Theophylline hypokalemia with

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. 

Salbutamol has additive effects with theophylline, which can potentiate the hypokalemic effect (SEDA-17, 164). In 14 healthy volunteers, theophylline increased salbu-tamol-induced hjrpokalemia and in some individuals there was profound hypokalemia (less than 2.5 mmol/1) (35). Combining theophylline with salbutamol increased the tachycardia resulting from the salbutamol infusion. Salbutamol infusion caused a fall in diastolic and a rise in systolic blood pressure, which was not altered by theophylline. 

A 73-year-old man took an unknown number of theophylline modified-release tablets and furosemide 40 mg tablets. He developed a tachydysrhythmia, vomiting, and restlessness. His maximum theophylline concentration was 67 pg/ml and he had hypokalemia (2.8 mmol/1) and hyponatremia (123 mmol/1). The maximum creatine kinase activity was (32 mol/1 [sic]) and the serum myoglobin concentration was 3789 pg/l. He was treated with oral activated charcoal, continuous venovenous hemodialysis, intravenous potassium and sodium chloride, forced diuresis, and continuous intravenous meto-prolol, and survived without sequelae. 

These cases of interactions of aminophylline with macro-lide antibiotics illustrate that serious, even fatal, adverse effects can occur when possible interactions are not considered. In both cases, experienced physicians prescribed appropriate antimicrobial drugs, but omitted to consider the possibility of interactions with aminophylline, and failed to reduce the dose of aminophyUme or to measure theophylline concentrations. In the first case the development of tachycardia, hypokalemia, acidosis, vomiting, and convulsions can be explained on the basis of theophylline toxicity caused by ciprofloxacin, while in the second the anxiety, tremor, and cardiac arrests could all have resulted from an interaction of aminophylline and erythromycin. These cases add to an extensive literature that emphasizes the potential for interaction between aminophylline and drugs metabolized by CYP1A2. 

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. 

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). 

IV. Diagnosis is based on the history of ingestion. The findings of tachycardia, hypotension with a wide pulse pressure, tremor, and hypokalemia are strongly suggestive. Theophylline overdose (see p 354) may present with similar manifestations. 

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