Dopamine 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. 

Low-dose dopamine is not without adverse reactions and most studies have failed to evaluate its potential toxicities. Adverse reactions that may be associated with low-dose dopamine include tachycardia, arrhythmias, myocardial ischemia, depressed respiratory drive, and gut ischemia. Low-dose dopamine has also been postulated to impair resistance to infection through a reduction in prolactin concentrations.21 Furthermore, significant overlap in receptor activation occurs. Therefore, doses considered to activate only dopamine receptors may increase cardiac output and blood pressure through dopamine s effect on 3- or a-adrenergic receptors. 

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. 

Sertindole is one of the newer antipsychotic medications available. It is classified chemically as a phenylindole derivative and has activity at dopamine and serotonin receptors. It is not associated with sedative effects. Sertindole was voluntarily withdrawn from the market late 1998 due to concerns over the risk of cardiac arrhythmia s. The European Commission recommended lifting the marketing restrictions on sertindole in 2005 with a regulatory requirement of ECG monitoring. 

Succinylcholine-induced hyperkalemia may lead to cardiac arrhythmia and arrest when plasma reaches 7 and 10 mM, respectively. The drug also may precipitate a fulminant attack of malignant hyperthermia in susceptible individuals (not to be confused with neuroleptic malignant hyperpyrexia, which involves dopamine and the CNS). Treatment in either case consists of cooling the body and administering oxygen and dantrolene sodium (discussed later). 

Dopamine Dopamine receptor agonist higher doses activate 13 and a adrenoceptors Increases renal blood flow higher doses increase cardiac force and blood pressure Acute decompensated heart failure shock IV only duration a few minutes Toxicity Arrhythmias Interactions Additive with sympathomimetics... 

Another cardiac response to catecholamine release is Increased vulnerability to ventricular fibrillation. Recent studies (13) have shown that bromocriptine produced an increase of 50% in the ventricular fibrillation threshold In anesthetized dogs, and that pretreatment with the peripheral D-2 dopamine antagonist domperidone abolished this effect. This suggests that adrenergic induced cardiac arrhythmia may be inhibited by peripheral presynaptic dopamine agonists. 

Interactions The vitamin pyridoxine (B6) increases the peripheral breakdown of levodopa and diminishes its effectiveness (Figure 8.6). Concomitant administration of levodopa and monoamine oxidase (MAO) inhibitors, such as phenelzine (see p. 124), can produce a hypertensive crisis caused by enhanced catecholamine production therefore, caution is required when they are used simultaneously. In many psychotic patients, levodopa exacerbates symptoms, possibly through the buildup of central amines. In patients with glaucoma, the drug can cause an increase in intraocular pressure. Cardiac patients should be carefully monitored because of the possible development of cardiac arrhythmias. Antipsychotic drugs are contraindicated in parkinsonian patients, since these block dopamine receptors and produce a parkinsonian syndrome themselves. 

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... 

Addition of dopamine in "renal" doses (1-5 mcg/kg per minute) may help maintain good renal blood flow and blood pressure Pulmonary edema can be managed with cautious use of diuretics short courses of albumin may also be beneficial Patients with history of cardiac arrhythmias may require cardiac monitoring during IL-2 administration... 

Dopamine hydrochloride is used only intravenonsly. The drug initially is administered at a rate of 2 to 5 J,g/kg per minnte this rate may be increased gradually up to 20 to 50 pg/kg per minute or more, as the clinical situation dictates. Dnring the infnsion, patients require clinical assessment of myocardial fnnction, perfnsion of vital organs such as the brain, and the prodnction of nrine. Most patients shonld receive intensive care, with monitoring of arterial and venons pressnres and the ECG. Rednction in urine flow, tachycardia, or the development of arrhythmias may be indications to slow or terminate the infusion. The duration of action of dopamine is brief, and hence the rate of administration can be nsed to control the intensity of effect. 

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