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Biomedical subjects

K Ghose

Publications and source records attributed to K Ghose.

At least 19 recordsLinked to original sources
PubMed2000

Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers.

OBJECTIVES: To determine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of S- and R-verapamil (given as racemates) at steady state. METHODS: Nine healthy male volunteers followed a randomised cross-over study comprising two treatment periods. Pretreatments of 200 ml orange juice (control) or grapefruit juice twice daily for 5 days and 120 mg verapamil (orally) twice daily for 3 days were given. On the study day, the subjects received the morning dose of verapamil with either orange juice (control) or grapefruit juice. Plasma and urine samples were collected for measurement of S- and R-verapamil and the metabolites S- and R-norverapamil. Blood pressure (BP), heart rate (HR) and PR-interval were monitored. RESULTS: During the grapefruit juice period, the steady-state peak and trough concentrations of S-verapamil were moderately increased (peak 41+/-25 ng ml(-1) versus 26+/-13 ng ml(-1), trough 14+/-7 ng ml(-1) versus 12+/-6 ng ml(-1), P=0.08). Grapefruit juice significantly increased the area under the plasma concentration-time curve during the 12-h dose interval (AUC0-12 h) of S-verapamil by 36% (292+/-146 ng h ml(-1) versus 215+/-102 ng h ml(-1), P=0.04). Similar results were obtained for peak and trough concentrations of R-verapamil. The AUC0-12 h of R-verapamil was increased by 28% (1022+/-412 ng h ml(-1) versus 800+/-316 ng h ml(-1), P=0.04). Elimination half-life and renal clearance of both S- and R-verapamil were not affected. Considerable inter-subject variability in interaction was shown. There were no significant differences in the pharmacodynamic parameters (BP, HR and PR-interval). CONCLUSIONS: The present study has demonstrated an interaction between verapamil and grapefruit juice, which is likely due to an inhibition of intestinal metabolism resulting in increased oral bioavailability.

Adult↗
PubMed1998

Mode of action and adverse effects of lipid lowering drugs.

Serum lipids, cholesterol and triglycerides are incorporated into hydrophilic lipoproteins, which include chylomicrons, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL). An elevated level of these lipoproteins, except for HDL, is the basis of all hyperlipidemias. However, only some of the lipoprotein fractions, particularly LDL and remnant particles, are potential risk factors for atherogenesis and subsequent cardiovascular disease. Several classes of pharmacological agents are currently available to increase the breakdown and reduce the synthesis of LDL and remnant factors. These include nicotinic acid and its analogs, fibric acid derivatives (e.g., clofibrate, gemfibrozil, bezafibrate), bile acid resins (e.g., cholestyramine), HMG-CoA reductase inhibitors (e.g., lovastatin, simvastatin, pravastatin) and probucol. Lipid lowering drugs of different classes have a synergistic effect on lipid metabolism and combination therapy is often used. Lipid lowering drugs are prescribed as long-term preventive therapy in apparently asymptomatic people. Several studies indicate that secondary prevention with lipid lowering drugs is cost-effective, particularly in patients with symptomatic coronary artery disease.

Journal Article↗
PubMed1998

Prophylactic sodium valproate therapy in patients with drug-resistant migraine.

We assessed the efficacy of sodium valproate as a prophylactic agent in migraine headache. A prospective randomized study was conducted in adult patients who previously derived no significant benefit from most conventional prophylactic therapy for migraine. Twenty-seven patients with a diagnosis of migraine with aura or migraine without aura from a headache clinic received low dose sodium valproate for 3 months. Response to therapy was defined as 50% or greater reduction in the frequency of headache. Plasma drug level monitoring helped to identify four noncompliers who were excluded from the study. Seventeen (71%) patients observed improvement within 4-6 weeks of medication and remained well for 12 weeks. They were further followed up for 12-24 months. Two patients for side effects and 1 for nondrug-related problems were withdrawn from follow-up study. Twelve patients (60%) maintained their response for 12 months or longer. Clinical improvement (percentage reduction in the frequency of migraine attacks) correlated inversely with the plasma drug levels at 13-24 months and daily dose of valproate, among the responders, suggestive of a possible therapeutic window. In other words, patients who do not respond to low dose valproate are unlikely to benefit from further increase in dosage.

Adolescent↗
PubMed1994

Chronic lithium neurotoxicity presenting as Parkinson's disease.

A 71 year old man who had been on lithium for 9 years for mania presented with an encephalopathic illness which was almost certainly due to lithium intoxication. Having recovered from this acute episode (although he was left with some sequelae) he was recommenced on lithium for his manic symptoms with a careful control of his blood levels. After remaining fairly stable for 8 years he presented with features suggestive of Parkinsonism and was admitted to hospital for investigation. There was no history of taking additional medication such as antidepressants or antipsychotics. He died in hospital and a post-mortem examination confirmed the cause of death as acute myocardial infarction. However histological examination of the brain revealed neurological sequelae of chronic lithium intoxication. There was no evidence of degenerative condition such as Parkinsonism or Alzheimer's disease.

Aged↗
PubMed1993

Cystitis and nonsteroidal antiinflammatory drugs: an incidental association or an adverse effect?

AIMS: Cystitis, a rare adverse effect of systematically administered drugs, was first reported to be associated with a nonsteroidal antiinflammatory drug, tiaprofenic acid, in 1991. Similar reports of adverse effect of tiaprofenic acid were received by a number of national drug monitoring centres. It was therefore decided to investigate the frequency of cystitis associated with tiaprofenic acid and to see whether this association is typical of tiaprofenic acid or also occurs with other nonsteroidal antiinflammatory drugs. METHODS: The Medicines Adverse Reaction Monitoring Centre has been monitoring drug related events/reactions since 1965. An analysis of the spontaneous adverse reaction reports received at this centre during the period 1965-92 was carried out. RESULTS: Haemorrhagic cystitis was reported to be associated with tiaprofenic acid (n = 3) and indomethacin (n = 3). In addition 11 other reports of haematuria (not associated with any coagulopathy and/or hepatic disorders) in relation to other nonsteroidal antiinflammatory drugs, such as diclofenac, ketoprofen, naproxen and piroxicam were received. Five patients who were rechallenged with the suspect drug, suffered from recurrence of cystitis/haematuria. CONCLUSIONS: In addition to tiaprofenic acid, cystitis appears to be associated with indomethacin and possibly also with other nonsteroidal antiinflammatory drugs. An allergic or immunological mechanism is probably responsible for this reaction. Although our centre received the first report of cystitis in relation to indomethacin in 1966, judging by the number of reports received, this association appears to be poorly recognised.

Adolescent↗
PubMed1993

Nurses' attitudes to and knowledge of medicines.

Nurses are often required to give information about prescribed medication to patients. This study obtained information about the attitudes to, and knowledge of, prescribed medication from a group of 70 students and 24 registered nurses at the Otago Polytechnic. A self administered questionnaire, previously used in a community survey in Southampton, UK, was used for this purpose. No significant difference between the two groups was observed. Thirty three (35%) of all the responders kept their unused medicines, 19 (20%) disposed them in the household wastes and only 6 (6.3%) returned them to the pharmacist. About 13 (14%) admitted taking medication prescribed for someone else and 16 (17%) allowed others to use their prescribed medication. Out of the 51 responders who took a prescribed medicine in the past month, only 31 (61%) were aware of potential side effects. Although it is reassuring to know that students and registered nurses are aware of potential problems related to taking medication, clearly there is considerable room for improvement. This should include further information and appreciation of safe disposal methods, what to do if a dose is missed and the dangers of taking another person's prescribed medications.

Adult↗
PubMed1990

Pharmacokinetics and pharmacodynamics of the ace inhibitor benazepril hydrochloride in the elderly.

The pharmacokinetics and pharmacodynamics of a single oral dose benazepril.HCl 10 mg have been studied in 15 healthy volunteers aged 65 to 80 y. The kinetics of unchanged benazepril and its active metabolite benazeprilat did not differ significantly in males and females, so the combined kinetic data from all 15 elderly subjects were compared with a historical control group of 19-32 year-old healthy men treated in the same way. The disposition of benazepril was not affected by age. The time to maximum plasma concentration, tmax (0.5 h) and elimination half-life (0.6 h) in the elderly were the same as in young subjects. The kinetics of benazeprilat was slightly changed in the elderly; although its tmax (1.5 h) was not affected, Cmax and the AUC were 20-40% greater. The elimination half-life of benazeprilat during the first 24 h after dosing in the elderly was increased by about 20% to 3.2 h. The renal plasma clearance of benazeprilat (18.1 ml.min-1) was about 20% smaller than in the young subjects. An average of 18.5% of the dose was recovered as benazeprilat in the 24 h urine from the elderly subjects, which was similar to the recovery in the young subjects. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 95%, respectively). Mean systolic and diastolic blood pressures in the elderly were reduced by a maximum of 37/16 mm Hg at 6 h, in association with a small rise in pulse rate. Treatment was generally well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Pharmacokinetics of lofepramine and amitriptyline in elderly healthy subjects.

Pharmacokinetics of 3 doses (70 mg, 105 mg and 140 mg) of lofepramine were compared with amitriptyline (50 mg) in 6 healthy drug free elderly subjects aged between 65 and 72 years. Pharmacokinetics of lofepramine in the elderly appear to be similar to young adults as published before. Peak plasma lofepramine and amitriptyline concentrations were achieved at about 1 h and 3 h of dosing respectively. Elimination half-life of lofepramine was 2.5 h and that of amitriptyline was 31 h. A 24-fold inter-individual variation in peak plasma lofepramine concentrations was observed, but amitriptyline levels in plasma showed less variation. Pharmacokinetic parameters of amitriptyline were comparable to other published studies involving elderly people. Compared to placebo and lofepramine, amitriptyline produced drowsiness and dry mouth, reduced salivary volume and increased movement reaction time. These effects correlated with the plasma amitriptyline levels.

Aged↗
PubMed1989

Pizotifen in deafferentation pain.

Deafferentation pain is known usually to be resistant to both narcotic and non-narcotic analgesics. Four cases of this condition are reported here in which benefit was obtained with pizotifen, a 5-hydroxytryptamine antagonist. Further controlled clinical studies are required to verify this observation.

Afferent Pathways↗
PubMed1987

A double-blind comparison of the pharmacodynamic effects of single doses of lofepramine, amitriptyline and placebo in elderly subjects.

In a double-blind five-way cross-over study, six drug free healthy elderly subjects received single oral doses of lofepramine (70 mg, 105 mg and 140 mg), amitriptyline (50 mg) and matched placebo tablets. A dose related increase in plasma drug levels and pharmacological effects of lofepramine was observed. Lofepramine (140 mg) improved psychomotor performance (choice reaction time and letter cancellation), but no such change was seen with lower dose regimes or placebo. No significant differences between lofepramine and placebo were observed in other parameters measured. Amitriptyline, as expected, reduced salivary volume, produced drowsiness and impaired psychomotor performance. These changes correlated with plasma amitriptyline levels. The incidence of subjective side-effects with amitriptyline was also higher than that of lofepramine or placebo. In the dosage used, lofepramine exhibited no deleterious effect on the peripheral cholinergic system or psychomotor performance. This drug therefore is likely to be a relatively safe antidepressant for the elderly, but further investigations during long-term medication are required to verify these observations.

Aged↗
PubMed1987

Oxpentifylline in dementia: a controlled study.

The effect of oxpentifylline on mental state of patients suffering from primary degenerative dementia (PDD) and multi-infarct dementia (MID) was investigated in a double-blind study. After an initial 2-weeks washout period, the patients were randomly selected to receive either 400 mg oxpentifylline thrice daily or matched placebo tablets for 12 weeks. Eighteen male and 18 female patients aged 60-88 years were included but 5 patients dropped out during the first 2 weeks of the trial due to poor motivation. Two patients for non compliance and one for protocol violation were further excluded from final analysis. The age and sex distribution of the patients receiving placebo were comparable to those of treated patients. The mean pre-entry severity of dementia, as assessed by Folstein's mini mental state (FMMS) and Sandoz Clinical Assessment Geriatric Scale (SCAGS), was greater in the latter group (p less than 0.05). Although both groups showed slight improvement at the end of 12 weeks' treatment, no significant drug-related progress was observed. However, the MID patients (n = 4) who received oxpentifylline showed greater improvement (p less than 0.05) than the MID patients (n = 7) who were treated with placebo. No such benefit was observed in oxpentifylline-treated PDD patients. It is, therefore, suggested, that oxpentifylline (a haemorrheological agent), is probably beneficial only in MID patients, but further long-term studies involving a larger number of patients are required.

Aged↗
PubMed1986

Diurnal variation of serum copper and zinc in epileptics receiving anti-convulsants.

Serial measurements of copper and zinc concentrations in serum were made at 06.00, 14.00, 22.00 and again at 06.00 hours in 37 male patients with epilepsy, aged between 9 and 19 years. Anticonvulsant drugs were administered at 08.00 and 20.00 hours, and standard hospital meals were allowed at 07.30, 12.00, 16.00 and 19.00 hours. Similar to our previous results, eight patients (21.6%) had serum copper levels greater than the reference range (11.0-20.5 mumol/l) and this hypercupraemia was associated with carbamazapine and/or phenytoin medication. No diurnal variation in serum copper level was observed. Serum copper concentration had no correlation with either 24 h urinary copper excretion or serum anti-convulsant drug levels. Serum zinc concentrations were within the reference range (10-16.5 mumol/l), confirming our previous report. No relation with anti-convulsant medication or serum copper levels was found. Diurnal variations in serum zinc levels with peak and trough concentrations at 06.00 and 14.00 hours, respectively, were observed. It is proposed that these variations in serum zinc concentrations are a normal physiological process and is unlikely to be related to anti-convulsant drugs or epilepsy.

Adolescent↗