Heart Cardiovascular

After highlighting the present top ten pharmaceuticals, let us now cover a number of other important drugs, both prescription and over-the-counter. We will attempt to categorize them by physiological action but will emphasize chemical structure and synthesis where appropriate. Our first type will be drugs affecting the heart. Cardiovascular agents are used for their action on the heart or on other parts of the vascular system. They modify the total output of the heart or the distribution of blood to certain parts of the circulatory system. 

A variety of responses in the body to different adrenergic drugs are based on their relative selectivity when binding with various receptors, which are exclusively found in and unevenly distributed in effector structures (heart, cardiovascular system, lungs, brain, peripheral nervous system, etc.). 

Cardiac. Pertaining to the heart. Cardiovascular. Pertaining to the heart and blood vessels. 

M. Tani, Y. Honma, H. Hasegawa, K.. Tamaki, Direct activation of mitochondrial KATP channels mimics preconditioning but protein kinase C activation is less effective in middle-aged rat hearts, Cardiovascular Research 49, 56-68 (2001). 

CYPs are membrane-bound enzymes and are found not only in the kidney and liver, but also the brain, heart, cardiovascular system and the lung, therefore their bioactive products have a myriad of functions in these tissues (Roman 2002). They are categorized according to the clan/family, subfamily, followed by a number. There are 18 mammalian CYP enzyme families, with 41 protein coding subfamilies, and 57 genes that are encoded in the human genome (Roman 2002 Nebert et al. 2013). 

Anon, lypes of aortic aneurysms. Heart, Vascular and Thoracic Care. University of Wisconsin - Madison, School of Medicine and Pubhc Health. 3/11/2013,2013, from http //www.uwhealth.org/heart-cardiovascular/types-of-aortic-aneurysms/ 10973... 

Saurin, AT, Pennington, DJ, RaaL NJ, Latchman, DS, Owen, MJ and Marber, MS (2002) T argeted disruption of the protein kinase C epsilon gene abohshes the infarct size reduction that follows ischaemic preconditioning of isolated huffer-perfused mouse hearts. Cardiovascular Research, 55, 672-680. 

Histamine in the Cardiovascular System. It has been known for many years that histamine is present in sympathetic nerves and has a distribution within the heart that parallels that of norepinephrine (see Epinephrine and norepinephrine). A physiological role for cardiac histamine as a modulator of sympathetic responses is highly plausible (15). A pool of histamine in rat heart located neither in mast cells nor in sympathetic nerves has been demonstrated. The turnover of this metaboHcaHy active pool of histamine appears to be maintained by normal sympathetic activity. 

Nontraditional Hormones. Novel hormones identified ia cardiovascular tissue have profound effects on maintenance of blood pressure and blood volume ia mammals. Atrial natriuretic hormone (ANH) is a polypeptide hormone secreted from the atria of the heart. When the cardiac atrium is stretched by increased blood volume, secretion of ANH is stimulated ANH ia turn increases salt and water excretion and reduces blood pressure (6). Endothelin is a polypeptide hormone secreted by endothehal cells throughout the vasculature. Although endothelin is released into the circulation, it acts locally in a paracrine fashion to constrict adjacent vascular smooth muscle and increase blood pressure (7). 

The isotope plutonium-238 [13981 -16-3] Pu, is of technical importance because of the high heat that accompanies its radioactive decay. This isotope has been and is being used as fuel in small terrestrial and space nuclear-powered sources (3,4). Tu-based radioisotope thermal generator systems dehvered 7 W/kg and cost 120,000/W in 1991 (3). For some time, %Pu was considered to be the most promising power source for the radioisotope-powered artificial heart and for cardiovascular pacemakers. Usage of plutonium was discontinued, however, after it was determined that adequate elimination of penetrating radiation was uncertain (5) (see PROSTHETIC AND BIOMEDICAL devices). 

Other cardiovascular diseases cover a long Hst of circulatory problems, including heart faHure, peripheral vascular disease, cardiomyopathy, and arrhythmias. 

Economic Aspects. The cardiovascular devices market is estimated to be approximately 2.9 biUion annually on a worldwide basis. This market can be further segmented as follows angiography and angioplasty, 644 x 10 arrhythmia control, 1500 x 10 cardiovascular surgery, 700 x 10 cardiac assist (intra-aortic balloon pump), 80 x 10 and artificial hearts, which are experimental. 

Lethal Arrhythmias. Arrhythmias are a second significant source of cardiovascular problems. An arrhythmia is an abnormal or irregular heart rhythm. Bradyarrhythmias result in heart rates that are too slow tachyarrhythmias cause abnormally fast rates. A bradyarrhythmia can be debiUtating, causing a person to be short of breath, unable to climb stairs, black out, or even to go into cardiac arrest. Tachyarrhythmias can be un settling and painful at best, life-threatening at worst. 

Arrhythmias. The first solution to cardiovascular problems arising from arrhythmias came about as a result of a complication caused by open-heart surgery. During procedures to correct congenital defects in children s hearts, the electrical conduction system often became impaired, and until it healed, the heart could not contract sufficiently without outside electrical stimulation. A system that plugged into a wall outlet was considered adequate until an electrical storm knocked out power, lea ding to the development of the first battery-powered external pacemaker. 

One of the more intriguing cardiovascular developments is cardiomyoplasty where implantable technologies are blended with another part of the body to take over for a diseased heart. One company, Medtronic, in close collaboration with surgeons, has developed a cardiomyoplasty system to accompany a technique of wrapping back muscle around a diseased heart which can no longer adequately pump. A combination pacemaker and neurological device senses the electrical activity of the heart and correspondingly trains and stimulates the dorsal muscle to cause the defective heart to contract and pump blood. Over 50 implants have been performed to date. 

Implantable valves, particularly mechanical valves which continue to encroach on tissue valves, are unique. Methods such as valvuloplasty, mitral valve repair, or use of ultrasound are unlikely to reduce the number of valve replacements into the twenty-first century. Valve selection remains in the hands of the surgeon because of the critical nature of the procedure. If anything goes wrong, the result can be catastrophic to the patient. Cost of a valve, from 3000— 4000, is a relatively small part of the cost of open-heart surgery which can mn as high as 30,000. Growth of the cardiovascular valve market has slowed in the United States with the decline of the threat of rheumatic fever. 

The Class I agents have many similar side effects and toxicities. The anticholinergic side effects include dry mouth, constipation, and urinary hesitancy and retention. Common gastrointestinal (GI) side effects include nausea, vomiting, diarrhea, and anorexia. Cardiovascular adverse effects are hypotension, tachycardia, arrhythmias, and myocardial depression, especially in patients with congestive heart failure. Common central nervous system (CNS) side effects are headache, dizziness, mental confusion, hallucinations, CNS stimulation, paraesthesias, and convulsions. 

The heart, a four-chambered muscular pump has as its primary purpose the propelling of blood throughout the cardiovascular system. The left ventricle is the principal pumping chamber and is therefore the largest of the four chambers in terms of muscle mass. The efficiency of the heart as a pump can be assessed by measuring cardiac output, left ventricular pressure, and the amount of work requHed to accomplish any requHed amount of pumping. 

Other Cardiovascular Agents Effecting Atherosclerosis. A large amount of clinical data is available concerning semm Upid profiles in patients subjected to dmg therapy for other cardiovascular diseases. Atheroma, for example, may be the underlying cause of hypertension and myocardial infarction. There are on the order of 1.5 million heart attacks pet year in the United States (155). 

Hypertension is one of the two principal risk factors of many cardiovascular diseases, such as coronary heart disease (CHD), stroke, and CHF. Individuals are considered hypertensive if their systoHc arterial blood pressure is over 140 mm Hg (18.7 Pa) or their diastoHc arterial blood pressure is over 90 mm Hg (12 Pa). Over 60 million people, or one-third of the adult population in the United States are estimated to be hypertensive (163). About 90% of these patients are classified as primary or essential hypertensive because the etiology of their hypertension is unknown. It is generally agreed that there is a very strong genetic or hereditary component to this disease. 

It is well accepted that hypertension is a multifactorial disease. Only about 10% of the hypertensive patients have secondary hypertension for which causes, ie, partial coarctation of the renal artery, pheochromacytoma, aldosteronism, hormonal imbalances, etc, are known. The hallmark of hypertension is an abnormally elevated total peripheral resistance. In most patients hypertension produces no serious symptoms particularly in the early phase of the disease. This is why hypertension is called a silent killer. However, prolonged suffering of high arterial blood pressure leads to end organ damage, causing stroke, myocardial infarction, and heart failure, etc. Adequate treatment of hypertension has been proven to decrease the incidence of cardiovascular morbidity and mortaUty and therefore prolong life (176—183). 

A third study (85) enrolled 7825 hypertensive patients (55% males and 45% females) having diastoHc blood pressures (DBP) of 99—104 mm Hg (13—14 Pa) there were no placebo controls. Forty-six percent of the patients were assigned to SC antihypertensive dmg therapy, ie, step 1, chlorthaUdone step 2, reserpine [50-55-5] or methyldopa [555-30-6], and step 3, hydralazine [86-54-4]. Fifty-four percent of the patients were assigned to the usual care (UC) sources in the community. Significant reductions in DBP and in cardiovascular and noncardiovascular deaths were noted in both groups. In the SC group, deaths from ischemic heart disease increased 9%, and deaths from coronary heart disease (CHD) and acute myocardial infarctions were reduced 20 and 46%, respectively. 

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