Hypertension systemic arterial

Increased intrahepatic resistance to portal flow increases pressure on the entire splanchnic bed an enlarged spleen (splenomegaly) is a common finding in cirrhotic patient and can result in thrombocytopenia due to splenic sequestration of the platelets. Portal hypertension mediates systemic and splanchnic arterial vasodilation through production of nitric oxide and other vasodilators in an attempt to counteract the increased pressure gradient. Nitric oxide causes a fall in systemic arterial pressure unfortunately, this activates both the renin-angiotensin-aldosterone and sympathetic nervous systems and... 

It is nsed for treating stable forms of pulmonary hypertension in newborns, and in cases where systemic arterial oxygenation cannot be achieved in the usual manner under careful observation of professionals. Synonyms of this drug are prixol, prixofen, imadalin, and others. 

Mechanism of Action An antiplatelet that directly dilates pulmonary and systemic arterial vascular beds, inhibiting platelet aggregation. Therapeutic Effect Reduces symptoms of pulmonary arterial hypertension associated with exercise. Pharmacokinetics Rapidly, completely absorbed after subcutaneous infusion 91% bound to plasma protein. Metabolized by the liver. Excreted mainly in the urine with a lesser amount eliminated in the feces. Half-life 2-4 hr... 

Systemic arterial hypertension ( high blood pressure ) does not typically make the afflicted individual feel unwell however, after many years, it leads to vascular damage and to the secondary complications thereof hence, the designation of hypertension as the silent killer. The ultimate aim of the pharmacological management of hypertension is to prevent these complications and thus to prolong not only life expectancy but also quality of life. 

Figure 2. Possible Contributions to Maintenance of Systemic Arterial Pressure during Neurogenic Hypertension and Its Subsequent "Cure by Sympathectomy or Adrenergic Blockade A. Normal...

There appears to be a strong link between arterial compliance or stiffness and atherosclerosis and systolic hypertension. In humans, supplementation with soy protein or isoflavones appears to improve com-pliance. In one placebo controlled, randomized, cross-over clinical trial on peri- and postmenopausal women, treatment with 80 mg/day purified soy isoflavones for 5 weeks resulted in improvement of ca. 26% in systemic arterial compliance, even though there was no reduction in blood lipids. Only one study demonstrated a significant decrease in blood pressure, reported in 51 non-hypertensive women after ingestion of 34 mg/day isoflavones,but other studies failed to show a significant effect. ... 

A 72-year-old woman, who underwent emergency resection of a giant left atrial myxoma, had pulmonary hypertension (pulmonary artery pressure 40 mmHg) and a low cardiac output (2.21/minute). Inhaled nitric oxide, 40 ppm, before cardiopulmonary bjrpass resulted in pulmonary vasodilatation and a fall in pulmonary artery pressure from 39 to 31 mmHg. This was accompanied by a fall in cardiac output from 2.4 to 1.5 1/minute and a fall in mixed venous oxygen saturation. After bypass, inhaled nitric oxide improved pulmonary and systemic hemodynamics and resulted in a rise in cardiac output from 3.0 to 3.5 l/minute. 

Rapid i.v. administration of tetracyclines can result in hypotension and collapse. This has been attributed to intravascular chelation of calcium and/or a decrease in blood pressure owing to the drug vehicle. The i.v. administration of doxycycline to horses causes tachycardia, systemic arterial hypertension, collapse and death. This reaction may be caused by the highly lipid-soluble doxycycline chelating intracellular calcium, resulting in cardiac neuromuscular blockade. 

An important advance in NO inhalation therapy would be to develop an ambulatory treatment regime that allows the patient to leave the hospital and resume normal activities without being bmdened by cumbersome gas handling equipment. With this in mind, Hampl et al. tested the ability of periodically administered DETA/NO (Figure 2) to relieve pulmonary hypertension in rats whose lungs had been injured by monocrotaline exposure (20). They found that once-a-day inhalation of aerosolized DETA/NO lowered these animals PAP to normal levels with no observed effect on overall blood pressure (i.e., mean systemic arterial pressure, or MAP) or other signs of toxicity. 

Standardized mortality ratio (SMR) in the subgroup was 328 (5 observed/1.52 expected deaths, 95% confidence interval [Cl] 33-61, p value not reported). Kimbrough et al. (1999a) found no significant increases in mortality related to ischemic heart disease, hypertension with heart disease, other diseases of the heart, cerebrovascular disease, or circulatory system (arteries, veins, pulmonary circulation) in a study of 7,075 male and female capacitor workers. One of the subgroups (male salaried workers) in this study had a significantly decreased risk of mortality from ischemic heart as indicated by an SMR lower than 100 (44 observed/97.5 expected deaths, SMR=45, 95% Cl 107-766, p<0.01). Neither of these studies reported adequate quantitative exposure data. The inconsistent results of these studies could be due to differences in exposure levels, durations, and latencies, as well as types of Aroclors and cohort sizes. Additional information on these studies is provided in Section 3.2.8.2.I. 

Pulmonary hypertension is characterized by a chronically elevated pulmonary artery pressure. As described in previous sections of this chapter, under normal conditions, the pulmonary artery pressure has a systolic value of 18 to 25 mm Hg, a diastolic value of 6 to 10 mm Hg, and a mean value ranging from 12 to 16 mm Hg. Pulmonary hypertension exists when the pulmonary artery systolic and mean pressures exceed 30 and 20 mm Hg, respectively. In the disease state, the pressure in the pulmonary artery may fluctuate widely and is often so high that it equals the blood pressure in the systemic arterial bed. As would be expected, pulmonary vascular resistance is also extremely high in patients with pulmonary hypertension. In addition, patients with this disease exhibit an enlarged right ventricle and an enlargement of the main pulmonary artery and its branches. Systemic hemodynamic parameters, however, such as cardiac output, cardiac index, systemic artery pressure, and pulmonary artery wedge pressure are usually not elevated. 

Direct vascular smooth-muscle relaxants evaluated in primary pulmonary hypertension include hydralazine, isosorbide dinitrate, and diazoxide. In general, the hemodynamic effects of these drugs include modest reduction in mean pulmonary artery pressure, which parallels a significant reduction in systemic arterial pressure, decreased pulmonary vascular resistance, and increased cardiac output. 

Hydralazine is the first systemic vasodilator drug advocated for initial treatment in patients with primary pulmonary hypertension. Rubin and Peter (1980) reported that short-term and long-term administration of hydralazine (200-300 mg/day) improved hemodynamics during rest and exercise in patients with primary pulmonary hypertension. The use of hydralazine, however, is not without hazard. In one study with 13 patients (Danahy et al., 1979), hydralazine produced only modest decreases in pulmonary arteriolar resistance and serious adverse effects that included hypotension (resulting in one death), renal insufficiency, and systemic arterial hypoxemia. 

Hypertension is defined as persistently high systemic arterial blood pressure above 140/90 mmHg, although this does depend on age. For older people, a more realistic... 

Epoprostenol is a peripheral vasodilator, with a direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. It is indicated in long-term IV treatment of primary pulmonary hypertension. 

FIGURE 6 Bedside monitor recording of systemic artery pressure (SAP) and pulmonary artery pressure (PAP) in a 7-month-old child with postoperative pulmonary hypertension refractory to treatment, including hyperventilation with oxygen, anesthesia, alkalosis, nitroprus-side, prostaglandin E, and acetylcholine. Administration of 80-ppm inhaled nitric oxide produced an immediate reduction in PAP, with little effect on SAP. 

In 9 healthy subjects, oral indometacin 50 mg every 6 hours for 4 doses abolished the hypotensive response to intravenous hydralazine 150 mierograms/kg, and the subjects only responded when given another dose of hydralazine 30 minutes later. A study in 7 patients with pulmonary hypertension given indometacin 50 mg and hydralazine 350 mierograms/kg, both intravenously, either alone, or concurrently, also found that the effects of hydralazine (reduction in systemic arterial pressure, heart rate, cardiac index) were reduced by indometacin. In contrast, another study in 9 healthy subjects found that oral indometacin 25 mg four times daily for 2.5 days did not affect the hypotensive response to a single 200-mierogram/kg intravenous dose of hydralazine. 

Some of the profound hemodynamic changes seen in endotoxin induced shock, viz. pulmonary hypertension, platelet aggregation and systemic hypotension, have also been correlated with an increased thromboxane biosynthesis [379-384]. Mortality in endotoxic shock was significantly reduced following administration of the thromboxane synthetase inhibitors, imidazole and carboxyheptyl-imidazole, as well as of the thromboxane Aj antagonist, 13-azaprostanoic acid [380,381]. However, the increased PGIj production associated with the systemic arterial hypotension is more likely the cause of the often fatal outcome of this event [384]. 

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