Adjustable maintenance dosing with budesonide/formoterol in a single inhaler provides effective asthma symptom control at a lower dose than fixed maintenance dosing.

Asthma guidelines suggest a stepwise approach to maintenance pharmacological treatment of persistent asthma until control is attained, and a 3 month review of the fixed maintenance dosing for step-up or step-down adjustment. This 12-week study compared the efficacy and safety of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler 160/4.5 or 80/4.5 microg) given as adjustable maintenance or fixed maintenance dosing. Patients (n = 2358) were randomised to budesonide/formoterol fixed maintenance dosing (two inhalations bid) or adjustable maintenance dosing (two inhalation bid; stepping up to four inhalations bid if asthma worsened for a maximum of 14 days; stepping down to two inhalations once nocte or one inhalation bid if symptoms were controlled) for 12 weeks, following a 4-week run-in period on budesonide/formoterol two inhalations bid. Primary efficacy variables were frequency of asthma exacerbations and changes in patients' asthma symptom severity. Secondary variables were asthma control, safety and health economics. Both adjustable maintenance dosing and fixed maintenance dosing were associated with similar low frequency of exacerbations (5% both groups; ns) and similarly improved lung function, with similarly fewer nocturnal awakenings and less asthma symptoms compared with the mean value of the run-in period. However, patients on adjustable maintenance dosing used 24% fewer study drug compared with fixed maintenance dosing (2.95 versus 3.86 inhalations daily; p < 0.0001) and incurred in a significant (p <0.0001) reduction in total costs (direct+indirect) compared with fixed maintenance dosing. In conclusion, adjustable maintenance dosing with budesonide/formoterol effectively controls asthma at a reduced drug load with lower costs than fixed maintenance dosing.

Nebivolol and airway responsiveness in the rabbit.

Beta-adrenergic receptor antagonists are currently used as first-line therapy in the treatment of hypertension and angina pectoris, but are contraindicated or used with caution in patients with bronchospastic syndromes. In this study we evaluated in vivo the effects of nebivolol on airway responsiveness compared to atenolol, pindolol, and propranolol. In New Zealand white rabbits total lung resistance (R(L)) and dynamic compliance (Cdyn) were calculated. In acute protocol, the animals were intravenously injected with the beta-blockers at different doses while in the chronic protocol, animals were daily injected for 30 days. Furthermore, the changes induced by beta-blockers (higher doses) in R(L) and Cdyn after a treatment with salbutamol were calculated. In acute treatment, airway responsiveness to histamine was not modified by nebivolol at any dosage, but increased significantly following the exposure to the higher doses of the other beta-blockers. In chronic treatment, the thirty-day exposure to nebivolol, did not modify the airway responsiveness to histamine, whereas the other beta-blockers significantly increased airway responsiveness. Moreover, nebivolol affected the salbutamol-induced relaxation less markedly than other beta-blockers do. These data demonstrate that nebivolol respect the other beta-blockers used in this study, does not significantly affect the airway responsiveness, therefore it could be used in patients with both cardiovascular and bronchial diseases more safely than other beta-blockers drugs.

Antibiotic drug prescription in respiratory tract infections: a pharmacoepidemiological survey among general practitioners in a region of Italy.

Data concerning patients undergoing antibiotic treatment for upper (URTI) or lower (LRTI) respiratory tract infections were collected from 23 General Practitioners (GPs) in the Campania Region of Italy from November 15, 1997 to March 15, 1998. The objectives of the study were: a) to assess the occurrence of URTIs and LRTIs; b) to document the factors that influence GPs' choice of therapy; c) to correlate antibiotic choice with duration and outcome of treatment; d) to assess the incidence of unwanted effects. 2198 questionnaires were collected. Patients were +/-43.9 of age. URTIs were diagnosed in 65.4% and 34.6% LRTIs. The mean duration of antibiotic treatment was 4.5 days in URTIs and 5.6 days in LRTIs. The choice of antibiotic treatment was influenced by clinical assessment of infections (67.1%). The most commonly used antibiotic categories in URTIs were macrolides (39.3%), penicillins (27.4%) and cephalosporins (23.8%) whereas for LRTIs mainly cephalosporins (63.8%), penicillins (9.2%) and fluoroquinolones (7.4%) were used. Adverse events were experienced by 3.9% of patients.

[Pharmacology of ritodrine]. / Farmacologia della ritodrina.

Tocolytic drugs are used in order to delay or to abolish preterm labour. These drugs inhibit uterine contractions and have different pharmacological properties. The most used tocolytic agents today are beta 2-adrenergic agonists (isoxuprine, ritodrine). The pharmacological actions, pharmacokinetics, toxicological and clinical aspects of ritodrine, a synthetic beta 2-adrenergic agonist with tocolytic properties are described. Findings of many clinical trials are also discussed.

[Benefit/risk ratio of antibiotic therapy] / Il rapporto beneficio/rischio dell'antibioticoterapia.

This publication evaluates critically the benefit/risk profile of several antibiotics currently at our disposal. The considered antibiotics are divided into pharmacological classes, because generally the drugs of the same class share the same adverse events. Moreover, the high therapeutic profile of the antibiotics puts them at the top of the safest drugs. Therefore the choice of an antibiotic is based above all on the evaluation of the patient and of the pathology to be treated, in terms of severity and possibility of achieving a response to treatment. An accurate anamnesis, the identification of the correct dosage and of the therapy duration minimise the potential risks of the chosen treatment. Detailed knowledge of the safety profile of these drugs is a further element in order for the antibiotic to perform at its best

Antibiotic prophylaxis for surgical procedures: a survey from an Italian university hospital.

The aims of this study were: 1) to evaluate the surgical prophylaxis regimens adopted by surgeons of the University Hospital of the Faculty of Medicine and Surgery of the 2nd University of Naples during the period January-March 1996; 2) to compare uses of antibiotic prophylaxis carried out in surgical departments to standard international guidelines; 3) to assess the cost of surgical prophylaxis. Data from 1,085 surgical patients from January 1, 1996 to March 31, 1996, were collected, reporting surgical department, type of surgery, antibiotics used, dosage, and length of the prophylactic treatment. Collected data underwent computer-assisted evaluation and comparison to the international guidelines. Four-hundred and twenty-five patients with concomitant diseases, who did not meet inclusion criteria into standard guidelines, were excluded from the study. The remaining patients (N = 660) underwent clean or clean-contaminated surgical procedures. Two-hundred and twenty patients underwent clean surgical procedures, with prophylactic antibiotic treatment lasting from 1.1 +/- 0.3 to 4.6 +/- 2.8 days. Four-hundred and forty patients underwent a clean-contaminated surgical procedure, with antibiotic prophylaxis lasting from 3.6 +/- 2.4 to 5.2 +/- 3.7 days. Third generation cephalosporins were the most frequently used antibiotics both in patients undergoing clean (163 patients = 74.1%), and clean-contaminated surgical procedures (321 patients = 73%). The resulting costs were about ten-fold higher than costs of antibiotic prophylaxis carried out according to international guidelines. In conclusion, our research highlights the habit of non-compliance with standard guidelines for antibiotic prophylaxis both in terms of drug choice and treatment duration.

[Intensive hospital monitoring of adverse reactions to benzodiazepines and neuroleptic agents]. / Monitoraggio intensivo ospedaliero delle reazioni avverse da benzodiazepine e neurolettici.

BACKGROUND: The main aims of the programme were to highlight the incidence of adverse reactions to the drugs monitored and to define the risk/benefit ratio taking account of the main physiological and physiopathological variations of patients. This paper reports the results of the programme regarding to adverse effects correlated to the use of some psychiatric drugs (benzodiazepines and neuroleptics). METHODS: A total of 73 records were compiled for 64 patients treated with benzodiazepines and/or neuroleptics. RESULTS: A very high mean incidence of adverse events was documented (48%) without any severe undesirable effects. 92% of patients treated with neuroleptics reported adverse events. Haloperidol, which caused adverse effects in 80% of patients, revealed mild or moderate forms of parkinsonism (15%), spasm (15%), rigidity (10%), akathisia (5%), reversible postural hypotension (10%), temporary reduction of the visual field (10%), delayed menstrual flow (5%), xerostomia (10%), excessive sweating (10%) and sialorrhea (10%). All the patients treated with clozapine showed adverse effects including postural hypotension (29%), persistent tachycardia (14%), sialorrhea (29%), excessive sweating (14%) and akathisia (14%). Spasms (25%), rigidity (25%) and akathisia (25%) were correlated to the use of clothiapine, whereas postural hypotension was referred to clopenthixol. 44% of patients treated with benzodiazepines showed undesired effects. 20% of those taking chlordemethyldiazepam showed somnolence (33%), sedation (22%) and dysar-thria (44%). Prolonged sedation was observed in 30% of all patients treated with lorazepam. Prazepam was correlated with adverse effects in 75% of cases. No adverse event was documented with bromazepam. CONCLUSIONS: A higher incidence of adverse events was documented than literature data. Further periods of intensive monitoring will be required to obtain a greater quantity of data from the intensive monitoring of adverse events through the MIO '97 programme.

[Hospital intensive monitoring of adverse reactions of ACE inhibitors]. / Monitoraggio intensivo ospedaliero delle reazioni avverse da ACE-inibitori.

BACKGROUND AND AIMS: Angiotensin II converting enzyme (ACE) inhibitors represent one of the most important pharmacological instruments for the treatment of arterial hypertension and are currently also used for other cardiovascular indications. The actions of ACE-inhibitors mainly depends on blocking the ACE enzyme in the renin-angiotensin-aldosterone system. However, the ACE enzyme also has a kinase activity. The inhibition of this enzyme may also cause an accumulation of tissue mediators (bradykinin) responsible for a number of adverse reactions. METHODS: An intensive hospital monitoring programme of adverse reactions to drugs, known as MIO[symbol: see text]'96, was carried out by the Centre of Pharmacoepidemiology of the Faculty of Medicine and Surgery at the Second University of Naples during the period 25 March-18 April 1996. The main aims of the programme were to highlight the incidence of adverse reactions to the drugs monitored and the definition of the risk/benefit ratio taking account of the main physiological and pathophysiological variations of patients. This paper reports the results of the programme of adverse effects correlated to the use of ACE-inhibitors. A total of 175 records were compiled for 105 patients receiving antihypertensive treatment with a number of ACE-inhibitors (captopril, enalapril, lisinopril); a very high mean incidence of adverse events was documented (22%) without any severe undesirable effects. RESULTS: The following adverse events were documented (the cumulative incidence is given in brackets): dysgeusia (17%), flush (8%), headache (33%), exanthema (17%), diarrhoea (8%), vertigo (8%), xerostomia (8%). Coughing was not reported in any patient. CONCLUSIONS: Further periods of intensive monitoring will be required to obtain a greater quantity of data from the Intensive Monitoring of adverse events through the MIO[symbol: see text]'97 programme.

Pharmacology of nebivolol.

Nebivolol is a new selective beta 1-adrenergic blocking agent, that possesses a peculiar pharmacodynamic profile and an original chemical structure, by which it differs from traditional beta 1-blockers. Nebivolol is a racemic mixture of two enantiomers in equal ratios. It is endowed with a highly selective beta 1-blocking activity, and does not show an intrinsic sympathomimetic activity. Nebivolol is endowed with peripheral vasodilating properties mediated by the modulation of the endogenous production of nitric oxide. It does not significantly decrease airway conductance compared with atenolol and propranolol. Nebivolol does not compromise the left ventricular function, but it may increase stroke volume, and does not reduce heart inotropism during exertion. Nebivolol is quite safe and is well tolerated, also when compared to traditional beta-blockers. The most common adverse effects are dizziness, headache and fatigue. Owing to its combined dual mechanism of action, nebivolol leads to a unique haemodynamic and therapeutic profile by which it may be advantageous in essential hypertension, ischaemic heart disease and congestive heart failure.

[Local administration of somatostatin in joint diseases in athletes]. / Somatostatina per via locale nelle patologie articolari degli sportivi.

Somatostatin is a hormone produced by the hypothalamus, and is widely diffused outside the CNS. It inhibits the secretion of many glands. Recently it has been shown that somatostatin has been proposed in the treatment of phlogistic diseases of the joints by intra-articular administration. The authors show the results of a study conducted in 16 patients (athletes) with arthrosynovitis or tendinitis of the knee or of the ankle, in which somatostatin was administered (250 mg/treatment, 1 treatment/week). Somatostatin significantly reduced pain, improved movement function and decreased the effects of pain on daily activities. The treatment was very well tolerated locally and generally. In conclusion, somatostatin may be considered useful in the treatment of articular and tendineous phlogistic diseases, almost in athletes.

[The therapy of arterial hypertension: a comparison between ACE inhibitors and angiotensin-II-receptor antagonists]. / Terapia dell'ipertensione arteriosa: confronto tra ACE-inibitori e antagonisti recettoriali dell'angiotensina II.

The efficaciousness of ACE inhibitors in arterial blood hypertension is well known. These drugs decreased the incidence of hypertension and myocardial infarction in population. However, they increase tissue levels of some kinines, that may be responsible of some adverse reactions (cough, etc.). Angiotensin-receptor antagonists can minimize the adverse reactions due to kinine accumulation and may increase the safety of the antihypertensive drug-treatment. Pharmacological and clinical aspects of angiotensin-receptor antagonists are discussed.

Effects of in vitro 5-HT1 receptor activation in guinea pig trachea.

5-hydroxytryptamine (5-HT) has been reported to show some effects in respiratory tissues by activation of different subtype receptors. It has been demonstrated that 5-HT2 receptor activation causes in vivo and in vitro airways contraction and enhances effects of cholinergic nerve-mediated responses, whereas 5-HT1 receptor activation seems to be related to a relaxant effect. Moreover, in isolated guinea pig ascendens colon preparations 5-HT1 activation causes relaxation by involvement of nitric oxide (NO). The aim of this study was to investigate the effects of 5-HT1 receptor activation in guinea pig trachea as well as NO probable role in this activation. In tissues pretreated with both ketanserin (10 microM), an antagonist of 5-HT2 receptors, and ondansetron (10 microM), an antagonist of 5-HT3 receptors, 5-HT (from 10 nM to 10 mM) relaxed guinea pig trachea precontracted with acetylcholine (ACh, 100 microM). Carboxamidotryptamine (5-CT, from 10 nM to 10 mM), an agonist of 5-HT1 receptors, as well relaxed guinea pig trachea precontracted with ACh (100 microM). A pretreatment with NAN-190 (from 10 nM to 100 microM), a 5-HT1A selective antagonist, reduced the 5-HT and 5-CT relaxant effects but only at very high concentrations. Finally, a pretreatment with L-nitro-arginine-methyl-ester (L-NAME, 1 mM), an inhibitor of NO-synthase, and L-arginine (L-ARG, 1 mM), a precursor of NO synthesis, did not modify 5-HT and 5-CT responses in guinea pig trachea. In conclusion, this study suggests a 5-HT relaxant activity in guinea pig trachea via a 5-HT1 receptor activation without any NO pathway involvement. However, further investigations are needed to clarify which 5-HT1 receptor subtype is involved in 5-HT relaxant effect.

Effect of atenolol and ramipril on regression of left ventricular hypertrophy: comparative echocardiographic assessment.

Left ventricular hypertrophy (LVH) dramatically worsens hypertensive illness. Because the genesis of LVH appears to be multifactorial, antihypertensive treatment should aim to reduce not only pressor values but also the hypertrophic ventricular mass. This result can be obtained only when drugs able to act on both pathogenetic factors are used. To evaluate the effectiveness of antihypertensive therapy on regression of LVH, 21 patients with stage 2 essential hypertension were treated for a year with either atenolol (120 mg/d orally), a cardioselective beta-blocker without intrinsic sympathomimetic activity, or ramipril (5 mg/d orally), an angiotensin-converting enzyme inhibitor with high tissue activity. Both treatments produced significant control of hypertension and regression of LVH. No statistically significant difference between treatments was noted, except for heart rate, which was substantially unchanged by ramipril but significantly decreased by atenolol. Both drugs were well tolerated. Atenolol and ramipril have a major role in the long-term treatment of hypertension and in the regression of hypertension-associated LVH.

K+ channels and guinea-pig trachea: a possible functional modulation by GABAB receptors.

K+ channel activators represent a novel class of smooth muscle relaxant agents. There is now much evidence demonstrating that K+ channels, localized to prejunctional neurons and post-junctional smooth muscle membranes, can regulate airway smooth muscle activity, inducing smooth muscle cell membrane hyperpolarization. K+ channel activity may be influenced by some neurotransmitters, such as adenosine, serotonin and noradrenaline. More recently, it has been observed that the stimulation of GABAB receptors influences K+ channels in the hippocampus, dorsal rafe and spinal cord neurons. The aim of this study was to investigate the effects of levcromakalim in guinea-pig trachea at pre- and post-junctional sites and to evaluate whether GABAB receptors may modulate K+ channel activation. Levcromakalim (from 1 nM to 1 microM) relaxed guinea-pig trachea (IC50 10 +/- 0.9 nM) previously contracted by KCl (30 mM). This effect was reversed by a pretreatment with tetraethylammonium (10 mM) (IC50 120 +/- 0.7 nM). A 30-min pretreatment with baclofen (1 microM) or phaclofen (1 microM) failed to modify the effects of levcromakalim (IC50 18 +/- 1.0 nM and 14 +/- 0.6 nM, respectively). The contractile responses to electrical field stimulation (71.20 +/- 5.12% of acetylcholine--100 microM--contraction) was significantly (P < 0.05) reduced by a pretreatment with levcromakalim (10 nM) (54.00 +/- 6.68%). This reduction was antagonized by tetraethylammonium (10 nM) (72.20 +/- 14.27%).(ABSTRACT TRUNCATED AT 250 WORDS)

Wizards and scientists: the pharmacologic experience in the Middle Ages.

During the Dark ages, Greco-Roman science survived in the eastern Roman Empire and the most important advances in pharmacology and pharmacy were made in Byzantium. As the Arab empires spread in the 7th and 8th centuries, they incorporated earlier learning, and the most important contribution of Arabic medical writers was probably the introduction of formularies to aid in the preparation of medicines. In turn, the later spread of Arabic knowledge to the West introduced little-known plants and fostered an interest in collecting and cultivating them, and also introduced the palatable dose forms preferred by the Arabic doctors. In the West, however, the Christian Church taught a doctrine of unquestioning faith, and despite the centers of learning, e.g. at Salerno, most ordinary people depended on the healing power of faith, religious relics and traditional folk medicine. Hydrology was also well developed in the Middle Ages. The formularia that survive describe many indigenous plants, but with few illustrations. Their gathering and preparation is generally guided by magic ceremonies and ritual, and plants often took their properties from their habitat, e.g. the wayside plantain was thought good for tired or wounded feet. Concepts of therapeutic plants were also influenced by alchemy and were linked to related metals and planets.

[Cocaine: the historical aspects]. / Cocaina: aspetti storici.

The habitual use of drugs acting on the human mental faculties is very ancient. An overview on the history of cocaine, from the pre-Colombian populations of South-America to our days, is reported.