Avoiding asthma fatalities in family practice.

Epidemics of sudden death in patients with asthma are more likely to result from inadequate realization of severity and insufficient or inappropriate drug therapy than from toxic drug reactions. The authors review management in children and adults involving step-by-step addition of different classes of drugs according to the severity and persistence of the asthma.

Salsolinol in urine following chocolate consumption by social drinkers.

Several studies have shown that there are differential levels of salsolinol excretion between consumers of varying levels of alcohol. The excreted salsolinol may arise during metabolism of alcohol, reflect endogenous biosynthesis of the compound, or result from ingestion of exogenous salsolinol. A previous study identified that salsolinol excretion in urine distinguished light and heavy social drinkers, who had consumed chocolate (containing salsolinol) in combination with a test dose of alcohol. The present study was designed to examine the relationship between social drinking level and the excretion of salsolinol after ingesting dietary salsolinol alone. Participants were 120 volunteers, balanced for gender, social drinking level (abstainers, light, moderate and heavy), and dose of salsolinol. Urine samples were taken on entry, and at 90 minutes and 3 hours after consumption of chocolate. Analysis revealed a dose effect on salsolinol excretion. There were no main or interactive effects of gender or social drinking on salsolinol excretion. The results indicate that the appearance of salsolinol in urine following dietary consumption alone is insufficient to distinguish alcohol consumption levels in social drinkers.

A Review of Fatalities Reported as Associated with NSAID Treatment in Ontario.

This article reviews reports of 61 deaths associated with non-steroidal anti-inflammatory drugs (NSAIDs). These fatalities occurred in Ontario, between February 1, 1981 and January 1, 1986. The average age of these patients at death was 78.6 years, and 59% were female. One or more gastro-intestinal hemorrhages preceded death in 48 patients (79%), and perforation of ulcers with peritonitis and shock were reported in five cases. Other reports indicated that edema and renal failure had occurred in three patients, and bone-marrow depression in another three. The NSAIDs most frequently implicated in these deaths were piroxicam and naproxen, but without data on the numbers of patients taking the various NSAIDs, no conclusions can be drawn about the relative frequencies of severe reactions.

The influences of ethanol and other factors on the excretion of urinary salsolinol in social drinkers.

Salsolinol, a substance that may participate in the development of alcoholism, has been identified in urine and other biological samples from alcoholics. Differentials have been observed between alcoholics and controls. Salsolinol forms when dopamine reacts with acetaldehyde, which may exist in higher concentrations in the blood of alcoholics after alcohol ingestion. Hence, it was postulated that there is a relationship between level of social drinking and the elaboration of salsolinol. Salsolinol is also found in certain food and beverage products. Eighty volunteers, balanced for gender, social drinking level, ethanol dose administered and experimental diet provided urine samples 90 minutes and three hours after ethanol was consumed. Salsolinol levels were analysed in urine using high performance liquid chromatography. A 24 hour carryover effect was observed. Diet, ethanol dose and social drinking level had main and interactive effects on excreted quantities of salsolinol. Gender, situational stress and cigarette smoking had minor if any influence on salsolinol excretion. While there was no evident difference in amounts of salsolinol excreted by light and heavy drinkers in the absence of external sources of salsolinol, heavy social drinkers excreted less salsolinol than did light drinkers after consuming a "salsolinol-enriched" diet, suggesting that they differ in some aspect of absorption, distribution, or metabolism of salsolinol after drinking ethanol. Accordingly, studies that attempt to determine whether salsolinol has any relationship to drinking behaviour in humans should be particularly concerned with salsolinol that occurs in exogenous sources.

Adverse Drug Reaction Reporting Program of the Ontario Medical Association: the first 3 years.

This paper describes the Adverse Drug Reaction Reporting Program developed and operated by the Committee on Drugs and Pharmaco-therapy of the Ontario Medical Association. Analyses were done to demonstrate some of the trends derived from the reports. Some of the clinical observations based on the reports, which are published quarterly and circulated to physicians and to pharmacy, nursing and hospital organizations, are also reviewed.

Reducing the number of anticonvulsant drugs taken by severely retarded epileptic patients.

Recent reports imply potential benefits to patients taking longterm, multiple anticonvulsants if the number of concurrent drugs could be safely reduced. Attempts to reduce the doses of one anticonvulsant were made at monthly intervals in a selected group of 33 closely supervised, ambulatory, chronic epileptic patients with severe mental retardation. Phenytoin dosage was increased in over half the patients as the other drug was decreased. Over 18 months of observation, phenobarbital was completely withdrawn from 19 patients, primidone from four, ethosuximide from one and phensuximide from one. There was no deterioration of behavior or loss of seizure control in these patients. Seizures reappeared after a year in five patients who continued to take phenytoin after phenobarbital or primidone was withdrawn. A second anticonvulsant was given to these patients. This study shows that one anticonvulsant can be successfully withdrawn from many, but not all, chronic epileptic patients with multiple handicaps.

A guide to the pharmacology of placebos.

The placebo effect is capable of relieving pain in a substantial proportion of patients; affective disorders also respond to the administration of inert medication. Changes in objective measures, such as blood pressure and blood glucose levels, demonstrate the action of placebos. The underlying mechanisms are not yet known, but because the nature and strength of the placebo response are governed by the patient's perceptions, both positive and negative results may be obtained. The complexity of human perception has made it extremely difficult to characterize the people who react. In clinical situations the placebo may be underused as a therapeutic agent, while in clinical trials the effect may be inadequately evaluated; the power and nature of the placebo effect truly warrant greater recognition.

A probable role for norepinephrine in feeding after hypothalamic injection of morphine.

When morphine is instilled directly into the ventromedial hypothalamus of rats there is a latent period followed by a prolonged bout of feeding. This enhanced activity may be mediated by the release of norepinephrine; for morphine-induced feeding was depressed by the alpha-adrenergic receptor blocker phentolamine. Several neurotransmitter agonists and antagonists failed to duplicate this action: propranolol, serotonin, methysergide, apomorphine and haloperidol were ineffective in modifying ingestion elicited after morphine. Unlike apomorphine, dopamine augmented morphine's feeding effect. This difference may exist because dopamine acts as a precursor for norepinephrine formation in local ventromedial hypothalamic neurons.

The influence of single daily heroin injections on drinking patterns in the rat.

The licking behavior of male Sprague-Dawley rats individually housed in a controlled environment with a 12-h lighting schedule and food and water available ad libitum was recorded every 30 min. Body weight and 24-h fluid intake were measured daily at 0800 hours, after which subcutaneous injection was given. When saline (0.3 mL/100 g) was injected as a control for 5 days, only a small percentage of total daily licking behavior occurred during the light hours. Heroin hydrochloride (5 or 20 mg/kg) was then injected for the next 10 days. The first injection of heroin caused a cessation of licking behavior followed by a bout of daytime drinking so that the percentage occurring during the light hours increased. This "stimulated" licking occurred progressively earlier as heroin injections were repeated. Total daily fluid intake and rate of weight gain during heroin treatment were not significantly different from those in the control period, although they tended to be less with the higher dose. Withdrawal from this dose led to mild transient hyperirritability (Teiger scores) during the first 36 h and another change of licking behavior. The results suggest that the diurnal licking pattern of rats drinking ad libitum is especially vulnerable to disruption by heroin.

Zinc tannate salts of heroin, LAAM and hydromorphone attenuate opiate withdrawal syndrome.

The effects of long-acting narcotic agonist preparations on the severe withdrawal syndrome following abrupt cessation of daily injections of codeine phosphate were studied in rats. Twelve hours after the last codeine injections, one injection of either a high or low dose of the zinc tannate salt of heroin, levo-alpha-acetylmethadol (LAAM) or hydromorphone in slow-release vehicle (SRV) was administered. Body weight, core temperature and hyperirritability scores (Teiger, 1974) were recorded every 6 h for the next 3 days. With the exception of the group that received the lower dose of heroin zinc tannate, all drug-treated groups lost significantly less weight than the SRV controls. All rats injected with either LAAM or hydromorphone zinc tannate exhibited prolonged marked hyperthermia, but the low, the high dose heroin groups and the SRV groups showed no significant differences in diurnal temperature patterns. Rats treated with the narcotic agonists were generally less irritable, as indicated by lower Teiger scores. These results indicate that a single injection of heroin, LAAM or hydromorphone zinc tannate can ameliorate the characteristic and intense signs of abstinence following withdrawal from codeine.

Dependence in rats after one injection of heroin-, LAAM- or hydromorphone-zinc tannate.

Complex zinc tannate salts of heroin, hydromorphone and l-alpha-acetylmethadol were synthesized and injected in a slow-release vehicle, into rats. One, 3, 7, 10 and 14 days after the drug was administered rats were injected with naloxone hydrochloride (10 mg/kg) and during the following 4 hours body weights, core temperature and behavioral signs such as diarrhea, writhing, teeth chattering and wet dog shakes were recorded. On every naloxone testing day the narcotic-treated groups presented behavioral signs of abstinence, but weight loss and temperature changes were much less consistent. Reduction of core temperature following naloxone administration seems to be an earlier indicator of physical dependence than weight loss. According to the parameters tested a level of physical dependence can persist for at least two weeks after a single injection of these narcotic salts.

Measurement of diurnal core temperatures of rats in operant cages by AM telemetry.

A special AM telemetric system of recording core temperature was developed for rats working in individual, adjacent operant conditioning chambers within a sound-attenuated room. The system monitored core temperatures of each rat continuously and recorded them, in degrees Celsius, every 30 min so that diurnal patterns and fluctuations after saline or drug injections could be determined. Periodic comparisons showed close agreement with temperatures recorded by a rectal probe.