Norepinephrine arrhythmia with

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. 

All antiarrhythmic dra are used cautiously in patients with renal or hepatic disease. When renal or hepatic dysfunction is present, a dosage reduction may be necessary. All patients should be observed for renal and hepatic dysfunction. Quinidine and procainamide are used cautiously in patients with CHF. Disopyramide is used cautiously in patients with CHF, myasthenia gravis, or glaucoma, and in men with prostate enlargement. Bretylium is used cautiously in patients with digitalis toxicity because the initial release of norepinephrine with digitalis toxicity may exacerbate arrhythmias and symptoms of toxicity. Verapamil is used cautiously in patients with a history of serious ventricular arrhythmias or CHF. Electrolyte disturbances such as hypokalemia, hyperkalemia, or hypomagnesemia may alter the effects of the antiarrhythmic dru . Electrolytes are monitored frequently and imbalances corrected as soon as possible... 

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. 

The answer is b. (Kn.lzu.ng, p 5.38.) Crack is the free-base (nonsalt) form of the alkaloid cocaine. It is called crack because, when heated, it makes a crackling sound. Heating crack enables a person to smoke it the drug is readily absorbed through the lungs and produces an intense euphoric effect in seconds Use has led to seizures and cardiac arrhythmias. Some of cocaine s effects (sympathomimetic) are due to blockade of norepinephrine reuptake into presynaptic terminals it does not block receptors. Flashbacks can occur with use of LSD and mescaline but have not been associated with the use of cocaine. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Hypotension Hypotension (postural) occurs regularly in about 50% of patients while they are supine, manifested by dizziness, light-headedness, vertigo, or faintness. Tolerance occurs unpredictably but may be present after several days. Hypotension with supine systolic pressure above 75 mm Hg need not be treated unless symptomatic. If supine systolic pressure falls below 75 mm Hg, infuse dopamine or norepinephrine to increase blood pressure use dilute solution and monitor blood pressure closely because pressor effects are enhanced by bretylium. Perform volume expansion with blood or plasma and correct dehydration where appropriate. Transient hypertension and increased frequency of arrhythmias Transient hypertension and increased frequency of arrhythmias may occur due to initial release of norepinephrine from adrenergic postganglionic nerve terminals. 

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. 

Contraindications for antipsychotic therapy are few they may include Parkinson s disease, hepatic failure, hypotension, bone marrow depression, or use of CNS depressants. Overdoses of antipsychotics are rarely fatal, except for thioridazine, which is associated with major ventricular arrhythmias, cardiac conduction block, and sudden death. For other agents gastric lavage should be attempted even if several hours have elapsed since the drug was taken, because gastrointestinal motility is decreased and the tablets may still be in the stomach. Moreover, activated charcoal effectively binds most of these drugs and can be followed by a saline cathartic. The hypotension often responds to fluid replacement or pressor agents such as norepinephrine. 

Cocaine differs from the other local anesthetics with respect to its cardiovascular effects. Cocaine s blockade of norepinephrine reuptake results in vasoconstriction and hypertension, as well as cardiac arrhythmias. The vasoconstriction produced by cocaine can lead to local ischemia and, in chronic abusers who use the nasal route, ulceration of the mucous membrane and damage to the nasal septum have been reported. The vasoconstrictor properties of cocaine can be used clinically to decrease bleeding from mucosal damage or surgical trauma in the nasopharyneal region. 

Several agents are available that inhibit activity at adrenergic synapses by interfering with the release of norepinephrine. Rather than directly blocking the postsynaptic receptor, these drugs typically inhibit or deplete the presynaptic terminal of stored norepinephrine. These drugs are used primarily to decrease peripheral adrenergic influence and to treat problems such as hypertension and cardiac arrhythmias. 

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. 

Local anesthetics block the sodium channels, are cardiac depressants, and bring about a ventricular conduction defect and block that may progress to cardiac and ventilatory arrest if toxic doses are given. In addition, these agents produce arteriolar dilation. Circulatory failure may be treated with vasopressors such as ephedrine, metaraminol (Aramine), or mephentermine (Wyamine). Artificial respiration and cardiac massage may also become necessary. Among the local anesthetics, only cocaine blocks the uptake of norepinephrine, causes vasoconstriction, and may precipitate cardiac arrhythmias. 

Cocaine also blocks the reuptake of norepinephrine in the PNS the combination of central and peripheral actions leads to a high probability of toxicity. The cardiovascular system is particularly sensitive to the actions of cocaine, and cardiac arrhythmias, marked increases in blood pressure, cerebral hemorrhage, myocardial ischemia, and outright heart failure are not uncommon with cocaine use. Even young, otherwise healthy individuals with normal coronary and cerebral arteries have died suddenly after cocaine use from cerebral hemorrhage or ventricular fibrillation. There have been several deaths of famous athletes attributed to cocaine cardiotoxicity. These cardiotoxic effects may be related to increased intracellular calcium levels and involve both cardiac and vascular actions of the drug. 

MAO inhibitors were the first widely used antidepressants, but because of various undesirable side effects they are employed today in only a more limited number of cases. People who are treated with MAO inhibitors, for example, must be careful of their diet. They should not eat food rich in tyramine or other biologically active amines. These foods include cheese, beer, and red wine. Individuals on MAO inhibitors are unable to inactivate tyramine present in the food. Because tyramine causes the release of endogenous norepinephrine, patients are susceptible to increased blood pressure (e.g., potential lethal cerebral hemorrhages) and cardiac arrhythmias. 

Endogenous norepinephrine stimulates cardiac beta receptors. Receptor-linked cAMP-dependent protein kinases phosphorylate calcium channels to increase intracellular calcium. Elevated intracellular calcium increases conduction velocity (phase 0) and decreases the threshold potential in normal SA and AV node cells (see Figure 12.13). Beta blockers slow spontaneous conduction velocity in the SA node by approximately 10-20 percent. In addition, beta blockers can slow conduction velocity while increasing the refractory period of the AV node. These effects control the ventricular rate in atrial fibrillation or flutter and terminate paroxysmal supraventricular tachycardias. They are also safer, although somewhat less effective, than other drugs for suppression of premature ventricular complexes (PVCs). Drugs in this class approved by the FDA for treatment of various arrhythmias include propranolol, acebutolol, and esmolol. Problems with the beta blockers include drowsiness, fatigue, impotence, and depressed ventricular performance. 

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... 

LEVODOPA, SELEGILINE, POSSIBLY RASAGILINE, ENTACAPONE, TOLCAPONE MAOIs Risk of adrenergic syndrome -hypertension, hyperthermia, arrhythmias - and dopaminergic effects with selegiline Levodopa and related drugs are precursors of dopamine. Levodopa is predominantly metabolized to dopamine, and a smaller proportion is converted to epinephrine and norepinephrine. Effects are due to inhibition of MAOI, which breaks down dopamine and sympathomimetics Avoid concurrent use. Onset may be 6-24 hours after ingestion. Carbidopa and benserazide, which inhibit dopa decarboxylase that converts L-dopa to dopamine, is considered to minimize this interaction. However, MAOIs should not be used in patients with Parkinson s disease on treatment with levodopa. Imipramine and amitriptyline are considered safer by some clinicians... 

When this enzyme is inhibited, the concentrations of norepinephrine within adrenergic neurons increase and drugs that stimulate its release can bring about an exaggerated response. Interactions between MAO inhibitors and indirectly acting sympathomimetic amines (e.g., amphetamine) develop by this mechanism. If amphetamine is administered to a patient whose stores of norepinephrine have been increased by MAO inhibition, the patient may experience severe headache, hypertension (possibly a hypertensive crisis), and cardiac arrhythmias. The serious consequences associated with these interactions contraindicate the use of these agents in combination. 

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