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J E Peachey

Publications and source records attributed to J E Peachey.

At least 19 recordsLinked to original sources
PubMed2002

Interactions between cutaneous afferent inputs to a withdrawal reflex in the decerebrated rabbit and their control by descending and segmental systems.

Previous studies have suggested that activation of nociceptive afferents from the heel recruits a supraspinal mechanism, which is modulated by adrenergic descending inhibition, that augments withdrawal reflexes in medial gastrocnemius (MG) motoneurones. To test this idea, we have studied the temporal evolution of reflexes evoked in MG by electrical stimulation of sural nerve A(beta)-, A(delta)- and C-fibre axons at 1 Hz, in decerebrated rabbits. Reflexes were analysed in three time bands, estimated to accord to afferent drive from A(beta)- (phase 1), A(delta)- (phase 2) and C-fibre (phase 3) inputs. Stimulation of A(delta)- and C-fibres gave significant temporal summation of all reflexes. The alpha(2)-adrenoceptor antagonist RX 821002 ((2-(2,3-dihydro-2-methoxy-1,4-benzodioxin-2-yl)-4,5-dihydro-1-H-imidazole)-HCl) (100 microg intrathecal (i.t.)) potentiated, and the alpha(2)-agonist dexmedetomidine (1-30 microg i.t.) depressed all reflexes per se, but the effects of these drugs on temporal summation were secondary to changes in baseline excitability. When C-fibres were stimulated, the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (1 mg i.t.) reduced temporal summation of phase 2 and 3 but not phase 1 reflexes. Spinalisation at L1 in the absence of drugs increased phase 2 and 3 reflexes but had no effect on phase 1, whereas spinalisation after RX 821002 resulted in decreased phase 1 responses with no significant change in later phases. Spinalisation in the presence of dizocilpine resulted in small reductions in phase 3 reflexes only. In all cases spinalisation virtually abolished temporal summation. In spinalised animals, dizocilpine selectively reduced late reflexes, and the opioid antagonist naloxone (100 microg i.t.) augmented all reflexes but gave rise to temporal subtraction of reflexes when C-fibres were stimulated.The present experiments have revealed a number of novel and important features of the sural-MG reflex pathway: (i) activity in fine afferent axons augments the reflexogenic potential of all subsequent afferent input, thereby allowing all afferent drive from the sural field to contribute to withdrawal of the heel; (ii) endogenous adrenergic control of this reflex pathway is completely non-selective; (iii) there is a non-adrenergic element of descending inhibition that is selective for the late components of MG reflex responses, and this element is directed particularly against transmission through NMDA receptors; (iv) temporal summation in this reflex is dependent on NMDA receptor-dependent and -independent mechanisms; and (v) this temporal summation is in some way dependent on the integrity of descending pathways.

Adrenergic alpha-Agonists↗
PubMed1998

Safety of ipsapirone treatment compared with lorazepam: discontinuation effects.

OBJECTIVE: To determine discontinuation effects of ipsapirone, a novel azapirone and partial 5-HTIA agonist that has anxiolytic effects clinically and has not caused dependence or withdrawal symptoms in animals, and to compare these effects with those of the benzodiazepine lorazepam, owing to concern about dependence or withdrawal symptoms following use of these drugs. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient and inpatient treatment. PARTICIPANTS: Sixty-five healthy male volunteers who had experience with sedative-hypnotics or anxiolytics and did not meet DSM-III-R criteria for abuse or dependence. INTERVENTIONS: Participants were randomized to receive ipsapirone 15 mg per day (n = 17), ipsapirone 22.5 mg per day (n = 16), lorazepam 3 mg per day (n = 16), or placebo (n = 16) as outpatients for 36 days (treatment) followed by single-blind placebo as inpatients for 3 days and as outpatients for 6 days (withdrawal). OUTCOME MEASURES: Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Scale (HAM-D), Spielberger State Anxiety Scale, Sleep Quality Questionnaire, General Symptom Checklist, self-rated intoxication, Clinical Institute Withdrawal Assessment--Benzodiazepines (CIWA-Benzo), psychomotor testing and urine drug screen. RESULTS: Only 45 subjects completed the study; discontinuation rates did not significantly differ among treatment groups. At day 39, fewer and less severe symptoms (e.g., insomnia and fatigue) were found on the CIWA-Benzo scale after treatment with ipsapirone or placebo than after treatment with lorazepam (p < 0.05). Subjects reported longer sleep latency and poorer sleep quality after receiving lorazepam than after receiving ipsapirone or placebo. Scores on the HAM-D, Spielberger State Anxiety and HAM-A scales did not change from baseline. CONCLUSIONS: Withdrawal symptoms were detected after discontinuation of therapeutic doses of lorazepam. Significantly fewer symptoms were observed after withdrawal from anxiolytic doses of ipsapirone.

Adult↗
PubMed1992

The use of calcium carbimide in relapse prevention counselling: results of a randomized controlled trial.

The effect of combining relapse prevention counselling with use of an alcohol-sensitizing drug was examined. Fifty-six alcoholic subjects who participated in a clinical trial of the short-acting alcohol sensitizing drug, citrated calcium carbimide, were randomly assigned to: (i) a Physician Advice condition in which subjects took the drug within a context designed to reinforce the medical management of their drinking problem; and (ii) a Relapse Prevention condition in which subjects were instructed to pair use of the drug with planned entry into high risk drinking situations and to gradually reduce reliance on the drug by developing alternative coping behaviour patterns. As predicted, subjects receiving carbimide in conjunction with relapse prevention counselling showed significant growth in internal attribution for change; whereas those receiving carbimide under more traditional medical management showed no movement toward internality. On measurement of alcohol consumption at 6, 12 and 18 months follow-up, there was some indication of superior maintenance of treatment gains at 18 months post-treatment for subjects who had received relapse prevention counselling, although the effect did not reach a conventional level of significance (F = 2.82; P less than 0.06). The findings are interpreted as consistent with a cognitive social-learning analysis of the maintenance of behaviour change.

Adult↗
PubMed1989

Calcium carbimide in alcoholism treatment. Part 2: Medical findings of a short-term, placebo-controlled, double-blind clinical trial.

Drug-induced toxicity in chronic alcoholics who participated in a 4-month placebo (Pl)--controlled clinical trial of the efficacy of calcium carbimide (CC) is reported. Daily monitoring of patients' compliance indicated that 85% of study medications were taken, and very little drinking took place during the study. Patients did not report more symptoms or experience more medical problems during CC administration than during placebo administration. There was no evidence of hepatotoxicity, or behavioural toxicity. Mean white blood cell count was slightly increased during CC treatment, and returned to baseline values when CC was stopped. Thyroid function was not affected by CC in patients with normal pretreatment function. However one patient with pretreatment reduced thyroid function became hypothyroid after CC administration, which indicates a need for systematic monitoring. We conclude that CC is safe for use in alcoholics with normal thyroid function, and may be the preferred alcohol-sensitizing drug in some situations.

Administration, Oral↗
PubMed1989

Calcium carbimide in alcoholism treatment. Part 1: A placebo-controlled, double-blind clinical trial of short-term efficacy.

A randomized, double-blind, placebo-controlled single cross-over study of the alcohol sensitizing drug, calcium carbimide (CC), was conducted in 128 patients with alcohol dependence. Seventy-one (55%) completed the 4-month study. Patients reported drinking and pill-taking behaviour, and submitted urines (for analysis of alcohol and the tablet marker riboflavin) on 97%, and 91% of treatment days, respectively. All of the 69 analyzable completers were abstinent on at least 85% of days, and 58% (40) were alcohol-free during the study. Medications were taken on at least 85% of days. Symptoms and adverse clinical findings were not increased in frequency during CC, compared to placebo. Seventy-eight per cent of the patients believed they had received CC throughout the study, suggesting that CC exerts a strong psychological deterrent effect. Alcohol consumption was significantly reduced to the same extent with CC and placebo, compared to pre-treatment levels.

Adult↗
PubMed1987

Clinical observations of agonist-antagonist analgesic dependence.

The agonist-antagonist opioids are clinically effective analgesics with generally low abuse potential. Four agonist-antagonists are currently available for use as analgesics. Pentazocine, butorphanol and nalbuphine produce morphine-like effects in low doses and, to varying degrees, dysphoric effects as the dose is increased. Buprenorphine, an antagonist opioid of slow onset but long duration of action, produces morphine agonist effects at lower doses, and as the dose is increased, antagonist effects with minimal or no dysphoria. Clinical experience with pentazocine indicates that abuse is possible and consists of two main types: misuse (and abuse) of the drug alone by patients during treatment for pain and, abuse of the drug, often taken together with other psychoactive agents, as a substitute for the preferred drug of abuse. Few reports of abuse have appeared for butorphanol, nalbuphine and buprenorphine; however, considerable care is recommended in their use in patients, especially where there is the possibility for abuse as might occur in patients who require long-term treatment, with a history of drug abuse, and where the drug is easily obtained.

Analgesics, Opioid↗
PubMed1986

Monitoring drinking behavior with the alcohol dipstick during treatment.

The present communication is the first report on the clinical use of the alcohol dipstick to continuously monitor alcoholics' drinking during treatment. Daily urine samples from 34 alcoholics were tested for alcohol by the clinical staff using the alcohol dipstick. The patients also provided self-reports of drinking daily. Patients' compliance for submitting urine samples and for completing daily monitoring sheets (DMS) was 93 and 95%, respectively. Over 75% of the patients drank on at least one occasion; about half of these patients denied drinking detected by the urine tests. Drinking was confirmed by both methods in 39% of the patients who drank, and by the urine testing alone in 54%. The patients in treatment for less than 2 months were abstinent on 85% of the days compared to 98% for those in treatment for 6 months or longer. Seventy-two percent of all alcohol-positive urine samples were submitted by patients on days when they denied drinking. Monitoring of patients' drinking was useful in their clinical management. The alcohol dipstick was a simple, inexpensive, and rapid alcohol measuring procedure that could be used by the clinical staff in the treatment setting.

Adult↗
PubMed1984

The role of drugs in the treatment of alcoholism.

Many drugs are used in alcoholism treatment with the aim of reducing alcohol consumption and correcting alcohol-related psychosocial problems that lead to excessive drinking or result from it. Alcohol-sensitising drugs are used to reduce alcohol consumption with the expectation that improvement in other problem areas will follow. Drugs that share sedative-hypnotic actions with and cross-dependence to alcohol are often used during acute alcohol withdrawal reactions for symptomatic relief, to prevent major withdrawal symptoms, and to prevent and treat seizures. Alcohol abuse may be a form of self-medication, and treatment of an underlying psychiatric disorder, such as depression (with antidepressants), anxiety (with anxiolytics) or psychosis (with antipsychotics), is expected to reduce alcohol consumption. Pretreatment medical and psychiatric assessment of the patient is necessary to ensure that the drug therapy is appropriate to the patient's therapeutic goals and medical/psychological status. Use of the drug must be systematic and carefully monitored; the duration of treatment is determined individually for each patient on the basis of the response to the treatment as well by the development of adverse clinical effects. Ideally, the drug therapy allows the patient to establish resources necessary for continued abstinence after the drug treatment is stopped.

Acetaldehyde↗
PubMed1984

Pharmacologic treatment of chronic alcoholism.

Of the many drug therapies mentioned in this review, only the alcohol-sensitizing drugs have current therapeutic applications in primary alcoholics. When alcohol abuse occurs in association with anxiety, depression, or schizophrenia, treatment with the anxiolytic, antidepressant, and neuroleptic drugs, respectively, may facilitate the alcoholic's ability to participate in other programs. Patients should receive drugs that are appropriate to treatment goals as well as to their psychosocial status. Even if a drug therapy is shown to be efficacious under controlled experimental conditions, its effectiveness may be compromised by a large number of factors that include poor compliance by the patient, a lack of a treatment strategy, or failure to optimize the treatment conditions. New pharmacotherapies with actions directed at central neurochemical pathways mediating alcohol consumption are urgently needed. However, even if such agents become available, they too will only be adjuncts to behavioral and social therapies directed at stabilizing all aspects of the alcoholic's life.

Acetaldehyde↗
PubMed1983

A placebo-controlled double-blind comparative clinical study of the disulfiram- and calcium carbimide-acetaldehyde mediated ethanol reactions in social drinkers.

Treatment for 2 days with disulfiram (3.5 mg/kg once daily) and calcium carbimide (0.7 mg/kg twice daily) in social drinkers produced, as compared to controls, similar blood ethanol values, 2- to 3-fold increases in blood acetaldehyde, respectively, and increased heart rate, pulse pressure, skin temperature, and flushing following 0.15 g/kg of ethanol taken 12 hr after the last drug administration. Peak blood acetaldehyde concentration was greater for calcium carbimide compared to disulfiram (p less than 0.05) and subjects treated with calcium carbimide experienced greater discomfort compared to disulfiram due to palpitations and shortness of breath, and they reported less intention to drink during the reaction. However, neither drug produced sufficient aversion to curtail further drinking totally. With repeated drinks, there was an overall reduction of blood acetaldehyde concentration for calcium carbimide of 85% and for disulfiram of 35%. These data may provide a biochemical basis for the claims of certain alcoholics that they can drink to "burn off" the effects of these drugs.

Acetaldehyde↗