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Biomedical subjects

R F Maronde

Publications and source records attributed to R F Maronde.

At least 19 recordsLinked to original sources
PubMed1989

Underutilization of antihypertensive drugs and associated hospitalization.

The association of underutilization of drugs prescribed for the treatment of hypertension and acute-care hospital readmissions was evaluated. The data base consisted of computerized hospitalization records and computerized out-patient pharmacy records, checked by chart audit for validity. The number of days' supply of antihypertensive agents was estimated by dividing the quantity of drugs dispensed by the daily dose indicated by the prescription instructions. All patients had been admitted to an acute-care hospital during a 6-month period with the diagnosis of hypertension. Following discharge from the hospital, drug utilization and readmission status were determined for a minimum of 1 year. The drug compliance of a group of patients who were readmitted to the hospital was compared with the patients who were not readmitted. The readmitted group had a significantly higher ratio of days when they were without any antihypertensive agents relative to the length of time in the study. There were no statistically significant differences in demographic features or blood-pressure levels between the patient groups. These findings indicate that underutilization of antihypertensive drugs may be associated with hospitalization, which could be prevented if patients had complied with their medication schedules.

Adult↗
PubMed1986

Hypokalemia in thiazide-treated systemic hypertension.

Potassium supplementation in diuretic-induced hypokalemia (serum potassium less than 3.5 mmol/liter) in patients being treated for hypertension is a common event. In a previous study 40 mmol/day of orally administered potassium was not effective in preventing diuretic-induced hypokalemia in patients who had previously developed hypokalemia while being treated for hypertension with hydrochlorothiazide. In the study reported here dosages as high as 60 to 80 mmol/day of orally administered potassium failed to prevent hypokalemia in 7 of 19 hypertensive patients who were receiving hydrochlorothiazide. Potassium supplementation was compared with the potassium-sparing diuretic amiloride. The study design was open label and subject matched with crossover of therapeutic regimens.

Aldosterone↗
PubMed1985

Pharmacodynamics of intravenous labetalol and follow-up therapy with oral labetalol.

The effectiveness, safety, and pharmacodynamics of repeated doses of intravenous labetalol for rapid reduction of severe hypertension and of subsequent oral labetalol dosing were studied. Twelve patients with severe hypertension were admitted to the hospital after the withholding of antihypertensive therapy for 2 to 14 days. Thirty minutes after an injection of vehicle only, labetalol, 0.25 mg/kg body weight, was injected and followed by repeat injections of 0.5 mg/kg every 15 minutes until the supine diastolic blood pressure (BP) was reduced to less than 90 mm Hg or a total of 3.25 mg/kg had been administered. Twenty-four hours after the last injection, oral labetalol was started at an initial dosage of 100 or 200 mg b.i.d., then increased every 2 days until the standing diastolic BP was less than 90 mm Hg or a maximum daily dosage of 2400 mg was reached. The initial injection achieved mean falls in supine systolic/diastolic BPs of 11/7 mm Hg. Subsequent injections produced additional falls in a dose-related fashion; the mean falls after the last injection (total cumulative dose 2.7 mg/kg) were 40/20 mm Hg. The effect lasted for 12 hours or more in most patients and tended to be biphasic, with one peak at approximately 5 minutes and another much less pronounced peak at about 4 hours. There was no evidence of precipitous falls in BP. All patients were able to ambulate 6 hours after the last injection without symptoms of postural hypotension. Oral labetalol effectively and safely restored and maintained the BP reductions achieved with intravenous labetalol.

Administration, Oral↗
PubMed1984

Plasma levels of free and total catecholamines and two deaminated metabolites in man--rapid deconjugation by heat in acid.

We have described a procedure for deconjugation of plasma catecholamines, norepinephrine (NE), epinephrine (E) and dopamine (DA) and two catecholamine metabolites 3,4-dihydroxymandelic acid (DOMA) and 3,4-dihydroxyphenylglycol (DOPEG). Heat at 100 degrees C of the acidified specimen, pH 0.8, produced complete deconjugation of catecholamines in 7 minutes and of metabolites in 5-7 minutes. Subsequently all five products were simultaneously measured with a radioenzymatic assay. However, hydrolysis for 7 minutes produced approximately a loss of 5% in DA and E, 15% in NE and 50% in the metabolites. The percent of free compound in the plasma of 11 normotensive and healthy subjects was 23 +/- 16 for NE, 20 +/- 8 E, 0.8 +/- 1 DA, 20 +/- 7 DOMA and 42 +/- 12 for DOPEG. Similar results were obtained in a random specimen of six patients with primary hypertension. In a group of four patients with pheochromocytoma free levels of NE, DOPEG and DOMA were significantly greater than in the other two groups, whereas conjugates were not. The intravenous administration of NE or the activation of sympathetic nervous system by standing combined with exercise for 15 minutes did not produce a change in the levels of plasma conjugates. These findings suggest that short changes in plasma catecholamines are better reflected in the free than the conjugated part.

Catecholamines↗
PubMed1984

Oral potassium chloride and amiloride in hydrochlorothiazide-induced potassium loss.

To compare the effect of amiloride with that of oral potassium chloride (KCl) in hypokalemia, metabolic balance studies were carried out in hospitalized subjects with mild hypertension without edema who developed negative potassium balance after 4 days on hydrochlorothiazide (HCTZ). Subjects' diets contained measured amounts of sodium and potassium. While HCTZ treatment continued, oral preparations of either KCl solution or amiloride was added for 5 additional days. Potassium balance in the KCl-treated group further decreased by -44.9 +/- 32.3 mEq K+, while subjects on amiloride went into positive balance that averaged +51.7 +/- 24.1 mEq K+. Hypokalemia after HCTZ did not respond to KCl, while K+ levels rose from 3.32 +/- 0.22 to 3.67 +/- 0.26 mEq/l after amiloride.

Administration, Oral↗
PubMed1984

Role of conjugation and red blood cells for inactivation of circulating catecholamines.

We investigated the extent of catecholamine (CA) conjugation in plasma and accumulation inside red blood cells (RBCs) after forced immobilization of the rat. A control blood sample was obtained from undisturbed rats resting in home cages via an indwelling aortic catheter. Then rats were immobilized for 2 h, and blood samples were taken during stress at 15 min and 2 h and at 30 min poststress. Both sulfate and glucuronide conjugates were deconjugated by enzymatic hydrolysis and measured by radioenzymatic thin-layer chromatographic methods. In plasma of resting rats, the major conjugate of norepinephrine (NE) is sulfate and that of epinephrine (E) and dopamine (DA) is glucuronide; total conjugates in plasma are 53, 57, and 97% of total NE, E, and DA, respectively. During stress, sulfate conjugates of NE, E, and DA increased significantly along with free NE, E, and DA. DA glucuronide unexpectedly declined at 2 h of stress and 30 min poststress. Concentrations of free CAs rose in RBCs during stress, as did NE sulfate, the only conjugate present in RBC lysate. We conclude that both CA conjugation and RBC accumulation are enhanced when large amounts of free CA enter the circulation as a result of immobilization stress and that the relative importance of these inactivation pathways is different for the three CAs.

Animals↗
PubMed1984

Role of conjugation and red blood cells for inactivation of circulating normetanephrine.

Plasma and red blood cell (RBC) concentrations of normetanephrine (NMN), in both free and glucuronide-conjugated forms, were measured before, during, and after forced immobilization, an intense stressor of the sympathoadrenal system of rats. In this study NMN glucuronide was deconjugated by enzymatic hydrolysis; free and total NMN were assayed by radioenzymatic, thin-layer chromatographic procedures. In plasma, free NMN and NMN glucuronide are 777 +/- 99 and 792 +/- 74 pg/ml, respectively, when rats are at rest. Both free NMN and NMN glucuronide increased about 200% after 15 min of stress; in absolute amounts, increases were equivalent to that of the simultaneous increase in norepinephrine (NE). At 2 h of stress, NMN glucuronide, but not free NMN, increased further and significantly. The mean concentration of RBC-free NMN is about 50 times higher than that of plasma-free NMN, and it did not change significantly during stress; RBCs do not contain conjugated NMN. RBC NMN levels showed a strong correlation with RBC catechol methyltransferase activity. The latter seems to operate under conditions of substrate saturation; an acute release of NE leads to temporary storage of NE in RBCs but not conversion to NMN. The results indicate that conjugation of NMN with glucuronic acid is an important route for inactivation of plasma NMN formed during forced immobilization stress, whereas free NMN does not accumulate in RBCs during stress.

Animals↗
PubMed1983

Study of single and multiple dose pharmacokinetic/pharmacodynamic modeling of the antihypertensive effects of labetalol.

This was an open-label, two-phase crossover study of labetalol in 11 patients with mild to moderate hypertension. A two- to four-week outpatient placebo phase was followed by a three-day inpatient placebo period. Patients were then randomly assigned to receive either labetalol, 200 mg, as a single dose and three times a day for three days and, on the final day, another single dose or a similar sequence with 300 mg as the single dose and multiple twice a day treatment. A two-week placebo outpatient period was followed by the second phase of the study in which the treatment regimen was reversed for the two groups. Blood samples for the determination of free and conjugated labetalol plasma levels were collected, and blood pressures and heart rate were recorded sequentially for 24 hours after the first and last dose of labetalol, and during the multiple dose treatment period before and two hours after each dose as well as four times daily with the patient supine and upright. Of the 11 patients analyzed, five were men and six were women, ranging in age from 33 to 62 years. Labetalol (200 mg and 300 mg) was rapidly absorbed with peak concentrations achieved in approximately one hour. The pharmacokinetic data best fit a two-compartment pharmacokinetic model with first order absorption. At steady state, the absorption, distribution, and elimination kinetics were similar for both dosage regimens with elimination half life of 7.65 and 7.92 hours for the 200 mg three times a day and 300 mg twice a day regimens, respectively. During the multiple dosing period average steady-state plasma drug concentrations were 0.149 mg/ml and 0.145 mg/ml for the 300 mg twice a day and 200 mg three times a day regimens, respectively. Approximately 12 percent of total plasma labetalol was free drug. The balance was conjugated. The first dose of 200 mg or 300 mg of labetalol significantly (p less than 0.01) lowered standing and supine mean blood pressure over a period of eight to 12 hours, respectively, with peak effects occurring at two (standing) and four (supine) hours. A significant reduction (p less than 0.01) in supine mean blood pressure was present 24 hours after the initial dose of 300 mg. At steady state the antihypertensive effects of the 200 mg three times a day and the 300 mg twice a day dosage regimens were similar.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1983

Treatment of severe hypertension with labetalol compared with methyldopa and furosemide. Results of a long-term, double-blind, multicenter trial.

Eighty-one severely hypertensive patients were enrolled in a multicenter, double-blind, parallel group study evaluating the efficacy and safety of labetalol alone or in combination with furosemide versus methyldopa in combination with furosemide. A one day to four week placebo lead-in phase was followed by a one- to six-week titration period and a one-year maintenance period. Treatment with labetalol alone or in combination with furosemide, as well as methyldopa plus furosemide, was associated with significant reductions in supine and standing blood pressure levels. Moreover, after six months and one year of treatment, respectively, labetalol caused a significantly (p less than 0.05) greater reduction in the systolic blood pressure than the methyldopa regimen. The antihypertensive effect of labetalol was associated with small, yet significant reductions in heart rate; in contrast, resting tachycardia was observed in methyldopa-treated patients. Side effect profiles of the two treatments were different, with nausea being the most commonly reported side effect during labetalol therapy, and asthenia, somnolence, and dry mouth during methyldopa therapy. Overall, 33 of 65 (53 percent) labetalol-treated and 28 of 60 (47 percent) methyldopa-treated patients had at least a good response (that is, standing diastolic blood pressure 90 to 94 mm Hg) to therapy, including 26 (40 percent) and 22 (37 percent) patients, respectively, who had standing diastolic blood pressure levels of less than 90 mm Hg. Thus, labetalol is a potentially safe and effective agent in the long-term management of the patient with severe hypertension.

Adult↗
PubMed1983

Response of thiazide-induced hypokalemia to amiloride.

The effects of amiloride hydrochloride on thiazide-induced hypokalemia were evaluated. In metabolic balance studies, amiloride reversed thiazide-induced urinary potassium loss, restored plasma bicarbonate concentration and pH to pretreatment levels, and produced further increases in aldosterone secretion. Effects of long-term administration of hydrochlorothiazide and an amiloride-hydrochlorothiazide combination were compared in outpatients who had experienced thiazide-induced hypokalemia while receiving oral potassium supplements. After eight weeks, those given hydrochlorothiazide alone had an average serum potassium level of 3.01 +/- 0.08 mEq/L). Those given the amiloride-hydrochlorothiazide combination had an average serum potassium level of 3.75 +/- 0.008 mEq/L, not significantly different from the control value (3.82 +/- 0.08 mEq/L). Both groups had increased plasma aldosterone concentrations and plasma renin activity. The potassium-conserving effect of amiloride persisted with extended therapy.

Aldosterone↗
PubMed1983

Medroxalol combined with hydrochlorothiazide in the treatment of hypertension.

The antihypertensive effect and safety of hydrochlorothiazide administration as a single drug and together with medroxalol were determined in 20 patients with primary hypertension. Following two biweekly intervals on placebo and hydrochlorothiazide, medroxalol was started at 100 mg three times a day and titrated against blood pressure response up to a maximum of 300 mg three times a day. In nine patients the effect of the single and the combined drug therapy on blood pressure during isometric handgrip exercise, on plasma renin activity, and on plasma catecholamines and their deaminated metabolites was investigated. The administration of hydrochlorothiazide was associated with a significant decrease in blood pressure, but heart rate did not change. The addition of medroxalol produced a substantial decrease in blood pressure and heart rate in both the recumbent and upright positions (P less than 0.001). Due to careful titration of medroxalol, orthostatic hypotension was observed only in one patient. Neither hydrochlorothiazide alone nor the combined drug regimen prevented or diminished the rise in blood pressure with exercise. Although plasma renin activity decreased during the combined drug therapy, there was no correlation between the initial levels or the change in plasma renin activity and the extent of decrease in blood pressure. The concentration of plasma epinephrine increased during the combined drug period, whereas catecholamine metabolites increased significantly during both periods of the study. It is concluded that medroxalol combined with hydrochlorothiazide constituted a potent and safe antihypertensive therapy for the duration of the present study.

Adrenergic alpha-Antagonists↗
PubMed1983

Plasma clonidine levels in hypertension.

Ten patients with essential hypertension were treated orally with clonidine, and the dose was titrated until the diastolic pressure fell below 90 mm Hg or at least 10 mm Hg below baseline, or until a maximum dose of clonidine of 1.2 mg/day was reached. After at least 2 wk on a constant dose of clonidine, the patients were hospitalized and blood pressure and plasma clonidine concentrations were measured by a highly specific and sensitive gas chromatographic, electron-capture method (sensitivity as low as 0.1 ng clonidine/ml). There was good correlation between daily clonidine dose and plasma clonidine concentration. The average blood pressure reduction during 12 hr after clonidine correlated poorly with steady-state plasma levels of clonidine, but when the individual maximum decrease in mean blood pressure was paired with the corresponding peak plasma concentration of clonidine, the correlation was strong.

Adult↗
PubMed1983

Hemodynamic effect of lofexidine with a diuretic in hypertension.

We measured the first dosage effect and the long-term effect of lofexidine on blood pressure, heart rate, plasma catecholamines, and their major metabolites in 16 patients with primary hypertension who were receiving 50 mg hydrochlorothiazide twice a day while they were recumbent and upright and during isometric handgrip contraction. We also measured the first dosage effect of lofexidine on forearm blood flow and its long-term effect on plasma renin activity. Lofexidine, both in a single dose and after long-term therapy, induced a substantial fall in blood pressure of patients in recumbent and upright positions, whereas it decreased heart rate in both positions only during long-term dosing. Lofexidine did not prevent or diminish the pressure and heart rate rise by isometric handgrip contractions. Single and long-term lofexidine dosing induced a fall in plasma levels of catecholamines and their metabolites. There was a positive correlation between the fall in blood pressures and the reduction in plasma norepinephrine during long-term therapy. There was a positive correlation between the decrease in blood pressure induced by single doses and by long-term dosing, which suggests that lofexidine in a single dosage at the start of therapy may facilitate identification of responders.

Adult↗
PubMed1981

Catecholamines and their major metabolites in plasma and cerebrospinal fluid of man.

In 36 patients undergoing elective surgery under spinal anesthesia, plasma and cerebrospinal fluid (CSF) concentrations of catecholamines and their major metabolic products were determined. The development of specific and sensitive radioenzymatic assays make these determinations possible. The levels of norepinephrine, epinephrine, and the O-methylated metabolite, normetanephrine, were greater in the plasma then the CSF, although the difference was significant for norepinephrine and epinephrine only (P less than 0.01 for both) On the other hand the levels of both deaminated metabolites dihydroxyphenylglycol (DOPEG) and dihydroxymandelic acid (DOMA) were greater in the CSF the in plasma, but the difference was significant for DOPEG only (P less than 0.01). Although there was a positive and significant correlation between the levels in plasma and CSF of all these compounds, their concentrations in CSF may reflect metabolism of catecholamines in the central nervous system.

Adult↗
PubMed1980

Indices of sympathetic activity in the sinoaortic-denervated hypertensive rat.

Blood pressure and circulating levels of norepinephrine (NE), epinephrine (Epi), and dopamine-beta-hydroxylase (DBH) were measured sequentially in sinoaortic-denervated (SAD) Wistar rats and in sham-operated (SO) rats. Systolic tail pressure, plasma NE and E, and plasma DBH all increased significantly within 2 days in SAD rats. In separate studies of rats with indwelling arterial catheters, arterial pressure and plasma NE and DBH were increased in SAD rats in home cages; restraint caused similar increases of pressure and catecholamines in both groups. Systolic pressure remained increased up to 4 mo and plasma DBH for 10 wk in SAD rats; plasma NE and E, however, declined by 3 wk and thereafter remained close to values of SO rats. Additionally, DBH was increased in heart, mesenteric blood vessels and adrenal glands of SAD rats up to 6 wk; tissue monoamine oxidase activity was also increased up to 4 mo. These findings suggest that activation of the sympathetic nervous system initiates and probably sustains hypertension in SAD rats up to 6 wk after operation; thereafter some other mechanism(s) sustains the hypertension.

Animals↗
PubMed1980

Increased plasma normetanephrine in spontaneously hypertensive rats.

Plasma catecholamine and total plasma normetanephrine concentrations were determined in 11 spontaneously hypertensive rats (SHR) and in 11 age and sex matched Wistar Kyoto control rats (WKy). Plasma norepinephrine concentration, obtained from tail vein blood of restrained rats, was 356 +/- 67 pg/ml in SHR and 297 +/- 61 in WKy (NS), whereas epinephrine was 1079 +/- 117 in SHR and 695 +/- 107 in WKy (p < 0.05). Total plasma normetanephrine concentration was 1825 +/- 472 pg/ml in SHR and 535 +/- 109 in WKy (p < 0.02). Since normetanephrine is mainly an extraneuronal metabolite of norepinephrine, its plasma concentration could reflect the amount of the neurotransmitter which reaches effector cell sites suggesting enhanced sympathetic function accounts for blood pressure elevation in SHR. A simple and specific radioenzymatic assay for measurement of total plasma normetanephrine in rat was described.

Animals↗
PubMed1979

Effects of metoprolol on blood pressure and plasma renin activity in thiazide-resistant hypertensive patients.

Twenty patients with mild to moderate hypertension whose blood pressures were not adequately controlled by a thiazide diuretic were treated for 4 wk with metropolol. Normotension (diastolic pressure less than 90 mm Hg) or reduction in diastolic pressure of at least 10 mm Hg was achieved in 12 of the patients 1 wk after metoprolol (200 mg/day) was added to the hydrochlorothiazide (100 mg/day) regimen. In the other 8 patients, pressure reduction was attained with larger doses (300 to 400 mg/day) of metoprolol. After 1 wk of combined therapy, heart rate decreased by 11% (p less than 0.001) and plasma renin activity (PRA) decreased 48% (p less than 0.001). The individual changes in mean blood pressure did not correlate with either the premetoprolol PRA level (r = 0.14) or the changes in PRA after metoprolol (r = 0.03) but did correlate with steady-state metoprolol plasma levels (r = 0.61, p less than 0.01). Pressure and heart rate reductions were sustained during the last 3 wk of combined therapy but the PRA decrease did not persist; levels gradually rose to near control by the fourth week. Urinary sodium excretion was not consistently changed on metoprolol therapy.

Adult↗