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Biomedical subjects

M K Romach

Publications and source records attributed to M K Romach.

27 records · Page 2Linked to original sources
PubMed1992

Characteristics of long-term alprazolam users in the community.

The widespread use of benzodiazepines remains a source of concern to the medical profession and the general public, especially as newer compounds come on the market. Our goal was to characterize long-term alprazolam users in the community and to determine whether such use represented abuse or behavioural dependence. We conducted three community surveys to learn about the natural history of long-term alprazolam use. Current long-term alprazolam users (those using the drug for 3 months or longer) were recruited on three separate occasions 1 year apart by identical newspaper advertisements in the metropolitan Toronto area. All respondents were mailed a questionnaire with a stamped, addressed return envelope. Our data from 312 respondents show that: (1) the majority of patients have a substantial history of prior medication use for symptom control (65%), (2) dose escalation is not a characteristic of long-term use, (3) patients change their initial pattern of regular use to one of symptom control only when required, (4) most physicians do not discuss discontinuation of the drug with their patients, (5) patients frequently try to stop their drug use (with a median of 2 attempts) and often report symptoms upon discontinuation, and (6) patients perceive a need for medication use and indicate that alprazolam is effective (75%). We conclude that some patients persistently use alprazolam but that this use does not represent abuse or behavioral dependence.

Alprazolam↗
PubMed1992

Comparative drug effects and abuse liability of lorazepam, buspirone, and secobarbital in nondependent subjects.

The pharmacologic effects of lorazepam (2 mg), buspirone (20 mg, 10 mg), secobarbital (100 mg), and placebo were compared in 15 male, experienced, intermittent nontherapeutic drug users. All drugs produced a "drug effect," however, buspirone 20 mg was significantly less liked than were lorazepam, secobarbital, or buspirone 10 mg (p less than .05) but not placebo. Lorazepam was liked better than were other drugs only at 1 hour and only compared with buspirone 20 and placebo. Compared with other drugs, lorazepam drug effects were greater and resulted in more prolonged impairment of a motor tracking task, standing steadiness, and memory. Buspirone 20 mg significantly impaired memory at 1 hour compared with placebo. Subjects were more likely to identify buspirone as unfamiliar. Because buspirone 20 mg was less liked than were other drugs, dose escalation as part of drug abuse is not likely to occur. Lorazepam also was not particularly liked and was not different from placebo on most subjective abuse-relevant measures.

Adult↗
PubMed1991

Pharmacotherapy of alcohol and drug problems.

Substantial progress has been made in the pharmacotherapy of withdrawal syndromes and organic complications of alcohol and drug abuse. Diazepam loading (alcohol withdrawal), phenobarbital loading (barbituate withdrawal) and diazepam tapering (benzodiazepine discontinuation) have considerably simplified treatment of withdrawal syndromes and have enhanced efficacy. Propylthiouracil shows considerable promise in the out-patient treatment of alcoholic liver disease. New medications, particularly those modifying serotonergic function, have efficacy in decreasing alcohol consumption and show considerable therapeutic potential. Human pharmacology and pharmacotherapy should be a central part of training programmes in the field in order that further advances can be made.

Journal Article↗
PubMed1991

Management of the alcohol withdrawal syndrome.

People who suffer acute alcohol withdrawal should be admitted to a hospital if they have a concurrent medical or surgical complication or severe symptoms. Careful assessment, supportive care, and pharmacotherapy, especially loading with a long half-life benzodiazepine such as diazepam, are the essential components of treatment. Patients with milder withdrawal can be managed effectively and safely on an out-patient basis or with nonmedical treatment. The need for pharmacotherapy should be determined on an individual basis. The management of alcohol withdrawal includes offering and initiating long-term treatment to reduce alcohol consumption.

Alcohol Withdrawal Delirium↗
PubMed1991

Opportunities for treatment of psychoactive substance use disorders with serotonergic medications.

The authors review both the preclinical and the clinical evidence for a role of serotonin (5-HT) systems in the regulation of drug-taking behavior. Animal studies show that pharmacologic treatments that enhance 5-HT function, notably selective reuptake inhibitors, reduce the self-administration of a variety of substances of abuse, including ethanol and cocaine. These treatments also tend to suppress consummatory behavior in general. In contrast to the broad spectrum of suppression following 5-HT enhancement, selective antagonists at the 5-HT3 receptor subtype have been reported to reduce ethanol but not cocaine or food intake. Although essentially limited to alcohol abusers, clinical studies seem to support the preclinical findings that a number of 5-HT reuptake inhibitors decrease interest in and intake of alcohol in mild-moderate ethanol-dependent individuals. Furthermore, other serotonergic drugs may show utility in the treatment of alcohol abuse. Another way in which serotonergic medications can be used in treating substance abuse is by the treatment of comorbid psychoactive illness for which such drugs are already known to be effective, e.g., depression and anxiety disorders.

Alcoholism↗
PubMed1991

Long-term alprazolam use: abuse, dependence or treatment?

Concern about persistent benzodiazepine use should be informed by data about reasons for such use. Consecutive long term alprazolam users (n = 25) admitted to an advertised outpatient program for discontinuation were characterized with respect to alprazolam use patterns and lifetime and current Axis I and II disorders. Patient characteristics were: females 50 percent; mean age, 46 +/- 12 yrs; prior medication use--benzodiazepines, 47 percent, antidepressants, 23 percent; median duration of use 104 +/- 96 wks; median daily dose, 0.5 mg; continued effectiveness of alprazolam 50 percent. Over the duration of use patients shifted their initial pattern of use from as prescribed to a self-controlled "as required" basis (p less than .05). Interviews using the Structured Clinical Interview for DSM-III-R (SCID) yielded diagnoses of DSM-III-R alprazolam dependence in all patients plus at least one additional psychiatric diagnosis in 65 percent (Axis I 65%; Axis II 39%). Most persistent alprazolam use does not represent abuse or addiction as usually understood. These data are most consistent with the interpretation that alprazolam is the most recent benzodiazepine used by patients to help control clinically important psychopathology and that most users make efforts to control or stop use.

Adult↗
PubMed1981

Methadone binding to orosomucoid (alpha 1-acid glycoprotein): determinant of free fraction in plasma.

The distribution of basic drugs in blood differs qualitatively from that of acidic drugs. The binding of racemic, d-methadone, and l-methadone to human plasma and isolated protein fractions was studied by equilibrium dialysis at 37 degrees. In plasma samples from 29 healthy subjects free fraction of dl-methadone was (mean% +/- SD) 10.62 +/- 1.43. There were significant variations among subjects (p less than 0.001). The free fraction of the d-isomer was 9.24 +/- 1.61% and of the l-isomer, 12.44 +/- 1.53%. Plasma albumin concentration and degree of binding do not correlate, but in normal hypoalbuminemic subjects the free fraction of dl-methadone correlates negatively with the concentration of alpha 1-acid glycoprotein (alpha 1-AGP), an acute-phase reactant protein. Percentage dl-methadone bound to purified human serum albumin (HSA) (4.1 mg/dl) was 36.60% (mean +/- SD). Isolated alpha 1-AGP bound dl-methadone more avidly. As the alpha 1-AGP increased from 0.05 to 2.0 gm/l, free fraction fell from 92.40% to 8.80%. Addition of alpha 1-AGP (0.05 to 2.0 gm/l) to a physiologic concentration of purified HSA or to whole plasma progressively increased methadone binding. In eight monozygotic twin pairs, within-pair differences in binding of dl-methadone were less than in eight dizygotic twin pairs. Less than 20% of naloxone, codeine, morphine, heroin, pentazocine, and diphenoxylate bound to alpha 1-AGP. Elevations of alpha 1-AGP that occur in a variety of diseases may alter the kinetic and pharmacologic activity of methadone.

Adult↗
PubMed1979

Inter- and intrasubject variation in diazepam free fraction.

The extent of intersubject variation in diazepam free fraction was measured in fasting plasma of 74 unrelated subjects. Free fraction differences between subjects were significant and ranged from 0.97% to 1.99%. Diazepam free fraction in 29 males was normally distributed about a mean of 1.25% (range, 1.05% to 1.47%), but the distribution in females was skewed to higher free fractions and 40% had values above the highest in males. Albumin concentration (r = -0.27, p less than 0.002) and age (r = 0.44, p less than 0.001) only accounted for a small part of the variation. Within-pair variances were not greater in 11 dizygotic than in 18 monozygotic twin pairs, indicating a greater contribution of environmental than of genetic factors to diazepam binding. The prehemodialysis free fractions of diazepam in 9 uremic patients ranged from 3.44% to 6.69%, and decreased (p less than 0.005) in 7 after 6 hr of hemodialysis. In 10 subjects determination of intrasubject variation in diazepam free fraction between 14-hr fasting and 2-hr postprandial plasma samples indicated that because subjects differ in their pattern of change in free fraction (p less than 0.001), the overall decrease in mean free fraction did not achieve statistical significance (p = 0.10). The mean relative percent change in free fraction within subjects after feeding was 15.2%.

Adult↗