Studies of the effect of thyroid dysfunction on the elimination of beta‐ adrenoreceptor blocking drugs.

Bell, JM; Russell, CJ; Nelson, J. K.; Kelly, J.G.; McDevitt, DG

doi:10.1111/j.1365-2125.1977.tb00672.x

Cited by 24 publications

(17 citation statements)

References 11 publications

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“…The results of the present study are consistent with the previous findings (Bell et al, 1977;. Eichelbaum, 1976) is known to be increased in hyperthyroidism.…”

supporting

confidence: 83%

“…In a previous study, the rate of elimination of oral propranolol was not found to differ significantly between a group of patients with hyperthyroidism and another group with hypothyroidism (Bell, Rus-selL Nelson, Kelly & McDevitt, 1977). In apparent contrast, have reported that the mean plasma steady state propranolol level was significantly increased when hyperthyroid patients became euthyroid following surgery.…”

mentioning

confidence: 86%

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Propranolol kinetics in hyperthyroidism [proceedings]

Riddell¹,

Neill²,

Kelly³

et al. 1979

Brit J Clinical Pharma

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The mean increase over baseline for the young subjects was 2.0 pmol/106 cells at a concentration of 10-8 M isoprenaline and rose to a maximum (11.3 pmol/106 cells) at 10-1 M isoprenaline. In the elderly subjects the mean concentration of cAMP at 10-1 M isoprenaline showed no increase over baseline while a maximum (5.4 pmol/106 cells) was observed at 10-4 M isoprenaline. The increase in cAMP in both young and old was a linear function of the log concentration of isoprenaline between 10-I M and 10-6 M isoprenaline. Covariance analysis of these linear portions showed no significant difference in slopes, but there was a significant difference in elevation (P < 0.01) with the line for the elderly displaced to the right.These findings support the suggestion that altered receptor function plays a role in the changed responsiveness to drugs observed in the elderly. In particular, they are consistent with the observation of Shand, Vestal & Woods (1978) of a decreased cardiac responsiveness to isoprenaline in the elderly.

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“…The results of the present study are consistent with the previous findings (Bell et al, 1977;. Eichelbaum, 1976) is known to be increased in hyperthyroidism.…”

supporting

confidence: 83%

mentioning

confidence: 86%

Propranolol kinetics in hyperthyroidism [proceedings]

Riddell¹,

Neill²,

Kelly³

et al. 1979

Brit J Clinical Pharma

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“…However, the effect of hyperthyroidism on the clearance of single oral doses of propranolol is less clear. As indicated above, the earlier studies of Bell et aL (1977) and Rubenfeld et aL (1978) did not detect any change, and indeed this has also been the conclusion of a number of other workers (Ishizaki et aL, 1980;Riddell et aL, 1980;Tawara et aL, 1981) who used the more appropriate within-subject comparison (table II). On the other hand, using a similar study design, both Aro et aL (1982) and Hallengren et aL (1982) reported a significant increase in clearance.…”

Section: Pharmacokinetics Of Propranolol In Hyperthyroidism After Orasupporting

confidence: 52%

“…The first studies from Belfast by Bell et al (1977), however, concluded that the kinetics of propranolol following a single oral dose were not markedly altered by thyroid disorders (table II). This study and that of Rubenfeld et al (1978Rubenfeld et al ( , 1979 compared 2 separate groups of subjects, hyperthyroid to hypothyroid patients and hyperthyroid to euthyroid controls, respectively.…”

Section: Pharmacokinetics Of Propranolol In Hyperthyroidism After Oramentioning

confidence: 96%

Clinical Pharmacokinetics of ??-Adrenoceptor Blocking Drugs in Thyroid Disease

Feely

1983

Clinical Pharmacokinetics

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3-Adrenoceptor blocking drugs (;3-blockers) have an established place in the management of patients with thyroid disease. Thyroid hormones, however, markedly alter hepatic, renal and cardiovascular function and thus may significantly influence drug disposition. In hyperthyroidism the clearance of propranolol following intravenous administration is increased by approximately 50%, an effect that may be attributed to the marked increase in liver blood flow that occurs in this condition. On the other hand, the increased clearance of propranolol during long term oral therapy is presumably due to increased hepatic drug metabolising enzyme activity. However, following single oral doses the clearance of propranolol has been reported both to be unchanged and increased in hyperthyroid patients. Both during single dose and long term therapy the elimination half-life of propranolol is unaltered, in part due to an increased apparent volume of distribution. The degree of plasma protein binding of propranolol appears to be slightly reduced in the hyperthyroid state.There is evidence to suggest that the clearance of metoprolol, which like propranolol undergoes extensive hepatic metabolism, is also increased in hyperthyroidism. In contrast, the oral clearance of renally excreted ;3-blockers such as sotalol and atenolol, and probably practolol also, is not altered in hyperthyroidism.In general, all ;3-blockers produce a similar degree of symptomatic response. Those with intrinsic sympathomimetic activity (e.g. oxprenolol) do not reduce heart rate to the same extent as propranolol. Recent studies have shown a significant relationship between plasma propranolol levels and the objective measures (reduction in exercise tachycardia, serum triiodothyronine concentration and weight change) but not the subjective measures of therapeutic response. Concentration-response relationships are also becoming apparent for other ;3-blockers such as metoprolol and nadolol. The 20-jold interindividual variation in propranolol plasma concentrations, which may be largely attributed to age and smoking habits, emphasises the need for individualisation of dosage. This may also explain the reported cases of thyroid crisis, particularly postoperatively in patients receiving a fixed dosage regimen. In the latter situation surgery may also markedly alter the handling of propranolol.The effect of hypothyroidism on the disposition of ;3-blockers has not been definitively studied. In hypothyroidism the elimina/ion half-life of propranolol following a single oral dose may be prolonged although clearance is not affected. During long term therapy, pre-

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“…The metabolism of certain drugs is altered in patients with thyroid dysfunction (Eichelbaum, 1976;Bell, Russell, Nelson, Kelly & McDevitt, 1977). In addition, hypersensitivity to catecholamines has been said to exist in patients with hyperthyroidism (Turner, 1974).…”

mentioning

confidence: 99%