Lawrence H. Golden

Effect of cimetidine on the pharmacokinetics and pharmacodynamics of quinidine.

The influence of cimetidine (1.2 g/day for 7 days) on the disposition and pharmacodynamic effects of a single oral dose of quinidine was studied in 6 normal volunteers. Cimetidine reduced the mean apparent oral clearance of quinidine (+/- standard error of the mean) from 25.5 +/- 2.7 to 16.2 +/- 1.4 liters/h (p less than 0.05). This was reflected in a 55% (range 30 to 109) increase in the mean half-life from 5.8 +/- 0.2 to 9.0 +/- 0.6 hours (p less than 0.05). Peak quinidine plasma concentrations and times to peak were also increased (p less than 0.05). Plasma protein binding and urinary excretion of quinidine were unchanged by cimetidine treatment. Alterations in the pharmacokinetic variables of quinidine were mirrored in simultaneously measured electrocardiographic parameters. Changes in Q-T, rate-corrected Q-T, QRS, and R-R intervals after a single oral dose of quinidine sulfate (400 mg) were significant. Treatment with cimetidine potentiated these pharmacodynamic changes, but failed to achieve significant differences from quinidine alone. Thus, cimetidine impairs the elimination of oral quinidine in normal volunteers. This interaction may lead to quinidine toxicity in patients in whom cimetidine is concomitantly administered.

Safety and Efficacy of Procainamide Infusions

Thirty-four patients who were resistant to conventional doses of lidocaine received procainamide intravenously according to a pharmacokinetically designed two infusion technique. A mean peak serum concentration of 7.1 mg/liter was achieved with an average loading dose of 989 mg administered over 1 hour. A mean steady state serum concentration of procainamide of 6.5 mg/liter was achieved with a mean dose of 64.4 mg/kg body weight for the first 24 hours of treatment. Dose, renal impairment, the degree of congestive heart failure and acetylator status influenced the steady state serum concentration of procainamide. Dangerous ventricular arrhythmias were abolished in 74% of the patients at a steady state level of 6.9 +/- 3.7 mg/liter (mean +/- standard deviation). Nonresponders to procainamide had a mean steady state serum concentration of procainamide of 4.2 +/- 2.1 mg/liter (P less than 0.05). Systolic and diastolic blood pressures decreased moderately (10 and 8%, respectively), and heart rate decreased 11%. The infusion was interrupted in one patient because of hypotension. The duration of electrocardiographic conduction intervals was increased slightly in some patients. It is concluded that procainamide administered by this two infusion method is effective and well tolerated by most patients.

Clinical Pharmacokinetics of Procainamide Infusions in Relation to Acetylator Phenotype

The pharmacokinetics of procainamide was determined in 21 lidocaine-resistant patients who received the drug according to a pharmacokinetically designed double-infusion technique. Thirteen patients were phenotyped as slow acetylators, seven as fast, and one as intermediate. The total body clearances (ClT) of PA in slow and fast acetylators were 22.6 and 34.8 liters/hr, respectively. The fraction of PA cleared by the formation of NAPA in the corresponding acetylator group was 0.2 and 0.4. Renal impairment affected the pharmacokinetics of PA more profoundly as the ClTs of PA in patients with and without renal impairment were 17.9 and 31.2 liters/hr, respectively. None of the calculated volumes of distribution was affected by acetylator phenotype or renal impairment. These data identify the contribution of at least two of the major factors accounting for variability in PA disposition in patients undergoing therapy.

Pharmacokinetic approach to intravenous procainamide therapy

SummaryA pharmacokinetic approach was employed to design a dosing regimen for the i. v. use of procainamide (PA) which consisted of a loading infusion given over one hour followed by a maintenance infusion. Therapeutic serum concentrations of PA were achieved in less than 15 min, and toxic serum concentrations were avoided in 12 patients. A mean maximum serum concentration of PA of 5.78 mg/l was obtained with a loading infusion of 16.6 mg/min PA HCl. An average steady-state serum concentration of PA of 5.05 mg/l was obtained with a mean maintenance infusion of 222 mg/hour PA HCl. The total body clearance of PA in slow and fast acetylators averaged 31 and 43 l/h respectively. Use of PA in cardiac patients by i. v. infusion can be safe and effective therapy.

The “Nona” Electrocardiogram: Findings in 100 Patients of the 90+ Age Group

The electrocardiograms of 100 men and women, all past the age of 90, were analyzed for conduction times, axis deviation, summed frontal QRS and T amplitudes. The ECG patterns were classified, and limited clinical correlations were made. The heart rate, R‐T and QRS intervals remained virtually unchanged with age. An increase in PR intervals, a left axis shift and a reduction in summed frontal T values were noted. The high incidences of atrial fibrillation, left anterior hemiblock, extra systoles and delayed AV conduction were probably a result of the widespread use of digitalis. The two most common ECG abnormalities were left ventricular hypertrophy (evidently a natural consequence of advanced age) and myocardial infarction (often undiagnosed clinically).

Normalization of hypertensive responses during ambulatory surgical stress by perioperative music

Objective The purpose of this study was to determine whether cognitive appraisals of stress level and hypertensive responses to ambulatory ophthalmic surgery can be ameliorated by patient-selected music. Methods We studied 40 elderly individuals requiring ophthalmic surgery, 20 in an experimental group (mean age, 74 years) and 20 in a control group (mean age, 77 years). All patients had an established resting blood pressure <140/90 mm Hg. In the experimental group self-selected music was provided by headphones throughout the preoperative, surgical, and postoperative periods. In the control group patients had neither headphones nor music. All patients received similar (weight-determined) doses of alfentanil and midazolam during surgery. Heart rate, blood pressure, and patient-reported stress and coping levels were the dependent variables. Results In both groups, blood pressure values were normal (approximately 129/82 mm Hg) during screening examinations 1 week before surgery. On the day of surgery both groups displayed increased preoperative blood pressures (approximately 159/92 mm Hg) associated with increases in heart rate (by approximately 17 beats/min). Intraoperative blood pressures in the experimental group returned quickly to screening baseline values, whereas the control group experienced persistent elevations in intraoperative blood pressure similar to preoperative levels. Over the course of the surgical experience, patients with music reported significant reductions in perceived stress and increases in coping abilities (p < .001), whereas those without music did not. Conclusions The perceived stress of ambulatory surgery in geriatric patients is associated with a clinical hypertensive response that is ameliorated by self-selected perioperative music, which also decreases perceived stress and increases patients’ sense of personal control and well-being.