Biomedical subjects

D R Jasinski

Publications and source records attributed to D R Jasinski.

At least 19 recordsLinked to original sources

PubMed2006

Development and preliminary experience with an ease of extractability rating system for prescription opioids.

One important factor in the abuse potential of an opioid product is the ease with which active drug can be extracted. There are currently no standards for testing or reporting extractability. This article describes the development of an Extractability Rating System for use by the pharmaceutical industry and regulators. Despite several limitations, this effort serves as a call for standardized testing and reporting so that products can be accurately rated, and should help establish goals for drug developers who wish to develop "abuse-resistant" opioid products.

Algorithms↗

PubMed2003

Highly active antiretroviral therapy outcomes in a primary care clinic.

This paper compares antiretroviral outcomes of patients at a primary care clinic with those previously reported at HIV specialty clinics and examines risk factors for treatment failure. A retrospective medical record review was undertaken at an academic primary care practice in Baltimore, Maryland. One hundred and twenty-three patients were included who had not previously received HAART and who were started on a regimen that included a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor and at least one other new antiretroviral medication. HIV RNA levels, CD4 lymphocyte counts, missed appointment rate, HAART regimen, demographic variables, and their association with the achievement of a viral RNA of 500 or less at 7-14 months were analyzed. Forty-seven per cent of the patients had an HIV RNA level of 500 or less at 7-14 months after initiation of HAART. Factors associated with treatment failure included missed appointment rate, injection drug use and previous exposure to antiretroviral medication. On multivariate analysis, only missed appointment rate and lower baseline CD4 lymphocyte count were independently associated with treatment failure. The antiretroviral outcomes of patients started on HAART by experienced health care providers in this primary care practice were comparable to those reported in specialty clinics. As with previous reports, most patients did not maintain viral suppression. Missed appointment rate was the most important risk factor for treatment failure.

Adult↗

PubMed2001

Buprenorphine treatment of pregnant opioid--dependent women: maternal and neonatal outcomes.

This open-label prospective study examined maternal and neonatal safety and efficacy outcome measures during and following prenatal buprenorphine exposure. Three opioid-dependent pregnant women received 8 or 12 mg sublingual buprenorphine tablets daily for 15-16 weeks prior to delivery. Results showed that buprenorphine in combination with comprehensive prenatal care was safe and effective in these women. Prenatal exposure to buprenorphine resulted in normal birth outcomes, a mean of 4.33 days (minimum possible=4) hospitalization, and a 'relatively mild' neonatal abstinence syndrome comprised primarily of tremors (disturbed), hyperactive moro and shortened sleep after feeding. The infants required no pharmacological treatment. Onset of neonatal abstinence signs occurred within the first 12 h after birth, peaked by 72 h and returned to below pre-12 h levels by 120 h. It is concluded that buprenorphine has potential utility for the treatment of pregnant opioid-dependent women.

Adult↗

PubMed2001

One-, three-, and six-month outcomes after brief inpatient opioid detoxification.

The purpose of this study was to investigate short-term outcomes of a 3-day inpatient medical detoxification. Heroin abusers (n = 116; 66% male, 77% African-American, X = 38 years old), completed the Addiction Severity Index during detoxification, and at 1, 3, and 6 months after detoxification; 94.5% of the postdetoxification interviews were completed. During the 30 days before detoxification, mean days of self-reported use for heroin was 28, for cocaine 19, and for alcohol 14; a mean of $1,975 was spent on drugs. Across the postdetoxification interviews, mean days of reported heroin use ranged from 11 to 14; 21-30% of patients reported no heroin use, whereas 25-36% reported almost daily use. Reported use of cocaine and alcohol showed similar reductions from pre- to postdetoxification. Reports of heroin and cocaine abstinence were generally verified through urine tests. Other psychosocial factors improved as well from pre- to postdetoxification (e.g., employment increased and needle use decreased). During the 6-month evaluation, at least 41% reported engaging in formal inpatient or outpatient treatment; another 25-33% reported attending self-help groups. Engaging in formal treatment (at least 7 days duration) was associated with significantly better outcome. Nevertheless, pre- to postdetoxification changes were significant and robust for the entire study sample. These findings demonstrate that brief inpatient detoxification is followed by reduced drug use over several months and is accompanied by substantial treatment-seeking behavior. Thus brief detoxification may serve as an effective harm-reduction intervention.

Adult↗

PubMed2000

Abuse potential of morphine/dextromethorphan combinations.

The potentiation of morphine analgesia by dextromethorphan raises the issue of whether dextromethorphan also potentiates those actions of morphine that lead to abuse. Clinical pharmacology experiments indicated that dextromethorphan does not potentiate the euphorigenic and miotic actions of morphine. Morphine suppresses the dysphoric action of dextromethorphan. A second set of experiments indicated that dextromethorphan does not alter the response to naloxone-precipitated withdrawal. In a third set of experiments, dextromethorphan did not alter the morphine-induced depression in the slope of the increase in minute volume in response to breathing increased CO2. In contrast to potentiation of analgesia, dextromethorphan does not enhance the euphorigenic, physical dependence, and respiratory depressant actions of morphine. These findings indicate that dextromethorphan does not enhance the abuse potential of morphine and that the potentiation of analgesia appeared to be selective.

Analgesics, Opioid↗

PubMed2000

An evaluation of the abuse potential of modafinil using methylphenidate as a reference.

Modafinil is a unique wake-promoting agent. Preclinical studies indicate a mechanism of action which is distinct from that of amphetamine or methylphenidate. To compare the pharmacodynamic profiles of modafinil, methylphenidate, and placebo in humans, a double-blind Latin square crossover study was conducted in 24 male volunteers with a history of polysubstance abuse that included the stimulant cocaine. Each subject was given single oral doses of methylphenidate (45 mg or 90 mg), modafinil (200 mg, 400 mg or 800 mg) and placebo. Measures of subjective, behavioural, and physiological responses were evaluated at fixed intervals during 72 h after each dosing occasion. Subjects discriminated both modafinil and methylphenidate from placebo. Subjects liked the effects of both drugs. However, modafinil differed from methylphenidate in its lack of a significant response on the Amphetamine Scale of the Addiction Research Center Inventory. The profile of physiological effects for modafinil differed from methylphenidate in that it showed greater inhibition of observed and reported sleep, less facilitation of orthostatic tachycardia and less reduction of caloric intake. These findings are consistent with preclinical pharmacological data suggesting that modafinil is not an amphetamine-like agent.

Adult↗

PubMed1997

Cocaine effects on digital blood flow and diffusing capacity for carbon monoxide among chronic cocaine users.

PURPOSE: To determine the acute effects of intravenous (i.v.) cocaine on primarily digital skin blood flow and diffusion capacity for carbon monoxide (CO), and secondarily on subjective and cardiovascular measures. PATIENTS AND METHODS: A double-blind, Latin-square, placebo-controlled, dose-response study was conducted in an inpatient general clinical research center and clinical pharmacology unit of a university teaching hospital. Twelve adult males with histories of illicit drug use including i.v. cocaine received 0, 25, and 50 mg of i.v. cocaine given as 1-minute infusions, on 3 consecutive test days. Digital cutaneous blood flow was determined via laser doppler flowmetry and skin temperature. Diffusing capacity for carbon monoxide (DCO) was measured with standard techniques. Subjective responses were measured by oral report of a numerical ranking of strength of drug effect. Heart rate and blood pressure responses were measured by electronic sphygmomanometer. RESULTS: A maximal decrease in skin blood flow occurred at 2 to 3 minutes after infusion, and was not distinguished among drug conditions. Blood flow returned to baseline more rapidly after placebo than after cocaine: 7 minutes (placebo), 35 minutes (25 mg cocaine), 50 minutes (50 mg cocaine). Skin temperature decreased by 1.25 degrees C after placebo and by 2.75 and 3.25 degrees C after 25 and 50 mg of cocaine, respectively. DCO changed by -1.02 (mean) +/- 0.25 (standard deviation), 0.16 +/- 1.22, and 0.21 +/- 1.63 ml/min/mm Hg following placebo, 25, and 50 mg of cocaine, respectively. Typical subjective, chronotropic, and pressor responses to cocaine were demonstrated, and these occurred in close temporal relationship to digital blood flow and skin temperature responses. CONCLUSIONS: The digital cutaneous circulation is highly sensitive to vasoconstrictor effects of cocaine. Pulmonary blood volume tends to be preserved after i.v. cocaine. Subjective effects and cardiovascular responses occur in concert with peripheral blood flow changes. The peripheral vasoconstrictor effects have implications for cocaine users with concurrent vasospastic or vasculopathic disorders.

Adult↗

PubMed1997

Tolerance and dependence to opiates.

In the 19th century, investigators recognized that addiction to opiates involves tolerance and dependence. In the United States, the National Academy of Sciences and the Public Health Service initiated systematic investigations into opiate addiction in 1929. Tolerance and dependence to morphine, the prototype for opiate drugs, were the emphasis of human studies for the next fifty years. This presentation highlights salient features of tolerance and dependence learned in these studies and relates these findings to clinical use in treating pain.

Analgesics, Opioid↗

PubMed1997

Abuse liability of testosterone.

Anabolic-androgenic steroids (AAS) are used by athletes to enhance performance and physique. Case reports and observations propose that AAS have mood elevating properties and that chronic use leads to addiction. The aim of this study was to evaluate the subjective and physiological effects of single doses of testosterone. In a double-blind fashion, according to a balanced Latin square, 10 paid adult male volunteers received doses of i.m. testosterone (50, 100 and 200 mg), morphine (10 mg) or placebo for five consecutive days. Subjective and physiological responses were measured during each drug condition. Testosterone produced no significant changes in self-reported or observed measures, unlike morphine, which produced statistically significant changes in several measures, including 'feel the drug', 'like the drug' and 'feel high'. There were no adverse effects of administering high doses of testosterone. In conclusion, single doses of testosterone are devoid of the usual pharmacologic effects that are associated with abuse.

Adult↗

PubMed1997

l-alpha-Acetylmethadol, l-alpha-acetyl-N-normethadol and l-alpha-acetyl-N,N-dinormethadol: comparisons with morphine and methadone in suppression of the opioid withdrawal syndrome in the dog.

l-alpha-Acetyl-N-normethadol (nor-LAAM) and l-alpha-acetyl-N, N-dinormethadol (dinor-LAAM) are active metabolites of the opiate l-alpha-acetylmethadol (LAAM), and they contribute to the prolonged actions of the parent compound. Single doses of nor-LAAM, dinor-LAAM, LAAM, methadone and morphine were given intravenously to the chronic spinal dog to determine acute, single-dose effects and their ability to suppress withdrawal in morphine-dependent dogs. These opioids produced dose-dependent antinociception, decreases in body temperature and pupillary constriction. For these measures, dinor-LAAM was 1.5 to 3 times and nor-LAAM 6 to 12 times as potent as LAAM. Five hours after the acute administration of LAAM or either of the metabolites, a 1-mg/kg dose of naltrexone given intravenously produced withdrawal, indicating the presence of acute physical dependence. In dogs physically dependent on a daily dose of 125 mg of morphine, nor-LAAM was 9 times as potent as either LAAM or dinor-LAAM in suppressing spontaneous withdrawal 40 hr after the last dose of morphine. The efficacies of LAAM and its demethylated metabolites in the dog for producing acute opiate effects were comparable with those of morphine and methadone. There was a trend, however, for LAAM to suppress the expression of abstinence more fully than either metabolite. The usefulness of LAAM as a treatment for opiate addiction is likely due in part to the equivalent efficacies and higher potencies of its nor and dinor metabolites.

Analgesics, Opioid↗

PubMed1996

Ritanserin in the treatment of alcohol dependence--a multi-center clinical trial. Ritanserin Study Group.

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT2 receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects' QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence.

Adult↗

PubMed1994

Psychopharmacology and abuse potential of transnasal butorphanol.

The effects of butorphanol administered by a nasal spray (transnasal, TN) and by intramuscular (IM) injection were compared to determine the onset of action, relative potency, profile of effects, and relative abuse liability of TN butorphanol. TN/IM placebo and TN and IM butorphanol (1, 2, and 4 mg) were tested in seven male opioid abusers not currently physically dependent on opioids using a double-blind, double-dummy, Latin square design. Measures of subjective, behavioral and physiological response were assessed. The onset and duration of action of butorphanol administered by the IM and TN routes were similar at low doses, but onset of TN butorphanol 4 mg was slower than that of 4 mg IM. IM butorphanol produced miosis, some opiate-like behavioral and subjective effects, and increasing dysphoric sedation and perceptual effects with increasing dose. TN and IM butorphanol 1 and 2 mg produced effects that were qualitatively and quantitatively similar; however, TN butorphanol 4 mg was less potent than 4 mg IM. Pharmacodynamic evidence suggests that the abuse potential of TN butorphanol is not different from that of IM butorphanol.

Administration, Intranasal↗

PubMed1994

Buprenorphine reduces cerebral glucose metabolism in polydrug abusers.

Buprenorphine is a mixed opioid agonist-antagonist, which acts as a partial mu agonist and a kappa antagonist. The present study evaluated the acute effects of buprenorphine on cerebral glucose metabolism (CMRglc) in six human substance abusers using a double-blind, placebo-controlled, counterbalanced, crossover design. Each subject participated in two positron emission tomographic (PET) studies, 1 week apart, following the injection of buprenorphine (1 mg, intramuscularly) and placebo. Buprenorphine significantly reduced CMRglc and the regional cerebral metabolic rate for glucose (rCMRglc) by up to 32% in all but three of 22 bilateral and in 4 midline regions (p < .05). No region showed an increase in rCMRglc. Buprenorphine also produced miosis, respiratory depression, and subjective ratings of euphoria and sedation in comparison to placebo (p < .05). These observations extend previous findings of reduced CMRglc following acute treatment with morphine and other nonopioid euphorigenic drugs.

Adult↗

PubMed1993

Prevalence of hepatitis C in a chemically dependent population.

BACKGROUND: Drug abuse is the major risk factor for hepatitis C in the United States. The objective of this study was to determine the prevalence of hepatitis C virus (HCV), to identify risk factors for HCV, and to correlate HCV and liver function in patients presenting for inpatient detoxification of substances of abuse. METHODS: A total of 687 patients were tested for the presence of antibody to HCV (anti-HCV). Histories related to drug use, sexually transmitted diseases, blood transfusion, and human immunodeficiency virus were obtained, as were serum tests for human immunodeficiency virus, syphilis, hepatitis B, aminotransferases, total bilirubin, and alkaline phosphatase. RESULTS: The overall prevalence of anti-HCV was 63%: 68% in men vs 54% in women (P < .001), with no difference by race. Remarkably, 86% of injecting drug users tested positive for anti-HCV. Identified risk factors for anti-HCV were injecting drug use (P < .001), human immunodeficiency virus infection (P = .003), exposure to hepatitis B virus (P < .001), and a positive rapid plasma reagin test (P = .04). Previous transfusion and history of previous infection with gonorrhea or syphilis did not correlate with the presence of anti-HCV. Patients positive for anti-HCV had significant elevations in aspartate aminotransferase and alanine aminotransferase levels when compared with patients negative for anti-HCV: 50.8 vs 36.7 U/L (P = .002) and 56.0 vs 36.9 U/L (P < .001), respectively. CONCLUSION: Injecting drug users have an extremely high prevalence of anti-HCV. This is the first demonstration, to our knowledge, that the presence of anti-HCV in drug users is associated with significantly increased levels of serum aminotransferases.

Adult↗

PubMed1993

Single-dose pharmacodynamics of diazepam and pentobarbital in substance abusers.

The likelihood that a given drug will be misused is related to its ability to alter mood, feeling, thinking, and perception in a manner that is liked by substance abusers. The subjective and behavioral effects of diazepam (10, 20, and 40 mg), pentobarbital (120 and 240 mg as a positive control), and placebo (negative control), were evaluated in 12 subjects with histories of substance abuse by use of a double-blind, Latin square crossover study design. Drug administration was separated by a minimum of 3 days. Pharmacodynamic measures included subjective (euphoria, subject liking, sedation, and symptoms) and behavioral (signs and observed liking) responses. The time course and profile of subjective and behavioral responses were similar for diazepam and pentobarbital. Valid relative potency estimates for the pharmacodynamic measures indicated that diazepam is approximately 10 times as potent as pentobarbital. The study indicates that the reinforcing effects of diazepam are similar to pentobarbital in substance abusers.

Adult↗

PubMed1992

Psychoactivity and abuse potential of sumatriptan.

Sumatriptan is a 5-HT1D agonist of therapeutic use in migraine and cluster headaches. To determine the profile of psychoactivity and abuse potential, a double-blind Latin-square crossover study was conducted in 12 male subjects with histories of substance abuse. The effects of subcutaneous placebo, sumatriptan (8 and 16 mg), and morphine (10 and 20 mg) were assessed on measures of subjective, behavioral, and physiologic responses including signs, symptoms, Addiction Research Center Inventory scales, onset of drug effects and miosis. Sumatriptan was psychoactive, was discriminated from placebo, produced a dose-related decrease on euphoria scores, elevated scores on measures of apathetic sedation and disliking, and lacked identification as a prototypic drug of abuse. There were no clinically significant effects on heart rate, pupil size, or blood pressure. In contrast, morphine (the positive control) produced expected dose-response relationships on measures of reinforcing and physiologic effects. The study suggests that sumatriptan has a low abuse potential.

Adult↗

PubMed1991

Abuse liability studies of opioid agonist-antagonists in humans.

Prediction of the abuse liability of a drug before it reaches the market is complicated by the fact that there are many factors that influence the actual abuse of a drug. Laboratory methods used in humans to assess the abuse liability of the opioids are reviewed and illustrative studies of morphine and the agonist-antagonist opioids, pentazocine, butorphanol, nalbuphine and buprenorphine, are presented. Three assessment methods, subjective effect measurement, self-administration and drug discrimination, provide information relevant to measuring reinforcing efficacy, a major determinant of the degree to which a drug is sought and self-administered by abusers. Physical dependence capacity, which can contribute to sustained drug use, is evaluated in direct addiction and substitution/suppression studies. Withdrawal precipitation studies measure antagonist activity which might limit abuse. The results of testing the agonist-antagonist opioids are generally consistent across these various methods and consistent with historical experience with these drugs, suggesting that these methods are useful in predicting abuse liability of novel opioids.

Arousal↗

PubMed1991

Abuse potential and pharmacological comparison of tramadol and morphine.

The purpose of the study was to assess the abuse potential of the opioid analgesic tramadol. Tramadol (75, 150 and 300 mg), morphine (15 and 30 mg) and placebo were tested intramuscularly in volunteer non-dependent opiate abusers. Subjective, behavioral and miotic changes were assessed prior to dosing and intermittently for 12 h after drug administration. Morphine produced typical subjective effects, opiate identifications and miosis. Tramadol 75 and 150 mg were not different from placebo. Although tramadol 300 mg was identified as an opiate, it produced no other morphine-like effects. These findings suggest that tramadol has a low abuse potential by the parenteral route.

Adult↗