Asthma PDF

ASTMA Do Aga Daniel  INTRODUCTION Asthma the Greek word A meaning diff...

ASTMA Do Aga Daniel  INTRODUCTION Asthma the Greek word A meaning difficulty breathing. is in is from characterized : dirically by recurrent bout shortness breath of of - heat tightness - coughing ↑ wheezing - reversible narrowing of the bronchial airways - - markedincrease in brondal responsiveness to inhaled stimul. These are the physiological pattern. The pathological patterns are : Lymphocytic cosinophotic inflammation of the bronchial mucosa - bronchial reticulars Remodelling of the with thickening of the Lamina - mucosa - Hyperplasia of cells of all structured elements of the airway vessels smooth , muscles secretory glands and goblet cells. , TRIGGERS OF ASTHMA. 1 Genetic & Polymorphisa Upper respiratory tract. 2 infection dust danders , 30 4 Allergins eg. , pollens , smoke GRACE cold air. 5 Exercise Status Asthmations This is a life threatening condition that requires hospitalization aggressive , treatment.A is as defined unresponsiveness to standard therapy. Treatment Strategies/Objective of Therapy normal. To return 1 lung function to as near disease as possible. 2 To prevent acute exacerbation of the.  CLASSIFICATION OF DRUGS FOR ASTHMA There dasses antrasthmatic are 3 broad of drugs 1 Bronchodilators 2.Anti-inflammatore res agents => BRONCHOILATORS · B-adrenergic agonists Mathoxanthines g · Anticholinergic agents They used both maintenance and needed to are in therapy as reverse relievers Al often attack. They also are referred to they produce rapof as relief but they do not affect the fundamental disease - process => ANT-INFLAMMATORY AGENTS · Corticosteroids steroids They must be used in conjunction with bronchodilators in all but the mildest asthmatic. The are called controllers bla they provide long-term stabilization. Examples : - Hydrocortisone - Pretoisotone => ALTERNATIVE THERAPIES · Leukotriene modulators ↑ Cromoya sodium ↑ Nadocromil sodium.  regimen should include behavioural all In addition to trug treatment , changes ducation targeting or : - compliance to medication Symptom recognition - - Prophylactic strategies BRONCHODILATORS · -ADRENERGIC AGONISTS Examples Terbaraline Epinephrine - - - Ephedrine - Salmeter of - Isoproternd - Albutero These agents are used to reverse acute episodes of bronchospason to prophylactically - Maintain airway parency over long time. a , muscle and ratbot release of bronchoconstrictions They relax airway smouth the - , motiators from the mast cells. inhibit microvascular They leakages and uncrease mucocillary transport by - increasing cillary activities. In other structures , B agonists increase adeny cyclase and increase formation of untracellular CAMp. Side - Effects - - lachycardia Sederal muscle tremor -.  Route of Administration The best is route which results the local raholatory on greatest effect on airway Muscles. Clinical Uses · Epinephrine bronchodilator This is a rapidly-acting Route Dos Danofliloa : - Subcutaneous ; - Inhalatory ; Dosage Bronchodilation is after administrationa lasts for 60-90 mins achieved 13 min - safe effects include Tachycardia Arrhythmia Angina pectors These are · , , - epinephrine stimulate X Bi Be. , , Ephedrine · This has ocal. a longer duration and its route is · Be-selective Adrenoceptors Albutero Examp ales : - - Terbutaine - Probatero - Metaproterend Be agonists are the mostly widely used sympathomimetics for asthora treatment. Maximum bronchodilation They are available in Inhaler. is achieved within minutes 3-4 hours They alsoun form of nobules 15-30 lasting : are : e-selectives are mixture of S and Risomers. The R-isomer activates against receptor while the Sisomer promotes inflammation -  Newgeneration B2-selective agonists partial agonist ~ i re ar For motorol full against - selective agonist with long-lasting turation up to Both are potent 2 12 hours as a result of tipot solubility thus permit them todissolve high , & small cell membrane They interact with inhaled storout to improve · Asthma- They are not recommended as monotherapy pla they have no antiinflammatory activity. Toxicity Cardiac arrhythmia - · METHYLXANTHINES Examples - Theophylline - Theobromine Caffeine - Their sources are plant alkaloids. Theophyte Theo s, hylline has proven efficacy as bronchodilators in the management of asthma. It was first line but is now relegatedC of narrow therapeutic windows and requires monitoring. Nocturnal asthma can be improved with slow releasing theophylline preparations - Like other interventions such Inhaled ucocorticoids 4 salmateos effective - as are most -  Clinical Uses Thpholline is the most effective bronchodilator used to relieve air flow obstruction a cute asthma and relieve in severity of symptoms - Intravenous theophylline · amintheophylline are not given by IV push they are rather given slonty at intervals If given byN push · of can cause , cardraw arrest - Mechanism of Action of action of methyl xanthine cellular bases Inhibition of phosphodiesterase PDz thereby increasing the intracellular CAMP. - affect Ca2 levels + Direct Untracellular CAMP concentration CAMP can - effect on. by activating catchannels & pumps. - Indirect effect on intracellular cat concentration with cell membrane & - Uncoupling of intracellular cast increase with muscle contractile element. - Antagonism of admosing receptor Major evidence suggest that this · antagonism The major important factor responsible for the pharmacological is action of methylxanthine. Adenosine is a chemical that can of airways cause constriction and inflammation in the body. Theophyrline blocksasthma the effects of adenosing , which can help to reduce inflammation and Pharmacokinetics. Absorption : Readily absorbed after the oral route rectal and parenteral , Distribution : Distributed well in all body compartments crosses placenta , and also into the milk passes. - The methylxanthines inhibit phosphodiesterase (PDE), the enzyme that degrades cAMP to AMP and thus increase cAMP.  · ANTICHOLINERICS Examples binds to M3 receptors and inhibit I pratropium bromide - The ragally-mediated contraction of Trotropium bromide and airway smooth mo secretion - mucous. - Homatropone , etc - The hasdrownedfollowing Leagentofinhala ed foun bromot this use of agent B-atwenergia agonist. asthmatic in subjects develop slowly and is usually less intense than MOTR that produced by atteneric agent. Combined treatment with pratropium ↑ agonist results slightly 2 in bronchodilation greater and more prolonged than ther agent above and is more effective ANTI-INFLAMMATORY AGENTS When compared glucocorticoids , most potent A widely are used and can be givensystemical sofinan offers advantage of less side effect andalso o available as nebulizer solution - · GLUCOCORTICOLDS Systemic glucocorticord is employed in treatment of patients with severe chronic asthma or severe acute exacerbation. Aerosolic formulations improve its motorate asthma- safety in Subjects who inholed 2 times require agonists more than four = Inhaled. e i 4 times are candidates for glucocorticoids - Glucocorticoids inhibit phospholipase 2 that converts minor membrane component to arachidonic acid.  Inhaled - Funcasone Rudesonide Mometasone , , Systemic - Dexamethasone Prednisolone , Hydrocortisone , Inhaled Glucocorticots The close of the inhaled strout must be emperically determined for each amount patient and should be based on of ding rather than number of inhalation - Mid-moderate asthma 300-400Ng/day Severa as thona M to 2000 Ng/day - Asthma patients on unhaled glucocorticoids show improvement symptoms in and lower with requirement for rescue agonist. Glucocorticoids Systemic These are used acute asthma exacerbation and chronic severe for asthma 40-60mg prednisoline daily 3 days; 1-2 mg/kg/day in children Glucocorticoids Toxicity of Inhaled : - Oropharyngeal ↓ bone canchdrasis with dyspepsia mineral density espin female - Side effects Inhaled Systemic > - Increased mood disturbance - Suppression of hypothalamo pituitary, axis Increased Bone ~ appetite - resorption - Candidiasis - Disorder in CHO and Lipid metabolism - Loss of glucose in DM - Cataract - skin thinning Skin purpura ~ ~ Dysphoria - Candidiasis Growth retardation. -  ALTERNATIVE THERAPIES CROMOLYN SODIUM AND NECROMIL SODIUM Mechanism of action This to is relatively poorly defined ; however attempt focused reduce accumulation intracellular cast unduced is on its ability of by antigen in sensi- cell #zed mast cells. It is believed to rnhibr pulmonary mast degradation stimul interaction btw mast cell bount ~ response to variety of inducing IgE and specific antigens - The release of histamina and other granular contents as well as the production of leukotriene have been shown to be remarkably reduced in-vitro by crombin inhanced phosphorpation of dalton proteins - cromolyn sodium can prevent the release of histamine and other chemicals from cells which can help to improve Pharmacimination mast asthma and allergies Symptoms of. Given by Inhal realized solution sol usingenter derib saris verd -I by specific Inhaler. pharmacological topiadecositionof The The of the the effects are no o the luno Only about 1 % from. Once absorbed excreted and Excretion : , it is unchanged in the wine bile in about equal proportion. Nebulizers are liquid medication into devices that turn finemistthat canbeInhalinthe us that releaseafine mist of liquid gas or Side &facts. - Bronchospason - Angoedema - taryngeal edena - Nansra Cough - - Junt swelling , - Pain ~ Rash  Uses # -moderate brondrial asthon a To prevent asthmatic attack · LEUROTRIENE PATHWAY INHINITORS Leukotrienes result acid and of 5-hopoxygenase arachidonic the action from on are s athenzed by a variety of inflammatory cells in the airways including cosinophits , mast cells , macrophages and basophils. Leukotriene BH LTBH is a potent neutrophil chemo attractant and LTCP and LTDA exert many effects known to occur in asthma including bronchoconstriction , increased bronchial in activity uncosal vedema and mucus hypersecretion. , Lenmotene B4 and crystin) lentivenes LTCH , LTD4 and LED are from arachidonic acid. 3-pooxygenase is found of myeloid origin in cells such as mast cells , basophils eisinophils and neutrophils , There are 2 approaches to the inhibition of this pathway ; Inhibition of 3-lipogenase thereby preventing emotione synthesis i. , ii. Inhibition of binding of system lenmotrines to receptor on target lissues - Zoenton is inhibitor 5-lipoxy, en use - a Montelurast and Zagirmast are selective I antagonist of the cystim lemotrine I - - , receptor CysLT and they block the effect of cystein lenitenes ,. Pharmacokinetics These and agents are orally active highly protein bound -. They undergo extensive hepatic metabolism - - zilentor and its metabolites are excreted in urea whereas Zaghunast , Montelukast and their metabolites undergo biliary secretion.  Adverse Effects Elevation in serum hepatic enzymes. ANTIGE · MONOCIONAL ANTIBODIES - Omalanmal is a monoclonal antibody that selectively kinds to human 1. This leads to decreased binding of loE to its receptor the surface of mast on cells and basophils. - Monoclonal antibodies mepolizumab , benralizumab and radizionals are intertempin 3 antagonist -. IL-3 is the cytokine involved major in recruitment activation and survival of , cosinophils in eosinophilic asthma-