Cardiac failure vasodilators

Vasodilators are a group of dtugs, which relax the smooth muscle cells of the blood vessels and lead to an increased local tissue blood flow, a reduced arterial pressure and a reduced central venous pressure. Vasodilators reduce the cardiac pre-load as well as after-load and thereby reduce cardiac work. They are used in a variety of conditions including hypertension, cardiac failure and treatment/prevention of angina pectoris. Major groups are Ca2+-channel blockers (e.g. dihydropyridines), NO-donators (e.g. organic nitrates), K+-channel openers (minoxidil), phosphodiesterase inhibitors (e.g. sildenafil), Rho-kinase inhibitors (e.g. Y27632) or substances with unknown mechanism of action (e.g. hydralazine). Inhibitors of the... 

Possible uses. Arteriolar vasodilators are given to lower blood pressure in hypertension (p. 312), to reduce cardiac work in angina pectoris (p. 308), and to reduce ventricular afterload (pressure load) in cardiac failure (p. 132). Venous vasodilators are used to reduce venous filling pressure (preload) in angina pectoris (p. 308) or cardiac failure (p. 132). 

Digoxin remains the mainstay of treatment for patients with chronic myocardial failure. Other drugs with inotropic and/or vasodilator properties, including the catecholamines and phosphodiesterase III (PDE) inhibitors, are used in the treatment of acute cardiac failure. The inotropic actions of most of these drugs result from a direct or indirect elevation of [Ca2-i-]i (intracellular Ca2+ concentration). This acts as a trigger for a process which leads to increased contractile state and cardiac contraction (Figures 8.3 and 8.4). Myofilament calcium sensitisers increase the sensitivity of contractile proteins to calcium. Some newer drugs, such as vesnarinone, have multiple mechanisms of action. 

Hawthorn is stated to possess cardiotonic, coronary vasodilator, and hypotensive properties. Traditionally, it is used for cardiac failure, myocardial weakness, paroxysmal tachycardia, hypertension, arteriosclerosis, and Buerger s disease. 

Nicorandil is an effective vasodilator through two actions. It acts as a nitrate by activating cyclic GMP (see above) but also opens the ATP-dependent potassium channel to allow potassium efflux and h5rperpolarisation of the membrane which reduces calcium ion entry and induces muscular relaxation. It is indicated for use in angina, where it has similar efficacy to p-blockade, nitrates or calcium channel blockade. It is administered orally and is an alternative to nitrates when tolerance to these is a problem, or to the other classes when these are contraindicated by asthma or cardiac failure. Adverse effects to nicorandil are similar to those of nitrates, with headache reported in 35% of patients. It is the only antianginal drug for which at least one trial has demonstrated a beneficial influence upon outcome. ... 

Inhibitors of a heart-specific subtype (type III) phosphodiesterase, which are positive inotropics, may be used in the short-term treatment of severe congestive cardiac failure, e.g. amrinone, enoximone and milrinone. However, developments of oral formulations of drugs of this type have been halted by the results of the PROMISE trial (Prospective Randomised Milrinone Survival Evaluation trial) which documented a paradoxical increase in mortality in class IV heart failure patients randomised to receive milrinone. However, some benzimidazole derivatives with class III phosphodiesterase inhibitor actions seem to be beneficial in heart failure. The agent vesnarinone is an orally active compound that may act as a class III phosphodiesterase inhibitor but appears to be a vasodilator with multiple mechanisms. See HEART FAUURE TREATMENT INOTROPIC AGENTS. 

Arterial blood pressure is the product of cardiac output and systemic vascular resistance. Conditions that may lower blood pressure in the critically ill include cardiac failure or hypovolemia (by lowering of cardiac output) and vasodilation (by sepsis, drugs, or neurotrauma). 

ACE inhibitors and angiotensin 11 receptor inhibitors limit the action of angiotensin II and suppress aldosterone production. These effects have benefits in the treatment of cardiac failure and hypertension because the resulting vasodilation and water loss lowers blood pressure. 

Sodium nitropmsside is a short-acting parenterally administered vasodilator used to treat severe hypertension and cardiac failure. It is also used to induce hypotension for certain surgical procedures. Toxicity may occur with acute high-dose nitroprus-side treatment or with prolonged infusions. 

Cardiovascular system symptoms—If the thiamin deficiency persists, the heart muscles weaken and heart failure may result Also, the smooth muscles of the vascular system may be involved, causing peripheral vasodilation. As a result of cardiac failure, peripheral ema may be observed in the extremities. 

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

Treatment of acute heart failure targets relief of congestion and optimization of cardiac output utilizing oral or intravenous diuretics, intravenous vasodilators, and when appropriate, inotropes. 

FIGURE 8-2. General treatment algorithm for acute decompensated heart failure (ADHF) based on clinical presentation. IV vasodilators that may be used include nitroglycerin, nesiritide, or nitroprusside. Metolazone or spironolactone may be added if the patient fails to respond to loop diuretics and a second diuretic is required. IV inotropes that may be used include dobutamine or milrinone. (D/C, discontinue HF, heart failure SBP, systolic blood pressure.) (Reprinted and adapted from J Cardiac Fail, Vol 12, pages el-el 22, copyright 2006, with permission from Elsevier.)... 

Minoxidil is a more potent vasodilator than hydralazine, and the compensatory increases in heart rate, cardiac output, renin release, and sodium retention are more dramatic. Severe sodium and water retention may precipitate congestive heart failure. Minoxidil also causes reversible hyper-... 

Shock refers to conditions manifested by hemodynamic alterations (e.g., hypotension, tachycardia, low cardiac output [CO], and oliguria) caused by intravascular volume deficit (hypovolemic shock), myocardial pump failure (cardiogenic shock), or peripheral vasodilation (septic, anaphylactic, or neurogenic shock). The underlying problem in these situations is inadequate tissue perfusion resulting from circulatory failure. 

Fluid retention may occur, perhaps as a result of peripheral vasodilation and/or improved insulin sensitization with a resultant increase in renal sodium and water retention. A dilutional anemia may result, which does not require treatment. Edema is reported in 4% to 5% of patients when glitazones are used alone or with other oral agents. When used in combination with insulin, the incidence of edema is about 15%. Glitazones are contraindicated in patients with New York Heart Association Class III and IV heart failure and should be used with great caution in patients with Class I or II heart failure or other underlying cardiac disease. 

Mention should also be made of the possibility of affecting cardiac function in angina pectoris (p. 306) or congestive heart failure (p. 132) by reducing venous return, peripheral resistance, or both, with the aid of vasodilators and by reducing sympathetic drive applying 3-blockers. 

ACE-inhibition will cause a reduction of cardiac afterload and preload in patients with heart failure. In addition, the ACE-inhibitors exert a favourable effect on the neuro-endocrine activation process associated with chronic heart failure. They are more effective than classic vasodilators such as hydralazine and isosorbide, which do not influence these neuroendocrine mechanisms in a favourable manner. 

Chapter 12 Vasodilators the Treatment of Angina Pectoris Chapter 13 Drugs Used in Heart Failure Chapter 14 Agents Used in Cardiac Arrhythmias Chapter 15 Diuretic Agents... 

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