Epinephrine arrhythmia with

In an undated study, HCFC-141b was administered to male SpragueDawley rats at concentrations of 5,000, 10,000, or 20,000 ppm for 30 min (Eger, unpublished data). As exposure continued, bolus intravenous epinephrine, characterized as three times the dose that produced arrhythmias in the same rats anesthetized with halothane, was administered. The dose of epinephrine was defined as a maximum of 12 fig/kg. For this study, three or more premature ventricular contractions was considered an arrhythmic response (Table 4—5). Marked arrhythmias occurred at all concentrations. The author further compared the concentrations of halothane and HCFC-141b that produced arrhythmias with administration of various doses of exogenous epinephrine. The nominal chamber concentration for HCFC-141b did not differ from that of halothane. Furthermore, the arrhythmias were characterized as relatively mild and within acceptable limits for surgical anesthesia in humans. 

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. 

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]. 

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. 

Although it is an optimized model, the end point of cardiac sensitization is relevant as humans exposed at high concentrations of some halocarbons may develop cardiac arrhythmias. The concentration of 80,000 ppm along with intravenous epinephrine, which induced a marked cardiac response in the dog, was used as the basis for the AEGL-3 values. Because the dog heart is considered an appropriate model for the human heart, an interspecies UF of 1 was applied. Because the cardiac sensitization test is a conservative test, the 80,000 ppm concentration was adjusted by an intraspecies UF of 3 to protect potentially susceptible individuals. Blood concentrations were close to equi... 

Trochimowicz, H,J. 1997. Experience with the epinephrine sensitivity test for arrhythmia induction. In R.Snyder, K.S.Bakshi, and B.M.Wagner, Abstracts of the Workshop on Toxicity of Alternatives to Chlorofluorocarbons. Inhal. Toxicol. 9 775-810. 

Cardiac arrhythmias were induced in rats injected with exogenous epinephrine and exposed to HCFC-141 b at 5,000 ppm. However, the intravenous dose of epinephrine required was 3-fold that which induced arrhythmias in the same rats administered halothane, a common clinical anesthetic. Furthermore, the arrhythmias were characterized as mild. The threshold for cardiac sensitization for dogs was approximately 5,200 ppm. Deaths occurred in one study at 10,000 ppm and in another study at 20,000 ppm (with no deaths between concentrations of 9,000 and 19,000 ppm). 

Humans exposed at high concentrations of some halogenated hydrocarbons can develop cardiac arrhythmias. The cardiac sensitization test in dogs is considered an effective determination of potential cardiac sensitization in humans. Cardiotoxicity was observed at concentrations well below those associated with any acute toxic signs but only in the presence of greater-than-physiological doses of exogenous epinephrine. 

Data adequacy Humans exposed to halocarbons may develop cardiac arrhythmias. The cardiac sensitization test with the dog is a good model because the test is highly sensitive (i.e., the exogenous dose of epinephrine is at much greater than physiological levels). The concentration of 1,700 ppm is far below ... 

Rats did not survive when exposed for longer than 12-18 minutes to 12,000ppm. When exposed repeatedly to 470 ppm, they showed liver and kidney injury. Cardiac arrhythmias owing to sensitization of the myocardium to epinephrine have been observed with certain other chlorinated hydrocarbons, but exposure of dogs to perchloroeth-... 

Drugs metabolized by COMT Administer drugs known to be metabolized by COMT (ie, isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, methyidopa, apomorphine, isoetherine, bitolterol) with caution in patients receiving entacapone regardless of the route of administration (including inhalation), as their interaction may result in increased heart rates, arrhythmias, and excessive changes in blood pressure. 

The greatest hazards of accidental overdosage with epinephrine and norepinephrine are cardiac arrhythmias, excessive hypertension, and acute pulmonary edema. Large doses of isoproterenol can produce such excessive cardiac stimulation, combined with a decrease in diastolic blood pressure, that coronary insufficiency may result. It also may cause arrhythmias and ventricular fibrillation. Tissue sloughing and necrosis due to severe local ischemia may follow extravasation of norepinephrine at its injection site. 

Patients treated with recommended dosages of epinephrine will complain of feeling nervous or anxious. Some will have tremor of the hand or upper extremity and many will complain of palpitations. Epinephrine is dangerous if recommended dosages are exceeded or if the drug is used in patients with coronary artery disease, arrhythmias, or hypertension. The inappropriate use of epinephrine has resulted in extreme hypertension and cerebrovascular accidents, pulmonary edema, angina, and ventricular arrhythmias, including ventricular fibrillation. 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

Drugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effective because they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine and epinephrine) on the heart.5,28 This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowing heart rate.5 Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of the atrioventricular node.21 Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation.23 Some ventricular arrhythmias may also respond to treatment with beta blockers. 

Beta blockers bind to beta-1 receptors on the myocardium and block the effects of norepinephrine and epinephrine (see Chapter 20). These drugs therefore normalize sympathetic stimulation of the heart and help reduce heart rate (negative chronotropic effect) and myocardial contraction force (negative inotropic effect). Beta blockers may also prevent angina by stabilizing cardiac workload, and they may prevent certain arrhythmias by stabilizing heart rate.40 These additional properties can be useful to patients with heart failure who also have other cardiac symptoms. 

In contrast to phenoxybenzamine, phentolamine [fen TOLE a meen] produces a competitive block of ai and a2 receptors. The drug s action lasts for approximately 4 hours after a single administration. Like phenoxybenzamine, it produces postural hypotension and causes epinephrine reversal. Phentolamine had been used in the diagnosis of pheochromocytoma and in other clinical situations associated with excess release of catecholamines. Phentolamine-induced reflex cardiac stimulation and tachycardia are mediated by the baroreceptor reflex and by blocking the a2 receptors of the cardiac sympathetic nerves. The drug can also trigger arrhythmias and anginal pain and is contraindicated in patients with decreased coronary perfusion. 

DIRECT ANAESTHETICS-GENERAL 1. Risk of arrhythmias when inhalational anaesthetics are coadministered with epinephrine or norepinephrine 2. Case report of marked t BP when phenylephrine eye drops given during general anaesthesia... 

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