[Pain assessment in terminally-ill cancer patients on admission in hospice and its modification after the first three days of care. A monocentric experience]. / Il dolore nel paziente oncologico terminale: valutazione del sintomo all'ingresso in hospice e delle sue modifi cazioni nei primi tre giorni di assistenza. Esperienza monocentrica.

AIMS: Pain is among the most frequent and distressing symptoms in terminally-ill cancer and, to date, many patients still experience uncontrolled pain. In this paper we evaluated prevalence and intensity of pain on admission in our palliative care center and during the first three days of care. PATIENTS AND METHODS: From September 2009 to October 2009 we consecutively recruited 96 terminally-ill cancer patients : on admission more than 50% had severe pain and only 4% referred to be pain-free. 54% of patients was on treatment with strong opioids. RESULTS: After three days from admission in our palliative care unit only 7% of patients experienced severe pain, 25% reported absence of pain and 80% of patients was on treatment with strong opioids. CONCLUSIONS: The beginning of palliative care led to a meaningful and rapid reduction of pain in the vast majority of terminally-ill cancer patients evaluated in this study.

Altered blood pressure variability in patients with congestive heart failure.

OBJECTIVE: Congestive heart failure (CHF) is characterized by sympathetic overactivity but reduced variability of heart interval and sympathetic nerve activity; little information exists, however, about the alterations in blood pressure variability in this syndrome, especially during excitatory manoeuvres such as tilting or exercise. DESIGN AND METHODS: Nine patients with CHF (age 62+/-1 years, NYHA class II-III, ejection fraction 33+/-1%, peak VO2 14.1+/-3.2 ml/min per kg body weight [mean +/- SEM]) and eight healthy control subjects (age 58+/-1 years) with normal left ventricular function were studied. Blood pressure (Finapres), R-R interval (ECG) and respiration (nasal thermistor) were recorded during 15-min periods of supine rest, 70 degree head-up tilting, submaximal bicycling exercise and post-exercise recovery. Total variance and the power of the spectral components of blood pressure (HF, respiratory-related; LF, 0.03-0.14 Hz; and VLF, 0.02-0.003 Hz) were measured. RESULTS: Compared with control subjects, CHF patients have, first, a normal overall blood pressure variability during supine rest but a failure to increase this variability in response to head-up tilt and exercise; second, a suppressed LF spectral component of blood pressure at rest and in response to head-up tilt and exercise; and third, reappearance of LF blood pressure power during postexercise recovery. CONCLUSIONS: In CHF patients, overall blood pressure variability and its LF spectral component are altered at rest and during sympathoexcitatory manoeuvres. Somewhat paradoxically, however, the depressed LF blood pressure power is partially restored during a 15-min recovery period, indicating that at least part of the CHF-related alterations of blood pressure variability have the potential to revert back towards normal under appropriate physiological circumstances.

Nadolol prevents the exercise-induced rise in lymphocyte beta-receptor number in borderline hypertension.

Thirteen borderline hypertensives were investigated at rest and during dynamic exercise, before and after therapy with nadolol (40-80 mg/day for 7-28 days), in order to evaluate regulation of the number of lymphocyte beta-receptors. Systolic blood pressure and the heart rate were measured before and after 15 min of bicycle exercise, both with and without nadolol therapy; blood samples were withdrawn for adrenaline, noradrenaline and lymphocyte beta-receptor determinations. Nadolol induced a significant decrease in systolic blood pressure and the heart rate at rest, while plasma catecholamines and lymphocyte beta-receptors did not change significantly. Of the physiological responses to dynamic exercise (increases in systolic blood pressure, heart rate, plasma noradrenaline levels and adrenaline and lymphocyte beta-receptors), only the rise in beta-receptors was entirely prevented, and the increase in the heart rate was significantly attenuated by nadolol. It is suggested that the lack of a rise in the number of beta-receptors during exercise may contribute to the blunted exercise-induced tachycardia in patients taking nadolol.

Advantages and limitations of diuretic therapy in essential hypertension.

The diuretics previously considered the "cornerstone" of the antihypertensive treatment have recently undergone a reevaluation and have been considered as a potential cause of the lack of "cardioprotection" found in different epidemiological studies. The reduction in plasma potassium and the changes in lipoproteins should represent the mechanisms of the negative interference of diuretics at cardiac levels. In spite of this common opinion, there is no clinically consistent evidence that the lowering of serum potassium and the changes in lipoproteins are responsible for the lack of cardioprotection during antihypertensive therapy. It is possible that other causes, for instance the reflex activation of sympathetic nervous system and/or renin secretion, may play an important role in determining the cardiac effects of antihypertensive therapy. However, it is also true that diuretics have been used in the past at doses that were too high, and the changes in serum potassium and lipoproteins can be minimized by administering lower doses of diuretics without decreasing their antihypertensive efficacy.

Systemic haemodynamic and humoral changes during urapidil treatment in hypertensive patients.

Urapidil, a new antihypertensive agent exerting a peripheral alpha 1-postsynaptic blocking action and an additional action at the central level, has some characteristics which may correct the underlying pathophysiological abnormalities found in the great majority of hypertensive patients. When administered acutely and chronically, urapidil significantly lowers blood pressure in hypertensive patients by reducing total peripheral resistance, while cardiac output is unchanged or only slightly elevated. The blood pressure reduction can cause a decrease in cardiac mass in patients with left ventricular hypertrophy. Urapidil has been successfully administered also in patients with congestive heart failure and in hypertensive crises during or following surgical procedures; in all these conditions urapidil lowers total peripheral resistance, but blood pressure is lowered only in patients with hypertensive crises and no clinically relevant reduction in blood pressure is found in patients with congestive heart failure. The acute administration of urapidil has shown a trend towards a rise in plasma renin activity, in plasma aldosterone and in plasma catecholamines; on the whole, however, the activation of these systems has been mild.

Nifedipine does not blunt the aldosterone and cardiovascular response to angiotensin II and potassium infusion in hypertensive patients.

The antihypertensive response of calcium antagonists of the dihydropyridine series, although accompanied by a significant increase in plasma renin activity (PRA), is generally not associated with a comparably significant rise in plasma aldosterone (PA). This has been suggested to be due to the adrenal glomerular cell responsiveness being dependent on calcium entry. To investigate this hypothesis, angiotensin II (AII; 0.15, 0.375, and 0.750 micrograms/min, each step for 20 min) and KCl (30 mmol/50 min) were infused on separate days in 11 hypertensive patients kept at a constant daily intake of 100 mmol sodium and 40 mmol potassium, before and after 1 week of nifedipine treatment (20 mg b.i.d.). Supine blood pressure (BP) was significantly (p less than 0.01-p less than 0.001) reduced after nifedipine treatment; supine PRA increased significantly (p less than 0.01), while PA did not change significantly. No change in plasma potassium level was seen during nifedipine treatment. The dose-dependent mean BP rises induced by AII were slightly blunted during nifedipine treatment, whereas the PRA decreases and the PA rises after the peak infusion were not significantly different before and during nifedipine administration. Potassium infusion had no significant effect on BP, and caused a significant and similar rise in PA before and during nifedipine administration, while PRA decrease was more pronounced after nifedipine treatment. As previously shown in normotensive subjects, and also in hypertensive patients, aldosterone responses to two major stimulants, such as AII and potassium, do not appear to be blunted by treatment with a calcium antagonist.

Calcium antagonists and responsiveness of the adrenal glands to aldosterone-releasing stimuli in hypertensive patients.

This study was designed to determine whether a reduced responsiveness of adrenal zona glomerulosa to physiological stimuli could be responsible for the lack of a proportional rise in plasma renin activity and plasma aldosterone during administration of calcium antagonists. We selected 11 hypertensive patients and measured the rise in plasma aldosterone in response to infusions of angiotensin II or potassium chloride before and after a 7-day treatment with fully antihypertensive doses of nifedipine (20 mg twice a day), while the patients were kept on a constant daily intake of sodium (100 mmol) and potassium (40 mmol). The treatment with nifedipine induced a significant reduction in both systolic and diastolic blood pressures; the infusions of angiotensin II (0.150, 0.375 and 0.750 microgram/min, each rate for 30 min) and of potassium chloride (50 mmol in 500 ml of 5% glucose in 50 min) caused similar rises in plasma aldosterone before and during the administration of the calcium antagonist. Therefore, our results indicate that responsiveness of the adrenal zona glomerulosa to physiological stimuli is maintained despite blockade of calcium channels capable of significantly lowering arterial blood pressure.

Renal effects of felodipine in hypertension.

The results of 2 recent studies on the renal effects of felodipine in hypertensive patients are described. Antihypertensive doses of felodipine (10mg bid) displayed a clear natriuretic and diuretic effect associated with a constant glomerular filtration rate and an increase in renal plasma flow. With higher doses of felodipine (up to 50mg tid), the natriuretic effect was reversed to an antinatriuretic effect, accompanied by a reduction in glomerular filtration rate. The natriuretic effect of felodipine 10mg bid was evident during the first 2 days of administration, but a negative sodium balance was still present at the end of the seventh day. The mechanisms of the renal effects of calcium antagonists are discussed as well as the relevance of the natriuretic effect for the antihypertensive action of these compounds.

Resting and postexercise hemodynamic effects of carvedilol, a beta-adrenergic blocker and precapillary vasodilator in hypertensive patients.

Carvedilol is a recently developed antihypertensive drug that combines in the same molecule a nonselective beta-adrenoceptor blocking effect and a vasodilating precapillary activity. In our study, we have investigated the effects of carvedilol 25 mg b.i.d. on blood pressure, heart rate, and plasma noradrenaline in hypertensive patients at rest and during exercise after acute and repeated oral administration for 7 days. The daily average supine blood pressure of the 12 patients with essential hypertension was 178 +/- 10/107 +/- 3 mm Hg (means +/- SD of 8 measurements in each patient) after placebo and was significantly (p less than 0.01) reduced to 162 +/- 17/99 +/- 8 mm Hg on the first day and to 158 +/- 15/96 +/- 8 mm Hg on the seventh day of carvedilol treatment. Similar values were found in the upright posture. Heart rate was slightly but significantly lowered during acute and repeated administration. The exercise-induced increase in systolic blood pressure was significantly reduced by carvedilol 25 mg b.i.d., while there was a nonsignificant reduction in the tachycardic response. There was a significantly greater rise in plasma noradrenaline during exercise on the seventh day of carvedilol treatment. Carvedilol significantly lowered blood pressure and heart rate at rest and the exercise-induced rise in systolic blood pressure.

Effects of single and repeated doses of the calcium antagonist felodipine on blood pressure, renal function, electrolytes and water balance, and renin-angiotensin-aldosterone system in hypertensive patients.

Doses of 10 mg b.i.d. of the new dihydropyridine calcium antagonist, felodipine, were tested for seven consecutive days in 11 hospitalized hypertensive patients. A significant reduction of both systolic and diastolic blood pressures, with patients in both the supine and upright positions, occurred immediately after the first dose and was maintained (daily average 15%) throughout the following days. An increase in heart rate was observed after the first dose (15 and 23 beats/min, in supine and upright postures), and subsequently declined to average values of 8 and 14 beats/min on the seventh day. There was a marked natriuretic response during the first and second day, during which an average negative sodium balance of 95 mmol developed; on the following days sodium output was not significantly different from control, but a negative balance averaging 135 mmol was still present on the seventh day of felodipine administration. A moderate negative potassium balance also progressively developed and reached -48 mmol on the seventh day. Glomerular filtration rate was unchanged, but renal plasma flow increased significantly during administration of felodipine. Plasma renin activity and plasma aldosterone were also increased very moderately by felodipine. Compared with previous observations by our group with higher doses of felodipine (12.5, 25, and 50 mg t.i.d.), 10 mg b.i.d. of this new calcium antagonist appear to exert a marked and prolonged blood pressure reduction, accompanied by a definite natriuretic instead of an antinatriuretic effect.

Does beta 1-selective agonistic activity interfere with the antihypertensive efficacy of beta 1-selective blocking agents?

In order to investigate whether addition of beta 1-selective agonism can interfere with the antihypertensive efficacy of beta 1-selective adrenoceptor blockers, two separate studies were carried out to evaluate the effects on blood pressure and heart rate of three beta 1-selective blockers with or without varying degree of beta 1-selective agonism. In hypertensive patients at rest, the greatest blood pressure reduction and bradycardia were found with atenolol, a beta 1-selective blocker without any agonistic activity; a consistently smaller effect on blood pressure and heart rate was observed with Visacor (ICI 141 292), a beta 1-selective blocker with moderate beta 1-selective agonism, whereas no clinically relevant decrease in blood pressure occurred with Corwin (ICI 118 587), the beta 1-selective blocker with high beta 1-selective agonism. In contrast, during exercise-induced sympathetic activation, all three compounds reduced systolic blood pressure and heart rate to a similar degree.

Renal and antihypertensive effects of felodipine in hypertensive patients.

The effects of small doses of felodipine (10 mg twice daily) on blood pressure, renal function and sodium and water balance were studied in 11 patients with arterial hypertension. Felodipine significantly reduced systolic and diastolic blood pressure: most of the antihypertensive effect was already evident on day 1 of administration (-18/-11 mmHg) and only slightly increased during the subsequent week. Heart rate rose moderately only during day 1 of felodipine administration (+7 beats/min). Sodium excretion was increased during days 1 and 2, and no signs of water and electrolyte retention was observed in the week during which the balance study could be performed (Na, -135 +/- 65 mmol/7 days). At relatively low doses felodipine appears to be an effective antihypertensive agent, initially exerting some diuretic and natriuretic action and subsequently being devoid of a water- and sodium-retaining action.

Antihypertensive and water and sodium balance effects of felodipine, a new vasodilating calcium antagonist, in hypertensive patients.

Felodipine, a new dihydropyridine derivative with a selective action on vascular smooth muscle, was investigated in 2 short term studies in hypertensive patients. In the first study, oral administration of felodipine 12.5 mg three times daily in a preliminary tablet formulation for 3 days significantly reduced supine and upright blood pressure with only a slight increase in heart rate and no clinically relevant signs of sodium and water retention. By increasing each dose to 25 and 50 mg three times daily, there was a further, but quite moderate, decrease in blood pressure; however, this was accompanied by an increase in heart rate and a tendency towards a reduction of creatinine clearance and urinary sodium output. In the second study, a new oral formulation containing 10 mg felodipine, administered twice daily for 7 days, was effective in lowering blood pressure without a clinically relevant tachycardia. Following the first dose of felodipine, urinary sodium excretion was slightly increased while potassium excretion showed only minor changes. The new calcium antagonist, felodipine, lowers blood pressure without the clinically relevant adverse reactions commonly related to other direct vasodilator antihypertensive drugs.

Felodipine, a new vasodilating drug: blood pressure, cardiac, renal, and humoral effects in hypertensive patients.

We studied the antihypertensive action of felodipine, a new dihydropyridine vasodilator interfering with intracellular calcium mechanisms, in 11 patients with essential hypertension whose supine blood pressure averaged 181/109 mm Hg after 5 days of placebo administration. Felodipine, 12.5 mg t.i.d., for 3 days, caused a marked reduction (-39/-19 mm Hg) of supine systolic and diastolic pressures. Doses of 25 and 50 mg t.i.d., for three consecutive days, caused only a slight further reduction of blood pressure. At the highest dose tested all patients had their supine blood pressure brought down to values below 150 mm Hg systolic and 90 mm Hg diastolic at all six daily measurements. The antihypertensive effect was of the same magnitude when the patients lay supine or stood upright. Lowering of blood pressure was accompanied by tachycardia, which was quite moderate after the 12.5 mg t.i.d. dose, but more conspicuous with the two higher doses. There was some increase in plasma renin activity and in plasma aldosterone. A significant decrease in renal sodium and water excretion occurred only during administration of the highest dose of 50 mg t.i.d., when reduction in blood pressure was pronounced and there were reflex increases in plasma renin activity and plasma aldosterone.

Acute hypotensive and renin-stimulating actions of captopril before and during treatment with a beta-blocking drug.

There is no general agreement on the relation between the hypotensive effect of captopril and the pretreatment plasma renin levels of hypertensive patients. To determine whether the hypotensive effect of captopril was directly related to plasma renin, the angiotensin-converting enzyme inhibitor was administered acutely to 10 essential hypertensive patients with normal or suppressed plasma renin activity before and after inhibition of renin secretion with propranolol. Captopril was equally effective in reducing blood pressure both when administered alone (25 mg: -29/-17; 50 mg: -37/-23 mm Hg) and after chronic treatment with propranolol (25 mg: -33/-20; 50 mg: -30/-20 mm Hg). The increase in renin induced by captopril was not decreased by propranolol therapy. The persistence of the hypotensive effect of captopril after renin suppression by propranolol suggests that this drug has some blood pressure decreasing properties independent of plasma renin.

Comparison of cardiovascular, renal, and humoral effects of acute administration of two calcium channel blockers in normotensive and hypertensive subjects.

The acute effects of two calcium channel blockers, nifedipine and verapamil, were compared in eight normotensive subjects and eight patients with essential hypertension. Nifedipine 10 mg and verapamil 160 mg orally had no effect on blood pressure of normal subjects, but reduced systolic and diastolic pressures of hypertensive patients to the same extent. The blood pressure reduction caused by nifedipine was more prompt and of lesser duration than that caused by verapamil. In both normal subjects and hypertensive patients nifedipine caused a transient rise in heart rate and plasma renin activity, and plasma catecholamines showed a tendency to increase; verapamil did not affect these variables. Nifedipine induced a marked increase in urine volume and renal sodium excretion in hypertensive patients, with a much smaller change in normotensives. Verapamil did not influence water and sodium excretion in either direction. Thus, this study shows similarities and differences between the effects induced by acute oral administration of the most-used vasodilating calcium antagonists.