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Acta Med Scand. 1982;211(5):375-80.
Abrupt and gradual change from clonidine to beta blockers in hypertension.

Lilja M, Jounela AJ, Juustila HJ, Paalzow L.

Elective change of antihypertensive therapy from clonidine to beta-blockers was studied in 18 hypertensive inpatients on diuretic treatment. An abrupt cessation of clonidine (0.3 mg t.i.d.) and start of treatment 12 hours later with atenolol (50 mg b.i.d.) resulted, within 24-36 hours, in severe rise of blood pressure and intolerable symptoms of clonidine withdrawal in all 4 patients studied. Plasma noradrenaline levels were elevated 18-24 hours after the last dose of clonidine. Halving the previous daily clonidine dose (0.15 mg t.i.d.) and discontinuing it after three days on concomitant treatment with atenolol or timolol in increasing doses proved successful and caused only few side-effects in 14 hypertensive inpatients.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6126070&dopt=Abstract




BMJ. 1993 Mar 6;306(6878):609-11.
Incidence of and mortality from cancer in hypertensive patients.

Hole DJ, Hawthorne VM, Isles CG, McGhee SM, Robertson JW, Gillis CR, Wapshaw JA, Lever AF.

West of Scotland Cancer Surveillance Unit, Ruchill Hospital, Glasgow.

OBJECTIVES--To assess incidence of and mortality from cancer in hypertensive patients taking atenolol, comparing the findings with two control populations and with hypertensive patients taking other drugs. DESIGN--Retrospective analysis of patients first seen in the Glasgow Blood Pressure Clinic between 1972 and 1990. Patients' records were linked with the registrar general's data for information on mortality and with the West of Scotland Cancer Registry for information on incident and fatal cancers. Cancers were compared in patients and controls and in patients taking atenolol, beta blockers other than atenolol, and hypotensive drugs other than beta blockers. SUBJECTS--6528 male and female patients providing 54,355 years of follow up. SETTING--Hypertension clinic in Glasgow. MAIN OUTCOME MEASURES--Observed numbers of cancers in clinic patients were compared with expected numbers derived from cancer rates in two control populations adjusted for age, sex, and time period of data collection. RESULTS--Cancer mortality was not significantly different in clinic patients as a whole and controls. Incident and fatal cancers were not significantly increased in male or female patients taking atenolol. Cancer incidence did not rise in the clinic after a large increase in prescriptions for atenolol after 1976. CONCLUSION--This analysis does not suggest a link between atenolol and cancer.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8461810&dopt=Abstract




J Cardiovasc Pharmacol. 1990 Oct;16(4):646-53.
Selective beta 1-receptor full agonists, T-0509 and T-1583, increase the force monophasically and cyclic AMP biphasically in canine ventricular muscle.

Kurosawa H, Satoh E, Yanagisawa T, Taira N.

Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.

In canine right ventricular muscle, we investigated the mechanism of action of the positive inotropic effects of T-0509 and T-1583, derivatives of denopamine, a new selective beta 1-partial agonist. T-1583 has already been characterized as a selective beta 1 full agonist (pD2 = 7.39). T-0509 also behaved as a full agonist (pD2 = 8.27) and its positive inotropic effect was antagonized competitively by atenolol (pA2 = 7.53) and noncompetitively by carbachol, and potentiated by 3-isobutyl-1-methylxanthine. With increasing concentrations of T-0509 (10(-9) to 10(-7) M) and T-1583 (10(-8) to 10(-6) M), cyclic AMP increased and increases reached plateaus approximately 40% above the baseline levels with approximately 10(-7) M T-0509 and approximately 10(-6) M T-1583, at which their positive inotropic effects reached maxima. However, with further increasing concentrations, cyclic AMP again started to increase and increases amounted to approximately 120% above the baseline levels with 10(-5) M T-0509 and with 10(-4) M T-1583. These results suggest the following: Like denopamine, the selective beta 1 full agonists, T-0509 and T-1583, at lower concentrations produce positive inotropic effects accompanied by only a small increase in cyclic AMP via stimulation of high-affinity beta 1-receptors. In higher concentrations, unlike denopamine, the two full agonists produce large increases in cyclic AMP loosely coupled to positive inotropy via stimulation of low-affinity beta 1-receptors.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1706808&dopt=Abstract












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