PubMed Health⌕ Search

Biomedical subjects

E B Nelson

Publications and source records attributed to E B Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1993

How well have animal studies with losartan predicted responses in humans?

AIM: To compare the biological activity of losartan as seen in several animal studies with results from similar clinical studies in hypertensive patients or normal volunteers. RESULTS: With regard to oral bioavailability and estimates of oral angiotensin II blocking activity, the animal models were reasonably good predictors of the human response. Although formation of the major losartan metabolite E 3174 differs according to species, both animal and human studies suggest an association between plasma drug levels and angiotensin II blockade. The finding that losartan demonstrated increased sensitivity during salt depletion in animals was confirmed in humans. Possible beneficial effects on renal function await further detailed clinical trials. CONCLUSIONS: Losartan has been shown to lower blood pressure in patients with essential hypertension. However, cross-species comparisons are difficult because, unlike humans, animal models of hypertension follow clearly defined hypertensive mechanisms. Differing profiles of E 3174 metabolite formation also make cross-species comparisons difficult.

Angiotensin Receptor Antagonists↗
PubMed1989

Review of the effects of doxazosin, a new selective alpha 1-adrenergic inhibitor, on lipoproteins in patients with essential hypertension.

Control of high blood pressure has failed to reduce the risk of atherosclerotic coronary heart disease (CHD). Hypercholesterolemia, which is common among hypertensive patients, cigarette smoking, and hypertension are the major risk factors for CHD. To minimize CHD risk, elevated blood pressure and atherogenic lipid levels should be lowered, but various antihypertensive agents appear to adversely affect lipid levels, actually precluding the CHD risk reduction expected from blood pressure control. Doxazosin, a once-daily, long-acting, alpha 1-adrenergic inhibitor, not only is effective therapy for essential hypertension but also has a favorable impact on lipids. During controlled studies of doxazosin's antihypertensive efficacy, the following blood lipid levels were measured: total cholesterol, total triglycerides, high-density lipoprotein (HDL) cholesterol (including HDL2 and HDL3), low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein cholesterol, and apoproteins (apos) AI and B. Results showed total cholesterol (-0.8 to -8.9 percent), total triglycerides (-5.0 to -17.4 percent), and LDL (-9.0 to -16.9 percent) were reduced. The positive prognostic indicators, HDL (+0.7 to +13.0 percent) and HDL:total cholesterol ratio (+3.1 to +26.3 percent), were increased. Apo B decreased, but apo AI remained unchanged. In these hypertension studies, doxazosin has favorably reduced two major CHD risk factors. As part of a new, long-term, controlled, multicenter trial, the prospective benefits of these risk factor reductions on CHD morbidity and mortality will be quantified for doxazosin and other antihypertensive agents.

Adrenergic alpha-Antagonists↗
PubMed1989

Spectrum of dysautonomia in mitral valvular prolapse.

PURPOSE: Symptoms suggesting altered autonomic regulation of cardiovascular function have been noted in some patients with mitral valvular prolapse (MVP) but may also occur in patients with other disorders. We evaluated cardiovascular responses to autonomic stimuli in 118 patients with symptoms of dysautonomia, 78 of whom had MVP, and 40 of whom did not, to determine if unique patterns of these responses distinguished patients in one symptomatic subgroup from another. SUBJECTS AND METHODS: The responses of patients to standing, quantitated Valsalva maneuver, facial immersion in ice water, and administration of isoproterenol, phenylephrine, and tyramine were compared with those in 12 asymptomatic patients with MVP and 23 normal volunteers. RESULTS: Constitutional, cardiovascular, and neuropsychiatric symptoms occurred with similar frequency in the two symptomatic patient groups. The most common pattern of abnormal responses in symptomatic patients with or without MVP was (1) an increased heart rate and elevated plasma norepinephrine levels while supine and then while standing quietly for five minutes, (2) an exaggerated increase in heart rate during phase II of Valsalva, (3) a diminished bradycardic response during phase IV of Valsalva, and (4) an exaggerated heart rate response to administration of isoproterenol. The increased heart rate during Valsalva, but not the exaggerated sensitivity to isoproterenol, was correlated with the magnitude of the chronotropic response to standing only in symptomatic patients with MVP. Exaggerated hypertensive overshoot during phase IV of Valsalva was observed in only a few symptomatic patients. No consistent pattern of these abnormalities, however, was noted in any of the patient subgroups. Hemodynamic responses to autonomic stimuli in asymptomatic MVP patients were generally indistinguishable from those observed in normal subjects. CONCLUSION: These findings suggest that abnormal cardiovascular responses to autonomic stimuli may occur in any patient with symptoms of dysautonomia regardless of the presence or absence of MVP and that the pattern of these abnormal responses may be diverse. It is therefore important to characterize the pattern of altered autonomic regulation of cardiovascular function in each patient when considering mechanistic implications or making therapeutic decisions about these patients.

Adolescent↗
PubMed1989

Drug substitution and rational therapeutics. Old problems and new challenges.

Drug substitution is a reality of current medical practice. Physicians need to be aware of how it affects patients both medically and economically. Continuing education in clinical pharmacology is essential. Although generic substitution and formulary restriction are usually acceptable, therapeutic substitution is not. The responsibility of instituting therapy by writing a prescription must not be delegated to non-physicians. This could ultimately lead to more problems with adverse drug reactions and poor clinical outcome.

Drug Prescriptions↗
PubMed1989

Consequences of angiotensin-converting enzyme inhibitor overdose.

Overdose with angiotensin-converting enzyme (ACE) inhibitors is still a relatively underreported phenomenon. We report here a case of an unintentional overdose of enalapril (100 mg) together with other medications. The patient experienced no adverse consequences. Pharmacokinetic evaluation revealed a t 1/2 for enalaprilat (prodrug) of seven hours and for enalapril at 36 hours. Based on this case report as well as others, guidelines for assessment and treatment of these patients are proposed. Management of hypotension is the primary therapeutic intervention.

Aged↗
PubMed1989

Isradipine vs propranolol in hydrochlorothiazide-treated hypertensives. A multicenter evaluation.

A randomized, parallel, controlled study was conducted to evaluate the safety and efficacy of isradipine, 2.5 to 10 mg orally twice a day, compared with propranolol hydrochloride, 60 to 240 mg orally twice a day, in 78 hypertensives whose supine diastolic blood pressure was greater than 95 mm Hg while receiving 50 mg/d or more of hydrochlorothiazide. Isradipine or propranolol was titrated during a 10-week double-blind phase to achieve a supine diastolic blood pressure below 90 mm Hg while a fixed dose of hydrochlorothiazide was maintained. Supine diastolic blood pressure was reduced by 10 mm Hg in 88% of the isradipine/hydrochlorothiazide-treated and 83% of the propranolol/hydrochlorothiazide-treated groups and to less than 90 mm Hg in 55% of the isradipine/hydrochlorothiazide-treated and 69% of the propranolol/hydrochlorothiazide-treated patients. There was no significant difference in supine blood pressure reduction between either group, but there was a 3-to 4-beats per minute increase in supine heart rate in isradipine-treated patients and an expected 15- to 20-beats per minute decrease in heart rate in propranolol-treated patients. Five of 7 patients in the isradipine-treated group and 8 of 9 patients in the propranolol-treated group discontinued the therapy because of adverse reactions or treatment failure. Using Fisher's Exact Test, we found no significant difference in the relative frequency of individual adverse reactions between groups, although the absolute adverse reaction frequency was significantly higher with isradipine. This study demonstrates the effectiveness and safety of supplemental isradipine in the treatment of hypertension not controlled by hydrochlorothiazide alone.

Adult↗
PubMed1988

Clinical experience and rationale for angiotensin-converting enzyme inhibition with lisinopril as the initial treatment for hypertension in older patients.

Hypertension is a major health problem for patients over 65 years of age. Control of elevated blood pressure reduces cardiovascular morbidity and mortality rates among older hypertensive patients. Increased total peripheral vascular resistance is the primary hemodynamic abnormality in these patients. Initially, diuretics were used alone to lower total peripheral vascular resistance, and thus blood pressure, in older patients. The antihypertensive efficacy of angiotensin-converting enzyme inhibitors has been questioned in this age group, in which low-renin hypertension is common. The latter condition might be thought to favor blood pressure control with diuretics and impair the response to angiotensin-converting enzyme inhibitor therapy. However, recent studies with lisinopril, a new long-acting, nonsulfhydryl angiotensin-converting enzyme inhibitor, indicate that reductions in systolic and diastolic blood pressure in older hypertensive patients receiving either angiotensin-converting enzyme inhibitor or hydrochlorothiazide monotherapy were not significantly different. These data demonstrate that angiotensin-converting enzyme inhibitor monotherapy can effectively lower blood pressure in older hypertensive patients.

Adult↗
PubMed1988

Effects of food on the bioavailability of CGS 16617, an angiotensin-converting enzyme inhibitor, in healthy subjects.

CGS 16617, a direct-acting angiotensin-converting-enzyme inhibitor, was administered as a single dose of 20 mg in aqueous solution to 12 healthy male volunteers on two occasions in a randomized, cross-over design study. On one occasion, the dose was administered after an overnight fast; on the other occasion, it was administered after subjects ate a standard breakfast. Administration of CGS 16617 after food was associated with statistically significant decreases in peak plasma concentrations (58%) and areas under the plasma concentration-time curves (23%) compared with drug administration in the fasted state. Also, the time to peak plasma concentration was increased (57%) in a statistically significant manner when CGS 16617 was administered after food. Thus, the ingestion of food decreased both the rate and extent of absorption of this drug, but the mechanism of the interaction is unknown at present.

Adult↗
PubMed1988

Effect of doxazosin monotherapy on blood pressure and plasma lipids in patients with essential hypertension.

The efficacy and safety of doxazosin (DOX) for the treatment of hypertension was investigated. A multicenter, double-blind, placebo-controlled, parallel design was employed. A 4-week placebo runin period was followed by a 9-week double-blind period during which patients were randomly assigned to placebo or 2, 4, or 8 mg doxazosin. Blood pressures (BP) and heart rates (HR) were measured 24 hours postdose. The mean changes in standing BP (mmHg) were -6.2/-6.9 (2-mg regimen), -5.7/-5.8 (4-mg regimen), -8.5/-7.7 (8-mg regimen) for DOX patients and 0.7/-2.9 for placebo patients. The mean changes in supine BP (mmHg) were -3.2/-4.7 (2-mg regimen), -4.0/-5.1 (4-mg regimen), -4.6/-5.6 (8-mg regimen) for DOX patients and -0.5/-3.3 for placebo patients. There was no evidence of a dose-response relationship for DOX; however, DOX serum levels were linearly related to the dose. Responder rate for the combined DOX patients was 38% (32/84) and for the placebo patients 27% (8/30). HR (24 hours postdose) was not modified by DOX. Patients in the 8-mg regimen had a significantly higher gain in mean body weight (+ 1.3 +/- 0.3 kg; P less than 0.05) compared to the 2-mg regimen, 4-mg regimen, and placebo groups. Plasma norepinephrine was not significantly modified by DOX. DOX had a favorable effect on plasma lipids. DOX lowered LDL cholesterol (P less than 0.05), total cholesterol, and apoprotein B and increased HDL/(LDL + VLDL) ratio (0.05 less than or equal to P less than 0.1) compared to placebo. Dropout rate and treatment-related side effects were equally distributed among the DOX and placebo groups. No patients had the dose of medication reduced because of side effects. Three DOX patients were withdrawn because of postural dizziness.

Blood Pressure↗
PubMed1987

Pharmacokinetic consequences and toxicologic implications of metyrapone-induced alterations of acetaminophen elimination in man.

This study examined the effect of metyrapone on the elimination rate of acetaminophen and on the apparent formation rate of acetaminophen metabolites in man. Metyrapone treatment, 1.5 g, increased the half-life of acetaminophen, decreased the fraction of the dose recovered in the urine as the glucuronide and increased the fraction of the dose recovered in urine as the sulfate and mercapturate conjugates. The apparent rate constant for the formation of acetaminophen glucuronide was significantly decreased by metyrapone while the apparent rate constants for the formation of the sulfate and mercapturic acid metabolites were unchanged or slightly increased, respectively. These data indicate that metyrapone inhibits acetaminophen glucuronidation and possibly enhances the oxidation of acetaminophen to its quantitatively minor yet highly toxic reactive metabolite. The extent to which the parallel pathways of acetaminophen elimination are also affected by inhibitors of cytochrome P-450-mediated oxidation will limit the efficacy of these types of potential antidotes for the treatment of acetaminophen overdose.

Acetaminophen↗
PubMed1987

Localization of ectopic pheochromocytomas by magnetic resonance imaging.

Magnetic resonance imaging (MRI) was utilized to localize ectopic pheochromocytomas in two patients. In both cases, MRI proved superior to computed tomography. Differentiation from surrounding tissue was excellent. MRI permits spatial localization and by assessment of signal contrast intensity provides a suggestion as to the characteristics of the tumor without the use of invasive procedures or intravenous injections. MRI should be considered as an alternative to computed tomography when evaluating patients with a suspected pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1987

The effect of propylene glycol on antipyrine clearance in humans.

To evaluate the potential interaction of propylene glycol on hepatic drug oxidation, antipyrine disposition was measured in 10 healthy subjects who received 1.2 gm antipyrine alone on one occasion and 1.2 gm antipyrine with propylene glycol on a second occasion. Propylene glycol was given as a 5 ml dose every 4 hours during the 48 hours of the study. Propylene glycol had no effect on antipyrine half life (11.7 hours control vs. 12.1 hours treatment), clearance (42.6 vs. 39.2 ml/min), or volume of distribution (42.1 vs 41.9 L). At a dose similar to that used as a vehicle for administration of other drugs, propylene glycol had no significant effect on antipyrine clearance in humans.

Adult↗
PubMed1987

Controlled multicenter study of the antihypertensive effects of lisinopril, hydrochlorothiazide, and lisinopril plus hydrochlorothiazide in the treatment of 394 patients with mild to moderate essential hypertension.

Lisinopril (LIS) is a lysine analog of enalaprilat, the active metabolite of enalapril, an angiotensin-converting enzyme inhibitor (ACEI). Unlike enalapril, the precursor of enalaprilat, LIS is not a prodrug but has equal ACEI efficacy and potency and a slightly longer duration of action after oral administration. Short-term (12 weeks) and long-term (24 weeks) blood pressure control has been studied with LIS, hydrochlorothiazide (HCTZ), and LIS + HCTZ when given once a day. Drug treatment had three phases: (i) 2-4 weeks of single-blind placebo washout; (ii) 12 weeks of double-blind comparison therapy with LIS 20, 40, and 80 mg vs. HCTZ 12.5, 25, and 50 mg, vs. LIS + HCTZ 20 + 12.5, 40 + 25, and 80 + 50 mg; (iii) 13-24 weeks single-blind LIS vs. LIS + HCTZ. Starting double-blind therapy at the lowest dose, all three groups doubled the dose at weeks 4 and 8 if BP was not controlled with sitting diastolic BP (SDBP) less than 90 mm Hg. At the end of 12 weeks of double-blind therapy, uncontrolled HCTZ-only and LIS-only treatment groups were advanced to combination LIS + HCTZ therapy but uncontrolled LIS + HCTZ patients were dropped. Mean BP reductions (systolic/diastolic, mm Hg) for all three groups after 12 weeks of double-blind comparison therapy were: (i) LIS (n = 162), -16.6/-12.5; (ii) HCTZ (n = 155), -10.4/-6.8; (iii) LIS + HCTZ (n = 74), -23.9/-18.2 with p less than 0.01 for all groups compared to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Pharmacology of angiotensin converting enzyme inhibitors. A review.

Two angiotensin converting enzyme inhibitors are currently available for clinical use. Captopril, a sulfhydryl-containing compound, is a direct acting enzyme inhibitor. Enalapril is a non-sulfhydryl pro-drug that requires enzymatic conversion to enalaprilic acid, a potent angiotensin converting enzyme inhibitor. Both drugs lower blood pressure, suppress blood pressure response to angiotensin I infusion, and elevate plasma renin activity. Enalapril bioavailability is unaffected by food, whereas captopril availability is suppressed by food. Dose adjustments are necessary for patients with congestive heart failure and renal failure.

Angiotensin I↗
PubMed1986

Antihypertensive activity of isradipine in humans: a new dihydropyridine calcium channel antagonist.

Isradipine (Sandoz PN 200-110), a new dihydropyridine calcium channel antagonist, was evaluated in a randomized, double-blind, placebo-controlled trial for antihypertensive efficacy in 24 patients with essential hypertension. Two groups were studied: one received placebo throughout the entire study (n = 12) and the other received isradipine (n = 12), 2.5 mg b.i.d., for the first week, 5 mg b.i.d. the second week, and 10 mg b.i.d. the third week after an initial 3-week baseline placebo period. Blood pressure was measured approximately 3 hours after dosing. Isradipine, at a total daily dose of 10 mg, lowered average supine diastolic blood pressure 11.8 mm Hg, with only a 3.5 mm Hg decrease in systolic blood pressure compared with baseline. At a total daily dose of 20 mg, average supine diastolic blood pressure decreased 14.8 mm Hg and supine systolic blood pressure declined 13.9 mm Hg; both were significantly decreased compared with placebo or baseline. Heart rate was increased only minimally by isradipine. Renin level activity was increased slightly by isradipine. No serious adverse clinical or laboratory experiences were noted. Isradipine appears to be effective in lowering blood pressure without reflex tachycardia.

Adult↗