Preload drugs reducing

Hypertension (blood pressure >140/90 mmHg) may be caused by an elevation in cardiac output or excessive vasoconstriction. Diuretics are used in these patients to reduce cardiac output. Assume that the hearts of these individuals are operating on the ascending portion of the cardiac function curve. As the plasma volume is reduced in response to treatment with diuretic drugs, venous return and preload are reduced, as are ventricular filling and stroke volume, and cardiac output, thus bringing blood pressure back within the normal range. 

Sodium nitroprusside is used in the management of hypertensive crisis. Although it is effective in every form of hypertension because of its relatively favorable effect on cardiac performance, sodium nitroprusside has special importance in the treatment of severe hypertension with acute myocardial infarction or left ventricular failure. Because the drug reduces preload (by venodila-tion) and after load (by arteriolar dilation), it improves ventricular performance and in fact is sometimes used in patients with refractory heart failure, even in the absence of hypertension. 

Verapamil s major effect is on the slow Ca channel. The result is a slowing of AV conduction and the sinus rate. This inhibition of the action potential inhibits one limb of the reentry circuit believed to underlie most paroxysmal. supraventricular tachycardias that use the A V node as a reentry point. It is categorized as a class IV antiarrhythmie drug (see Classes of Antiarrhythmie Drugs" below). Hemodynami-cally. verapamil causes a change in the preload, afterload, contractility, heart rate, and coronary blood flow. The drug reduces systemic vascular resistance and mean blood pressure, with minor effects on eardiae output. 

Drug therapy consists of (1) furosemide or bumetanide, potent diuretics which reduce vascular volume, leading to a shift of fluid from the lungs into the vasculature and (2) morphine, a venodilator which decreases preload and reduces anxiety through its actions on opiate receptors in the brain (Tables 4.3A 3.6A). Nitrates and/or bronchodilators may be added to reduce ischemic damage and improve ventilation, respectively (Tables 4.5 5.1). 

Diuretics work by inhibiting the reabsorption of sodium from the nephron, which, in turn, decreases the amount of water that is normally reabsorbed with sodium, thus increasing water excretion. This effect reduces congestion caused by fluids retained in the body and decreases cardiac preload by excreting excess fluid in the vascular system. Chapter 21 provides a more detailed discussion on the mechanism of action of diuretic drugs. 

Additional studies suggest that ACE inhibitors are also valuable in asymptomatic patients with ventricular dysfunction. By reducing preload and afterload, these drugs appear to slow the rate of ventricular dilation and thus delay the onset of clinical heart failure. Thus, ACE inhibitors are beneficial in all subsets of patients, from those who are asymptomatic to those in severe chronic failure. 

Vasodilators such as nitrates, ACE inhibitors, and hydralazine have been discussed previously. These agents are used to decrease arteriolar (afterload) or venous resistance (preload). A discussion of cardiodynamics is beyond the scope of this book. However, by decreasing preload and afterload these drugs decrease the work that the heart has to do to increase cardiac output this improves perfusion pressure on the arterial side and venous return on the venous side, which contributes to reduced peripheral edema. 

Nitroprusside [nye troe PRUSS ide] is administered intravenously, and causes prompt vasodilation, with reflex tachycardia. It is capable of reducing blood pressure in all patients, regardless of the cause of hypertension. The drug has little effect outside the vascular system, acting equally on arterial and venous smooth muscle. [Note Because nitroprusside also acts on the veins, it can reduce cardiac preload.] Nitroprusside is metabolized rapidly (t1/2 of minutes) and requires continuous infusion to maintain its hypotensive action. Sodium nitroprusside exerts few adverse effects except for those of hypotension caused by overdose. Nitroprusside metabolism results in cyanide ion production, although cyanide toxicity is rare and can be effectively treated with an infusion of sodium thiosulfate to produce thiocyanate, which is less toxic and is eliminated by the kidneys (Figure 19.14). [Note Nitroprusside is poisonous if given orally because of its hydrolysis to cyanide.]... 

GTN is a nitrate. This class of drugs are potent vasodilators. At therapeutic doses the main effect of nitrates is to act on vascular smooth muscle to dilate the veins, thus reducing central venous pressure (preload) and ventricular end-diastolic volume. The overall effect is to lower myocardial contraction, wall stress and oxygen demand, thereby relieving the angina. Nitrates also promote vasodilation of the coronary blood vessels. 

Possible uses. Arteriolar vasodilators are given to lower blood pressure in hypertension (p.314), to reduce cardiac work in angina pectoris (p.318), and to reduce ventricular afterload (pressure load) in cardiac failure (p.322). Venous vasodilators are used to reduce venous filling pressure (preload) in angina pectoris (p. 318) or congestive heart failure (p.322). Practical uses are indicated for each drug group. 

Nitroglycerin is only marketed for the prevention of angina pectoris in humans and the US Food and Drug Administration did not approve its use for the treatment of CHF. If therapeutic plasma concentrations can be achieved in horses, nitroglycerin would be useful for reducing venous return and preload in horses with acute CHF. However, there are no data to support its use in CHF in any veterinary species. 

These drugs are potent coronary vasodilators and can increase blood flow to the myocardium. However, in many cases of angina, the coronary arteries are partially occluded and blood flow through them does not increase significantly. Nitrates appear to dilate collateral coronary blood vessels allowing partially blocked arteries to be bypassed. In addition, they dilate veins. This brings about a reduction in venous return and reduces the preload on the heart. This decreases the workload of the left ventricle and myocardial oxygen consumption is reduced. 

In patients with elevated systemic vascular resistance and normal-to-elevated systemic blood pressure, afterload reduction with nitroprusside is logical it should be emphasized that nitroprus-side also increases venous capacitance, thereby also decreasing preload. In the context of myocardial dysfunction, afterload reduction will typically lead to improved forward cardiac output. Nitroprusside may also be effective when the systemic vascular resistance is elevated and systemic blood pressure is reduced the caveat in this more complex hemodynamic setting is that the load reduction produced by nitroprusside must be counterbalanced by an increase in stroke volume. This derivative increase in stroke volume may not occur in the patient with advanced heart failure rather, the result will be a further reduction in mean arterial pressure and the potential risk of peripheral organ hypoperfusion. An alternative approach would be the use of an inotropic-dilator drug such as milrinone, which will provide both preload and afterload reduction its concurrent positive inotropic effect may offset the reduction in mean arterial pressure that can occur from vasodilation alone. 

Figure 4.1 Sites of action for drugs used to treat heart failure. Drugs that work in the hmrt enhance myocardial contractility, whereas drugs that work at other sites reduce preload or afterload. Diuretics do so by decreasing blood volume. Vasodilators increase the space provided for the blood (thus reducing pressure). Angiotensin convertin enzyme (ACE) inhibitors inhibit the synthesis of the vasoconstricting substance, angiotensin II, by blocking ACE in the lungs, where it is produced. ACE inhibitors also reduce aldosterone secretion, which leads to water loss and subsequent blood vdume reduction.

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