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Drugs Used in Asthma and COPD

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Drugs Used in Asthma and COPD Drugs used in Asthma and COPD Objective : 1. Different types of drugs used for treatment of asthma 2. Differentiate between treatment and prophylactic therapy for asthma 3. Recognize the different types of bronchodilators regarding pharmacokinetics, pharmacodynamics, uses and side effects. 4. Identify the different anti-inflammatory drugs for asthma in respect to kinetics, dynamics, uses and side effects. § Addi-onal Notes § Important § Explanaon –Extra- For any correc-on, sugges-on or any useful informaon do not hesitate to contact us: [email protected] Bronchial Asthma It is a chronic inflammatory disorder of bronchial airways that result in airway obstruction in response to external stimuli (as pollen grains, cold air and tobacco smoke). • Asthma produces recurrent episodic attack of : Acute bronchoconstriction, Shortness of breath, Chest tightness, Wheezing, Rapid respiration, Cough. Symptoms • Symptoms can happen each time the airways are irritated by inhaled irritants or allergens. • Infection, Stress, Exercise (cold air), Pets, Seasonal changes, Emotional conditions, Some drugs as aspirin, β- blockers. Causes • Airway hyper-reactivity: abnormal sensitivity of the airways to any external stimuli. • Inflammation:↑ edema, swelling +↑ Thick mucus production. Characters • Bronchospasm (constriction of the bronchial smooth muscles). of airways Irritant receptors in upper airways. We want to enhance the Afferent nerves sympathetic or (sensory) inhibit the C-fiber receptors in lower airways. parasympathetic in this case. Airways Innervations Parasympathetic supply M3 receptors in smooth muscles and glands: Bronchoconstriction and Increase mucus secretion. Efferent nerves (motor nerves) No sympathetic supply but β2 receptors in smooth Afferent nerves (sensory) are stimulated by: muscles and glands: Bronchodilatation, Decrease mucus - Exogenous chemicals or irritants secretion. - Physical stimuli (cold air) - Endogenous inflammatory mediators e.g. histamine 1. Quick relief medications (Bronchodilators): Bronchodilators used to rapid relieve acute episodic Anti-Asthmatic drugs attacks of asthma. • Short acting β2-agonists • Anti-muscarinic • Xanthine preparations (this substance has effects like coffee and tea “caffeine “) Mechanism of Action: - Direct β2 stimulation ⎯→ stimulate adenyl cyclase ⎯→ ↑ cAMP → Bronchodilatation. - Increase mucus clearance by (increasing ciliary activity). - Stabilization of mast cell membrane. When cAMP increase in the cell.. Ca+ levels decrease which prevents contraction and cause Bronchodilatation. ______________________________________ 2. Control therapy (prophylactic drugs): Anti-inflammatory drugs used to reduce the frequency of attacks, and nocturnal awakenings (attacks at night). β • Corticosteroids: -Given as prophylactic medications, used alone or combined with 2 agonists. -Effective in allergic, exercise, antigen and irritant-induced asthma. -Systemic corticosteroids are reserved for: Status asthmaticus (i.v.). β Inhaled steroids should be considered for adults, children with any of the following features : using inhaled 2 agonists three times/week , symptomatic three times/ week or more; or waking one night/week. • Mast cell stabilizers. • Leukotriene's antagonists ATP β-agonists (Increase) • Anti-IgE monoclonal antibody Adenyl cyclase • Long acting ß2-agonists Bronchodilaon cAMP What do they do ? Phosphodiesterase ↓ bronchial hyper-reactivity. ↓ reduce inflammation of airways Methylxanthines (inhibit) ↓ reduce the spasm of airways 3,5,AMP Bronchodilators These drugs can produce rapid relief of bronchoconstriction - β2 adrenoreceptor –agonists (Sympathomimetics) Classification Non selective β agonists Selective β2 – agonists (Preferable) Salbutamol of β agonists epinephrine isoprenaline Terbutaline Salmeterol Formeterol (albuterol) -combined with inhaled corticosteroids to control asthma. Potent bronchodilator - (decreases the number and severity of asthma attacks). - Rapid action (maximum effect within 15 Short acting ß2 agonists Long acting ß2 agonists min) – different than onset of action - Have rapid onset of action Duration of 12 hours Bronchodilators due to where it works in 5 minutes - (15-30 min). action high lipid solubility (creates depot - Has short duration of action (60-90 min) - short duration of action (4-6 effect). – because it’s natural - hr) inhalation, Inhalation, Inhalation Administration Given subcutaneously, S.C. orally, s.c. orally, i.v. -is the preferable way in asthma-. - not used to relieve acute episodes of asthma –because the onset of Drug of choice for acute anaphylaxis used for acute episodic attack Uses action is delayed - (hypersensitivity reactions). of asthma (drugs of choice). الربو) used for nocturnal asthma - .(drugs of choice) ( الليلي Non selective = many side effects - Not effective orally - will be broken -Skeletal muscle tremors. down by COMT and MAO. - Nervousness Dis- - Hyperglycemia, Skeletal muscle tremor. - Tolerance (β-receptors down regulation) – decrease number of advantages CVS side effects: tachycardia, arrhythmia, receptors à No response - hypertension. - Overdose may produce tachycardia due to β stimulation . - Not suitable for asthmatic patients with 1 hypertension or heart failure. Contra- CVS patients, diabetic patients - indications Minimal CVS side effects and suitable for asthmatic patients with CV Advantages - disorders as hypertension or heart failure. Bronchodilators Con. Anti-muscarinics Xanthine preparations (Methylxanthines) - Are phosphodesterase inhibitor → increases cAMP → (Muscarinic antagonists) Bronchodilatation. –this is the main mechanism- Mechanism of Act by blocking muscarinic receptors - Universal Adenosine receptors (A1) antagonists → prevent Action (Inhibit bronchoconstriction and mucus bronchoconstriction. secretion) - Increase diaphragmatic contraction. - Stabilization of mast cell membrane. Classification of β agonists Ipratropium Tiotropium Theophylline aminophylline Administration given by aerosol inhalation à local given orally . is given as slow infusion . -Main choice in chronic obstructive pulmonary diseases (COPD). Second line drug in asthma. For status asthmatics -it is not used in Saudi Arabia and (aminophylline, is given as Uses -In acute severe asthma combined with β it’s very cheap-. slow infusion). 2 agonists & corticosteroids. -metabolized by Cyt P450 enzymes in liver -has short -T ½= 8 hours Pharmaco- duration of kinetics & -has longer -has many drug interactions. action 3-5 hr duration of action -Enzyme inducers: as phenobarbitone and rifampicin → ↑metabolism of Duration of (Have delayed (24 h) theophylline → ↓ ½T . action onset of action) Enzyme inhibitors: as erythromycin→ ↓ metabolism of theophylline → ↑½T. Quaternary derivatives of atropine - Bronchial muscle relaxation (polar) -↑contraction of diaphragm → improve ventilation CVS: ↑ heart rate, ↑ force of contraction Pharmacological -Does not diffuse into the blood GIT: ↑ gastric acid secretions Effects & -Do not enter CNS Kidney: ↑renal blood flow, weak diuretic action characterized by β -Less effective than 2-agonists. CNS stimulation: -No anti-inflammatory action only - stimulant effect on respiratory center. bronchodilator - decrease fatigue & elevate mood. -Low therapeutic index (narrow safety margin) monitoring of theophylline blood level is necessary. They have slow onset of action - β2 -CVS effects: hypotension- may lead to reflex tachycardia-, Disadvantages blockers are better arrhythmia. -GIT effects: nausea & vomiting -CNS side effects: tremors, nervousness, insomnia, convulsion Advantages Have minimal systemic side effects - Mast cell Leukotriene's Anti-IgE monoclonal stabilizers antagonists antibody Corticosteroids zafirlukast Cromoglycate montelukast Omalizumab Nedocromil pranlukast - Inhibition of phospholipase A2 - Not bronchodilators -↓ prostaglandin and - Not effective in acute Leukotriene B4: chemotaxis leukotrienes attack of asthma. of neutrophils. Any drug ends with -↓ Number of inflammatory - Prophylactic anti- suffix (-mab) means cells in airways. inflammatory drug Cysteinyl leukotrienes C4, that it deals with Me- -Mast cell stabilization →↓ - Reduce bronchial hyper- D4 & E4: antibodies.. So it’s a chanism histamine release. reactivity. - Bronchoconstriction protein, and it can’t be of Action -↓ capillary permeability and - Effective in exercise, - increase bronchial hyper- taken orally because mucosal edema. antigen and irritant-induced reactivity proteins will be broken -Inhibition of antigen-antibody asthma. - ↑ mucosal edema. by stomach gastric. reaction. - Children respond better ↑ β - mucus secretion. Upregulate 2 receptors (have than adults additive effect to B2 agonists). (Pharmacodynamics) -Anti-inflammatory actions, Immunosuppressant effects, Metabolic effects, Hyperglycemia. -are selective, reversible antagonists of cysteinyl -↑ protein catabolism, ↓ protein -is a monoclonal leuko Taken orallytriene anabolism antibody directed receptors (CysLT receptors). -Stimulation of lipolysis - fat 1 against human IgE -Are bronchodilators Pharm- redistribution -prevents IgE binding acolo- Mineralocorticoid effects: -Have anti-inflammatory - with its receptors on gical -sodium/fluid retention, Increase action mast cells & actions potassium excretion (hypokalemia), -Less effective than inhaled basophiles. Increase blood volume corticosteroids -↓ release of allergic (hypertension), Behavioral -Have glucocorticoids changes: depression, Bone loss mediators. sparing effect (potentiate (osteoporosis) due to Inhibit
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