Search

This study determined whether the development of delayed ischemic sequelae due to cocaine use--after the return of arterial blood pressure (BP) and heart rate to near-baseline values--may be attributable to regional vasoconstriction which persists beyond the acute systemic hemodynamic response. Five cocaine-using volunteers received intravenous infusions of saline placebo and cocaine 0.50 mg/kg several days apart in a double-blinded cross-over design. The intensity and duration of the cocaine-induced decrease in peripheral blood flow (as documented by laser Doppler flowmetry of the finger) were compared to the increases in BP (obtained with a Dinamap) and heart rate using paired t-test and repeated-measures analysis of variance. A significant increase in BP and a significant decrease in finger flow were noted by the first time point (5 min). Within 15 min, cocaine induced a 36% +/- 5% increase in BP and a 73% +/- 18% decline in finger flow (P < 0.05 for difference between percent change in BP and percent change in flow). Dinamap(systolic) and Dinamap(diastolic) returned to within 15% of baseline within 30 min, while finger flow remained more than 50% below baseline for the remainder of the 60-min study period (P < 0.05). Changes in heart rate paralleled those in BP. Except for isolated cases of documented coronary vasoconstriction in patients presenting with complications after cocaine use, this study is the first to document the persistence of cocaine-induced vasoconstriction of a sensitive vascular bed beyond the hypertensive response. It thus helps to explain the development of ischemic injury after cocaine use despite a stable rate-pressure product.

The PsyConsult Adventure Simulation program presents a case simulation of consultation in a general hospital. Exploring this computerized case helps trainees prepare for the complexities of consultation that they will face on the hospital wards. The simulation provides a distinctive approach, modeling the process of an actual consultation and allowing trainees to explore on their own initiative. It presents general techniques of psychiatric consultation as well as specifics of diagnosis and treatment. The program demonstrates the feasibility of using case simulation with a personal computer system as a supplement to bedside teaching of consultation psychiatry.

Intravenous challenges with placebo and cocaine doses ranging from 0.125 to 0.5 mg/kg were administered to five subjects using a within subjects design during placebo and active desipramine (DMI) maintenance at a fixed dose of 150 mg daily for at least 10 days. The "high" reported after cocaine infusion was not altered by DMI, but "desire for cocaine" after a single dose was attenuated. Together with the results of clinical trials of DMI for cocaine abuse, these laboratory results suggest that DMI may reduce cocaine craving both during and between cocaine binges. Physiologically, baseline heart rate was higher on DMI, but the incremental heart rate response to cocaine was attenuated.

The Electric Resident System is an experimental arrangement of software for the personal computer. It is designed to help residents in the educational cycle of patient interview, literature review, write-up, attending review, and patient treatment. The authors emphasize the system's immediate utility and ease of operation, using a graphical interface. Within a year of operation this system was in daily use on a consultation service with minimal formal instruction. Usage data show a positive correlation between the number of patients seen per month and the number of computer-assisted MEDLINE literature searches performed. Residents' comments indicate not only acceptance of the system but increased interest in computer applications in medical care. The Electric Resident System is meant to be the first step toward a computer-aided residency.

The same plasma drug concentration may induce different effects depending on whether the concentration is rising or falling. We described a new method of modeling kinetics of drug effects that can handle such "dissociation" phenomena, that does not depend on compartmental theory, and that allows quantitative comparisons between experiments. As applied to cocaine, it is shown that the resulting models are independent of drug dose or route of administration and give good predictions of the time course of response.

The application of reversed-phase high-performance liquid chromatography to the measurement of benzoylecgonine and cocaine in urine is described. Following a simple extraction and clean-up procedure, chromatography is performed using a column containing an octadecylsilica coated packing, elution with 17% acetonitrile in pH 2.7 phosphate buffer and ultraviolet detection at 200 or 235 nm. The detection limit is ca.0.1 microgram of drug per ml urine, and using the ethyl ester of benzoylecgonine as an internal standard, benzoylecgonine and cocaine are quantified with coefficients of variation of 7.0 and 2.8%, respectively. The procedure has been applied to urines from subjects receiving intranasal cocaine, and compared to the enzyme multiplied immunoassay technique. The chromatography procedure also permits the separation of norcocaine and benzoylnorecgonine.

We compared the psychological effects of three doses of intranasal cocaine hydrochloride (.2, .75, and 1.5 mg/kg) with cocaine plasma concentrations in four volunteers. Intranasal lidocaine hydrochloride (.2 mg/kg) was used as a topically active placebo. Peak "high" ratings were related to both dose and peak plasma concentrations. At a given plasma concentration, "high" ratings were greater when plasma levels were increasing than when they were decreasing. This indicates that acute tolerance by tachphylaxis occurred after single doses. The cocaine "high" was a pleasant feeling but was without distinctive sensations. The dramatic effects of intranasal cocaine on the street may be related to larger or repeated doses as well as the setting.

Eighteen patients undergoing coronary artery surgery were observed to examine whether cocaine in a clinically used dose exerts sympathomimetic effects during general anesthesia. Eleven patients received cocaine hydrochloride as a 10% solution (1.5 mg/kg) applied topically to the nasal mucosa before nasotracheal intubation. Seven patients had a similar procedure without cocaine. Blood pressure, pulse rate, cardiac index, left ventricular stroke work index, total peripheral vascular resistance, and pulmonary vascular resistance were measured. There were no important differences in cardiovascular function between patient groups. The rapid rise in plasma cocaine concentration, reaching 331 ng/mL at 30 minutes and 320 ng/mL at 45 minutes, bore no apparent relationship to any changes in cardiovascular function. We conclude that under conditions of this study, administration of topical cocaine does not exert any clinically significant sympathomimetic effect and appears to be well tolerated in anesthetized patients with coronary artery disease.

Although it is widely held that the magnetic fields encountered during magnetic resonance imaging (MRI) and other procedures have no discernible effect on biological systems, we find that at early times of incubation, the amount of binding of the neurotoxin, alpha-bungarotoxin, to nicotinic acetylcholine receptor is significantly reduced in a constant 2.0-T magnetic field. This finding suggests that steady magnetic fields can directly affect the functional activity of biologically important macromolecules, in this particular case a neurotransmitter receptor.

We conducted a double-blind, random assignment, six-week comparison of desipramine hydrochloride (n = 24), lithium carbonate (n = 24), and placebo (n = 24) treatments for cocaine dependence. Subjects were 72 outpatient cocaine abusers who met DSM-III-R dependence criteria for cocaine but not for other substance abuse. Subjects in each treatment group were similar in history of cocaine and other substance abuse, cocaine craving, sociodemographics, and other psychiatric comorbidity. Desipramine, compared with both other treatments, substantially decreased cocaine use. Lithium treatment outcome did not differ from that of placebo. Desipramine-treated subjects attained contiguous periods of abstinence substantially more frequently than subjects receiving lithium or placebo. Fifty-nine percent of the desipramine-treated subjects were abstinent for at least three to four consecutive weeks during the six-week study period, compared with 17% for placebo and 25% for lithium. Cocaine craving reductions were also substantially greater in the desipramine-treated subjects. Establishment of initial abstinence is the first stage in recovery from cocaine dependence. Our findings indicate that desipramine is an effective general treatment, for this first treatment stage, in actively cocaine-dependent outpatients.

Cocaine was stable (93.6 +/- 5.0 (SD)% remaining after 120 minutes) when incubated in plasma from six patients with histories of succinylcholine sensitivity and low dibucaine numbers (phenotype A), but was rapidly hydrolyzed (40.6 +/- 6.6% remaining after 120 minutes) when incubated in plasma obtained from normal subjects (phenotype U). Intermediate decay (69.4 +/- 9.0% remaining) occurred in three heterozygous offspring of the succinylcholine-sensitive patients. Since serum cholinesterase has recently been implicated in the human metabolism of cocaine, patients who are homozygous for the atypical enzyme may be at greater risk for a toxic reaction when administered this drug. We recommend caution in using cocaine for topical anesthesia in patients with histories of succinylcholine sensitivity or low dibucaine numbers.

Actions of morphine include analgesia, sleep, euphoria, and depression of respiration. Transmitter or modulator substances in the brain that have actions similar to morphine may control these functions in man. This hypothesis proposes that enkephalin is a controlling neurotransmitter and its binding to opiate receptors determines mood state as well as influencing respiratory and sleep patterns. Lithium may act through modification of the opiate receptor affinity for an endogenous morphine-like substance. The theory predicts blocking action of naloxone in mania and in most drug-induced euphorias. It implies a new chemical pathophysiological basis for the phenomenology of mental illness.

Plasma cocaine levels were determined in 7 subjects after intranasal and oral cocaine. Intranasal doses of 0.19, 0.38, 0.75, 1.5, and 2.0 mg/kg were given as a 10% aqueous solution; 0.38 mg/kg was given as crystalline cocaine HCl. Oral cocaine was administered in doses of 2.0 and 3.0 mg/kg. Intranasal cocaine kinetics were described by a 1-compartment open model with 2 consecutive first-order input steps and first-order elimination. Oral cocaine disposition was described by a 1-compartment open model with a lag time followed by a single first-order input phase and first-order elimination. The mean elimination half-life (t 1/2) for cocaine by the intranasal route to 7 subjects was 75 +/- 5 min (mean +/- SE). The mean t 1/2 after oral administration to 4 subjects was 48 +/- 3 min. The relative bioavailability [as determined by the area under the concentration-time curve (AUC)] for the 2.0-mg/kg dose by the intranasal and oral routes was not different. There was a linear increase in AUC with increasing intranasal dose.

Cigarettes containing cocaine paste were administered to experiences volunteer smokers in Peru, and plasma concentrations of cocaine were measured. Cocaine concentrations as high as 462 ng/ml were obtained after only three minutes of smoking cocaine paste. Subjects titrated their rate of consumption so as to achieve remarkably constant plasma concentrations during the smoking period. Areas under curve (AUC), adjusted for dose, were approximately 70% that obtained with oral or intranasal administration of cocaine to different subjects in previous experiments.

Endorphins and exogenous opiates inhibit the activity of the noradrenergic nucleus locus coeruleus (LC). This discovery of endorphin transmitters and their interaction with the LC has supported our studies which have suggested that the majority of the signs and symptoms of opiate withdrawal are mimicked by electrical or chemical activation of the LC. We hypothesize that this endorphin-LC connection is critical to opiate action and the withdrawal syndrome. This hypothesis suggests that chronic opiate administration inhibits LC activity and that opiate abstinence after addiction results in a release from inhibition with resultant LC hyperactivity. This hypothesis is supported by recent data suggesting that clonidine as a drug which inhibits the LC and LC-mediated noradrenergic activation, is an efficacious non-opiate treatment for opiate withdrawal. This hypothesis can be tested in man by evaluating drugs which inhibit the LC and LC-mediated behaviors for anti-withdrawal efficacy.