Altered pharmacokinetics of propranolol in hyperthyroidism [proceedings].
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Humans↗
Biomedical subjects
J Feely
Publications and source records attributed to J Feely.
Propranolol, triiodothyronine, reverse triiodothyronine and thyroid disease.
Propranolol alone was given to sixteen hyperthyroid, and concomitantly with thyroxine therapy to ten hypothyroid patients. Following treatment of the hyperthyroid group for 1-2 weeks there was a significant decrease in serum triiodothyronine (T3) which correlated with the plasma propranolol steady state concentration. The serum reverse T3 (rT3) rose significantly. Weight loss ceased in this group while weight gain occurred in patients who had a marked fall in serum T3. One patient with T3 toxicosis went into remission. The reduction in serum T3 was maintained in six patients receiving propranolol for more than 1 month. In the hypothyroid group the mean serum T3 level achieved with 0.15 mg thyroxine per day was significantly lower than in a control group who did not receive propranolol. In five patients following propranolol withdrawal there was a significant rise in T3, a fall in rT3 and TSH, and weight loss. Propranol may therefore have a clinically significant and direct action on the peripheral conversion of thyroxine to T3 and rT3.
Adolescent↗
The physiology of thyroid function in pregnancy.
Pregnancy has a variety of effects on maternal thyroid function. Thyroid gland enlargement is common particularly in areas of relative iodine deficiency. The renal clearance of iodine is increased in pregnancy and together with an increased volume of iodine distribution, leads to a low plasma inorganic iodine and thus increases the thyroidal iodine clearance. However, the absolute iodine uptake and hormone production rate remain unchanged. There is an increase in the serum thyroxine (T4)and triiodothyronine (T3) concentration largely due to an increase in thyroid hormone-binding proteins. Free thyroxine and free T3 remain unchanged in pregnancy as does the Free Thyroxine Index, which gives the single most accurate measure of thyroid function. The placenta secretes a number of thyroid stimulators including human chorionic gonadotrophin and possibly chorionic thyrotrophin and molar thyrotrophin whose physiological role is to date poorly understood. The fetal thyroid develops independently, and although fetal T4 CONCENTRATION RISES PROGRESSIVELY To maternal by term, the T3 concentration is markedly reduced owing to preferential formation of inactive reverse T3.
Female↗
The effect of age and hyperthyroidism on plasma propranolol steady state concentration [proceedings].
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Aging↗
Haemochromatosis presenting as angina and responding to venesection.
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Adult↗
A positive monospot test in a diabetic with sarcoidosis.
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Adult↗
Simple preparation of the major urinary metabolites of flunitrazepam and nitrazepam.
An alarming increase in the misuse/abuse of nitrobenzodiazepine derivatives, especially flunitrazepam, prompted us to establish reliable analytical protocols for their routine detection. Whilst the parent drugs are readily available from a number of commercial sources, it was found difficult to obtain samples of the corresponding amino metabolites which were required as analytical standards. This lead us to develop the straightforward synthetic protocol described here, to convert the readily available parent drugs, namely flunitrazepam and nitrazepam, to their respective 7-amino derivatives. The method requires minimum laboratory facilities. It involves the reduction of the nitro functionality in the parent drug to an amino group using tin (II) chloride under mild conditions, using ultrasonication at room temperature. The method is simple and should give toxicology laboratories better access to these much needed compounds.
Anti-Anxiety Agents↗
Ethnic differences in the frequency distribution of serum cholinesterase activity.
We studied the activity of the enzyme pseudocholinesterase (serum cholinesterase) and its sensitivity to inhibition by dibucaine and fluoride in 400 (200 Iranian and 200 Irish) healthy subjects. The results show Irish subjects have significantly higher serum cholinesterase activity than Iranian subjects (7.82 +/- 0.14 vs 5.22 +/- 0.09 u/ml, mean +/- SEM, p < 0.01). Furthermore, the percent of inhibition of enzyme activity by dibucaine (82.19 +/- 0.68 vs 69.29 +/- 0.68) and fluoride (79.90 +/- 70.13 +/- 0.62) was also significantly higher (p < 0.001) in Irish than in Iranian subjects. One subject (Iranian) with very low pseudocholinesterase activity and a dibucaine number below 20 (atypical) had a history of apnoea following succinylcholine (suxamethonium). These data indicate that the frequency of atypical and heterozygote genes for cholinesterase activity leading to prolonged apnoea is much higher in Iranian than Irish populations. This study emphasises the importance of ethnic pharmacology.
Adult↗
Lipid peroxidation and antioxidant vitamins C and E in hypertensive patients.
Lipid peroxidation is a free radical process which is implicated in the formation of atherosclerosis. Vitamins C and E are important natural antioxidants which inhibit lipid peroxidation and a high intake of these vitamins, particularly vitamin E, is related to a reduced incidence of ischaemic heart disease. Hypertension is an independent risk factor for atherosclerosis and its relationship to antioxidant status is undetermined. In this study, we investigated free radical activity by measuring plasma malondialdehyde (MDA) using high-performance liquid chromatography (HPLC), vitamin C status measured as plasma ascorbic acid and vitamin E status measured as plasma lipid standardized alpha-tocopherol and erythrocyte alpha-tocopherol. We compared 28 patients with essential hypertension to 31 healthy subjects. Results showed that in comparison with the healthy subjects, the hypertensive patients had significantly higher plasma MDA levels (0.95 +/- 0.28 vs 0.69 +/- 0.21 mumol/l, mean +/- SD, p < 0.001) and significantly lower levels of plasma ascorbic acid (34.83 +/- 12.88 vs 51.76 +/- 13.34 mumol/L, p < 0.01). In addition, erythrocyte alpha-tocopherol concentration, which may reflect vitamin E protection in cell membranes, was significantly lower in hypertensive patients when compared with the normotensive controls (3.87 +/- 0.53 vs 4.82 +/- 1.01 mumol/l, p < 0.001), although plasma alpha-tocopherol levels were similar in the two groups (25.07 +/- 10.45 vs 23.96 +/- 6.07 mumol/l). Our results suggest that hypertensive patients may have increased lipid peroxidation and reduced protection from vitamins C and E. This may contribute to the propensity in such patients to develop atherosclerosis.
Adult↗
Underreporting of adverse drug reactions: attitudes of Irish doctors.
Despite the fundamental importance of reporting of suspected adverse drug reactions, less than 10 per cent of serious adverse drug reactions are reported. To further enhance our understanding of doctors' knowledge and attitudes to the current Adverse Drug Reaction (ADR) reporting scheme we surveyed 158 doctors, including some 106 general practitioners and 23 hospital-based doctors. The response rate was 39.5 per cent. The majority had experience of reporting an ADR. Seriousness of the ADR appears to be the most important reason for reporting. Uncertainty that the adverse drug reaction was definitely caused by the medicine, that the adverse drug reaction was too trivial to report or that it was too well known a reaction to report are common reasons for not reporting. Of concern 84 per cent of doctors are unaware of the criteria of the National Drug Regulatory Agency indicating the need for additional education and information in this regard. We also found considerable disagreements in doctors' understanding of the meaning of common, occasional, rare, or very rare as applied to ADRs.
Adverse Drug Reaction Reporting Systems↗
The detection and quantitation of 7-aminoflunitrazepam, the major urinary metabolite of flunitrazepam, by gas chromatography/mass spectrometry.
A sensitive gas chromatography/mass spectrometry method for the detection and quantitation of 7-aminoflunitrazepam, the major urinary metabolite of flunitrazepam, is described. The method is based upon solvent extraction followed by derivatisation with methyl-bis-trifluoroacetamide (MBTFA), to give a trifluoroacetyl derivative. A profile of 7-aminoflunitrazepam urinary concentrations following ingestion of 0.5 to 4 mg oral doses is reported. The method has been found to be reproducible and can be used for the confirmation of flunitrazepam administration.
Chromatography, Gas↗
Adherence to clinical guidance in the prescribing of oral antithrombotic medication in patients with atrial fibrillation.
BACKGROUND: Atrial fibrillation is the commonest cardiac rhythm disturbance and is an independent risk factor for stroke; however, use of oral antithrombotic therapy is reported to be suboptimal in clinical practice. AIM: The aim of the study was to evaluate the prescribing rates of oral antithrombotic therapy in patients with atrial fibrillation to determine if prescribing patterns reflected published clinical guidance. METHOD: Patients with atrial fibrillation, admitted to hospital over a 12-week period were identified and their antithrombotic therapy regimen was analysed using statistical methods. RESULTS: Although 87/100 patients identified were prescribed OAT, the regimen was suboptimal in 35 patients. Patients aged 75 years and older were more likelyto be receiving suboptimal oral antithrombotic treatment compared with younger patients CONCLUSIONS: The benefits and suitability of oral antithrombotic therapy for patients of all ages need to be more comprehensively communicated to prescribers.
Aged↗
Changes in prevalence of and prescribing for ischaemic heart disease in Ireland 1990-2002.
BACKGROUND: Secondary prevention therapies, such as angiotension converting enzyme (ACE) inhibitors, beta-blockers and statins, are known to reduce cardiovascular morbidity and mortality. OBJECTIVE: The aim of the study was to examine the prevalence of coronary heart disease (CHD) and the prescribing of secondary preventive therapies in the period 1990-2002. METHODS: The General Medical Services prescription database was used to identify the study cohort, those with CHD, in each year 1990-2002. CHD was defined in two ways: prescription of any nitrate, and co-prescription of nitrate and aspirin. In addition, co-prescription of secondary preventive agents including statins, ACE inhibitors and beta blockers were examined. RESULTS: We found a significant increasing prevalence of CHD from 1990 to 2002 in both men and women. There was a significant increase (p < 0.0001) in the prescribing rate for beta blockers, ACE inhibitors, and for statins, buta significant decrease (p < 0.0001) for calcium channel blockers. CONCLUSION: These trends reflect the growing evidence base on the effectiveness of secondary preventive therapies, and the implementation of the National Cardiovascular Health Strategy.
Adrenergic beta-Antagonists↗
Acute haemodynamic effects of cigarette smoking in healthy young subjects.
BACKGROUND: Invasive studies in middle-aged patients suggest an acute adverse haemodynamic effect of smoking. AIMS: To study acute changes in blood pressure (BP), cardiac output, peripheral resistance and aortic compliance following cigarette smoking in healthy young subjects. METHODS: Using a non-invasive photoplethysmographic technique we compared the effects of smoking one cigarette with sham smoking in 12 healthy volunteers (22-25 years). Data was analysed using JMP version 5.0. RESULTS: In contrast to sham smoking there was a prompt increase in blood pressure with a maximum effect at 15 min (123 +/- 7/75 +/- 5 to 143 +/- 6/86 +/- 6 mmHg, mean +/- SEM, p < 0.01) which is attributed to a rise in cardiac output (p < 0.05) rather than changes in peripheral vascular resistance. There was also a significant (p < 0.05) increase in heart rate and a reduction in aortic compliance. CONCLUSION: These results suggest that healthor young age do not protect from the adverse effects of smoking.
Adult↗
Regional variation in prescribing for chronic conditions among an elderly population using a pharmacy claims database.
BACKGROUND: Age, gender and geographical regions are recognised factors in inequalities in prescribing for chronic diseases in the elderly. AIM: To compare the health board regional distribution of chronic disease among the elderly and to examine variation in quality prescribing across age, gender and regions. METHODS: Population based study of prescribing for chronic disease using a national pharmacy claims database. All individuals aged 70 years and over (n = 271,518) were eligible. RESULTS: Over 60% of the elderly in all regions received cardiovascular related medication. The South Eastern, North Western and Western Health Boards had below average prescribing for many chronic conditions. Logistic regression identified age, gender and regional variations in prescribing of preventative therapies for CVD and diabetes. CONCLUSION: There is a high prevalence of prescribing for chronic conditions in the elderly in Ireland, and there is evidence of gender, age and residing health board inequalities in prescribing.
Age Factors↗
Pharmacoeconomics in Ireland. Concepts and terminology.
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Cost-Benefit Analysis↗
Acute inhibitory effect of alcohol on sodium-lithium countertransport.
To assess a possible acute effect of environmental factors on sodium-lithium countertransport (SLC), we determined the activity of this transport system in 14 healthy volunteers, who are nonhabitual drinkers, before and 1 hour after intake of alcohol (0.8g/kg) with "Coke" as the vehicle. Alcohol significantly increased the "leak pathway" component of lithium efflux from a baseline value of 0.21 +/- 0.02 to 0.24 +/- 0.02 mmol/Lcell.h(p < 0.003); and reduced the Vmax of the transporter (0.38 +/- 0.05 to 0.31 +/- 0.04mmol/Lcell.h;p < 0.0005) without significantly changing its affinity for external sodium. The reduction in Vmax was dependent on the initial activity of the transporter (r2 = 0.5). A plot of reduction in Vmax against the product of initial Vmax value and blood alcohol level in each subject revealed a stronger relationship (r2 = 0.86), suggesting that the observed change in Vmax was also dependent on blood alcohol level. Coke alone did not change any of the parameters. We conclude that alcohol acutely inhibits SLC as well as alters erythrocyte membrane in a manner that increases passive lithium efflux.
Adult↗