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Choice of therapy :

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Choice of therapy :

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  1. Management of asthmaAsthma is a reversible airways obstruction in which sensitization and inflammation play an important role . There are two phases , initial phase mediator-induced bronchospasm , followed by a second or late phase ( 6 to12 hours later ) which is believed to be a manifestation of the inflammatory response being more refractory to b\ds treatment than the initial phase , corticosteroids give a better effect .

  2. Clinically , asthma is divided into extrinsic and intrinsic . Extrinsic asthma is a manifestation to immunologic reactivity to environmental agents . Patients with this type give a history of atopy , onset during childhood or adolescence , seasonal occurrence , and response to environmental stimuli . Intrinsic asthma occurs in the third or fourth decade of age , there is no identifiable extrinsic allergen associated with the asthmatic attack .

  3. Principles of MT : The goals of therapy are to prevent attacks and effectively reduce hyperresponsiveness in patients who suffer attacks . Before initiating therapy , it is important to verify that wheezing is not due to a non-asthmatic cause such as pulmonary oedema , embolism , foreign body or infection .

  4. MT of acute attacks and chronic active disease : Most patients with acute asthmatic attacks can be managed as on an out- patient basis , provided that therapy is promptly and properly instructed . Most of the patients seeking ER care do not need parenteral therapy . Most of them presented to ER they have no available medication , relied on over-counter, preparations , used fixed combination tablets or suppository forms that do not permit proper dosing

  5. Anti- inflammatory therapy ( AIT ) : Gluco-corticosteroids , cromolyn and nedocromil now emerge as the corner-stone of treatment , with bronchdilators relegated to an adjunctive role . All patients with active disease should started and maintained on continuous AIT and B\Ds should be used only for symptomatic relief of mild acute exacerbations and for prevention of post-exertional flares .

  6. Glucocorticosteroides are AIT of choice in most adults with asthma . Their action is 6 to 12 hours after administration . The inhaled preparations ( beclomethasone , triamcinoline , flunisolide ) are preferable to oral therapy because systemic absorption is minimal and hence steroids adverse effects are eliminated . Although highly effective , oral and parenteral systemic glucocortcoids ( prednisone , methylprednisalone , hydrocontisone ) should be reserved for refractory cases and used for a short period . Their prolonged daily use side effects are osteoporotic fractures , adrenal suppression , skin changes , aseptic necrosis of bone and aggravation of diabetes mellitus .

  7. Inhaled glucocorticoids , topically active have got the advantage of long steroid therapy without systemic side effects . The principal metered- dose – inhaler ( MDI ) preparations include beclomethasone dipropionate ( vanceril , beclovent ) , flunisolide ( aerobid ) , and triamcinoline ( azmacort ) , they can be used up to 20 puffs \ day . Tapering dose should be considered when switching from prolonged systemic oral steroids to MDI ,to prevent adrenal suppression . Oral thrush and hoarseness are sometimes problems with prolonged use of MDI , but can be prevented by rinsing and gargling with water after each dose or by using a spacer . The onset of action is within 2 to 8 hours and their response lasts 6 to 8 hours . The daily dose is 2 to 4 doses , but in refractory cases up to 20 puffs \ day may be used , then reduced gradually as the condition improves .

  8. Prednisone 5 mg , half –life 12 to 24 hours , a short term course 7 to 10 days , beginning with a high dose ( 40 to 60 mg \ day ) and rapidly tapering dose is optimal for control of a severe acute attack that is refractory to all other measures , only patients with chronic disabling bronchospasm refractory to all measures should be considered as candidates for long –term daily systemic steroid therapy .

  9. Beta-agonists : The selective inhaled beta-agonistsare the b\ds for treatment of asthma , because of their relative selectivity for bronchial beta-receptors , their rapid onset of action ( 2 to 5 min . ) when taken as MDI , sustained duration of action ( up to 6 hours ) and paucity side effects . Albuterol ( provventil , ventolin ) , metapioterenol ( aluperit , metraprel ) , bitolterol ( tornalate ) , terbutaline ( brethine , bricanyl ) and pributerol ( maxair ) are the main drugs in this class . Most of them are available in both oral and inhalation forms , terbutaline is available in s\c injections . Inhaled forms are preferred because of rapid onset and less systemic side effects . Oral terbutaline may cause troublesome tremor . Albuterol is a reasonable choice for most patients requiring an inhaled semiselective beta-agonists .

  10. Theophylline and its derivatives : The methylxanthines ( theophylline & aminophylline ) were the first orally active b\ds . Their role has become limited as faster , safer , more effective therapies ,beta-agonists have been developed . The theophyllines low cost , clearly measured therapeutic range ( 10-20 gm\ml ) and availability of sustained-release preparations facilitate their utilization . They help patients bothered by nocturnal exacerbations , and they can reduce systemic steroid requirements in some patients with refractory disease . Adverse effects are proportional to their serum level with levels > 20gm\ml associated with a marked increase in risk of toxic side effects . When levels > 35gm\ml , life-threatening ventricular arrhythmia can occur .

  11. Anticholinergics : Ipratropium , a topically active muscarinic blocking agent similar to atropine , is available in MDI preparation . It is useful in COPD , but its efficacy is less in asthma .

  12. Leukotriene receptor antagonists : These are drugs that inhibit leukotriene activity ( e.g. zileuton ) . These agents show a possible future role in treatment of asthma . They achieve b\d and symptomatic improvement .

  13. Prophylaxis: Once an acute attack subsides , the goal of MT shifts to prevention of episodes by : identification of the responsible allergen skin antigenic screening test and desensitization avoidance of the offending agents anti-inflammatory therapy , and reduction in dependence on chronic b\d treatment cromolyn sodium , the inhaled steroids , and prednisone are the important anti-inflammatory agents for prophylaxis teach the patient the proper use of PEFM , MDI , spacer ( spacehaler ) and breath-activated inhalers for persons who can not use MDI .

  14. Choice of therapy : 1. Mild intermittent disease ( MID ) : Inhaled beta-adrenergics are the drugs of choice in MID and exercise-induced asthma . 2. Mild chronic disease ( MCD ) : Inhaled topical steroid is the treatment of choice . Nocturnal attacks can be prevented by a long-acting-controlled-release theophylline before bed time , serum theophylline levels should be monitored . 3. Acute disease : An inhaled beta-agonist ( e.g. albuterol 3 puffs 6 hourly ) is the Rx of choice . Those with bronchospasm that lessens but does not resolve within 24 hours are candidates for short , rapidly tapering course of oral steroids ( 7-10 days course of prednisone , starting with full doses 40-60 mg\day ) . Tapering should be followed by a course of inhaled steroid . 4. Chronic refractory disease ( CRD ) : Daily doses of oral corticosteroid , regular use of inhaled steroid ( 20 puffs \ day ) may be an effective alternative .

  15. Monitoring therapy : Patients subjective assessment of severity , inspiration \ expiration ratio , PEFR , FEV1.0 , pulsus paradoxus , sternocleidomastoid retraction are among the meaningful guides to assess the clinical status and severity of disease .

  16. Indications for admission : Some authors have developed an index to predict need for admission : Ps> 120\min , RR> 30\min , pulsus paradoxus > 18mm Hg , PEFR< 120L\min , moderate to severe dyspnoea , accessory muscle use , and wheezing . Lacking more definitive means of prediction , clinical status and response to therapy remain the most helpful guidelines for decision making . Admission is indicated for those with an acute attack , who manifest one of the following : 1. Subjective report of severe difficulty in breathing 2. Failure to respond fully and promptly to inhaled beta-agonist therapy that is followed promptly by full doses of prednisone . 3. Use of accessory muscles of respiration ( sternocliedomastoid retraction ) 4. Pulsus paradoxus > 10 mm Hg 5. FEVi.o < 1.0 L\sec 6. Arterial PCO2, inappropriately high for respiratory rate 7. Underlying cardiac condition 8. Inadequate home situation or a history of incompliance.

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