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Pathway Description
Acebutolol Action Pathway
Homo sapiens
Drug Action Pathway
Acebutolol is a cardioselective beta blocker. It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. In bronchial and vascular smooth muscle, acebutolol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, acebutolol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Acebutolol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis.
References
Acebutolol Pathway References
De Bono G, Kaye CM, Roland E, Summers AJ: Acebutolol: ten years of experience. Am Heart J. 1985 May;109(5 Pt 2):1211-3. doi: 10.1016/0002-8703(85)90712-4.
Pubmed: 2859785
Singh BN, Thoden WR, Wahl J: Acebutolol: a review of its pharmacology, pharmacokinetics, clinical uses, and adverse effects. Pharmacotherapy. 1986 Mar-Apr;6(2):45-63. doi: 10.1002/j.1875-9114.1986.tb03451.x.
Pubmed: 3012486
Ryan JR: Clinical pharmacology of acebutolol. Am Heart J. 1985 May;109(5 Pt 2):1131-6. doi: 10.1016/0002-8703(85)90697-0.
Pubmed: 2859776
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