Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Dec 1988
Randomized Controlled Trial Clinical TrialThe combination of ibuprofen and oxycodone/acetaminophen in the management of chronic cancer pain.
Thirty subjects with chronic moderate to severe pain who were receiving oxycodone/acetaminophen (oxy/APAP) for analgesia were initially evaluated for at least 7 days for oxy/APAP requirements for pain control. Each subject then received, in a randomized double-blind fashion, either 600 mg ibuprofen or placebo for an additional 7 days while hospitalized. Oxy/APAP usage was recorded daily along with efficacy and toxicity parameters. ⋯ Overall global scores showed a marked preference for the ibuprofen combination over placebo (p less than 0.01). Daily pain intensity (p less than 0.05) and pain relief scores (p less than 0.05) also improved with the addition of ibuprofen. This study indicates that ibuprofen is efficacious in the management of chronic cancer pain, resulting in both enhanced analgesia and a reduction in concomitant narcotic use.
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Preliminary data have suggested that phenytoin systemic clearance may increase during initial therapy in critically ill patients. The objectives for this study were to model the time-variant phenytoin clearance and evaluate concomitant changes in protein binding and urinary metabolite elimination. Phenytoin was given as an intravenous loading dose of 15 mg/kg followed by an initial maintenance dose of 6 mg/kg/day in 10 adult critically ill trauma patients. ⋯ Phenytoin free fraction increased in a majority of patients during the study period, with a binding ratio inversely related to albumin. Measured urinary p-HPPH data were consistent with the proposed model. A loading and constant maintenance dose of phenytoin frequently yielded a substantial, clinically significant fall in plasma concentrations with a pattern of apparently increasing clearance that may be a consequence of changes in protein binding, induction of metabolism, or the influence of stress on hepatic metabolic capacity.
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Clin. Pharmacol. Ther. · Oct 1988
Hydromorphone levels and pain control in patients with severe chronic pain.
To better understand the use of narcotic analgesics, the hydromorphone concentration was measured in serum samples from 43 patients with chronic severe pain who were receiving this drug. At the time of blood sampling, pain intensity, mood, and cognitive performance were assessed. There was large individual variation in the dose-drug level relationship. ⋯ Poor mood correlated with high pain intensity and low drug level. Impaired cognitive performance was not related to drug level. Knowing that there is a low concentration of narcotic in the blood of a patient with chronic severe pain who is receiving high drug doses and who shows lack of both efficacy and side effects may reassure health care professionals that further narcotic dosage escalation is appropriate.
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Clin. Pharmacol. Ther. · Oct 1988
Prediction of efficacy and tolerance of oral mexiletine by intravenous lidocaine application.
In a controlled crossover trial, 15 patients with frequent ventricular arrhythmias were treated with lidocaine to predict efficacy and safety of oral mexiletine. After an initial control period, patients received intravenous lidocaine (bolus infusion of 200 mg/20 min followed by 3.6 gm/24 hr and for 7 days oral mexiletine (200 mg four times a day). Efficacy was controlled by 24-hour Holter monitoring (responders = suppression of single premature ventricular beats [PVB] greater than 84% and of complex PVB greater than 90%). ⋯ After mexiletine, five of 15 patients (33%) were responders (mean PVB reduction: 81%); efficacy was closely related to the plasma concentration. When efficacy of both agents was compared, lidocaine infusion had a positive predictive value of only 50%; however, the negative predictive value was 100%. Thus in nonresponders to lidocaine, mexiletine is very likely to fail in the suppression of ventricular ectopy.
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Clin. Pharmacol. Ther. · Aug 1988
Comparative StudyImpaired vasodilation during long-term beta 1-selective beta-blockade in hypertensive patients.
In eight patients with essential hypertension the effect of 50 mg atenolol, once daily for 6 months, on vasodilation during epinephrine infusion and submaximal dynamic exercise was studied. The normal decrease of diastolic blood pressure during bicycle exercise, reflecting a decrease in total peripheral resistance not mediated by circulating epinephrine, disappeared during atenolol treatment. Low-dose infusion of epinephrine had no influence on systolic blood pressure both before and after atenolol. ⋯ Forearm vascular resistance decreased before and during atenolol to the same extent. So the normal physiologic vasodilation during submaximal dynamic exercise seems impaired during long-term treatment with atenolol. In addition the normal vasodilating response to an increase of circulating epinephrine to levels occurring during daily life stress seems impaired even with the low dose of this beta 1-selective beta-blocker.