Treatment of atherosclerotic renovascular disease

Treatment of atherosclerotic renovascular disease is controversial and revascularization is not a beneficial approach to all patients. Conditions as progressive deterioration of renal function, refractory hypertension or accelerated cardiovascular disease, especially recurrent pulmonary edema, could profit from renal angioplasty with stent placement. Surgical revascularization is a good option for patients who will need concomitant surgical corrections of abdominal aortic lesions. Treatment of all other patients must be individualized. Medical therapy is indicated for all patients with atherosclerotic renovascular disease. Observational studies pointed out to the beneficial effect of controlling blood pressure (<130/80 mm Hg), glucose and lipids profile, lifestyle modifications, specific use of platelet antiaggregant therapy, Angiotensin Conversion Enzyme Inhibitors (ACEI) and statins. All others cardiovascular risk factors must be controlled. The evaluation and management of other systemic atherosclerotic vascular lesions is important, especially coronary, carotid and abdominal aortic. This paper presents a review of evidences to rationale the atherosclerotic renovascular disease treatment. © 2008 Bentham Science Publishers Ltd.

Adherence, adaptation and acceptance of elderly chronic heart failure patients to receiving healthcare via telephone-monitoring

Background: Although the potential to reduce hospitalisation and mortality in chronic heart failure (CHF) is well reported, the feasibility of receiving healthcare by structured telephone support or telemonitoring is not. Aims: To determine; adherence, adaptation and acceptability to a national nurse-coordinated telephone-monitoring CHF management strategy. The Chronic Heart Failure Assistance by Telephone Study (CHAT). Methods: Triangulation of descriptive statistics, feedback surveys and qualitative analysis of clinical notes. Cohort comprised of standard care plus intervention (SC + I) participants who completed the first year of the study. Results: 30 GPs (70% rural) randomised to SC + I recruited 79 eligible participants, of whom 60 (76%) completed the full 12 month follow-up period. During this time 3619 calls were made into the CHAT system (mean 45.81 SD ± 79.26, range 0-369), Overall there was an adherence to the study protocol of 65.8% (95% CI 0.54-0.75; p = 0.001) however, of the 60 participants who completed the 12 month follow-up period the adherence was significantly higher at 92.3% (95% CI 0.82-0.97, p ≤ 0.001). Only 3% of this elderly group (mean age 74.7 ±9.3 years) were unable to learn or competently use the technology. Participants rated CHAT with a total acceptability rate of 76.45%. Conclusion: This study shows that elderly CHF patients can adapt quickly, find telephone-monitoring an acceptable part of their healthcare routine, and are able to maintain good adherence for a least 12 months. © 2007.

Common and rare variants of the renin-angiotensin system and their relation to antihypertensive drug responses

Most of the diseases affecting public health, like hypertension, are multifactorial by etiology. Hypertension is influenced by genetic, life style and environmental factors. Estimation of the influence of genes to the risk of essential hypertension varies from 30 to 50%. It is plausible that in most of the cases susceptibility to hypertension is determined by the action of more than one gene. Although the exact molecular mechanism underlying essential hypertension remains obscure, several monogenic forms of hypertension have been identified. Since common genetic variations may predict, not only to susceptibility to hypertension, but also response to antihypertensive drug therapy, pharmacogenetic approaches may provide useful markers in finding relations between candidate genes and phenotypes of hypertension. The aim of this study was to identify genetic mutations and polymorphisms contributing to human hypertension, and examine their relationships to intermediate phenotypes of hypertension, such as blood pressure (BP) responses to antihypertensive drugs or biochemical laboratory values. Two groups of patients were investigated in the present study. The first group was collected from the database of patients investigated in the Hypertension Outpatient Ward, Helsinki University Central Hospital, and consisted of 399 subjects considered to have essential hypertension. Frequncies of the mutant or variant alleles were compared with those in two reference groups, healthy blood donors (n = 301) and normotensive males (n = 175). The second group of subjects with hypertension was collected prospectively. The study subjects (n=313) underwent a protocol lasting eight months, including four one-month drug treatment periods with antihypertensive medications (thiazide diuretic, β-blocker, calcium channel antagonist, and an angiotensin II receptor antagonist). BP responses and laboratory values were related to polymorphims of several candidate genes of the renin-angiotensin system (RAS). In addition, two patients with typical features of Liddle’s syndrome were screened for mutations in kidney epithelial sodium channel (ENaC) subunits. Two novel mutations causing Liddle’s syndrome were identified. The first mutation identified located in the beta-subunit of ENaC and the second mutation found located in the gamma-subunit, constituting the first identified Liddle mutation locating in the extracellular domain. This mutation showed 2-fold increase in channel activity in vitro. Three gene variants, of which two are novel, were identified in ENaC subunits. The prevalence of the variants was three times higher in hypertensive patients (9%) than in reference groups (3%). The variant carriers had increased daily urinary potassium excretion rate in relation to their renin levels compared with controls suggesting increased ENaC activity, although in vitro they did not show increased channel activity. Of the common polymorphisms of the RAS studied, angiotensin II receptor type I (AGTR1) 1166 A/C polymorphism was associated with modest changes in RAS activity. Thus, patients homozygous for the C allele tended to have increased aldosterone and decreased renin levels. In vitro functional studies using transfected HEK293 cells provided additional evidence that the AGTR1 1166 C allele may be associated with increased expression of the AGTR1. Common polymorphisms of the alpha-adducin and the RAS genes did not significantly predict BP responses to one-month monotherapies with hydroclorothiazide, bisoprolol, amlodipin, or losartan. In conclusion, two novel mutations of ENaC subunits causing Liddle’s syndrome were identified. In addition, three common ENaC polymorphisms were shown to be associated with occurrence of essential hypertension, but their exact functional and clinical consequences remain to be explored. The AGTR1 1166 C allele may modify the endocrine phenotype of hypertensive patients, when present in homozygous form. Certain widely studied polymorphisms of the ACE, angiotensinogen, AGTR1 and alpha-adducin genes did not significantly affect responses to a thiazide, β-blocker, calcium channel antagonist, and angiotensin II receptor antagonist.

Étude de la pharmacologie de ligands du récepteur EP4 de prostaglandine E2

La prostaglandine E2 est une hormone lipidique produite abondamment dans le corps, incluant dans le rein où elle agit localement pour réguler les fonctions rénales. Un couplage à la protéine Gαs menant à une production d’AMPc a classiquement été attribué au récepteur EP4 de PGE2. La signalisation d’EP4 s’est cependant avérée plus complexe et implique aussi un couplage aux protéines sensibles à la PTX Gαi et des effets reliés aux β-arrestines. Il y a maintenant plusieurs exemples de l’activation sélective de voies de signalisation indépendantes par des ligands des récepteurs couplés aux protéines G (RCPG), et ce concept désigné sélectivité fonctionnelle pourrait être exploité dans le développement de nouveaux médicaments plus spécifiques et efficaces. Dans une première étude, la puissance et l’activité intrinsèque d’une série de ligands d’EP4 pour l’activation de Gαs, Gαi et de la ß-arrestine ont été systématiquement déterminées relativement au ligand endogène PGE2. Dans ce but, trois essais de transfert d’énergie de résonance de bioluminescence (BRET) ont été adaptés pour évaluer les différentes voies dans des cellules vivantes. Nos résultats montrent une sélectivité fonctionnelle importante parmi les agonistes évalués et ont une implication pour l’utilisation d’analogues de la PGE2 dans un contexte expérimental et possiblement clinique, puisque leur spectre d’activité diffère de l’agoniste naturel. La méthodologie basée sur le BRET utilisée lors de cette première évaluation systématique d’une série d’agonistes d’EP4 devrait être applicable à l’étude d’autres RCPG. Dans une deuxième étude, des peptides reproduisant des régions juxtamembranaires extracellulaires du récepteur EP4 ont été conçus selon le raisonnement que des peptides ciblant des régions éloignées du site de liaison du ligand naturel ont le potentiel de ne moduler qu’une partie des activités du récepteur. L’insuffisance rénale aiguë est une complication médicale grave caractérisée par un déclin brusque et soutenu de la fonction rénale et pour laquelle il n’y a pas de traitement efficace à l’heure actuelle. Nos résultats montrent que le peptidomimétique dérivé d’EP4 optimisé (THG213.29) améliore significativement les fonctions rénales et les changements histologiques dans une insuffisance rénale aiguë induite par cisplatine ou par occlusion des artères rénales dans des rats Sprague-Dawley. Le THG213.29 ne compétitionnait pas la liaison de la PGE2 à EP4, mais modulait la cinétique de dissociation de la PGE2, suggérant une liaison à un site allostérique d’EP4. Le THG213.29 démontrait une sélectivité fonctionnelle, puisqu’il inhibait partiellement la production d’AMPc induite par EP4 mais n’affectait pas l’activation de Gαi ou le recrutement de la ß-arrestine. Nos résultats indiquent que le THG213.29 représente une nouvelle classe d’agent diurétique possédant les propriétés d’un modulateur allostérique non-compétitif des fonctions du récepteur EP4 pour l’amélioration des fonctions rénales suite à une insuffisance rénale aiguë.

Doença pulmonar obstrutiva crônica

Chronic obstructive pulmonary disease (COPD) is an extremely common disorder that all primary care physicians should be able to manage. In this review we will define the entities incorporated in COPD and will present various aspects of the diagnoses and treatment. We could not cover every aspect of this broad topic even providing a detailed review of those areas but some facets of therapy like smoking cessation, drug therapy, oxygen therapy, nutrition, and respiratory rehabilitation will be described.

HIPERTENSAO ARTERIAL NA CRIANCA

The objective of this report was to summarily review the concept and the prevalence of arterial hypertension in children, its peculiarities and the difficulties in measuring of blood pressure at this age. Considerations of clinical picture, diagnosis, laboratory and drug-induced test (Captopril) were discussed. The authors presented various therapies utilized in hypertension and hypertensive crisis.

TRATAMENTO DA HIPERTENSAO ARTERIAL LEVE E MODERADA COM FOSINOPRIL. COMPARACAO DE EFEITOS ADVERSOS COM OUTROS ANTI-HIPERTENSIVOS

Purpose - To evaluate the adverse reactions of fosinopril with other antihypertensives used as monotherapy. Methods - Out-patients (n = 2,568) with diagnostic of mild to moderate hypertension, diastolic blood pressure (DBP) 95-115 mmHg, with no antihypertensive treatment for 15 days, were included to treatment initially with fosinopril (F) 10mg, once daily, for six weeks. After this period, patients with DBP >95mmHg had the dosage, once daily, increased to 20 mg, while the others were maintained with the same dosage for six more weeks. Adverse reactions of 822 patients treated as monotherapy were grouped as absent, musculoskeletal, cardiovascular, cough, gastrointestinal, neurological, genital-urinary dysfunctions and dermatological and compared with 1,568 with F. Monotherapy consist in α-methyldopa (100 patients); β-blocker (129); calcium blocker (106); diuretic (394); and another ACE inhibitors (93). Results - At the end of the period without treatment, the blood pressure (BP), 165 ± 16/105 ± 7 mmHg decreased significantly at 6(th) week to 144 ± 15/91 ± 9 mmHg (p < 0.05 vs week 0) with further lowering to 139 ± 13/86 ± 7 mmHg till the end of 12(th) week. BP response (DBP ≤90 mmHg) was obtained in 89% of the patients with F. Absence of adverse reactions were ≥70% in patients with F compared to other drugs. Conclusion - Fosinopril has demonstrated therapeutic efficacy and less adverse reactions compared to antihypertensives used previously as monotherapy.

INFLUENCIA DO ACRESCIMO DE MANITOL A SOLUCAO NUTRIENTE NO DESEMPENHO MECANICO E NO GRAU DE EDEMA MIOCARDICO DE CORACOES ISOLADOS DE RATOS

Purpose - To analyse the influence of mannitol added to Krebs-Henseleit (KH) solution on the myocardium edema and myocardial function. Methods - Isolated rat heart under isovolumetric contractions studied according to Langendorff's technique were perfused with KH solution at constant flow during 90 min. The coronary perfusion pressure, diastolic and systolic pressures were recorded at every 15 min. At the end of the experiment, myocardium water content was measured in hearts perfused with KH solution (group I, n = 9) and in hearts perfused with KH solution plus 8 mM mannitol (group II, n = 8). These results were compared to non-perfused control heart (n = 9). Results - Myocardial water content was statistically higher in group I (80.8 ± 1.3%) compared to group II (78.1 ± 0.7%) and control group (75.5 ± 0.5%). Systolic arterial pressure was statistically higher in group I (86.2 ± 11.5 mmHg) compared to group II (72.7 ± 21.1 mmHg). There was no difference in the diastolic pressure between the two groups. Coronary perfusion pressure (Pp) increased progressively during the experiment in both groups. However, Pp was lower in group II than in group I. Conclusion - Mannitol added to KH solution significantly attenuates the myocardium edema in the isolated perfused rat heart.

Consumo de medicamentos por idosos segundo prescrição médica em Jaú-SP

This study was carried out in order to identify the interactions that occur most often between prescribed drugs as they are taken by elderly patients attending municipal public health centers in the city of Jaú, São Paulo State, Brazil. It is known that older people frequently have to live with chronic health problems, which oblige them to use the health service a great deal and to consume large quantities of medicines. When concomitant diseases are present, and polytherapy is being applied, the likelihood of adverse reactions and interactions between drugs increases. The population under study consisted of 148 persons aged 65 or more who frequented the pharmacy at the Núcleo de Gestão Assistencial (Municipal Health Centre, NGA25) in Jaú, between August and December 2004. Data were collected from medical prescriptions, the independent variables being the age and sex of the patient. For each patient, the pharmacological classes of drugs taken and drug-drug interactions were recorded. It was found that the mean numbers of drugs consumed were 3.8 among women and 3.9 among men. In terms of age, the highest number of drugs (4.2) was used in the group aged 75 to 84 years. The most frequently prescribed classes, in decreasing order, were: antihypertensives, 25.0%, heart drugs, 15.5%, diuretics, and anti-diabetic drugs, 10.7%. It was concluded that the classes most involved in drug-drug interactions were heart drugs, diuretics and antihypertensives. The most problematic active constituents were digoxin, amiodarone, frusemide, captopril, propranolol and nifedipine.

Síndrome de Eisenmenger na gravidez

Eisenmenger's syndrome consists of pulmonary hypertension with a reversed or bidirectional shunt at the atrioventricular, or aortopulmonary level. Eisenmerger's syndrome in pregnancy is usually associated with high mortality rates (nearly 30-50%). Unfortunately, pulmonary hypertension is aggravated during pregnancy and often leads to an unfavorable outcome. Here, we report a successful pregnancy in a woman with Eisenmenger syndrome.

Farmacología en la tercera edad: Medicamentos de uso continuo y peligros de la interacción medicamentosa

Introduction: It was observed a considerable growth of elderly people. They are who use more medicines. The physiological changes associated with the age advancing can make pharmacokinetic and pharmacodynamic alterations. The cognitive decline, physical limitations and associate chronic pathology affect the medications appropriately use ability. Aims: Based in a literature review, appoint the main pharmacological groups prescribed to the elderly and the drug-drug interaction risks. Conclusion: The most of elderly use continually at least 3 medicines, the most prescribed are to cardiovascular and psychic diseases treatment.