Systemic Hemodynamic Actions

not all NO donors produce the same profile of vascular dilatation or therapeutic outcome. 

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The systemic hemodynamic actions of nicorandil are occasionally associated with a transient increase in heart rate of up to 18% (9,10). Larger doses are associated with cardiac depression, a dose-dependent fall in sinus rate and atrioventricular conduction velocity (11), and shortening of the cardiac action potential duration (12). However, no prodysrhythmic effects have been observed in man (13,14). Single oral doses over 40 mg have been associated with severe postural hypotension, dizziness, and syncope (10,15). 

Nitrates (e.g., ISDN) and hydralazine were combined originally in the treatment of HF because of their complementary hemodynamic actions. Nitrates are primarily venodilators, producing reductions in preload. Hydralazine is a direct vasodilator that acts predominantly on arterial smooth muscle to reduce systemic vascular resistance (SVR) and increase stroke volume and cardiac output. Evidence also suggests that the combination may provide additional benefits by interfering with the biochemical processes associated with HF progression. 

From a hemodynamic standpoint, chlorothiazide has been shown to exert a diphasic action on systemic hemodynamics first, the decrease in blood pressure is associated with a decrease in blood... 

Ruppin H 1987 Loperamide a potent antidiarrhoeal drug with actions along the alimentary tract. Alimentary Pharmacology and Therapeutics 1 179-190 Rutkowski J A, Eades S C, Moore J N 1991 Effects of xylazine butorphanol on cecal arterial blood flow, cecal mechanical activity and systemic hemodynamics in horses. American Journal of Veterinary Research 52 1153-1158... 

Dopexamine (Dopacard) is a synthetic analog related to dopamine with intrinsic activity at dopamine Dj and D2 receptors as well as at P2 receptors it may have other effects such as inhibition of catecholamine uptake. It appears to have favorable hemodynamic actions in patients with severe CHF, sepsis, and shock. In patients with low cardiac output, dopexamine infusion significantly increases stroke volume with a decrease in systemic vascnlar resistance Tachycardia and hypotension can occnr, bnt nsnally only at high infusion rates. 

When infused intrarenally in animals, PAF decreases renal blood flow, glomerular filtration rate, urine volume, and excretion of Na without changes in systemic hemodynamics. These effects are the result of a direct action on the renal circulation. PAF exerts a receptor-mediated biphasic effect on afferent arterioles, dilating them at low concentrations and constricting them at higher concentrations. The vasoconstrictor effect appears to be mediated, at least in part, by COX products, whereas vasodilation is a consequence of the stimulation of NO production by endothelium. 

Nicotine Nasal Spray (Nicolrol NS) [Smoking Deterrent/ Cholinergic] Uses Aid to smoking cessation, relieve nicotine withdrawal Action Systemic delivery of nicotine Dose 0.5 mg/actuation 1-2 sprays/h, 10 sprays/h max Caution [D, M] Contra Life-threatening arrhythmias, unstable angina Disp Nasal inhaler SE Local irritation, tach, HA, taste p v sion Interactions T Effects W/ cimetidine, black cohosh t effects OF catecholamines, cortisol T hemodynamic AV blocking effects OF adenosine EMS See Nicotine Gum OD See Nicotine Gum... 

The hemodynamic effects of compounds supposed to affect the cardiovascular system are evaluated by measuring preload and afterload of the heart, contractility, heart rate, cardiac output and peripheral or coronary flow. To measure these cardiovascular parameters accurately, the use of larger animals such as dogs or pigs is necessary. This experimental model allows the classification of test drugs according to their action as having ... 

No therapy for advanced/decompensated heartfailure studied to date has been shown conclusively to influence mortality. Treatment goals are directed toward restoration of systemic oxygen transport and tissue perfusion, relief of pulmonary edema, and limitation of further cardiac damage. Maximizing oral therapy and using combinations of shortacting intravenous medications with different cardiovascular actions often are needed to optimize cardiac output, relieve pulmonary edema, and limit myocardial ischemia. Invasive hemodynamic monitoring usually is required to provide immediate feedback on treatment efficacy and adverse effects. 

Drugs lower blood pressure by actions on peripheral resistance, cardiac output, or both. In patients with isolated systolic hypertension, complex hemodynamics in a rigid arterial system contribute to increased blood pressure drug effects may be mediated by changes in peripheral resistance but also via effects on large artery stiffness. 

SODIUM NITROPRUSSIDE Sodium nitroprusside (NITROPRESS) is a prodrug and potent vasodilator that reduces both ventricular filling pressures and systemic vascular resistance. It has a rapid onset (2-5 minutes) and offset (quickly metabolized to cyanide and NO, the active vasodilator) of action and its dose can be titrated expeditiously to achieve the desired hemodynamic effect. For these reasons, nitroprusside is commonly used in intensive-care settings for rapid control of severe hypertension and for the management of decompensated heart failure. The basic pharmacologic properties of this drug are described in Chapter 32. 

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