Cardiac failure drugs used

Relatively selective stimulation of Pi-adrenergic receptors can be achieved with dobutamine. This is a racemic drug of which both isomers activate the Pi-receptor, and in addition the (-) isomer activates ( -receptors whereas the (+) isomer activates p2-receptors the simultaneous activation of ai- and p2-receptors results in no major net effect on peripheral resistance, and thus the overall cardiovascular effects are mediated by Pi-stimulation leading to increases in cardiac contractility and output. Dobutamine is used for the short-term treatment of acute cardiac failure and for diagnostic purposes in stress echocardiography. 

Patients with decompensated cardiac failure requiring the use of IV inotropic therapy (such patients should first be weaned from IV therapy before initiating carvedilol) bronchial asthma (see Warninas) or related bronchospastic conditions second- or third-degree AV block sick sinus syndrome or severe bradycardia (unless a permanent pacemaker is in place) cardiogenic shock clinically manifest hepatic impairment hypersensitivity to the drug. 

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. 

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... 

The sites of action within the kidney and the pharmacokinetics of various diuretic drugs are discussed in Chapter 15. Thiazide diuretics are appropriate for most patients with mild or moderate hypertension and normal renal and cardiac function. More powerful diuretics (eg, those acting on the loop of Henle) such as furosemide are necessary in severe hypertension, when multiple drugs with sodium-retaining properties are used in renal insufficiency, when glomerular filtration rate is less than 30 or 40 mL/min and in cardiac failure or cirrhosis, in which sodium retention is marked. 

Hypertension is the most common cardiovascular disease. Thus, the third National Health and Nutrition Examination Survey (NHANES III), conducted from 1992 to 1994, found that 27% of the USA adult population had hypertension. The prevalence varies with age, race, education, and many other variables. Sustained arterial hypertension damages blood vessels in kidney, heart, and brain and leads to an increased incidence of renal failure, coronary disease, cardiac failure, and stroke. Effective pharmacologic lowering of blood pressure has been shown to prevent damage to blood vessels and to substantially reduce morbidity and mortality rates. Many effective drugs are available. Knowledge of their antihypertensive mechanisms and sites of action allows accurate prediction of efficacy and toxicity. As a result, rational use of these agents, alone or in combination, can lower blood pressure with minimal risk of serious toxicity in most patients. 

When cardiac output is reduced by disease, the resultant changes in blood pressure and blood flow to the kidney are sensed as hypovolemia and thus induce renal retention of salt and water. This physiologic response initially expands the intravascular volume and venous return to the heart and may partially restore the cardiac output toward normal (see Chapter 13 Drugs Used in Heart Failure). 

The use of spironolactone as a diuretic is discussed in Chapter 15 Diuretic Agents. The drug has benefits in heart failure greater than those predicted from its diuretic effects alone (see Chapter 13 Drugs Used in Heart Failure). Adverse effects reported for spironolactone include hyperkalemia, cardiac arrhythmia, menstrual abnormalities, gynecomastia, sedation, headache, gastrointestinal disturbances, and skin rashes. 

Although theophylline has been shown to reduce CSA events in a small number of compensated cardiac failure patients [148], the drugs arrhythmogenic potential in advanced cardiac failure patients probably precludes its long-term use. 

Propranolol is the [3-adrenergic antagonist most widely used in the treatment of cardiac arrhythmias. However, Pi-specific drugs, such as metoprolol (see p. 77) reduce the risk of bronchospasm, and drugs with partial agonist activity, such as pindolol (see p. 77), may decrease the frequency of cardiac failure. 

Other diseases and conditions that can have an effect on the kinetics include cardiac failure, diabetes, and (severe) obesity [35], Dermal disease and lesions can affect the absorption (unintended) of a compound through the skin. Therefore it may be useful to at least include safety endpoints when testing drugs for psoriasis and dermatitis in animal models. 

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. 

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