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RS Pharmacology

Respiratory System Pharmacology-Treatment of Bronchial Asthma

QuestionAnswer
Late asthmatic response is prevented by: Corticosteroids
Which factors trigger asthma? Exercise / cold air Smoking Stress/anxiety Animal dander Allergens (grass, trees, molds, cockroach) Pollutants (sulfur dioxide, ozone, etc) Fumes/toxic substances Medications (ASA, NSAID’s, others)
Diagnosis of asthma is done by: Cough,dysnpea, past and family history- subjectively Reduced FEV1/FVC ratio, FEFR, reversibility with bronchodilators, increase in expired NO - objectively
Asthma is A chronic disease Possibly fatal
Asthma medications are: NOT addictive DO NOT become ineffective
How is asthma generally treated? Oxygen Hydration: Oral or Intravenous Expectorants Antimicrobials
Examples of Quick relief asthma medications: Inhaled Short acting Beta-2 Agonists Inhaled Anticholinergics Systemic Corticosteroids
Examples of Long-term control medications: Inhaled Corticosteroids Inhaled Cromolyn Na and Nedocromil Oral Methylxanthines (Theophyllines) Inhaled Long-acting Beta-2 Agonists (LABA) Oral Leukotriene modifiers (LTRA)
Pharmacological actions of Beta 2 adrenergic receptors: Bronchodilation Tremor Tachycardia Fall in blood pressure Slight fall in plasma potassium
What is the DOC for acute exacerbations? Beta 2-Adrenergic Agonists
Function of Beta 2 adrenergic receptors: Relax airway smooth muscle Inhibit release of mediators Enhance muco-cilliary activity Decrease vascular permeability Inhibit eosinophil activation
General characteristics of epinephrine: Not selective, can stimulate α, β1 receptors Not effective orally Inhalation Subcutaneous( in status asthmaticus)
General characteristics of isopretenol: Stimulates β1 and β2 receptors Convenient, pocket- sized multidose inhaler Considerable tachycardia and pounding
Examples of Short Acting Beta 2-Adrenergic Agonists: Albuterol Terbutaline Pirbuterol Metaproterenol Isoetharine Ancient Tyrants Pursued Mysterious Iodine
General characteristic of short acting beta 2 adrenergic agonists: Beta 2 selective
Onset of short acting beta 2 adrenergic agonists: 3-5 minutes.
Maximal effect of short acting beta 2 adrenergic agonists: 30-60 minutes
DOA of short acting beta 2 adrenergic agonists: 4-6 hours
Examples of Long Acting Beta 2-Adrenergic Agonists(LABA) Salmeterol Formeterol
DOA of long acting beta 2 adrenergic agonists: 12 hours
General characteristics of LABA: Suppress nighttime attacks Controllors with steroids No tachyphylaxis.
Problems of Metered Dose Inhalers(MDI) Cap not removed prior to use in some patients Timing of canister actuation to inspiration is critical - only first air gets into the right place. Inspiration too rapid - should take 4 - 5 seconds Nasal inspiration contains no medication
Short-acting formulations are to be used only In necessary situations Regular use is associated with tachyphylaxis and diminished control
Toxicity of beta 2 adrenergic agonists cause: Nervousness and Anxiety Tremor Tachycardia Increased mortality due to cardiac toxicity
Pharmacogenetics of Beta 2-Adrenergic Agonists Patients homozygous for glycine at the B-16 locus of the β receptor improved with regular use of albuterol or salmeterol. Patients homozygous for arginine at the B-16 locus of the β receptor deteriorated with regular use of albuterol or salmeterol
Examples of Methylxanthines: Theophylline Aminophylline
Which drugs were the mainstay treatment for asthma? Methylxanthines
How are Methylxanthines administered? Oral IV
Methylxanthines are classified as: CNS stimulants: active ingredients in coffee, tea, and cocoa Cardiovascular stimulants: arrhythmias, Nausea, GIT irritation, diarrhea
MOA of Methylxanthines: Phosphodiesterase inhibition Adenosine receptor stimulation Antiinflammatory activity
Problems with Methylxanthines: Toxic: CNS, Cardiac, GIT Optimal dosing is difficult Wide inter-individual variation in hepatic metabolism Subject for food and drug interactions (erythromycins and ciprofloxacin) Blood monitoring-required
What is the half life of Methylxanthines? 3-16 hours
Use of low dose theophylline significantly inhibits Late Asthmatic Reaction (LAR) Airway inflammatory infiltration
Examples of anti-cholinergic agents: 1) Atropine 2) Ipratropium Bromide
Function of atropine: Reduces secretions and impairs mucociliary clearance leading to impaired clearance of airway secretions
Ipatropium bromide doesn't: Impair clearance of airway secretions
How is ipatropium bromide administered? As metered dose inhaler and as a solution for nebulization
Main uses of ipatropium bromide: Mainly useful for COPD Might be very useful only in special conditions of asthma( beta blocker- induced asthma, resistant attacks, cardiac patients)
Onset and potency of ipatropium bromide: Slow onset (10-15 minutes) and low potency
Examples of Anti-inflammatory Agents and Alternative Therapy: Coricosteroids Inhibitors of Mast Cell Degranulation Leukotriene Pathway Modifiers Immunomodulatory Agents
Functions of corticosteroids: Inhibit the synthesis and release of histamine, PGs and cytokines Suppress the inflammatory process Relax bronchial smooth muscle Enhance beta-adrenergic responsiveness Decrease quantity of secretion Inhibit IgE
MOA of corticosteroids: Highly lipophilic Bind to cytosolic receptors Drug-receptor complex enters the nucleus Influence transcription of target genes Decrease transcription of genes coding for pro inflammatory cytokines
How long do corticosteroids need to work? Several hours to days
How are corticosteroids administered? Orally Injected
Examples of corticosteroids (oral/injectable) Cortisone, Prednisolone, Dexamethasone
When are corticosteroids administered? Short term use indicated in severe refractory attacks Long term use indicated in ”Steroid Dependant” asthma
What is the most effective way to avoid systemic adverse effects? Aerosol treatment
Examples of corticosteroids administered by inhalation: Beclomethasone Triamcinolone Flunisolide Budesonide Fluticasone Toxic Boys Brew Furious Fathers
Local side effects of corticosteroids: Hoarsness of voice (dysphonia) Sore throat and cough Candida infection
Systemic side effects of corticosteroids: Osteoporosis, cataract, glaucoma, growth retardation, adrenal suppression, CNS effects and behavioral disturbances, increased susceptibility to infections, and teratogenicity
Examples of Inhibitors of Mast Cell Degranulation: Cromolyn Na and Nedocromil Na
Functions of IMCGs: Inhibit the release of inflammatory mediators from mast cells (Mast Cell Stabilizers) Prophylactic for mild to moderate asthma
How often are IMCGs used? Regular use ( 4 times daily)
In what case can IMCGs not be used? Acute asthma
MOA of IMCGs: Phosphorylate a cell membrane protein, so, mediator release is inhibited despite antigen-IgE interaction Might decrease Ca++ Might decrease neural pathways, plasma exudation and inflammation, in general
Side effects of IMCGs: None related to the drug
Leukotrienes are synthesized by: Mast cells and eosinophils
Created by: Ulaisl