Interaction between narcotic antagonist (naloxone) and lysergic acid diethylamide (LSD) in the rat

LSD administration in rats elicited a diphasic reaction consisting of a brief excitable period (up to 8 min) followed by a prolonged catalepsy(8 min–1 h). While the cataleptic response was antagonized by a single injection of naloxone (given 30 min after LSD administration), pretreatment with naloxone shortened the excitable phase and potentiated the catalepsy.     

Diminished effect of sympathetic nerve stimulation in cats pretreated with 5-hydroxydopa; formation and liberation of false adrenergic transmitters

Summary Pretreatment of cats with 5-hydroxydopa (3×200 mg/kg i.p., given over a period of 28 hours) resulted in a marked depletion of norepinephrine in sympathetically innervated organs (heart 5%, spleen 3%, iris 16% and nictitating membrane 12% of controls) and in a greatly diminished response of the spleen and nictitating membrane to sympathetic nerve stimulation. The decreased contractile response of the isolated perfused spleen was accompanied by a corresponding diminution of the norepinephrine output. The effect of intravenously injected norepinephrine on the blood pressure and nictitating membrane did not differ significantly from that of untreated controls.The chromatographic analysis of amines present in the spleen and heart after administration of 5-hydroxydopa and [³H]5-hydroxydopamine revealed the accumulation of 5-hydroxydopamine, of two not yet definitely identified -hydroxylated metabolites (most probably the -hydroxylated derivatives of 5-hydroxydopamine and of one of its O-methylated metabolites) and three O-methylated derivatives chromatographically identified as 4-methoxy-3,5-dihydroxyphenethylamine, 3-methoxy-4,5-dihydroxyphenethylamine and 3,4-dimethoxy-5-hydroxyphenethylamine. 5-Hydroxydopamine, its two -hydroxylated and its two monomethoxylated metabolites were liberated as sympathetic transmitters. Their direct sympathomimetic effect (the -hydroxylated derivatives were not available as references) on the nictitating membrane and spleen was 300–10000 times weaker than that of norepinephrine. It is concluded that the diminished contractile response of the nictitating membrane and spleen to sympathetic nerve stimulation results from a reduction of the physiological transmitter available for liberation and its replacement by less potent transmitter substances.Preliminary results of this report have been communicated to the German Pharmacological Society in Mainz at the Spring Meeting 1967.     

A simple method for sampling murine pulmonary and cardiac tissues for analysis of cyclic nucleotide levels

Summary A simple method for the rapid removal and freezing of mouse cardiac and pulmonary tissues is described. Samples thus obtained were judged to be suitable for valid estimation of in vivo levels of cyclic AMP and cyclic GMP based on the following findings: (a) the samples could be obtained and frozen in the very short time period of a few seconds; (b) no indication of adverse effects of the collection procedure was found upon examination of chemical indicators of energy metabolism; (c) the apparent rates of change of cyclic AMP and cyclic GMP levels during the first seconds after tissue isolation could produce small, but acceptable errors; and (d) dose-dependent elevations of pulmonary cAMP levels consistent with known effects in vitro were found after in vivo administration of isoproterenol.Abbreviations cAMP adenosine-3,5-cyclic monophosphate - cGMP guanosine-3,5-cyclic monophosphate     

Effect of phenothiazine neuroleptic drugs and tricyclic antidepressants on phosphodiesterase activity in rat cerebral cortex

The activity of phosphodiesterase (PDE) of rat cerebral cortex following the administration in vitro and in vivo of various concentrations of neuroleptic phenothiazine drugs and tricyclic antidepressive drugs has been investigated. It has been shown that PDE activity is inhibited by phenothiazine neuroleptic drugs (fluphenazine > trifluperazine > thioproperazine > chlorpromazine = thioridazine). Tricyclic antidepressants nortriptyline, chlorimipramine, protiptyline, imipramine and desipramine at a concentration of 10^–3 M caused 60–80% inhibition of PDE activity. It has also been found that the investigated phenothiazine compounds inhibit the high affinity PDE activity more than the PDE activity of low affinity to the substrate.The results obtained suggest that the mechanism of the neuroleptic action of phenothiazine drugs is partially connected with their influence on cyclic 3,5-AMP metabolism.Supported by Polish Academy of Sciences, 09.4.1.5.     

Different effects of lipolytic hormones and phosphodiesterase inhibitors on cyclic 3′,5′-AMP levels in isolated fat cells

Summary Cyclic AMP levels of isolated fat cells of rats were increased about 50-fold by noradrenaline (1 M) and isoprenaline (1 M) within 4 min of incubation and had declined markedly after 10 min. The effect of a variety of lipolytic hormones on cyclic AMP levels was dose-dependent over a wide range of concentrations, ACTH and glucagon being most potent on a molar basis. Among the adrenergic compounds tested isoprenaline elicited the grea test response. Glucagon, in maximally effective concentrations, caused only half the increase in cyclic AMP values produced by other hormones. This pattern was largely paralleled by the lipolytic effects of the hormones as measured by glycerol production. Various inhibitors of cyclic AMP phosphodiesterase had only small effects on cyclic AMP accumulation. Methylxanthines caused only a 3- to 5-fold elevation of cyclic AMP levels at concentrations which induced maximal lipolytic effects. Papaverine (0.5 mM) and phentolamine (0.1 mM) had virtually no effect and did not potentiate hormone effects on cyclic AMP production. However, theophylline (1 mM) caused a nearly tenfold increase in the effects of isoprenaline when added to 100 000 cells per ml in the medium. At a concentration of 20 000 fat cells per ml isoprenaline alone increased cyclic AMP levels 300-fold and the addition of theophylline had no further stimulatory effect. Our results suggest that lipolysis induced by hormones is mainly mediated by an accumulation of cyclic AMP, whereas methylxanthines must have additional effects. The potentiation of lipolytic hormones by methylxanthines cannot be attributed to an inhibition of phosphodiesterase alone, but seems to be due mainly to their antagonism with an inhibitory factor, which is produced by fat cells and released into the incubation medium.     

Effects of methacholine,histamine and atropine on pulmonary guanosine-3′, 5′-monophosphate levels in hypersensitive mice

Summary Pulmonary levels of cGMP and cAMP in mice sensitized to methacholine and histamine with b. pertussis were examined to determine whether sensitization could be the result of an alteration in the metabolism of these cyclic nucleotides. The results presented show that in sensitized mice, methacholine raised cGMP to levels that were about double those produced without sensitization. In analogous experiments, histamine raised cGMP by approximately 100% in sensitized mice without producing significant increases in nonsensitized groups. Atropine completely blocked the cGMP rises produced by methacholine but did not eliminate those produced by histamine, thus indicating that cholinergic, but not the histaminergic elevation of cGMP involves activation of muscarinic receptors. The influence of pertussis on cAMP appeared to be opposite in direction from cGMP, i.e., a small but significant drop in cAMP levels was found following methacholine administration to sensitized, but not to nonsensitized mice. It was concluded that pertussis sensitization increases the responsiveness of the pulmonary guanylate cyclase-cGMP system to methacholine and histamine, and that the altered patterns of cGMP accumulation may contribute to the biochemical mechanism of sensitization.     

Effect of six virustatic nucleoside analogues on the development of fetal rat thymus in organ culture

The effects of the virustatic agents zidovudine (azidothymidine, AZT) 23-dideoxycytidine (ddC), 23-dideoxyinosine (ddI), acyclovir (ACV), ganciclovir (GCV), and vidarabine phosphate (VP) on the in vitro development of thymic lobes of 17-day-old rat fetuses were tested in an organ culture system. The virustatics were added to the medium for a culture period of 7 days. All nucleoside analogues inhibited the proliferation and differentiation of lymphatic cells. However, differences were observable with respect to the potency of the six drugs to interfere with thymic development. Compared to untreated controls, reduction in the number of thymocytes was significant at concentrations of 30 M AZT and ddI. In the case of ACV, GCV, VP, and ddC concentrations as low as 10 M were sufficient to cause a significant reduction, ddC being the most potent derivate. Increasing concentrations of the nucleoside analogues led to a dose-dependent further inhibition of cell proliferation. At a concentration of 30 M flow cytometry revealed a decrease in the relative number of double positive CD4⁺ CD8⁺ and single positive CD4⁺ CD8^– cells but an increase in the relative number of CD4-CD8⁺ cells. At the same concentration the expression of the CD5 antigen was reduced by the antimetabolites, indicating that maturation of the thymocytes was inhibited. Distribution of the forward light scatter, a cell size-related parameter, showed that the formation of small thymocytes was reduced by the nucleoside analogues. Light and electron microscopic investigations indicated cytotoxic effects of the drugs on the thymocytes, whereas the epithelium was only slightly affected.     

Induction of immunotoxicity in mice by polyhalogenated biphenyls

Acute administration of Aroclor-1254 (500 mg/ kg) or 3,4,5,3,4,5-hexabromobiphenyl (HBB) (2–6 mg/ kg) IP, profoundly inhibited the plaque forming response to subsequent challenge with sheep erythrocytes in Ah locus positive (C57B1/6N or B6C3F1N) mice. These studies showed: 1) the immunotoxicity results paralleled enzyme induction results insofar as HBB was approximately 100 times more potent than Aroclor 1254; (2) neither Aroclor nor HBB treatment caused significant induction in the Ah locus negative DBA/2N mice; 3) when B6C3F1 mice were challenged with sheep red blood cells (SRBC) 6 or 16 weeks post Aroclor 1254 treatment, substantial recovery of a PFC response was observed; 4) when these compounds were administered to older (76-week-old) (B6C3F1 mice, severe depression of a PFC response was observed. In contrast to its profound depression of a PFC response, Aroclor-1254 (up to 1250 mg/kg) caused slight increases in lymphocyte proliferation induced by either T or B cell mitogens. A single 500 mg/kg dose of Aroclor-1254 also suppressed the ability of recipient B6C3F1 animals to reject a challenge with either the syngenic fibrosarcoma (PYB6) or the gram negative pathogen (Listeria monocytogenes).     

Regional differences in the effects of capsaicin and tachykinins on motor activity and vascular permeability of the rat lower urinary tract

Summary 1. The effects of capsaicin, substance P (SP) and neurokinin A (NKA) on motor activity and vascular permeability was investigated in the rat lower urinary tract (bladder dome and neck, proximal urethra and ureters). 2. Capsaicin produced contractions of the rat bladder dome and neck and of the proximal urethra in vitro, which were unaffected by tetrodotoxin and abolished by ganglionectomy. SP and NKA were almost equipotent in producing a contraction of the rat isolated bladder dome or neck and urethra. However, the maximal response to NKA was about twice that of SP on the urethra and bladder neck. 3. Capsaicin did not affect motility of the unstimulated rat isolated ureter, while NKA or SP activated rhythmic contractions, NKA being about 850 times more potent than SP. Either capsaicin or field stimulation produced a transient inhibition of the NKA-activated rhythmic contractions of the rat isolated ureter which was prevented by capsaicin-desensitization. 4. The capsaicin-(1 M) or field stimulation-induced inhibition of NKA-activated rhythmic contractions of the rat isolated ureter were unaffected by removal of pelvic ganglia but abolished by cold storage (72 h at 4°C). 5. Intravenous capsaicin induced an inflammatory response (Evans blue leakage) in the bladder, proximal urethra and ureters in vivo. Plasma extravasation was greater in the ureters, urethra and bladder neck than in the dome. SP, NKA and histamine produced a dose-dependent dye leakage in all segments of the rat urinary tract, the response being slightly greater in the bladder neck than in the dome. 6. The capsaicin-induced inflammatory response was abolished by systemic capsaicin-desensitization and reduced, to a variable extent, by pelvic ganglionectomy, in the various tissues examined. Topical application of tetrodotoxin on the bladder dome failed to affect the capsaicin-induced plasma extravasation in the urinary bladder. 7. These findings indicate that chemoceptive, capsaicin-sensitive nerves are present throughout the whole rat lower urinary tract and their activation determines a variety of visceromotor responses and an increase of vascular permeability. In various instances the response to capsaicin may be explained by the action of tachykinins but some effects may involve other sensory neuropeptides. Send offprint requests to C. A. Maggi at the above address     

The antinociception induced by \-endorphin administered intrathecally is mediated by the activation of μ and κ-opioid receptors in the rat

The antinociception induced by -endorphin given supraspinally has been previously demonstrated to be mediated by the stimulation of -, but not -, - or -opioid receptors in rats and mice. The present study was designed to determine what types of opioid receptors in the spinal cord are involved in the antinociception induced by intrathecally (i.t.) administered -endorphin. Antinociception was assessed by the tailflick test in male Sprague-Dawley rats. CTOP (0.9–6.6 nmol), a selective -opioid receptor antagonist, or nor-BNI(13.6–95.3 nmol), a selective -opioid receptor antagonist, given i.t. dose-dependently reversed i.t. administered -endorphin-induced inhibition of the tail-flick response. On the other hand, naltrindole (6.6–44.4 nmol), a selective -opioid receptor antagonist, or -endorphin (1–27) (1–6.7 nmol), a selective -opioid receptor antagonist given i.t., did not antagonize the inhibition of the tail-flick response induced by i.t. administered -endorphin. The results are consistent with the previous study in mice [Tseng LF and Collins KA (1992) Eur J Pharmacol 214: 59–65] that the antinociception induced by -endorphin given i.t. is mediated by the stimulation of - and -, but not - and -opioid receptors.Abbreviations i.t. Intrathecal - CTOP D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH₂ - nor-BNI Norbinaltorphimine     

Cardiostimulatory effects of prenalterol,a beta-1 adrenoceptor partial agonist,in vivo and in vitro

Summary The cardiostimulatory effects of prenalterol, a beta-1-adrenoceptor partial agonist, were studied in vivo and in vitro and compared to those evoked by isoprenaline, a full agonist, and to those of other partial agonists.In the anaesthetized rat, prenalterol and terbutaline were found not to elevate the myocardial cyclic AMP content; this was in sharp contrast to isoprenaline. Both partial agonists did, however, produce significant effects on heart rate.In the anaesthetized cat, prenalterol exhibited chronotropic and inotropic intrinsic activities of 88 and 76% respectively in relation to isoprenaline. No statistically significant increase in myocardial cyclic AMP content could however be detected.Prenalterol did not stimulate adenylate cyclase significantly in the cat myocardial homogenate. This was also true of the beta-2-adrenoceptor selective partial agonist procaterol. In this preparation, isoprenaline, noradrenaline and adrenaline acted as full agonists. Furthermore, prenalterol produced a concentration-dependent inhibition of isoprenaline-activated adenylate cyclase.Our data indicate that maximal cardiac stimulation occurs at a low level of adenylate cyclase activation and low myocardial cyclic AMP concentration when provoked by a full beta-adrenoceptor agonist. The maximal physiological effects of a partial agonist such as prenalterol may consequently be achieved at a marginal activation of the adenylate cyclase.The present data may thus support the hypothesis of a large beta-adrenoceptor reserve for full agonists in the heart.     

The effect of microelectrophoretically applied clonidine on single cerebral cortical neurones in the rat

Summary The technique of microelectrophoresis was used in order to examine the effects of clonidine on single neurones in the somatosensory cortex of the rat, and to compare its actions with those of noradrenaline and phenylephrine. Clonidine evoked only excitatory responses on cortical neurones. The clonidine-sensitive neurones were also excited by noradrenaline and phenylephrine. Clonidine had a consistently lower apparent potency than either noradrenaline or phenylcphrine. Responses to clonidine had a slower time-course than responses to the other two adrenoceptor agonists, both the latencies to onset and the recovery times being longer for responses to clonidine than for responses to noradrenaline and phenylephrine. When the mobilities of clonidine and phenylephrine were compared using an in vitro method, no significant difference was found between the mobilities of the two ionic species, suggesting that they have similar transport numbers. Thus the difference between the potencies and time-courses of responses to clonidine and phenylephrine are presumably of biological origin. Responses to clonidine were antagonised by microelectrophoretically applied prazosin; responses to phenylephrine were equally antagonised, while responses to acetylcholine were not affected. Clonidine could reversibly antagonise excitatory responses to both noradrenaline and phenylephrine, whithout affecting responses to acetylcholine. The results suggest that clonidine may act as a partial agonist at excitatory ₁-adrenoceptors on cortical neurones.     

The effect of repeated electroconvulsive shock on corticosterone responses to centrally acting pharmacological stimuli in the male rat

The effect of repeated and single electroconvulsive shocks (ECS) on the corticosterone response to pharmacological stimuli has been studied in male rats. Plasma corticosterone concentrations are elevated by oxotremorine, a muscarinic agonist, and by 5-hydroxy-l-tryptophan, a precursor of serotonin. Both these agonists probably stimulate corticotrophinreleasing-factor release from the hypothalamus. The log dose-response curves of the corticosterone response to oxotremorine and to 5-hydroxy-l-tryptophan are shifted to the left after a single ECS given daily for 10 days compared with sham-shocked controls. Plasma corticosterone concentrations are elevated by treatment with -methyl-p-tyrosine methyl ester (400 mg/kg IP). This rise is suppressed by clonidine. The log dose-response curve for the corticosterone response to clonidine after -methyl-p-tyrosine methyl ester is also shifted to the left by repeated ECS, compared with controls. There is no difference in the corticosterone response of ECS and sham-treated groups given vasopressin, which is thought to act directly on the pituitary to release ACTH.A single ECS produces a slight enhancement of the response to 5-hydroxy-l-tryptophan, a slight decrease in the response to oxotremorine and no change in the response to clonidine after -methyl-p-tyrosine.The disappearance of the difference in response between ECS and sham-treated animals was also studied 1,3, and 6 days after a series of ten ECS or sham procedures. Significant differences in the corticosterone responses to oxotremorine, 5-hydroxy-l-tryptophan and clonidine after -methyl-p-tyrosine between ECS and sham-treated animas were found 24 h after the last ECS or sham shock. These differences were in decline 3 days after the last procedure and had completely disappeared by day 6. The decline was largely due to an increase in plasma corticosterone responsiveness to pharmacological stimuli of the shamshocked controls. Responses in the ECS-treated groups remained constant.It is apparent that the anaesthetic procedure suppresses the effect of oxotremorine, 5-hydroxy-l-tryptophan and clonidine after -methyl-p-tyrosine on corticosterone concentrations in plasma. This effect is spontaneously reversible. Repeated ECS reverses the effect of the anaesthetic procedure but produces no reversible enhancement of its own.     

Consumers'' perceptions of community pharmacy in Portugal: a qualitative exploratory study.

Objective: Pharmacists are health professionals who are ideally positioned to perform a primary health care role. However, the definition of professional value needs to be considered not just as professional education and skills, but also in terms of how consumers perceive it. The main aim of this work was to explore the publics perceptions and attitudes towards community pharmacy in Portugal. Methods: A pure qualitative approach was undertaken. The data were collected through a semi-structured interview, conducted with a snowball like sample. First, individuals (n = 15) were interviewed, allowing for adjustment and validation of the interview schedule, followed latter by group interviews with adults in rural and urban areas. Group participants (n = 25) were asked about their behaviour and beliefs, resulting from their perceptions of community pharmacies, pharmacists and medicines. Future expectations regarding the community pharmacy service were also explored. The interviews were tape recorded and transcribed verbatim. An iterative, reflexive coding process was applied, assisted by the qualitative software package QSR NUD*IST v4. The inductive analysis of the extracted codes assembled those codes into themes. Results and discussion: This article will mainly focuses on community pharmacy service representations and cognitions (theme A) and community pharmacy evaluative perceptions and behaviours (theme B). Participants displayed general and contradictory ideas about the actual functions of the pharmacist, including weak conceptualizations and a positive demand for services in relation to product supply. This superficial understanding is in line with previous results from satisfaction studies, confirming a low expectation level. The publics poor knowledge and low expectations can justify a reduced desire for an extended role of the pharmacist in the community. This uncertain service conceptualization does not define the professional responsibility from a consumers perspective. Conclusions: Although these results allow for the development of a framework to describe the perceptions of community pharmacy users, further research is needed to determine the prevalence of these and other possible results.     

Influence of plasma protein binding kinetics on hepatic clearance assessed from a “tube” model and a “well-stirred” model

The potential influence of protein binding kinetics on elimination from liver sinusoids was evaluated by means of a well-stirred model (I) and a tube model (II). When the dissociation rate constant (k_–1) is at the estimated maximum, equilibrium is maintained during the passage of drug through the eliminating organ, and hence dissociation as such has no limiting effect on elimination. When, however, k_–1 is at the estimated minimum, equilibrium is not maintained, the unbound fraction is reduced during the passage, and a significant decrease in the extraction ratio occurs when the unbound fraction is 0.01 or less. The models were furthermore used to investigate the effect of saturation, of both the binding protein and the elimination process, on elimination.Part of the results from this work were presented at the 7th International Congress of Pharmacology, Paris, 1978.     

The functional pool of brain catecholamines: Its size and turnover rate

Behavioral data are reviewed that give evidence for an indiscriminate involvement of brain catecholamines (CA), especially dopamine (DA), in nervefunction, regardless of the time elapsed from their synthesis. Critical analysis of biochemical and pharmacological studies shows that a clear-cut distribution of brain catecholamines in two compartments [newly synthesized (NS) and main storage] is not at all established, and moreover that there is no adequate proof that the difference in turnover rates attributed to these two supposed pools is due to a preferential extraneuronal release of NS-CA during nerve function rather than to a preferential (nonfunctional) intraneuronal deamination of NS-CA, or at least of NS-DA.     

Effects of GABA,dopamine, and substance P on the release of newly synthesized 3H-5-hydroxytryptamine from rat substantia nigra in vitro

Summary The effects of GABA, substance P and dopamine on the release of newly synthesized ³H-5-HT were investigated, using slices of rat substantia nigra superfused with l-³H-tryptophan in vitro. GABA (50 M) had no inhibitory effect on the potassium-evoked-release of ³H-5-HT. Substance P (50 M) and eledoisin (50 M) stimulated the spontaneous release of ³H-5-HT. This effect seems to be indirect and is possibly mediated by dopaminergic neurones, since the dopamine antagonist drug -flupenthixol (1 M) abolished the substance P-evoked release of 5-HT. Furthermore, it was found that substance P (10 M) stimulated ³H-dopamine release from nigral slices in vitro and the dopaminergic agonist apomorphine (50 M) also stimulated ³H-5-HT release. Substance P may, therefore, activate nigral dopaminergic neurones which then release dopamine from their dendrites. The release of dopamine may in turn stimulate 5-HT release from terminals of the raphe-nigral pathway.     

Disposition of 2′, 3′-dideoxyadenosine and 2′, 3′-dideoxyinosine in mice

Summary Mice were dosed with [³H]2,3-dideoxyadenosine ([³H]ddA) in three procedures: intravenously, intraperitoneally, and interperitoneally following a dose of 2 -deoxycoformycin (dCF). For mice dosed intravenously, the content of radioactivity in plasma and tissue samples were essentially constant after 30 min. Of the radioactivity in plasma and brain samples collected between 30 min and 24 hr, more than 94% was present as ³H₂O, indicating that most of the tritium from [³H]ddA had exchanged with water. No intact ddA was detected, and the deamination product, 2,3 -dideoxyinosine (ddI), was present only transiently. In the urine, the major radioactive material was [³H]ddI. Also detected were ³H₂O and small amounts of [³H]hypoxanthine and [³H]ddA. Following intraperitoneal doses to mice, levels of radioactivity in plasma, liver, and kidney increased to a maximum by 15–30 min after dosing but dropped to essentially constant levels thereafter, again indicating that the tritium had exchanged with water. At 5, 15, and 30 min after dosing, ddI was the major radioactive component in plasma. Only small amounts of ddA were present. When dCF was administered 24 hr prior to intraperitoneal [³H]ddA, levels of radioactivity in plasma, liver, and kidney reached a maximum at 30 to 60 min after dosing and decreased to essentially constant levels thereafter. The dCF transiently inhibited the deamination of ddA to ddI, since, in plasma, [³H]ddA was the main radioactive component at 5 and 15 min after dosing. Comparison of HPLC assays based on radioactivity detection and UV absorbance showed that they were equivalent for measuring ddA and ddI in samples derived from dosed mice. Therefore, exchange of tritium must have occurred at a metabolic step beyond ddI.For mice dosed intravenously and orally with unlabeled ddI, there was evidence of a saturated process. Nevertheless, for the high and low intravenous doses of ddI, the percent of dose excreted in the urine as unchanged drug was the same.     

The effect of DAS on respiration and pulmonary vascular resistance

Summary In stored blood as well as in various organs, a substance appears which causes a marked drop of systemic blood pressure after intravenous injection. The active principle was called depressor active substance (DAS). In order to study the circulatory effects of DAS the systemic and the pulmonary vascular resistance (SVR and PVR) and the ventilation volume were measured. DAS stopped respiratory movements by exciting afferent vagus fibres and led to an abnormal cardiac activity and to bronchoconstriction by stimulation of the vagotonus. Furthermore, DAS showed a direct bronchoconstrictor effect. The application of DAS caused a strong increase of PVR. This effect was strong enough to produce an abrupt drop of the systemic blood pressure because of a reduced diastolic filling of the left ventricle. Higher quantities of DAS led to an acute insufficiency of the right ventricle.Part of these results was presented at the meeting of the German Pharmacological Society, Mainz, March 21st–24th 1971.     

Community pharmacists'' views and beliefs about the treatment of symptoms suggestive of vaginal thrush in community pharmacies

Objective: To investigate the views and beliefs of community pharmacists about the benefits and disadvantages to the customer, pharmacy and pharmacist of treating women with symptoms suggestive of vaginal thrush. Design: Semistructured interviews.Setting: Community pharmacists from within Grampian Primary Care NHS Trust.Outcome Measures: Pharmacists' views and beliefs analysed using content analysis.Results: Of the 26 pharmacists contacted, 19 (73%) pharmacists from 16 pharmacies completed interviews. The pharmacists were generally positive towards the treatment of women with vaginal symptoms and perceived few disadvantages. Immediate access to treatment and rapid symptom relief were perceived to be the greatest advantages to the customer. The main problems were customer embarrassment, cost and the risk of masking a serious condition. Customer embarrassment was perceived to be influenced by lack of privacy and the gender of the member of staff involved in the consultation. Five pharmacists perceived vaginal thrush to be an infection that could be spread by sexual transmission. Discussion: There is a need to make pharmacists aware of the current evidence regarding the treatment of vaginal thrush, particularly that sexual partners of women with acute, uncomplicated thrush do not require treatment with an antifungal. The main difficulties that community pharmacists reported with the treatment of this condition were obtaining an accurate history and this was influenced by customer embarrassment. The gender of pharmacy staff and lack of private consultation facilities were suggested as factors that are associated with customer embarrassment and hence, the ability to obtain an accurate history.