Medicine Dr. Kawa Lecture 4 - Treatment of asthma : Avoiding allergens. Hyposensitization :Subcutaneous injections of inially very small, but gradually increasing doses of allergens (desensitization or immunotherapy ). Drugs. Drug treatment : Can be divided in to 2 general categories : Quick relief medications : Drugs that act as relaxants of tracheobronchial smooth muscle ; (bronchodilators ) : β- adrenergic agonists, methylxonthines & anticholinergics. Long term control medications (Agents that prevent &/or reverse inflammation ) : glucocorticoids, leukotriene inhibitors & receptor antagonists, cromolyn sodium, nedocromils 1- Adrenergic stimulants: Short acting β-adrenergic(β2 selective) agonist: Salbutamol, Terbutaline, Metaproterenol, Pirbuterol, bitolterol. B- Long acting β-adrenergic(bselective)agents: salmeterol, fenoterol & formoterol C- Other adrenergic agonists : Catecholamines : adrenaline. 2-Methylxanthines(phosphodiesterase inhibitor ) : Theophylline 3-Anticholinergic agent: Ipratrupium bromide and atropin. glucocorticoids : For treatment of asthma it is available as inhalation, tablets, syrup & injections. Inhaled corticosteroid : -Preparations available are :beclomethasone, budesonide, flunisolide, fluticasone,triamcinolone. Side effects of inhaled steroid : oral candidates, glossitis, sore throat, hoarseness,dysphonia, increase systemic absorption with large doses of inhaled steroid (produce adrenal suppression, cataract, decrease growth in children.). 5-mast cell stabilizing agents: Cromolyn sodium & Nedocromil sodium. 1 P a g e
6-Antileukotrienes : Zafirlukast & Montelukast ( leukotriene receptor antagonist ) Zileuton (inhibitor of leukotriene synthesis ). 7- Antihistamines : Astemizole &Terfenadine 8- Ketotifen : 9-Other agents : Steroid dependent pt. might benefit from the use of immunosuppressant agents (used as steroid sparing agents),like : Methotrexate, Gold salt, & cyclosporine. Methotrexate, Gold salt may produce lung toxicity. Have limited role in the manegement off asthma. Not used as standered therapy for asthma. Omalizumab MECHANISM OF ACTION Omalizumab is an IgG monoclonal antibody which inhibits IgE binding to the IgE receptor on mast cells and basophils. By decreasing bound IgE, the activation and release of mediators in the allergic response (early and late phase) is limited. Long-term treatment in patients with allergic asthma showed a decrease in asthma exacerbations and corticosteroid usage. USE Treatment of moderate-to-severe, persistent allergic asthma not adequately controlled with inhaled corticosteroids CONTRAINDICATIONS Hypersensitivity to omalizumab & in status asthmaticus ADMINISTRATION For SubQ injection only Quick-Relief Used in acute episodes Generally short-acting beta 2 2agonists How to Use a Spray Inhaler Inhalers and Spacers Spacers can help patients who have difficulty with inhaler use and can reduce potential for adverse effects from medication. Nebulizer Machine produces a mist of the medication Used for small children or for severe asthma episodes 2 P a g e
Treatment of episodic asthma : Mild & infrequent episodes can be controlled by salbutamol inhaler. In pt. with more frequent episodes add sodium cromoglicate & beclomethasone inhaler. Treatment of exercise induced asthma Common in children &young adults,give 2 doses of salbutamol inhaler few minutes befor exercise, if not effective then add sodium cromoglicate & beclomethasone inhaler. Treatment of chronic persistent asthma : Step 1 : occasional use of inhaled short acting β2 agonist. As salbutamol or terbutaline,used by inhalation as required. If the pt. is using β2 agonist more than once daily, move to step 2 Step 2 :low dose inhaled steroid. Inhaled salbutamol is used as required + regular inhaled steroid (beclomethasone) up to 800 microgram daily. Step 3 : high dose inhaled steroids or low dose inhaled steroids + long acting inhaled β2 agonist. Inhaled salbutamol is used as required +inhaled steroid in dose range 800-2000 microgram daily. alternatively a long acting β2 agonist as salmeterol 50 microgram 12-hourly, or a sustainedrelease theophylline may be added. Step 4 : high dose inhaled steroids & regular bronchodilaters. Inhaled salbutamol is used as required + inhaled corticosteroid (800 2000 microgram dail ) + one or more of the following (as therapeutic trial ) : Inhaled long acting B2 agonist ( salmeterol ). Leukotriene recepror antagonist (montelukast ). Inhaled ipratropium bromide. Long acting oral B2 agonist( sustained release salbutamol or terbutaline preparations ). Sodium cromoglicate. Step 5 : addition of regular oral steroid therapy. Step 4 treatment is given +regular prednisolone tablets prescribed in the lowest amount necessary to control symptoms as a single daily dose in the morning. Occationally you can increase a step (step up) to control exacerbetions. You can decrease a step (step down) if good symptom control for 3 months or more. Only think of withdrawing anti inflammatory treatment if pt. well for at least 6 months. In general it is better to start with a treatment regimen which is likely to achieve disease control rapidly,& then step down, rather than to start with inadequate treatment & then have to step up. Management of acute sever asthma (status asthmaticus ): The aims of management are to prevent death & to restore pulmonary function as quick as possible. 3 P a g e
We should assess the pt. for the features of severity. According to the severity we can classified sever asthma in to : Acute sever asthma. Life threatening asthma. Near fatal asthma. Features of acute sever asthma : PEF< 50% of expected (<200 L/min). Respiratory rate >25 /min. Heart rate >110 beat /min. Inability to complete sentences in one breath. Features of life threatening asthma : Unrecordable PEF (<100 L/min). Pa O 2 < 8 kpa (especially if being treated with O 2 ). Silent chest. Cyanosis. Bradycardia or arrhythmias. Hypotention. Exhaustion. Confution. Coma. Features 0f near fatal asthma : Increase PaCO2 & / or Requirement for mechanical ventillation. Immediate treatment for acute sever asthma : 1-Oxygen: should be given at the highest concentration available ( usually 60 % ). Then the concentration adjusted according to the arterial blood gas measurement (PaO2 should be maintained > 9 kpa ). 2-High dose inhaled B2 agonist : B2 agonist should be nebulized using O2. Salbutamol 2.5 5 mg. or Terbutaline 5-10 mg. given initially & can be repeated within 30 min.if necessary. 3-Systemic corticosteroid: IV Hydrocortisone 200 mg. or oral Prednisolone 30-60mg Subsequent management of acute sever asthma If features of severity persist you should continue the management as following: 4 P a g e
1-Close monitoring & continue O2 therapy. 2-Continue nebulized B2 agonist : every 15-30 min ( reduce to 4 hourly once clear clinical response) 3-Ipratropium bromide 0.5 mg. should be added to the nebulized B2 agonist. 4-Continue systemic steroid : Hydrocortisone 200mg. IV. 6 hourly. 5-Magnesium sulphate : 25 mg /kg. IV. 6- Aminophylline IV. 7- Mechanical ventillation. Indications for assisted ventillation in acute sever asthma. Coma. 2-Respiratory arrest. 3-Exhaustion, Confution, Drowsiness. 4-Deterioration of arterial blood gas tention despite optimal therapy : -PaO2 < 8 kpa & falling. -PaCO2 > 6 kpa &rising. -PH low & falling. Monitoring of Treatment PEF recording should be made every 15-30 min. then PEF chart 4-6 hourly during hospital stay. 2-Repeated measurment of arterial blood gas tension or using pulse oxymetry. Managing Asthma: Peak Expiratory Flow (PEF) Meters Allows patient to assess status of his/her asthma Prognosis of asthma -The prognosis of individual asthma attacks is generally good. Complete remission of asthma is relatively common in children ( episodic asthma ), as many as 25% remain asymptomatic from adolescence onward. In adults ( chronic asthma ), prolonged remission of asthma symptoms are less common. Patients older than 65 years tend to have sever asthma that infrequently goes into remission, in these patients asthma is less reversible. There is occationally a fatal outcome especially if treatment is inadequate or delayed. -Atopic asthma is usually worse in the summer( heavely exposed to allergens ). -Chronic asthma is usually worse in the winter (increase frequency of viral infection 5 P a g e