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Biomedical subjects

A Pottage

Publications and source records attributed to A Pottage.

At least 19 recordsLinked to original sources
PubMed1995

Effects of acid suppression on microbial flora of upper gut.

Decreased acid secretion, due to therapy or disease, predisposes to increased bacterial counts in gastric juice. As bacterial numbers increase, the number of nitrate-reducing strains and the concentration of luminal nitrite usually also increase. However, there is controversy (mainly because of assay problems) about whether decreased acid increases generation of N-nitroso compounds: these may be produced by acid or by bacterial catalysis, and the relative contributions of each are still uncertain. Other potentially important factors include ascorbate secretion (can prevent nitrite conversion to nitroso compounds) and the particular spectrum of nitroso compounds produced. Nitrosation of several histamine H2-receptor antagonists has been demonstrated experimentally, but under conditions that are very unlikely to be encountered clinically. Some acid suppressant therapies have been claimed to aid eradication of Helicobacter pylori, but more work is needed to evaluate this. If ulcer treatment regimens do not also address eradication of H. pylori (when present), gastritis will progress, and the recently documented association between H. pylori and gastric carcinoma needs to be considered. Enteric flora probably also increase if acid secretion is markedly reduced: this does not appear to have nutritional consequences but probably reduces the resistance to occasional infections, of which cholera is the best documented.

Antacids↗
PubMed1988

Reduced felodipine bioavailability in patients taking anticonvulsants.

Felodipine is a dihydropyridine calcium antagonist, structurally related to nifedipine, which undergoes extensive first-pass hepatic metabolism and normally has an oral bioavailability of 15%. Felodipine disposition was studied in 10 patients who had microsomal enzyme induction due to chronic anticonvulsant therapy, and in 12 normal volunteers matched for age and sex. Plasma felodipine concentrations after a 5 mg oral dose were grossly reduced in the epileptic patients: the mean peak concentration was 1.6 (vs 8.9) nmol/l, and the area under the curve was only 2.0 (vs 30.0) nmol.h/l. The relative bioavailability of felodipine in the epileptic patients was thus only 6.6% of that in the normal subjects, and less than 1% of the oral dose was systemically available. Patients on anticonvulsant treatment will require substantially higher doses of felodipine to achieve plasma concentrations equivalent to those in non-induced subjects.

Administration, Oral↗
PubMed1987

Dose of inhaled budesonide required to produce clinical suppression of plasma cortisol.

Increasing dose of budesonide, each dose given for a minimum of 1 month, were administered via a Nebuhaler to 14 patients. Two consecutive abnormally low fasting morning plasma cortisol values, taken 2 weeks apart, were accepted as evidence of hypothalamo-pituitary-adrenal (HPA) hypofunction. Data from nine of the 14 patients entering the study were available for analysis. One patient developed HPA hypofunction while inhaling 2.4 mg budesonide per day and another retained normal HPA function on a dose of 12 mg. In the remaining patients, intermediate doses resulted in suppression, or the patients were withdrawn unsuppressed for other reasons (n = 3). The results in this small patient sample suggest that budesonide administered via the Nebuhaler in doses up to 1.6 mg daily does not significantly affect plasma cortisol.

Administration, Inhalation↗
PubMed1986

The pharmacokinetics of R- and S-tocainide in patients with acute ventricular arrhythmias.

The pharmacokinetics of R(-) and S(+)- tocainide were studied in twelve patients requiring intravenous tocainide. In all patients, a progressive increase in the S(+):R(-) ratio was observed during the infusion. Mean +/- s.d. ratios increased from 1.03 +/- 0.05 at 2 min to 1.76 +/- 0.35 at 48.5 h. Data from eight patients were fitted to a two-compartment model and there was a significant difference (Wilcoxon matched-pairs test P less than 0.01) in the clearance estimates for the two enantiomers. The median values were: S(+)-tocainide = 6.25 l h-1 and R(-)-tocainide = 9.31 l h-1. There was no differences in V1 or Vss.

Acute Disease↗
PubMed1986

Charcoal-column haemoperfusion does not significantly enhance chlormethiazole removal.

A 26-year-old man had convulsions after taking an overdose of slow-release aminophylline tablets. The convulsions were treated with an infusion of chlormethiazole and theophylline was removed by charcoal-column haemoperfusion. It has been suggested that haemoperfusion might be useful for removing chlormethiazole and this was investigated. There was no evidence that charcoal-column haemoperfusion could remove clinically significant amounts of chlormethiazole.

Adult↗
PubMed1983

Clinical profiles of newer class I antiarrhythmic agents--tocainide, mexiletine, encainide, flecainide and lorcainide.

New class I antiarrhythmic drugs differ in potency, adverse effects and pharmacokinetics. Encainide and flecainide can totally suppress arrhythmias in some patients, but arrhythmia induction can also occur. At effective dose levels, neurologic and gastrointestinal adverse effects are uncommon. Flecainide pharmacokinetics are suitable for oral use but encainide disposition is complex with variable bioavailability and active metabolites that contribute substantially to activity. Lorcainide is also potent, but neurologic adverse effects are common and dose-dependent bioavailability and an active metabolite may complicate long-term oral therapy. Tocainide and mexiletine can suppress arrhythmias in acute myocardial infarction, during convalescence from myocardial infarction and in patients with arrhythmias resistant to other therapy. Dose-related neurologic and gastrointestinal adverse effects are common, but hemodynamic effects are minor and arrhythmia induction is rare. Tocainide disposition is reasonably predictable and stable in patients, but mexiletine disposition is less so because of variation in distribution and clearance. Although all of the newer agents have some disadvantages, their availability should increase the likelihood of success in the high-risk patient.

Administration, Oral↗
PubMed1983

Pharmacokinetics of tocainide in patients with combined hepatic and renal dysfunction.

The disposition of tocainide following an i.v. infusion of tocainide HCl 100 mg was studied in 6 patients with decompensated cirrhosis (ascites) and renal dysfunction. In one patient with active hepatic necrosis the terminal plasma half-life was 57.4, and in the others the half life ranged from 16.0 to 29.0 h. The increase in half-life was correlated with biochemical evidence of renal dysfunction, but not with individual tests of hepatic function. Non-renal clearance of tocainide was similar to values reported previously in healthy subjects and patients with acute myocardial infarction. The apparent volume of distribution of tocainide was increased and the pattern of distribution was abnormal in some patients, as plasma concentrations increased after an initial fall and the elevated concentrations then persisted for several hours. This abnormality appeared to be most marked in patients with the greatest degree of liver dysfunction.

Adult↗
PubMed1983

Pharmacokinetics of tocainide in patients with renal dysfunction and during haemodialysis.

The disposition of tocainide was studied in 15 patients with renal dysfunction. In 9 with total renal failure, the plasma half-life ranged from 16.6 to 42.7 h and total plasma clearance from 35 to 94 ml/min. The longest half-lives were found in 1 patient with cirrhosis, 3 taking the enzyme inhibitor allopurinol, and 1 on cimetidine. The mean half-life in the remaining patients was 22.3 +/- 4.8 h (+/- SD). During a 4 h haemodialysis, the half-life in the 9 patients decreased to 8.5 +/- 4.6 h, which was calculated to correspond to removal of 25 +/- 14% of the drug from the body. In 6 patients with impaired renal function (creatinine clearance 10-55 ml/min) the tocainide half-life ranged from 13.2 to 22.0 h and total plasma clearance from 72 to 122 ml/min. One patient was taking allopurinol and 1 dihydralazine, and the mean half-life in the others was 19.2 +/- 4.0 h. The apparent volume of distribution was similar to that found previously in healthy subjects. The results suggest that tocainide elimination is predictably reduced in patients with renal disease.

Aged↗
PubMed1983

Mexiletine disposition: individual variation in response to urine acidification and alkalinisation.

The disposition of mexiletine has been studied in five subjects on two occasions with urine pH controlled at 5.0 and at 8.0. With acid urine total plasma clearance was similar in all subjects (462 to 497 ml min-1) and the plasma half-life ranged from 3.8 to 9.2 h (mean 6.7 h). With alkaline urine the total plasma clearance varied considerably (239 to 441 ml min-1); the mean half-life, 9.7 h, (range 7.6 to 12.7 h) was not significantly different from that in the acid urine study. Renal clearance fell greatly in every subject on alkalinisation of the urine. The total plasma clearance fell by a similar amount in two. In the remaining three the fall in total clearance was much smaller because of an increase in non-renal clearance. The reduction in total plasma clearance only just achieved statistical significance. The increase in predicted steady-state plasma mexiletine concentrations during infusion with change in urine pH from 5 to 8 varied between +5% and +95% (mean +39%). Changes in urine pH have a predictable effect upon renal clearance of mexiletine. However, disposition is changed in an unpredictable manner and inter-subject variation in distribution volume and non-renal clearance are important factors.

Adult↗
PubMed1983

Cardiovascular effects of zimeldine.

Sinus tachycardia is common after zimeldine overdosage, but major changes in blood pressure, conduction defects, prolonged repolarization and arrhythmias appear to be much less of a problem than with tricyclic antidepressants. At therapeutic dosage, there is no evidence of significant impairment of myocardial contractility or conduction with zimeldine. A fall in blood pressure was reported in one study, but not in others, and postural hypotension, though it may occur, is not common. These findings suggest that the use of zimeldine may be associated with a lower risk of cardiovascular toxicity than has been found with the tricyclic antidepressants.

Adult↗
PubMed1980

Paracetamol pharmacokinetics in thyroid disease.

The absorption, distribution and elimination of oral paracetamol have been studied in patients before and after treatment of thyrotoxicosis (n = 7) and hypothyroidism (n = 4). Absorption was faster in patients with untreated thyrotoxicosis than when subsequently euthyroid. The peak paracetamol concentration, however, was lower in thyrotoxic patients due to an apparent increase in the total body clearance and a shorter plasma half-life. Both absorption and elimination rates were reduced in hypothyroid patients, but were not significantly different from the euthyroid results. When estimated using a two compartment model the total volume of distribution and the hybrid distribution rate constants were unrelated to thyroid status, but the apparent volume of the central compartment was significantly greater in the thyrotoxic group. These changes in drug disposition may contribute to differences in drug response seen in thyroid disease.

Acetaminophen↗