Vascular resistance, peripheral congestive heart failure

Hydralazine and dihydralazine are predominantly arterial vasodilators which cause a reduction in peripheral vascular resistance but also reflex tachycardia and fluid retention. They were used in the treatment of hypertension, in combination with a -blocker and a diuretic. Long-term use of these compounds may cause a condition resembling lupus erythematodes with arthrosis, dermatitis and LE-cells in the blood. This risk is enhanced in women and in patients with a slow acetylator pattern. When combined with the venous vasodilator isosorbide (an organic nitrate) hydralazine was shown to be mildly beneficial in patients with congestive heart failure (V-HEFT I Study). Hydralazine and dihydralazine have been replaced by other therapeutics, both in hypertension treatment and in the management of heart failure. 

Enalapril maleate is an orally active angiotensin converting enzyme (ACE) inhibitor, it lowers peripheral vascular resistance without causing an increase in heart rate. The maleate salt (enalapril) allows better absorption after oral administration. It is an ideal drug for hypertensive patients who are intolerant to beta-blocker therapy. It also shows promise in the treatment of congestive heart failure. Following oral adminishation, enalapril is rapidly absorbed and hydrolysed to... 

Hypertension is defined as a sustained diastolic blood pressure greater than 90 mm Hg accompanied by an elevated systolic blood pressure (>140 mm Hg). Hypertension results from increased peripheral vascular smooth muscle tone, which leads to increased arteriolar resistance and reduced capacitance of the venous system. Elevated blood pressure is an extremely common disorder, affecting approximately 15% of the population of the United States (60 million people). Although many of these individuals have no symptoms, chronic hypertension—either systolic or diastolic—can lead to congestive heart failure, myocardial infarction, renal damage, and cerebrovascular accidents. The incidence of morbidity and mortality significantly decreases when hypertension is diagnosed early and is properly treated. 

Numerous neuroendocrine biomarkers correlate with severity of cardiac dysfunction. Heart failure is associated with increase in peripheral vascular resistance due to increases in sympathetic tone, norepinephrine, renin, angiotensin II, arginine vasopressin, and endothelin-1. The increased venous pressure causes atrial distension that stimulates production and release of atrial and brain natriuretic peptides (ANP, BNP) from the atria and ventricles, respectively. ANP inhibits the renin-angiotensin-aldosterone system. In humans and mammals, BNP has been found to be an early biomarker of left ventricular hypertrophy developing with doxorubicin cardiotoxicity, congestive heart failure, or occult dilated cardiomyopathy (Erkus et al. 2006 Walker 2006 Oyama, Sisson, and Solter 2007). 

ADHD, attention-deficit/hyperactivity disorder AV, atrioventricular BPH, benign prostatic hypertrophy CAD, coronary artery disease CHF, congestive heart failure COPD, chronic obstructive pulmonary disease CV, cardiovascular DA, dopamine Dl, subtype 1 dopamine receptor Epi, epinephrine FFA, free fatty acids 5-HT, serotonin ISA, intrinsic sympathomimetic activity MI, myocardial infarction NE, norepinephrine NO, nitric oxide PVR, peripheral vascular resistance. 

PHARMACOLOGICAL EFFECTS The adrenergic agonists lower arterial pressure by an effect on both cardiac output and peripheral resistance. In the supine position, when the vascular sympathetic tone is low, the major effect is to reduce both heart rate and stroke volume however, in the upright position, when sympathetic outflow to the vasculature normally increases, these drugs reduce vascular resistance and may lead to postural hypotension. The decrease in cardiac sympathetic tone leads to reduced myocardial contractility and heart rate, possibly promoting congestive heart failure in susceptible patients. 

Cardiovascular system Decreased peripheral vascular resistance, increased heart rate, stroke volume, cardiac output, pulse pressure high-output congestive heart failure increased inotropic/chronotropic effects arrhythmias angina Increased peripheral vascular resistance, decreased heart rate, stroke volume, cardiac output, pulse pressure low-output congestive heart failure ECG bradycardia, prolonged PR interval pericardial effusion... 

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