Potentiation of the adverse effects of intravenous terbutaline by oral theophylline.

Smith, S. R.; Kendall, M. J.

doi:10.1111/j.1365-2125.1986.tb05221.x

Cited by 23 publications

(8 citation statements)

References 16 publications

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“…The intravenous infusion rate of salbutamol used was in the lower half of the recommended intravenous dosage schedule for the treatment of severe asthma (A.B.P.I., 1985). A previous study has demonstrated that theophylline potentiated the hypokalaemic action of intravenous terbutaline (Smith & Kendall, 1986). We have confirmed and extended these observations.…”

Section: Discussionsupporting

confidence: 87%

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Salbutamol induced hypokalaemia: the effect of theophylline alone and in combination with adrenaline.

Whyte

Reid

Addis

et al. 1988

Brit J Clinical Pharma

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1 We have previously shown that salbutamol induced hypokalaemia, like adrenaline induced hypokalaemia, is the result of stimulation of a membrane bound 132-adrenoreceptor linked to Na+/K+ ATPase. We have also demonstrated that adrenaline induced hypokalaemia is potentiated by therapeutic concentrations of theophylline. 2 In a single-blind study of 14 normal volunteers, we infused salbutamol in doses used in clinical practice and examined the effects of the addition of theophylline alone or combined with (-)-adrenaline on plasma potassium levels, heart rate and blood pressure. The combinations studied were (i) salbutamol + vehicle control adrenaline infusion + placebo theophylline; (ii) salbutamol + vehicle control adrenaline infusion + theophylline; (iii) salbutamol + adrenaline + theophylline. 3 In a randomised, balanced placebo controlled design oral slow release theophylline or placebo was given for 9 days. Subjects were studied twice on the active limb (days 7 and 9) and once on the placebo limb (day 9) and the procedure was identical on each of the 3 study days except for the solutions administered. 4 Theophylline increased salbutamol induced hypokalaemia and in some individuals profound hypokalaemia (< 2.5 mmol 1-1) was observed with these relatively low doses of salbutamol and theophylline. Adrenaline did not further increase the magnitude of the fall in potassium observed. Combining theophylline with salbutamol increased the tachycardia resulting from the salbutamol infusion. Salbutamol infusion caused a fall in diastolic and rise in systolic blood pressure on all 3 study days and this was not altered by either theophylline or adrenaline alone or together. 5 We conclude that theophylline significantly increases salbutamol induced hypokalaemia and tachycardia and that the addition of adrenaline does not further increase hypokalaemia. Intensive bronchodilator therapy with these two agents in acutely ill, hypoxic patients with asthma or chronic obstructive lung disease may increase the risk of serious cardiac arrhythmias secondary to hypokalaemia.

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Section: Discussionsupporting

confidence: 87%

“…I., 1985). A previous study has demonstrated that theophylline potentiated the hypokalaemic action of intravenous terbutaline (Smith & Kendall, 1986). We have confirmed and extended these observations.…”

Section: Haemodynamic Measurements Discussionsupporting

confidence: 79%

Salbutamol induced hypokalaemia: the effect of theophylline alone and in combination with adrenaline.

Whyte

Reid

Addis

et al. 1988

Brit J Clinical Pharma

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“…terbutaline, are frequently used concomitantly by asthmatics and an additive bronchodilating effect of terbutaline when given together with theophylline has been demonstrated (Wolfe et al 1978;Baadsgaard et al, 1985;Vandewalker et al, 1986). Some studies indicated increased side effects (Wolfe et al, 1978;Wilson et al, 1981;Roddick et al, 1979;Barclay et al, 1981;Lonnerholm etal., 1981;Smith & Kendall, 1986) when both drugs were administered together. The adverse effects of theophylline -1-adrenoceptor agonist interactions have been reviewed by Nicklas & Balazs (1986).…”

Section: Introductionmentioning

confidence: 99%

Theophylline‐terbutaline, a steady state study on possible pharmacokinetic interactions with special reference to chronopharmacokinetic aspects.

Jonkman

Borgström

Boon

et al. 1988

Brit J Clinical Pharma

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1 The pharmacokinetic interaction of terbutaline and theophylline and chronopharmacokinetics of both drugs were studied in a three-way crossover study with repeated administration of terbutaline (Bricanyl Depot®) 7.5 mg twice daily, theophylline (TheoDurg) 300 mg twice daily alone or the combination of both for 7 days to 12 healthy volunteers (six male and six female). 2 After the morning dose on day 7, blood and urine were sampled for 12 h, and after the evening dose on day 7, blood and urine were sampled for 48 h. Theophylline concentrations in plasma and concentrations of unchanged drug and metabolites in urine were determined by two selective high performance liquid chromatography methods. Terbutaline concentrations in plasma and urine were measured with a gas chromatography-mass spectrometry method. Area under the plasma concentration-time curve, fluctuations in plasma concentration, mean residence time, elimination half-life, renal clearance as well as maximal, minimal and average plasma concentration at steady state were evaluated. 3 The addition of terbutaline to the repeated administration of theophylline lowered the relative bioavailability of theophylline by approximately 11% during the night interval, The rate of elimination of theophylline and mean residence time were influenced accordingly. No significant changes in excretion of the theophylline metabolites were observed, but the excretion of 3-methylxanthine was slightly reduced by the concomitant terbutaline administration. None of the observed changes should be of any clinical importance.4 The addition of theophylline did not influence any of the calculated pharmacokinetic parameters of terbutaline. 5 It can be concluded that no dosage adjustment is necessary when terbutaline and theophylline are given together. 6 Significant differences between the rates of absorption at day-time and at night-time were observed, both for theophylline and for terbutaline. The extent of absorption, however, was not different.

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“…One group suggested that this could be ameliorated by concomitant oral theophylline treatment [60]. Additional problems include local reactions [134], risk of hypokalaemia [139,140] and a skeletal myositis with elevation of creatine kinase [141].…”

Section: Subcutaneous Terbutaline Infusionmentioning

confidence: 99%

Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where?

Bush

Pedersen²,

Hedlin³

et al. 2011

European Respiratory Journal

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There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided into medications used in lower doses for children with less severe asthma, and those used in other paediatric diseases but not for asthma (for example, methotrexate). In the first category are high-dose inhaled corticosteroids (ICS) (f2,000 mg?day -1 fluticasone equivalent), oral prednisolone, the anti-immunoglobulin (Ig)E antibody omalizumab, high-dose long-acting b 2 -agonists, low-dose oral theophylline and intramuscular triamcinolone. If peripheral airway inflammation is thought to be a problem, the use of fine-particle ICS or low-dose oral corticosteroids may be considered. More experimental therapies include oral macrolides, cyclosporin, cytotoxic drugs such as methotrexate and azathioprine, gold salts, intravenous infusions of Ig, subcutaneous b 2 -agonist treatment and, in those sensitised to fungi, oral antifungal therapy with itraconazole or voriconazole. Those with recurrent severe exacerbations, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both at the time of exacerbations can be considered. There is no evidence regarding which therapeutic option to recommend. Better evidence is required for all these treatment options, underscoring the need for the international and co-ordinated approach which we have previously advocated.

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Potentiation of the adverse effects of intravenous terbutaline by oral theophylline.

Cited by 23 publications

References 16 publications

Salbutamol induced hypokalaemia: the effect of theophylline alone and in combination with adrenaline.

Salbutamol induced hypokalaemia: the effect of theophylline alone and in combination with adrenaline.

Theophylline‐terbutaline, a steady state study on possible pharmacokinetic interactions with special reference to chronopharmacokinetic aspects.

Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where?

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