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Biomedical subjects

A Whelton

Publications and source records attributed to A Whelton.

At least 37 records · Page 2Linked to original sources
PubMed1992

Sustained antihypertensive activity of diltiazem SR: double-blind, placebo-controlled study with 24-hour ambulatory blood pressure monitoring.

A new polymeric matrix technology provides a sustained-release formulation of diltiazem hydrochloride (diltiazem SR) suitable for once-daily therapy. The efficacy and safety of diltiazem SR were evaluated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a single-blind, placebo lead-in period, 275 patients with mild to moderate essential hypertension were assigned to receive placebo or diltiazem SR 120, 240, 360, or 480 mg once daily for 4 weeks. The efficacy evaluation was based on office and 24-hour ambulatory blood pressure monitoring. Twenty-four hours after the last dose in the 4-week, double-blind treatment period, the mean reduction from baseline in supine diastolic blood pressure ranged from 5.1 to 10.6 mm Hg in the diltiazem SR 120- to 480-mg groups, resulting in a significant linear trend across all treatments (P less than .001). Reductions in systolic blood pressure were similar. Ambulatory blood pressure monitoring, performed in 138 patients, confirmed the dose-response relationship and showed consistent antihypertensive activity throughout the 24-hour dosing interval. The percentage of patients reporting adverse events was similar in the placebo- and active-treated groups. The results of this study indicate that diltiazem SR is well tolerated, lowers blood pressure in a dose-related manner, and provides sustained activity throughout the 24-hour dosing interval.

Adolescent↗
PubMed1992

Cholestyramine-induced hyperchloremic metabolic acidosis.

Cholestyramine is a nonabsorbable anion exchange resin that is used predominantly for the treatment of hypercholesterolemia in adults and the management of acute diarrhea in children. The authors report two cases of severe hyperchloremic nonanion gap metabolic acidosis associated with the use of cholestyramine therapy. The authors recommend that patients taking cholestyramine who have concomitant renal insufficiency or who are volume depleted or who are taking spironolactone be monitored carefully for the emergence of a hyperchloremic metabolic acidosis.

Acidosis↗
PubMed1992

Twenty-four hour blood pressure effect of once-daily lisinopril, enalapril, and placebo in patients with mild to moderate hypertension.

This multicentre, double-blind, parallel-group, placebo-controlled study compared the antihypertensive effects of equal doses of two long-acting angiotensin converting enzyme (ACE) inhibitors. After a two-week, placebo run-in phase, 110 patients with mild to moderate hypertension were randomised to receive 10 mg lisinopril or enalapril, or placebo for 4 weeks. Office BPs were measured at regular intervals throughout the study. Twenty-four hour ambulatory blood pressure (ABP) was measured at baseline and after the first and final doses of study drug. Serum ACE activity and aldosterone were obtained concomitantly with each ABP monitoring. Office BP differences from placebo reached (P less than 0.05) or approached (P less than 0.10) statistical significance at all observations for the lisinopril group but were not significant for any observation in the enalapril group and approached significance on two occasions. After four weeks of treatment, ABP analysis revealed that the lisinopril and enalapril groups, when compared with placebo, had similar and significant systolic and diastolic AUC reductions (P less than 0.01) from baseline over the 24 h dosing interval. During the second half of the dosing interval, 13-24 h post drug administration, the lisinopril group was significantly different from placebo (systolic BP, P = 0.002; diastolic BP, P = 0.005) while the enalapril group was not. Both drugs were well tolerated. The results indicate that monotherapy with 10 mg of lisinopril is as effective as with 10 mg of enalapril, and that ABP monitoring is useful in more precisely depicting the clinical effect of the known pharmacokinetic properties of these two agents.

Adult↗
PubMed1992

Nonsteroidal antiinflammatory drugs: effects on kidney function and implications for nursing care.

The nonsteroidal antiinflammatory drugs are in wide use today. The use of these drugs, both over-the-counter and prescription strength, has risen dramatically for acute and chronic ailments. Of concern are patients with mild-to-moderate renal disease who may not recognize their increased risk of complications with the use of this category of drug. Understanding pathophysiology, educating patients, and performing comprehensive nursing assessments will be of great importance to this at-risk population.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Nonsteroidal anti-inflammatory drugs: effects on kidney function.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are capable of inducing a variety of renal function abnormalities, particularly in high-risk patients with decreased renal blood perfusion who depend on prostaglandin synthesis to maintain normal renal function. Fluid retention is the most common NSAID-related renal complication, occurring to some degree in virtually all exposed individuals; however, clinically detectable edema occurs in less than 5% of patients and is readily reversible on discontinuation of the NSAID. Other electrolyte complications, notably hyperkalemia, are seen infrequently and occur in specific at-risk patients. The next most worrisome complication is acute deterioration of renal function, which occurs in high-risk patients and is also reversible. Nephrotic syndrome with interstitial nephritis is a rare problem of NSAID use and is reversible. Papillary necrosis is the only permanent complication of NSAIDs and is very rare. Altogether, these renal function abnormalities, with the exception of mild fluid retention, are clinically detectable in approximately 1% of exposed patients. Given the number of patients who take NSAIDs on a prescription or over-the-counter basis, the absolute number of at-risk patients is relatively large. Consequently, an appreciation for the risk factors and pathophysiology of NSAID-induced renal function abnormalities is required for optimal use of these drugs.

Acute Kidney Injury↗
PubMed1991

Ambulatory monitoring of blood pressure.

When ambulatory monitoring results differ from office values it is very likely that the ambulatory readings more accurately reflect patient status. Thus, a determination of 24-hour antihypertensive control and comparison of the efficacy of drug regimens can help to prevent undertreatment as well as overtreatment.

Adult↗
PubMed1991

24-hour activity of lisinopril: clinical advantage in blood pressure control.

We have conducted a multicentre study in patients with mild to moderate hypertension. Lisinopril monotherapy, 10, 20, or 40 mg once daily (n = 35), was compared with captopril monotherapy, 25, 50, or 100 mg twice daily (n = 35). Blood pressure assessments were conducted using both office and 24-hour ambulatory blood pressure monitoring. Area under the curve analysis of ambulatory blood pressure reductions demonstrated significant differences between once-daily lisinopril and twice-daily captopril, with lisinopril producing the most significant reduction in pressure. These therapeutic results reflect the clinical-pharmacological profile of these two angiotensin-converting enzyme inhibitors and provide important clinical implications.

Adult↗
PubMed1991

Application of ambulatory blood pressure monitoring to clinical therapeutic decisions in hypertension.

The antihypertensive efficacies of lisinopril and captopril were compared using office sphygmomanometry and 24-h ambulatory blood pressure monitoring. In a double-blind, prospective, randomly allocated trial, the patients were given increasing doses of captopril at 25-100 mg twice a day or lisinopril at 10-40 mg once a day until a clinical response was achieved or the highest dose was reached. A response was defined as a reduction in diastolic pressure below 90 mmHg or a fall of at least 10 mmHg from baseline. The ambulatory monitoring showed that lisinopril reduced blood pressure from baseline to the final value and maintained the reduction to a greater degree than captopril throughout 24-h periods of observation. The office measurements showed a similar trend, but the intertreatment differences did not reach statistical significance. No first-dose side effects were observed with either drug. Once a day lisinopril appeared to be a more effective antihypertensive regimen than twice a day captopril.

Antihypertensive Agents↗
PubMed1990

Renal effects of ibuprofen, piroxicam, and sulindac in patients with asymptomatic renal failure. A prospective, randomized, crossover comparison.

STUDY OBJECTIVE: To evaluate the effects of three chemically distinct nonsteroidal anti-inflammatory drugs (NSAIDs) on renal function in patients with asymptomatic, mild but stable chronic renal failure. DESIGN: Prospectively randomized, triple-crossover study with at least 1-month washout between each of three treatment periods. SETTING: Inpatient and outpatient clinical research center of a university teaching hospital. PATIENTS: Convenience sample of 12 women with serum creatinine levels between 130 and 270 mumols/L (1.5 and 3.0 mg/dL). Mean glomerular filtration rate +/- standard error was 0.36 +/- 0.03 mL/s.m2 (37 +/- 3 mL/min.1.73 m2); mean effective renal plasma flow was 1.6 +/- 0.18 mL/s.m2 (166 +/- 19 mL/min.1.73 m2). INTERVENTIONS: Patients received ibuprofen, 800 mg three times daily; piroxicam, 20 mg daily; and sulindac, 200 mg twice daily for 11 days. Treatment was discontinued if serum creatinine rose by 130 mumols/L (1.5 mg/dL) or serum potassium exceeded 6 mmol/L (6 mEq/L). MEASUREMENTS AND MAIN RESULTS: Three patients met our criteria for stopping ibuprofen by day 8; however, all patients completed piroxicam and sulindac therapy. When the three patients in whom ibuprofen was withdrawn were rechallenged with ibuprofen, 400 mg three times daily, two again developed evidence of acute renal deterioration. All three regimens suppressed renal prostaglandin production. CONCLUSIONS: These findings indicate that a brief course of ibuprofen, a compound widely used on a nonprescription basis, may result in acute renal failure in patients with asymptomatic, mild chronic renal failure. Additional studies are needed to assess the risk of piroxicam and sulindac in patients with more pronounced renal impairment and in patients receiving longer courses of therapy, which, according to our data, may result in drug accumulation.

Adult↗
PubMed1990

Once-daily lisinopril compared with twice-daily captopril in the treatment of mild to moderate hypertension: assessment of office and ambulatory blood pressures.

This multicenter, double-blind, parallel-group study compared the antihypertensive effects of two angiotensin-converting enzyme inhibitors, lisinopril and captopril, in 70 patients (35 lisinopril, 35 captopril) with mild-to-moderate essential hypertension. Doses of 10, 20, and 40 mg once-daily lisinopril or 25, 50, and 100 mg bid captopril were increased at biweekly intervals until patients responded to treatment, as defined by a decrease in office diastolic pressure to less than 90 mm Hg or at least a 10 mm Hg decrease from baseline. Patients who responded to a 2-week titration dose remained at that dose for another 2 weeks. Blood pressure assessments were made using both office and ambulatory blood pressure monitoring. Area under the curve analysis of ambulatory blood pressure reductions showed significant differences between treatment groups for both systolic (P = .023) and diastolic (P = .007) blood pressures, with lisinopril-treated patients showing the most significant reduction in pressure. Greater reductions (P less than .05) were also noted in patients receiving lisinopril at hours 10 to 12, suggesting two blood pressure troughs for those receiving captopril. Both drugs were well tolerated, and no patients withdrew from either treatment group. The authors concluded that after at least 4 weeks of therapy, once-daily lisinopril administration was more effective than twice-daily captopril administration in reducing blood pressure, when measured by 24-hour ambulatory blood pressure monitoring.

Ambulatory Care↗
PubMed1989

Sulindac kinetics and effects on renal function and prostaglandin excretion in renal insufficiency.

The purpose of this study was to evaluate the pharmacokinetics of sulindac, a purported "renal sparing" nonsteroidal anti-inflammatory drug, and its effects on renal function and prostaglandin excretion in patients with reduced glomerular filtration rate. Twelve female patients (glomerular filtration rate 37 +/- 4 mL/min) were treated with sulindac 200 mg bid for 11 days. Urinary PGE2, 6-keto-PGF1 alpha and serum thromboxane (TxB2) generation were measured by radioimmunoassay (RIA) following extraction on C-18 columns. Glomerular filtration rate and effective renal plasma flow were measured by 99TC-DPTA and 131I-para-aminohippuric acid clearance. In six patients serum and urine levels of sulindac and its metabolites were measured by high-pressure liquid chromatography (HPLC). Sulindac was rapidly absorbed and converted to sulindac sulfide with peak levels 2 hours after a single dose, but steady state levels were not reached prior to drug discontinuation. Sulindac sulfide AUC (0-5 hours micrograms min/mL) progressively increased from 382 to 3,030 on day 11. It did not appear in the urine. Baseline urinary PGE2 and 6-keto-PGF1 alpha excretion were 23.8 +/- 5.6 and 18.9 +/- 2.7 ng/hr respectively and were reduced by 68% and 47% by day 4 of therapy. TxB2 generation fell by 34% after one dose and by 67% by day 11. There was a significant increase in serum creatinine from 1.88 +/- 0.13 mg/dl before treatment to 2.16 +/- 0.15 mg/dL (P less than .05) after eleven days.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1989

Profile of clinical pharmacologists in the United States.

The need for clinical pharmacology in research and education, drug development, and health care delivery is well known. However, a current profile of those working in the field is not available. The ACCP authorized a survey of clinical pharmacologists to provide such a profile. Members of the ACCP or ASCPT were solicited by mail with a self-assessment questionnaire. A response rate of 37% was obtained. Demographic findings agree well with a previous study2 limited to those with the M.D. Our results reveal that most clinical pharmacologists are between 30-59 years of age, have an MD, PhD or PharmD degree; most of those with MDs list their primary specialty as internal medicine, pediatrics, psychiatry, or anesthesiology. They affiliate with the respective departments (including pharmacology) in academia or hold positions in industry or government, but few are in clinical therapeutics per se. About 20% of those with only a MD or PharmD degree cite employment in health care delivery. However, a higher percentage of these respondents work in research and education rather than in drug development or health care delivery. For those with only a PhD, more work in drug development and research and education than in health care delivery. The highest proportion of respondents with any doctoral degree work in the Northeast. The average income is a function of rank, doctoral degree, specialty, department appointment, and type and location of employer. The profile of a typical clinical pharmacologist is presented. An analysis of clinical pharmacology manpower from several perspectives reveals a marked deficit, but the field itself is professionally and economically attractive. Lack of a well defined career track in academia and a poorly defined clinical role for MD clinical pharmacologists are proposed as reasons limiting entry of trainees. These and other results of the survey support an increased emphasis on training programs. Clinical pharmacologist involvement in health care delivery and drug development must be increased if the safe and effective use of new drugs is to be realized. Nine assessments and initiatives are formulated to accomplish this goal within the next decade.

Adult↗
PubMed1988

Treatment of gram-negative infections in patients with renal impairment: new alternatives to aminoglycosides.

Aminoglycosides have become an indispensable component in the armamentarium against serious gram-negative infections. In spite of the availability of effective guidelines for prevention, the frequency of toxic side effects associated with aminoglycoside therapy is an impetus for the substitution of safer and equally efficacious alternatives, particularly in the setting of renal impairment. Recently, three new classes of antibiotics with potent gram-negative activity have become available. These are the monobactams, the carbapenems, and the fluorinated 4-quinolones. The antimicrobial spectrum of aztreonam, a monobactam, closely resembles that of aminoglycosides. Imipenem, a carbapenem, is a broad spectrum antibiotic with activity against gram-negative aerobes as well as gram-positive aerobes and many anaerobes. Ciprofloxacin, an orally active quinolone, has gram-positive and gram-negative coverage against aerobes but not anaerobes. These agents offer an alternative therapeutic option to aminoglycosides and, in the setting of pre-existing renal impairment, are particularly attractive in view of their safety.

Aminoglycosides↗