Showing papers by "Arduino A. Mangoni published in 2003"
TL;DR: This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.
Abstract: Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiological stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.
1,296 citations
TL;DR: After adjusting for gender, smoking status, and blood pressure, age and body mass index independently predicted QT interval in healthy subjects by contrast, age is not a predictor of QTd.
Abstract: Objective: although the isolated effects of age on QT interval and QT dispersion (QTd) have been previously investigated, no data are available on the simultaneous effects of age and other physiological or lifestyle factors on QT interval and QTd in healthy subjects. We studied the effects of age, gender, body mass index, smoking status, and blood pressure on these electrocardiographic parameters. Design: observational study. Setting: academic medical centre. Participants and measurements: age, gender, body mass index, smoking status, and blood pressure were obtained from 191 consecutive healthy subjects (101 males and 90 females, age range 19–89 years). The subjects were divided into three groups according to their age: -30 (n=56), 30–65 (n=49), and )65 years (n=86). Results: heart-rate corrected QT interval (QTc, Bazett’s formula) progressively increased with advancing age (389" 3v s. 411"4 vs. 418"3 ms, means"SEM; P-0.01). By contrast, no differences in QTd were observed across the three groups (36" 2v s. 35" 3v s. 40" 2m s,P=NS). A multivariate regression analysis showed that age (P-0.01) and body mass index (P=0.04) independently predicted QT interval while gender was a weak (P=0.09) predictor of QTd. Conclusions: after adjusting for gender, smoking status, and blood pressure, age and body mass index independently predicted QT interval in healthy subjects. By contrast, age is not a predictor of QTd. The increase of QT interval associated with ageing and body mass index might be secondary to cardiac hypertrophy and myocardial action potential prolongation.
128 citations
TL;DR: The main changes include loss of large artery compliance, dysfunction of some of the systems modulating resistance vessel tone, increased activity of the sympathetic nervous system, and reduced haemodynamic responses to inotropic agents.
Abstract: The ageing process is associated with important changes in the responses of the cardiovascular system to pharmacological stimuli. They are not limited to the arterial system, involved in the modulation of cardiac afterload and vascular resistance, but they also involve the low-resistance capacitance venous system and the heart. The main changes include loss of large artery compliance, dysfunction of some of the systems modulating resistance vessel tone, increased activity of the sympathetic nervous system, and reduced haemodynamic responses to inotropic agents. This review focuses on the effects of ageing on arterial and venous reactivity to drugs and hormones, the autonomic nervous system, and the cardiovascular responses to inotropic agents. Some of the age-related changes might be at least partially reversible. This may have important therapeutic implications.
72 citations
TL;DR: This review addresses the research evidence on epidemiology of prescribing in elderly patients, methods of measuring the quality, and the role of the prescriber and the multidisciplinary team in the day-to-day optimization of drug therapy.
Abstract: The hazards of prescribing many drugs, including side-effects, drug interactions, and difficulties of compliance, have long been recognized as particular problems when prescribing for elderly people The need for appropriate and rational prescribing for elderly patients has been prioritized in the National Service Framework for Older People This review addresses the research evidence on epidemiology of prescribing in elderly patients, methods of measuring the quality, and the role of the prescriber and the multidisciplinary team in the day-to-day optimization of drug therapy
63 citations
TL;DR: Folic acid might have an anti-thrombotic effect in this high-risk group independent of the homocysteine lowering effect, and induced a significant reduction in plasma fibrinogen and D-dimer concentrations in healthy chronic smokers.
41 citations
TL;DR: The technique of functional magnetic resonance imaging is discussed in detail as a tool to assess the effects of therapeutic agents on the central nervous system and monitor the progression of diseases.
Abstract: Stroke and dementia represent a major health burden for elderly subjects as they are associated with significant morbidity and mortality. The rates of stroke and dementia are progressively increasing due to the ageing population in most westernized countries. Therefore, both these conditions represent a major therapeutic target. However, the therapeutic options available for the management of stroke and dementia remain largely unsatisfactory, the main reason being the difficulty in transferring the results obtained in animal and in vitro studies to the clinical setting. This review focuses on the recent advances in pathophysiology and treatment of these conditions and future directions for research. Moreover, the technique of functional magnetic resonance imaging is discussed in detail as a tool to assess the effects of therapeutic agents on the central nervous system and monitor the progression of diseases. Finally, an overview of the issue of drug delivery into the central nervous system is presented.
11 citations
TL;DR: In this article, the authors compared low-dose enalapril (5 mg) with intermediate dose (10 mg) and high-dose (20 mg) in patients aged 18-85 years with NYHA class II-IV w4x.
Abstract: Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, frequency of hospitalisation for heart failure and slow the progression of left ventricular systolic dysfunction w1,2x. These benefits are independent of baseline use of diuretics, aspirin and beta-blockers and of the type of ACE inhibitor prescribed. Since the original descriptions of outcome benefit from ACE inhibitors, attention has been focussed on examining the dose–response relationship. The ATLAS study demonstrated reduction in the combined endpoint of mortality and hospitalisation (hazard ratio 0.85, 95% CI 0.78–0.93) with lisinopril 32.5–35 mg daily vs. 2.5–5 mg daily but there is no significant benefit in all-cause mortality and cardiovascular mortality w3x. The NETWORK trial, conducted by general practitioners and hospital physicians in the UK, compared low dose enalapril (5 mg) with intermediate dose (10 mg) and high dose (20 mg) in patients aged 18–85 years with NYHA class II–IV w4x. The study did not demonstrate a relationship between dose of enalapril and clinical outcome (hospitalisation for heart failure, worsening heart failure, death). However, this study had limited power since it treated patients for only 6 months and reported few deaths and hospitalisations. An American study of elderly patients discharged from hospital on ACE inhibitors showed significantly lower mortality at 1 year in patients treated with high dose ACE inhibitors (enalapril 20 mg a day, lisinopril 20 mg a day and captopril 150 mg a day) w5x. The results of the ongoing ACHIEVE trial comparing quinapril 10 vs. 40 mg are
8 citations
TL;DR: To elucidate the pathophysiological mechanism of the vasodepressor form (VD) of carotid sinus syndrome by maneuvers designed to induce generalized sympathetic activation after baroreceptor unloading or direct peripheral adrenoreceptor stimulation via local administration of norepinephrine.
Abstract: OBJECTIVES: To elucidate the pathophysiological mechanism of the vasodepressor form (VD) of carotid sinus syndrome (CSS) by maneuvers designed to induce generalized sympathetic activation after baroreceptor unloading (lower body negative pressure, LBNP) or direct peripheral adrenoreceptor stimulation via local administration of norepinephrine (NA).
DESIGN: Subjects were identified with VD of CSS through diagnostic testing.
SETTING: Research laboratory.
PARTICIPANTS: Eleven young controls (YC) (mean age ± standard error of mean = 22.8 ± 0.7), eight elderly controls (EC) (72.6 ± 0.6), and eight elderly patients with VD (78.7 ± 1.7).
MEASUREMENTS: Forearm arterial blood flow (FABF) was measured in the left and right arms by venous occlusion plethysmography. Measurements were performed during baseline conditions, LBNP (−20 mmHg), and intra-arterial NA infusion in the left brachial artery at three progressively increasing rates (60, 120, and 240 pmol/min).
RESULTS: During LBNP, FABF significantly decreased in YC (baseline 3.61 ± 0.30 vs −20 mmHg 2.96 ± 0.24 mL/100 g/min, P = .030) and EC (4.05 ± 0.74 vs 3.69 ± 0.65 mL/100 g/min, P = .033) but increased in elderly patients with VD (3.65 ± 0.60 vs 4.54 ± 0.80 mL/100 g/min, P = .020). During NA infusion, a significant forearm vasoconstriction occurred in YC (FABF left:right ratio 1.00 ± 0.05 at baseline; 0.81 ± 0.08 at 60 pmol/min, P = .034; 0.81 ± 0.05 at 120 pmol/min, P < .001; 0.72 ± 0.04 at 240 pmol/min, P < .001), whereas no significant FABF changes were observed in EC (1.04 ± 0.06; 0.96 ± 0.07, P = .655; 0.89 ± 0.10, P = .401; 0.94 ± 0.10, P = .590) or elderly patients with VD (1.04 ± 0.06; 1.16 ±0 .10, P = .117; 1.04 ± 0.08, P = .602; 1.11 ± 0.10, P = .305).
CONCLUSION: VD of CSS is associated with a paradoxical vasodilatation during LBNP and an impairment of peripheral α-adrenergic responsiveness, which may be age-related.
8 citations
TL;DR: In the DAN‐PH group, the renin‐angiotensin‐aldosterone system response to O was relatively preserved compared with A and NA responses, whereas the reduced A response was a feature of DAN regardless of PH.
Abstract: Objective: The pathophysiological mechanisms involved in the progression of autonomic neuropathy (AN) and development of postural hypotension (PH) in type 2 diabetes (T2D) are largely unknown. The aim of this study was to address this issue by investigating the neurohormonal responses during active orthostatism (O) in T2D patients with and without PH. Methods: Plasma noradrenaline (NA, pmol/L), adrenaline (A, pmol/L), plasma renin activity (PRA, angiotensin I, nmol/L/h) and aldosterone (ALD, pmol/L) were measured in the supine position (baseline) and after 2, 5, and 20 min O in 10 healthy subjects (C), 9 T2D patients without AN (D), 14 T2D patients with AN and without PH (DAN), and 7 T2D patients with AN and PH (DAN‐PH). Results: NA concentrations were significantly increased in the C, D and DAN groups during O. In the DAN‐PH group, NA increased less markedly with no significant changes at 20 min O (+354±89 pmol/L at 2 min, p<0.05; +756±171 at 5 min, p<0.05; +656±295 at 20 min, p=NS). Absolute NA incremen...
4 citations
Journal Article•
TL;DR: High intravenous doses of steroids were given with a dramatic improvement in the patient's breathing and radiographic findings, and the pathophysiological mechanisms of acute interstitial pneumonia and current therapeutic options are discussed.
Abstract: A previously healthy 37-year-old man was admitted with a two-month history of increasing shortness of breath and high temperature. A chest X-ray demonstrated bibasal shadowing and small bilateral pleural effusions; arterial blood gases demonstrated low pO2. Despite intravenous antibiotics no significant improvement was observed. A high-resolution chest computed tomography showed diffuse ground-glass opacification with segmental and subsegmental airways opacification, indicating fine fibrosis. Subsequently, open lung biopsy showed diffuse alveolar damage and a histopathological diagnosis of acute interstitial pneumonia (Hamman-Rich syndrome) was made. Antibiotics were stopped and high intravenous doses of steroids were given with a dramatic improvement in the patient's breathing and radiographic findings. The pathophysiological mechanisms of acute interstitial pneumonia and current therapeutic options are discussed.
01 Jan 2003
TL;DR: The study did not demonstrate a relationship between dose of enalapril and clinical outcome (hospitalisation forHeart failure, worsening heart failure, death) and had limited power since it treated patients for only 6 months and reported few deaths and hospitalisations.
Abstract: Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, frequency of hospitalisation for heart failure and slow the progression of left ventricular systolic dysfunction w1,2x. These benefits are independent of baseline use of diuretics, aspirin and beta-blockers and of the type of ACE inhibitor prescribed. Since the original descriptions of outcome benefit from ACE inhibitors, attention has been focussed on examining the dose–response relationship. The ATLASstudy demonstrated reduction in the combined endpoint of mortality and hospitalisation (hazard ratio 0.85, 95% CI 0.78–0.93) with lisinopril 32.5–35 mg daily vs. 2.5–5 mg daily but there is no significant benefit in all-cause mortality and cardiovascular mortality w3x. The NETWORK trial, conducted by general practitioners and hospital physicians in the UK, compared low dose enalapril ( 5m g ) with intermediate dose (10 mg) and high dose (20 mg) in patients aged 18–85 years with NYHA class II–IV w4x. The study did not demonstrate a relationship between dose of enalapril and clinical outcome (hospitalisation for heart failure, worsening heart failure, death). However, this study had limited power since it treated patients for only 6 months and reported few deaths and hospitalisations. An American study of elderly patients discharged from hospital on ACE inhibitors showed significantly lower mortality at 1 year in patients treated with high dose ACE inhibitors (enalapril 20 mg a day, lisinopril 20 mg a day and captopril 150 mg a day) w5x. The results of the ongoing ACHIEVE trial comparing quinapril 10 vs. 40 mg are