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[Platelet stimulation and hypotensive action of carrageenans in the rat].

We studied the hypotensive effect of three carrageenans and of dextran sulphate in Brown Norway (BN) rats. The plasma of these BN rats is devoid of high molecular weight kininogen and poor in plasma prekallikrein. The hypotensive effect in BN rats was greatly reduced in comparison with the effects in normal rats. It was proportional to the thrombocytopenia induced by the sulphated polysaccharides and absent in rats made thrombopenic by antiplatelet serum. The hypotensive effect in BN rats was reduced by bromophenacyl bromide, mepacrine, aspirin, methysergide, promethazine and CCI 17810, and was unchanged after the administration of cobra venom factor, heparin, amino caproic acid, chloroquine, dexamethazone, lidocaine, propranolol, indomethacin, phenidone, imidazol, adenosine and cyproheptadine. The thrombopenic effect was reduced by methysergide and CCI 17810 and was not modified by bromophenacyl bromide and chloroquine.

Animals↗
PubMed1984

Sympathomimetic activity of mazindol on rat anococcygeus muscle and vas deferens.

Mazindol contracted the isolated anococcygeus muscle of the rat. This effect was prevented by pretreatment with reserpine and antagonized by phentolamine but not by atropine, cocaine, hexamethonium, methysergide or promethazine. The drug potentiated the contractile response of the rat anococcygeus to noradrenaline and field stimulation and released tritium from the rat vas deferens and anococcygeus preloaded with [3H]-noradrenaline. The release of radioactivity was unaffected by incubation of the tissue in calcium free or high potassium (60 mM) solution.

Animals↗
PubMed1978

[Peripheral arteriographies under intraarterial analgesia (author's transl)].

45% contrast medium, to which lignocaine had been added in a concentration of 0.1%, was injected for 44 translumbar aortograms, 26 femoral arteriograms and 4 brachial arteriograms under premedication with pethidine-promethazine. Few patients described their sensations spontaneously; most patients graded their pain as minimal and described only the sensation of heat. When the contrast medium was injected, first without and then with lignocaine, the pain was markedly reduced by lignocaine. No patient showed signs of CNS-toxicity. After the injection of the mixture of contrast medium and lignocaine, the heart rate rose slightly, the arterial blood pressure fell slightly, both not more than after injection of the contrast medium only. The ECG showed no anomalies. The addition of lignocaine to a contrast medium in low concentration represents a simple and, for the patient, acceptable method of analgesia as well as a safe alternative to general, spinal or epidural anesthesia.

Anesthesia, Local↗
PubMed1980

[Evaluation in vitro of the local anesthetic effect by means of the dose/stabilization effect curve].

The effect "in vitro" and "in vivo" of local anesthetics is normally evaluated at fixed time or considering the time required to obtain a per cent effect. We have attempted to estimate the dose/effect correlation at steady state using "in vitro" preparation of sciatic nerve-trunk of frog. Such an experiment is possible only if the concentrations of drugs tested are lower than those used in previous methods, so as not to inhibit the nerve fibres completely. The drugs tested were: lidocaine, procaine, promethazine and imipramine. Using linear regression analysis, it is possible to compare both the DE50 of the drugs tested and slopes of linear regression. In this manner we can better characterize the pharmacodynamic properties of local anesthetics.

Anesthetics, Local↗
PubMed1978

Spin-label study of phenothiazine interactions with erythrocyte ghost membranes: a possible membrane-mediated antisickling action.

Erythrocyte membrane alterations by 11 phenothiazine derivatives known to inhibit the sickling phenomenon in vitro have been evaluated in ghosts by the spin-labeling technique. Four sulfydryl-reactive spin labels were employed: 4-maleimido-2,2,6,6-tetramethylpiperidinooxyl; 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidinooxyl; 3-[(2-iodoacetamido)methyl]-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl; and 3-(maleimidomethyl)-2,2,5,5-tetramethyl-1-pyrrolidiny-loxyl. The latter spin label was judged most useful since its spectrum was sensitive to subtle perturbations by drugs spanning a considerable potency range. An increase in spin-probe immobilization was induced by each drug with approximate relative potencies given by the order: desmethylchlorpromazine congruent to thioridazine congruent to fluphenazine congruent to prochlorperazine congruent to trifluoperazine greater than acetophenazine congruent to triflupromazine congruent to chlorpromazine greater than promazine greater than promethazine greater than perphenazine. This order correlates (P less than .01) with their antisickling potency in vitro.

Antisickling Agents↗
PubMed1982

Interactions between drugs and intravenous delivery systems.

The loss of 45 drugs from intravenous solutions during simulated infusions through plastic infusion sets; factors affecting such losses; and ways to minimize these losses are investigated. A total of 43 drugs was studied in 0.9% sodium chloride solution; one drug was in 5% dextrose solution and one in a solvent supplied by the manufacturer. Drug loss was studied in plastic infusion sets, with and without burette chambers, and glass infusion bottles; polyethylene and silastic tubing with glass syringes on an infusion pump; and single-use all-plastic syringes. Variables studied were flow rates, infusion times, drug concentrations, pH, and tubing lengths and radii. Clomethiazole edisylate, chlorpromazine hydrochloride, diazepam, promazine hydrochloride, promethazine hydrochloride, thiopental sodium, thioridazine hydrochloride, and trifluoperazine dihydrochloride were lost from solution during infusions through at least one system. The loss of most drugs during infusion was slow, time-dependent, and concentration-independent, indicating a diffusion-controlled sorption process rather than a binding, adsorptive process. Drug loss was lowest in short lengths small-diameter tubing with low permeability constants. None of the drugs was lost stored in all-plastic single-use syringes. It is concluded that loss of drugs through sorption processes can be minimized by administering infusions through short lengths of small-diameter tubing made of inert plastics.

Adsorption↗
PubMed1982

[Biotransformation of fentanyl. II. Acute drug interactions in rats and men (author's transl)].

Rat tissue homogenates were used to study fentanyl biotransformation. The liver was shown to be the most important metabolizing organ, whereas extrahepatic metabolism occurred only to a minor degree in the kidneys. The products of oxidative desalkylation, phenylacetic acid and norfentanyl, could be identified as well as small amounts of p-hydroxy-(phenethyl)fentanyl, which is pharmacologically still active. Major sex differences were observed, male rats showing nearly twice as much activity as female animals. Several anaesthetic agents, often used in combination with fentanyl, were tested with respect to their influence on fentanyl metabolism. Most of them caused an inhibition of biotransformation and/or variations in product distribution, when they were added to in-vitro incubations or given to the animals prior to enzyme preparation. This experimental design proved to be useful as a screening method to predict metabolic drug interactions. Halothane and enflurane, which are strong inhibitors in rats, were demonstrated to delay fentanyl metabolism in man, too. Fentanyl plasma levels under halothane anaesthesia were found to be more than twice as high as during neuroleptanaesthesia. The importance of other agents, e.g. ketamine, promethazine or local anaesthetics, remains to be examined. Variations of biotransformation reactions among patients as well as the reported drug interactions might explain some differences in fentanyl blood concentrations reported in the past, but must also be taken into account when intensity and duration of effects or side-effects are discussed.

Adult↗
PubMed1981

Hypotensive action of synthetic fragments of parathyroid hormone.

Parathyroid hormone (PTH) and its N-terminal 1-34 fragment were shown to be hypotensive in dogs. In this study, synthetic bovine PTH fragments containing the N-terminal amino acids 1-34, 24-34, 24-28 and 25-27 [bPTH-(1-34), bPTH-(24-34), bPTH-(24-28) and bPTH-(24-27)] were synthesized and tested for hypotensive activity in dogs. bPTH-(1-34) is the most potent of these. The tripeptide is ineffective at doses as high as 2 mg/kg. bPTH-(24-34) and bPTH-(24-28) exhibited hypotensive activity but were less effective than bPTH-(1-34). A decrease in chain length decreased the hypotensive activity. The maximum response produced by bPTH-(1-34) was greater than that of either bPTH-(24-34) or bPTH-(24-28). The maximum responses, however, of bPTH-(24-34) and bPTH-(24-28) were similar. Another striking difference between bPTH-(1-34) and the other two effective fragments was the duration of action. Whereas the action of bPTH-(1-34) at ED50 lasted for up to 6 min the action of bPTH-(24-34) and bPTH-(24-28) lasted for less than 1 min. The hypotensive effect of these three bPTH fragments was not affected by propranolol, phentolamine, atropine, promethazine or cimetidine. In the perfused rat hindlimb, bPTH-(24-28) produced log dose-related sustained vasodilation.

Animals↗
PubMed1981

Comparative effects of age and sedation on sinus node automaticity and atrioventricular conduction.

Corrected sinus node recovery time (CSNRT) and atrioventricular node effective refractory period are longer in nonsedated adults than in sedated children at cardiac catheterization. We attempted to ascertain the relative contributions of age and catheterization sedation on these differences by studying adult beagles and beagle puppies previously instrumented with atrial pacing wires. We found that CSNRT was similar in adults and puppies prior to drug administration. CSNRT shortened significantly after meperidine, promethazine, and chlorpromazine (DPT) administration in both adult dogs and puppies. Atrioventricular node effective refractory period (AVERP) was shorter in puppies than adults prior to DPT, and did not shorten in in either group after DPT. These findings suggest that the difference between CSNRTs in children and adults can be at least partly explained by the sedation used in children. This is an important consideration when premedicating children for electrophysiologic studies, particularly in children with suspected sinus node dysfunction.

Aging↗
PubMed1981

Blood pressure lowering effects of N,N-di-n-propyl-dopamine in rats: evidence for stimulation of peripheral dopamine receptors leading to inhibition of sympathetic vascular tone.

In conscious or pentobarbital-anesthetized hypertensive or normotensive rats, N,N-di-n-propyl-dopamine (DPDA) produced sustained decreases in mean systemic arterial blood pressure. In anesthetized normotensive animals, these responses were not significantly changed by vagotomy, desipramine, indomethacin, methylatropine, promethazine or propranolol, were markedly reduced by phenoxybenzamine or phentolamine, were entirely blocked by domperidone, haloperidol or sulpiride and were reverted to an alpha adrenoceptor-mediated pressor response after removal of central sympathetic tone. In phenoxybenzamine-pretreated pithed rats in which the blood pressure was elevated to prepithing levels with vasopressin, DPDA, in contrast to dopamine, produced no hypotensive effect. In the pithed rat, DPDA reduced the pressor responses elicited by electrical stimulation of the spinal cord and this effect was inhibited by haloperidol or sulpiride. DPDA slightly enhanced the pressor effects of norepinephrine but modified neither the blood pressure increases produced by epinephrine, phenylephrine, 5-hydroxytryptamine or angiotension II nor the vasodepressor effects of acetylcholine, histamine or salbutamol. Intracerebroventricular administration of DPDA produced blood pressure decreases which were slightly smaller in magnitude but longer in duration than those elicited by i.v. DPDA. However, DPDA leaked from the cerebroventricular space into the peripheral circulation. These results indicate that in the rat DPDA lowers blood pressure via activation of peripheral dopamine receptors possibly located presynaptically on vascular sympathetic neurons. The stimulation of these receptors induces a decrease in norepinephrine release which in turn is followed by a passive relaxation of the vascular beds under active sympathetic constriction.

Anesthesia↗
PubMed1980

Intravenous anaesthetics for minor gynecological operations.

Ten intravenous anaesthetic combination were used for anaesthesia in 470 women undergoing minor gynecological operations and examinations. Their effects on respiration, pulse rate, blood pressure as well as the incidence of complications and satisfaction of operating conditions were studied. Ketamine-diazepam combination was found most satisfactory and more superior to ketamine alone in operations of about 30 minutes duration. Thiopentone and althesin-preferably after diazepam - appeared to suit shorter operations, while propanidid may be useful only for very quick maneuvers. Pethidine-diazepam-promethazine mixture proved to be valuable for evacuations particularly in poor risk and non-prepared patients. Both hexobarbitone and buthalitone were found unsatisfactory.

Adolescent↗
PubMed1980

Local anesthesia for ophthalmic surgery: patient preparation and management.

Many ophthalmic procedures are performed in elderly patients who have serious concurrent disease. Local anesthesia with sedation can be a safe, advantageous method of management. Uneventful ophthalmic surgery under local anesthesia depends on proper patient selection, preparation, and perioperative management. Patients should understand the procedures and be cooperative. Preparation includes a through medical evaluation. Medical problems must be stable and appropriately managed. The goal of premedication is to have a calm, cooperative patient. Narcotic and an antiemetic sedative such as either promethazine, hydroxyzine, or droperidol should be given according to age and weight. A benzodiazepine may be added for amnesia and anxiolytic effect. Naloxone or physostigmine are available to specificity reverse the effects of narcotics or benzodiazepines, respectively. Awareness of the toxicity and limitations of local anesthetics is important for their safe use.

Aged↗
PubMed1980

Reserpine abolishes movement-correlated atropine-resistant neocortical low voltage fast activity.

Following a large dose of atropine, rats display large amplitude slow waves in the neocortex during immobility, tremor, tooth-chattering and face-washing (Type II behavior) but display low voltage fast activity (LVFA) during walking, struggling, postural changes and head movement (Type I behavior). Rats treated with a large dose of reserpine usually continue to display LVFA during immobility as well as during movement although large amplitude slow waves are present more frequently than normal. A combination of reserpine and atropine abolishes all LVFA even during intense sensory stimulation or electrical stimulation of the reticular formation. Chlorpromazine, lysergic acid diethylamide, methysergide, phenoxybenzamine, pimozide, promethazine, propranolol and trifluoperazine do not have this effect when combined with atropine. In rats treated with nialamide prior to reserpine and atropine, LVFA continues to occur in association with Type I behavior just as in rats given atropine alone. It is proposed that the occurrence of LVFA in the neocortex is determined by two distinct reticulocortical systems. A cholinergic system produces all LVFA occurring during Type II behavior and a second system, dependent on a monoamine, produces LVFA in association with Type I behavior. The view that LVFA is a correlation of arousal or the sleep-waking cycle is criticized.

Animals↗
PubMed1980

[Changes in intraocular pressure in anesthesia induced with althesin and maintained with methoxyflurane].

Intraocular pressure and arterial blood pressure were studied in 27 patients undergoing anaesthesia induced by 0,6-1 mg/kg of Althesin iv and maintained by methoxyflurane-N2O-O2 on spontaneous ventilation. All patients were scheduled to undergo various types of eye surgery, including open-eye surgery. Patients with glaucoma and cataract were administered 20% mannitol two hours prior to surgery. In all cases premedication was based on meperidine, promethazine and atropine sulphate im. During the entire period of anaesthesia the intraocular pressure and, generally, arterial blood pressure appeared to be lowered.

Adolescent↗
PubMed1995

Ligand binding properties of muscarinic acetylcholine receptor subtypes (m1-m5) expressed in baculovirus-infected insect cells.

Five subtypes of muscarinic acetylcholine receptors (m1-m5) have been expressed in insect cells (Spodoptera frugiperda, Sf9) using the baculovirus system. Up to 6 nmol of muscarinic acetylcholine receptors were produced by 1 liter culture; 0.3 to 0.6 (human m1), 3 to 6 (human m2), 2 to 4 (rat m3), 1 to 2 (rat m4) and 0.5 to 1 (human m5) nmol. Pirenzepine, AF-DX116 and hexahidrosiladifenidol showed the highest affinity for the m1, m2 and m3 subtype, respectively, indicating that these receptors expressed in Sf9 cells retain the same substrate specificity as those in mammalian tissues or cultured cells. Among 32 kinds of muscarinic ligands examined in the present studies, prifinium was found to have the highest affinity for the m4 subtype, and pilocarpine, oxotremorine, McN-A343 and promethazine the highest affinity for the m5 subtype, although the differences in the affinities among the five subtypes were less than 10-fold. Alcuronium increased the binding of [3H]N-methylscopalamine to the m2 subtype, but not the m1, m4 and m5 subtypes and only slightly to the m3 subtype. Similar but smaller effects of fangchinoline and tetrandrine were found for [3H]N-methylscopalamine binding to only the m3 subtype. These effects may also be useful for the discrimination of individual subtypes.

Animals↗
PubMed1995

Classification of the presynaptic muscarinic receptor subtype that regulates 3H-acetylcholine secretion in the guinea pig urinary bladder in vitro.

The experiments were done to investigate the presence and subtype of functionally presynaptic muscarinic receptors in cholinergic nerves of the guinea pig urinary bladder. Bladder strips were incubated with 3H-choline and superfused with Tyrode's solution containing eserine. Secreted 3H-acetylcholine was separated from 3H-choline. The electrically evoked 3H-acetylcholine secretion increased with the stimulation frequency. 3H-Acetylcholine secretion was enhanced by muscarinic antagonists, was depressed by carbachol and by alpha adrenoceptor agonists but was not influenced by drugs acting at beta adrenoceptors or purinoceptors. The rank order for the enhancing effect of muscarinic antagonist EC50 values was propantheline < atropine < methylatropine < N-desethyloxybutynin < UH-AH 37 < benzhexol < AQ-RA 741 < 4-DAMP < procyclidine < emepronium < secoverine < oxybutynin < tropicamide < promethazine < himbacine < hexahydrosiladifenidol < methoctramine = pirenzepine < dicyclomine < AF-DX 116, and the EC50 values correlated best with constants for the M4/m4 muscarinic receptor subtype. The enhancing effect of atropine was counteracted by carbachol; the effects of atropine and emepronium were not additive. The 3H-acetylcholine secretion was also enhanced by forskolin, 3-isobutyl-1-methylxanthine, 8-bromo cyclic AMP and dibutyryl cyclic AMP. The combined effects of atropine and forskolin were additive. These results suggest that the 3H-acetylcholine secretion in the guinea pig urinary bladder is regulated by a presynaptic muscarinic autoreceptor of the M4 subtype that is not coupled to adenylate cyclase.

Acetylcholine↗
PubMed1995

[Psychiatric drugs as risk factor in fatal heat stroke].

Two men aged 33 and 31 years suffered a fatal heat stroke on a warm summer day. One of them used pimozide and clomipramine, the other zuclopenthixol, dexetimide, droperidol, promethazine and propranolol as psychiatric medication. Both of them had a body temperature > 42.3 degrees C, without perspiring. At first only a comatose situation with practically normal laboratory values existed; this was rapidly followed by massive liver damage, disseminated intravascular coagulation, anaemia, thrombopenia and acute renal failure. In spite of adequate and rapid treatment these complications were fatal. Both patients used medication with an antidopaminergic and anticholinergic (side) effect. The set point of the temperature regulation centre can be elevated by the antidopaminergic activity of antipsychotics. Use of anticholinergic medication can disturb the thermoregulation via inhibition of the parasympathicomimetically mediated sweat secretion. It is recommended to point out the danger of unusually high outdoor temperatures to patients using this medication.

Adult↗
PubMed1995

Mobitz type I heart block after pokeweed ingestion.

The leaves of Phytolacca americana (pokeweed), when ingested, typically produce a self-limited but severe gastroenteritis characterized by intense vomiting and frothy diarrhea. Although cardiac effects have been reported in previous cases of pokeweed ingestion, no cardiac toxin has ever been identified in pokeweed. We report the case of a family who ingested raw and/or cooked pokeweed leaves, and 1 member who developed a Mobitz type I heart block associated with vomiting which resolved after i.v. promethazine. This suggests the possibility that some cardiac effects of pokeweed are secondary to the increased vagal tone seen with severe gastrointestinal colic.

Adult↗