Potentiation of isoprenaline‐induced plasma cyclic AMP response by aminophylline in normal and asthmatic subjects.

Trembath, Peter W.; Shaw, John M.

doi:10.1111/j.1365-2125.1978.tb00873.x

Cited by 15 publications

(6 citation statements)

References 12 publications

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“…However, if the /-receptor is stimulated significantly, such as by the upright posture, then this amplification is clinically evident. This explanation fits well with data showing potentiation of the rise in plasma cAMP seen with isoprenaline inhalation by theophylline although theophylline alone caused no significant elevation of plasma cAMP (Trembath & Shaw, 1978). It may also explain why theophylline fails to bronchodilate normal resting subjects (Estenne et al, 1980) but is a very effective bronchodilator in acutely ill patients (Piafsky et al, 1975;Senior et al, 1975) who presumably have a greater level of sympathetic activity.…”

Section: Discussionsupporting

confidence: 77%

“…However, this was shown with concentrations of theophylline of approximately 200 mg/l and it has therefore been suggested that the therapeutic concentration of free theophylline in plasma (approximately 10-20 mg/l) is insufficient to inhibit phosphodiesterase in vivo (Horrobin et al, 1977;Polson et al, 1978). This is confirmed by the failure to show a significant change in plasma cyclic AMP following theophylline administration in normal subjects (Jones et al, 1979;Parrott et al, 1976;Trembath & Shaw, 1978). Alternative mechanisms of action have therefore been proposed such as modulation of prostaglandin metabolism (Vinegar et al, 1976), blockade of adenosine receptors (Fredholm & Sydbom, 1980), increased secretion of adrenaline by the adrenal medulla (Atuk et al, 1967) and alteration of intracellular calcium (Brisson et al, 1972).…”

Section: Introductionmentioning

confidence: 98%

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The effect of posture on the sympathoadrenal response to theophylline infusion.

Warren¹,

Turner²,

Dalton³

et al. 1983

Brit J Clinical Pharma

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1 We studied the effect of posture on the sympathoadrenal response to intravenous theophylline in six normal subjects. On three separate occasions they received an intravenous infusion of either theophylline (6 mg/kg) while supine, theophylline (6 mg/kg) while standing or saline as placebo while standing. 2 With the subjects standing theophylline caused tremor, a peak heart rate of 99 + 6 beats/min, and an elevation of plasma cyclic AMP from 9.3 + 0.7 to 15.1 + 1.7 nmol/l (mean + s.e. mean). There was a small, but significant, elevation of plasma adrenaline, noradrenaline and glucose. The elevation in plasma catecholamines was insufficient to explain either the sympathomimetic effects of theophylline or the rise in plasma cyclic AMP. Theophylline had little or no effect with the subjects supine. 3 The mean peak theophylline concentration following infusion was significantly higher with the subjects upright than when supine (18.3 c.f. 12.4 mg/l, P < 0.025). However, adequate plasma levels of theophylline were obtained in all subjects when lying or supine. Analysis of individual data suggests that differences in plasma levels of theophylline are unlikely to account for the increased effects seen on standing. 4 The mechanism of action of theophylline cannot be explained by increased secretion of catecholamines alone. Theophylline appears to amplify the increased sympathetic activity associated with standing and this is probably by phosphodiesterase inhibition.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 98%

The effect of posture on the sympathoadrenal response to theophylline infusion.

Warren¹,

Turner²,

Dalton³

et al. 1983

Brit J Clinical Pharma

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“…Its possible interaction with f2-adrenoceptor agonists has not yet been fully explored either at molecular level (Miech & Lohman, 1975;Trembath & Shaw, 1978) or in patients with airways narrowing. Conventional doses have been shown to have some additive effect when combined in asthmatics (Campbell, Middleton, Mackenzie, Shetter, McHardy & Kay, 1976;Wolfe, Tashkin, Calvarese & Simmons, 1978;Marlin, Hartnett & Berend, 1978) but these studies are incomplete since they ignore both individual differences in response and in theophylline clearance.…”

Section: Introduction Methodsmentioning

confidence: 99%

Theophylline‐salbutamol interaction: bronchodilator response to salbutamol at maximally effective plasma theophylline concentrations.

Barclay¹,

Whiting²,

Modesti³

et al. 1981

Brit J Clinical Pharma

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1 The effect of inhaled salbutamol following a maximally effective dose of theophylline given by intravenous infusion was determined in 12 patients with chronic bronchitis. 2 An initial single intravenous dose study was performed to estimate each patient's theophylline kinetics and to identify those patients who would respond to theophylline. 3 Pulmonary function was assessed at hourly intervals during four to five incremental steady state theophylline infusions over the concentration range 5‐25 mg/l. 4 Inhaled salbutamol (400 micrograms) was administered after the maximum effect from theophylline had been achieved or when theophylline concentrations reached 25 mg/l without maximum effect: pulmonary function was again assessed. 5 Ten patients achieved a further significant improvement in pulmonary function after salbutamol: in five, predicted values for FVC were exceeded. 6 Patients with chronic bronchitis may benefit from the combination of theophylline and salbutamol if steady state theophylline concentrations of 15‐20 mg/l are achieved.

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“…Furthermore, other potent PDE inhibitors such as dipyridamole [58-32-2] are not bronchodilators (73). Finally, although clinical studies have shown that neither po nor continuous iv theophylline has a direct effect on circulating cyclic AMP levels (74,75), one study has shown that iv theophylline significant potentiates the increase in cyclic AMP levels induced by isoproterenol (74).…”

Section: Xanthine Derivativesmentioning

confidence: 99%

Antiasthmatic Agents

Bernstein¹

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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Asthma is an extremely complex condition characterized by variable and reversible airways obstruction combined with nonspecific bronchial hypersensitivity. Asthma affects 3–5% of the population and is one of the most common chronic illnesses. Clinically, there are several ways of classifying asthma, and treatment varies depending upon the classification. In extrinsic asthma, also called allergic asthma, experienced by adults and, most commonly, by children, it is possible to demonstrate specific causal agents, usually antigens, eg, animal danders, foods, drugs, house dust, pollens, or mold spores. Intrinsic asthma, also called idiopathic asthma, usually develops in adulthood; allergic factors are not demonstrable in intrinsic asthma. Episodes may be triggered by a variety of stimuli, eg, emotional state, exposure to cold air, or inert dusts. Both intrinsic and extrinsic asthmatics can be prone to exercise‐induced attacks. Individuals who experience a combination of extrinsic and intrinsic asthmatic reactions have mixed asthma. Current asthma treatments are not curative and historically have relied on pharmacologic intervention with bronchodilators. More recently the focal points of both treatment and research efforts have shifted from bronchodilators to agents which reduce the underlying inflammatory state. Management of extrinsic asthma usually includes manipulation of the patient's environment to minimize or completely eliminate the causal agent. Improvements in asthma treatment include the development of more effective, safer formulations of known drugs. Also, the use of reliable sustained release formulations has revolutionized the use of oral xanthines which have a very narrow therapeutic index. For many individuals, asthma symptoms tend to worsen at night and the inhaled bronchodilators do not usually last through an entire night's sleep. β 2 ‐Agonists are widely used in the symptomatic treatment of asthma. Although both oral and aerosol formulations of these bronchodilators have been available for many years, advances have occurred in delivery technology with the development of dry powder aerosols. Nonselective β‐agonists can produce many undesirable side effects. Some selectivity in action was needed. Isoproterenol is a selective agonist at the β receptor. Aerosol administration of isoproterenol produces a prompt (2–5 min) intense bronchodilatation of relatively short (1‐h) duration, and has been widely used for many years. A significant advance in β‐agonist therapy occurred with the discovery of metaproterenol, C 11 H 17 NO 3 , which has a longer (4‐h) duration of action. Terbutaline, C 12 H 19 NO 3 , is an orally active agent having a duration of action of from 6–7 h. Terbutaline has about six times the selectivity of isoproterenol and is claimed to produce fewer side effects. Albuterol, C 13 H 21 NO 3 , also called salbutamol, is the most widely prescribed β 2 ‐agonist for either aerosol or oral administration both in the United States and worldwide. There are several longer acting agents currently under clinical evaluation, eg, bitolterol, C 28 H 31 NO 5 ; clenbuterol, C 12 H 18 Cl 2 N 2 O; and salmeterol, C 25 H 37 NO 4 . For many years oral xanthines were the preferred first‐line treatment for asthma in the United States. Within this class of compounds theophylene, ie, 1,3‐dimethylxanthine, is one member of a class of naturally occurring alkaloids. Common side effects of theophylline therapy for asthma include headache, dyspepsia, and nausea. More serious side effects can occur if blood levels are too high. Many derivatives of theophylline have been prepared. However, the most universal solution has resulted from the development of reliable sustained‐release formulations. The effectiveness of theophylline in the treatment of asthma seems to result from a combination of biological properties not clearly understood. Its predominant mode of action appears to be bronchodilation. Although the benefit of theophylline treatment is without question, its use is decreasing. Steroids use for the preventative treatment of asthma appears to be increasing, because of the identification of asthma as an inflammatory disease. It is known that steroids bind to cytosolic receptors. The steroid–receptor complex then enters the cell nucleus where the complex acts at specific sites and affects protein synthesis. The effect is to reduce the inflammatory response. While disodium chromoglycate (DSCG), C 23 H 14 Na 2 O 11 , enjoys modest success as a preventative antiasthmatic agent, it has never achieved the same level of popularity in the United States as in other markets, eg, the United Kingdom. Although it is considered one of the safest available antiasthmatic agents, it seems to work best as an adjunct to other therapy. The beneficial effect of atropine, used for centuries, is in preventing exercise‐induced asthma; it and other anticholinergic agents have no effect on bronchial hyperresponsiveness, the release of other mediators, or on the inflammatory process. Ipratropium bromide, C 20 H 30 BrNO 3 , a newer anticholinergic agent, seems to be useful in patient populations that show limited response to β 2 ‐adrenergic agonists.

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Potentiation of isoprenaline‐induced plasma cyclic AMP response by aminophylline in normal and asthmatic subjects.

Cited by 15 publications

References 12 publications

The effect of posture on the sympathoadrenal response to theophylline infusion.

The effect of posture on the sympathoadrenal response to theophylline infusion.

Theophylline‐salbutamol interaction: bronchodilator response to salbutamol at maximally effective plasma theophylline concentrations.

Antiasthmatic Agents

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