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Biomedical subjects

J G Kelly

Publications and source records attributed to J G Kelly.

117 records · Page 7Linked to original sources
PubMedDate not supplied

Human lymphocyte beta-adrenoceptor density in relation to age and hypertension.

beta-Adrenoceptor density was measured in lymphocytes from neonates and from normotensive and hypertensive adults aged from 18 to 85 years. Receptor density did not differ in young and elderly people. In normotensive but not in hypertensive people there was a peak in beta-adrenoceptor density in middle life; otherwise, receptor densities were similar in normotensive and hypertensives. Neonates had a lower lymphocyte receptor density than adults. Decreases in beta-adrenoceptor-mediated responses in old age may be due to alterations in postreceptor events.

Adolescent↗
PubMedDate not supplied

Antiarrhythmic and cardiovascular effects of MP 115.

We studied the effects on experimental cardiac arrhythmias of MP 115, a tertiary amine, in dogs anaesthetised with pentobarbitone sodium. Low doses of the drug (0.2-2.1 mg/kg i.v.) abolished ventricular tachycardia resulting from cardiotoxic doses of ouabain in 12 of 15 experiments. The ventricular arrhythmic response to the intravenous administration of adrenaline was prevented in dogs respired with 1% halothane in room air. Higher doses given intravenously to conscious dogs by sequential injections or infusion abolished the ventricular tachycardia 1 day after ligation of the anterior descending branch of the left coronary artery (effective plasma concentration, 5.0 +/- 1.6 micrograms/ml). Studies in normal dogs anaesthetised with pentobarbitone sodium (30 mg/kg) showed that the drug (0.1-1.0 mg/kg) caused reductions in arterial blood pressure and peripheral resistance. In isolated rabbit ear arteries perfused at a constant flow rate, MP 115 (1-10 microM) competitively antagonised the vasoconstrictor response to noradrenaline and had a more potent effect on the responses to 5-hydroxytryptamine. The vasoconstrictor responses to histamine, barium, and potassium were only reduced at higher concentrations. Poor oral absorption and central nervous system toxicity limit further development of this compound.

Animals↗
PubMedDate not supplied

Nitrates in the elderly. Pharmacological considerations.

Although a significant proportion of patients receiving nitrates are elderly, surprisingly little published work is available describing the pharmacokinetics and pharmacodynamics of these agents in elderly patients. The lack of pharmacokinetic data is related to the difficulty in assaying nitrates and there are at present no definitive data describing the effect of aging on their bioavailability or elimination. A common finding in old age is of decreased hepatic first-pass metabolism. This would affect isosorbide-2-mononitrate and isosorbide-5-mononitrate less than isosorbide dinitrate and nitroglycerin (glyceryl trinitrate). Venous responsiveness to nitrates does not appear to alter with age, so that pharmacodynamic properties would not be expected to alter. However, decreased baroreflex function causes an increased tendency for posturally related side effects to occur. Mechanisms of tolerance are likely to be unaltered but any possible alteration in quantitative aspects of tolerance has not been studied. Nitrate therapy in the elderly would benefit from systematic investigation. At the moment, therapy needs to be titrated to the individual patient, with care taken to avoid age-related side effects by careful initiation of therapy and appropriate reviews of each patient.

Absorption↗
PubMedDate not supplied

Calcium antagonists in the elderly.

The calcium antagonists are associated with a number of advantages over other antihypertensive agents, such as a lack of metabolic, vascular and respiratory adverse events, yet are effective in reducing blood pressure. The currently available calcium antagonists are widely used, and new members, particularly of the dihydropyridine group, continue to emerge. These agents may well be considered for use in the management of hypertension and angina in elderly people. They undergo significant first-pass metabolism and tend to have high values of hepatic clearance with minimal amounts of unchanged drug in the urine. Plasma concentrations tend to be higher in elderly people and for that reason it may be prudent to initiate therapy with lower dosages. With this caveat, adverse effect profiles seem to be qualitatively and quantitatively similar in younger and older people. At equivalent plasma concentrations, the antihypertensive effect appears similar in young and elderly patients, and clinical studies point to comparable efficacy with other drug classes. Calcium antagonists do not have adverse renal, respiratory, cardiovascular, metabolic or peripheral vascular effects and therefore may be useful in patients with relevant concomitant disease.

Aged↗
PubMedDate not supplied

Clinical pharmacokinetics of oral anticoagulants.

Warfarin is clinically the most widely used oral anticoagulant and its properties have been extensively studied. Assay method for these compounds have until recently been relatively nonspecific. The advent of chromatographically based techniques has enabled re-evaluation of the pharmacokinetics of oral anticoagulants, but most work continues to involve warfarin. The most important recent work has concerned the different anticoagulant potencies and metabolic pathways of the optical isomers of some of these drugs. The effects of age and some diseases on pharmacokinetics of warfarin have been examined but much remains to be done, especially with oral anticoagulants other than warfarin. There are several well established pharmacokinetic drug interactions with warfarin. There is a wide awareness of the drugs most likely to reduce anticoagulant effects by enzyme induction and alternative drugs can be used. Mechanisms of some interactions have been re-investigated. In vivo drug displacement interactions are complicated by the correlation between hepatic clearance of these drugs and the size of the unbound fraction in plasma. The interactions between phenylbutazone and warfarin and metronidazole and warfarin, resulting in potentiation of anticoagulant effect have been suggested to be due mainly to an inhibition of the metabolism of the more potent S isomer of warfarin.

Aged↗