Epinephrine, blood

Isoflurane is a respiratory depressant (71). At concentrations which are associated with surgical levels of anesthesia, there is Htde or no depression of myocardial function. In experimental animals, isoflurane is the safest of the oral clinical agents (72). Cardiac output is maintained despite a decrease in stroke volume. This is usually because of an increase in heart rate. The decrease in blood pressure can be used to produce "deHberate hypotension" necessary for some intracranial procedures (73). This agent produces less sensitization of the human heart to epinephrine relative to the other inhaled anesthetics. Isoflurane potentiates the action of neuromuscular blockers and when used alone can produce sufficient muscle relaxation (74). Of all the inhaled agents currently in use, isoflurane is metabolized to the least extent (75). Unlike halothane, isoflurane does not appear to produce Hver injury and unlike methoxyflurane, isoflurane is not associated with renal toxicity. 

Desflurane is less potent than the other fluorinated anesthetics having MAC values of 5.7 to 8.9% in animals (76,85), and 6% to 7.25% in surgical patients. The respiratory effects are similar to isoflurane. Heart rate is somewhat increased and blood pressure decreased with increasing concentrations. Cardiac output remains fairly stable. Desflurane does not sensitize the myocardium to epinephrine relative to isoflurane (86). EEG effects are similar to isoflurane and muscle relaxation is satisfactory (87). Desflurane is not metabolized to any significant extent (88,89) as levels of fluoride ion in the semm and urine are not increased even after prolonged exposure. Desflurane appears to offer advantages over sevoflurane and other inhaled anesthetics because of its limited solubiHty in blood and other tissues. It is the least metabolized of current agents. 

These agents are often combined with a vasoconstrictant such as epinephrine [51-43-4]. By using such a combination, the local anesthetic is held in the area for a longer period of time and its effect extended hemorrhage is minimized, blood loss prevented, and a better surgical repair obtained. 

Neuronal Norepinephrine Depleting Agents. Reserpine (Table 6) is the most active alkaloid derived from Rauwolfia serpentina. The principal antihypertensive mechanism of action primarily results from depletion of norepinephrine from peripheral sympathetic nerves and the brain adrenergic neurons. The result is a drastic decrease in the amount of norepinephrine released from these neurons, leading to decrease in vascular tone and lowering of blood pressure. Reserpine also depletes other transmitters including epinephrine, serotonin [50-67-9] dopamine [51-61-6] ... 

Storage and utilization of tissue glycogen, maintenance of blood glucose concentration, and other aspects of carbohydrate metabolism are meticulously regulated by hormones, including insulin, glucagon, epinephrine, and the glucocorticoids. 

Epinephrine itself does find some use in clinical medicine. The drug is used in order to increase blood pressure in cases of circulatory collapse, and to relax the bronchial muscle in acute asthma and in anaphylactic reactions. These activities follow directly from the agent s physiologic role. The biogenetic precursor of epinephrine, norepinephrine, has activity in its own right as a mediator of sympathetic nerve action. (An apocryphal story has it that the term nor is derived from a label seen on a bottle of a key primary amine in a laboratory in Germany N ohne... 

The adrenergic dragp are important in the care and treatment of patients in shock. Shock is defined as a life-threatening condition of inadequate perfusion. In shock, there is an inadequate supply of arterial blood flow and oxygen delivery to the cells and tissues. The body initiates compensatory mechanisms to counteract the symptoms of shock (eg, the release of epinephrine and norepinephrine), hi some situations, the body is able to compensate and blood pressure is maintained. However, if shock is untreated and compensatory mechanisms of the body fail, irreversible shock occurs and... 

The COMT inhibitors should not be administered with the monoamine oxidase (MAO) inhibitors (see Chap. 31) because there is an increased risk of toxicity. If the COMT inhibitors are administered with norepinephrine, dopamine, dobutamine, methyldopa, or epinephrine, there is a risk of increased heart rate, arrhythmias, and excessive blood pressure changes. 

Ephedrine enhances the release of the hormone norepinephrine in the body, and also binds to the same receptors as that hormone, causing excess calories to be converted to heat instead of being stored as fat. It also raises blood pressure. Epinephrine and norepinephrine are also known as adrenaline and noradrenaline. Ephedrine thus acts to stimulate an adrenaline rush. 

While epinephrine is usually well tolerated in young and healthy individuals, there may be problems in elderly patients with cardiac arrhythmia or previous myocardial infarction episodes [31-33]. Pharmacological effects of epinephrine include rapid rise in blood pressure, pallor, anxiety, tachycardia, headache and tremor as well as vertigo. Most commonly these effects occur after intravenous injection or after overdosing epinephrine. Cardiac arrhythmia or pulmonary edema may develop in serious cases [33, 34]. 

Epinephrine is widely used in clinical medicine for its multiple pharmacologic effects particularly for its potent vasoconstrictor effects. For example, in a dilute solution of 1 100,000, it provides a surgical tourniquet and facilitates a blood-free operating field. It is administered by nebulizer and face mask for post-intubation croup and for viral croup. 

Serious adverse effects of epinephrine potentially occur when it is given in an excessive dose, or too rapidly, for example, as an intravenous bolus or a rapid intravenous infusion. These include ventricular dysrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in blood pressure, and cerebral hemorrhage. The risk of epinephrine adverse effects is also potentially increased in patients with hypertension or ischemic heart disease, and in those using (3-blockers (due to unopposed epinephrine action on vascular Ui-adrenergic receptors), monoamine oxidase inhibitors, tricyclic antidepressants, or cocaine. Even in these patients, there is no absolute contraindication for the use of epinephrine in the treatment of anaphylaxis [1,5,6]. 

In an anesthetized, ventilated canine model of anaphylactic shock defined as hypotension with blood pressure maintained at 50% of baseline, epinephrine infusion produces an improvement in blood pressure, associated with positive inotropy [21]. 

PNMT catalyzes the N-methylation of norepinephrine to form epinephrine in the epinephrine-forming cells of the adrenal medulla. Since PNMT is soluble, it is assumed that norepinephrine-to-epinephrine conversion occurs in the cytoplasm. The synthesis of PNMT is induced by glucocorticoid hormones that reach the medulla via the intra-adrenal portal system. This special system provides for a 100-fold steroid concentration gradient over systemic arterial blood, and this high intra-adrenal concentration appears to be necessary for the induction of PNMT. 

During phase I, each seizure causes a sharp increase in autonomic activity with increases in epinephrine, norepinephrine, and steroid plasma concentrations, resulting in hypertension, tachycardia, hyperglycemia, hyperthermia, sweating, and salivation. Cerebral blood flow is also increased to preserve the oxygen supply to the brain during this period of high metabolic demand. Increases in sympathetic and parasympathetic stimulation with muscle hypoxia can lead to ventricular arrhythmias, severe acidosis, and rhabdomyolysis. These, in turn, could lead to hypotension, shock, hyperkalemia, and acute tubular necrosis. 

Both vasoconstrictors and vasodilators have been used in the treatment of priapism. Vasoconstrictors are thought to work by forcing blood out of the cavernosum and into the venous return. Aspiration of the penile blood followed by intracavenous irrigation with epinephrine (1 1,000,000 solution) has been effective with minimal complications.37 In severe cases, surgical intervention to place penile shunts has been used, but there is a high failure rate, and the risk of complications, from skin sloughing to fistulas, limits its use. 

Epinephrine is a nonspecific a- and P-adrenergic agonist. Epinephrine can increase cardiac index and produce significant peripheral vasoconstriction. However, it can also increase lactate levels and impair blood flow to the splanchnic system. Because of these undesirable effects, epinephrine should be reserved for patients who fail to respond to traditional therapies.24,27-28... 

This blood pressure and the plasma epinephrine and norepinephrine (2 and 3 above) effect of caffeine disappear after a few days, even if heavy coffee consumption continues. 

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