Catecholamines vasoconstriction effects

Vasopressin causes vasoconstrictive effects that, unlike adrenergic receptor agonists, are preserved during hypoxia and severe acidosis. It also causes vasodilation in the pulmonary, coronary, and selected renal vascular beds that may reduce pulmonary artery pressure and preserve cardiac and renal function. However, based on available evidence, vasopressin is not recommended as a replacement for norepinephrine or dopamine in patients with septic shock but may be considered in patients who are refractory to catecholamine vasopressors despite adequate fluid resuscitation. If used, the dose should not exceed 0.01 to 0.04 units/min. 

The duration of action of a local anaesthetic is proportional to the time that the drug remains bound to the sodium channels. Measures that prolong contact time will prolong the duration of the local anaesthetic effect. Cocaine has a vasoconstricting effect on blood vessels and prevents its own absorption. Many local anaesthetics are prepared with adrenaline (epinephrine) in order to achieve this effect. Concentrations are usually of the order of 1 200000 or more dilute than this. Care should be exercised when using adrenaline-containing solutions in the presence of halothane as it is known to sensitise the myocardium to the effects of catecholamines. 

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. 

Noradrenaline and adrenaline increase blood pressure, although in various organs the perfusion can actually be reduced. Since adrenaline, in contrast to noradrenaline, stimulates a-and jSi-adrenoceptors and the jSi-subtype as well, its vascular effects are more complex than those of noradrenaline. In many vessel beds like the splanchnic area and the skin the O -adrenoceptor-mediated vasoconstriction is dominant. However, in others, like the active skeletal muscles, the jS2-adrenoceptor-mediated vasodilatation increases the blood flow. In the lower concentration range adrenaline induce an increase in blood pressure without elevated diastolic values. Catecholamines reduce the permeability of the vascular endothelium which might be of some importance for their antiallergic properties. 

The pharmacologic actions of phenoxybenzamine are primarily related to antagonism of -receptor-mediated events. The most significant effect is attenuation of catecholamine-induced vasoconstriction. While phenoxybenzamine causes relatively little fall in blood pressure in normal supine individuals, it reduces blood pressure when sympathetic tone is high, eg, as a result of upright posture or because of reduced blood volume. Cardiac output may be increased because of reflex effects and because of some blockade of presynaptic k2 receptors in cardiac sympathetic nerves. 

Cocaine, which blocks the uptake of catecholamines, produces dose-dependent effects, initially causing euphoria, vasoconstriction, and tachycardia, and in toxic doses, convulsions, myocardial depression, ventricular fibrillation, medullary depression, and death. Cocaine is able to block nerve conduction and currently is used only for topical anesthesia. 

The most serious toxic effects of cocaine involve changes in the cardiovascular system. These include cardiac arrhythmias, myocardial ischaemia and infarction, and cerebrovascular spasm, all of which can be largely explained by the facilitation of the action of catecholamines on the cardiovascular system. Another explanation of the cardiotoxicity of cocaine lies in the direct vasoconstrictive properties of its major metabolite, norcocaine. It seems likely... 

Cardiovascular effects include tachycardia, hypertension, and increased cardiac irritability large intravenous doses can cause cardiac failure. Cardiac dysrhythmias have been ascribed to a direct toxic effect of cocaine and a secondary sensitization of ventricular tissue to catecholamines (17), along with slowed cardiac conduction secondary to local anesthetic effects. Myocardial infarction has increased as a complication of cocaine abuse (7,8). Dilated cardiomyopathies, with subsequent recurrent myocardial infarction, have been associated with long-term use of cocaine, raising the possibility of chronic effects on the heart (18). Many victims have evidence of pre-existing fixed coronary artery disease precipitated by cocaine (SEDA-9, 35) (19-21). However, myocardial infarction has been noted even in young intranasal users with no evidence of coronary disease (22), defined by autopsy or angiography (23,24). If applied to mucous membranes, cocaine causes local vasoconstriction, and, with chronic use, necrosis. 

Peripheral Pharmacological Actions of Nicotine. Nicotine effects on the cardiovascular system include tachycardia and peripheral vasoconstriction, which leads to elevated blood pressure. Because the cardiovascular effects are mainly caused by elevated levels of catecholamines and cortisol, tolerance to these effects does not occur. Other pharmacological actions of nicotine include increased gastrointestinal motility caused by parasympathetic ganglionic stimulation and skeletal muscle contraction caused by the effect on nicotinic receptors in the neuromuscular junction (184). 

This endothelial effect and the permissive effect of glucocorticoids on catecholamine-induced vasoconstriction inhibit edema and swelling. Use of glucocorticoids to reduce inflammation due to bacterial infection should not be undertaken without concurrent use of antibiotics. 

Circulating angiotensin II can elevate BP through pressor and volume effects. The pressor effects include direct vasoconstriction, stimulation of catecholamine release from the adrenal meduUa, and centrally mediated increases in sympathetic nervous system activity. Angiotensin II also stimulates aldosterone synthesis from the adrenal cortex. This leads to sodium and water reabsorption that increases plasma volume, total peripheral resistance, and ultimately, BP. Clearly, any disturbance in the body that leads to activation of the RAAS could explain chronic hypertension. 

Dobutamine, a synthetic catecholamine, is a - and 82-receptor agonist with some a -agonist effects (see Table 14—14). Unhke dopamine, dobutamine does not cause release of NE from nerve terminals. The overall hemodynamic effects of dobutamine are the result of its effects on adrenergic receptors and reflex-mediated actions. Its P2-receptor-mediated effects are greater than those of dopamine, and /82-receptor-mediated vasodilation will tend to offset some of the -receptor-mediated vasoconstriction. Thus the uet vascular effect is usually vasodilation. The positive inotropy is primarily a P -receptor-mediated effect. Cardiac -receptor stimulation by dobutamine causes an increase in contractility but generally no significant change in heart rate and may provide an explanation for the apparently more modest chronotropic actions of dobutamine compared with dopamine. 

Dopamine often is recommended as the initial catecholamine in sepsis because it increases blood pressure by increasing myocardial contractility and vasoconstriction. Dopamine has been described to have dose-related receptor activity at DAj-, DA2-, fi -, and i-receptors. Unfortunately, this dose-response relationship has not been confirmed in critically ill patients. In patients with septic shock, there is a great overlap of hemodynamic effects even at doses as low as 3 mcg/kg per minute. Tachydysrhythmias are common owing to the release of endogenous norepinephrine by dopamine entering the sympathetic nerve terminal. Dopamine may increase the PAOP through pulmonary vasoconstriction. This drug also may depress ventilation and worsen hypoxemia in patients dependent on the hypoxic ventilatory drive. 

Catecholamine vasopressors may result in adverse peripheral vasoconstrictive, metabolic, and dysrhythmogenic effects that limit or outweigh their positive effects on the central circulation. Norepinephrine, phenylephrine, and epinephrine can produce a lactic acidosis secondary to excessive constriction in peripheral arterioles. 

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