[Antihypertensive agents: specific molecules with therapeutic combinations].
The main goal of combination therapy in current antihypertensive treatment strategy is to achieve an additive or hopefully synergistic effect at a lower dose, hence with fewer side-effects. In reality, no one antihypertensive has a monolithic action profile: the therapeutic effect is the combined result of one or several individual effects, and the consequence of one of several adaptive mechanisms involved in physiological regulation. The action profiles of beta-adrenergic receptor blockers and converting enzyme inhibitors provide a good example of this complexity. The strategy for therapeutic use of an antihypertensive, including possible combination with another drug, thus depends on the level of impairment in the target structure (beta-adrenergic receptor, converting enzyme, calcium channel etc.), modulation of other target structures by the drug, and on the amplitude of counter-regulatory mechanisms that may be brought into play, whether directly or indirectly. The latter have greatest impact on the long-term outcome of antihypertensive treatment, in terms of myocardial hypertrophy, vascular remodeling, and atherosclerosis. Despite the multiple pharmacological and pharmacokinetic interactions leading to the development of increasingly sophisticated activity profiles and despite the use of increasingly focussed combination therapies, we must not forget that the role of many potential pharmacological targets still awaits investigation.
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Service de Pharmacologie, Hôpital Pitié Salpêtrière, Paris, France.
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics
Les antihypertenseurs: des molécules spécifiques aux associations thérapeutiques.