typical antipsychotics are efficient in the treatment of the acute brain syndrome caused by Cronkhite-Canada syndrome. Acute brain syndrome is caused solely by the lack of electrolytes and other important nutrients because of a malabsorption syndrome, conditioned by a diffuse polyposis of intestines.

Effect of carbamazepine on the pharmacokinetics of promazine.

Combinations of neuroleptics and carbamazepine are administered to psychiatric patients in the therapy of mania, manic-depressive illness and schizophrenia. The present study was aimed at assessing the influence of carbamazepine on the pharmacokinetics of promazine. Male Wistar rats received promazine and/or carbamazepine twice daily for two weeks (promazine, 10 mg/kg ip; carbamazepine, 15 mg/kg ip during the 1st, and 20 mg/kg ip during the 2nd week of treatment). In a short time (1 h) after administration, carbamazepine had a tendency to increase the concentration of promazine in the blood plasma and brain. Lineweaver-Burk's analysis showed that carbamazepine added in vitro competitively inhibited the N-demethylation of promazine in liver microsomes, without affecting the sulphoxidation process. The effect was reflected in vivo (1 h) by an increased promazine/desmethylpromazine ratio. After a long time interval (6 h, 12 h), carbamazepine decreased the concentration of promazine and its metabolites. In vitro studies into the promazine metabolism, conducted on microsomes from rats treated with promazine and/or carbamazepine, did not show acceleration of its demethylation or sulphoxidation by carbamazepine. The obtained results suggest that induction of promazine metabolism by carbamazepine involves metabolic pathways other than N-demethylation or sulphoxidation. It has been concluded that when a phenothiazine neuroleptic, such as promazine, is administered jointly with carbamazepine, a slight increase in the neuroleptic concentration may be expected in a short time after administration, followed by its significant decrease.

The pharmacokinetics of promazine and its metabolites after acute and chronic administration to rats--a comparison with the pharmacokinetics of imipramine.

This study was aimed to investigate the pharmacokinetics of promazine (a phenothiazine analogue of imipramine) after its single and repeated administration. Male Wistar rats received promazine as a single injection (10 mg/kg ip) or they were treated chronically with the neuroleptic, once a day for two weeks. Plasma and brain concentration of promazine, desmethylpromazine and promazine sulphoxide were determined using the HPLC method devised by us. The results of the present study were compared with our earlier data obtained in analogous experiments with imipramine. The obtained data showed that the pharmacokinetics of promazine and imipramine was similar, though certain differences could be noticed. Both those drugs were unevenly distributed throughout the body, occurring in low concentrations in the blood plasma and reaching considerably higher concentrations in the brain. However, the uptake of promazine by the brain was more efficient than that of imipramine. The brain/plasma AUC ratio after a single dose amounted to 28.72 for promazine and 12.78 for imipramine. Their demethylated metabolites behaved in a similar way, where as the level of promazine sulphoxide in the brain was three times lower than that in the plasma. Chronic treatment with promazine or imipramine increased concentrations of the parent compounds and their demethylated metabolites, and prolonged their half-life in the plasma and brain. The plasma level of promazine sulphoxide did not change, and its brain level was decreased by chronic treatment with promazine. The half-life of promazine sulphoxide was prolonged in the plasma but shortened in the brain after repeated administration of promazine. The observed considerable amounts of desmethylpromazine and promazine sulphoxide, formed in vivo, suggest that the two compounds are major metabolites of promazine, and that the metabolic pattern of promazine in the rat and man is similar.

[Absolute bioavailability of chlorpromazine, promazine and promethazine]. / Absolute Bioverfügbarkeit von Chlorpromazin, Promazin und Promethazin.

The absolute bioavailability of the three phenothiazine neuroleptics, promazine (Sinophenin, CAS 58-40-2), chlorpromazine (Propaphenin, CAS 50-53-3) and promethazine (Prothazin, CAS 60-87-7) was tested in three single-dose cross-over studies. In each trial 12 to 14 healthy volunteers were enrolled. The single doses for promazine, promethazine and chlorpromazine were 100, 75 and 150 mg (orally) and 20, 50 and 50 mg (intravenously), resp. The serum concentrations of the three neuroleptics were measured by means of a selective HPLC-method. the distribution-free confidence intervals for the absolute bioavailability of the three phenothiazines were within 10.5 to 24.7% for chlorpromazine, 7.8 to 24.9% for promazine and 12.3 to 40% for promethazine. Promazine and chlorpromazine are pharmacokinetically very similar and differ substantially from promethazine.

Alfentanil/promazine versus meperidine/promazine as a sedative regimens during local analgesia for cataract operation.

The influence of two intravenous (IV) sedative regimens on intra-ocular pressure (IOP) was investigated in conjunction with retrobulbar local analgesia. Forty patients of either sex, and similar age with body weight within 40-90 kg were allocated equally and randomly to two groups: Group A (alfentanil/promazine) and group M (meperidine/promazine). Measurement of IOP, systolic pressure, pulse rate, respiratory rate, PaCO2, PaO2 and O2 saturation were made before operation, after premedication, after IV sedation and post-operatively. In the Alfentanil group there was significantly stronger decrease of IOP (p < 0.001). In group A the IOP dropped from 18.1 +/- 3.2 mm Hg to 10.3 +/- 2.7 mm Hg, i.e. 43%, while in group M the reduction IOP was from 17.6 +/- 3.5 mm Hg to 12.6 +/- 1.9 mm Hg, i.e. 28.4%. Meperidine caused a significant increase in PaCO2 (4.2 +/- 0.3 mm Hg), however this increase was not sufficient to cause the IOP alterations. The oxygen saturation was lower in group M (decreased by 1.5 +/- 1% in group M versus decrease by 1.0 +/- 1.2% in group A). Cardiovascular parameters were more stable in group A. In conclusion the alfentanil regimen produced a better reduction of the IOP with excellent sedation, operative condition and least anaesthetic side effects.

Severe ischemia of the hand following intra-arterial promazine injection: effects of vasodilation, anticoagulation, and local thrombolysis with tissue-type plasminogen activator.

Promazine hydrochloride was injected accidentally in the antecubital artery of a 42-year-old woman, resulting in severe ischemia of the second and third fingers of her right hand which lasted for four days before she was hospitalized. Vasodilation by combining axillary plexus block and intravenous sodium nitroprusside did not improve ischemia and local thrombolysis was performed using recombinant tissue-type plasminogen activator (50 mg over 8 hours), resulting in normalization of digital pressure in one of the two affected fingers. The outcome was favourable and amputation could be avoided.

[Comparative clinical studies of oral premedication in childhood with reference to various pharmaceuticals]. / Vergleichende klinische Untersuchungen zur oralen Prämedikation im Kindesalter unter Berücksichtigung verschiedener Pharmaka.

In a randomized prospective study of 206 children aged between one and 14, the influence of oral praemedication on the psychic condition and with regard to anaesthesiologic measures was investigated. Heart rate, inhibition of salivation and the kind and frequency of side-effects were also examined. The praemedication was carried out using diazepam (0.3 mg/kg), promazin (1.0 mg/kg), promethazin (1.0 mg/kg) and chlorphenaethazin (1.0 mg/kg). It was not possible to determine statistically relevant differences between the various drugs concerning the fixed criteria. In general, however, diazepam seems to achieve the best results. In the younger children (1 to 6 years) a frequent and insufficient effect of praemedication was noted immediately. Oral praemedication proved to be a valuable and practicable method which was well tolerated by the great majority of the children.

Chemical immobilization of red foxes (Vulpes vulpes).

Red foxes (Vulpes vulpes) were immobilized with one of the following drug combinations: ketamine/xylazine (n = 22), ketamine/promazine (n = 35), ketamine/midazolam (n = 13), or tiletamine/zolazepam (n = 22). Foxes given ketamine/xylazine had the shortest induction and longest recovery times relative to other drug combinations, whereas foxes given ketamine/midazolam had the longest induction times. Recommended doses for the various combinations are given. Foxes given ketamine/xylazine were given either 0.1, 0.2, 0.4 mg/kg yohimbine, or saline 40 min after anesthetic induction. Administration of yohimbine significantly shortened arousal and recovery times relative to control values (P less than 0.001).

[Respiratory failure in a newborn infant following repeated sedation for computerized tomography]. / Atemstillstand eines Neugeborenen nach wiederholter Sedierung zur Computertomographie.

In very young pediatric patients, computed tomography can only be performed successfully after adequate immobilization with sedatives. The special age- and maturity-related features of the premature and neonatal period have to be considered when selecting the drug and the form of administration. Oral, intramuscular, or rectal premedication cannot be recommended for CT sedation of premature and newborn children. Likewise, multiple or repeated medication with different forms of administration should be avoided. A case report of a newborn with respiratory arrest following repeated sedation for computed cranial tomography illustrates the risks associated with such measures. Recommendations concerning drugs and procedure for the sedation of high-risk neonates for CT examinations are given.

[Drug therapy of so-called postherpetic neuralgia, the only valid alternative. Clinical experience in 43 treated cases]. / La terapia farmacologica della cosiddetta nevralgia post-erpetica unica valida alternativa. Esperienza clinica di 43 casi trattati.

The efficacy of tricyclic antidepressants in association with neuroleptics having been demonstrated in patients suffering from so-called tardive post-herpetic neuralgia, 43 patients were given this treatment either alone or in association with transcutaneous nerve stimulation (TENS). Of the 33 patients given drug treatment alone, 25 found relief from pain in 3-18 months, 5 produced a partial result and in 3 the treatment failed. The results obtained suggest that this is the most effective treatment as long as it is continuous and given for at least 3-6 months. The use of TENS produced no benefit.

[Premedication and risks in computed tomography of newborn and infant children]. / Prämedikation and Risiken bei Computertomographien im Neugeborenen- und Säuglingsalter.

In very young pediatric patients CT-investigations require sedative-hypnotic drug treatment to ensure complete immobilisation during scanning. The case report of a neonate with respiratory arrest after a repeated CT-premedication underlines the high risk of these procedures, especially in patients with central nervous system disorders. We compared organisational requirements, risks and complication rates of 146 oral and intramuscular promazine medications for CT-scanning of the head in 146 infants and neonates (93.8% adequate sedation response) to those of reported alternative methods. Oral promazine proved to be a very effective and safe medication (average dosage in 57 patients without complications: 5.2 mg/kg body weight/90 minutes before CT-scanning; 96% successful sedation procedures) in comparison to 89 patients with i.m. promazine (average dosage: 2.3 mg/kg body weight/45 min before CT with 92% adequate sedations but a complication rate of 7.9%). For neuropediatric examinations of outpatients fast recovery and EEG-compatibility are further important advantages of oral promazine CT-medication.

Oral administration of diazepam and promazine hydrochloride to immobilize pronghorn.

Oral tranquilizers were mixed with a grain bait and fed to pronghorn (Antilocapra americana) in an attempt to immobilize and thus facilitate their capture. Diazepam, administered at 6 mg/kg body weight immobilized a tame pronghorn fawn within 30 min. Tranquilization was still apparent after 8 h. A minimum dose of 23 mg/kg body weight was necessary to immobilize a wild adult pronghorn. Immobilization occurred after 60 min and tranquilization was apparent 24 h post ingestion. Excitement severely impeded the effect of the drug and although easily captured, the animal struggled wildly when handled. Wild pronghorn fawns showed moderate tranquilization when administered diazepam at 23 mg/kg body weight but were unapproachable. Doses of diazepam between 13 and 23 mg/kg body weight were used to capture tame yearling and adult pronghorn held in a 132 ha enclosure. A dose of 23 mg/kg body weight was excessive in that the animals did not recover for 48 to 54 h post ingestion and had difficulty maintaining a sternal bedding position. Diazepam at 13 mg/kg body weight failed to tranquilize the animals sufficiently for easy capture. Promazine hydrochloride at doses of 2 to 17 mg/kg body weight, given orally to wild pronghorn fawns and an adult, did not produce visible signs of tranquilization. Animals refused to eat bait containing doses of promazine hydrochloride greater than 17 mg/kg body weight.