Reduction of Bronchial Inflammation PDF

█ REDU UCTION OF BRONCH HIAL INFLA AMMATION N ▌Cortiicosteroids Mecha anism of action a Corticoosteroids can efffectively ↓ bron...

█ REDU UCTION OF BRONCH HIAL INFLA AMMATION N ▌Cortiicosteroids Mecha anism of action a Corticoosteroids can efffectively ↓ bron nchial inflammmation and d hyperrea activity thrrough:  The ey inhibit B cell function → ↓ an ntigen-antibbody reacction.  The ey inhibit T cell functtions → ↓ mediators s and cytookine releaase.  The ey inhibit macrophag m ge activityy and stab bilize lyso osomal me embranes.  The ey inhibit mast m s → ↓ histtamine release cells andd capillary permeabili p ty.  The ey inhibit ph hospholipa ase A2 enzzyme →↓ synthesis s of o PGs & LT Ts.  Cortticosteroid ds cause up-regulatio on of β2 re eceptors. Use in asthma  Acuute severe asthma: hydrocorti h isone 2000 mg givenn by i.v. injjection. It may be repeeated everry 4 h if necessary.  Chrronic bronchial asthm ma: oral p prednisoloone 20 mg g/d or dexxamethazo one 4-8 mg//d, or by in nhalation (bbeclomethhasone).  Inhaaled cortiicosteroid ds (e.g. be eclometha azone): shhould be cconsidered d the 1st cho oice in newwly diagnos sed asthma a. They ha ave the follo owing advvantages:  Their efficacy e is equal e to in nhaled β2 agonists. a  Minimaal systemic c side effe ects. Advers se effects  If used systemically: …..see … enddocrine cha apter.  If us halation: → oropharyyngeal candidiasis. It could bee avoided by: sed by inh  Mouth wa ash and gaargle after e each inhala ation.  Candida infection ca an be treaated by nys uthwash o statin mou or amphottricin-B lozenges. Precau utions  Theey must be e withdraw wn gradua ally to avoid d acute Ad ddisonian ccrisis.  Dieet should be + b rich in K and prot eins and lo ow in NaCl and carbbohydrates s.  Con ntinuous check c for any a increaase in weight, edema, sugar in uurine or BP P.  If the patient develop ps acute infection, he mustt be treatted by ad dequate antiibiotics witth decreassed dose o of steroid. 238 █ PROPHYLACTIIC TREATM MENT The following classes of drugs aree not bron nchodilatorrs but aree used to reduce frequen ncy of asth hma exace erbations. ▌Leuk kotriene inhibitors i s: Zafirlukast and monteluka m ast  Theey block le eukotrienee (LTD4) re eceptors.  Zafiirlukast is given g twice e daily butt monteluk kast is given once da ily. Zileuto on  It in nhibits 5-lip pooxygena ase enzymee →↓ leuko otriene syn nthesis.  Zileeuton is microsomal m P450 inh ibitor and can inhib bit the mettabolism of o many drugs e.g. wa arfarin and theophyllin ne.  In clinical trials, leu ukotriene inhibitors s reduced d frequenncy of asthma exa acerbationss as equal to corticossteroids.  Monntelukast is approved to controol asthma in children n. ▌Mastt cell stab bilizers: Cromo olyn and nedocromiil  Cro omolyn sod dium (diso odium crom e) and ned moglycate docromil aare poorly soluble drugs and sho ould be giv ven as miccronized po owder thro ough spinhhaler.  Theey inhibit mast m cell de egranulationn by uncleear mechannism probaably by alte ering the funcction of chloride cha annels in th he mast celll membranne.  The ey were ussed to reduce freque ency of atttacks (i.e.. prophyla actic trea atment) in n some alllergic connditions e.g g. bronchia al asthma, allergic rh hinitis, andd allergic conjunctivittis.  The eir use now w become es very li mited and d has bee en largely replaced r by leukotrie ene inhibito ors.  Adv verse effe ects occurr at site off administration e.g.. local irrita ation of thhe throat, cchest tighttness, andd bronchosspasm. Ketotiffen  It iss a 2nd geneeration anttihistaminee and a ma ast cell stab bilizer.  It iss used as a eye drops to trreat allerg gic conjunctivitis, and orally y as a prophylactic treatment t in i bronchia al asthma and other seasonal aallergies. 239  █ OTHER DRUGS USED IN TREATMENT OF BRONCHIAL ASTHMA Expectorants and mucolytics: to reduce mucus viscosity. Mixture of oxygen (20%) and helium (80%): Heliox  Helium is an inert gas. Its low density facilitates O2 diffusion through obstructed airways → ↓ work of breathing. Anti-IgE monoclonal antibodies: Omalizumab  Omalizumab is a new drug that inhibits the binding of IgE to mast cells and prevents mast cell degranulation. It may also inhibit IgE synthesis by B cells.  It reduces frequency and severity of asthma even when the dose of corticosteroids is reduced. █ Stepwise approach for treatment of chronic asthma The management of stable asthma is now well established with a stepwise approach: Step 1: Inhaled short-acting B2 agonist (SABA) as required Step 2: Add inhaled steroid at 400 mcg/day Step 3:  Add inhaled long-acting B2 agonist (LABA)  Still inadequate: continue LABA and increase inhaled steroid dose to 800 mcg/day Step 4:  increase inhaled steroid up to 2000 mcg/day  Add a 4th drug e.g. Leukotriene antagonist, SR theophylline, oral B2 agonist tablets. Step 5:  Use oral steroid tablet in lowest dose in addition to the high dose inhaled steroid (2000 mcg/day).  Refer the patient for specialist care. █ Treatment of acute severe asthma (status asthmatics) Definition: acute severe asthma (status asthmatics) is a condition in which bronchodilators are poorly effective in relieving the attack. Management  Hospital admission.  Oxygen: to maintain peripheral capillary O2 saturation (SpO2) between 94-98%. 240