Health status of employed and unemployed methadone patients.
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Adult↗
Biomedical subjects
G J DiGregorio
Publications and source records attributed to G J DiGregorio.
Glycine enhances the central depressant properties of ethanol in mice.
The interaction between ethanol and glycine in the central nervous system was investigated in male Swiss-Webster mice. The loss of the righting reflex (LORR) was used as a measure of central nervous system depression. Mice were injected with ethanol (4.0 g/kg, IP), causing an ethanol-induced LORR. Immediately after the animals regained the righting reflex from ethanol administration, they received an intracerebroventricular (ICV) injection of saline or glycine (1, 15, 25, or 50 mumol/kg) in a volume of 5 microliters. Upon ICV injection of glycine, the mice lost the righting reflex once again. This effect of glycine in the presence of ethanol occurred rapidly and in a dose-dependent manner. Glycine induced a return to the LORR of 12.6 +/- 0.7, 24.5 +/- 1.3, 32.8 +/- 2.0, and 46.8 +/- 4.5 min when doses of 1, 15, 25, and 50 mumol/kg, respectively, were injected. D-Serine (15, 25, or 50 mumol/kg), an amino acid precursor of glycine, was injected (ICV) after the animals regained the righting reflex following ethanol injection (IP). Serine caused a return to the LORR of 0.5 +/- 0.5, 6.0 +/- 1.0, and 6.5 +/- 0.9 min when doses of 15, 25, and 50 mumol/kg, respectively, were injected. Strychnine was used to attenuate the ability of glycine and serine to cause a return to the LORR in the presence of ethanol. Strychnine, a competitive antagonist of glycine, significantly reduced the ability of glycine and serine to enhance the depressant action of ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Determination of cocaine usage in pregnant women by a urinary EMIT drug screen and GC-MS analyses.
In mothers who had no prenatal care and in their newborns, the presence of cocaine and benzoylecgonine (BE) was determined in urine, hair, and meconium. Samples of urine and hair were obtained from pregnant women who entered the hospital for delivery. Cocaine usage was assessed by a urinary enzyme-multiplied immunoassay technique (EMIT) and by gas chromatography-mass spectrometry (GC-MS). GC-MS was used to detect the presence of cocaine and BE in maternal urine and hair and in meconium and hair obtained from their newborns. In this study of 40 women, the EMIT assay for urinary BE identified 17 (42.5%) of the women as having used cocaine. Of these 17 women, all of their newborns were exposed to cocaine during gestation, based on the analysis of neonatal hair and meconium for cocaine or BE. From the maternal samples that were assayed for cocaine and BE by GC-MS, it appears that hair analysis identified the most cocaine users (70%) of the 40 women who participated in the study. When GC-MS was used to analyze the various samples from mothers and their newborns, 80% of the neonates showed exposure to cocaine. This study shows that women with no prenatal care who have a positive urinary drug screen by EMIT for BE have exposed their newborns to cocaine. The data from pregnant women with a negative drug screen for BE show that 52.2% of their newborns had prior fetal exposure to cocaine.
Cocaine↗
Management of low back and neck pain by analgesics and adjuvant drugs: an update.
Although recent advances in drug therapy for low back and neck pain may seem slight, some consolidation of knowledge has taken place. Opiates, NSAIDs, and acetaminophen remain the drugs of choice. New NSAIDs, especially ketorolac, have some advantages. Injections of steroids and other agents into the lumbar area do not offer any distinct advantages. The use of adjunctive drugs such as muscle relaxants and antidepressants has not materially changed in the last few years.
Analgesics↗
The accumulation and disappearance of cocaine and benzoylecgonine in rat hair following prolonged administration of cocaine.
Hair samples were obtained at various time periods from male Sprague-Dawley rats following the injection of cocaine hydrochloride in doses of 5, 10, and 20 mg/kg, ip, for 28 days. Hair samples were also taken continually after the dosing was stopped until the presence of cocaine and benzoylecgonine were no longer detected in hair. Cocaine and benzoylecgonine in hair and plasma were analyzed by gas chromatography/mass spectrometry. Both cocaine and benzoylecgonine were found in hair samples 4 days after the initiation of cocaine administration. When cocaine dosing was stopped after 28 days, approximately 25 to 30 days were required for cocaine and benzoylecgonine to disappear from rat hair in the group of animals that received the highest dose of cocaine. The disappearance of cocaine and benzoylecgonine followed first-order kinetics. The mean rate constant and mean half-life for cocaine disappearance from hair were 0.212 +/- 0.005 day-1 and 3.31 +/- 0.09 days, respectively, and the mean rate constant and mean half-life for benzoylecgonine disappearance from hair were 0.098 +/- 0.006 day-1 and 6.90 +/- 0.28 days, respectively. The mean plasma concentrations of cocaine on Day 25 for the 5, 10, and 20 mg/kg doses of cocaine were 508 +/- 42, 852 +/- 95, and 2027 +/- 75 ng/mL, respectively, and the mean plasma benzoylecgonine levels for the 5, 10, and 20 mg/kg doses of cocaine were 49.9 +/- 7.0, 103.3 +/- 9.3, and 191.0 +/- 16.0 ng/mL, respectively. There was a positive correlation between the doses of cocaine hydrochloride administered and the plasma levels of both cocaine and benzoylecgonine. This study showed that cocaine and benzoylecgonine can be measured in rat hair following the administration of cocaine and that it was possible to correlate the concentrations of cocaine and benzoylecgonine found in hair with the doses of cocaine that were administered.
Animals↗
The presence of cocaine and benzoylecgonine in rat cerebrospinal fluid after the intravenous administration of cocaine.
Cocaine hydrochloride, in doses of 0.5, 1.0, 2.0 and 4.0 mg/kg, iv, was administered to male Sprague-Dawley rats. Cerebrospinal fluid (CSF) was collected from the cisterna magna over a 20 min period and blood samples were obtained at 20 min after cocaine administration. In addition, blood samples for the 1 mg/kg dose of cocaine were collected at 2, 10, 20 and 30 min following drug injection. Gas chromatography/mass spectrometry was used for the analysis of cocaine and its metabolites in plasma and CSF. The disappearance of cocaine (1 mg/kg) from the plasma exhibited first order kinetics with a half-life of 18.11 +/- 3.22 min. Cocaine and benzoylecgonine were found in CSF and the concentrations of cocaine and benzoylecgonine increased in CSF as the doses of cocaine were increased. CSF flow rates were not altered by the iv administration of cocaine or benzoylecgonine. The CSF-to-plasma ratios for cocaine were quite similar to each other over the dosage range of cocaine that was administered; however, the CSF-to-plasma ratios for benzoylecgonine decreased as the concentrations of benzoylecgonine increased in plasma and CSF. When benzoylecgonine (2 mg/kg, iv) was given, the compound was detected in CSF indicating that benzoylecgonine can enter into the central nervous system from the peripheral blood. This investigation shows that cocaine and benzoylecgonine can be assayed in CSF and that the plasma levels of these compounds correlate with their concentrations in CSF.
Animals↗
Management of low back pain by analgesics and adjuvant drugs.
Ninety percent of all low back pain can be managed successfully by the skillful and appropriate use of the major analgesic drugs, NSAIDs, and the opioids. Adjunctive drugs, such as skeletal muscle relaxants and antidepressants, have their uses, but must be considered as temporary aids to the major analgesics. There is intensive research to develop new and more useful analgesic drugs. Ketorolac tromethamine, an NSAID recently approved by the Food and Drug Administration, is suitable for intramuscular administration for the short-term management of postsurgical and other acute pain.
Analgesics↗
The relationship between recent cocaine use and pregnancy outcome.
We conducted urine screening for cocaine metabolite in 500 consecutive women admitted to a labor and delivery unit. The pregnancy outcome of 411 of the women was determined at that admission. The prevalence of cocaine-positive urines was 15.3% (95% confidence interval 11.8-18.8%). A subset of this population that had not received prenatal care had a prevalence of 62% (95% confidence interval 47.2-76.6%). Women with positive urines were almost four times more likely to have preterm labor and over twice as likely to deliver a premature infant or one with a 1-minute Apgar score of 6 or lower. Our findings support the concept that urine drug screening for cocaine and/or other drugs of abuse should be considered in patients who present with no prenatal care, premature labor, premature delivery, and delivery of an infant with a 1-minute Apgar score of 6 or less. This strategy may enable us to identify and bring to therapy a population of women that could potentially go unrecognized.
Adult↗
Cocaine update: abuse and therapy.
The most striking pharmacologic effect of cocaine is intense sympathetic stimulation, both centrally and peripherally. Physical dependence is much less severe than in opiate abuse. Psychologic dependence, however, is intense and is the primary problem in cocaine addiction. Although withdrawal symptoms are both somatic and visceral, severe depression is the dominant symptom. Therapy for withdrawal symptoms is not specific, but desipramine, bromocriptine and lithium have shown considerable promise. Acute overdose requires life support therapy. Appropriate pharmacologic interventions include intravenous diazepam to control central nervous system symptoms and propranolol or labetalol to control arrhythmias and hypertension.
Cocaine↗
Marijuana pharmacology and urine testing.
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Cannabis↗
Adjuvant drug therapy for pain.
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Adrenal Cortex Hormones↗
The effect of acute hepatic injury on the disposition of vitamin A in the rat.
The distribution of vitamin A was measured in various body fluids and tissues in rats with carbon tetrachloride induced acute liver injury compared to vehicle treated controls. All rats received 25,000u of retinol palmitate intraperitoneally 24 hr prior to study and 50,000u on the day of the study. Rats with liver injury had significant elevations of unesterified retinol in plasma and saliva, and significant elevations of retinol palmitate in plasma, urine, and kidney. Also, liver disease caused a significant decrease in the liver concentration of retinol palmitate, and a significant decrease in the bile and kidney levels of unesterified retinol. These results suggest that redistribution of vitamin A from liver to other areas occurs after acute liver injury in rats. Also, increased levels of vitamin A in urine, saliva or plasma may be a noninvasive marker for liver injury in man after vitamin A challenge.
Acute Disease↗
The effect of delta-9-tetrahydrocannabinol on rat cerebrospinal fluid.
The effect of delta-9-tetrahydrocannabinol (THC) on cerebrospinal fluid (CSF) flow in rats was studied. The ventricular system of rats anesthetized with ketamine sulfate was cannulated via cisternal puncture, and CSF production was recorded. When administered in doses of 25 mg/kg to 45 mg/kg intraperitoneally, THC caused inhibition of CSF flow; in larger doses a smaller response was noted. In response to THC, CSF flow showed an initial drop, a return toward baseline, and a secondary decrease. It is postulated that this biphasic effect is due to a combination of THC's sympathomimetic effects on the CNS plus the local action that this drug has on choroidal synaptosomal neurotransmitters.
Animals↗
Toxicology of asbestos.
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Adenocarcinoma↗
Effect of amiodarone on the pharmacokinetics of phenytoin, quinidine, and lidocaine in the rat.
Previous studies have shown that amiodarone can depress certain aspects of hepatic drug metabolism in the rat. This effect was assessed in vivo by investigating the single dose intravenous pharmacokinetics of phenytoin (10 mg/kg), quinidine (25 mg/kg) and lidocaine (7.5 mg/kg) in rats pretreated for three days with a single daily 100 mg/kg intraperitoneal dose of amiodarone hydrochloride. Compared to vehicle treated controls, significant reductions of 61% and 35% in the respective total clearances of phenytoin and quinidine were observed in the presence of amiodarone. Likewise, the elimination half-lives of phenytoin and quinidine were also significantly prolonged after amiodarone pretreatment. Lidocaine pharmacokinetic parameters were unchanged in the presence of amiodarone. These results suggest that altered hepatic drug clearance may play a part in the recently described clinical drug interactions between amiodarone and either phenytoin or quinidine.
Amiodarone↗
Pharmacokinetics of pentobarbital, quinidine, lidocaine, and theophylline in the thermally injured rat.
Previous studies have shown that rats with 15% third-degree burns show a severe depression in various in vitro hepatic drug-metabolizing enzymes. This effect was assessed in vivo by measuring the disposition of four liver-metabolized drugs in 16% third-degree burned rats at 7 d postburn. Compared with pair-fed control rats, pentobarbital demonstrated a significantly prolonged clearance and elimination half-life without a change in volume of distribution. Quinidine demonstrated a significantly increased volume of distribution and a significantly decreased clearance without a change in elimination half-life. Lidocaine showed a significantly increased volume of distribution. Theophylline, which is only 50% metabolized in the rat, showed no changes in any pharmacokinetic parameters. The free drug fractions of quinidine and lidocaine were found to be significantly decreased at 1 d postburn and normal at 7 d postburn. These results warrant pharmacokinetic studies in human burn patients.
Animals↗
5-Fluorouracil concentrations in rat plasma, parotid saliva, and bile and protein binding in rat plasma.
The pharmacokinetics of 5-fluorouracil were studied over a 60-min period in rats that received 12.5, 25.0, and 50.0 mg/kg iv. The plasma concentration-time relationship and the detectability in bile and parotid saliva (a route of elimination heretofore given little or no attention) were examined. Protein binding of 5-fluorouracil at concentrations chosen to approximate those found in plasma was determined by equilibrium dialysis. Bile-plasma and parotid saliva-plasma concentration ratios were calculated. 5-Fluorouracil concentrations were quantitated by high-performance liquid chromatography. Plasma concentrations at all doses studied appeared to rapidly decline. The half-life, however, at the 50.0-mg/kg dose (27 min) was significantly longer (p less than 0.025) than the corresponding half-life at the 25.0-mg/kg dose (22 min). This may be attributed to an easily saturable hepatic degradation. Although an observed decline in bile-plasma and parotid saliva-plasma concentration ratios at higher doses may represent saturation of these excretary routes, the small amounts of 5-fluorouracil detected in bile and parotid saliva probably contribute negligibly to the elimination of the total drug equivalents administered. Parotid saliva-plasma concentration ratios were not useful in predicting plasma protein binding as determined by equilibrium dialysis. Excretion of intravenously administered 5-fluorouracil in saliva, however, exposes the upper GI tract to this agent and may play a part in causing stomatitis in patients receiving the drug by this route.
Animals↗