ABSTRACT
Title
A case of haemorrhagic cystitis and conjunctivitis by inhaled albuterol and beclomethasone
Authors
C. Carnovale1, A. Piazza3, S. Antoniazzi1, V. Perrone1, E. Clementi1,2and S. Radice1
1Unit of Clinical Pharmacology, Dept. of Clinical Sciences, Univ. Hospital “Luigi Sacco”; University of Milan; 2E. Medea Scientific Institute, Bosisio Parini Lecco, Italy; 3Family Paediatricians, Territorial Services Monza/Brianza
1Unit of Clinical Pharmacology, Dept. of Clinical Sciences, Univ. Hospital “Luigi Sacco”; University of Milan; 2E. Medea Scientific Institute, Bosisio Parini Lecco, Italy; 3Family Paediatricians, Territorial Services Monza/Brianza
Abstract
Coadministration of inhaled corticosteroids and β2 adrenergic agonist is an effective treatment for acute asthma, and its effectiveness has been studied extensively. Rare case-control studies have associated albuterol inhalation with Urinary System Disorder (Urinary Tract Infection); the incidence rate was of at least 3.0%, and voiding difficulties (incidence less than 1%); instead, inhaled beclomethasone may play a role in the development of cataract in children and glaucoma. However, to our knowledge, no cases of haemorrhagic cystitis and conjunctivitis by inhaled albuterol and beclomethasone have been reported in literature so far.
We now report on the occurrence of such adverse reactions in a 8 year-old Caucasian girl treated for acute asthma control and cough with inhaled albuterol (8 drops 3/day) and beclomethasone ( ½ flacon 2/day) for 5 days. During the last day of pharmacological therapy she experienced haemorrhagic cystitis and conjunctivitis. The ADRs remitted when she stopped taking albuterol/beclomethasone. Cystitis was treated with antibacterial drug (phosphomycin 2 g), while conjunctivitis spontaneously resolved in few hours. Clinical records of the past two years, show that the patient experienced the same clinical experiences on challenge with the drugs.
Albuterol can increase plasminogen activator activity and tissue-type and urokinase-type plasminogen activator levels, thus activating the fibrinolytic system that may lead in the area perfusion to. Interestingly, previous reports showed that salbuterol, a drug sharing the same bronchodilator properties and mechanism of action of albuterol, may increase fibrinolysis.
Additionally, it has been shown that albuterol contributes to increase the basal platelet Nitric Oxide synthase activity. The role of Nitric Oxide in controlling vascular homeostasis is well established and its action as a potent inhibitor of platelets adhesion and aggregation well known. It is possible that enhance Nitric Oxide generation contributed to the observed haemorrhagic reaction.
These mechanisms of action of albuterol are sufficient to explain the altered hemostatic balance and hemorrage we observed in a patient without disorders of coagulation.
The inflammation of the cystis may be explained by the concurrent adiminstration of beclomethasone as the immunosuppressive effects of steroid treatment can contribute to enhance the risk of developing urinary tract infection. Likewise, beclomethasone can explain the onset of conjunctivitis. In this respect the aerosolised way of administration may have played a relevant role. Aerosolized medications even if maximising clinical benefit by targeting the airways and minimising side effects because of the reduced systemic exposure, can still generate local adverse effects, especially in the eyes, as incorrect facemask usage may lead to deposit of the drugs on them and increased topical absorption.
Even if more studies are needed to confirm the association between this ADRs and the use of inhaled selective acting β2 agonist and corticosteroids, use of the Naranjo adverse drug reaction probability scale indicates a possible relationship between the patient’s development of ADRs and acute asthma pharmacological terapy. The resolution of the symptoms soon after the discontinuation of the drug and the positivity observed after rechallenge with the drugs further strengthens the hypothesis of their involvement in the ADRs.
We now report on the occurrence of such adverse reactions in a 8 year-old Caucasian girl treated for acute asthma control and cough with inhaled albuterol (8 drops 3/day) and beclomethasone ( ½ flacon 2/day) for 5 days. During the last day of pharmacological therapy she experienced haemorrhagic cystitis and conjunctivitis. The ADRs remitted when she stopped taking albuterol/beclomethasone. Cystitis was treated with antibacterial drug (phosphomycin 2 g), while conjunctivitis spontaneously resolved in few hours. Clinical records of the past two years, show that the patient experienced the same clinical experiences on challenge with the drugs.
Albuterol can increase plasminogen activator activity and tissue-type and urokinase-type plasminogen activator levels, thus activating the fibrinolytic system that may lead in the area perfusion to. Interestingly, previous reports showed that salbuterol, a drug sharing the same bronchodilator properties and mechanism of action of albuterol, may increase fibrinolysis.
Additionally, it has been shown that albuterol contributes to increase the basal platelet Nitric Oxide synthase activity. The role of Nitric Oxide in controlling vascular homeostasis is well established and its action as a potent inhibitor of platelets adhesion and aggregation well known. It is possible that enhance Nitric Oxide generation contributed to the observed haemorrhagic reaction.
These mechanisms of action of albuterol are sufficient to explain the altered hemostatic balance and hemorrage we observed in a patient without disorders of coagulation.
The inflammation of the cystis may be explained by the concurrent adiminstration of beclomethasone as the immunosuppressive effects of steroid treatment can contribute to enhance the risk of developing urinary tract infection. Likewise, beclomethasone can explain the onset of conjunctivitis. In this respect the aerosolised way of administration may have played a relevant role. Aerosolized medications even if maximising clinical benefit by targeting the airways and minimising side effects because of the reduced systemic exposure, can still generate local adverse effects, especially in the eyes, as incorrect facemask usage may lead to deposit of the drugs on them and increased topical absorption.
Even if more studies are needed to confirm the association between this ADRs and the use of inhaled selective acting β2 agonist and corticosteroids, use of the Naranjo adverse drug reaction probability scale indicates a possible relationship between the patient’s development of ADRs and acute asthma pharmacological terapy. The resolution of the symptoms soon after the discontinuation of the drug and the positivity observed after rechallenge with the drugs further strengthens the hypothesis of their involvement in the ADRs.