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Biomedical subjects

R S Porter

Publications and source records attributed to R S Porter.

At least 37 records · Page 2Linked to original sources
PubMed1990

Amiodarone-liposome interaction: a multinuclear NMR and X-ray diffraction study.

Amiodarone, a potent antiarrhythmic drug, is widely used in cardiology. Its electrophysiological effects, as well as many of its side effects, seem to involve lipids. We report here a multinuclear NMR and X-ray diffraction study of amiodarone in egg phosphatidylcholine liposomes and lipid multilayers. In proton NMR experiments, amiodarone alters the signal from the lipid trimethyl ammonium group for pH values ranging from 3.2 to 8.4; cholesterol does not cause this alteration. The addition of SCN- changes both the proton and phosphorus NMR spectra of liposomes containing amiodarone. For both proton and carbon NMR, amiodarone modifies the signal from the lipid methylene groups, but to a far lesser extent than does cholesterol. Incorporation of amiodarone in EPC bilayers also modifies the low-angle X-ray diffraction patterns, decreasing the lamellar repeat period at low water contents, but swelling the fluid spaces between bilayers at high water contents. Electron density profiles and modeling studies using the X-ray data indicate that amiodarone decreases the bilayer thickness and adds electron density at the interfacial region of the bilayer. Our analysis of the NMR and X-ray data indicates that the iodine atoms of amiodarone are located near the hydrocarbon/water interface and that the tertiary amine of amiodarone is in the headgroup region of the bilayer.

Amiodarone↗
PubMed1990

The pharmacology of adenosine.

Adenosine is a purine nucleoside present in every cell of the human body. It is released into the extracellular space under physiologic and pathophysiologic conditions characterized by increased oxygen demand:supply ratio. Adenosine can exert a wide spectrum of effects in various organs and tissues. Exogenous adenosine has a wide spectrum of effects in experimental animal models as well as humans. The pharmacokinetics, pharmacodynamics, and the interaction of adenosine with other drugs are reviewed.

Adenosine↗
PubMed1989

Reassessment of cross-reactivity of spironolactone metabolites with four digoxin immunoassays.

Spironolactone and one of its metabolites, canrenone, cross-react with some digoxin immunoassays to result in erroneous serum digoxin concentrations. Recently, additional compounds, 7-alpha-thiomethylspirolactone (7-a-TMS) and 6-beta-hydroxy-7-alpha-thiomethylspirolactone (6-B-OH-7-a-TMS), have been reported to be quantitatively important metabolites of spironolactone. This study was initiated to evaluate the cross-reactivity of these metabolites, canrenone, and spironolactone with four different digoxin immunoassays. Blank serum was spiked with each compound to yield concentrations reported to occur in vivo. Samples were analyzed in duplicate by each of the following immunoassays: fluorescence polarization immunoassay (FPIA); affinity-column-mediated immunoassay (ACMIA); radioimmunoassay (RIA); and enzyme immunoassay (EIA). The 7-a-TMS metabolite cross-reacted with both the RIA and ACMIA methods. Apparent digoxin concentrations were as great as 0.39 ng/ml for this metabolite at the highest concentration evaluated, 600 ng/ml. At the lowest concentrations evaluated with the 7-a-TMS metabolite, 50 ng/ml, apparent digoxin concentrations as high as 0.28 ng/ml were reported. The 6-B-OH-7-a-TMS metabolite did not cross-react to a significant extent with any of immunoassays studied. Canrenone cross-reacted with the ACMIA method at a concentration of 100 ng/ml. The EIA method exhibited no apparent cross-reactivity with any of the compounds, whereas the FPIA method exhibited minimal cross-reactivity. The results of this study indicate that the 7-a-TMS metabolite cross-reacts to a significant extent with some immunoassays; however, this is not true for the 6-B-OH-7-a-TMS metabolite.

Adult↗
PubMed1989

T wave inversion associated with severe theophylline toxicity.

Adverse cardiovascular effects are commonly seen in severe theophylline poisoning. Primary ST-T wave changes have not been described previously. We report T wave inversion associated with severe theophylline toxicity in a 33-year-old woman with no evidence of organic heart disease. The T wave inversion resolved after treatment. Physicians should be alerted to possible T wave abnormalities in patients with severe theophylline poisoning.

Adult↗
PubMed1987

Esmolol-digoxin drug interaction.

An open-label baseline-controlled study was conducted in 11 healthy male subjects to study the possible interaction between the cardioselective, short-acting beta blocker esmolol and digoxin when administered concurrently under steady-state conditions. Steady-state concentration, elimination half-life, and the total body clearance of esmolol were not changed significantly (P greater than .05) by digoxin. Digoxin peak concentration and the time to reach the peak concentration were not affected by esmolol. However, the digoxin AUC during the six-hour esmolol infusion increased from 2.60 +/- 0.59 to 2.88 +/- 0.75 ng.hr/mL (P less than .05). There were no clinically significant changes in the heart rate and blood pressure during this drug interaction study. The PR intervals were similar between digoxin monotherapy and esmolol plus digoxin combined treatment. Although digoxin did not influence the kinetics of esmolol, the small increase seen in digoxin serum concentration during the combination therapy warrants that caution be exercised during concurrent administration of esmolol and digoxin to patients.

Adolescent↗
PubMed1986

Plasma norepinephrine in exercise-induced ventricular tachycardia.

The relation between plasma norepinephrine levels and the occurrence of ventricular tachycardia during exercise testing was prospectively evaluated in 17 patients. Ten patients had reproducible ventricular tachycardia exclusively during exercise or recovery, or both; 7 patients had ventricular tachycardia only during ambulatory electrocardiographic monitoring. The two groups did not differ in age, exercise duration, left ventricular ejection fraction at rest, heart rate throughout the exercise protocol, rest QTc interval, change in QTc interval during exercise, the presence of coronary artery disease or exercise-related myocardial ischemia. Furthermore, there was no difference between groups in plasma norepinephrine levels at rest, peak exercise or in the recovery period. Myocardial ischemia was detectable by thallium perfusion scan in only 2 of the 10 patients with exercise-induced ventricular tachycardia. The 10 patients with exercise-induced ventricular tachycardia underwent repeat exercise testing immediately after maximal intravenous beta-adrenergic blockade with propranolol. Although they had no change in exercise duration, ventricular tachycardia did not occur in 9 of these 10 patients. Plasma norepinephrine levels were significantly decreased compared with levels before beta-adrenergic blockade (p less than 0.0002). Thus, plasma norepinephrine levels do not distinguish patients with reproducible exercise-induced ventricular tachycardia from otherwise comparable patients. Propranolol is highly effective in abolishing this arrhythmia and this effect is associated with decreased norepinephrine levels.

Adult↗
PubMed1986

Lethal accumulation of procainamide metabolite in severe renal insufficiency.

Four patients, 64-80 years of age, with severe renal dysfunction and heart disease received conventional doses of procainamide as treatment for cardiac arrhythmias. Serum procainamide concentrations at these times ranged from 6.2 to 13.3 micrograms/ml and were within the recently expanded therapeutic range for resistant ventricular arrhythmias. All 4 patients demonstrated marked and delayed accumulation of the active metabolite N-acetylprocainamide, with highest observed serum concentrations ranging from 42.0 to 59.4 micrograms/ml. Cardiotoxicity associated with these levels included progressive widening of the QRS and corrected Q-T intervals, induction of polymorphic non-sustained ventricular tachycardia (torsades de pointes), and severe depression of left ventricular function which appeared to be important factors in the deaths of these patients. The use of lower procainamide doses and careful anticipatory monitoring of serum concentrations of procainamide and N-acetylprocainamide are essential in this high-risk group.

Acecainide↗
PubMed1985

Clinical pharmacology, pharmacodynamics and interactions with esmolol.

The clinical pharmacology and pharmacodynamic data from several clinical trials are summarized. The pharmacokinetic profile of esmolol alone and in the presence of digoxin, morphine and warfarin was studied. Conversely the effect of esmolol on these drugs was monitored. No clinically important effects were observed on vital signs, blood chemistry or hematology. The pharmacokinetic interactions associated with administration of these drug combinations were statistically significant in several cases, but they were not considered to be of clinical importance.

Adrenergic beta-Antagonists↗
PubMed1985

Drug clearance by diarrhea induction.

Perfusion of the gastrointestinal tract with electrolyte solution has been used as an equivalent to peritoneal dialysis in patients with renal failure. It was hypothesized that the back-diffusion into the gastrointestinal tract induced by this procedure could affect systemically circulating drugs as well. Nine dogs were given intravenous phenobarbital and subjected to gastrointestinal perfusion in attempt to lower serum levels. All dogs served as their own controls. Decline in serum phenobarbital level was used to calculate the amount of drug removed from circulation. Five hours after initiation of gastrointestinal perfusion, the experimental dogs had cleared 24.8% of the initial dose of phenobarbital, while controls cleared 3.13% of the initial dose of phenobarbital. This procedure could be of potential benefit to patients in emergency departments who have ingested toxic substances.

Animals↗
PubMed1985

Comparison of intravenous and oral routes of theophylline loading in acute asthma.

In a prospective, randomized clinical trial, 19 patients with an acute exacerbation of asthma were given a loading dose of aminophylline by the IV (n = 10) or oral route (n = 9) of administration following treatment with epinephrine. Plasma concentrations of theophylline were measured prior to giving the loading dose, and one, two, three, and 24 to 48 hours later. Therapeutic effectiveness was evaluated by analyzing spirometric measurements prior to giving the loading dose, and one, three, and 24 to 48 hours later. Side effects also were recorded. In the IV group, the mean peak plasma theophylline concentration was 15.1 micrograms/mL one hour after loading, and in the oral group the mean peak serum theophylline concentration was 14.2 micrograms/mL three hours after loading. There was no correlation between theophylline concentrations and normalized change in spirometric values. There was no significant difference in spirometric values between the IV and oral groups. Nausea was slightly more common in the IV group. We conclude that there is no therapeutic advantage to giving a loading dose of aminophylline by the IV route rather than orally in patients with mild-to-moderate exacerbation of asthma initially treated with epinephrine.

Acute Disease↗
PubMed1984

Effects of nifedipine and verapamil on isometric and dynamic exercise in normal subjects.

Effects of single- and multiple-dose nifedipine and verapamil in 10 healthy men were compared with the effect of placebo during static and dynamic physical activity. Blood pressure (BP), heart rate (HR), and plasma catecholamine and plasma potassium levels were assessed and quantified at rest and at peak levels of 50% handgrip and at rest and peak treadmill activity during placebo, single- and at 2 multiple-dose levels of each of the drugs. Peak BP responses were blunted by a maximal dosage of 120 mg of verapamil administered twice daily during static activity. No blunting of HR response was observed. BP and HR did not change significantly at any dosage level of nifedipine during static exercise. During isotonic exercise the only significant alteration was a progressive decrease in the peak exercise HR with both verapamil and nifedipine. The plasma potassium level increased with both static and dynamic activity but to no greater level than that seen with placebo. Plasma norepinephrine concentration increased at rest after administration of maximal dosage of nifedipine during both isometric and isotonic phases of the study. This is probably related to the underlying mild to moderate increase in sympathetic tone induced by nifedipine. Overall, the hemodynamic responses to exercise are not blunted with calcium-channel antagonists at the dosages studied.

Blood Pressure↗
PubMed1984

Factors determining efficacy of NSAIDs.

This article reviews the efficacy of NSAIDs and their pharmacokinetic and pharmacodynamic properties. The assumption that classic pharmacokinetic dose/plasma concentration response relationships can be applied to NSAIDs has tenuous support in the biomedical literature. Comparative efficacy studies, using ASA and indomethacin as the standards for comparison, ignore the fact that the major outcome variables are subjective responses among patients, not among drugs. Comparing inhibition of platelet malonyldialdehyde, synovial drug concentrations, urinary prostaglandin metabolites, and plasma free and total concentration with the clinical outcome provides no guidelines to serve as predictors of response. The individual agents, indomethacin, salicylates, sulindac, piroxicam, and naproxen, illustrate the complexities of NSAID pharmacotherapy. Recent proliferation of newer NSAIDs will not add significantly to the efficacy of these agents in the treatment of pain and inflammatory disease states. However, knowledge of pharmacokinetic population parameters for the individual NSAIDs will increase the likelihood of therapeutic success and diminish the possibilities for adverse reactions.

Anti-Inflammatory Agents↗
PubMed1984

The clinical pharmacology of antihypertensive drugs.

Antihypertensive drugs act centrally (methyldopa, clonidine, guanabenz), peripherally (prazosin, guanadrel, guanethedine, hydralazine, minoxidil), centrally and peripherally (beta-adrenergic blocking drugs) and systemically [angiotensin converting enzyme (ACE) inhibitors and diuretics]. Centrally-acting antihypertensives decrease blood pressure by diminishing sympathetic outflow from the vasomotor centre. Peripherally-acting antihypertensives act by depleting or inhibiting the release of catecholamines from the peripheral nerve ending or altering the response at alpha 1- and alpha 2-receptor sites. Beta-adrenergic blocking drugs act through a variety of mechanisms by either decreasing cardiac output, decreasing renin release, inhibiting prejunctional release of norepinephrine or through central mechanisms. Diuretics act as indirect vasodilators by depleting salt and water not only within the intravascular compartment but within the intramural portion of the arteriole, thereby diminishing its responsiveness to catecholamine and angiotensin II stimulation. ACE inhibitors such as captopril and enalapril act by inhibiting the conversion of angiotensin I to angiotensin II thereby decreasing the vasoconstrictor effect of angiotensin II and the aldosterone production secondary to angiotensin II stimulation. The main differences between captopril and enalapril is that enalapril does not possess the potentially toxic sulphydryl group and can be given twice-daily. Both drugs may show accumulation in patients with impaired renal function.

Adrenergic alpha-Agonists↗