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Biomedical subjects

R R Luther

Publications and source records attributed to R R Luther.

42 records · Page 3Linked to original sources

Carteolol treatment of essential hypertension: a long-term study of safety and efficacy.

The long-term safety and antihypertensive efficacy of carteolol were evaluated in an open-label, multicenter trial of 245 hypertensive patients. For those patients maintained on carteolol monotherapy, three months of treatment with once-daily oral doses of carteolol ranging from 2.5 to 60 mg reduced the mean recumbent blood pressure by 12/14 mm Hg from baseline values of 151/100. Blood pressure reductions observed at three months were maintained throughout the study. The final daily dose of carteolol for most patients was 10 mg or less. Carteolol was shown to be safe and well tolerated by most patients.

Adult↗

Terazosin: a new alpha 1-blocker for the treatment of hypertension: a review of randomized, controlled clinical trials of once-daily administration as monotherapy.

Terazosin, a new selective long-acting alpha1-adrenergic blocking agent, has been shown to be an effective once-daily antihypertensive agent in four of five randomized double-blind placebo-controlled studies of patients with mild to moderate hypertension. In one trial, 24-h monitoring revealed that terazosin produced a sustained blood pressure lowering effect throughout the day. In three fixed-dose trials, steady patterns of blood pressure response during maintenance therapy indicated that tolerance to terazosin did not develop. Favourable changes in the plasma lipid profile were observed, while laboratory data suggested the development of haemodilution. Overall, terazosin was well tolerated. Asthenia, dizziness and peripheral oedema were significantly more common in patients treated with terazosin than with placebo.

Adrenergic alpha-Antagonists↗

Ziconotide, a new N-type calcium channel blocker, administered intrathecally for acute postoperative pain.

BACKGROUND AND OBJECTIVES: Voltage-sensitive calcium channel conductance is essential for the nervous system to signal a painful event. However, intrathecal administration of L-type calcium channel blockers does not provide analgesia. The present investigation was designed to assess the safety and analgesic efficacy of ziconotide, a new N-type calcium channel blocker, when administered intrathecally to patients with acute postoperative pain. METHODS: This randomized, double-blind, pilot study included patients undergoing elective total abdominal hysterectomy, radical prostatectomy, or total hip replacement. After intrathecal injection of local anesthetic and before surgical incision, a continuous intrathecal infusion of either placebo or 1 of 2 doses of ziconotide (0.7 microg/h or 7.0 microg/h) was started and continued for 48 to 72 hours postoperatively. Primary and secondary efficacy variables were the mean daily patient controlled analgesia (PCA) morphine equivalent consumption and visual analog pain intensity (VASPI) scores, respectively. RESULTS: Thirty patients received study drug; 26 were evaluable for efficacy. Mean daily PCA morphine equivalent consumption was less in patients receiving ziconotide than in placebo-treated patients, and the difference was statistically significant between 24 and 48 hours (P = .040). VASPI scores during the first 8 hours postoperatively were markedly lower in ziconotide-treated than in placebo-treated patients. In 4 of 6 patients receiving the high-dose of ziconotide (7 microg/h), adverse events, such as dizziness, blurred vision, nystagmus, and sedation contributed to study drug being discontinued after 24 hours. After ziconotide discontinuation, these symptoms resolved. CONCLUSIONS: Ziconotide showed analgesic activity, as shown by decreased PCA morphine equivalent consumption and lower VASPI scores. Because of a favorable trend of decreased morphine consumption with an acceptable side-effect profile in the low-dose ziconotide group, 0.7 microg/h may be closer to the ideal dose than 7 microg/h. Large-scale studies are required to clarify this issue.

Acute Disease↗

Anaphylaxis: etiology and guidelines for management.

The successful management of anaphylaxis requires a thorough understanding of this syndrome and the application of various therapeutic agents. Although the mechanisms responsible for human anaphylaxis are not fully known, sufficient data and clinical experience are available to guide the anesthesiologist faced with this medical emergency.

Adrenal Cortex Hormones↗

Simultaneous modeling of the pharmacokinetic and pharmacodynamic properties of enalkiren (Abbott-64662, a new renin inhibitor). I: Single dose study.

This study describes the relationship between the measured effects (angiotensin I and renal plasma flow) and plasma drug levels using a combined pharmacokinetic-pharmacodynamic model after 90 min iv infusion of enalkiren in 15 healthy, salt-depleted subjects. Doses from 0.002 to 0.512 mg/kg were evaluated. One hour prior to enalkiren dosing, para-aminohippuric acid infusion was started for each subject and continued until 3 hr after the start of enalkiren infusion. Timed blood samples were obtained to measure enalkiren, para-aminohippuric acid, and angiotensin I levels in plasma. Enalkiren-induced effect changes lagged in time behind the plasma enalkiren level changes, showing a counterclockwise hysteresis loop. To relate the temporal relationship of effect changes accurately to plasma drug levels, a pharmacokinetic model was combined with a pharmacokinetic model that incorporated a hypothetical effect compartment. The magnitude of the time lag was quantified by the half-time of equilibration between concentrations in the hypothetical effect compartment and the plasma enalkiren levels (t1/2keo). The t1/2keo for angiotensin I (0.002 hr) is significantly shorter than that of renal plasma flow (0.267 hr), indicating that enalkiren equilibrates more rapidly with the angiotensin I-related effect compartment than the renal plasma flow-related effect compartment. Moreover, the model allows for estimation of the effect site concentration that causes one-half of the maximal predicted effect (EC50), which is a measure of an individual's sensitivity to enalkiren. The EC50 of angiotensin I (81.1 ng/ml) is substantially lower than that of renal plasma flow (4414 ng/ml), indicating that angiotensin I may be a more sensitive measure of enalkiren effects than renal plasma flow.

Adult↗