Question | Answer |
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 |