1
UI - 2
AU - Bowles TM
AU - Sommi RW
AU - Amiri M
AD - Department of Pharmacy Practice, School of Pharmacy, University of Missouri-Kansas City, Western Missouri Mental Health Center, USA
TI - Successful management of prolonged gamma-hydroxybutyrate and alcohol withdrawal
AB - A 27-year-old man was admitted with tremulousness, diaphoresis, tachypnea (28 breaths/min), full-body rigidity, irritability, paranoia, and auditory and visual hallucinations 2 days after stopping long-term gamma-hydroxybutyrate (GHB) and 8 hours after stopping alcohol intake. He received intravenous fluids and tapering dosages of lorazepam to control agitation and rigidity, and recovered with no significant sequelae after 8 days. Abrupt cessation of GHB after high-dosage abuse can precipitate a clinically significant withdrawal syndrome. Lorazepam should be considered for treatment of GHB withdrawal. Concomitant alcohol abuse may mask early GHB withdrawal symptoms and exacerbate withdrawal
UR - PM:11213862
SO - Pharmacotherapy 2001 Feb ;21(2):254-257
2
UI - 1
AU - Gulliford MC
AU - Ukoumunne OC
AD - Department of Public Health Sciences, GKT School of Medicine, King's College, London, UK. martin.gulliford@kcl.ac.uk
TI - Determinants of glycated haemoglobin in the general population: associations with diet, alcohol and cigarette smoking
AB - OBJECTIVE: We evaluated cigarette smoking, alcohol intake and consumption of different foods as determinants of glycated haemoglobin in a general population sample. DESIGN: Cross-sectional survey. SETTING: England. SUBJECTS: Representative sample of 15 809 adults aged 16 y and older. Data analysed for 9772 non-diabetic, white European subjects. MAIN OUTCOME MEASURES: Glycated haemoglobin (GHb). Analyses were adjusted for age, sex, body mass index (BMI), waist-hip circumference ratio, activity level, and educational attainment. RESULTS: After adjusting for confounding, GHb was 0.277% (95% confidence interval 0.218 to 0.336) higher in current smokers of 20 or more per day, compared with non-smokers. GHb was 0.189% (0.101 to 0.277) lower in those drinking 42 or more units of alcohol per week than in non-drinkers. GHb was not associated with frequency of consumption of pulses, fruit, vegetables and salads, cakes, bread or confectionery. GHb was higher in subjects who took sugar in tea (0.051%, 0.015 to 0.087%) or in coffee (0.069%, 0.034 to 0.105%). GHb was higher in subjects who used solid fat for cooking (0.082%, 0.022 to 0.142%), or who drank whole rather than reduced-fat milk (0.088%, 0.036 to 0.140%), or used butter or hard margarine rather than low-fat spreads (0.075%, 0.029 to 0.121%). CONCLUSIONS: In the general population, higher GHb may be associated with cigarette smoking, or frequent consumption of fat-containing foods. Consumption of alcohol may be associated with lower GHb. SPONSORSHIP: None
UR - PM:11464236
SO - Eur J Clin Nutr 2001 Jul ;55(7):615-623
3
UI - 3
AU - Beghe F
AU - Carpanini MT
AD - Clinical and Pharmacological Research Unit "Piertomaso Tessitore" and Pharmaco-surveillance Department, Laboratorio Farmaceutico C.T., Via Dante Alighieri 71, 18038, Sanremo, Italy
TI - Safety and tolerability of gamma-hydroxybutyric acid in the treatment of alcohol-dependent patients
AB - Gamma-hydroxybutyric acid (GHB) has been in clinical use in Italy since 1991 for treatment of alcohol dependence. Results of phase III and phase IV studies have shown that the drug is effective and well tolerated in the treatment of alcohol withdrawal syndrome and in reducing alcohol consumption and alcohol craving. Pharmacosurveillance indicates that abuse of gamma-hydroxybutyric acid is a limited phenomenon in clinical settings when the drug is dispensed under strict medical surveillance and entrusted to a referring familiar member of the patient
SO - Alcohol 2000 Apr ;20(3):223-225
4
UI - 9
AU - Poldrugo F
AU - Addolorato G
AD - Department of Psychiatry, University of Trieste, Italy
TI - The role of gamma-hydroxybutyric acid in the treatment of
alcoholism: from animal to clinical studies
AB - Since its discovery nearly 40 years ago,
gamma-hydroxybutyric acid (GHB) has attracted several waves of
scientific interest due to new developments in the knowledge of
its mechanisms of action and ideas for its potential use in
clinical practice. Its effects have been claimed to treat
different psychiatric conditions, but over time its use has
become limited to a few specific situations (e.g. sedating
patients in non-painful surgical procedures and narcolepsy). New
interest in the drug derives from its potential use in the
treatment of alcoholism. Recent studies demonstrated a marked
effect of the substance in suppressing ethanol (ETOH) withdrawal
symptoms and in reducing craving for alcohol, compared to other
available drugs. However, GHB has to be given under very careful
supervision because of its side-effects, including the risk of
abuse and dependence and possible interference with the
metabolic pathways of endogenous GHB and ETOH. This short review
discusses these and related issues and we hope that it will
stimulate further interest in GHB
UR - PM:0010075397
SO - Alcohol Alcohol 1999 Jan ;34(1):15-24
5
UI - 15
AU - Rosen MI
AU - Pearsall HR
AU - Woods SW
AU - Kosten TR
AD - Yale University School of Medicine, Department of
Psychiatry, New Haven, CT, USA
TI - Effects of gamma-hydroxybutyric acid (GHB) in
opioid-dependent patients
AB - Gamma-hydroxybutyric acid (GHB) is a GABA metabolite used
clinically for sleep induction. The abuse liability of GHB is
controversial. As part of a study of the effect of GHB
pretreatment on naloxone- precipitated opiate withdrawal, eight
opioid-stabilized subjects received a balanced, randomized,
double-blind sequence of oral placebo, GHB 15 mg/kg and 30
mg/kg. GHB had no consistent physiological effects. After GHB
and prior to naloxone, subjects rated "sluggish,"
"spaced," "carefree," and
"good-mood" higher after GHB 30 mg/kg than after
placebo. Subjects identified the 30 mg/kg dose as most similar
to placebo (n = 3), benzodiazepine (n = 2), opiate (n = 2), and
alcohol (n = 1)
UR - PM:0009258859
SO - J Subst Abuse Treat 1997 Mar ;14(2):149-154
6
UI - 19
AU - Rosen MI
AU - Pearsall HR
AU - Woods SW
AU - Kosten TR
AD - Yale University, Department of Psychiatry, New Haven,
Connecticut 06519, USA
TI - The effect of gamma-hydroxybutyric acid on
naloxone-precipitated opiate withdrawal
AB - Because gamma-hydroxybutyric acid (GHB), a GABA metabolite,
attenuated spontaneous opiate withdrawal in a prior study, we
studied GHB's effect on naloxone-precipitated opiate withdrawal.
Eight opiate-dependent inpatients were stabilized on the opioid
levorphanol, 18 mg daily. After an initial acclimatization
challenge, subjects underwent three double-blind challenges on
consecutive days. Pretreatment in a balanced randomization was
with either placebo, GHB, 15 mg/kg, or GHB, 30 mg/kg, followed
an hour later by intravenous naloxone, 0.4 mg/70 kg. GHB
produced no significant attenuation of multiple withdrawal
measures except for hot-cold feelings. GHB pretreatment slightly
accelerated respiration prior to naloxone. Differences with
prior studies may be due to (1) timing of GHB administration
(giving postwithdrawal in prior studies), (2) direct reversal of
GHB's anti-withdrawal effects by naloxone, or (3) differences
between naloxone-precipitated and spontaneous opiate withdrawal
UR - PM:0008866702
SO - Neuropsychopharmacology 1996 Mar ;14(3):187-193
7
UI - 29
AU - Ferrara SD
AU - Tedeschi L
AU - Frison G
AU - Castagna F
AU - Gallimberti L
AU - Giorgetti R
AU - Gessa GL
AU - Palatini P
AD - Centre of Behavioural and Forensic Toxicology, University
of Padova, Italy
TI - Therapeutic gamma-hydroxybutyric acid monitoring in plasma
and urine by gas chromatography-mass spectrometry
AB - A gas chromatographic-mass spectrometric (GC-MS) method for
the determination of therapeutic levels of gamma-hydroxybutyric
acid (GHB) in plasma and urine samples is described. GHB is
converted to its lactonic form gamma-butyrolactone (GBL) which
is extracted from biological fluids after the addition of the
internal standard delta- valerolactone. Final GC-MS analysis is
obtained under electron impact selected ion monitoring (SIM)
conditions. Mean relative recoveries of GHB from plasma and
urine are 75.5% (RSD% = 2.2) and 76.4% (RSD% = 2.4),
respectively. The assay is linear over a plasma GHB range of 2-
200 micrograms ml-1 (r = 0.999) and a urine GHB range of 2-150
micrograms ml-1 (r = 0.998). Intra- and inter-assay relative
standard deviations (n = 5) determined at 10 and 100 micrograms
ml-1 are below 5%. The method is simple, specific and accurate,
and may be applied for analytical purposes related to
pharmacokinetic studies and therapeutic drug monitoring
UR - PM:0008399519
SO - J Pharm Biomed Anal 1993 Jun ;11(6):483-487
8
UI - 28
AU - Gallimberti L
AU - Cibin M
AU - Pagnin P
AU - Sabbion R
AU - Pani PP
AU - Pirastu R
AU - Ferrara SD
AU - Gessa GL
AD - Addiction Treatment Service, Padova, Italy
TI - Gamma-hydroxybutyric acid for treatment of opiate
withdrawal syndrome
AB - In a double-blind placebo-controlled trial,
gamma-hydroxybutyric acid (GHB) (25 mg/kg orally) suppressed
most of the withdrawal symptomatology in 14 heroin addicts and
13 methadone-maintained subjects. The GHB effect was prompt
(within 15 minutes) and persisted for between 2 and 3 hours.
Subsequently, the same patients received GHB in an open study
every 2 to 4 hours for the first 2 days and 4 to 6 hours for the
following 6 days: most abstinence signs and symptoms remained
suppressed and patients reported felling well. Urine analysis
failed to detect any presence of opiate metabolites. No
withdrawal symptomatology recurred after 8 days of treatment
when GHB was suspended, and patients were challenged with an
intravenous injection of 0.4 mg naloxone. The results indicate
that GHB may be useful in the management of opiate withdrawal
UR - PM:0008397726
SO - Neuropsychopharmacology 1993 Aug ;9(1):77-81
9
UI - 27
AU - Marino A
AU - Costa R
AD - Istituto di Farmacologia Sperimentale e Clinica, II Facolta
di Medicina, Universita, Napoli
TI - [Alcoholism. Aspects of its pharmacology, clinical picture
and therapy]
AB - In every age and culture, people have had to distinguish
between positive and negative consequences of the use of
psychoactive substances. Since the ancient times it was known
that alcohol, easily available in wide quantities, could
facilitate social contacts. The abuse and the addiction
represent, on the other hand, a complicated social phenomenon
and are the expression of physiological adaptive mechanisms
brought to the extreme point. The high level of diffusion and
the complexity of these problems made it necessary to create
diagnostic classifications to classify illnesses on the basis of
definite and reliable principles, with the main goal of
obtaining therapeutic progress. The consequences of alcohol
abuse are both physical and psychic, thus therapeutic approaches
must take into account these two points. Some pharmacological
agents may lead to cross- tolerance with alcohol and, besides,
they are not necessary in case of a slight abstinence where
brief psychotherapies are sufficient. Recent advances in the
knowledge of the mechanisms which underlie alcohol addition
suggest approaches particularly aimed to correct imbalances of
neurotransmitters that can determine addiction. Among these, GHB
acid seems to be particularly important. At the end, on the
basis of the latest progress in psycho-immunopharmacology, the
relationships between alcohol and disease are considered
UR - PM:0008235037
SO - Recenti Prog Med 1993 Oct ;84(10):709-721
10
UI - 31
AU - Palatini P
AU - Tedeschi L
AU - Frison G
AU - Padrini R
AU - Zordan R
AU - Orlando R
AU - Gallimberti L
AU - Gessa GL
AU - Ferrara SD
AD - Department of Pharmacology, University of Padova, Italy
TI - Dose-dependent absorption and elimination of
gamma-hydroxybutyric acid in healthy volunteers
AB - Gamma-hydroxybutyric acid (GHB) is effective in treatment
of the alcohol and opiate withdrawal syndromes. Its absorption
and disposition kinetics have been studied in 8 healthy male
volunteers following oral administration of single doses of
12.5, 25 and 50 mg kg-1. The AUC increased disproportionately
with the dose and so the apparent oral clearance decreased
significantly as the dose was increased, whereas the terminal
half-life and mean residence time increased. The peak plasma
concentrations normalised to the lowest dose fell significantly
with increasing doses, whilst the corresponding peak times
increased. These findings suggest that both the oral absorption
and the elimination of GHB are capacity-limited processes. GHB
did not bind to significant extent to plasma proteins over the
therapeutic concentration range. The pharmacokinetic parameters
in healthy volunteers were not significantly different from
those previously observed in alcohol-dependent patients with
compensated alcoholic liver disease
UR - PM:0008299669
SO - Eur J Clin Pharmacol 1993 ;45(4):353-356
11
UI - 32
AU - Gessa GL
AD - Dipartimento di Neuroscienze, Universita, Cagliari
TI - [Guidelines for the drug therapy of alcoholism]
AB - In acute alcohol intoxication, treatment is symptomatic and
consists of correcting any physiological dysfunctions, as
possible acid-basic or electrolytic disorders hypoglycemia,
hypovitaminosis changes and of maintaining respiratory tracts
open. Recently, in some cases of acute intoxication, metadoxine
has been used with success, being capable of accelerating the
urinary elimination of ethanol and acetaldehyde. Moreover,
further studies have shown that Ro 15-4513 (an inverse agonist
of benzodiazepine receptors) reduces the anaesthesia time
induced by high doses of ethanol in rats. On the other hand, as
far as the alcohol withdrawal syndrome is concerned, drugs
commonly used are: alcohol itself, chloral hydrate, paraldehyde,
barbiturates, chlormetizole and benzodiazepines (administered at
high doses). Very recent experiments have been carried out using
gammahydroxybutyric acid (GHB), which can produce a rapid and
complete suppression of alcohol withdrawal symptoms. In
epileptic patients, it is suitable to administer
anticonvulsivant drugs together with the above compounds. In
alcohol dependence two main treatment strategies are followed,
the first is the administration of inhibitory drugs of aldehyde
dehydrogenase (disulfiram, calciumcyanamide) which, if given
before alcohol consumption, produce unpleasant and avversive
reactions, due to the accumulation of acetaldehyde in the blood.
Other drugs, recently used with great success, remove the desire
to drink without producing those unpleasant reactions described
for disulfiram; amongst these are GHB and serotonin uptake
inhibitors (fluoxetine, zimelidine)
UR - PM:0002359869
SO - Recenti Prog Med 1990 Mar ;81(3):171-175
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