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Biomedical subjects

T C Fagan

Publications and source records attributed to T C Fagan.

At least 37 records · Page 2Linked to original sources
PubMed1988

The influence of hydrochlorothiazide and tripamide on serum and urinary amylase.

Pancreatitis and asymptomatic elevations of serum amylase have been reported after therapy with thiazide diuretics. In the current study, the effects of hydrochlorothiazide and tripamide treatment on serum and urinary amylase excretion were investigated in 12 hypertensive volunteers. Two patients developed modest elevations of the serum amylase above the normal range after 12 weeks of treatment with hydrochlorothiazide 50 mg daily, but the mean serum amylase did not change. Hydrochlorothiazide did not produce a statistically significant increase in urinary amylase excretion but did reduce the ratio of salivary amylase/creatinine clearance in a two-hour urine collection. Tripamide 10 mg daily had no effect on serum or urinary amylase.

Adult↗
PubMed1988

Doxazosin in patients with hypertension.

The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mmHg in the supine and 13/18 mmHg in the standing position. Adverse effects were generally mild and of brief duration.

Adult↗
PubMed1988

Effects of ketorolac tromethamine on hemostasis in volunteers.

Ketorolac tromethamine, an analgesic agent with prostaglandin synthetase--inhibiting activity, is more active than aspirin in vitro in inhibiting collagen- or arachidonic acid-induced platelet aggregation. In this randomized, double-blind study, 26 volunteers received ketorolac, 30 mg intramuscularly four times a day for 5 days, and placebo, two capsules orally four times a day for at the last 2 study days. The effects of this treatment were compared with those of intramuscular placebo and oral aspirin, two 325 mg capsules, given on the same schedule to eight volunteers. Aspirin at a mean serum concentration of 84 micrograms/ml did not affect prothrombin time, partial thromboplastin time, platelet count, or bleeding time. Ketorolac produced a modest prolongation of the bleeding time, from 4.9 +/- 1.1 minutes (mean +/- SD) to 7.8 +/- 4.0 minutes (p less than 0.005). Ketorolac did not affect the prothrombin time or partial thromboplastin time but was associated with clinically insignificant change in the platelet count from 303 +/- 57 X 10(3)/m3 to 277 +/- 56 X 10(3)/mm3.

Adult↗
PubMed1988

Single versus triplicate measurements of blood pressure and heart rate.

The mean of rapidly repeated duplicate or triplicate measurements is often used in studies of antihypertensive drugs. Forty patients with hypertension had triplicate measurements of blood pressure and heart rate on two occasions, 1 week apart, during placebo treatment. The average difference between the first measurement and the mean of the triplicate measurements was -0.3 mm Hg. The average coefficient of variation for supine and standing, systolic and diastolic blood pressures was 8.4% for the single measurements and 8.0% for the mean of triplicate measurements. The correlations between the first measurements and the mean of triplicate measurements ranged from 0.90 to 0.98 (all p less than 0.01). The average difference between the two visits for all four blood pressure parameters was -0.6 mm Hg for the single measurements and -0.5 mm Hg for the mean of triplicate measurements (all p = NS). These results indicate that 1) blood pressure does not change further after 1 week of placebo treatment, and 2) use of the mean of triplicate measurements of blood pressure and heart rate gives the same result as use of single measurements, and the results are no less variable.

Adult↗
PubMed1987

Similar efficacy of nitrendipine in young and elderly hypertensive patients.

Calcium channel blockers have been postulated to be more effective as monotherapeutic antihypertensive agents in the elderly than in younger patients. To determine if a new dihydropyridine derivative, nitrendipine, is more effective in the elderly (older than 60 years) than in younger hypertensive subjects (younger than 60 years), nitrendipine was administered in a multicentered study to 21 elderly and 33 younger subjects with essential hypertension. After gradual discontinuation of previous antihypertensive therapy and 2 weeks of placebo, the daily dose of nitrendipine (10 to 40 mg) was titrated over 3 weeks to achieve a 10 mm Hg decrease in supine diastolic blood pressure (BP) for patients entering with 90 to 99 mm Hg. For patients entering with at least 100 mm Hg, the dose was titrated to diastolic BP no greater than 90 mm Hg. Titrated dose of nitrendipine was maintained for 4 additional weeks. Propranolol was added for "symptomatic" tachycardia. Nitrendipine reduced BP in 90% of patients completing all phases of the study (n = 49). The proportion of responders was 47% among the elderly and 44% among young subjects. Change in heart rate was similar in both groups (-0.1 +/- 9.9 and +2.9 +/- 8.8 beats/min, mean +/- standard deviation). Two elderly and 1 younger subject required addition of propranolol (difference not significant). There was no correlation between the age of patients and changes in supine systolic and diastolic BP or heart rate (r = 0.21, -0.15 and -0.21, respectively). Adverse effects occurred with equal frequency in older and younger subjects (19 of 21 vs 23 of 33 patients, difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Antihypertensive effects of parenteral nicardipine alone and in combination with captopril.

We studied the safety and efficacy of intravenous nicardipine alone and in combination with oral captopril. Sixteen patients with essential hypertension received a single oral dose of captopril, 50 mg, to be certain that excessive hypotension would not occur. Nicardipine was given intravenously as a 2 mg bolus, followed by an infusion at a rate designed to lower the supine diastolic blood pressure at least 10 mm Hg; then oral captopril, 50 mg, or placebo was given. The next week, nicardipine was again infused, but the alternate oral treatment was given. Intravenous nicardipine reduced blood pressure from 156 +/- 15/101 +/- 5 mm Hg (mean arterial blood pressure 120 +/- 6 mm Hg) to 140 +/- 11/88 +/- 4 mm Hg (mean arterial blood pressure 105 +/- 5 mm Hg). When captopril was added to nicardipine, the mean arterial blood pressure fell an additional 8 mm Hg but the heart rate did not increase. The combination of angiotensin-converting enzyme inhibition and calcium channel blockage produces additive antihypertensive effects without additional reflex tachycardia.

Administration, Oral↗
PubMed1987

Increased clearance of propranolol and theophylline by high-protein compared with high-carbohydrate diet.

The objective of this study was to determine whether changes in dietary protein and carbohydrate influence the oral clearance of propranolol, a high-clearance drug, and theophylline, a low-clearance drug. Six normal subjects studied in a clinical research center each received a single oral dose of propranolol, 80 mg, and theophylline, 5 mg/kg, after having been on each of two well-defined diets for a period of 10 days. When the diet was altered from high carbohydrate/low protein to low carbohydrate/high protein, the oral clearance of propranolol increased by 74% +/- 20% (mean +/- SE; range 9% to 156%; P less than 0.01) with no change in plasma half-life or plasma binding. This dietary change resulted in an increase in theophylline clearance of 32% +/- 6% (range 18% to 50%; P less than 0.02) and a corresponding decrease in plasma half-life of 26% +/- 6% (range 6% to 42%; P less than 0.05) with no alteration in the apparent volume of distribution. These observations reemphasize the importance of diet in drug disposition and suggest that the clearance of high-clearance drugs like propranolol is more susceptible than the clearance of low-clearance drugs to dietary manipulations, effects that may have to be considered in drug therapy.

Administration, Oral↗
PubMed1987

Effects of high protein, high carbohydrate, and high fat diets on laboratory parameters.

Six normal volunteers consumed high protein, high carbohydrate, and high fat isocaloric diets on a metabolic ward for 10 days each. On the high protein diet, serum creatinine, BUN, albumin, and total protein exceeded the normal range in from one to four subjects; the increases were directly related to the percentage of calories derived from protein (R = 0.82, 0.62, and 0.73 respectively; all p less than 0.01). Fasting serum glucose was higher on the high protein diet than on the high fat diet (p less than 0.01); values on the high carbohydrate diet were intermediate. Fasting serum glucose was not significantly related to the percentage of either total carbohydrates or simple carbohydrates in the diet. Within the range of diets frequently ingested in the United States, laboratory values can vary significantly and can exceed the normal ranges in healthy individuals. These variations may mislead clinicians and lead to further unnecessary tests.

Adult↗
PubMed1986

Postprandial alterations in hemodynamics and blood pressure in normal subjects.

The effects of a standardized mixed meal, a self-selected meal and a sham meal on heart rate, arterial pressure, cardiac output, total systemic resistance and echocardiographic indexes of left ventricular performance were examined in normal volunteers. Supine heart rate and cardiac output increased after the meals (p less than 0.07 to 0.001), but not after the sham meal. Supine diastolic blood pressure and total systemic resistance decreased after the meals but not after the sham meal (p less than 0.05 to 0.001). Ejection fraction and mean velocity of circumferential fiber shortening increased after the standard meal (p less than 0.01) and tended to increase after the self-selected meal, but did not increase after the sham meal. Meals of normal size may induce splanchnic vasodilation and a decrease in total systemic resistance. Ingestion of food also significantly affects heart rate, blood pressure, cardiac output and echocardiographic indexes of left ventricular performance. Patients should not eat during short-term evaluation of cardiovascular interventions because the cardiovascular effects of a meal may compromise interpretation of the cardiovascular effects of the primary intervention. The hemodynamic effects of food may also interact with the effects of cardiovascular disease processes.

Adult↗
PubMed1986

Antihypertensive and biochemical dose-response study of tripamide.

Tripamide is an experimental sulfonamide-derived diuretic antihypertensive agent. Twenty-four hospitalized patients with essential hypertension received placebo followed by 10, 25, 50, or 100 mg of tripamide daily in a randomized, double-blind design. All doses of tripamide significantly lowered standing arterial pressure. Changes in blood pressure, heart rate, and weight were not dose related, but the decrease in mean arterial pressure was significantly related to both age (P less than 0.02) and pretreatment blood pressure (P less than 0.05). Serum potassium levels were lowered significantly by the 25 and 100 mg daily doses of tripamide, whereas all doses of tripamide significantly reduced serum chloride levels and produced an increase in serum uric acid levels. Disparate time courses of antihypertensive and diuretic effects and the lack of a relationship between the increase in urine volume and the change in blood pressure suggest an additional antihypertensive action of tripamide or a delayed physiologic adaptation to volume depletion. Equal antihypertensive effects over the range of 10 to 100 mg/day, but greater hypokalemia at higher doses, suggest that future studies should employ the lower doses of tripamide.

Adult↗
PubMed1986

Effect of tripamide on glucose tolerance in patients with hypertension.

The effects of tripamide and hydrochlorothiazide on blood pressure and glucose tolerance were studied in 20 hypertensive patients, half of whom had type II diabetes mellitus. Each patient underwent intravenous glucose tolerance testing before and after 4 weeks of treatment with tripamide, 10 mg, and, at a separate time, hydrochlorothiazide, 50 mg. Both tripamide and hydrochlorothiazide lowered blood pressure; for both drugs, the magnitude of the reduction in mean arterial pressure was positively correlated with the pretreatment mean arterial pressure. Hydrochlorothiazide produced a greater fall in serum potassium than did tripamide. In the nondiabetics, neither drug produced a significant change in the glucose disappearance curve or the plasma insulin response. In the diabetics, hydrochlorothiazide produced an increase in serum glucose levels, but the plasma insulin response, which was blunted in comparison to the nondiabetics, did not change. Tripamide did not affect serum glucose or plasma insulin levels in either group of patients. Tripamide at a dose of 10 mg daily does not affect glucose tolerance in either nondiabetic hypertensive patients or patients with type II diabetes mellitus.

Administration, Oral↗
PubMed1986

Effects of meals on hemodynamics: implications for antihypertensive drug studies.

The ingestion of food is known to affect blood pressure and heart rate, but food is often allowed in patients under observation for antihypertensive drug effects. Seventy-seven patients with essential hypertension were observed for 8 hours after a 16-hour fast. Thirty-six continued to fast, 20 ate a high-carbohydrate meal, and 21 ate a meal of their own choice. Blood pressure and heart rate did not change during fasting, but both meals lowered mean supine and standing diastolic blood pressures during the subsequent 4 hours by 3 to 7 mm Hg (P less than 0.001). The high-carbohydrate meal reduced supine systolic blood pressure by 6 mm Hg (P less than 0.0001). Both meals increased supine and standing heart rates by 5 to 8 bpm (P less than 0.001). After the self-selected meal, standing systolic blood pressure increased in younger patients but decreased in older patients. Food ingestion during antihypertensive drug studies may interfere with the interpretation of results and should be avoided whenever possible.

Adult↗
PubMed1986

Acute hypotensive effects of oral and intravenous propranolol: early alterations in peripheral resistance.

The effects of single oral and intravenous doses of propranolol on blood pressure and hemodynamics were measured in normal volunteers. Systolic and diastolic blood pressure decreased 10% within 3 hours after the oral dose and by 3%-5% after the intravenous dose. Cardiac output decreased 16% after the intravenous dose and 10% after the oral dose. Total peripheral resistance transiently increased by 23% after the intravenous, but not after the oral dose. Change in mean arterial pressure was positively correlated with change in total peripheral resistance after both the oral and intravenous doses. In contrast, change in mean arterial pressure was negatively correlated with change in cardiac output after the intravenous dose. Single oral and intravenous doses of propranolol lowered blood pressure within 3 hours after administration, and the reduction was correlated with change in total peripheral resistance and not with change in cardiac output. At least part of the adaptation in peripheral resistance occurs within the first 3 hours after both oral and intravenous single doses of propranolol.

Administration, Oral↗
PubMed1984

Efficacy and safety comparison of nitrendipine and hydralazine as antihypertensive monotherapy.

One-hundred and five patients with hypertension received nitrendipine (10-40 mg/day) or hydralazine (50-200 mg/day) in a double-blind randomized design. Nitrendipine decreased supine blood pressure 15/10 mm Hg, and hydralazine decreased it 11/11 mm Hg. Standing blood pressure was decreased 15/12 mm Hg by nitrendipine and 12/11 mm Hg by hydralazine. Supine and standing heart rate rose significantly after both drugs. Blood pressure variation through one dosing interval increased 42% when hydralazine was given but was not altered by nitrendipine. Side-effects from the two drugs were similar in patients who completed the study, but six patients discontinued participation due to side-effects of hydralazine, while only one discontinued due to nitrendipine side-effects. Ten patients required propranolol for hydralazine side-effects, and only three required it for nitrendipine side-effects. Nitrendipine and hydralazine are equally effective as antihypertensive monotherapy in patients with mild to moderate hypertension for periods up to 7 weeks, but nitrendipine appears to be better tolerated.

Adult↗
PubMed1984

Stereoselective ring oxidation of propranolol in man.

The objective of this study was to elucidate stereoselective mechanisms of propranolol metabolism in man. Five normal subjects were given single 80 mg oral doses of deuterium-labeled pseudoracemates of propranolol, and the stereochemical composition of propranolol and its major metabolites in urine was determined by GC/MS. The (-)/(+)-enantiomer ratios for unchanged propranolol, 1.50 +/- 0.10 (mean +/- s.e. mean), and propranolol glucuronide, 1.76 +/- 0.10, were similar to previous findings in plasma. All products of side-chain oxidation also consisted mainly of the (-)-enantiomer, with an overall (-)/(+) ratio of 1.61 +/- 0.11. A (-)/(+) ratio of 1.04 +/- 0.17 for 4-hydroxypropranolol did not indicate stereoselectivity in ring oxidation. However, the ratio for its glucuronic acid conjugate of 1.78 +/- 0.19 and for its sulphate conjugate of 0.27 +/- 0.03 suggested stereoselectivity in either the glucuronidation or sulphation of 4-hydroxypropranolol, or both. When the stereoselectivity in these secondary pathways was taken into consideration, the overall ring oxidation strongly favoured (+)-propranolol with a (-)/(+)-enantiomer ratio of 0.59 +/- 0.09. The composite observations of the stereochemistry of propranolol metabolism in man are consistent with stereoselective ring oxidation of (+)-propranolol, leading to a greater bioavailability of the pharmacologically more active (-)-propranolol and subsequent preferential side-chain oxidation and glucuronidation of this enantiomer.

Adult↗
PubMed1982

Antihypertensive effects of lofexidine in patients with essential hypertension.

1 Single oral doses of lofexidine, 0.1, 0.3, and 0.6 mg produced dose related decreases in supine and standing arterial pressure and heart rate in nineteen patients with essential hypertension. 2 A mean oral antihypertensive threshold dose of less than 0.1 mg was estimated. 3 Lofexidine decreased mean urinary noradrenaline excretion 28% and caused significant retention of sodium and water. 4 The most prominent side effects were sedation and orthostatic dizziness. 5 Lofexidine is pharmacologically similar to, but apparently less potent than clonidine as an antihypertensive agent.

Adolescent↗