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[Otorhinolaryngological effects of cocaine and/or crack abuse in drug addicts].

PURPOSE: To assess if there are typical otorhinolaryngological findings in patients addicted to cocaine and/or crack. METHODS: Eighteen patients who were addicted to cocaine and/or crack, were studied. Their clinical history was obtained and were submitted to an otorhinolaryngological examination. RESULTS: It was impossible to find out a correlation between the time the patient is addicted to the drug, the amount of drug the patient is used to inhale, the frequency or the last time he used it and the nose and throat symptoms, as well as those factors and the otorhinolaryngological examination. CONCLUSION: Owing to the unspecificity on clinical findings during the otorhinolaryngological examination, it is necessary that the physician suspects the abuse of drugs when he is performing the clinical history; otherwise, he will not reach this important diagnosis.

Adolescent↗

Study of chemical composition of glue "RAZI" used by solvent abusers in Tbilisi.

The analysis of the glue "RAZI" was carried out at the Republican Chromatographic Center of Georgia, with high-efficient liquid chromatographic equipment "Millipore Waters" (USA), by I. Wagner's Method. We were able to determine presumable composition of the glue chemical components. The different substances were evaporated at different times fixed by appropriate peaks on chromatogram. There have been at least five toxic substances identified within the glue composition, which are used as industrial or household chemical goods and as some authors explain, may be used as inhaling psychoactive substances. These substances are: benzol (benzene), toluene (toluol), phenol (carbolic acid), chloroform, and methyl-ketone. The glue is inhaled with a small polyethylene bag. The substances are evaporated during inhalation and join arterial blood through lungs. In several minutes leap forward a situation similar to alcohol intoxication. The evaporated substances characterized by strong toxicity and influence to the organism in different ways. The results of chronic glue abuse is serious, such as lethal aplastic anemia, leukemia, marrow damage, chromosome aberrations, functional disorders of CNS, dystrophic changes in myocardium, cirrhosis, liver atrophy and so on. Abuse of the glue "RAZI" can lead to very serious medical consequences and represents emerging public health problem in Georgia.

Adhesives↗

Effect of a selective dopamine D1 agonist (ABT-431) on smoked cocaine self-administration in humans.

RATIONALE: Data in laboratory animals suggest that D1 receptor agonists may have potential utility for the treatment of cocaine abuse. OBJECTIVE: The effects of ABT-431, a selective agonist at the dopamine D1 receptor, on the reinforcing, cardiovascular and subjective effects of cocaine were investigated in humans. METHOD: Nine experienced cocaine smokers (8M, 1F), participated in nine self-administration sessions while residing on an inpatient research unit: three doses of ABT-431 (0, 2, 4 mg i.v.) were each given in combination with three doses of smoked cocaine (0, 12, 50 mg). ABT-431 was intravenously administered over a 1-h period immediately prior to cocaine self-administration sessions. A six-trial choice procedure (cocaine versus $5 merchandise vouchers) was utilized, with sessions consisting of: (a) one sample trial, where participants received the cocaine dose available that day, and (b) five choice trials, where participants chose between the available cocaine dose and one merchandise voucher. RESULTS: ABT-431 did not affect the number of times participants chose to smoke each dose of cocaine, but produced significant dose-dependent decreases in the subjective effects of cocaine, including ratings of "High," "Stimulated," dose liking, estimates of dose value, "Quality," and "Potency." Furthermore, there was a trend for ABT-431 (4 mg) to decrease cocaine craving. ABT-431 also increased heart rate, while decreasing systolic and diastolic pressure at each dose of cocaine. CONCLUSIONS: These data suggest that D1 agonists may have potential utility for the treatment of cocaine abuse.

Administration, Inhalation↗

Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide in healthy volunteers.

Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide (N(2)O) was studied across five sessions. Twelve volunteers with no history of drug dependence sampled 30% N(2)O and 100% oxygen for 10 min each, then chose nine times, once every 5 min, among N(2)O (e.g. "Agent A"), oxygen (e.g. "Agent B"), or "drug-free air." Choice varied across subjects but was stable within subjects. Quantitative differences in subjective effects occurred within and across subjects. Some subjective effects were correlated with choice and/or differed between subjects who were consistent choosers of N(2)O versus those who were not. However, drug liking and euphoria, two face-valid measures of abuse liability, were unrelated to choice. Thus, the present study found individual differences (i.e. between-subject variability) in subjective and reinforcing effects of N(2)O and, in terms of within-subject variability, suggested that subjective effects fluctuate across sessions to a relatively greater extent than do reinforcing effects. The varying degrees of correlation between N(2)O choice and its subjective effects emphasize the need for obtaining multiple measures when characterizing abuse liability of this drug.

Adult↗

Chirality of methamphetamine and amphetamine from workplace urine samples.

Several positive methamphetamine/amphetamine urine samples were reexamined to determine the chirality of the detected drug or drugs. (S)-N-(Trifluoroacetyl)prolyl derivatives were prepared and analyzed using GC/MS. In one case, pure d-isomers of methamphetamine and amphetamine were detected. In the remainder of the samples involving both drugs, skewed racemates were detected, with the l-isomer of methamphetamine and the d-isomer of amphetamine predominating slightly over their enantiomers. In samples involving amphetamine only, 50:50 mixtures of d- and l-isomers were detected. In no instance was pure i-methamphetamine (from a Vicks inhaler) detected.

Amphetamine↗

Commercial butane abuse: a disturbing case.

The case report discusses a 16-year-old girl with a history of commercial butane gas abuse over a year. As the patient had collected the empty cannisters, it was possible to calculate the quantity abused which is not usually possible due to lack of co-operation and lack of evidence. Other aspects discussed are the mode of inhalation, accessibility, and psychological consequences.

Adolescent↗

Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D1 receptor agonist, A-86929: preclinical pharmacology and clinical data.

Adrogolide (ABT-431; DAS-431) is a chemically stable prodrug that is converted rapidly (<1 min) in plasma to A-86929, a full agonist at dopamine D1 receptors. In in vitro functional assays, A-86929 is over 400 times more selective for dopamine D1 than D2 receptors. In rats with a unilateral loss of striatal dopamine, A-86929 produces contralateral rotations that are inhibited by dopamine D1 but not by dopamine D2 receptor antagonists. Adrogolide improves behavioral disability and locomotor activity scores in MPTP-lesioned marmosets, a model of Parkinson's disease (PD), and shows no tolerance upon repeated dosing for 28 days. In PD patients, intravenous (i.v.) adrogolide has antiparkinson efficacy equivalent to that of L-DOPA with a tendency towards a reduced liability to induce dyskinesia. The adverse events associated with its use were of mild-to-moderate severity and included injection site reaction, asthenia, headache, nausea, vomiting, postural hypotension, vasodilitation, and dizziness. Adrogolide can also attenuate the ability of cocaine to induce cocaine-seeking behavior and does not itself induce cocaine-seeking behavior in a rodent model of cocaine craving and relapse. In human cocaine abusers, i.v. adrogolide reduces cocaine craving and other cocaine-induced subjective effects. The results of animal abuse liability studies indicate that adrogolide is unlikely to have abuse potential in man. Adrogolide has also been reported to reverse haloperidol-induced cognitive deficits in monkeys, suggesting that it may be an effective treatment for the cognitive dysfunction associated with aging and disease. Adrogolide undergoes a high hepatic "first-pass" metabolism in man after oral dosing and, as a result, has a low oral bioavailability (approximately 4%). This limitation may potentially be circumvented by oral inhalation formulations for intrapulmonary delivery that greatly increase the bioavailability of adrogolide. As the first full dopamine D1 receptor agonist to show efficacy in PD patients and to reduce the craving and subjective effects of cocaine in cocaine abusers, adrogolide represents an important tool in understanding the pharmacotherapeutic potential of dopamine D1 receptor agonists.

Androstenes↗

Zygomycosis: an emerging fungal infection.

PURPOSE: The epidemiology, pathogenesis, clinical presentation and diagnosis, and management of zygomycosis are reviewed. SUMMARY: The frequency of zygomycosis has been increasing over the past 10 years; infections have been identified in up to 6.8% of patients at autopsy. The most common route of transmission for Zygomycetes fungi is inhalation of spores from the environment. Patients at highest risk for infections caused by Mucorales fungi include those with profound immunosuppression or diabetes, intravenous drug abusers, premature infants, those receiving deferoxamine, and recipients of bone marrow transplants. Mucormycosis commonly presents as rhinocerebral or pulmonary disease; gastrointestinal presentations also occur. Clinical manifestations of invasive mucormycosis are tissue necrosis and subsequent thrombosis. Common features of pulmonary disease include fever, dyspnea, hemoptysis, and cavitation upon radiologic examination. The mainstays of treatment are control or reversal of the underlying disease or immunosuppression, antifungal therapy, and aggressive surgical debridement. Posaconazole, a new triazole antifungal, has been used successfully in a number of cases that did not respond to amphotericin B. CONCLUSION: Zygomycosis appears to be on the rise in the United States. The standard treatment is a combination of amphotericin B therapy, surgical debridement, and reversal of the underlying disease or immunosuppression.

Amphotericin B↗

Chronic bronchitis: when and how to treat.

Chronic bronchitis, as defined by the magnitude and duration of sputum production, is a diagnosis that encompasses a variety of patients with physiological abnormalities ranging from mild to severe. The first element of therapy is the cessation of smoking, the single most frequent cause of chronic bronchitis. In assisting patients to stop cigarette abuse, nicotine-containing gum has been useful. Therapy directed at airway narrowing continues to be the most widely prescribed. The use of metered dose inhalers containing either beta-adrenergic stimulants or, more recently, ipratropium bromide, an atropine-like agent, continues to be the mainstream of therapy. Theophylline remains a widely prescribed bronchodilator. The use of corticosteroids remains controversial in the stable patient, but appears to be indicated clearly in the patient with an acute exacerbation. The usefulness of antibiotics in acute exacerbations is still uncertain; further studies are needed. Augmentation of survival by the use of chronic supplemental O2 is now certain; more efficient ways to administer O2 are now available. Finally, pulmonary rehabilitation provides a means of improving quality of life in severely disabled patients.

Adrenal Cortex Hormones↗

Sevoflurane use in Veterans Affairs medical centers: utility, safety, and cost-effectiveness.

It has long been realized that the Veterans Affairs (VA) patient has a high incidence of multiorgan system diseases, especially diseases of the pulmonary and cardiovascular systems. The typical Birmingham VA Medical Center patient presenting for surgery is male, with a national mean age of 60 years. More than one half of these patients have a significant history of current or prior tobacco abuse, and many have cardiovascular impairments. When sevoflurane became available, a careful review of the characteristics of the drug, as well as cost comparisons of inhaled agents, was done by our department of anesthesia. Sevoflurane appears to be an ideal inhaled anesthetic for the veteran patient population. If used appropriately, sevoflurane can be administered safely at a cost comparable to desflurane.

Aged↗

Comparison of intravenous and intranasal heroin self-administration by morphine-maintained humans.

Eight heroin-dependent individuals, maintained on divided daily doses of oral morphine, participated in a 2.5-week inpatient study comparing the effects of intranasal (IN) (placebo, 12.5, 25, 50, 100 mg) and intravenous (IV) (placebo, 6.25, 12.5, 25, 50 mg) heroin. Each morning, participants received $20 and a sample dose of heroin, and each afternoon they had the opportunity to self-administer all or part of the morning heroin dose or money amount. Participants responded under a modified progressive-ratio schedule (PR 50, 100, 200, 400, 800, 1200, 1600, 2000, 2400, 2800) during a ten-trial self-administration task. During each trial, participants could respond for 1/10th of the heroin dose or 1/10th of the money amount. The total amount of heroin and/or money chosen during the self-administration task was given at the end of the task. Thus, participants received drug and/or money twice each day: once during the morning sample session and once during the afternoon self-administration session. Participants received IV solution and IN powder simultaneously during each dosing; only one route contained active drug. Heroin produced dose-related increases in break point values by both routes of administration. Although IV heroin was approximately four-fold more potent than IN heroin, the maximal break point values for both routes were not significantly different. A similar difference in potency between the IV and IN routes was found for several ratings of subjective effects (e.g., "I feel a good drug effect," "I feel high"), but maximal subjective ratings were lower for IN compared to IV heroin. These results suggest that the reinforcing efficacy of heroin is similar by the two routes of administration, but that IN heroin is less potent than IV heroin. The results also underscore the importance of evaluating drug self-administration in the evaluation of the abuse liability of drugs.

Administration, Inhalation↗

Electro-encephalographic disturbances due to chronic toxin abuse in young people, with special reference to glue-sniffing.

A study was carried out in order to document any abnormalities in the electro-encephalogram (EEG) that might appear in young adolescents who have deliberately inhaled the range of volatile substances loosely referred to as 'glue'. The EEGs of a group of 'street children' being assisted in a Johannesburg shelter were examined. The records were analysed for any clinical abnormalities and also subjected to spectral analysis in order to examine the overall characteristics of frequency, power and spatial distribution. The EEGs clearly revealed that, although at the time of the examination the subjects were ostensibly abstinent, both clinical and normative evidence of continuing brain disturbance was present. It was concluded that glue sniffing is likely to have long term electrocerebral sequelae.

Adolescent↗

Acute changes in cranial blood flow after cocaine hydrochloride.

Cerebral blood flow (CBF) was measured with the 133Xenon inhalation technique and forehead skin flow with laser Doppler, before and twice after 0.3 milligram/kilogram of cocaine hydrochloride and a placebo given intravenously to six cocaine abusers, during two visits, separated by a minimum of one week. After cocaine, subjects showed significant increases in intoxication and tension. Systolic blood pressure and pulse rate also increased significantly after the drug but not after the placebo. CBF, with and without correction for end-tidal CO2, showed increases in left and right hemisphere after cocaine. The CBF increase was maximal in frontal, central and parietal regions. CBF changes correlated only with changes in a rated level of intoxication. Forehead skin flow did not change after cocaine or placebo. In habitual cocaine abusers, 0.3 mg/kg of cocaine, given intravenously produced increased CBF and no changes in forehead skin flow.

Adult↗

Lethal child neglect.

The jurisdiction of the Hannover Institute of Legal Medicine recently experienced an unusually high incidence of lethal child neglect, with three cases in a 5-month period in 1999. Case 1: A girl received an inappropriate and inadequate diet of tea and oatmeal. The child was never breastfed, nor did it ever receive any other formula. The parents report the infant to have been healthy until she suddenly began projectile vomiting at the age of 13 weeks. For the next 3 days the infant was not able to maintain an adequate intake. The mother reports finding the child dead in its bed on the morning of the fourth day. Attempts by medical personnel to revive the child were unsuccessful. Case 2: A mother began spoon-feeding the infant puree on the fourth day of life, which according to the manufacturer's specifications is suitable for children between 4 and 8 months of age. At the age of 5 weeks, the infant was reported to have vomited half the just previously ingested meal, after which she took a nap. Some time later the parents observed the infant to be quite pale, however, assumed this was a result of sleep. When the mother finally did pick her up, the child was lifeless, and the parents brought her to the hospital. Medical personnel could however, only declare the infant dead, documenting a rectal temperature of 30 degrees C. Case 3: A 3.5-year-old girl died after her mother left the locked apartment and did not return for several weeks. The body of the child was found lying dressed on the floor in a state of advanced decay and mummification. Common findings in all three cases include lack of prenatal care, home birth without the help of a midwife, low socioeconomic status or maternal alcohol abuse, body weights below the 3rd percentile, extreme dehydration, fatty hepatic degeneration, thymic atrophy and signs of aspiration.

Alcoholism↗

Solvent encephalopathy.

Nineteen children aged 8-14 years were admitted over a six-year period with an acute encephalopathy due to toluene intoxication. Seven had a history of euphoria and hallucinations. The remainder presented with coma (4), ataxia (3), convulsions (3), and behaviour disturbance with diplopia (2), A history of glue sniffing was elicited in 14, but in the remainder toluene assay confirmed the diagnosis. Thirteen children recovered completely; five still had psychological impairment and personality change on discharge from hospital but were lost to follow-up, and one has a persistent cerebellar ataxia one year after the acute episode, despite absence of further exposure. Toluene inhalation is an important cause of encephalopathy in children and may lead to permanent neurological damage. Diagnosis is most important if further damage due to continued abuse is to be prevented, and toluene assay is a valuable aid to diagnosis.

Adhesives↗

Cerebral hemodynamic and metabolic effects of chronic alcoholism.

The nervous system is particularly susceptible to the harmful effects of alcohol. These include Wernicke-Korsakoff syndrome, which is related to thiamine deficiency secondary to chronic alcohol abuse. Other neurotoxic effects of alcohol with cognitive impairments include delirium tremens, alcoholic seizures or "rum fits," and alcoholic neuropathies. It has become recognized in recent years that alcohol and its metabolites directly damage the nervous system even in the absence of nutritional deficiencies. Cerebral blood flow (CBF) measurements provide a noninvasive indirect monitor of cerebral metabolic activity. It has been shown conclusively that CBF measured by the 133Xe inhalation method is decreased in chronic alcoholism, correlating well with the amount of alcohol consumed. With abstinence, CBF returns toward normal levels provided the neurotoxic effects of chronic alcoholism are of recent onset. Clinical and pathological studies show significant loss of brain volume with ventricular dilatation after alcohol abuse even among young "social" drinkers. This toxic effect of alcohol is accompanied by varying degrees of cognitive impairments ranging from slight memory loss to frank dementia. Both the decrease in brain volume and the cognitive impairments, which occur with or without nutritional deficiency, are to a large extent reversible with abstinence and nutritional supplementation. Alcohol appears to accelerate age-related declines in CBF while nutritional deficiencies enhance the neurotoxic effects of alcohol. Measurements of local CBF (LCBF) and partition coefficients (L lambda) in deep cerebral structures, including the hypothalamus, thalamus, forebrain nuclei, and limbic system, can be achieved utilizing three-dimensional methods after inhalation of stable xenon as a contrast medium combined with serial computed tomographic imaging of the brain. Among chronic alcoholics, there are significant and diffuse reductions in cortical and subcortical gray matter CBF that are especially remarkable in hypothalamus and substantia innominata, which includes the nucleus basalis of Meynert, a major source of cholinergic input to neocortex and hippocampus. Reductions in LCBF are measurable in cognitively impaired patients with and without Wernicke-Korsakoff syndrome. Reductions of CBF include white matter and are more severe in patients with Wernicke-Korsakoff syndrome. Both types of encephalopathy improve with treatment, but recovery is usually more rapid and complete if nutritional deficiency is absent. Alcohol also appears to be a risk factor for stroke, possibly by depleting neuronal reserves and unfavorably influencing cardiovascular risks.

Alcoholism↗

Effectiveness of a universal drug abuse prevention approach for youth at high risk for substance use initiation.

BACKGROUND: Universal school-based prevention programs for alcohol, tobacco, and other drug use are typically designed for all students within a particular school setting. However, it is unclear whether such broad-based programs are effective for youth at high risk for substance use initiation. METHOD: The effectiveness of a universal drug abuse preventive intervention was examined among youth from 29 inner-city middle schools participating in a randomized, controlled prevention trial. A subsample of youth (21% of full sample) was identified as being at high risk for substance use initiation based on exposure to substance-using peers and poor academic performance in school. The prevention program taught drug refusal skills, antidrug norms, personal self-management skills, and general social skills. RESULTS: Findings indicated that youth at high risk who received the program (n = 426) reported less smoking, drinking, inhalant use, and polydrug use at the one-year follow-up assessment compared to youth at high risk in the control condition that did not receive the intervention (n = 332). Results indicate that a universal drug abuse prevention program is effective for minority, economically disadvantaged, inner-city youth who are at higher than average risk for substance use initiation. CONCLUSIONS: Findings suggest that universal prevention programs can be effective for a range of youth along a continuum of risk.

Adolescent↗