Heart attacks

Approximately 500,000 Americans suffer strokes each year. Many of the 80% that survive suffer paralysis and impaired vision and speech, often needing rehabiUtation and/or long-term care. Hence, whereas treatment using rt-PA is likely to be expensive (costs are 2200/dose for treating heat attacks), the benefits of rt-PA could outweigh costs. In the case of heart attacks, the 10 times less expensive microbiaHy derived streptokinase can be used. There is currentiy no competing pharmaceutical for treatment of strokes (18,19). Consequentiy, the cost of manufacture of rt-PA may not be as dominant an issue as would be the case of other types of bioproducts. 

The concentration of t-PA in human blood is 2—5 ng/mL, ie, 2—5 ppb. Plasminogen activation is accelerated in the presence of a clot, but the rate is slow. The dissolution of a clot requites a week or more during normal repair of vascular damage (17). Prevention of irreversible tissue damage during a heart attack requires that a clot, formed by mpture of an atherosclerotic plaque, be dissolved in a matter of hours. This rapid thrombolysis (dissolution of the clot) must be achieved without significant tibrinogenolysis elsewhere in the patient. 

Oxygen inhalators are used as a first-aid measure for a long Hst of emergencies, including heart attacks and suffocation, and as a result are carried routinely by rescue squads. Oxygen—helium mixtures have proved beneficial in asthmatic attacks, because these permit more rapid flow of gas into congested areas of the respiratory system. 

There is a close correlation between myocardial infarctions and tachyarrhythmias, illustrated by the presence of complex ventricular arrhythmias among heart attack victims which are estimated to affect one-third of the survivors each year. Frequendy, the immediate cause of sudden death is ventricular fibrillation, an extreme arrhythmia that is difficult to detect or treat. In the majority of cases, victims have no prior indication of coronary heart disease. 

Ca.rdia.c-AssistDevices. The principal cardiac-assist device, the intra-aortic balloon pump (lABP), is used primarily to support patients before or after open-heart surgery, or patients who go into cardiogenic shock. As of the mid-1990s, the lABP was being used more often to stabilize heart attack victims, especially in community hospitals which do not provide open-heart surgery. The procedure consists of a balloon catheter inserted into the aorta which expands and contracts to assist blood flow into the circulatory system and to reduce the heart s workload by about 20%. The disposable balloon is powered by an external pump console. 

The understanding of these actions of aspirin started in 1971 (45) and resulted in the recommendations of the medical community that small doses of aspirin, used under the care of the doctor, may be a prevention measure for heart attack, and stroke for those considered at risk in the population. Further reported work may expand health benefits to prevention of certain kinds of cancer (46). 

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). 

As of early 1992, the market for ceU culture-derived products approached 1 billion per year. The market is expected to grow substantially throughout the 1990s. CeU culture products include erythropoietin, 1991 sales of approximately 400 million, for the treatment of anemia associated with kidney dialysis, and tissue plasminogen activator, 1991 sales approximately 200 million, for treating heart attack victims with blocked arteries (see Cardiovascularagents). 

Indications for treatment with streptokinase include acute occlusion of arteries, deep vein thrombosis, and pulmonary embolism. Streptokinase therapy in coronary thrombosis, which is the usual cause of myocardial infarction (54,71,72), has proved to be valuable. In this frequently fatal condition, the enzyme is adrninistered intravenously at a dose of 1.5 million units over 60 min, or given by intracoronary infusion at a 20,000- to 50,000-unit bolus dose followed by 2000 to 4000 units/min for 60 min therapy must be instituted as soon as practicable after the diagnosis of heart attack is made. For deep vein thrombosis, pulmonary embolism, or arterial occlusion, streptokinase is infused at a loading dose of 250,000 units given over 30 min, followed by a maintenance dose of 100,000 units over a 60-min period. 

Coumarin/warfarin, given at a typical dosage of 4 to 5 mg/day, prevents the deleterious formation in the bloodstream of small blood clots and thus reduces the risk of heart attacks and strokes for individuals whose arteries contain sclerotic plaques. Taken in much larger doses, as for example in rodent poisons, Coumarin/warfarin can cause massive hemorrhages and death. 

Thromboxane A-2 has been implicated in a number of disorders of the circulatory system including coronary artery spasms, unstable angina pectoris, traumatic and endotoxic shock, and heart attacks. It is formed normally very near its receptors and is rapidly deactivated by metabolizing enzymes so circulating levels are quite low. Furthermore, it is opposed in its actions by the prostacyclins. When these controls are defective, pathology results and drugs can be the resort in attempts to restore the normal healthy balance. For one example, furegrelate (6) is a throm-... 

Because these compounds are acidic, they can cause stomach irritation unless taken with food or water. Beyond that, aspirin inhibits blood clotting, which explains why it is often prescribed to reduce the likelihood of a stroke or heart attack. Indeed, it is now recommended for a person in the throes of a heart attack. 

Nitric oxide (NO) is a minor but villainous component of the atmosphere. It is involved in the formation of both smog (Chapter 11) and acid rain (Chapter 14). You may be surprised to learn that small amounts of NO are also produced in the human body, where it has a generally beneficial effect. In particular, it has the ability to dilate blood vessels, lowering blood pressure and reducing the likelihood of strokes or heart attacks. Beyond that, NO is effective in treating what television commercials refer to as erectile dysfunction it increases blood flow to the penis. 

LDL, or "bad," cholesterol builds up as a plaque-like deposit on the interior walls of arteries. This process used to be called hardening of the arteries today it is referred to as atherosclerosis. It can lead to cardiovascular diseases, including strokes and heart attacks. In contrast, HDL or "good" cholesterol retards or even reduces arterial deposits. 

Atherogenesis is the process that leads to changes in the arterial blood vessels, including deposition of cholesterol (atherosclerosis). It is the pathophysiological process behind the vast majority of heart attacks. 

Atherosclerotic plaques are lesions in the arterial vessels which arise during the process of atherogenesis. Most cases of acute heart attacks are caused by rupture of an atherosclerotic plaque. 

Acetylsalicylic acid irreversibly inhibits both COX-1 and COX-2 by acetylating the enzymes. Since mature platelets lack a nucleus, they are unable to synthesise new enzyme. The anti-platelet effects of acetylsalicylic acid persist therefore throughout the lifetime of the platelet and the half-life of this effect is thus being much longer than the elimination half-life of acetylsalicylic acid (15 min). Since new platelets are continuously launched into the circulation, the clinically relevant anti-platelet effect of aspirin lasts for up to five days. This is the reason why low doses of acetylsalicylic acid (ca. 100 mg per day) are sufficient in the prophylaxis of heart attacks. 

The dosage of acetylsalicylic acid in the treatment of pain and fever is 1.5-3 g daily and in the prophylaxis of heart attacks 30-100 mg daily. 

These drugp are contraindicated in patients with known hypersensitivity to the drug or to any constituents of the drug, after a recent myocardial infarction (heart attack), or in patients with thyrotoxicosis. When hypothyroidism is a cause or contributing factor to a myocardial infarction or heart disease, the physician may prescribe small doses of thyroid hormone... 

MI myocardial infarction (heart attack) RF rheumatoid factor... 

Naproxen has been found to increase the risk of heart attack and stroke by 50 percent. 

They are useful against hypertension but also for cases of angina, heart failure, heart attack, arythmia, silent ischemia, stroke and senility. 

TISSUE PLASMINOGEN ACTIVATOR SUPERIOR THERAPY FOR HEART ATTACKS... 

---