Myocardial infarction agents

Technetium-99m tetrafosmin ( Tc-(V)02 (l,2-bis(bis(2-ethoxyethyl)phosphino)ethane) (see Fig. 3d)) is a myocardial perfusion agent. It is used as an adjunct in the diagnosis and localization of myocardial ischemia and/or infarction. 

Another example is the use of Tc-sestamibi, approved for use in the evaluation of coronary artery disease and myocardial infarction, in patients with breast cancer. Use in breast cancer is under investigation by a number of physicians. The data are not yet sufficient to determine the efficacy of this agent in this setting. Its safety, of course, has already been demonstrated as part of its initial evaluation for heart disease. 

Cardiac arrhythmias are an important cause of morbidity and mortality approximately 400,000 people per year die from myocardial infarctions (MI) in the United States alone. Individuals with MI exhibit some form of dysrhythmia within 48 h. Post-mortem examinations of MI victims indicate that many die in spite of the fact that the mass of ventricular muscle deprived of its blood supply is often quite small. These data suggest that the cause of death is ventricular fibrillation and that the immediate availability of a safe and efficacious antiarrhythmic agent could have prolonged a number of Hves. The goals of antiarrhythmic therapy are to reduce the incidence of sudden death and to alleviate the symptoms of arrhythmias, such as palpitations and syncope. Several excellent reviews of the mechanisms of arrhythmias and the pharmacology of antiarrhythmic agents have been pubflshed (1,2). 

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). 

Meticulous care needs to be used in the application of this tissue adhesive. Only a very thin layer of adhesive should be used to assist with reapproximation of the intima and adventitia. It is important to remember that the material should not be allowed to drip into or onto critical areas such as the ostium of the coronary arteries. Inadvertent placement of this agent in such areas can result in blockage of a critical artery and a potentially fatal myocardial infarction. In addition. 

Fondaparinux, the factor Xa-binding pentasaccharide (Arixtra, MW 1,728 Da), is prepared synthetically, unlike UFH, LMWH and danaparoid, which are obtained from animal sources. Despite only inactivating free factor Xa, clinical trials indicate that fondaparinux is an effective antithrombotic agent, both for venous thromboembolism prophylaxis and treatment, as well as for acute coronary syndrome and ST elevation myocardial infarction [4]. 

In rodent stroke models, statin pretreatment has been shown to reduce infarct volumes and improve outcomes. Similarly, several clinical studies have shown that prior statin use reduced the severity of acute ischemic stroke and myocardial infarction. Recent studies indicate that beneftt can be achieved even when treatment is initiated after the onset of symptoms. In rodents, atorvastatin and simvastatin have been shown to reduce the growth of ischemic lesions, enhance functional outcome, and induce brain plasticity when administered after stroke onset. A retrospective analysis of the population-based Northern Manhattan Stroke Study (NOMASS) showed that patients using lipid-lowering agents at the time of ischemic stroke have a lower incidence of in-hospital stroke progression and reduced 90-day mortality rates. Retrospective analysis of data of the phase III citicoline trial showed... 

Gent M. A systematic overview of randomised trials of antiplatelet agents for the prevention of stroke, myocardial infarction and vascular death. In Hass WK, Easton ID, editors. Ticlo-pidine, platelets and vascular disease. New York Springer-Verlag 1993 p99-116. 

Hypertension is the most common cardiovascular disease in fact, nearly 25% of adults in the U.S. are considered hypertensive. Hypertension is defined as a consistent elevation in blood pressure such that systolic/diastolic pressures are >140/90 mmHg. Over time, chronic hypertension can cause pathological changes in the vasculature and in the heart. As a result, hypertensive patients are at increased risk for atherosclerosis, aneurysm, stroke, myocardial infarction, heart failure, and kidney failure. There are several categories of antihypertensive agents ... 

Aspirin is maximally effective as an antithrombotic agent at the comparatively low dose of 81 to 325 mg per day. (The antipyretic dose of aspirin in adults is 325 to 650 mg every 4 h.) Higher doses of aspirin are actually contraindicated in patients prone to thromboembolism. At higher doses, aspirin also reduces synthesis of prostacyclin, another arachidonic acid metabolite. Prostacyclin normally inhibits platelet aggregation. The prophylactic administration of low-dose aspirin has been shown to increase survival following myocardial infarction, decrease incidence of stroke, and assist in maintenance of patency of coronary bypass grafts. 

In situations where inappropriate clot formation results in the blockage of a blood vessel, the tissue damage that ensues depends, to a point, upon how long the clot blocks blood flow. Rapid removal of the clot can often minimize the severity of tissue damage. Thus, several thrombolytic (clot-degrading) agents have found medical application (Table 12.5). The market for an effective thrombolytic agent is substantial. In the USA alone, it is estimated that 1.5 million people suffer acute myocardial infarction each year, and there are another 0.5 million suffer strokes. 

Alteplase has proven effective in the early treatment of patients with acute myocardial infarction (i.e. those treated within 12 h after the first symptoms occur). Significantly increased rates of patient survival (as measured 1 day and 30 days after the initial event) are noted when tPA is administered in favour of streptokinase, a standard therapy (see later). tPA has thus established itself as a first-line option in the management of acute myocardial infarction. A therapeutic dose of 90-100 mg (often administered by infusion over 90 min) results in a steady-state alteplase concentration of 3-4 mg l 1 during that period. However, the product is cleared rapidly by the liver, displaying a serum half-life of approximately 3 min. As is the case for most thrombolytic agents, the most significant risk associated with tPA administration is the possible induction of severe haemorrhage. 

Elevated blood pressure should remain untreated in the acute period (first 7 days) after ischemic stroke because of the risk of decreasing cerebral blood flow and worsening symptoms. The pressure should be lowered if it exceeds 220/120 mm Hg or there is evidence of aortic dissection, acute myocardial infarction, pulmonary edema, or hypertensive encephalopathy. If blood pressure is treated in the acute phase, short-acting parenteral agents (e.g., labetalol, nicardipine, nitroprusside) are preferred. 

The AHA/ASA guidelines recommend that antiplatelet therapy as the cornerstone of antithrombotic therapy for the secondary prevention of ischemic stroke and should be used in noncardioembolic strokes. Aspirin, dopidogrel, and extended-release dipyridamole plus aspirin are all considered first-line antiplatelet agents (see Table 13-1). The combination of aspirin and clopido-grel can only be recommended in patients with ischemic stroke and a recent history of myocardial infarction or coronary stent placement and then only with ultra-low-dose aspirin to minimize bleeding risk. 

Contraindications to these agents include hypertension, tachyarrhythmias, coronary artery disease, myocardial infarction, cor pulmonale, hyperthyroidism, renal failure, and narrow-angle glaucoma. 

Acute MI (myocardial infarction), 5 107 antianginal agents for, 5 110t and coronary arterial thrombosis, 5 170 Acute myelogenous leukemia (AML), and benzene exposure, 3 616 Acute oral toxicity... 

---