Venous hypertension

Nifedipine (Table 3) is a potent vasodilator that selectively dilates resistance vessels and has fewer effects on venous vessels. It does not cause reflex tachycardia during chronic therapy. Nifedipine is one of the first-line choices for black or elderly patients and patients having concomitant angina pectoris, diabetes, or peripheral vascular diseases. Nifedipine, sublingually, is also suitable for the treatment of hypertensive emergencies. Nifedipine does not impair sexual function or worsen blood Hpid profile. The side effects are flushing, headache, and dizziness. 

Vasodilators are a group of dtugs, which relax the smooth muscle cells of the blood vessels and lead to an increased local tissue blood flow, a reduced arterial pressure and a reduced central venous pressure. Vasodilators reduce the cardiac pre-load as well as after-load and thereby reduce cardiac work. They are used in a variety of conditions including hypertension, cardiac failure and treatment/prevention of angina pectoris. Major groups are Ca2+-channel blockers (e.g. dihydropyridines), NO-donators (e.g. organic nitrates), K+-channel openers (minoxidil), phosphodiesterase inhibitors (e.g. sildenafil), Rho-kinase inhibitors (e.g. Y27632) or substances with unknown mechanism of action (e.g. hydralazine). Inhibitors of the... 

Pulmonary hypertension develops late in the course of COPD, usually after the development of severe hypoxemia. It is the most common cardiovascular complication of COPD and can result in cor pulmonale, or right-sided heart failure. Hypoxemia plays the primary role in the development of pulmonary hypertension by causing vasoconstriction of the pulmonary arteries and by promoting vessel wall remodeling. Destruction of the pulmonary capillary bed by emphysema further contributes by increasing the pressure required to perfuse the pulmonary vascular bed. Cor pulmonale is associated with venous stasis and thrombosis that may result in pulmonary embolism. Another important systemic effect is the progressive loss of skeletal muscle mass, which contributes to exercise limitations and declining health status. 

FIGURE 19-1. The portal venous system. (From Timm EJ, Stragand JJ. Portal hypertension and cirrhosis. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 694, with permission.)... 

The splanchnic system drains venous blood from the GI tract to the liver. In portal hypertension there is increased resistance to drainage from the originating organ so collateral vessels (varices) develop in the esophagus, stomach, and rectum to compensate for the increased blood volume. Varices divert blood meant for hepatic circulation back to the systemic circulation this has the unintended deleterious effect of decreasing clearance of medications and potential toxins through loss of first-pass metabolism. Varices are weak superficial vessels, and any additional increase in pressure can cause these vessels to rupture and bleed.15... 

It is this reduction in preload that, in some cases, is beneficial to patients experiencing heart failure or hypertension. Unlike a healthy heart, a failing heart is unable to pump all of the blood returned to it. Instead, the blood dams up and overfills the chambers of the heart. This results in congestion and increased pressures in the heart and venous system and the formation of peripheral edema. Because the failing heart is operating on the flat portion of a depressed cardiac function curve (see Figure 14.2), treatment with diuretics will relieve the congestion and edema, but have little effect on stroke volume and cardiac output. 

Hypertension (blood pressure >140/90 mmHg) may be caused by an elevation in cardiac output or excessive vasoconstriction. Diuretics are used in these patients to reduce cardiac output. Assume that the hearts of these individuals are operating on the ascending portion of the cardiac function curve. As the plasma volume is reduced in response to treatment with diuretic drugs, venous return and preload are reduced, as are ventricular filling and stroke volume, and cardiac output, thus bringing blood pressure back within the normal range. 

The major circulating hormones that influence vascular smooth muscle tone are the catecholamines epinephrine and norepinephrine. These hormones are released from the adrenal medulla in response to sympathetic nervous stimulation. In humans, 80% of catecholamine secretion is epinephrine and 20% is norepinephrine. Stimulation of cy-adrenergic receptors causes vasoconstriction. The selective a,-adrenergic receptor antagonist, prazosin, is effective in management of hypertension because it causes arterial and venous smooth muscle to relax. 

The answer is d. (Hardman, pp 794-795.) Hydralazine, minoxidil, diazoxide, and sodium nitroprusside are all directly acting vasodilators used to treat hypertension. Because hydralazine, minoxidil, nifedipine, and diazoxide relax arteriolar smooth muscle more than smooth muscle in venules, the effect on venous capacitance is negligible. Sodium nitroprusside, which affects both arterioles and venules, does not increase cardiac output, a feature that enhances the utility of sodium nitroprusside in the management of hypertensive crisis associated with MI. 

Patients with acute stroke should be monitored intensely for the development of neurologic worsening, complications, and adverse effects from treatments. The most common reasons for clinical deterioration in stroke patients are (1) extension of the original lesion in the brain (2) development of cerebral edema and raised intracranial pressure (3) hypertensive emergency (4) infection (e.g., urinary and respiratory tract) (5) venous thromboembolism (6) electrolyte abnormalities and rhythm disturbances and (7) recurrent stroke. The approach to monitoring stroke patients is summarized in Table 13-3. 

Possible uses. Arteriolar vasodilators are given to lower blood pressure in hypertension (p. 312), to reduce cardiac work in angina pectoris (p. 308), and to reduce ventricular afterload (pressure load) in cardiac failure (p. 132). Venous vasodilators are used to reduce venous filling pressure (preload) in angina pectoris (p. 308) or cardiac failure (p. 132). 

The molecular mechanism of diuretics acting as antihypertensive agents is not completely clear however, use of diuretics causes a significant increase in the amount of water and electrolytes excreted in urine, which leads to a reduction in the volume of extracellular fluid and plasma. This in turn leads to a reduction of cardiac output, which is the main parameter responsible for a drop in arterial blood pressure and venous blood return. Cardiac output is gradually restored, but the hypotensive effect remains, possibly because of the reduced peripheral resistance of vessels. It is also possible that diuretics somehow lower vascular activity of noradrenaline and other factors of pressure in the organism. Methods of synthesizing thiazide diuretics used for hypertension are described in the preceding chapter. Chapter 21. 

Sodium nitroprusside is a powerful, instantaneous-acting intravenous drug used to lower blood pressure in hypertensive crises. The hypotensive effect is caused by peripheral vasodilation resulting from a direct effect on both arterial and venous vessels. 

Surgery patients - Adverse reactions 3% or more include the following pyrexia, nausea, constipation, skin reactions at injection site, vomiting, itching, insomnia, headache, dizziness, urinary tract infection, hypertension, anxiety, diarrhea, dyspepsia, edema, deep venous thrombosis. 

Puimonary edema If signs of pulmonary edema occur when inhaled iloprost is administered in patients with pulmonary hypertension, stop the treatment immediately. This may be a sign of pulmonary venous hypotension. 

Prazosin was the first example of a selective O -blocker. Its main application is hypertension, usually in combination with a -blocker and/or a diuretic. Orthostatic hypotension readily occurs as a result of venous dilatation. The problem may be avoided by a gradual increase of the dosage. The drug has a short duration of action and must be administered 2-3 times daily in order to achieve adequate control of blood pressure. 

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. 

Sodium nitroprusside (SNP) is both a venous and an arterial vasodilator. An important part of its vasodilator action is caused by the release of nitric oxide (NO), similarly as for the organic nitrates. SNP can only be administered via the intravenous route. It is a rapidly and short acting vasodilator. It has been used in the treatment of hypertensive emergencies and in the management of myocardial ischaemia. In spite of its vasodilator action it hardly influences heart rate, in contrast to hydralazine and minoxidil. The dosage of SNP should not be higher than 3 pg/kg/min within 48 h, in order to avoid the rise of cyanide ions and thiocyanate in the blood. 

The vasodilators decrease total peripheral resistance and thus correct the hemodynamic abnormality that is responsible for the elevated blood pressure in primary hypertension. In addition, because they act directly on vascular smooth muscle, the vasodilators are effective in lowering blood pressure, regardless of the etiology of the hypertension. Unlike many other antihypertensive agents, the vasodilators do not inhibit the activity of the sympathetic nervous system therefore, orthostatic hypotension and impotence are not problems. Additionally, most vasodilators relax arterial smooth muscle to a greater extent than venous smooth muscle, thereby further minimizing postural hypotension. 

Mechanism of Action A potent vasodilator used to treat emergent hypertensive conditions acts directly on arterial and venous smooth muscle. Decreases peripheral vascular resistance, preload and afterload improves cardiac output. Therapeutic Effect Dilates coronary arteries, decreases oxygen consumption, and relieves persistent chest pain. 

It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud s syndrome. Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins. 

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