Subject(s)
Malondialdehyde/blood , Thiobarbituric Acid Reactive Substances , Adult , Chromatography, High Pressure Liquid/methods , Humans , Porphyria Cutanea Tarda/blood , Porphyria, Erythropoietic/blood , Reference Standards , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Spectrophotometry/methodsABSTRACT
The clinical pharmacodynamics of temazepam were investigated in patients who received spinal anaesthesia. Total plasma and cerebrospinal fluid temazepam concentrations were measured and correlated with the clinical effects. Sedation was measured by three separate methods. None, including an aggregated score of all three measures, was correlated closely with either the plasma or the cerebrospinal fluid levels (p = 0.86 and 0.12 respectively). Anxiety was measured before and after premedication. The two scores were correlated but the change in anxiety after premedication did not correlate with either the plasma or the cerebrospinal fluid concentrations (p = 0.11 and 0.45 respectively). Short-term memory was measured before and after premedication. The decline in short-term memory ability was moderately well correlated with both the plasma and the cerebrospinal fluid levels (p = 0.0005 and 0.013 respectively). With temazepam, the variation in sedative and anxiolytic effects between subjects is explained not by differences in pharmacokinetics but rather by differences in the pharmacodynamic response. Because sedative and anxiolytic effects are poorly correlated, but the amnesic effect is well correlated with temazepam concentrations, different sites of action for these effects are suggested.
Subject(s)
Anxiety/drug therapy , Conscious Sedation , Memory, Short-Term/drug effects , Premedication , Temazepam/pharmacology , Aged , Aged, 80 and over , Anesthesia, Spinal , Anxiety/blood , Anxiety/cerebrospinal fluid , Dose-Response Relationship, Drug , Humans , Male , Middle Aged , Temazepam/blood , Temazepam/cerebrospinal fluidSubject(s)
Chromatography, Thin Layer/methods , Theophylline/urine , Drug Overdose , Humans , Infant , Theophylline/poisoningABSTRACT
In describing the clinical, biochemical, and family findings in five children with porphyria, we examine initial treatments and, where appropriate, the effectiveness of long-term therapy. We note that porphyria diagnosis, particularly in childhood, relies heavily on specialist laboratory investigations. Because disease expression in some porphyrias requires exposure to precipitating factors, it may be prevented or delayed by their avoidance.
Subject(s)
Oxidoreductases Acting on CH-CH Group Donors , Porphyrias/diagnosis , Porphyrias/therapy , Adolescent , Aged , Aminolevulinic Acid/urine , Child , Child, Preschool , Coproporphyrinogen Oxidase/blood , Female , Flavoproteins , Humans , Hydroxymethylbilane Synthase/blood , Male , Mitochondrial Proteins , Oxidoreductases/blood , Porphobilinogen/urine , Protoporphyrinogen Oxidase , Reference Values , Uroporphyrinogen Decarboxylase/bloodABSTRACT
Twenty-six patients received oral temazepam and subsequently spinal anaesthesia. Blood and lumbar cerebrospinal fluid temazepam levels were measured together with the degree of sedation. The plasma and cerebrospinal fluid concentrations correlated well with the temazepam dose but even better with the weight standardised dose (r = 0.65, p = 0.0003 and r = 0.75, p = 0.00001 respectively). Both the plasma and cerebrospinal fluid concentrations of temazepam were correlated with the patient's sedation (r = 0.42 p = 0.037, and r = 0.46 p = 0.021 respectively), but neither was strong. Thus, although the drug concentration at the receptor may be a major factor in producing sedation, other factors, possibly the receptor population or their responsiveness, are also important contributors.
Subject(s)
Anesthesia, Spinal , Temazepam/pharmacokinetics , Administration, Oral , Aged , Aged, 80 and over , Chromatography, Gas , Humans , Male , Middle Aged , Preanesthetic Medication , Spinal Puncture , Temazepam/blood , Temazepam/cerebrospinal fluidSubject(s)
Antifungal Agents/pharmacokinetics , Aspergillosis, Allergic Bronchopulmonary/drug therapy , Bronchoalveolar Lavage Fluid/metabolism , Ketoconazole/analogs & derivatives , Lung/metabolism , Adult , Antifungal Agents/therapeutic use , Humans , Itraconazole , Ketoconazole/pharmacokinetics , Ketoconazole/therapeutic use , MaleABSTRACT
We report a 12 month double-blind randomized crossover trial of fenfluramine in 20 children with the syndrome of autism. On active drug most of the children lost weight and blood serotonin levels fell by an average of 60%. There was a fall in urinary dopamine (DA) and noradrenaline (NA) levels and increased excretion of homovanillic acid (HVA). Some of the children showed improvement in tests of cognitive and language function, although the results did not achieve overall statistical significance. Event-related brain potentials (ERPs) were obtained in seven subjects on an auditory choice reaction time task. Side effects of the drug included irritability and lethargy. Fenfluramine may have a limited place in the management of some patients with autistic disorder.
Subject(s)
Autistic Disorder/drug therapy , Fenfluramine/therapeutic use , Adolescent , Arousal/drug effects , Autistic Disorder/blood , Autistic Disorder/psychology , Body Weight/drug effects , Child , Child, Preschool , Double-Blind Method , Fenfluramine/pharmacokinetics , Humans , Intelligence Tests , Randomized Controlled Trials as Topic , Serotonin/bloodABSTRACT
A child who was grossly malnourished and who showed increased excretion of porphyrin and porphyrin precursor had normal activity of erythrocyte porphobilinogen deaminase (EC 4.3.1.8) and leukocyte protoporphyrinogen oxidase (EC 1.3.3.4). Clinical symptoms, coincident with the excretion of rose-colored urine, were consistent with the diagnosis of an acute porphyria. The disease resolved spontaneously after the withdrawal of carbamazepine and sodium valproate and the commencement of parenteral nutrition with subsequent carbohydrate loading. In addition to normal concentrations of enzyme activities, the patient is unusual in presenting before puberty and in having no family history of porphyria.
Subject(s)
Liver Diseases/metabolism , Porphyrias/metabolism , Porphyrins/analysis , Acute Disease , Adolescent , Erythrocytes/analysis , Feces/analysis , Humans , Leukocytes/analysis , Male , Porphyrins/blood , Porphyrins/urineSubject(s)
Antifungal Agents/blood , Chromatography, High Pressure Liquid , Ketoconazole/analogs & derivatives , Acquired Immunodeficiency Syndrome/blood , Acquired Immunodeficiency Syndrome/microbiology , HIV/physiology , Hot Temperature , Humans , Itraconazole , Ketoconazole/blood , Microchemistry , Quality ControlABSTRACT
Thirteen male patients were administered 20 mg of temazepam orally 1 to 2 h prior to undergoing spinal anaesthesia for a urological procedure. Samples of blood and CSF were drawn just before insertion of the spinal and the concentration of drug estimated in these two media. The results obtained indicated that a highly significant correlation existed between the unbound concentration of temazepam in plasma and the concentration of drug present in CSF. Temazepam appeared to be an effective light pre-medicant in all of the subjects studied.
