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Biomedical subjects

R B Parker

Publications and source records attributed to R B Parker.

At least 19 recordsLinked to original sources
PubMed1991

Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects.

To evaluate the effects of calcium pretreatment on the disposition and electrocardiographic effects of verapamil, 8 healthy male volunteers received treatment in each of 3 phases in a randomized, double-blind, crossover manner. Phase I denoted 10 ml of 0.9% intravenous sodium chloride followed by 10 mg of intravenous verapamil; phase II denoted 10 ml of 10% intravenous calcium chloride followed by 4 ml of 0.9% intravenous sodium chloride; and phase III denoted 10 ml of 10% intravenous calcium chloride followed by 10 mg of intravenous verapamil. Blood samples for the determination of verapamil concentrations were drawn at 5, 10, 15, 20, 30, 45, 60 and 90 minutes, and at 2, 4, 6, 10 and 24 hours. Blood pressure, heart rate and PR intervals were also measured at these times. Pretreatment of verapamil with intravenous calcium did not alter the disposition of intravenous verapamil. Blood pressure was not significantly altered in any treatment phase, although calcium tended to increase mean arterial pressure and verapamil abolished this effect. Calcium had no significant affect on verapamil-induced PR prolongation (maximum percent change in PR interval: phase I = 19 +/- 11%, phase III = 18 +/- 7%; time to maximal prolongation: phase I = 0.38 +/- 0.21 hours, phase III = 0.37 +/- 0.26 hours; and area under the percent change in PR vs time curve: phase I = 15.5 +/- 10, phase III = 21 +/- 9). Verapamil caused a reflex increase in heart rate of similar magnitude in both phases I and III (24 +/- 10% and 21 +/- 7%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Hemodynamic and electrophysiological actions of cocaine. Effects of sodium bicarbonate as an antidote in dogs.

BACKGROUND: Cocaine abuse has been implicated as a cause of death due to sudden cardiac arrest. METHODS AND RESULTS: We examined the hemodynamic and electrophysiological effects of cocaine administered as a series of 5-mg/kg i.v. boluses coupled with a continuous infusion in anesthetized dogs. Sodium bicarbonate (50 meq i.v.) was administered as a potential antidote in 11 of 15 dogs, and intravenous 5% dextrose was given in the remaining four. In a dose-dependent fashion, cocaine significantly decreased blood pressure, coronary blood flow, and cardiac output; increased PR, QRS, QT, and QTc intervals and sinus cycle length; and increased ventricular effective refractory period and dispersion of ventricular refractoriness. No afterdepolarizations were noted in the monophasic action potential recording. Nonsustained monomorphic ventricular tachycardia occurred spontaneously in two dogs, and sustained ventricular tachycardia could be induced by programmed stimulation at the end of the dosing protocol in five of 11 animals. Sodium bicarbonate promptly decreased cocaine-induced QRS prolongation to nearly that measured at baseline but had no effect on the other electrocardiographic or hemodynamic variables. In one dog, sodium bicarbonate administration was associated with reversion of ventricular tachycardia to sinus rhythm. CONCLUSIONS: We conclude that high-dose cocaine possesses negative inotropic and potent type I electrophysiological effects. Sodium bicarbonate selectively reversed cocaine-induced QRS prolongation and may be a useful treatment of ventricular arrhythmias associated with slowed ventricular conduction in the setting of cocaine overdose.

Animals↗
PubMed1991

Evaluation and treatment of ventricular arrhythmias: an update.

An overall approach to evaluating and treating ventricular arrhythmias based on objective monitoring criteria is described. A clinically useful system classifies patients based on whether their ventricular arrhythmias are benign, potentially lethal, or lethal. Some clinicians believe that antiarrhythmic drug therapy improves survival in patients with potentially lethal arrhythmias. However, disappointing results from the Cardiac Arrhythmia Suppression Trial have led to a greater awareness of the potential adverse effects of antiarrhythmics. Various risk factors for arrhythmia-related death have been identified, such as the presence of frequent and complex ventricular ectopy, abnormal signal-averaged electrocardiography (SAECG) tracings, and poor left ventricular ejection fraction (LVEF). Antiarrhythmic drugs remain the primary mode of therapy for patients with recurrent symptomatic tachycardias. Antiarrhythmic drug efficacy has been evaluated by methods including symptom assessment, continuous ambulatory electrocardiographic monitoring (Holter monitoring), exercise testing, and invasive electrophysiologic testing. There may be an extremely wide range of effective serum concentrations for the class IA agents. Individual target concentrations of antiarrhythmic agents may be determined for individual patients and should assist the clinician in optimizing long-term antiarrhythmic drug therapy. The risk-to-benefit ratio of treatment should be weighed before antiarrhythmic drug therapy is begun, and careful, objective monitoring of drug efficacy should be performed. When pharmacologic treatment of ventricular arrhythmias is considered, treatment algorithms that incorporate LVEF measurements, Holter monitor recordings, and SAECG may aid the clinician.

Anti-Arrhythmia Agents↗
PubMed1990

von Willebrand heterotopic osteochondrofibrosis in Doberman pinschers: five cases (1980-1987).

Five cases involving female Doberman Pinschers, each with a mass composed of osseous, chondrous, or fibrous tissue, or a combination thereof, formed in or around the muscles of the hip, were reviewed. In each dog, the mass severely limited the coxofemoral joint range or motion, especially when the joint was extended. Surgical debulking resulted in a favorable outcome. All dogs tested had plasma concentrations of von Willebrand factor antigen below established normal limits. We believe that the low concentrations of von Willebrand factor antigen commonly found in Doberman Pinschers may predispose them to the development of this condition and its resulting pelvic limb lameness, presumably because of increased risk of microvascular bleeding. This association is presumptive because 2 dogs in our study had a history of excessive bleeding either before or after being treated for the hip condition. Trauma was associated in 2 cases. All 5 dogs, however, bled more than usual during the curative surgery. These 5 cases, plus additional reported cases, confirm this syndrome, which warrants recognition. The name von Willebrand heterotopic osteochondrofibrosis of Doberman Pinschers was selected because it identified the basic features of the syndrome.

Animals↗
PubMed1990

Adenosine in the episodic treatment of paroxysmal supraventricular tachycardia.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of adenosine in the treatment of episodes of paroxysmal supraventricular trachycardia (PSVT) are reviewed. Adenosine is an endogenous adenine nucleoside that markedly decreases heart rate and prolongs atrioventricular (AV)-nodal conduction. Adenosine is rapidly cleared from plasma by the cellular elements of the blood and by vascular endothelial cells and subjected to enzymatic metabolism. The drug has a half-life of 0.6 to 10 seconds. In noncomparative clinical trials, adenosine terminated 85% to 100% of induced or spontaneous episodes of PSVT involving the AV node in the reentrant circuit. In patients with arrhythmias that do not involve the AV node in the reentrant circuit, adenosine produces AV block and does not restore sinus rhythm. Prospective, randomized trials comparing adenosine with verapamil in adults have not yet been performed. The adverse effects of adenosine include flushing, dyspnea, headache, cough, chest pain, sinus bradycardia, atrial fibrillation, ventricular arrhythmias, and various degrees of AV block. Because of the short half-life of adenosine, these effects are transient and well tolerated. The initial dose of adenosine in treating acute PSVT is 6 mg given by rapid i.v. bolus injection, followed in one to two minutes by up to two additional 12-mg boluses if necessary. Adenosine has been found to be effective in terminating PSVT and thus offers an alternative to verapamil. Prospective, randomized trials comparing adenosine with verapamil are needed to definitively establish adenosine's role in the therapy of PSVT.

Adenosine↗
PubMed1989

Proarrhythmia: a paradoxic response to antiarrhythmic agents.

Antiarrhythmic drugs may effectively terminate and prevent symptomatic tachycardias, but they may also provoke life-threatening rhythm disturbances. The electrophysiologic mechanisms responsible for proarrhythmia can be extrapolated from the existing models of reentry and abnormal automaticity. Although all antiarrhythmic drugs may cause proarrhythmia with seemingly similar frequency, the profile of the disturbance with each class of agents appears somewhat distinct. All agents may cause an increased frequency of premature beats or new or worsened ventricular tachycardia, but the classic form of proarrhythmia due to type la agents is torsades de pointes. Recent information has provided clues to the underlying mechanism of drug-induced torsades de pointes and has provided a clinical picture of patients with this adverse effect. Types lb and lc agents only rarely precipitate torsades de pointes. The latter, however, may cause a rapid, sustained, monomorphic ventricular tachycardia in certain high-risk patients that can be resistant to resuscitation efforts. Amiodarone may cause a broad variety of arrhythmias that are complicated by their extended duration and difficulty in distinguishing proarrhythmia from simple inefficacy. Proarrhythmia is a relatively common, paradoxic side effect that necessitates the clinician to make careful risk-benefit decisions in choosing antiarrhythmic drug therapy.

Anti-Arrhythmia Agents↗
PubMed1989

Propafenone: a novel type Ic antiarrhythmic agent.

Propafenone is an investigational type Ic anti-arrhythmic agent that markedly slows conduction velocity in all cardiac tissues. Propafenone also possesses weak beta- and calcium-channel blocking properties. The bioavailability of propafenone is dose-dependent. Hepatic metabolism of this agent is polymorphic and appears to correlate with the ability of the liver to oxidize debrisoquin sulfate. Propafenone is effective in suppressing spontaneous ventricular ectopy; however, the drug may be less effective in patients with sustained ventricular tachycardia or ventricular fibrillation when evaluated using programmed stimulation. Propafenone is also useful in the treatment of supraventricular tachycardias including atrioventricular (AV) nodal reentrant tachycardia, AV reentrant tachycardia associated with the Wolff-Parkinson-White syndrome, and atrial fibrillation. Adverse reactions seen with propafenone affect the gastrointestinal, central nervous, and cardiovascular systems. Comparative studies with currently available type Ic agents are needed to better define propafenone's place in therapy.

Animals↗
PubMed1989

Flavodilol: a new antihypertensive agent that preferentially depletes peripheral biogenic amines.

Flavodilol, ((+/-)-7-[2-hydroxy-3-(propylamine)-propoxy]flavone maleate), a new orally effective antihypertensive agent, extensively depleted catecholamines and serotonin in heart tissue of normotensive and spontaneously hypertensive rats (SHR). Dose-response studies demonstrated that greater than or equal to 75% depletion of cardiac norepinephrine (NE) was accompanied by marked blood pressure decline in SHR. In contrast, whole brain biogenic amine levels were decreased only by 15-20% after acute or chronic treatment with antihypertensive doses (35-75 mg/kg). Adrenal epinephrine (EPI) stores were unaffected by acute treatment, although chronic treatment for 18 days with an antihypertensive dose of 75 mg/kg flavodilol decreased EPI by 70%. Acute treatment also decreased serotonin content of spleen by 70-80%. In dogs, a cumulative oral dose of 40 mg/kg decreased catecholamines by greater than or equal to 50% in aorta and heart muscle. Although hypothalamic catecholamine stores appeared to be more susceptible to depletion by flavodilol than catecholamines in other brain regions, these changes did not appear functionally related to blood pressure decreases since analogs of flavodilol without antihypertensive properties produced equivalent or greater depletion of hypothalamic catecholamine stores. In vitro flavodilol promoted spontaneous and potassium-evoked release of dopamine from isolated striatal nerve endings (0.3 microM) and blocked uptake of NE by hypothalamus and hippocampal nerve endings (1 microM), suggesting that biogenic amine depletion in vivo may be caused by an interference with storage and release mechanisms. Despite structural features reminiscent of beta-adrenergic antagonists, flavodilol had low affinity for beta-receptors. Neither was there any inhibition of tyrosine hydroxylase. These findings suggest that the antihypertensive activity of flavodilol results, at least in part, from depletion of sympathetic stores of NE in heart and vascular tissues that moderate adrenergic transmission, thereby decreasing heart rate (HR) and prevailing vascular tone.

Adrenergic beta-Antagonists↗
PubMed1987

Correlation between anorectic potency and affinity for hypothalamic (+)-amphetamine binding sites of phenylethylamines.

The potencies of a number of phenylethylamines and related compounds to inhibit food intake were compared with their relative affinities for hypothalamic (+)-amphetamine binding sites in vitro. There was a positive correlation (r = 0.78, P less than 0.001, n = 19) between potencies of these compounds to inhibit food intake and their potencies to inhibit [3H](+)-amphetamine binding. Individual enantiomers of amphetamine, ephedrine, norephedrine, pseudoephedrine and norpseudoephedrine all inhibited food intake with a two- to five-fold greater potency than that of their respective optical isomers. However, they did not exhibit a comparable stereospecificity to inhibit [3H](+)-amphetamine binding. Further, several compounds including imipramine and propranolol, without known anorectic properties were among the most potent agents to inhibit [3H](+)-amphetamine binding. Thus, although a positive correlation exists between relative binding affinity and potencies to inhibit food intake, the functional interrelationship is uncertain.

Animals↗
PubMed1987

Treatment of post-traumatic osteomyelitis.

Osteomyelitis is an inflammation of the bone, cortex, and/or periosteum. The author discusses the pathophysiology, clinical manifestations, diagnosis, and treatment of post-traumatic osteomyelitis.

Animals↗
PubMed1987

Flavones. 1. Synthesis and antihypertensive activity of (3-phenylflavonoxy)propanolamines without beta-adrenoceptor antagonism.

The synthesis of a series of (3-phenylflavonoxy)propanolamines is described. These compounds were evaluated for potential antihypertensive activity in spontaneously hypertensive rats, as well as for in vivo and in vitro evidence of beta-adrenoceptor antagonism. Some of the compounds of this series exhibited effective antihypertensive properties but did not antagonize beta-adrenergic receptors. These active compounds represent a unique series of effective antihypertensive agents that, despite possessing structural characteristics typical of beta-blockers, does not have beta-adrenergic receptor blocking activity.

Adrenergic beta-Antagonists↗
PubMed1985

Canine diffuse idiopathic skeletal hyperostosis.

The radiographic and necropsy findings in a case of canine diffuse idiopathic skeletal hyperostosis are reported. Radiographically, the disease was characterized by progressive development of para-articular mineral densities along joint surfaces of the appendicular skeleton; progressive osseous fusion of the ilium, pubis, femur, and ischium; and progressive flowing ossification of the dorsal spinous processes of cervical and thoracic vertebrae. The para-articular lesions were considered to develop as a consequence of fibrocartilaginous proliferation followed by endochondral ossification. Progression of the ossification process led to para-articular joint fusion and almost complete ossification of the metaplastic cartilage. A distinguishing feature was the sparing of intra-articular structures.

Animals↗
PubMed1981

Synthesis and angiotensin-converting enzyme inhibitory activity of 3-(Mercaptomethyl)-2-oxo-1-pyrrolidineacetic acids and 3-(Mercaptomethyl)-2-oxo-1-piperidineacetic acids.

A number of gamma- and delta-lactam derivatives were synthesized and their in vitro angiotensin-converting enzyme (ACE) inhibitory activities were compared. The structures of these compounds were designed to include many of the important features of captopril. The synthesis involved the preparation of a variety of novel 3-methylene-2-pyrrolidinones (3-5 and 16) and 3-methylene-2-piperidinones (3a-5a, 10-12, and 17). The key intermediate 3-methylenelactams 3 and 3a were obtained from 3-(hydroxymethyl)lactams 2 and 2a by a direct dehydration with dicyclohexylcarbodiimide using cuprous iodide as a catalyst. Introduction of the sulfhydryl group was accomplished by a Michael addition of these alpha, beta-unsaturated lactams. The compound with the highest in vitro activity was 3-(mercaptomethyl)-2-oxo-1-piperidineacetic acid (7a). The activity of the 7a both in vitro and in vivo (dog) was shown to be less than that of captopril by a factor of about 100.

Angiotensin-Converting Enzyme Inhibitors↗