Biomedical subjects

S K Guthrie

Publications and source records attributed to S K Guthrie.

25 records · Page 2Linked to original sources

PubMed1989

The treatment of alcohol withdrawal.

Abrupt cessation of regular use of alcohol in a dependent person causes a withdrawal syndrome that may range from mild to extremely severe. Most patients require pharmacologic intervention, especially those with severe symptoms. Historically, the pharmacotherapy of alcohol withdrawal has involved a wide variety of agents. Benzodiazepines are currently preferred due to their consistently high degree of efficacy and laudable record of safety. In addition, beta blockers and clonidine are useful, as both effectively combat the hypertension and tachycardia commonly associated with withdrawal. They are ineffective as anticonvulsants; however. Opinions differ concerning the best treatment for withdrawal seizures. Prophylaxis with benzodiazepines may be all that is required, although some authors advocate the use of phenytoin for 5 days, especially in persons with a history of prior seizures during alcohol withdrawal. Once established, delirium tremens are difficult to treat. Benzodiazepines are most commonly used to provide sedation, and extremely large doses may be required. Careful clinical assessment is essential to the proper treatment of patients undergoing alcohol withdrawal since the coexistence of medical problems may complicate the condition.

Alcoholism↗

PubMed1989

Acetylation phenotype in abstinent alcoholics.

No association between acetylation phenotype and alcoholism was discovered. Fifty-four percent of both the alcoholic patients and healthy volunteers were rapid acetylators. Acetylation phenotyping is not helpful to the investigation of the genetics of alcoholism.

Acetylation↗

PubMed1986

Reinterpretation of the pharmacokinetic mechanism of oral benzodiazepine ethanol interaction.

Previously published studies investigating the oral benzodiazepine ethanol interaction have utilized a single dose of ethanol, a single dose of oral benzodiazepine, and measured plasma benzodiazepine concentration over varying time periods. Most studies reported an increase or no change in benzodiazepine plasma concentrations following ethanol administration, which the investigators usually ascribed to an ethanol-induced increase in the benzodiazepine absorption rate constant. However, ethanol decreases the hepatic clearance of benzodiazepines that are biotransformed via the P450 enzyme system and this effect was not taken into account in evaluation of the results of these studies. Computer simulations have been used to investigate possible mechanisms of the oral benzodiazepine-ethanol interaction. The effects of a constant or transient decrease in clearance and an increase in absorption rate constant upon maximum concentration, time of maximum concentration, and area under the benzodiazepine plasma concentration curve (AUC) have been examined. A transient 75% decrease in benzodiazepine clearance resulted in a 13.6% increase in AUC (0-36 hr), a 3.4% increase in Cmax and a 5.7% increase in tmax. These changes are qualitatively consistent with, but quantitatively shy, of those observed in most studies. Consequently, an effect of ethanol upon benzodiazepine absorption must still be considered.

Absorption↗

PubMed1986

Different neurotransmitter metabolite concentrations in CSF samples from inpatient and outpatient normal volunteers.

Cerebrospinal fluid concentrations of the neurotransmitter metabolites 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were compared in two groups of healthy volunteer subjects. One group (outpatient) was composed of 27 subjects who were transported to the outpatient clinic on the day of the lumbar puncture (LP). The other group (inpatient) was composed of 10 subjects who were admitted to the NIMH Research Ward on the evening prior to the LP. After statistical adjustment for age, height, sex and season in which LP was performed the inpatient group had significantly higher concentrations of both 5HIAA and HVA (P less than 0.005 and P less than 0.05, respectively) than the outpatient group. The difference in DOPAC concentration approached significance (P = 0.056), but there was no difference in MHPG concentration between the groups. This result indicates the need for strict control of environment in studies of CSF monoamines and their metabolites.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Pharmacologic interventions for the treatment of opioid dependence and withdrawal.

This article discusses current pharmacologic methods in the treatment of heroin dependence and withdrawal. Methadone hydrochloride, the most commonly used opiate agonist, is used for both withdrawal and maintenance therapy. However, it produces dependence and withdrawal results upon abrupt discontinuation. Other opiate agonists including L-alpha acetyl methadyl (LAAM) and propoxyphene napsylate have been used for both withdrawal and maintenance therapy. LAAM is currently available only as an investigational agent and propoxyphene is easily accessible but has been associated with hallucinations and dysphoria at high doses. Alpha 2-adrenergic agonists decrease opiate withdrawal symptoms by decreasing the central adrenergic hyperarousal that is associated with withdrawal. Clonidine effectively attenuates but does not totally eliminate withdrawal symptoms. Other alpha 2-adrenergic agonists (e.g., lofexidine hydrochloride, guanfacine hydrochloride, and guanabenz) have undergone only preliminary investigations. Although alpha 2 agonists effectively decrease most withdrawal symptoms they often cause hypotension. Buprenorphine hydrochloride is a partial opiate agonist that shows some promise in the treatment of the heroin-dependent population. It attenuates opiate craving and causes only minimal withdrawal upon abrupt discontinuation. Because it is well accepted by the heroin-dependent population, however, it may ultimately become an abused substance. Naltrexone is a potent, orally acting opiate antagonist that blocks all opiate-agonist effects and causes no euphoria. Unfortunately, it has not been well accepted by the heroin-dependent population. Scant research has been conducted concerning the use of adjunctive medications during opioid withdrawal.

Humans↗

PubMedDate not supplied

Treatment of acute neuroleptic-induced movement disorders.

Acute extrapyramidal syndromes (EPS), including dystonia, parkinsonism, and akathisia, are associated with the use of virtually all neuroleptic agents. They may be alleviated by reducing the neuroleptic dosage, switching to a lower-potency drug, or administering an adjunctive agent such as an anticholinergic, amantadine, benzodiazepine, or beta-blocker. Akathisia may be only partly dispelled by anticholinergics; alternatives are beta-blockers, benzodiazepines, and clonidine. In patients receiving long-term neuroleptic therapy, both the prophylactic use and the duration of treatment with concomitant anti-EPS drugs are controversial. Administration of prophylactic anti-EPS drugs should be based on the likelihood that the patient will develop EPS, as well as the risk of adverse reactions resulting from extended use of the agents in a specific patient. The decision to continue anti-EPS therapy should be reevaluated frequently, especially in elderly patients.

Acute Disease↗

PubMedDate not supplied

Clinical issues associated with urine testing of substances of abuse.

Several factors may affect the validity and outcome of urine testing for abused drugs such as amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, ethanol, opiates, and phencyclidine. Urine is used for large-scale testing because acquisition of the sample is noninvasive and because most abused drugs can be detected in urine for a reasonable duration after ingestion. Urine testing for drugs of abuse is a two-step process. In the first step, screening assays are used to identify presumably positive specimens. Common screening tests are radioimmunoassays, enzyme immunoassays, fluorescence polarization immunoassay, and thin layer chromatography. Since they may be subject to cross-reactivity, once a possible positive sample has been identified by a preliminary test, a second more specific methodology, gas chromatography with mass spectrometry, is done to confirm the results. Knowledge of the pharmacology and pharmacokinetics of abused drugs affects selection and interpretation of test results.

Cross Reactions↗