Theophylline arrhythmia with

Concurrent use of the fluoroquinolones with theophylline causes an increase in serum theophylline levels. When used concurrently with cimetidine, the cimetidine may interfere with the elimination of the fluoroquinolones. Use of the fluoroquinolones with an oral anticoagulant may cause an increase in the effects of the oral coagulant. Administration of the fluoroquinolones with antacids, iron salts, or zinc will decrease absorption of the fluoroquinolones. There is a risk of seizures if fluoroquinolones are given with the NSAIDs. There is a risk of severe cardiac arrhythmias when the fluoroquinolones gatifloxacin and moxifloxacin are administered with drains that increase the QT interval (eg, quini-dine, procainamide, amiodarone, and sotalol). 

Hemoperfusion is like hemodialysis except that blood is circulated extracorporeally through a column with adsorbent material like resin or charcoal, which binds molecules electrostatically. The molecules likely to be removed are characterized as poorly dialyzable, lipid-soluble, protein bound. Among the indications for hemoperfusion in the management of poisoning include the presence of a poison in a patient with impairment of excretory system (i.e. damaged kidneys), intoxication of a drug known to produce delayed toxicity or metabolized to a more toxic metabolite (i.e. paraquat or methotrexate), deterioration of the clinical state of the poisoned patient despite conservative therapy (i.e. convulsions or cardiac arrhythmias following theophylline intoxication), or development of coma as a complication. 

The mercury ion is capable of causing local or systemic toxicity. For local irritation, they are combined with theophylline in an attempt to diminish the irritative toxicity at the site of injection. IV administration may lead to ventricular arrhythmias. They cause hepatocellular damage and even precipitate hepatic failure. They can also lead to low salt syndrome, hypochloraemic alkalosis and potassium depletion. 

Side effects are usually associated with the increasing serum concentration of theophylline and includes nausea, vomiting, headache, insomnia, tachypnea, epigastric pain, palpitation, hypotension, irritability. Higher doses can cause persistent vomiting, cardiac arrhythmias, intractable seizures, tachycardia. Other side effects include alopecia, hyperglycemia, inappropriate ADH syndrome, rash. 

Theophylline should be used only where methods to measure theophylline blood levels are available because it has a narrow therapeutic window, and its therapeutic and toxic effects are related to its blood level. Improvement in pulmonary function is correlated with plasma concentrations in the range of 5-20 mg/L. Anorexia, nausea, vomiting, abdominal discomfort, headache, and anxiety occur at concentrations of 15 mg/L in some patients and become common at concentrations greater than 20 mg/L. Higher levels (more than 40 mg/L) may cause seizures or arrhythmias these may not be preceded by gastrointestinal or neurologic warning symptoms. 

Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Alfa interferons are abortifacient in primates and should not be administered in pregnancy. Potential drug-drug interactions include increased theophylline levels and increased methadone levels. Co-administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias. 

Alterations in the serum potassium level are hazardous because they can result in cardiac arrhythmias. Drugs that may cause hyperkalemia despite normal renal function include potassium itself, 13 blockers, digitalis glycosides, potassiumsparing diuretics, and fluoride. Drugs associated with hypokalemia include barium, 13 agonists, caffeine, theophylline, and thiazide and loop diuretics. 

Cardiovascular toxicity is also frequently encountered in poisoning. Hypotension may be due to depression of cardiac contractility hypovolemia resulting from vomiting, diarrhea, or fluid sequestration peripheral vascular collapse due to blockade of -adrenoceptor-mediated vascular tone or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, tricyclic antidepressants, digitalis, and theophylline. 

Theophylline [the OFF i lin] is a bronchodilator that relieves airflow obstruction in chronic asthma, and decreases the symptoms of the chronic disease. Previously the main-stay of asthma therapy, theophylline has been largely replaced with (3-agonists and corticosteroids. Theophylline is well absorbed by the gastrointestinal tract, and several sustained-release preparations are available. The drug has a narrow therapeutic window, and an overdose of the drug may cause seizures or potentially fatal arrhythmias. Further, theophylline interacts adversely with many drugs. See pp. 450-451 for a description of newly approved drugs, zileuton, zafirlukast, and montelukast. 

INHALATIONAL- HALOTHANE TERBUTALINE, THEOPHYLLINE Cases of arrhythmias when these bronchodilators are co-administered with halothane Possibly due to sensitization of the myocardium to circulating catecholamines by the volatile anaesthetics to varying degrees Risk of cardiac events is higher with halothane. Desflurane is irritant to the upper respiratory tract, and t secretions can occur and are best avoided in patients with bronchial asthma. Sevoflurane is non-irritant and unlikely to cause serious adverse effects... 

Cardiac arrhythmia frequently accompanies poisoning, e.g. with tricyclic antidepressants, theophylline, P-adrenoceptor blockers. Acidosis, hypoxia and electrolyte disturbance are often important contributory factors the emphasis of therapy should be to correct these and to resist the temptation to resort to an antiarrhythmic drug. If arrhythmia leads... 

Interactions. Erythromycin and the other macro-lides are enzyme inhibitors and interfere with the metabolic inactivation of some drugs, e.g. warfarin, carbamazepine, theophylline, disopyramide, increasing their effects. Reduced inactivation of terfena-dine may lead to serious cardiac arrhythmias, and of ergot alkaloids may cause ergotism. 

Interactions. Several types of drug interfere with lithium excretion by the renal tubules, causing the plasma concentration to rise. These include diuretics (thiazides more than loop type), ACE inhibitors and angiotensin-11 antagonists, and nonsteroidal anti-inflammatory analgesics. Theophylline and sodium-containing antacids reduce plasma lithium concentration. The effects can be important because lithium has such a low therapeutic ratio. Diltiazem, verapamil, carbamazepine and pheny-toin may cause neurotoxicity without affecting the plasma lithium. Concomitant use of thioridazine should be avoided as ventricular arrhythmias may result. 

Overdose with theophylline has assumed greater importance with the advent of sustained-release preparations which prolong toxic effects, with peak plasma concentrations being reached 12-24 h after ingestion. Vomiting may be severe but the chief dangers are cardiac arrhythmia, hypotension, hypokalaemia and seizures. Activated charcoal should be given every 2-4 h until the plasma concentration is below 20 mg/1. Potassium replacement is important to prevent arrhythmias. Diazepam is used to control convulsions. 

In acute overdose, peak serum levels > 100 pg ml may be predictive of arrhythmias and seizures. The use of sustained-release formulations and the presence of pharmacobezors in the gut may make it difficult to determine peak serum levels. Sinus tachycardia is the most common cardiac sign of theophylline toxicity. Ventricular and supraventricular tachycardia, ectopic beats, hypotension, and cardiac arrest may occur. Metabolic acidosis, hypokalemia, hypercalcemia, and hyperglycemia may be seen. Tremulousness and agitation frequently occur. Intractable seizures may occur in severe intoxications, probably secondary to adenosine receptor antagonism in the brain. Onset of seizures is a poor prognostic indicator. Persistent vomiting is commonly seen and may interfere with attempts at therapy. 

Poisoning with slow-release theophylline preparations can lead to development al ter 24-48 h of severe arrhythmias, hypo-kalacmia and death. In cases of suspected poisoning, the theophylline concentration should be mciisured and its rise or fall monitored. Measures to aid elimination are of limited effect. 

Factors that commonly precipitate cardiac arrhythmias include hypoxia, electrolyte disturbances (especially hypokalemia), myocardial ischemia, and certain drugs (Table 34-1). For example, theophylline can cause multifocal atrial tachycardia, while torsades de pointes can arise not only during therapy with action potential-prolonging antiarrhythmics but also with other drugs, including erythromycin (see Chapter 46) pentamidine (see Chapter 40) and some antipsy-chotics, notably thioridazine (see Chapter 18). 

The primary indication for theophylline is as a controller medication for the treatment of bronchospasm of asthma and COPD. In addition to bronchodilation effects, theophylline dilates pulmonary blood vessels, acts centrally to stimulate respiration, acts as a diuretic, increases gastric acid secretion, and inhibits uterine contractions. Dosing requires the determination of plasma levels with 10 to 20 pg/mL being associated with the least incidence of side effects. Overdose of theophylline can result in a quick onset of ventricular arrhythmias, convulsions, or even death... 

Established interactions. The CSM in the UK advises that, as potentially serious hypokalaemia may result from beta2 agonist therapy, particular caution is required in severe asthma, as this effect may be potentiated by theophylline and its derivatives, corticosteroids, diuretics, and by hypoxia. Hypokalaemia with concurrent use of thiazide and loop diuretics may be reduced or even abolished by the addition of spironolactone or high-dose triamterene. Plasma potassium levels should therefore be monitored in patients with severe asthma. Hypokalaemia may result in cardiac arrhythmias in patients with ischaemic heart disease and may also affect the response of patients to drugs such as the digitalis glycosides and an-tiarrhythmics. 

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