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Biomedical subjects

U Busto

Publications and source records attributed to U Busto.

At least 37 records · Page 2Linked to original sources
PubMed1984

Diazepam tapering in detoxification for high-dose benzodiazepine abuse.

The clinical characteristics and management of patients who abuse high doses of benzodiazepines are not well described. In a prospective open study, 23 subjects who abused high doses of benzodiazepines were admitted for detoxification. Urine or blood test results confirmed benzodiazepine use in all but one subject and multiple drug use in eight (35%). Median benzodiazepine dose was 150 mg (range 40 to 500 mg) of diazepam equivalent. Initial plasma concentrations (diazepam: median = 1245 ng/ml; desmethyldiazepam: median = 2961 ng/ml) were 400% to 800% higher than usual therapeutic concentrations. For detoxification, subjects were given a loading dose of diazepam equal to approximately 40% their reported daily consumption. This was followed with daily tapering of diazepam by 10%. This regimen resulted in a slow and gradual decline in drug concentrations. Withdrawal symptoms were assessed daily. Sixteen subjects completed detoxification in the hospital without complications. One subject became paranoid and confused on day 7 of withdrawal. This was attributed to a too-low initial loading dose and too-rapid tapering, which resulted in rapid drug elimination. Gradual reduction of diazepam dose appears to be an effective and safe approach for detoxifying abusers of high doses of benzodiazepines.

Adult↗
PubMed1983

An intensive drug monitoring study suggesting possible clinical irrelevance of impaired drug disposition in liver disease.

1 Liver disease can alter the disposition and clinical effects of drugs. However, even though altered drug disposition occurs, there is no clinical evidence relating it to an increased susceptibility to adverse drug reactions (ADRs). 2 An intensive prospective drug monitoring study of 2,582 hospitalized patients was conducted. The adverse drug reactions probability scale (APS) was used to assess ADRs. Only non-mild, definite or probable ADRs (APS greater than or equal to 5) were included. Severity of liver dysfunction was assessed by a composite clinical and laboratory index (CCLI). 3 The frequency of ADRs was higher in 402 patients with cirrhosis (27.4%) than in 661 with renal dysfunction (22.8%) and in 249 with other parenchymatous liver diseases (13.7%) or in 1,270 patients with neither liver diseases nor renal dysfunction (10.9%) (chi 2 3 = 85.53, P less than 0.001). The frequency of ADRs in cirrhotics was highly correlated with the severity of the liver dysfunction measured by CCLI (r = 0.82, P less than 0.001). 4 Drugs predominantly eliminated by liver metabolism were not among those most commonly inducing ADRs or those causing severe reactions in cirrhotics. Thus, frusemide caused the most common and the most severe ADRs, whereas reactions induced by sedatives were uncommon. Drug-induced hepatic encephalopathy was more common in cirrhotics receiving diuretics (13.3%) than in those receiving sedatives (1.8%) (chi 2 y.c. = 5.29, P less than 0.025). Patients with alcoholic liver disease had more drug-induced hepatic encephalopathy (7.7%) than those with non-alcoholic liver disease (1.2%) (chi 2 y.c. = 11.86, P less than 0.001). 5 These results indicate that susceptibility to ADRs is increased only in severe cirrhosis and that the most common and severe ADRs seem more likely related to enhanced pharmacodynamic action than to impaired drug disposition.

Brain Diseases↗
PubMed1982

Difficulties in assessing adverse drug reactions in clinical trials.

1. The discovery of an adverse drug reaction (ADR) depends on: the relative frequencies of the drug-related and non-drug events; the mechanism of drug-induced toxicity; the number of patients exposed to the drug; and the methods used for detecting toxicity. Clinical trials are usually short-term studies conducted in a few hundred patients before marketing a drug. Therefore only the most common acute, dose-related ADRs are usually detected in the pre-marketing phase. 2. The detection and assessment of ADRs in clinical trials is still inadequate. Unstructured (open-ended questionnaires) and structured procedures (checklists) are the methods most commonly used. Since both methods have limitations, the discovery of ADRs in pre-marketing trials (phases I to III) should also rely on the complementary information provided by other methods: physiological and physical examinations, and pertinent laboratory tests. A more definite assessment of individual cases of ADRs should include the use of the adverse drug reaction probability scale (APS) or similar procedures. 3. Because the knowledge on the clinical toxicity of a drug will always be incomplete at the time of marketing, further investigation of the frequency and determinants of ADRs must be pursued in the post-marketing phase.

Arousal↗
PubMed1982

Comparison of two recently published algorithms for assessing the probability of adverse drug reactions.

1 A simple valid and reliable method for estimating the probability of adverse drug reactions (adverse drug reactions probability scale, APS) has been recently described (Naranjo et al., 1981a). 2 The results using APS were compared to those obtained with another more detailed algorithm (adverse reactions scoring system, ASS) described by Kramer et al. (1979). 3 Sixty-three randomly selected adverse drug reactions (ADRs) were rated by two observers, using APS and ASS one year apart. The cases were ordered in a random sequence. Between-raters reliability using APS (R(est) = 0.96 and ASS (R(est) = 0.86), was very high. 4 ADR scores obtained with both methods were highly correlated (r = 0.82, P less than 0.001). However, time spent using ASS was significantly longer (paired t-test, t = 1.70, P less than 0.05). 5 These results suggest that while ASS is somewhat more complex than APS both are equally reliable and will give very similar conclusions regarding the probability of ADRs. Such algorithms must be used if the clinical assessment of ADRs is to become acceptably reliable.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1982

Benzodiazepines and ethanol: assessment of the effects and consequences of psychotropic drug interactions.

Ethanol and benzodiazepines interact both pharmacokinetically and pharmacodynamically. However, the importance of these effects has been exaggerated. Kinetically, acute doses of ethanol impair the disposition of benzodiazepines that are metabolized by demethylation or hydroxylation, but not those that undergo glucuronide conjugation. On the other hand, chronic ethanol administration increases the clearance of benzodiazepines that are demethylated or hydroxylated. The pharmacodynamics of the ethanol-benzodiazepine combination is less clear. The sedative and psychomotor effects of the combination appear to be enhanced, compared to the effects of the drugs given alone. However, it is difficult to assess the proportion of the observed effects that is due to benzodiazepines, as ethanol appears to be the dominant partner in this combination. Studies attempting to control for this imbalance have been so hampered by methodological problems that no firm conclusions can be drawn. Moreover, a number of benzodiazepines have not been studied in combination with ethanol. We suggest, however, that the ethanol-benzodiazepine interaction is probably less important than those involving ethanol and other psychotropic drugs, such as cannabinoids, neuroleptics, stimulants, and antidepressants.

Alcoholism↗
PubMed1981

Acute and chronic drug abuse emergencies in Metropolitan Toronto.

From 3,548 drug overdose or abuse cases presenting at 21 Metropolitan Toronto hospitals' Emergency departments, data concerning demographic and medical characteristics, investigative and management procedures, drug analysis services, and disposition of patients were collected. Of the 3,548 cases, 2,723 (77%) were acute overdose and 816 (23%) were drug abuse. Drug overdose was more common than drug abuse for both sexes, but was more characteristic of females. The drugs most frequently alleged ingested were benzodiazepines (34%), ethanol (32%), salicylates (16%), and barbiturates (14%). The frequency with which particular classes of drugs are alleged in overdose corresponds closely to the frequency of prescribing these drugs in Ontario.

Adult↗
PubMed1980

Benzodiazepine-associated emergencies in Toronto.

In a prospective study of drug overdose patients admitted to emergency rooms of 21 Toronto hospitals, 39% said they had taken a benzodiazepine. Benzodiazepines were used more frequently by females than males and by suburban than core hospital patients. Patients who overdosed on benzodiazepines were admitted to the hospital less frequently and arrived with less disturbance of consciousness than those who had used other drugs. Patterns of prescription in Ontario and patterns of overdose in Metropolitan Toronto were highly correlated.

Adult↗
PubMed1980

Sex-related variations in the frequency and characteristics of adverse drug reactions.

Sex-related variations in the clinical effects of drugs may be observed. In an intensive prospective drug surveillance study of 1920 patients hospitalized at the Department of Medicine of the J. J. Aguirre Hospital in Santiago, Chile, the frequency of adverse drug reactions (ADR) was significantly higher in females than in males (p < 0.0005). Women presented more commonly gastrointestinal and cutaneous allergic reactions. In males electrolyte disturbances were more frequent. Drugs inducing ADR were very similar in both sexes. Eighty-three per cent of ADR in males and 93% in females were dose-related effects. Hospitalization was lengthened by a significantly higher proportion of ADR in men than in women. Other ADR's risk fators such as age, number of drugs administered and duration of hospitalization did not account for the differences observed. In males with ADR there was a higher proportion of patients with cirrhosis and renal insufficiency. These findings suggest that sex is a determinant of the frequency and characteristics of ADR.

Adolescent↗
PubMed1979

Furosemide-induced adverse reactions in cirrhosis of the liver.

Furosemide is frequently used for ascites and causes adverse reactions (AR). In an intensive prospective drug monitoring study of 1,920 patients, 172 (8.9%) had cirrhosis of the liver and received furosemide. Mean age was 53 years, and 66.3% were male; and 87% had alcoholic cirrhosis. Eighty-eight (51.2%) had 221 events that by consensus of the monitoring team and attending physicians were either definitely of probably related to furosemide. No AR was fatal but 24% of patients had severe reactions. Almost all reactions were dose-related (96%). The most common were electrolyte disturbances (23.3% of patients) and volume depletion (14%). Furosemide-induced coma occurred in 20 (11.6%) patients and was more frequent in patients with prior hepatic encephalopathy (p less than 0.0005). Higher total doses (p less than 0.001), hyerbilirubinemia (p less than 0.05), prolonged prothrombin time (p less than 0.02), and longer hospital stay (p less than 0.001) were associated with higher frequencies of AR to furosemide. The frequency of hypokalemia did not decrease when potassium chloride or potassium-sparing diuretics were added to furosemide therapy. Frequdncy of AR did not correlate with age, sex, renal impairment, serum albumin, transaminase, or alkaline phosphatase.

Administration, Oral↗