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Biomedical subjects

M Lader

Publications and source records attributed to M Lader.

At least 109 records · Page 6Linked to original sources
PubMed1986

The use of hypnotics and anxiolytics in the elderly.

Anxiety and insomnia are prevalent conditions in the elderly, and anxiolytics and hypnotic drugs are commonly used. Pharmacokinetic variables--absorption, distribution, metabolism and elimination--are all altered to a greater or lesser extent. As a general rule, the elderly are more sensitive to psychotropic drug actions than younger patients. This is particularly so in the over 80s. The elderly tend to suffer from physical conditions which may cause insomnia and anxiety, and medication for those physical complaints may interact with psychotropic medication. In the treatment of insomnia, short- or intermediate-acting benzodiazepines are preferable to long-acting compounds which tend to accumulate and produce confusional states and ataxia. Similarly, the benefit/risk ratio for anxiolytics is least in the elderly. Compounds of intermediate half-life and no active metabolites, such as oxazepam, are preferable. Anxiety syndromes occurring in other contexts, e.g. dementia may be better treated with low doses of antipsychotic drugs.

Aged↗
PubMed1986

The psychopharmacological and electrophysiological effects of single doses of caffeine in healthy human subjects.

The effects of single doses of anhydrous caffeine (250 mg and 500 mg) and placebo on physiological, psychological measures and subjective feelings were studied in a double-blind, cross-over study in nine healthy subjects who had abstained from caffeine-containing beverages for 24 h before each occasion. Caffeine and caffeine metabolites in plasma and urine were assayed. Peak plasma concentrations were observed at 1 to 2 h with an approximate half-life of 5 h. The concentrations of the metabolite 1,7-dimethylxanthine increased during the 5 h. The major urine metabolite was 1-methyluric acid. The EEG showed a dose-related decrease in log 'theta' power and a decrease in log 'alpha' power. Other dose-related effects were an increase in skin conductance level (sweat-gland activity) and self rating of alertness. Ratings of headache and tiredness were decreased by the caffeine. The study illustrates the complexities of studying a drug which is widely taken and which is often associated with withdrawal effects.

Administration, Oral↗
PubMed1986

States of anxiety and their induction by drugs.

Syndromes of anxiety include generalized anxiety states, various forms of phobic disorder and panic attacks. It is unclear whether panic attacks are a separate syndrome from anxiety states or a more severe form. Drug-induced states of anxiety should provide useful models of the mechanisms of anxiety and its treatment. High-risk populations might be identifiable. Catecholamine infusions produce marked peripheral changes without fully reproducing the central feelings. Lactate infusions also produce anxiety-like states lacking full credibility. Experience with the benzodiazepine-receptor contragonists, the beta-carbolines, is limited but panic states have been reproduced following their use. Caffeine produces an anxiety state in high dose and some panic states have been induced. The critical evaluation of drug-induced anxiety states is a promising way of elucidating the mechanisms, psychological and physiological, associated with clinical anxiety.

Animals↗
PubMed1985

Psychotropic effects of enalapril maleate in normal volunteers.

In order to establish any psychotropic effects of the angiotensin-converting enzyme inhibitor enalapril, the drug was administered in doses of 20 mg every morning for 14 days to 12 normal subjects, and compared with placebo on a battery of physiological, psychological and subjective tests, before and after the dose on the 1st and 14th days. Diastolic blood pressure was significantly reduced and heart-rate increased by enalapril as compared with placebo; one component (P1-N1) of the auditory evoked EEG response was increased and tapping rate quickened. The commonest side effect was tiredness. It was concluded that enalapril (unlike most other antihypertensive agents) did not lower mood but could enhance attention and alertness.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Effects of clorazepate dipotassium and placebo on psychomotor skills.

24 normal, healthy subjects were assigned randomly to 15 mg clorazepate dipotassium or placebo groups in a double-blind study. Their performance on a psychological test battery was assessed 45 min. later. Clorazepate dipotassium produced statistically significant impairment in attention and simple reaction time compared with placebo. Performance on more complex tests of cognitive functioning showed no drug effects.

Adult↗
PubMed1984

Benzodiazepine dependence.

Dependence to benzodiazepines is difficult to induce in animals but has been induced by high doses in man. Case reports of benzodiazepine dependence are rare compared with the usage of these drugs, but provide no proper epidemiological framework for the estimation of risk. Patients taking these drugs for four months or more may develop symptoms on withdrawal, characterized by anxiety, dysphoria, malaise, depersonalization, and by perceptual changes such as hyperacusis and unsteadiness. In our first study we compared four patients withdrawing from high doses of benzodiazepines with six patients withdrawing from therapeutic doses. In all patients the typical withdrawal syndrome was noted and was equal in intensity in both groups. In the second study, long-term, normal-dose benzodiazepine treatment was discontinued in 24 patients believed to be dependent on their medication. The withdrawal was gradual, placebo-controlled and double-blind. All experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to pre-withdrawal levels over the next two to four weeks. Electroencephalograhic (EEG) changes comprised marked reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was noted. It is concluded that a risk of dependencies present in all patients taking benzodiazepines even in therapeutic doses for more than a few months. Caution is urged in the prescribing of these drugs.

Animals↗
PubMed1984

The psychopharmacological effects of premazepam, diazepam and placebo in healthy human subjects.

Pharmacological studies of premazepam in animals predicted antianxiety activity without sedation and, in combination with diazepam, a reduction in the sedative effects of the latter. The effects of single doses of premazepam (25 and 50 mg), diazepam (10 mg), premazepam (25 mg) plus diazepam (10 mg), and a placebo on subjective feelings, psychological tests and the EEG were studied in a double-blind cross-over study in 10 healthy subjects. In a repeated dose study in eight subjects, the effects on subjective feelings, psychological tests and the EEG of premazepam (5 and 10 mg twice-daily), diazepam (5mg twice-daily) and a placebo were compared. Premazepam had a different EEG profile from diazepam, producing more slow and less fast wave activity. In the single dose study its effects were similar to diazepam for sedative action and most of the psychological tests, with a tendency towards greater psychomotor impairment. In the repeated dose study, however, premazepam caused less sedation and also tended to produce less psychomotor impairment. The combination dose of premazepam (25 mg) plus diazepam (10 mg) in the single dose study indicated an additive effect rather than an antagonistic one.

Adult↗
PubMed1984

Short-term versus long-term benzodiazepine therapy.

Anxiety syndromes are poorly defined and classified and none of the systems at present in use is entirely satisfactory: some attempt to define anxiety states purely in terms of symptoms, while others do so by viewing anxiety as the product of interactions between external events and innate tendencies. Whatever scheme is used, however, it is essential that the type and level of anxiety is assessed before undertaking drug treatment. In general, tranquillizers such as benzodiazepines are more effective in lessening acute or chronic sustained levels of anxiety than peaks, as in panic attacks. With sustained levels of anxiety, long-acting benzodiazepines such as diazepam and clorazepate are usually preferred, while episodic anxiety normally responds best to shorter-acting drugs such as oxazepam or lorazepam. Short-term use of benzodiazepines is justified in patients with severe symptomatic distress and/or impairment of ability to cope. Long-term use is only justified in patients with chronic severe anxiety in which the symptomatic relief and improved functioning outweigh the risk of dependence.

Anti-Anxiety Agents↗
PubMed1984

Rate of increase of plasma lorazepam concentrations: absence of influence upon subjective and objective effects.

This study was designed to investigate the relationship between subjective and objective effects of a benzodiazepine on the one hand, and the rate of increase of plasma concentration on the other. The pharmacokinetic variables of 10 normal volunteers were calculated following a single intravenous bolus injection of 1 mg of lorazepam, a benzodiazepine devoid of active metabolites. In six of the subjects rates of infusion could be calculated in order to achieve the same plasma concentration after 1 hour and 2 hours. In the main study, lorazepam was infused at two different rates on two separate occasions, with a third placebo infusion occasion. A balanced crossover design was used with single-blind procedures. Plasma concentrations, subjective ratings, quantified EEG recordings, and psychological performance tests were estimated before and at 1, 2, and 3 hours after the start of the infusions. The peak plasma concentrations achieved were the same at the end of the two drug infusions. EEG and some performance tests paralleled the plasma concentrations fairly closely, but subjective effects did not reach their maximum until the 3-hour point and were significantly greater after the 2-hour than after the 1-hour infusion. Drug doses, rate of penetration into the brain, and duration of exposure to the increasing concentrations of lorazepam seem more relevant factors for the time course and the intensity of the various initial effects of the drug than the rate of increase of plasma levels.

Adolescent↗
PubMed1983

Long-term benzodiazepine administration blunts growth hormone response to diazepam.

Growth hormone and prolactin responses to diazepam were measured in eight male patients who had been receiving long-term treatment with benzodiazepines and eight age-matched drug-free controls. The growth hormone response was significantly attenuated during benzodiazepine administration, but increased significantly after benzodiazepine treatment was discontinued. Growth hormone responses four days after the drug therapy withdrawal in patients, however, were still significantly less than in drug-free controls. Prolactin levels were unaltered after diazepam challenge, both in patients and in controls. The results clearly demonstrate tolerance to the growth hormone-releasing effect of diazepam, but do not suggest receptor supersensitivity after withdrawal of benzodiazepine therapy. It is possible that pituitary mammotropes lack benzodiazepine receptors.

Adult↗
PubMed1983

Comparative effects of a repeated dose regime of diazepam and buspirone on subjective ratings, psychological tests and the EEG.

Two doses of buspirone (5 and 10 mg tds), 1 dose of diazepam (5 mg tds) and placebo were administered to 8 normal subjects for a period of 8 days. Each subject received each drug in a balanced order with a minimum interval of 1 week between courses. Psychotropic effects were assessed with a battery of physiological, psychomotor and subjective tests on the first, third and last days of treatment both before the first daily dose and at 1 h and 3 h after it. Diazepam showed a characteristic profile of action producing EEG changes and psychological impairment after a single dose which were still present after a week's treatment. Such effects were minimal after buspirone. Both drugs increased subjective ratings of drowsiness but these feelings tended to decrease after a week's treatment on the clinical doses. Buspirone (10 mg tds) produced some unpleasant side-effects initially but tolerance to these invariably developed after 3 days treatment.

Adult↗