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46 Cards in this Set

  • Front
  • Back
What are the 3 major components of the pathophysiology of Asthma?
Airway inflammation
Bronchial hyperresponsiveness
airflow limitations
What is the most debilitating part of asthma and what are the major cells implicated?
Airway inflammation caused by Mast cells, lymphocytes, eosinophis and neutrophils
What some chemical mediators involved in inflammation associated with asthma?
IgE, Histamine, Tryptase, Leukotrienes, Platelet Activating Factor, Prostaglandins, Interleukins, Granulocyt0macrophage colony stimulating factor, tumor necrosis factor, Major Basic Protein, Eosinophil, Cationic Protein
What are some factors of bronchial hyperresponsiveness associated with asthma?
C-sensory receptors on the airways carry sensory information back up through the vagus
Efferent vagal neurons cause a reflex bronchoconstriction by stimulating muscarinic receptors
Reaction to cold air or high air flow rates
What are some factors associated with airflow limitations with respects to asthma?
Ultimately an obstruction of airflow with a biphasic response:
Early reaction - initial decrease FEV1 from 100-->75% in 15-20 min and return in an hour (tx with bronchodialators - due to released cytokines from mast cells)
Late reaction - due to inflammatory mediators released from lymphocytes and other cytokines
What is the only COPD that is reversible and completely treatable?
Asthma. The others are Emphysema and Bronchitis - goal of therapy is slow down progression
What are some general goals of asthma therapy?
Prevent chronic symptoms and asthma exacerbations
Maintain normal activity levels
Have normal or near normal lung function
Have no or minimal side effect while receiving optimal medications
How many stages of severity for asthma are acknowledged and what are they?
4:
Mild Intermittent
Mild Persistent
Moderate Persistent
Severe Persistent
What is the standard of therapy for long term Asthma control?
Beta-2 agonists for rapid relief and corticosteroids for long term treatment
What are the two primary pharmacological approaches to treating asthma?
Relievers: Short acting bronchodilators (Beta-2 adrenergic agents and anti-cholinergic agents)
Controllers: corticosteroids, Long acting bronchodilators (beta-2 adrenergic and methylxanthines), Cromolyn sodium, Leukotriene inhibitors, Anti-IgE monoclonal antibodies
What effects does theophylline have in regards to bronchodilation?
It blocks adenosine site preventing bronchoconstriction and it inhibits the breakdown of cAMP causing increased bronchodilation
What are the essential short acting bronchodilators that we must know and what subcategory of drug do they fall under?
Catecholamines:
Epinephrine
Isoproterenol
Isoetharine
Resorcinol Agents:
Metaproterenol
Saligenin Agents:
Albuterol
Class unsure:
Pirbuterol
Bitolterol
Increased use or daily use of short acting broncodilators such as beta 2 adrenergic agonists is indicative of?
It is a warning of deterioration of astham and indicated the need to institute or to intensify regular anti-inflammatory therapy.
What are the short acting anticholinergic (parasympatholytic) bronochodilators?
Tertiary ammonium compounds: atropine sulfate and scopolamine
Quarternary ammonium compounds: Ipratroprium (for those who can't tolerate short-actings b/c of tremor) and Tiotropium
What is the mechanism of action for short acting anticholinergic bronchodilators?
inhalation causing block of the effects of acetylcholine released from cholinergic nerves thereby reducing vagal tone in turn preventing reflexive allergy induced bronchoconstriction
What is the drug Combivent?
a combination of beta-2 and anticholinergic bronchodilators
What drug is the alternative short acting bronchodilator for those who experience adverse effects such as tachycardia, arrhythmias, and tremors from beta 2 agonists?
Ipatroprium
What is tachyphylaxis and what short acting bronchodilators do not show this effect?
It is a rapidly decreasing effectiveness with extensive use. And Beta 2 agonists do not show this.
What are the types of long term or "Controller" drugs?
Corticosteroids
Long-acting bronchodilators (Beta2 adrenergic and Methylxanthines)
Cromolyn Sodium/Neocromil
Leukotriene inhibitors
Anti-IgE monoclonal antibodies
What is the most effective anti-inflammatory for asthma?
Inhaled glucocorticoids
What are the inhaled glucocorticoid drugs?
Beclomethasone dipropionate - Prototype
Budesonide
Flunisolide
Fluticasone - becoming more common, especially in combo with albuterol or salmeterol called advair
Tramcinolone acetonide
What are the major side effects of INHALED glucocorticoid drugs?
Oropharyngeal Candidiasis
Occassional coughing
Dysphonia
What is the major side effect of SYSTEMIC glucocorticoid drugs?
Hypothalamic-pituitary axis suppression, osteoporosis, arterial hypertension, diabetes (everything associated), fatal herpes virus infections!??
Given the severe possible side effects of systemic glucocorticoids over oral glucocorticoids what reaason would you have to take systemics over inhaled and how are they administered?
Systemic long-term oral glucocorticoid may be required to control severe persistent asthma (I don't know if these means anything...?) Administered oral or parenteral
How long does a typical dose of albuterol last and what is a long acting adrenergic bronchodilator version of albuterol?
TYpically albuterol lasts 6-8hrs but in tablet form it leaks slowly and can last up to 12 hours (inhaled? haha j/K)
What is Salmeterol (Serevent) and how long does it last?
12 hour drug with a fairly substituted side chain. It is a long acting adrenergic bronchodilator.
What is the last drug in the adrenergic bronchodilator long acting sectiont that was mentioned with no additional information so that it doesn't really matter if you know it anyway?
Formoterol
What are the naturally occurring and synthetic derivatives of Xanthine agents used int he treatment of ASSTHAMA?
Naturally occuring agents: Caffeine, Theophylline, and Theobromine
Synthetic Derivatives: Dyphylline, Proxyphylline, Enprophylline
What are the modes of Xanthine agent administration?
oral or parenteral (caffeine injection!! hahah)
What are the effects of Xanthine agents on the LUNGS?
Phosphodiesterase inhibition (possibly) at high doses and anti-inflammatory effects (no fucking clue! - may be related to adenine receptor inhibition modulating adenylyl cyclase with a Uranium P32 module)
What are the side effects of Xanthine agents?
Ever taken a caffeine pill?
Gastrointestinal
Seizures (havent' had that one)
Cardiovascular
Pulmonary
Because of the indeterminate functionality of the Cromolyn and Nedrocromil sodium drugs what must be done with the patient (essentially guinea pig)?
3-4 week challenge to see if the drug even works with them
How is it presumed that Cromolyn and Nedrocromil sodium work and what is the mode of administration?
They partly inhibit the IgE mediated release from mast cells in a dose dependent manner (leading them to be called mast cell stabilizers possibly). They also possibly alter the function of delayed chloride channels in the cell membrane and you inhale it! (I hate writing indeterminate answers!!)
What is the role in therapy of Cromolyn and Nedrocromil Sodium?
Controller of persistent asthma
Administered prophylactically to inhibit early and late phase allergen-induced airflow limitation and acute after exposure to exercise, cold dry air, and sulfur dioxide
Minimal Side Effects so take it for fun! woohoo!
What are the various Leukotriene modifiers?
Cysteinyl Leukotriee 1 (CysLT1) receptor antagonists: Montelukast and Zafirlukast
Zileuton - 5-lipoxygenase inhibitor (blocks effects of LTB4 also)
What is the mode of administration of the leukotriene modifiers and what is their Mode of ACTION?
Oral
Receptor antagonists that block the CysLT1 receptor on airway smooth msucle inhibitng the effect os cystenyl leukotrienes that are released from mast cells and eosinophils
5-lipoxygenase inhibitors block synthesis of leukotrienes
What would be the effect and effectiveness of Leukotriene modifiers?
They have a small and variable bronchodilator effect preventing them from being used as a primary therapy but adjunctively may allow a decreased use of levels of glucocorticoids reducing systemic side effects
(it should be noted that they are less effective than long term inhaled beta 2 agonists)
What is a side effect of Zileuton and Leukotriene modifier therapy?
Zileuton is associated with liver toxicity
Leukotriene modifier therapy can cause Churg-Strauss syndrome (a small and medium vesel vasculitis due to autoimmunity)
What are the anti-IgE drugs and how do they work?
They are human monoclonal antibodies: rhuMAb and Omalizumab
They block the interaction of IgE with Mast cells or basophils
This in turn attenuates the early and late phase airway obstruction response to allergen and suppresses the accumulation of eosinophils in the airways
With regards to treatment protocols for asthma what is the utility of a peak flow meter?
Determines which of the 4 severity categories a patient may be in each day by measuring PEV or FEV1
What are the routes of administration for asthmatic drugs?
Inhaled:
Metered Dose Inhalers (MDI) - spacers and tubes that are attached to inhalers allow medication to be held in a chamber before it is inhaled - Lessens amount swallowed vs. inhaled
Dry powder inhalers (DPI) - capsules in to the DPI - puncture and breath into upper airway!
Nebulized "wet" aerosols - less portable?
Oral:
Parenteral:
Subcutaneous:
Intramuscular:
Intravenous:
What do the different color zones with regards to asthma patients imply?
Green = Go : 80-100% of PATIENT's best peak flow - utilize metered dose inhaler for acute exacerbation
Yellow = caution: 60-80% of patients personal best - MDI for acute exacerbations and begin fluticasone
Red = your dead! J/K Stop and get help!: <60% of patients best - go to hospital NOW!
What is the NIH Approach for treatment of Step 1: intermittent asthma?
Daily Controller Medication: None required
Reliever: Rapid-acting inhaled beta 2 agonists for symptoms (<1/wk)
Prophylaxis: Rapid-acting beta 2 agonist, cromolyn, leukotriene modifier before exercise or exposure to allergen
What is the NIGH Approach to Treating ashtma Step 2: Mild Persistent Asthma?
Daily controller medication: Inhaled glucocorticosteroid or sustained release theophylline, cromone, or leukotriene modifier
Reliever Medication: Rapid acting inhaled beta 2 agonists symptoms (<3-4x/day) or inhaled anticholinergics, short acting oral beta 2 agonists or short acting theophylline
What is the NIH Approach to Treating Asthma Step 3: Moderate Persistent Asthma?
Daily Controller medication: inhaled glucocorticosteroid plus long acting inhaled beta 2 agonists or inhaled glucocorticosteroid plus sustained release theophylline, inhaled glucocorticosteroid at higher dose or inhaled glucocorticosteroid with a leukotriene modifier
Reliever mediction: Rapid acting inhaled beta 2 agonists symptoms (<3-4x/day) or inhaled anticholinergic, short acting oral beta 2 agonists, or short acting theophylline
What is the NIH Approach to Treating Asthma Step 4: Severe Persistant Asthma?
Daily Controller: Inhaled Glucocorticoid (higher dose than for moderate) plus long acting beta 2 agonists plus one or more of the following - sustained release theophylline, leukotriene modifiere, or oral glucocorticosteroid
Reliever medications: Rapid acting inhaled beta 2 agonists - for symptoms (<3-4x/day) or inhaled anticholinergics, short acting orl beta 2 agonists or short acting theophylline
Try to modulate amount of steroids by supplementing with other drugs