0-Adrenergic receptors infarction

Serious adverse effects of epinephrine potentially occur when it is given in an excessive dose, or too rapidly, for example, as an intravenous bolus or a rapid intravenous infusion. These include ventricular dysrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in blood pressure, and cerebral hemorrhage. The risk of epinephrine adverse effects is also potentially increased in patients with hypertension or ischemic heart disease, and in those using (3-blockers (due to unopposed epinephrine action on vascular Ui-adrenergic receptors), monoamine oxidase inhibitors, tricyclic antidepressants, or cocaine. Even in these patients, there is no absolute contraindication for the use of epinephrine in the treatment of anaphylaxis [1,5,6]. 

Intravenous or oral doses of a P-blocker should be administered early in the care of a patient with STE ACS, and then oral agents should be continued indefinitely. Early administration of a P-blocker to patients lacking a contraindication within the first 24 hours of hospitalization is a quality care indicator.2,3 In ACS the benefit of P-blockers mainly results from the competitive blockade of P,-adrenergic receptors located on the myocardium. Pi-Blockade produces a reduction in heart rate, myocardial contractility, and blood pressure, decreasing myocardial oxygen demand. As a result of these effects, P-blockers reduce the risk for recurrent ischemia, increase in infarct size and risk of reinfarction, and occurrence of ventricular arrhythmias in the hours and days following MI.39... 

They are used for arrhythmias associated with nervous stress, myocardial infarction, and thyrotoxicosis accompanied by elevated adrenergic activity. Moreover, many antiarrhythmic drugs themselves can cause arrhythmia, especially in patients with ischemic heart disease. The examined 8-adrenergic receptor blockers are an exception. Having said that, practically all )3-adrenergic receptor blockers can be used as antiarrhythmics. 

Mechanism of action - Disopyramide is a class lA antiarrhythmic agent that decreases the rate of diastolic depolarization (phase 4), decreases the upstroke velocity (phase 0), increases the action potential duration of normal cardiac cells, and prolongs the refractory period (phases 2 and 3). It also decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium and does not affect alpha- or beta-adrenergic receptors. 

The necessity of PKA activation for successful preconditioning is demonstrated by the following (i) the beta-adrenergic receptor blocker alprenolol partially abolished ischemic preconditioning (Lochner et al. 1999) (ii) landiolol, a short-acting beta-blocker, blunted the infarct size limitation induced by ischemic preconditioning (Sanada et al. 2004) (iii) PKA inhibitors such as H89 (Sanada et al. 2004 Inserte et al. 2004) and Rp-cAMPs (Sanada et al. 2004) blunted ischemic and dibutyryl-cAMP-induced preconditioning. 

Quin, F., Yan, C., Patel, R., Liu, W., and Dong, E. 2006. Vitamin C and E attenuate apoptosis, p-adrenergic receptor desensitization, and sarcoplasmic reticular Ca2+ ATPase dowmegulation after myocardial infarction. Free Radic. Biol. Med. 40 1827-1842. 

The practically most important class of drugs directly acting on any adrenergic receptor are the p-blockers (Figure 10.12). They are mainly used to reduce the workload on a heart subject to impaired perfusion due to atherosclerotic blood vessel obliteration. The most severe consequence of this impaired perfusion is myocardial infarction, which consists in the irreversible damage to the regions of heart muscle tissue downstream of an obliterated artery. Patients... 

White DC, Hata JA, Shah AS, Glower DD, Lefkowitz RJ, Koch WJ. Preservation of myocardial P-adrenergic receptor signaling delays the development of heart failure after myocardial infarction. Proc Natl Acad Sci USA 2000 97 5428-5433. 

FIGURE 67 Metoprolol, a cardioselective betaj-adrenergic receptor antagonist, is an antihypertensive agent used in the treatment of acute myocardial infarction. 

MYOCARDIAL INFARCTION There is no evidence that Ca + channel antagonists are beneficial in the early treatment or secondary prevention of acute Ml. In several trials, higher doses of the short-acting formulation of the dihydropyridine nifedipine had a detrimental effect on mortality. Diltiazem and verapamil may reduce the incidence of reinfarction in patients with a first non-ST segment elevation infarction who are not candidates for a fl adrenergic receptor antagonist, but P blockers remain the preferred drugs. 

P receptor antagonists do not usually cause salt and water retention, and diuretic administration is not necessary to avoid edema or the development of tolerance. However, diuretics do have additive antihypertensive effects when combined with /5 blockers. The combination of a /5 receptor antagonist, a diuretic, and a vasodilator is effective for patients who require a third drug. /5 Adrenergic receptor antagonists are preferred drugs for hypertensive patients with conditions such as myocardial infarction, ischemic heart disease, or congestive heart failure. 

Another important indication for antiarrhythmic therapy is to reduce ventricular rate in atrial flutter or fibrillation. Rare forms of ventricular tachycardia appear to be DAD-mediated and respond to verapamil. Parenteral verapamil and diltiazem are approved for rapid conversion of PSVTs to sinus rhythm and for temporary control of rapid ventricular rate in atrial flutter or fibrillation. Oral verapamil may be used in conjunction with digoxin to control ventricular rate in chronic atrial flutter or fibrillation and for prophylaxis of repetitive PSVT Unlike adrenergic receptor antagonists, Ca + channel blockers have not been shown to reduce mortality after myocardial infarction. 

White, D. C., Hata, J. A., Shah, A. S., Glower, D. D., Lefkowitz, R. J., and Koch, W. J. 2000. Preservation of myocardial heta-adrenergic receptor signahng delays the development of heart failure after myocardial infarction. Proceedings of the National Academy of Sciences of the United States of America, 97, 5428-5433. 

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