Therapeutic Uses Of Sympathomimetic Drugs Shock

Shock is a life-threatening condition characterized by inadequate perfusion of tissues, hypotension, and, ultimately, failure of organ systems. Treatment of shock consists of specific efforts to reverse the underlying pathogenesis as well as nonspecific measures aimed at correcting hemodynamic abnormalities. Regardless of etiology, the accompanying fall in blood pressure generally leads to marked activation of the sympathetic nervous system. This, in turn, causes peripheral vasoconstriction and an increase in the rate and force of cardiac contraction. In the initial stages of shock, these mechanisms may maintain blood pressure and cerebral blood flow, although blood flow to the kidneys, skin, and other organs may be decreased, leading to impaired production of urine and metabolic acidosis.

The initial therapy of shock involves basic life-support measures (maintenance of blood volume, etc.). Specific therapy (e.g., antibiotics for patients in septic shock) should be initiated immediately. If these measures do not lead to an adequate therapeutic response, it may be necessary to use vasoactive drugs in an effort to improve abnormalities in blood pressure and flow. This therapy generally is empirically based on response to hemodynamic measurements. Many of these pharmacological approaches, while reasonable, are of uncertain efficacy. Adrenergic receptor agonists may be used in an attempt to increase myocardial contractility or to modify peripheral vascular resistance. In general terms, b receptor agonists increase heart rate and force of contraction, a receptor agonists increase peripheral vascular resistance, and DA promotes dilation of renal and splanchnic vascular beds, in addition to activating b and a receptors.

Cardiogenic shock due to myocardial infarction has a poor prognosis; therapy is aimed at improving peripheral blood flow. Medical intervention is designed to optimize cardiac filling pressure (preload), myocardial contractility, and peripheral resistance (afterload). Preload may be increased by administration of intravenous fluids or reduced with drugs such as diuretics and nitrates. Sympathomimetic amines have been used to increase the force of contraction of the heart. Some of these drugs have disadvantages: isoproterenol is a powerful chronotropic agent and can greatly increase myocardial O2 demand; NE intensifies peripheral vasoconstriction; Epi increases heart rate and may predispose the heart to dangerous arrhythmias. DA is an effective inotropic agent that causes less increase in heart rate than does isoproterenol and also promotes renal arterial dilation (possibly useful in preserving renal function). When given in high doses (>10—20 mg/kg/min), DA activates a receptors, causing peripheral and renal vasoconstriction. Dobutamine has complex pharmacological actions that are mediated by its stereoisomers; it increases myocardial contractility with little increase in heart rate or peripheral resistance.

In some patients, hypotension is so severe that vasoconstrictors are required to maintain a blood pressure sufficient for CNS perfusion. Alpha agonists (e.g., NE, phenylephrine, metaraminol, mephentermine, midodrine, ephedrine, Epi, DA, and methoxamine) have been used. This approach may be advantageous in patients with hypotension due to failure of the sympathetic nervous system (e.g., after spinal anesthesia or injury). In patients with other forms of shock, such as car-diogenic shock, reflex vasoconstriction generally is intense, and a receptor agonists may further compromise blood flow to organs such as the kidneys and gut and adversely increase the work of the heart. Indeed, vasodilating drugs such as nitroprusside are more likely to improve blood flow and decrease cardiac work in such patients by decreasing afterload if a minimally adequate blood pressure can be maintained.

The hemodynamic abnormalities in septic shock are complex and poorly understood. Most patients with septic shock initially have low or marginal peripheral vascular resistance, possibly reflecting excessive nitric oxide (NO) production. If the syndrome progresses, myocardial depression, increased peripheral resistance, and impaired tissue oxygenation occur. The primary treatment of septic shock is antibiotics. Therapy with vasoactive drugs must be individualized according to hemodynamic monitoring.

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