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Biomedical subjects

F J Morales-Olivas

Publications and source records attributed to F J Morales-Olivas.

At least 19 recordsLinked to original sources

[Are the Spanish hypertensive children therapeutic orphans?].

INTRODUCTION: According to current guidelines, hypertension in children should be treated with the same drugs as those used in adults, with adjustment of the dose to their body size. The term therapeutic orphans refers to the lack of information on how to use drugs in children. The aim of this study was to investigate whether the information in the International Vademecum (I-V) is sufficient for the correct use of antihypertensive drugs in children. MATERIAL AND METHOD: We reviewed the data on pediatric dosages of antihypertensive drugs in the I-V (44th and 45th editions). When there were several drugs for the same molecule, the last one marked with the Spanish Ministry of Health and Consumption's logo was selected. When information on a particular drug was not available, the entries for other drugs with the same active principle were reviewed. The information was compared with that provided by the Fourth Report of the National High Blood Pressure Education Program Working Group (NHBPEP). RESULTS: A total of 111 entries for 41 antihypertensive drugs were reviewed. Information on use in children is available for only 3 diuretics and 2 angiotensin converting enzyme inhibitors. The remaining entries either contain no information or indicate that the effectiveness and safety in children has not been evaluated. Some drugs are contraindicated in children. The Fourth Report of the NHBPEP includes pediatric dosages for 28 antihypertensive drugs. The Food and Drug Administration has authorized 10 antihypertensive drugs for use in children. CONCLUSIONS: The information in the V-I can be used to determine the correct dosage of only 5 antihypertensive drugs in children, making this age group authentic therapeutic orphans.

Antihypertensive Agents↗

[Effect of arterial pressure and age on renal function, The "Care for the Kidney" study].

BACKGROUND: The kidney is one of the principal target organs of hypertension. The mechanism by which hypertension damages the kidney and the relative contribution of high blood pressure to the progression of renal failure remains incompletely defined. The clinical quantification of renal function is usually thought to require determination of plasma clearance of endogenous creatinine (ClCr), an impractical test for epidemiological evaluation. For this reason several formulae have been proposed to estimate the ClCr from the serum creatinine concentration, such as sex, age, and body weight. The most often used formula is the one proposed by Crockroft and Gault in 1976. OBJECTIVE: To determine the prevalence of loss of renal function and the influence of hypertension and age on this loss in hypertensive and normotensive patients. PATIENTS AND METHOD: An observational, cross-sectional comparative study was carried out. 3,420 patients (1,171 normotensive and 2,249 hypertensive) were studied. Average age was 70 years (19.4% of patients < 65 years; 23.3% > 75 years). 98.1 of hypertensive patients were treated with drugs, 26.7% of them with more than one drug. 27.9% of treated patients achieved blood pressure control (< 140-90 mm Hg). The level of renal function was estimated by means of ClCr using the Crockroft and Gault formula. RESULTS: 3.9% of normotensive and 12.2% of hypertensive patients had serum creatinine values > 1.3 mg/dl, but 28.6% of normotensive and 40.4% of hypertensive had ClCr < 60 ml/min. The patients over 75 years had ClCr mean values < 60 ml/min. There was correlation between ClCr and age, but there was no correlation between ClCr and blood pressure values. CONCLUSIONS: The estimated ClCr decrease with age and there existed correlation between both variables. The ClCr is lower in hypertensive than in normotensive patients. Hypertension and age influence loss of renal function, but age is a determining factor. The estimated ClCr was a more sensible method of evaluating the loss of renal function than the serum creatinine values. The use of Crockroft and Gault formula can be useful for making diagnostic and therapeutic decisions in primary care.

Aged↗

Characteristics of histamine tachyphylaxis in rat uterine smooth muscle.

OBJECTIVE AND DESIGN: To study both the desensitisation induced by short-term exposure to histamine and the mechanism responsible in the isolated rat uterus. MATERIAL: Precontracted isolated uterus (37 mM KCl) from oestrogenised Wistar rats were used. TREATMENT: Repetitive responses to histamine (10(-6), 10(-5), 10(-4), 10(-3) M), dimaprit and clonidine (10(-4) M) were tested at 15, 30, 45 and 105 min., with their modifications by (5 mg/kg, 24 h before sacrifice) reserpine, 10(-7) M propranolol, 10(-8) M atropine, and 10(-6) M indomethacin. Dose-response curves for adrenaline were carried out as standard protocol. METHODS: In vitro techniques (de Jalon's solution, 31 degrees C, carbogen, isotonic registration, resting tension 1 g). Levels of cAMP were studied in response to histamine, adrenaline and isoproterenol by radioassay. RESULTS: Repeated histamine produced a rapid loss of inhibitory uterine response depending on the number of exposures and increase in concentration. The tachyphylaxis phenomenon is not modified by the different pretreatments used. Dimaprit, but not clonidine or adrenaline, produced tachyphylaxis. The second exposition to 10(-3) M histamine produced a 38.8% reduction in cAMP production. CONCLUSION: Histamine appears to induce homologous and probably cAMP-dependent desensitisation of H2-receptors.

Adrenergic alpha-Agonists↗

Adverse drug reactions in children reported by means of the yellow card in Spain.

OBJECTIVE: To analyze the case reports concerning children (14 years or younger) in the Spanish Pharmacovigilance System over a 10-year period (1982-1991). FINDINGS: The study of 1419 reports of adverse drug reaction (9.8% of all those received) showed the most commonly involved organs and systems to be the skin, digestive tract, and nervous system (62.8%). The most commonly involved pharmacological groups were antibiotics, respiratory medications, and vaccines (69%). The absolute number of reports is higher in children between 1 and 4 years of age (37.9%). There were more reports among males than in females. Less than 5% of the reports notified directly life-threatening or fatal reactions. CONCLUSIONS: Adverse drug reaction are not common in pediatric patients, and most are mild. However, due to limitations of clinical trials in children, pharmacoepidemiological studies may be the only source of information on the benefit-risk profile of drugs received by these patients, and as such require special attention.

Adolescent↗

A prospective study of adverse drug reactions in hospitalized children.

AIMS: There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. METHODS: An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. RESULTS: A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR=1.66, 95% CI 1.03-2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. CONCLUSIONS: Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients.

Child, Hospitalized↗

The effects of histamine on the isolated mouse uterus.

1. A study is made of the contractile and relaxant effects, and mechanism of action, of histamine on isolated uterus from mice treated with diethylstilboestrol, employing acetylcholine and adrenaline as contractile and relaxant standard agents. 2. Concentration-response curves for histamine agonists were obtained in the absence and presence of selective histaminergic blocking drugs (clemizole, ranitidine and thioperamide) and indomethacin. A number of experiments were carried out in uterus from reserpinised mice. Concentration-response curves for acetylcholine and adrenaline were also obtained in the absence and presence of their selective antagonist (atropine and propranolol). 3. In isolated oestrogenised mouse uterus, histamine and acetylcholine produced a concentration-related contractile response. When the uterus was precontracted with KCl, histamine at lower doses produced a slight contraction, though in the presence of clemizole it induced concentration-related relaxation, reminiscent of that produced by adrenaline. Atropine and propranolol antagonised the contractile and relaxant effects of acetylcholine and adrenaline, respectively. 4. In isolated uterus from reserpinised mice, histamine and 2-pyridylethylamine, but not 4-methylhistamine, produced a concentration-related contractile response. Ranitidine potentiated the contractile effect of histamine, though clemizole--in the presence of ranitidine--competitively antagonised the contractile effect of histamine (pA2 = 10.50 +/- 0.81). The concentration-relaxant curve of histamine in the presence of clemizole was not modified by ranitidine or indomethacin, but shifted to the right with thioperamide. The same displacement was also observed in the presence of clemizole plus ranitidine. 5. In mouse isolated uterus, histamine mainly produced contraction mediated by histamine H1-receptors, though the existence of histamine H2- or H3-receptors mediating relaxation could not be excluded.

Acetylcholine↗

Isolated human chorionic vascular reactivity: technical considerations for fresh preparations.

1. Sixty chorionic vascular rings from normal term placentas were immersed in an organ bath for isometric tension recording to study (A) the contractile response to 120 mM of potassium chloride (KCl) after adjustment and equilibration to 1-5 g of passive tension; and (B) the concentration-response curve to KCl after adjustment and equilibration to the optimal passive tension. 2. Adjustment to 4 g of passive tension elicited the maximal (P < 0.007) and the latest (P < 0.006) KCl-induced contraction among arterial rings. Venous rings showed the greatest contraction when adjusted to 3 g, but the differences were not significant except when compared to 1 g of passive tension (P < 0.03). 3. The EC50 for chorionic arteries and veins was 14.2 and 25.7 mM, respectively (P < 0.003). The maximal contraction was already obtained with 40 mM of KCl. 4. Our results suggest that (A) the optimal passive tension for fresh human chorionic arteries is 4 g; (B) chorionic venous reactivity is less influenced by the initial tension; and (C) the optimal concentration of KCl to be used as a contracting agent of these tissues is 40 mM.

Arteries↗

The effects of epinine on arterial blood pressure and regional vascular resistances in anesthetized rats.

1. We carried out experiments in anesthetized rats to study the hemodynamic effects of intravenous injections of epinine. 2. Epinine (1-320 micrograms/kg) produced a biphasic effect on mean arterial blood pressure (n = 30). At doses lower than 40 micrograms/kg, arterial blood pressure decreased (by as much as 21.5 +/- 3.4%), though at higher doses it increased dose dependently (by as much as 73.2 +/- 14.5%). Epinine also produced bradicardia in a dose-dependent manner (by as much as 26.4 +/- 4.9%). Sulpiride (100 micrograms/kg) suppressed the hypotensive effect of epinine but did not change the hypertensive effect. In the presence of prazosin (1,000 micrograms/kg), arterial blood pressure remained significantly decreased at all doses of epinine. Neither sulpiride nor prazosin changed the bradycardic effect of epinine. 3. Prazosin produced a significant decrease in renal vascular resistance. Epinine (5 micrograms/kg) after prazosin reverted the effects of prazosin in renal vascular resistance, without any significant modification in the renal blood flows. However, 20 micrograms/kg epinine increased the renal vascular resistances and, moreover, produced a significant decrease in the blood flows of both kidneys. Neither prazosin nor epinine produced modifications in the intestinal vascular bed. 4. Although epinine possesses significant dopamine and alpha-adrenergic activities that are involved in the biphasic effect of the agent on mean arterial blood pressure in anesthetized rats, in the presence of prazosin, it is not possible to manifest dopaminergic activity involved in the increase in renal or mesenteric blood flow; this may be due to the low tone of the vascular wall induced by the alpha-adrenergic antagonist, though an alpha 2-activity cannot be discarded.

Anesthetics, Intravenous↗

Fluoxetine-associated stomatitis.

OBJECTIVE: To describe two cases of stomatitis related to fluoxetine given for the treatment of depression that were detected in the hospital emergency department. DATA SYNTHESIS: Two women developed stomatitis after the intake of fluoxetine for the treatment of depression. One of the patients had six recurrent episodes of stomatitis without suspecting an association with fluoxetine. No other drugs were administered during these episodes. The second patient was treated concurrently with fluoxetine and bentazepam. In both patients the lesion improved upon discontinuation of fluoxetine, even though the second patient continued to take a different benzodiazepine. DISCUSSION: Stomatitis related to fluoxetine has not been previously reported in clinical trials or in the literature. According to the causal algorithm used by the Spanish Drug Surveillance Schemes, the first case constituted a defined adverse reaction and the second was probable. CONCLUSIONS: Our observations suggest that fluoxetine may be considered as a probable cause of stomatitis. The reporting of isolated cases of adverse drug reactions (ADRs) makes it possible to define the toxicity profile of recently marketed drugs such as selective serotonin-reuptake inhibitors, including fluoxetine. Emphasis is placed on the potential role played by emergency departments in detecting ADRs.

Adult↗

Are the adverse drug reactions of amoxycillin and amoxycillin-clavulanic acid similar?

UNLABELLED: In an attempt to assess the relative toxicity of amoxycillin and amoxycillin-clavulanic acid, we compared the adverse drug reactions reports collected using the spontaneous reporting system of a Regional Drug Surveillance Centre of Spain for both drugs between November 1986 and December 1992. During the 7-year period 1986-92, the 247 reports of amoxycillin-clavulanic acid represent twice the number of reports of amoxycillin alone, and the number of reports related with sales received concerning the association were higher than those concerning amoxycillin alone. The adverse effects classified as severe were quantitatively and qualitatively similar for both drugs and gastrointestinal and skin are the most common system-organ affected by both drugs. With amoxycillin-clavulanic acid there is a higher proportion of stomatological reactions reported and a later onset of adverse drug reactions related with oropharyngeal lesions, and the reaction of the resistance mechanism when compared with the other organs and systems affected. The duration of the adverse drug reactions to amoxycillin-clavulanic acid is longer than for amoxycillin alone. IN CONCLUSION: (i) the adverse drug reactions profile of both drugs is different; (ii) the higher reporting rate for amoxycillin-clavulanic acid may be due to more recent marketing; and (iii) amoxycillin-clavulanic acid produces proportionately more gastrointestinal and fewer skin adverse reactions than amoxycillin alone.

Journal Article↗

A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital.

1. A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). the proportion of suspected ADRs related to hospital admissions was 4.3%. 2. The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3. The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each). 4. There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37-2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72-5.42). 5. The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group.

Child, Preschool↗

Isolated human colon strips as a pharmacological tool.

The spontaneous activity of isolated human colon strips was studied to obtain homogeneous results with a reproducible model. The strips of macroscopically normal appearance were mounted in an organ bath containing Krebs solution at 32 degrees C or Tyrode solution at 37 degrees C. Mechanical activity was recorded by an isometric transducer. Spontaneous motility did not occur in all preparations. Moreover, when observed, it could not always be evaluated. The percentage of strips with spontaneous activity was lower with Tyrode solution than with Krebs solution (65 vs. 81%). KC1 did not induce a plateau contraction. Acetylcholine induced concentration-dependent contractions, with a significantly different pD2: 4.43 +/- 0.39 and 5.59 +/- 0.16 for Krebs and Tyrode, respectively. Isoprenaline abolished spontaneous motility in Krebs solution. Only 20% of specimens presented evaluable motility. Krebs solution may be the best conditions for studying the effects of drugs on spontaneous motility, while Tyrode solution can be used to investigate the effects of contractile agents.

Acetylcholine↗

No evidence for dopamine-induced relaxation in isolated human mesenteric arterial strips from elderly patients.

1. We investigate the effects of dopamine in isolated mesenteric artery from elderly patients. 2. Noradrenaline (10(-11) to 10(-4) M) and dopamine (2.7 x 10(-6) to 1.4 x 10(-3) M) induced a concentration-dependent contraction that was antagonized by prazosin. Fenoldopam (10(-8) to 10(-4) M) and clonidine (10(-9) to 10(-4) M) did not produce any contractile effects. 3. Potassium chloride (80 mM) produced a well-maintained plateau contraction and dopamine-induced contraction in these conditions, which was decreased by prazosin (10(-8) M). Neither fenoldopam nor isoprenaline (10(-10) to 10(-5) M) modified the well-maintained plateau. 4. Our results suggest that post-synaptic dopamine receptors are not present in this preparation but alpha1-adrenoceptors are present.

Aged↗

[Adverse reactions from angiotensin-converting enzyme inhibitor drugs reported by the yellow card].

BACKGROUND: The aim of the present study was to analyze the adverse reactions (AR) to captopril (CP) and enalapril (EN) reported by voluntary notification by the yellow card (YC) over the first five years of the foundation of the Drug Surveillance Center of the Valencian Community. METHODS: The AR described were classified by organs and systems, evaluating the age and the sex of the patient, the indication for the drug, dosage used, and the level of health care assistance received since notification. Previous knowledge of the reported AR was analyzed, as was the possible relation of causality with the drug and severity of the same. The rates of notification were calculated with respect to the consumption of both drugs, expressed in daily dosage defined (DDD). RESULTS: Two hundred one YC were evaluated, 111 for CP and 90 for EN referring 160 and 133 clinical manifestations, respectively. The rate of notification was 2.51 YC/million DDD for CP and 5.57 for EN. The AR in the respiratory tract were the most frequently reported with cases of dry cough representing 33.7% of the total YC for CP and 33.8% for EN. Cutaneous AR followed for both drugs. Angioedema was reported in 0.09 AR/million DDD for CP and 0.56 for EN. Reactions were most frequently observed in patients over the age of 50 with a predominance of the female sex, being usually slight and with 80% having been notified from primary health care centers. CONCLUSIONS: The high number of reports of cough demonstrate that this is the most frequently observed adverse reaction. The distribution of reactions and the characteristics of the patients with the same coincide with other studies. The low number of yellow cards reporting severe adverse reactions may support the favorable safety profile of this pharmacologic group, or, to the contrary, be a consequence of the under-reporting of adverse reactions.

Adult↗

Effect of histamine on the longitudinal and circular muscle of the oestrogen dominated rat uterus.

The response of the longitudinal and circular myometrial strips to histamine was studied in oestrogen-treated rats. Histamine produced a dose-related inhibitory response in KCl-contracted longitudinal and circular uterine strips. Histamine was equipotent in producing the relaxant response but the maximal effect achieved in the longitudinal muscle was higher than the circular one. Ranitidine antagonized the histamine-induced relaxation with a similar dose ratio in both longitudinal and circular strips. Clemizole and reserpine treatment did not produce any modification of the dose-response curve to histamine. In the longitudinal and circular strips which were not preconstricted by KCl, neither histamine nor 2-pyridylethylamine, even in strips pretreated with ranitidine, produced any effect when added to the organ bath. Our results show that the response of histamine in both longitudinal and circular uterine layers of the oestrogen-treated rats are mediated exclusively by histamine H2-receptors.

Animals↗