Bronchial Asthma Treatment PDF

PRESENTATION BY DR/ MOHAMED ABDEL AZIZ Bronchial asthma  Lines of treatment: I-Quick relief medications: 1-Bronchodilators: a) B2 selective agonists ( Salbutamol-Salmetrol) b) B-non selective agonists (Epinephrine-isoprenaline) c) Drugs inhibit adenosine A...

PRESENTATION BY DR/ MOHAMED ABDEL AZIZ Bronchial asthma  Lines of treatment: I-Quick relief medications: 1-Bronchodilators: a) B2 selective agonists ( Salbutamol-Salmetrol) b) B-non selective agonists (Epinephrine-isoprenaline) c) Drugs inhibit adenosine A1 receptors (Theophylline – methylxanthine) d) Drugs inhibit cholinergic M3 receptors (Ipratropium) 2-Corticosteroids II-Long term control medications :( prophylaxis) As quick relief medications +: 1-Cromolyn-like drugs 2-Leukotrienes modifiers  B2 selective agonists Members: Short acting: Salbutamol, Terbutaline Long acting: Salmetrol Route: Inhalation (MDI) is the best (least dose &fewer side effects) Oral & parenteral may be used  Mechanism of action: Stimulation of B2 receptor activates Gs protein that stimulates adenyl cyclase enzyme that increase c-AMP and decrease intracellular calcium leading to: 1-Bronchodilation (used in acute attack) 2-Mast cell stabilizer, inhibit mediator release (used in prophylaxis) 3-Improve mucociliary transport  Adverse effects: 1-Throbbing headache 2-Tremors 3-Tachycardia 4-Tolerance 5-Locked lung syndrome & hypoxia (with large dose) 6-Constipation 7-Hyperglycemia & hypokalemia (with IV) Methylxanthines (theophylline & caffeine) Mechanism of action: Block adenosine A1 receptors inhibit phosphodiestrase enzyme leading to increase in c-AMP (act as before) Pharmacological actions: 1-Smooth muscle relaxation (bronchodilatation) 2-Skeletal muscle contraction (diaphragmatic contraction) 3-Cardiac stimulation (positive inotrope & chronotrope) 4-CNS stimulation (delay fatigue, insomnia & respiratory stimulation)  Indications: 1-Bronchial asthma: both in acute attack (IV) & prophylaxis (oral or rectal) 2-GOPD (generalized obstructive pulmonary disease) 3-Cardiac asthma (bronchospasm due to HF) 4-Biliary colic 5-Caffeine is used in migraine (cause cerebral VC & help ergot absorption)  Adverse effects: (the only drug in bronchial asthma that can lead to death as it has small therapeutic index (narrow safety margin) : 1-CNS adverse effect at 15ug/ml: anxiety, headache, palpitation& vomiting 2-CVS adverse effect at 20ug/ml: hypotension (VD) & palpitation 3-Death at 40ug/ml due to: convulsion & arrhythmia As it is irritant it causes: 1-Phlebitis on undiluted IV 2-Proctatitis on repeated rectal 3-Peptic ulcer & constipation on oral use 4-Cardiac arrest on rapid IV Pharmacokinetic of theophylline ( metabolized in liver) ⚫ We must Increase doses in patients with highly active liver enzymes as: Cigarette smokers --Children --Enzyme inducers (phenytoin) ⚫ We must Decrease doses in patients with lower liver enzymes activity as: Liver cirrhosis---Extreme of age---Enzyme inhibitor (cimetidine)---Heart failure  Anticholinergic drugs (Ipratropium) ⚫ Mechanism: Block muscarinic receptors (M3) receptors in bronchi to antagonize cholinergic effect and induce smooth muscle relaxation and bronchodilatation ⚫ Route: Inhalation (least dose & fewer side effects than atropine) may be combined with B2 agonist Indications: Preferred in patients intolerable to B2 agonist or xanthines (cardiac and thyrotoxicosis patients) Adverse effects: 1-Delayed onset 2-Tolerance Antiinflammatory drugs used in bronchial asthma: 1-Hormone (Corticosteroids) 2-Non hormone (cromolyn like drugs-- leukotrien modifier)  Corticosteroids ⚫ Mechanism: ⚫ Inhibit phospholipase A2, inhibiting inflammatory mediators synthesis (LTs) acting as anti- inflammatory and immunosuppressive. Indications: 1-During attack in Status asthmaticus (severe resistant attack), given by IVI 2-The best Prophylaxis, as corner stone in persistent asthma, given by inhalation Adverse effects: 1- Inhalation: -Oral candidiasis (avoided by mouth wash or spit after use) -Hoarseness of voice 2- Systemic: Adrenal suppression,osteoporosis,glaucoma & cataract Preparations: 1-Inhalation: beclomethasone-betamethasone-fluticasone- Triamcinolone- Budesonide 2-IV: Hydrocortisone 3-Oral: prednisolone  Cromolyn – like drugs (Disodium cromoglycate - Nedocromil) Mechanism: 1-Mast cell stabilizer inhibit mediator release by phosphorylation of cell membrane &blocking calcium channels. 2-Inhibit IgE synthesis  Indications: Used only in prophylaxis as it act after 4 days 1-Bronchial asthma (inhalation) 2-Allergic conjunctivitis (eye drops) 3-Allergic rhinitis (nasal drops) 4-Ulcerative colitis (oral)  Adverse effects :( local irritation) 1-Wheezes, cough (avoided during acute attack and give B2 agonist before use) 2-Nasal congestion 3-Stinging sensation in eye  Leukotriens modifiers 1- Zileuton: -Inhibit 5 lipooxygenase enzyme, inhibiting LTs synthesis -Used as alternative to corticosteroids in prevention of antigen induced ,aspirin or exercise induced asthma -But it is enzyme inhibitor & hepatotoxic (elevate liver enzymes) 2- Zafirlukast & Monteleukast: Block LTs receptors Used as zileuton It causes vasculitis &congenital limb defects (lerss side effects than ziluton) NB. LTs modifier are not recommended for acute episodes of asthma. Treatment of status asthmaticus:( acute severe asthma) 1-B2 stimulant by nebulizer 2-Hydrocortisone IV 3-Theophylline IV infusion 4-Magnesium sulphate 4-Oxygen, antibiotics, mucolytics and rehydration Drugs precipitate bronchial asthma : contraindicated 1- B blockers especially non selective 2- Adenosine 3- Cholinomimetics (neostigmine) 4- Morphine & curare (release histamine) 5- NSAID (increase LTs) 6- Cromolyn without B2 agonist