Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: AstraZeneca UK Limited., 600 Capability Green, Luton, LU1 3LU, UK
Pharmacotherapeutic group: Beta-blocking agents, selective, and other diuretics
ATC code: C07CB03
Tenoret tablets combines the antihypertensive activity of two agents, a beta-blocker (atenolol) and a diuretic (chlortalidone).
Atenolol is beta1-selective (i.e. acts preferentially on beta1-adrenergic receptors in the heart). Selectivity decreases with increasing dose.
Atenolol is without intrinsic sympathomimetic and membrane-stabilising activities and, as with other beta-blockers, has negative inotropic effects (and is therefore contraindicated in uncontrolled heart failure).
As with other beta-blockers, the mode of action in the treatment of hypertension is unclear.
It is unlikely that any additional ancillary properties possessed by S (-) atenolol, in comparison with the racemic mixture, will give rise to different therapeutic effects.
Atenolol is effective and well-tolerated in most ethnic populations. Black patients respond better to the combination of atenolol and chlortalidone, than to atenolol alone.
The combination of atenolol with thiazide-like diuretics has been shown to be compatible and generally more effective than either drug used alone.
Chlortalidone, a monosulfonamyl diuretic, increases excretion of sodium and chloride. Natriuresis is accompanied by some loss of potassium. The mechanism by which chlortalidone reduces blood pressure is not fully known but may be related to the excretion and redistribution of body sodium.
Absorption of atenolol following oral dosing is consistent but incomplete (approximately 40-50%) with peak plasma concentrations occurring 2-4 hours after dosing. The atenolol blood levels are consistent and subject to little variability. There is no significant hepatic metabolism of atenolol and more than 90% of that absorbed reaches the systemic circulation unaltered. The plasma half-life is about 6 hours but this may rise in severe renal impairment since the kidney is the major route of elimination. Atenolol penetrates tissues poorly due to its low lipid solubility and its concentration in brain tissue is low. Plasma protein binding is low (approximately 3%).
Absorption of chlortalidone following oral dosing is consistent but incomplete (approximately 60%) with peak plasma concentrations occurring about 12 hours after dosing. The chlortalidone blood levels are consistent and subject to little variability. The plasma half-life is about 50 hours and the kidney is the major route of elimination. Plasma protein binding is high (approximately 75%).
Coadministration of chlortalidone and atenolol has little effect on the pharmacokinetics of either.
Tenoret tablets is effective for at least 24 hours after a single oral daily dose. This simplicity of dosing facilitates compliance by its acceptability to patients.
Atenolol and chlortalidone are drugs on which extensive clinical experience has been obtained. Relevant information for the prescriber is provided elsewhere in the Summary of Product Characteristics.
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