Bronchodilation and safety of supratherapeutic doses of salbutamol or ipratropium bromide added to single dose GSK961081 in patients with moderate to severe COPD.

BACKGROUND: There are few data on the bronchodilatory effects of adding short-acting bronchodilators (SABA) to maintenance, long-acting bronchodilator therapy. This study assessed the additional bronchodilation and safety of adding supratherapeutic doses of salbutamol (SALB) or ipratropium bromide (IPR) to the novel bi-functional molecule (or dual pharmacophore) GSK961081 400 µg (MABA 400) or 1200 µg (MABA 1200). METHODS: This randomised, double-blind, complete, crossover study in 44 patients with moderate to severe COPD, evaluated 6 treatments with a washout of at least 7 days between treatments: single doses of MABA 400 or MABA 1200 followed by cumulative doses of either SALB (3× 200 µg at 20 min intervals), IPR (20 µg, 20 µg and 40 µg at 20 min intervals) or placebo (PLA) (three doses at 20 min intervals) at 1 h, 12 h and 24 h post-MABA dose. The primary endpoint was maximal increase in FEV1, from pre-dose bronchodilator (SABA/PLA), measured 15 min after each cumulative dose of SALB, IPR or PLA. Systemic pharmacodynamics (potassium, heart rate, glucose and QTc), adverse events and systemic pharmacokinetics were also assessed. RESULTS: The additional bronchodilatory effects at 12 h and 24 h for both SALB and IPR were of a similar magnitude and statistically significant relative to PLA; mean differences (SE) (L) following MABA 400 dosing: 0.139 (0.023) after SALB at 12 h; 0.123 (0.022) after SALB at 24 h; 0.124 (0.023) after IPR at 12 h; 0.141 (0.021) after IPR at 24 h; and after MABA 1200 dosing: 0.091 (0.023) after SALB at 12 h; 0.126 (0.022) after SALB at 24 h; 0.055 (0.023) after IPR at 12 h; 0.122 (0.022) after IPR at 24 h. Any additional bronchodilator effects at 1 h were small and not clinically significantly different from PLA. There were small, non-clinically significant increases in mean heart rate after both MABA doses plus SALB, and decreased potassium levels in four patients after MABA 1200 plus SALB (×3) or PLA (×1) were observed but overall all treatments were well tolerated and raised no significant safety signals. CONCLUSION: The additional bronchodilation achieved following supratherapeutic doses of SALB and IPR on top of single doses of MABA 400 or 1200 was comparable for the two agents and neither were associated with any clinically relevant systemic pharmacodynamic effects other than the small transient hypokalemic effect in a 3 out of 41 patients receiving additional high dose salbutamol and MABA 1200. Either short-acting bronchodilator could potentially be used as rescue medication on top of MABA therapy.

Seasonal allergic rhinitis: limited effectiveness of treatments.

(1) Seasonal allergic rhinitis, otherwise known as hayfever, is a harmless condition, although it can cause major discomfort and interfere with activities of daily living. We conducted a review of the literature, based on our in-house methodology, to determine the risk-benefits of treatments used in this setting. (2) Placebo-controlled trials show that sodium cromoglicate relieves symptoms, especially if it is used before symptoms appear. Adverse effects are rare with sodium cromoglicate nasal solutions and eye drops. (3) Nasal steroids have well-documented efficacy. Beclometasone is the best choice. Adverse effects include epistaxis, nasal irritation and, occasionally, systemic disorders. (4) Oral antihistamines are less effective than nasal steroids. They also provoke adverse effects, especially drowsiness. Nasal azelastine seems to have a similar efficacy as oral antihistamines. (5) The adverse effects of systemic steroids must not be overlooked, especially with long-term use. Oral administration is an alternative for severe symptoms that do not respond to other treatments, although this is rarely the case. Long-acting intramuscular steroids carry an increased risk of adverse effects. (6) Despite evaluation in several randomised controlled trials, there is no firm evidence that homeopathic preparations have any specific efficacy in allergic rhinitis. (7) Vasoconstrictors, ipratropium and montelukast, have negative risk-benefit balances in hay fever. (8) When a single allergen is responsible (grasses, ragweed, birch), clinical trials suggest that specific desensitisation can provide a modest improvement. However, this treatment carries a risk of local adverse effects, as well as a risk of rare but severe anaphylactic reactions, especially in patients who also have unstable severe asthma. (9) Sublingual desensitisation seems to be even less effective than subcutaneous desensitisation in adults. Follow-up is too short to know whether there is a risk of severe anaphylactic reactions. The results of paediatric studies are even less convincing. (10) In practice, when drug therapy is needed to relieve symptoms of seasonal allergic rhinitis, sodium cromoglicate is the first-line treatment. If a nasal steroid solution is chosen, it should be used for the shortest possible period.

Type I hypersensitivity in an asthmatic child allergic to peanuts: was soy lecithin to blame?

BACKGROUND: Soy lecithin is widely used as an emulsifier, not only in topical skin care products but also in various drugs administered either topically, orally, or intravenously or by inhalation. Patients strongly allergic to soy and/or peanuts can develop an anaphylactic reaction when exposed to soy lecithin. METHOD: We report a 3-year-old asthmatic boy, allergic to peanuts, who was treated at the emergency department for an exacerbation of asthma following an upper respiratory tract infection. Within an hour after receiving the second of two inhalations of an ipratropium bromide (Atrovent) metered dose inhaler, he developed respiratory distress and generalized urticaria, an adverse event that regressed within 48 hours of withdrawal of the suspected drug. Soy lecithin, contained as an excipient in the metered dose inhaler, was strongly suspected of being responsible for this reaction. CONCLUSION: Drug products containing soy lecithin can cause severe allergic reactions in patients allergic to peanuts or soy. Physicians should be aware that adverse drug reactions can be due to both the active medical component and the excipient ingredients.

Broncodilatadores en síndrome bronquial obstructivo del lactante / Bronchodilator agents in obstructive bronchial syndrome in infants

Se evalúa la respuesta clínica a diferentes broncodilatadores en 100 lactantes con síndrome bronquial obstructivo que, por la intensidad de éste requerían hospitalización, mediante un estudio prospectivo doble ciego, en el que se asignaron 25 niños menores de lactantes por grupo. Los niños del grupo I recibieron ipratropio (I), los del grupo II cloruro de sodio 9 por ciento (NaCI), en el grupo III se empleó fenoterol-ipratropio (FI) y en el grupo IV salbutamol (S), en todos los casos por nebulización. La calificación de Tal era similar al ingreso en los 4 grupos (día 0). Al día 1 del tratamiento era significativamente menor (p<0,05) en FI, como también el día 2 (p<0,01): (promedios día 1: 4,6 (I); 4,5 (NaCI); 3,8 (FI); 4,6 (S); día 2: 3,8 (I) 4,1 (NaCI); 2,1 (FI); 3,9 (S); día 3: 3,0 (I); 3,4 (NaCI); 1,6 (FI); 3,2 (S). El promedio de días estada fue I: 4,64 ñ 1,29; NaCI: 5,44 ñ 1,61; FI: 3,08 ñ 1,28; S: 5,28 ñ 1,69; p<0,001 a favor de FI. Los niños tratados con NaCI requirieron con mayor frecuencia terapia adicional con broncodilatadores (p<0,05) en claro contraste con los manejados con FI, que requirieron menos broncodilatadores adicionales que el resto (p<0,01) desde el día 1 del ingreso. No se registraron efectos secundarios indeseables con los diferentes regímenes aplicados