51 results
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2. THE ASSESSMENT OF POTENTIAL DRUG INTERACTIONS WITH A NEW TRICYCLIC ANTIDEPRESSANT DRUG
- Author
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C.F. George and R.H. Briant
- Subjects
Pharmacology ,Drug ,chemistry.chemical_classification ,integumentary system ,business.industry ,medicine.drug_class ,media_common.quotation_subject ,Tricyclic antidepressant ,Tricyclic antidepressant drugs ,Long-term potentiation ,Enzyme ,chemistry ,Papers ,Microsome ,Medicine ,Antidepressant ,Pharmacology (medical) ,business ,Bethanidine ,media_common - Abstract
1 Methods for the investigation of possible interactions with tricyclic antidepressant drugs are described. These methods have been applied to a new compound, Ciba 34276-Ba, which has been shown to have antidepressant activity. 2 In five normal volunteers tested before and during treatment with Ciba 34276-Ba, no abnormalities of resting or post-exercise electrocardiographs occurred. A three-fold reduction in tyramine-responsiveness was seen in three normal subjects studied, but no potentiation of the noradrenaline pressor effect occurred. One of six patients given Ciba 34276-Ba whilst on long-term treatment with bethanidine showed loss of blood pressure control. 3 The metabolic clearance of antipyrine was unaltered in two subjects studied, showing no evidence of induction or inhibition of hepatic microsomal oxidizing enzymes by Ciba 34276-Ba.
- Published
- 1974
3. PHENYTOIN DOSE ADJUSTMENT IN EPILEPTIC PATIENTS
- Author
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G.E. Mawer, Margaret Rodgers, A.J. Robins, P. W. Mullen, and S.B. Lucas
- Subjects
Pharmacology ,Phenytoin ,medicine.medical_specialty ,Test dose ,business.industry ,digestive, oral, and skin physiology ,Serum concentration ,medicine.disease ,nervous system diseases ,Phenytoin Sodium ,stomatognathic diseases ,Epilepsy ,Therapeutic index ,Endocrinology ,Internal medicine ,Papers ,otorhinolaryngologic diseases ,medicine ,Pharmacology (medical) ,Steady state (chemistry) ,Phenytoin Dose ,business ,medicine.drug - Abstract
1 A preliminary survey showed that many outpatients with partially controlled epilepsy had serum concentrations of phenytoin below the recommended therapeutic range (10-20 μg/ml). A phenytoin tolerance test was devised with the intention of predicting a more adequate daily dose for such a patient. 2 Fifteen patients were each given an oral test dose of 600 mg phenytoin sodium and the serum concentration of phenytoin was measured at intervals over 48 h; the concentration rose during the first 4 h and decayed between 12-48 h as an almost linear function of time. 3 The serum concentration/time curves were fitted by an interative computer program based on the Michaelis-Menten equation. The mean saturated rate of elimination of phenytoin was 435 mg/day and the serum concentration (K(m)) corresponding with 50% saturation was 3.8 μg/ml. The mean calculated dose of phenytoin sodium required for a steady state serum concentration of 10-20 μg/ml was 345-400 mg/day. 4 The Michaelis-Menten principle was used to predict steady state serum phenytoin concentrations in individual patients receiving daily doses of phenytoin sodium adjusted by steps of 100 mg. The serum concentrations tended to be either too low or too high. The steep relationship between phenytoin concentration and dose indicates that when the concentration reaches 5-10 μg/ml it is then appropriate to adjust dose by small steps of about 25 mg.
- Published
- 1974
4. THE ALIMENTARY ABSORPTION OF DIAMORPHINE AND MORPHINE IN MAN AS INDICATED BY URINARY EXCRETION STUDIES
- Author
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R.G. Twycross, P.D. Wills, and D.E. Fry
- Subjects
Pharmacology ,business.industry ,Urinary system ,Urine ,Absorption (skin) ,Elixir ,Malignant disease ,Urinary excretion ,Diamorphine Hydrochloride ,Papers ,Morphine ,medicine ,Pharmacology (medical) ,business ,medicine.drug - Abstract
1 Urine was collected over 24 h from 40 patients with advanced malignant disease who had received a known four-hourly oral dose of either diamorphine or morphine in an elixir or of diamorphine by injection for at least 3 days. 2 Samples were assayed for total urinary morphine (free and conjugated) by gas-liquid chromatography. 3 The percentage of the administered dose recovered as morphine was: (a) diamorphine hydrochloride by injection: 70% (s.d. 25) (b) diamorphine hydrochloride by mouth: 77% (s.d. 27) (c) morphine sulphate by mouth: 56% (s.d. 21) 4 It is suggested that diamorphine hydrochloride is completely absorbed by the gastro-intestinal tract but that morphine sulphate is only some two-thirds absorbed.
- Published
- 1974
5. OBSERVATIONS ON THE EFFECT OF β-ADRENOCEPTOR BLOCKING DRUGS ON GLYCERYL TRINITRATE TACHYCARDIA
- Author
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J. M. Kofi Ekue, M.J. Walsh, and Robin G. Shanks
- Subjects
Pharmacology ,Tachycardia ,Supine position ,business.industry ,musculoskeletal, neural, and ocular physiology ,organic chemicals ,digestive, oral, and skin physiology ,Propranolol ,Placebo ,medicine.anatomical_structure ,Tongue ,Oral administration ,Anesthesia ,Papers ,Heart rate ,cardiovascular system ,medicine ,Pharmacology (medical) ,cardiovascular diseases ,medicine.symptom ,business ,Practolol ,circulatory and respiratory physiology ,medicine.drug - Abstract
1 The administration of 0.5 mg glyceryl trinitrate by chewing and keeping under the tongue increased heart rate in normal subjects in the supine and erect posture. 2 There was no significant difference between the responses in the same subject on repeated administration of glyceryl trinitrate on different days but there was a significant difference between the responses in different subjects. 3 The oral administration of practolol and propranolol reduced the responses to glyceryl trinitrate. The two drugs progressively reduced the increase in heart rate produced by glyceryl trinitrate; there was no significant difference between their effects. Propranolol produced a significantly greater reduction than practolol in the maximum heart rate that was produced by glyceryl trinitrate. 4 The administration of practolol (300 mg) twice daily by mouth to patients after an acute episode of ischaemic heart disease significantly reduced the increases in heart rate produced by standing and by glyceryl trinitrate in comparison to the responses in similar patients receiving a placebo.
- Published
- 1974
6. THE EFFECT OF PREDNISONE TREATMENT ON THE HALF-LIFE OF INTRAVENOUS HYDROCORTISONE
- Author
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Gillian M. Shenfield, J.F. Costello, James W. Paterson, and O. Ijaduola
- Subjects
Pharmacology ,Prednisone treatment ,business.industry ,Half-life ,medicine.disease ,Bioinformatics ,respiratory tract diseases ,Peak plasma ,Prednisone ,Anesthesia ,Papers ,medicine ,Pharmacology (medical) ,business ,hormones, hormone substitutes, and hormone antagonists ,Hydrocortisone ,medicine.drug ,Asthma - Abstract
1 The half-life of hydrocortisone (cortisol) has been measured in six patients before and after a three-week course of prednisone given for asthma. 2 There was considerable variation in peak plasma level of cortisol both within and between patients, but on both occasions the plasma half-lives were the same. 3 It was concluded that short courses of prednisone have no effect on the handling of hydrocortisone.
- Published
- 1974
7. THE EFFECTS OF SALBUTAMOL AND TERBUTALINE ON PHYSIOLOGICAL TREMOR, BRONCHIAL TONE AND HEART RATE
- Author
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Alan Richens and Judith M. Watson
- Subjects
Pharmacology ,Tachycardia ,business.industry ,medicine.drug_class ,Terbutaline ,respiratory system ,Placebo ,respiratory tract diseases ,Bronchodilatation ,Blood pressure ,Anesthesia ,Bronchodilator ,Papers ,Heart rate ,medicine ,Salbutamol ,Pharmacology (medical) ,medicine.symptom ,business ,medicine.drug - Abstract
1 The effects of oral doses of the bronchodilator drugs, salbutamol (4 and 8 mg) and terbutaline (5 and 10 mg), on physiological tremor, bronchial tone, heart rate and blood pressure were studied in six normal subjects. 2 Both drugs produced a significant increase in physiological tremor, compared with placebo. Terbutaline, but not salbutamol, produced a dose related response. No significant differences were observed between drugs. 3 Terbutaline (5 and 10 mg) and salbutamol (8 mg) produced a significant bronchodilatation compared with placebo. Dose related responses were obtained with both drugs, although this reached significance only with terbutaline. 4 Both doses of each drug produced a tachycardia, although this was only statistically significant with the high doses. 5 No significant change in blood pressure was observed with either drug. 6 Peak effects of salbutamol occurred between 1 and 3 h and terbutaline between 1 and 4 hours. Both drugs were still active at 6 hours.
- Published
- 1974
8. A CONTROLLED TRIAL OF PRACTOLOL IN MILD HYPERTENSION
- Author
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I D Strickland, D.M. Chaput, D.W. Vere, De Saintonge, and Clive J. Roberts
- Subjects
Pharmacology ,Pediatrics ,medicine.medical_specialty ,Supine position ,business.industry ,Diastole ,Placebo ,Crossover study ,law.invention ,Double blind ,Blood pressure ,Randomized controlled trial ,law ,Anesthesia ,Papers ,medicine ,Pharmacology (medical) ,business ,Practolol ,medicine.drug - Abstract
1 Fifteen patients with diastolic blood pressures between 90 and 120 mmHg were admitted to a trial comparing placebo with practolol at doses up to 500 mg 12 hourly. 2 The trial was a double blind cross over study. Treatments were allocated at random and each treatment block lasted 12 weeks. 3 Ten patients completed the trial, and none of those who withdrew experienced serious unwanted effects. 4 Practolol caused significant falls in standing systolic and diastolic pressures and the supine diastolic pressure.
- Published
- 1974
9. THE ASSESSMENT OF β-ADRENOCEPTOR BLOCKING DRUGS IN HYPERTHYROIDISM
- Author
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A. Ghosal, Robin G. Shanks, D. G. McDevitt, S.G. Carruthers, and J.K. Nelson
- Subjects
Tachycardia ,endocrine system ,medicine.medical_specialty ,Supine position ,Propranolol ,β adrenoceptor ,Internal medicine ,Heart rate ,polycyclic compounds ,medicine ,Pharmacology (medical) ,In patient ,cardiovascular diseases ,Practolol ,Pharmacology ,business.industry ,Percentage reduction ,respiratory system ,Endocrinology ,Papers ,cardiovascular system ,Cardiology ,medicine.symptom ,business ,circulatory and respiratory physiology ,medicine.drug - Abstract
1 Intravenous propranolol and practolol both reduced resting supine heart rate in patients with hyperthyroidism. Propranolol produced a significantly greater reduction than practolol, which did not have a dose-dependent effect. 2 The effect of these drugs on resting heart rate was much less than their effect on the tachycardias produced both by severe exercise and by standing upright in hyperthyroid patients. Propranolol again produced a significantly greater reduction than practolol in each situation, but practolol did have a dose dependent effect on exercise heart rate. 3 The percentage reduction of standing tachycardia produced by the two drugs appeared to parallel closely the reduction in exercise tachycardia. 4 It is concluded that a simple and convenient way of assessing the activity of β-adrenoceptor blocking drugs in hyperthyroid patients would be to measure their effect on the tachycardia induced by standing. Their effect on resting heart rate should not be used. 5 Practolol may be useful in the management of hyperthyroidism in patients in whom propranolol and similar non-selective β-adrenoceptor blocking drugs are contraindicated.
- Published
- 1974
10. A PILOT STUDY OF ORALLY ADMINISTERED Δ1-TRANS-TETRAHYDROCANNABINOL IN THE MANAGEMENT OF PATIENTS UNDERGOING RADIOTHERAPY FOR CARCINOMA OF THE BRONCHUS
- Author
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R.M. Weatherstone, J.D.P. Graham, B.H. Davies, and R.D. Griffiths
- Subjects
Pharmacology ,Tachycardia ,medicine.medical_specialty ,Bronchus ,business.industry ,organic chemicals ,medicine.medical_treatment ,Placebo ,medicine.disease ,Surgery ,Radiation therapy ,Mood ,medicine.anatomical_structure ,Anesthesia ,Papers ,mental disorders ,medicine ,Carcinoma ,Ingestion ,Pharmacology (medical) ,medicine.symptom ,Tetrahydrocannabinol ,business ,medicine.drug - Abstract
1 Δ(1)-trans-tetrahydrocannabinol (Δ(1)-THC; 10 mg) or a placebo was given orally on 7 days to two groups of six patients on a cross-over pattern with 7 days rest between. 2 The patients were hospitalized, suffering from inoperable bronchogenic carcinoma, subjected to radiation therapy, and anxious. 3 Self-rating mood scales were filled in before, and 2 and 6 h after ingestion on the first and seventh day of medication. 4 Records of sleep, pain, general well-being, temperature, cardiovascular and gastrointestinal parameters were kept. 5 Δ(1)-THC caused drowsiness and improved night sleep, reduced pain, increased fatigue and confusion and reduced elation and vigour; it caused slight tachycardia and hypotension as also did placebo. 6 The effects of Δ(1)-THC were stronger after 2 h than 6 h and no tolerance had developed at 7 days. 7 The management of stressful patients was considered to have been improved by the drug.
- Published
- 1974
11. EFFECT OF THE IMIDAZOLINE-DERIVATIVE ST-91 ON HEART RATE AND BLOOD PRESSURE IN HEALTHY MAN
- Author
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K.I. Saunamäki
- Subjects
Pharmacology ,Bradycardia ,medicine.medical_specialty ,business.industry ,Imidazoline receptor ,RESTING HEART RATE ,Blood pressure ,Oral administration ,Internal medicine ,Papers ,Healthy volunteers ,Heart rate ,medicine ,Cardiology ,Pharmacology (medical) ,medicine.symptom ,business - Abstract
1 ST-91, 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride produces in animal experiments bradycardia, and in larger doses, also hypertension, due to α-sympathomimetic activity and probable central sympathetic inhibition. 2 The effects of ST-91, after oral administration, were studied in 10 healthy volunteers. A dose-dependent, significant decrease of the heart rate was observed. On average the resting heart rate was reduced by 11-19 beats/min (15-29%). During exercise the decrease of the heart rate was less pronounced. After the largest dose there was a fall of the systolic blood pressure during exercise averaging at 14-15 mmHg (11-12%). Otherwise the blood pressure remained unchanged. 3 Eight out of the 10 test-subjects complained of hair-raising and goose-flesh after all doses, due to the α-sympathomimetic effect of the drug. No toxic effects were observed.
- Published
- 1974
12. CHARCOAL HAEMOPERFUSION FOR PARACETAMOL OVERDOSE
- Author
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R.P.H. Thompson, R. A. Willison, B. G. Gazzard, Roger Williams, and M. J. Weston
- Subjects
inorganic chemicals ,Pharmacology ,business.industry ,digestive, oral, and skin physiology ,respiratory system ,equipment and supplies ,Paracetamol overdose ,carbohydrates (lipids) ,visual_art ,Anesthesia ,Papers ,Blood platelet counts ,visual_art.visual_art_medium ,Medicine ,Pharmacology (medical) ,Charcoal ,business - Abstract
1 A controlled trial of charcoal haemoperfusion as an early treatment for paracetamol overdose showed no benefit. 2 The plasma clearances of paracetamol by the charcoal column were variable and disappointingly small (range 4-119 ml/minute). The cumulative amounts removed were also low, mean 1.4 g (range 0.2-5.2 g). 3 No clinical problems were encountered with the technique of haemoperfusion and in particular the drop in blood platelet counts was small (mean fall 16%).
- Published
- 1974
13. INVESTIGATION OF SALBUTAMOL TOLERANCE
- Author
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B.A. Sims
- Subjects
Pharmacology ,Evening ,business.industry ,Airways disease ,Significant difference ,respiratory system ,Placebo ,respiratory tract diseases ,Double blind ,Anesthesia ,Papers ,Salbutamol ,Medicine ,Pharmacology (medical) ,business ,medicine.drug - Abstract
1 A double blind cross-over study was carried out on patients with reversible airways disease attending an out-patient clinic. 2 Twenty patients were given either salbutamol (200 μg) or propellant by aerosol for two week periods and in another study twelve patients were given identical tablets containing either salbutamol (4 mg) or placebo for four week periods. Both forms of therapy were taken four times per day but stopped the evening before attending the clinic. 3 The improvement in FEV1 10 min following salbutamol (200 μg) by aerosol was measured after previous treatment with either salbutamol or placebo administered by aerosol and orally and the results were compared statistically. This failed to show a significant difference and suggests that regular treatment with salbutamol does not lead to a decreased response.
- Published
- 1974
14. PHYSIOLOGICAL RESPONSE TO PROPRANOLOL AND DIAZEPAM IN CHRONIC ANXIETY
- Author
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P.J. Tyrer and M.H. Lader
- Subjects
Pharmacology ,medicine.diagnostic_test ,Respiratory rate ,business.industry ,Propranolol ,Electroencephalography ,Placebo ,Somatic anxiety ,Peripheral ,Anesthesia ,Papers ,Medicine ,Anxiety ,Pharmacology (medical) ,medicine.symptom ,business ,Diazepam ,medicine.drug - Abstract
1 Twelve chronically anxious psychiatric out-patients, comprising six with somatic anxiety and six with psychic anxiety, were treated with (±)-propranolol, diazepam and placebo for one week each in flexible dosage using a balanced cross-over experimental design. 2 After each treatment, in addition to ratings completed by patient and psychiatrist, finger tremor, EEG, averaged auditory evoked response, skin conductance, heart and respiratory rate were measured. 3 Diazepam significantly increased the amount of fast activity (13.5-26 Hz) in the EEG but produced few peripheral effects apart from a reduction in finger tremor. 4 Propranolol had no central physiological effects but reduced both pulse rate and finger tremor. 5 The physiological effects of propranolol in chronic anxiety are different from those of diazepam and therapeutic benefit appears to be due to a direct effect on certain somatic symptoms.
- Published
- 1974
15. ACUTE EFFECT OF ANTIPYRETIC ANALGESICS, ALONE OR IN COMBINATION WITH ALCOHOL, ON HUMAN PSYCHOMOTOR SKILLS RELATED TO DRIVING
- Author
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Mauri J. Mattila, Markku Linnoila, and Timo Seppälä
- Subjects
Pharmacology ,Psychomotor learning ,business.industry ,education ,Poison control ,Acute effect ,Alcohol ,Placebo ,030226 pharmacology & pharmacy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Anesthesia ,Papers ,Phenylbutazone ,medicine ,Pharmacology (medical) ,Antipyretic ,business ,Volunteer ,030217 neurology & neurosurgery ,medicine.drug - Abstract
1 The effect of acetylsalicylic acid (1 g), indomethacin (50 mg), and phenylbutazone (200 mg) on psychomotor skills was examined double blind on 180 volunteer students. Ninety students received ethyl alcohol (0.5 g/kg) and 90 subjects an equal volume of placebo drink in combination with the drugs. 2 Psychomotor skills were measured with a choice reaction test, two co-ordination tests, and a divided attention test, having correlation with traffic behaviour. The subjects assessed their feelings of performance by means of a rating scale. The tests were done 30, 90 and 150 min after the administration of the agents. 3 Acetylsalicylic acid proved inactive whereas both indomethacin and phenylbutazone impaired eye-hand co-ordination and divided attention. Acetylsalicylic acid did not interact with alcohol to a measurable extent whereas indomethacin in combination with alcohol proved less harmful than without it. The deleterious effects of phenylbutazone and alcohol were additive. 4 An impairment of psychomotor skills related to driving by indomethacin and phenylbutazone should be considered when prescribing these drugs to active out-patients.
- Published
- 1974
16. A PHARMACOKINETIC INTERACTION IN MAN BETWEEN PHENOBARBITONE AND FENOPROFEN, A NEW ANTI-INFLAMMATORY AGENT
- Author
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Ridolfo As, Alan Rubin, L. Helleberg, Robert L. Wolen, Charles M. Gruber, and Rodda Be
- Subjects
Pharmacology ,Fenoprofen ,medicine.drug_class ,business.industry ,Urine ,Metabolism ,Anti-inflammatory ,Drug metabolizing enzymes ,Papers ,medicine ,Pharmacology (medical) ,business ,Pharmacokinetic interaction ,medicine.drug - Abstract
1 The effect of repeated administration of phenobarbitone on the plasma disposition of fenoprofen (±-2-(3-phenoxyphenyl) propionic acid) was investigated in rats and man. 2 The plasma elimination rate constants increased significantly and the rats excreted proportionately more metabolized fenoprofen in the urine. These findings are consistent with an increase in the rate of metabolism of fenoprofen. 3 This interaction between phenobarbitone (and presumably other inducers of drug metabolizing enzymes) and fenoprofen should be considered when evaluating the clinical usefulness of fenoprofen.
- Published
- 1974
17. SOME EFFECTS OF KÖ 1313 IN ANIMALS AND MAN
- Author
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Robin G. Shanks and J. M. Kofi Ekue
- Subjects
Pharmacology ,Tachycardia ,medicine.medical_specialty ,business.industry ,Increased heart rate ,Blood flow ,Propranolol ,Femoral artery ,Endocrinology ,Oral administration ,Internal medicine ,Isoprenaline ,medicine.artery ,Papers ,Heart rate ,medicine ,Pharmacology (medical) ,medicine.symptom ,business ,medicine.drug - Abstract
1 Ko 1313 competitively inhibited the increases in heart rate produced by isoprenaline in anaesthetized dogs. 2 Ko 1313 was 35 times more active than propranolol in blocking an isoprenaline induced tachycardia in anaesthetized dogs but only three times more active in blocking the increase in femoral blood flow produced by the injection of isoprenaline into the femoral artery. These observations suggest that Ko 1313 may have some cardio-selective activity. 3 When a series of doses of Ko 1313 was injected intravenously into anaesthetized dogs, the lower doses decreased heart rate while the larger doses increased heart rate. The same doses of propranolol reduced heart rate. 4 In lightly anaesthetized dogs, a series of doses of Ko 1313 progressively increased heart rate while propranolol produced little change. These observations indicate that Ko 1313 has slight intrinsic sympathomimetic activity. 5 The oral administration of Ko 1313 and propranolol had no effect on resting heart rate in man but reduced the increases produced by head-up tilt, standing and exercise.
- Published
- 1974
18. ACETYLATION OF PROCAINE AMIDE IN MAN STUDIED WITH A NEW GAS CHROMATOGRAPHIC METHOD
- Author
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B. Norlander, Lilian Molin, Erling Karlsson, and Folke Sjöqvist
- Subjects
Pharmacology ,Drug ,business.industry ,media_common.quotation_subject ,Metabolite ,Isoniazid ,Renal function ,Urine ,chemistry.chemical_compound ,chemistry ,Acetylation ,Amide ,Papers ,Medicine ,Pharmacology (medical) ,Benzamide ,business ,media_common ,medicine.drug - Abstract
1 A specific gas-chromatographic method was developed for determination of N-acetylprocaine amide in plasma and urine, using 4-amino-N-(2-piperidinoethyl)benzamide as an internal standard. The investigation was performed in 50 cardiac patients who had reached steady-state plasma concentrations of procaine amide. 2 The plasma concentrations of the acetylated metabolite varied between 1.0 and 15.0 μg/ml and were thus of the same order of magnitude as those of the parent drug. Especially high plasma levels of the metabolite were seen in patients with poor kidney function. 3 The urinary excretion of the metabolite varied markedly between individuals and ranged between 6 and 52% of the administered daily dose. There was a clear tendency towards higher rates of acetylation of procaine amide in patients with short plasma half-lives of isoniazid, i.e. the phenotype rapid acetylators. Because of coexisting therapy with other drugs and impaired renal function in some patients studies are required in healthy human volunteers to ascertain whether the acetylation of procaine amide and isoniazid are mediated by the same enzyme system.
- Published
- 1974
19. ACUTE EFFECTS OF VARYING DOSES OF PROPRANOLOL UPON OXYGEN HAEMOGLOBIN AFFINITY IN MAN
- Author
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C.T. Dollery, J. Lyonnais, R.T. Card, J W Kane, and Michael C. Brain
- Subjects
Pharmacology ,Acute effects ,medicine.medical_specialty ,P50 ,Red Cell ,chemistry.chemical_element ,Propranolol ,Oxygen ,chemistry.chemical_compound ,Plasma phosphate ,Endocrinology ,chemistry ,Internal medicine ,Papers ,medicine ,Pharmacology (medical) ,sense organs ,Adenosine triphosphate ,medicine.drug - Abstract
1 The effect of propranolol 2 h following doses of 10, 30, or 100 mg upon the blood oxygen-haemoglobin dissociation curves has been studied in four normal subjects. 2 The pO2 at 50% saturation (p50) was not changed significantly under control conditions or after 10 and 100 mg doses. There was a just significant increase of 2 mmHg in the p50 value after the 30 mg dose. 3 There was no significant change in red cell adenosine triphosphate or 2, 3-diphospho-glycerate nor in plasma phosphate. 4 There was no correlation between plasma propranolol concentration and changes in blood p50.
- Published
- 1974
20. THIOPURINOL: COMPARATIVE ENZYME INHIBITION AND PROTEIN BINDING STUDIES WITH ALLOPURINOL, OXIPURINOL AND 6-MERCAPTOPURINE
- Author
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H.A. Simmonds, David Perrett, B.M. Dean, and R. Grahame
- Subjects
Pharmacology ,Oxipurinol ,business.industry ,Allopurinol ,Plasma protein binding ,Human serum albumin ,Blood proteins ,chemistry.chemical_compound ,Biochemistry ,chemistry ,Papers ,medicine ,Uric acid ,Pharmacology (medical) ,business ,Hypoxanthine ,medicine.drug ,Whole blood - Abstract
1 The metabolites of thiopurinol have been investigated in intact human and pig erythrocytes using [6-(14)C]-thiopurinol, high voltage electrophoresis and automated cation exchange chromatography. 2 Pre-incubation of human erythrocytes in vitro with thiopurinol increased the formation of hypoxanthine from [8-(14)C]-inosine and simultaneously reduced IMP synthesis. 3 Reduced inosine formation, following one week of thiopurinol therapy, has also been observed in vitro using the intact red cells from three patients suffering from gout. 4 Binding of thiopurinol, and to lesser extents of 6-mercaptopurine, uric acid, oxipurinol and allopurinol, has been demonstrated electrophoretically to human and pig serum proteins. 5 Thiopurinol is shown to have a greater binding capacity for purified human serum albumin than uric acid or 6-mercaptopurine at varying substrate and albumin concentrations covering the physiological range. Under these conditions the binding of uric acid is reduced in the presence of thiopurinol. 6 A comparison of the distribution of thiopurinol, 6-mercaptopurine, allopurinol and oxipurinol in whole blood has revealed that allopurinol and oxipurinol are not irreversibly bound to cellular proteins; whereas 30% and 13% of the total cellular uptake was irreversibly bound in the case of thiopurinol and 6-mercaptopurine respectively at substrate levels of 1 nmol per μl blood.
- Published
- 1974
21. THE PERSISTENCE OF ADRIAMYCIN IN MAN AND RAT
- Author
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P. M. Wilkinson and G.E. Mawer
- Subjects
Pharmacology ,Intravenous dose ,business.industry ,Compartment (ship) ,Spleen ,Persistence (computer science) ,medicine.anatomical_structure ,Papers ,Plasma concentration ,Toxicity ,polycyclic compounds ,medicine ,Pharmacology (medical) ,Bone marrow ,business ,Half time - Abstract
1 Adriamycin was administered as a single intravenous dose. The plasma concentration in man and rat decayed as a double exponential function of time. 2 A two compartment model was used to predict plasma and tissue concentrations in man and the rat. The validity of the tissue concentration predictions was confirmed experimentally in the rat. 3 Tissue components had a high capacity for the drug. There was evidence in the rat of preferential accumulation in the liver, spleen and bone marrow. 4 The large tissue capacity and the prolonged half time for elimination predispose to accumulation. This may be responsible for the greater toxicity of treatment schedules with short intervals between consecutive doses.
- Published
- 1974
22. Ro 3-4787, A NEW β-ADRENOCEPTOR BLOCKING AGENT: STUDIES IN NORMAL VOLUNTEERS
- Author
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Paul Turner and J.R. Kilborn
- Subjects
Pharmacology ,business.industry ,Propranolol ,Plasma levels ,β adrenoceptor ,Normal volunteers ,Papers ,Heart rate ,medicine ,Pharmacology (medical) ,Bicycle ergometer ,Inverse correlation ,business ,Fasting state ,medicine.drug - Abstract
1 A new β-adrenoceptor blocking agent, Ro 3-4787, was administered orally to resting subjects. Peak levels of 106.2 ± 15.5 ng/ml were reached after 20 mg given in the fasting state. After intravenous administration, an inverse rectilinear relationship was shown between the log dose (2 mg-20 mg) and the heart rate during vigorous exercise on a bicycle ergometer. 2 A double-blind study in five normal subjects using 0.03 mg/kg and 0.15 mg/kg showed that propranolol and Ro 3-4787 were equally effective in reducing the exercise heart rate. There was an inverse correlation between the log plasma level before exercise and the heart rate during exercise for both drugs over the range studied.
- Published
- 1974
23. THE EFFECT OF DIFFERENT NEBULIZERS WITH AND WITHOUT INTERMITTENT POSITIVE PRESSURE BREATHING ON THE ABSORPTION AND METABOLISM OF SALBUTAMOL
- Author
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Gillian M. Shenfield, James W. Paterson, and Marion E. Evans
- Subjects
Pharmacology ,Lung ,medicine.drug_class ,business.industry ,Positive pressure ,Absorption (skin) ,respiratory system ,Nebulizer ,medicine.anatomical_structure ,Intermittent positive pressure breathing ,Bronchodilator ,Anesthesia ,Papers ,medicine ,Salbutamol ,Asthmatic patient ,Pharmacology (medical) ,business ,medicine.drug - Abstract
1 The absorption and metabolism of [3H]-salbutamol have been studied to assess whether intermittent positive pressure breathing (IPPB) or a particular nebulizer have any advantages in delivering bronchodilator drugs to asthmatic patients. 2 [3H]-salbutamol (10 mg) was given to asthmatic patients from either the Bird Mark 7 ventilator without intermittent positive pressure, the Bird micronebulizer attached to an electric air compressor, or the Wright's nebulizer attached to the same compressor. 3 All patients showed a high early plasma level of radioactivity due mainly to free salbutamol. This pattern suggests absorption from the lung and is similar to that seen after giving the drug from the Bird nebulizer using IPPB. 4 In all cases less than 20% of the original dose was absorbed by the patient. 5 Improvement in forced expiratory volume in one second (FEV1) was seen with all three treatments.
- Published
- 1974
24. THE INFLUENCE OF URINARY pH ON THE ELIMINATION OF MEXILETINE
- Author
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Moira A. Kiddie, Paul Turner, C.M. Kaye, and T. R. D. Shaw
- Subjects
Pharmacology ,Intravenous dose ,Drug ,business.industry ,media_common.quotation_subject ,Urinary system ,Urine ,Mexiletine ,Papers ,medicine ,Pharmacology (medical) ,business ,media_common ,medicine.drug - Abstract
1 The plasma elimination half-life of mexiletine was measured in four subjects when the urine was rendered (a) acidic and (b) alkaline. 2 Urinary acidification (pH 5.0) was associated with a plasma elimination half-life of 2.8 h and 57.5% of the intravenous dose was excreted in the urine within 48 hours. When the urine was alkaline (pH 8.0) the half-life increased to 8.6 h with negligible amounts of drug appearing in the urine. 3 Urinary pH varies widely in cardiac patients and should be controlled or monitored to provide better therapeutic precision with mexiletine.
- Published
- 1974
25. PRELIMINARY ASSESSMENT OF RX 72601, A NEW ANTICHOLINESTERASE IN MAN: REVERSAL OF COMPETITIVE NEUROMUSCULAR BLOCKADE
- Author
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P.W. Dettmar, G. Metcalf, M.H. Smith, Alan Richens, G B Gillett, and A. Hedges
- Subjects
Pharmacology ,Neuromuscular Blockade ,business.industry ,Stimulation ,Acetylcholinesterase ,Neostigmine ,chemistry.chemical_compound ,Atropine ,Blood pressure ,chemistry ,Anesthesia ,Papers ,Muscarinic acetylcholine receptor ,medicine ,Pharmacology (medical) ,business ,medicine.drug ,Whole blood - Abstract
1 The effect of RX 72601, neostigmine plus atropine, or saline on neuromuscular blockade with (+)-tubocurarine was studied in a double blind trial in four healthy male volunteers. 2 The methods used to assess neuromuscular function were voluntary grip strength and indirectly evoked muscle twitches. The muscarinic action was assessed by measuring intestinal motility with a pressure sensitive radio pill, and auscultation of the abdomen. Blood pressure and pulse rate were also recorded. The degree of acetylcholinesterase inhibition achieved in whole blood was determined before and at intervals after the administration of the anticholinesterases. 3 Both RX 72601 (0.66-0.83 mg) and neostigmine (2.5 mg) completely reversed the neuromuscular blockade produced by tubocurarine, but the time course of reversal differed. RX 72601 (0.66-0.83 mg) produced similar inhibition of acetylcholinesterase in whole blood to neostigmine (2.5 mg). The doses of RX 72601 used caused minimal stimulation at muscarinic sites as evidenced by the limited effect on pulse rate and intestinal activity. 4 It was concluded that RX 72601 could be safely used to reverse the effects of neuromuscular blockade without the need for premedication with atropine.
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- 1974
26. BIOAVAILABILITY OF DIGOXIN FROM RAPIDLY DISSOLVING PREPARATIONS
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B. F. Johnson and Susan Lader
- Subjects
Pharmacology ,Chromatography ,Digoxin ,business.industry ,digestive, oral, and skin physiology ,Absorption (skin) ,Intestinal absorption ,Bioavailability ,Tablet dissolution ,Urinary excretion ,Papers ,medicine ,Ingestion ,Pharmacology (medical) ,business ,Dissolution ,medicine.drug - Abstract
1 Intestinal absorption of digoxin was assessed by determination of peak plasma concentrations, areas under plasma concentration curves over 80 h, and 10 day urinary excretion. Absorption was equal after ingestion of single doses of standard Lanoxin (Wellcome) tablets, tablets and capsules of ultra-rapid dissolution rate material, or an oral solution of digoxin in water. 2 Mean plasma concentrations and dosage-interval urinary excretion were highly similar during 14 day courses of either Lanoxin or ultra-rapid dissolution tablets. Increased bioavailability does not result from encapsulation of solid dosage presentations, nor from increasing tablet dissolution rate beyond 75% in 15 minutes. 3 Fourteen day courses of tablets of slow dissolution rate produced lower and less consistent mean plasma concentrations and urinary excretion. Slow dissolution rates are associated with greater individual variability in absorption.
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- 1974
27. DRUGS AND DRIVING.
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SILVERSTONE, T.
- Published
- 1974
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28. THE CLINICAL PHARMACOLOGY OF SALMEFAMOL.
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EVANS, MARION E., SHENFIELD, GILLIAN M., and PATERSON, J.W.
- Abstract
The absorption, excretion and metabolism of [
3 H]-salmefamol, a new sympathomimetic bronchodilator drug, have been studied in asthmatic patients., Following oral administration of 1 or 2 mg to four patients the drug was well absorbed, peak plasma levels occurring from 0.6-2.0 h after administration. An improvement in forced expiratory volume in 1 s (FEV1 ) (ranging from 12-50% above baseline) was seen., Following aerosol administration of 0.22-0.34 mg to four patients a rapid rise in FEV1 was seen (range 26-117%). The plasma and urinary pictures following this route were similar to those seen after oral administration, suggesting that the majority of the dose was swallowed., Very little free salmefamol was found in plasma or urine, the majority being present as metabolites. Urinary radioactivity was mainly present in the form of sulphate conjugates of at least two compounds, one of which was salmefamol. The other compound has not been identified but it is suggested that it may be an active metabolite. [ABSTRACT FROM AUTHOR]- Published
- 1974
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29. THIOPURINOL: COMPARATIVE ENZYME INHIBITION AND PROTEIN BINDING STUDIES WITH ALLOPURINOL, OXIPURINOL AND 6-MERCAPTOPURINE.
- Author
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DEAN, B.M., PERRETT, D., SIMMONDS, H.A., and GRAHAME, R.
- Abstract
The metabolites of thiopurinol have been investigated in intact human and pig erythrocytes using [6-
14 C] -thiopurinol, high voltage electrophoresis and automated cation exchange chromatography., Pre-incubation of human erythrocytes in vitro with thiopurinol increased the formation of hypoxanthine from [8-14 C]-inosine and simultaneously reduced IMP synthesis., Reduced inosine formation, following one week of thiopurinol therapy, has also been observed in vitro using the intact red cells from three patients suffering from gout., Binding of thiopurinol, and to lesser extents of 6-mercaptopurine, uric acid, oxipurinol and allopurinol, has been demonstrated electrophoretically to human and pig serum proteins., Thiopurinol is shown to have a greater binding capacity for purified human serum albumin than uric acid or 6-mercaptopurine at varying substrate and albumin concentrations covering the physiological range. Under these conditions the binding of uric acid is reduced in the presence of thiopurinol., A comparison of the distribution of thiopurinol, 6-mercaptopurine, allopurinol and oxipurinol in whole blood has revealed that allopurinol and oxipurinol are not irreversibly bound to cellular proteins; whereas 30% and 13% of the total cellular uptake was irreversibly bound in the case of thiopurinol and 6-mercaptopurine respectively at substrate levels of 1 nmol per μl blood. [ABSTRACT FROM AUTHOR]- Published
- 1974
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30. THE NEW JOURNAL.
- Author
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WILSON, G.M.
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- 1974
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31. THE EFFECTS OF ORAL AH 5158, A COMBINED α AND β-ADRENOCEPTOR ANTAGONIST, IN HEALTHY VOLUNTEERS.
- Author
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RICHARDS, D.A., WOODINGS, E.P., STEPHENS, M.D.B., and MACONOCHIE, J.G.
- Abstract
In healthy male volunteers after single oral doses, AH 5158 produced inhibition of exercise induced tachycardia, falls in systolic and diastolic pressure at rest and in response to exercise, which are probably related to combined β- and α-adrenoceptor antagonism., At increasing doses from 100 mg to 400 mg there exists a dose related antagonistic effect, though the dominant effect of β-adrenoceptor antagonism is more easily demonstrable than is α antagonism., As indicated by the pattern of pharmacological effects, absorption of the oral drug is good and the duration of action of a 400 mg dose is approximately 8 hours., Despite being administered in β-adrenoceptor blocking doses, AH 5158 had no adverse effects upon peak expiratory flow at rest or in response to exercise., It is concluded that the pharmacological profile of this combined α- and β-adrenoceptor antagonism suggests a potential therapeutic role as an antihypertensive drug. [ABSTRACT FROM AUTHOR]
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- 1974
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32. COMPARISON OF THE THERAPEUTIC EFFECTIVENESS OF APRINDINE, PROCAINAMIDE AND QUINIDINE IN CHRONIC VENTRICULAR DYSRHYTHMIAS.
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DURME, J.P., BOGAERT, M.G., and ROSSEEL, M.T.
- Abstract
A cross-over study with aprindine (100 mg daily after a loading dose of 200 mg), procainamide (4 times 1000 mg daily) and quinidine bisulphate (2 times 750 mg daily), all given orally, was performed in seventeen patients with stable chronic premature ventricular contractions following healed myocardial infarction., The effectiveness of the treatment was evaluated during three consecutive weeks by continuous ambulatory tape recording of the electrocardiogram and repeated determinations of plasma levels were done., The results showed that aprindine was more effective than procainamide and quinidine., For the three drugs the therapeutic plasma levels varied markedly from patient to patient, but for each patient taken individually, the therapeutic activity could be correlated with the plasma levels. [ABSTRACT FROM AUTHOR]
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- 1974
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33. A PRELIMINARY STUDY OF THE EFFECT OF NORFENFLURAMINE ON LIPOGENESIS BY HUMAN ADIPOSE TISSUE In vitro.
- Author
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ASHWELL, MARGARET
- Abstract
Norfenfluramine is thought to be the major active metabolite of fenfluramine in man. Therefore its in vitro effect on lipogenesis in human adipose tissue from twelve patients was investigated., Although inhibition of lipogenesis was demonstrated, the concentrations of norfenfluramine necessary (>1 mM) were much higher than normal blood levels of the drug., There was no correlation between the degree of inhibition by norfenfluramine in vitro and fat cell size, age or relative weight of the subject. Greater degrees of inhibition were however associated with samples of tissue from patients with higher blood glycerol concentrations and lower blood triglyceride concentrations. [ABSTRACT FROM AUTHOR]
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- 1974
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34. PHYSIOLOGICAL RESPONSE TO PROPRANOLOL AND DIAZEPAM IN CHRONIC ANXIETY.
- Author
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TYRER, P.J. and LADER, M.H.
- Abstract
Twelve chronically anxious psychiatric out-patients, comprising six with somatic anxiety and six with psychic anxiety, were treated with (±)-propranolol, diazepam and placebo for one week each in flexible dosage using a balanced cross-over experimental design., After each treatment, in addition to ratings completed by patient and psychiatrist, finger tremor, EEG, averaged auditory evoked response, skin conductance, heart and respiratory rate were measured., Diazepam significantly increased the amount of fast activity (13.5-26 Hz) in the EEG but produced few peripheral effects apart from a reduction in finger tremor., Propranolol had no central physiological effects but reduced both pulse rate and finger tremor., The physiological effects of propranolol in chronic anxiety are different from those of diazepam and therapeutic benefit appears to be due to a direct effect on certain somatic symptoms. [ABSTRACT FROM AUTHOR]
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- 1974
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35. LITHIUM TREATMENT STRONGLY INHIBITS CHOLINE TRANSPORT IN HUMAN ERYTHROCYTES.
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LEE, G., LINGSCH, C., LYLE, P.T., and MARTIN, K.
- Abstract
The influx of [
14 C] -choline and the efflux of22 Na in human erythrocytes were measured in vitro using blood from patients treated with lithium, patients not on lithium and healthy individuals., The administration of lithium to patients significantly reduces the transport of choline; during the first 6 weeks of treatment the influx of choline is about half the normal rate, later it falls to around 10%., This inhibition of choline transport is not dependent on the presence of lithium in the incubation medium. 4 The active and passive efflux of sodium are apparently not affected by lithium treatment. [ABSTRACT FROM AUTHOR]- Published
- 1974
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36. DIALYSIS OF DRUGS in vitro.
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CLARKE, LESLEY
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- 1974
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37. PHYSIOLOGICAL AND PSYCHOLOGICAL EFFECTS OF ±-PROPRANOLOL, +-PROPRANOLOL AND DIAZEPAM IN INDUCED ANXIETY.
- Author
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TYRER, P.J. and LADER, M.H.
- Abstract
Four equal-sexed groups of eight normal subjects were given single doses of either (±)-propranolol (120 mg), (+)-propranolol (120 mg), diazepam (6 mg) or placebo using double-blind procedure and their effects studied under three types of experimental stress and at rest., Finger tremor, EEG, averaged auditory evoked response, skin conductance, heart rate and respiratory rate were measured at each time of testing, and subjects also completed performance tests (reaction time, tapping speed and symbol copying) and subjective mood scales., Neither (+)- nor (±)-propranolol had any beneficial effects on mood and physiological tests showed that, although adequate β-adrenoceptor blockade was achieved, there was no evidence of sedation., Diazepam reduced subjective anxiety, significantly lessened the main amplitude of the auditory evoked response and also reduced the proportion of slower rhythms in the EEG., The results suggest that (+)- and (±)-propranolol have no psychotropic effects on induced anxiety and that their modes of action are fundamentally different from that of diazepam. [ABSTRACT FROM AUTHOR]
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- 1974
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38. A COMPARISON OF THE EFFECTS OF PROSTAGLANDIN E2 AND SALBUTAMOL BY INTRAVENOUS INFUSION ON THE AIRWAYS OBSTRUCTION OF PATIENTS WITH ASTHMA.
- Author
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SMITH, A.P.
- Abstract
The effects of intravenous infusion of prostaglandin E
2 (PGE2 ) on forced expiratory volume in 1 second (FEV1 ) were studied in ten asthmatic patients and compared with the effects of intravenous salbutamol., PGE2 at infusion rates of 5, 10 and 20 μg/min for three 15 min periods resulted in a small bronchodilator effect in four patients, bronchoconstriction in four, and had no measurable effect on FEV1 in two patients; side effects were frequent and it was concluded that PGE2 was unsuitable for use in the management of attacks of asthma., In the same subjects bronchodilatation occurred during infusion of salbutamol at flow rates of 5, 10 and 20 μg/min (six patients), 10, 20 and 40 μg/min (two patients) and 20, 40 and 80 μg/min (two patients). Serious cardiovascular effects were not encountered at flow rates of less than 20 μg/minute. [ABSTRACT FROM AUTHOR]- Published
- 1974
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39. THE CLINICAL PHARMACOLOGY OF VILOXAZINE HYDROCHLORIDE-A NEW ANTIDEPRESSANT OF NOVEL CHEMICAL STRUCTURE.
- Author
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BAYLISS, P.F.C. and DUNCAN, S.M.
- Abstract
The clinical pharmacological properties of viloxazine hydrochloride (ICI 58, 834, Vivalan), a new antidepressant of novel chemical structure, have been investigated in a series of double-blind randomized studies comparing it with placebo and imipramine. Throughout the studies, viloxazine hydrochloride was given in single doses of 100 mg (expressed as base), and imipramine hydrochloride was given in single doses of 50 mg (expressed as salt)., The effect of viloxazine upon the following parameters was measured: pulse rate, blood pressure, forced expiratory volume, reaction time, critical flicker frequency, salivary flow, pupil size and palpebral fissure size. In addition, the possible interaction between viloxazine and alcohol was investigated using measurements of reaction time., Both viloxazine and imipramine produced a transient tachycardia, but no consistent effect on blood pressure was seen. Neither drug had any effect upon forced expiratory volume., The differences that emerged between viloxazine and imipramine were that viloxazine depressed critical flicker frequency whereas imipramine did not, and imipramine prolonged reaction time whilst viloxazine did not. Imipramine reduced salivary flow and increased the size of the pupil and palpebral fissure. Viloxazine did neither., Imipramine was shown to potentiate alcohol whereas, at the doses used, viloxazine did not., It is concluded that viloxazine appears to have less anticholinergic and possibly less sympathomimetic properties than imipramine. It is also concluded that viloxazine, unlike imipramine, does not potentiate alcohol. [ABSTRACT FROM AUTHOR]
- Published
- 1974
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40. PLASMA CONCENTRATIONS OF METHIMAZOLE, A METABOLITE OF CARBIMAZOLE, IN HYPERTHYROID PATIENTS.
- Author
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SKELLERN, G.G., STENLAKE, J.B., WILLIAMS, W.D., and McLARTY, D.G.
- Abstract
Carbimazole was administered to nine hyperthyroid patients, and blood samples were taken at various time intervals for analysis of carbimazole, and its metabolite methimazole., A technique was developed for the measurement of methimazole in serum, using a High-Pressure Liquid Chromatograph, which could detect nanogram quantities of this metabolite., After a single oral dose, the patients' blood levels appeared to fall into two groups, either those with a maximum concentration of methimazole between 30 and 60 min, or those whose maximum was 2 to 3 hours., The results would suggest that there could be a correlation between the high level of methimazole in serum and the high thyroxine concentration found in some patients. [ABSTRACT FROM AUTHOR]
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- 1974
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41. CHARCOAL HAEMOPERFUSION FOR PARACETAMOL OVERDOSE.
- Author
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GAZZARD, B.G., WILLSON, R.A., WESTON, M.J., THOMPSON, R.P.H., and WILLIAMS, R.
- Abstract
A controlled trial of charcoal haemoperfusion as an early treatment for paracetamol overdose showed no benefit., The plasma clearances of paracetamol by the charcoal column were variable and disappointingly small (range 4-119 ml/minute). The cumulative amounts removed were also low, mean 1.4 g (range 0.2-5.2 g)., No clinical problems were encountered with the technique of haemoperfusion and in particular the drop in blood platelet counts was small (mean fall 16%). [ABSTRACT FROM AUTHOR]
- Published
- 1974
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42. THE PERSISTENCE OF ADRIAMYCIN IN MAN AND RAT.
- Author
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WILKINSON, P.M. and MAWER, G.E.
- Abstract
Adriamycin was administered as a single intravenous dose. The plasma concentration in man and rat decayed as a double exponential function of time., A two compartment model was used to predict plasma and tissue concentrations in man and the rat. The validity of the tissue concentration predictions was confirmed experimentally in the rat., Tissue components had a high capacity for the drug. There was evidence in the rat of preferential accumulation in the liver, spleen and bone marrow., The large tissue capacity and the prolonged half time for elimination predispose to accumulation. This may be responsible for the greater toxicity of treatment schedules with short intervals between consecutive doses. [ABSTRACT FROM AUTHOR]
- Published
- 1974
- Full Text
- View/download PDF
43. EFFECT OF CAFFEINE ON SLEEP: EEG STUDY IN LATE MIDDLE AGE PEOPLE.
- Author
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BŘEZINOVÁ, VLASTA
- Abstract
The effect of caffeine alkaloid base (300 mg) on whole night sleep was investigated by electrophysiological techniques in six late middle age subjects (mean age 56 years), comparison being made with decaffeinated coffee and with no drink prior to sleep, using each condition five times in a balanced order on non-consecutive nights., After caffeine the mean total sleep time decreased on average by 2 h, the mean sleep latency increased to 66 minutes. The number of awakenings increased and the mean total intervening wakefulness was more than doubled after caffeine., In the first 3 h of sleep a decreased amount of stage 3 + 4 was observed, accompanied by an increased amount of stage 2 and of intervening wakefulness, without a significant change in the amount of rapid eye movement sleep., The change in sleep pattern observed suggests an increased capability for arousal and decreased ability to develop or sustain deeper stages of non-rapid eye movement sleep after caffeine. [ABSTRACT FROM AUTHOR]
- Published
- 1974
- Full Text
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44. PHENYTOIN DOSE ADJUSTMENT IN EPILEPTIC PATIENTS.
- Author
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MAWER, G.E., MULLEN, P.W., RODGERS, MARGARET, ROBINS, A.J., and LUCAS, S.B.
- Abstract
A preliminary survey showed that many outpatients with partially controlled epilepsy had serum concentrations of phenytoin below the recommended therapeutic range (10-20 μg/ml). A phenytoin tolerance test was devised with the intention of predicting a more adequate daily dose for such a patient., Fifteen patients were each given an oral test dose of 600 mg phenytoin sodium and the serum concentration of phenytoin was measured at intervals over 48 h; the concentration rose during the first 4 h and decayed between 12-48 h as an almost linear function of time., The serum concentration/time curves were fitted by an iterative computer program based on the Michaelis-Menten equatioa The mean saturated rate of elimination of phenytoin was 435 mg/day and the serum concentration ( K
m ) corresponding with 50% saturation was 3.8 μg/ml. The mean calculated dose of phenytoin sodium required for a steady state serum concentration of 10-20 μg/ml was 345-400 mg/day., The Michaelis-Menten principle was used to predict steady state serum phenytoin concentrations in individual patients receiving daily doses of phenytoin sodium adjusted by steps of 100 mg. The serum concentrations tended to be either too low or too high. The steep relationship between phenytoin concentration and dose indicates that when the concentration reaches 5-10 μg/ml it is then appropriate to adjust dose by small steps of about 25 mg. [ABSTRACT FROM AUTHOR]- Published
- 1974
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45. EFFECTS OF FOOD AND EXERCISE ON THE ABSORPTION OF EFFERVESCENT ASPIRIN.
- Author
-
VOLANS, G.N.
- Abstract
The absorption of effervescent aspirin was studied in normal volunteers of both sexes under varied conditions of activity in both fasting and non-fasting states., Moderate activity resulted in no significant changes in absorption compared with that at rest., In non-fasting subjects the absorption was reduced but this reduction was attenuated with time until after 60 min the plasma levels were similar., There was no interaction between the resting/non-resting and fasting/non-fasting absorption. [ABSTRACT FROM AUTHOR]
- Published
- 1974
- Full Text
- View/download PDF
46. Ro 3-4787, A NEW β-ADRENOCEPTOR BLOCKING AGENT: STUDIES IN NORMAL VOLUNTEERS.
- Author
-
KILBORN, J.R. and TURNER, P.
- Abstract
A new β-adrenoceptor blocking agent, Ro 3-4787, was administered orally to resting subjects. Peak levels of 106.2 ±15.5 ng/ml were reached after 20 mg given in the fasting state. After intravenous administration, an inverse rectilinear relationship was shown between the log dose (2 mg-20 mg) and the heart rate during vigorous exercise on a bicycle ergometer., A double-blind study in five normal subjects using 0.03 mg/kg and 0.15 mg/kg showed that propranolol and Ro 3-4787 were equally effective in reducing the exercise heart rate. There was an inverse correlation between the log plasma level before exercise and the heart rate during exercise for both drugs over the range studied. [ABSTRACT FROM AUTHOR]
- Published
- 1974
- Full Text
- View/download PDF
47. OBSERVATIONS ON THE EFFECT OF β-ADRENOCEPTOR BLOCKING DRUGS ON GLYCERYL TRINITRATE TACHYCARDIA.
- Author
-
EKUE, J.M. KOFI, SHANKS, R.G., and WALSH, M.J.
- Abstract
The administration of 0.5 mg glyceryl trinitrate by chewing and keeping under the tongue increased heart rate in normal subjects in the supine and erect posture., There was no significant difference between the responses in the same subject on repeated administration of glyceryl trinitrate on different days but there was a significant difference between the responses in different subjects., The oral administration of practolol and propranolol reduced the responses to glyceryl trinitrate. The two drugs progressively reduced the increase in heart rate produced by glyceryl trinitrate; there was no significant difference between their effects. Propranolol produced a significantly greater reduction than practolol in the maximum heart rate that was produced by glyceryl trinitrate., The administration of practolol (300 mg) twice daily by mouth to patients after an acute episode of ischaemic heart disease significantly reduced the increases in heart rate produced by standing and by glyceryl trinitrate in comparison to the responses in similar patients receiving a placebo. [ABSTRACT FROM AUTHOR]
- Published
- 1974
- Full Text
- View/download PDF
48. THE EFFECT OF INDORAMIN ON PERIPHERAL BLOOD FLOW.
- Author
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ROYDS, R.B. and LOCKHART, J.D.F.
- Abstract
The effect of indoramin, a new hypotensive agent, on peripheral blood flows of six normal subjects was determined and compared to placebo in a double-blind, randomized study., Indoramin (0.25 mg/kg), administered intravenously, resulted in an increased forearm muscle volume as measured by strain gauge plethysmography and an increase in the skin temperature of the hand but not to the skin of the chest., It is concluded that these effects are the result of α-adrenoceptor blockade. [ABSTRACT FROM AUTHOR]
- Published
- 1974
- Full Text
- View/download PDF
49. SOME EFFECTS OF KÖ 1313 IN ANIMALS AND MAN.
- Author
-
EKUE, J.M. KOFI and SHANKS, R.G.
- Abstract
Kö 1313 competitively inhibited the increases in heart rate produced by isoprenaline in anaesthetized dogs., Kö 1313 was 35 times more active than propranolol in blocking an isoprenaline induced tachycardia in anaesthetized dogs but only three times more active in blocking the increase in femoral blood flow produced by the injection of isoprenaline into the femoral artery. These observations suggest that Kö 1313 may have some cardio-selective activity., When a series of doses of Kö 1313 was injected intravenously into anaesthetized dogs, the lower doses decreased heart rate while the larger doses increased heart rate. The same doses of propranolol reduced heart rate., In lightly anaesthetized dogs, a series of doses of Kö 1313 progressively increased heart rate while propranolol produced little change. These observations indicate that Kö 1313 has slight intrinsic sympathomimetic activity., The oral administration of Kö 1313 and propranolol had no effect on resting heart rate in man but reduced the increases produced by head-up tilt, standing and exercise. [ABSTRACT FROM AUTHOR]
- Published
- 1974
- Full Text
- View/download PDF
50. THE DISTRIBUTION OF PROPRANOLOL BETWEEN BLOOD AND PLASMA IN HYPERTENSIVE PATIENTS.
- Author
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SAWCHUK, R.J., ROBAYO, J., and MILLER, K.W.
- Published
- 1974
- Full Text
- View/download PDF
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