The clinical significance of intrinsic sympathomimetic activity

Northcote, Robin J.

doi:10.1016/0167-5273(87)90309-3

Cited by 5 publications

(2 citation statements)

References 93 publications

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“…30,31 Ces deux dernières catégories diminuent les résistances vasculaires périphériques 3 2 en stimulant les bêta-2 récepteurs vasodilatateurs. 33 Ils ralentissent moins la fréquence cardiaque au repos que les BB dépourvus d'ASI. dernier effet demande des doses beaucoup plus élevées que celles nécessaires au bêta-blocage.…”

Section: Cardiosélectivitéunclassified

Intérêt des bêta-bloquants en médecine périopératoire. Première partie: notions fondamentales

Piriou

Aouifi

Lehot

2000

Can J Anesth/J Can Anesth

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Objectif : Rappeler les notions de pharmacologie et de physiopathologie nécessaires à l'utilisation des bêta-bloquants (BB) en médecine périopératoire.Sources : Recherche manuelle et informatisée de la littérature. (mots-clés : anesthesia and beta-blocker, surgery and beta-blocker).Constatations principales : Les BB cardiosélectifs bloquent préférentiellement les bêta-1 récepteurs, induisant une diminution de la fréquence cardiaque et de l'inotropisme, conduisant à la diminution de la consommation d'oxygène myocardique. Les BB non cardiosélectifs bloquent également les bêta-2 récepteurs, induisent une élé-vation des résistances vasculaires périphériques et bronchiques et augmentent les contractions utérines. Cependant, certains BB possèdent des effets vasodilatateurs (carvédilol, céliprolol, labétalol). Les contre-indications des BB résultent logiquement de leurs effets pharmacologiques. Le traitement BB tend à augmenter la densité des bêta-récepteurs membranaires, expliquant les manifestations d'hyperactivité du système nerveux sympathique observées lors de leur sevrage. Depuis la découverte du propranolol en 1964, les BB ont connu des fortunes diverses en anesthésie. Initialement, la sympatholyse partielle qu'ils induisent a été redoutée dans les situations de stress provoquées par les agents anesthésiques et surtout les manipulations chirurgicales. Cependant, les travaux publiés à partir de 1973 ont suggéré un effet hémodynamique protecteur. Conclusion :Les travaux récents ont démontré le caractère bénéfique de la poursuite des traitements BB jusqu'à l'anesthésie à l'exception des manifestations d'intolérance telles que l'hypotension ou la bradycardie sévère.Purpose: To review the pharmacologic and pathophysiologic information necessary to prescribe beta-blockers (BB) in perioperative medicine. Data source: Manual retrieval and electronic research of the literature using MEDLINE (key-words: anesthesia and beta-blocker; surgery and beta-blocker).Data synthesis: Cardioselective BB inhibit preferentially beta-1 receptors, inducing a decrease in heart rate and cardiac inotropism leading to reduction of oxygen myocardial consumption. Non-cardioselective BB inhibit also beta-2 receptors, increasing bronchial and peripheral vascular resistances and uterine contractions. However, some BB are also vasodilators (carvedilol, celiprolol, labetalol). Contraindications to BB result logically from their pharmacological effects. Treatment with BB increases membrane beta-receptor density; this explains sympathetic overactivity observed during weaning of treatment. Since the discovery of propranolol in 1964, the use of BB has been controversial in anesthesia. Formerly, the adverse effects of partial sympatholysis during anesthesia and surgery were feared. However, since 1973, experimental and clinical data have suggested a protective hemodynamic effect.Conclusion: Continued administration of BB up to the time of anesthesia has been encouraged except in patients with signs of intolerance such as hypotension or excessive bradyca...

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Section: Cardiosélectivitéunclassified

Intérêt des bêta-bloquants en médecine périopératoire. Première partie: notions fondamentales

Piriou

Aouifi

Lehot

2000

Can J Anesth/J Can Anesth

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“…Rather they possess weak-to-moderate agonist activity resulting in stimulation of cardiac ß-adrenoceptors and increases in heart rate; this activity is referred to as intrinsic sympathomimetic activity (ISA) [5]. Despite initial optimism regarding clinical efficacy of ß-adrenoceptor antagonists with ISA [6], evidence now indicates that ISA offers no clear advantage over pure competitive antagonists (which lack ISA) in the treatment of hypertension. Indeed, the presence of ISA may actually be detrimental in the treatment of congestive heart failure and myocardial infarction.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Intrinsic Sympathomimetic Activity of Bucindolol and Carvedilol in Rat Heart

Willette

Mitchell²,

Ohlstein³

et al. 1998

Pharmacology

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Many β-adrenoceptor antagonists are weak partial agonists, possessing significant intrinsic sympathomimetic activity (ISA). Under certain conditions, ISA may be deleterious through stimulation of β₁- and/or β₂-adrenoceptors in the heart. Drugs with ISA are particularly problematic in the treatment of congestive heart failure since agents that activate cardiac β-adrenoceptors, such as xamoterol, have been associated with increases in the incidence of arrhythmia and mortality. Carvedilol was recently approved for the treatment of congestive heart failure, and bucindolol is currently in large clinical trials for this indication. In the present study, the ISA of bucindolol and carvedilol was evaluated in a standard model used to investigate ISA, the pithed rat. Both compounds produced dose-dependent inhibition of the positive-chronotropic effects of the non-selective β-adrenoceptor agonist, isoproterenol, confirming that these drugs are β-adrenoceptor antagonists. However, cumulative administration of bucindolol (10–1,000 µg/kg i.v.) in the pithed rat produced a significant dose-related increase in heart rate. The maximal increase in heart rate produced by bucindolol was 44% of that obtained with isoproterenol (90 ± 6 vs. 205 ± 11 bpm, respectively). In marked contrast, cumulative administration of carvedilol (10–1,000 µg/kg i.v.) had no significant effect on resting heart rate in the pithed rat. The maximal increase in heart rate elicited by bucindolol (1,000 µg/kg i.v.) was inhibited by treatment with the competitive β-adrenoceptor antagonist, propranolol (99 ± 8.7 vs. 26 ± 2.6 bpm), confirming that the ISA observed with bucindolol was mediated through stimulation of myocardial β-adrenoceptors. Carvedilol, which had no ISA, antagonized the ISA of bucindolol, and was as effective as propranolol in blocking the ISA of bucindolol (99 ± 8.7 vs. 27 ± 2.3 bpm). In summary, bucindolol and carvedilol are both potent β-adrenoceptor antagonists in the pithed rat; however, only bucindolol possesses β-adrenoceptor-mediated ISA.

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Tricuspid valve surgery is an independent risk factor in long-term survival in surgery for infective endocarditis

Ariyaratnam

Kotidis

Loubani

2014

International Journal of Cardiology

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The clinical significance of intrinsic sympathomimetic activity

Cited by 5 publications

References 93 publications

Intérêt des bêta-bloquants en médecine périopératoire. Première partie: notions fondamentales

Intérêt des bêta-bloquants en médecine périopératoire. Première partie: notions fondamentales

Evaluation of Intrinsic Sympathomimetic Activity of Bucindolol and Carvedilol in Rat Heart

Tricuspid valve surgery is an independent risk factor in long-term survival in surgery for infective endocarditis

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