Gender differences in early life risk factors for substance use/abuse: a study of an African-American sample.

Gender differences in risk and protective factors for substance use/abuse in early adulthood were studied. Comprehensive systematic data on African-American males (N = 318) and females (N = 322), from birth to 7 years of age, were available from the National Collaborative Perinatal Study. These subjects were retrieved for assessment at average age 24. There are more differences between males and females than there are similarities in regard to the early childhood variables that predict substance use in early adulthood. However, high activity and intensity of response during infancy (measured at 8 months of age) was found to predict later substance use for both males and females. This type of behavior is considered by use to be a trait of temperament and to suggest the possibility of a genetic predisposition. More risk factors were found for female than for males. The risk factors for females were primarily of two types: 1) Related to experiences with mother and with the family environment; and 2) Poor levels of intellectual functioning and academic performance, and abnormal mental status.

Hispanics and illicit drug use: a review of recent findings.

This manuscript presents a comprehensive assessment of the current illegal drug use problem among Hispanics by analyzing the recent findings on this subject. Information is provided on the prevalence of illegal drug use by drug type, age, and specific Hispanic group, and on the accessibility and availability of drug treatment facilities to Hispanics. The consequences of illegal drug use upon the well-being of Hispanics are discussed. Recommendations on additional research are made.

Cutaneous adverse reactions associated with calcium channel blockers.

The calcium channel blockers, nifedipine, verapamil, and diltiazem, are widely used for the treatment of cardiovascular disease. In spite of their widespread use, little data about the frequency and spectrum of cutaneous reactions associated with these agents have been published. Based on reports provided to the FDA's Division of Epidemiology and Drug Surveillance, and the American Academy of Dermatology's Adverse Drug Reaction Reporting System, it appears that the frequency of adverse cutaneous events associated with these drugs is low, but that occasionally severe reactions are associated with the use of these drugs. Among the more serious reactions associated with the calcium channel blockers are toxic epidermal necrolysis with diltiazem, Stevens-Johnson syndrome and erythema multiforme, which have been associated with all three drugs in this class, and exfoliative dermatitis, which has also been reported with all three agents. Most serious reactions associated with these agents occur within two weeks of initiating drug therapy. These findings suggest that calcium channel blockers are occasional causes of a wide spectrum of cutaneous reactions and should be considered as possible causative factors in patients who develop adverse cutaneous reactions while using these drugs.

Toxic interaction between narcotic analgesics and inhibitors of catechol-O-methyltransferase.

A lethal synergism between morphine and tropolone, an inhibitor of catechol-O-methyltransferase, was previously noted in adult male Holtzman rats. The present research demonstrates that this phenomenon generalizes across factors of sex, age, strain (Sprague--Dawley, Wistar) and species (Swiss albino mice). Acute toxicity was also significantly increased (1.5--1.9 times) in the case of codeine, methadone, meperidine and levorphanol, but to a lesser extent than for morphine (4.0 times) in the S-D strain. Another COMT inhibitor, 3,5-dihydroxy-4-methoxybenzoic acid, interacted with morphine in S-D rats to an equal degree as did tropolone. Post-treatment with 1 mg/kg of naloxone in rats or naltrexone in mice reduced the high lethality associated with morphine plus tropolone. There was a pronounced lowering of whole brain norepinephrine (NE) level after morphine plus tropolone in Wistar rats with doses of each component that alone caused no change in NE. Brain dopamine (DA) was elevated by tropolone and by its combination with morphine. Each drug alone caused slight lowering of brain serotonin. Enhancement by tropolone of the toxicity of (+)-amphetamine in mice and rats was of similar magnitude as for morphine. The possible role of brain NE and/or DA in the sensitivity to acute toxic effects of opioids in rodents is suggested by these data, as well as a parallel in this regard with amphetamine-type stimulants.

Studies on the characterization and inhibition of rat brain phenylethanolamine N-methyltransferase.

The existence of phenylethanolamine N-methyltransferase (PNMT) activity in the rat brain and spinal cord was confirmed using both substrate specificity and selective inhibitors of the adrenal enzyme as biochemical tools. The enzyme was not generally localized throughout the central nervous system but was found primarily in the brain stem and spinal cord with lesser amounts occurring in the midbrain. No significant PNMT activity was found in markedly inhibited both in vitro and in vivo by low concentrations (doses) of SK&F 64139, a potent inhibitor of the adrenal enzyme.

Noradrenergic role in the self-administration of morphine or amphetamine.

The role of brain noradrenergic neurons in mediating the reinforcing properties of small intravenous doses of morphine and d-amphetamine was investigated by pretreatment of rats with the norepinephrine-depleting agents diethyldithiocarbamate and U-14,624, inhibitors of dopamine-beta-hydroxylase (DBH). Such treatment prevented the reacquisition of a self-administration response (bar-press) for morphine (32 mug/kg/injection) or d-amphetamine (15 mug/kg/injection) made available on a CRF schedule. Pretreatment with a DBH inhibitor also prevented the development of a secondary (conditioned) reinforcer based on primary reinforcement assosiated with either drug. Observations indicating that the orienting reflex was intact are taken as evidence that depressant effects of the DBH inhibitors were not severe enough to disrupt the associative process. Therefore, any effect on learning does not seem sufficient to explain the present results. Thus, it is inferred that the mechanisms mediating reinforcement for both morphine and amphetamine were disrupted by the inhibition of central noradrenergic functions.