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78 Cards in this Set

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What are the 2 physiologic features of Asthma?
1. increased bronchial and tracheal responses to stimuli

2. widespread narrowing of airway passages
What are the pathologic features associated with Asthma?
1. Contraction of airway smooth muscles
2. Mucosal thickening from edema and cellular infiltration
3. thickening in the airway lumen of viscid mucus plugs
Bronchoconstriction from smooth muscle contraction is most easily reversed by __1__ drugs, while reversal of edema and cellular infiltration requires sustained treatment with __2__ drugs
1. Bronchodilator

2. Anti-inflammatory
Antiasthmatic drugs classified as "short-term releivers"? "Long-term" controllers?
Short-term = Bronchodilators

Long-term = Anti-inflammatory agents
Explain the Immunopathogenesis of the Early Rxn of Asthma (occurs within 2 hrs)
1. initial allergen exposure
2. production of IgE that bind to mast cells of airway mucosa
3. Re-exposure to allergen cross-links Ag-Ab complexes
4. Mast cell degranulation of Anaphylatoxins
5. Smooth muscle contraction
6. Bronchoconstriction and immediate fall in FEV1
The early reaction of Asthma is mediated by these factors
Histamine
Tryptase
PGD2
LTC4
PAF
Explain the immunopathogenesis of the late reaction of Asthma (occurs 2-8 hrs later)
1. release of cytokines, IL's, and various factors from T cell and Mast cells
2. Activate Eosinophils and Neutrophils that release proteins and PAF
3. Edema, mucus hypersecretion, Smooth muscle contractions
4. Bronchoconstriction and increased bronchial reactivity with late fall in FEV1
Describe the Reflex response causing Bronchoconstriction
1. Afferent vagal pathway sends signal to CNS upon irritant stimulation
2. Efferent vagal pathway goes to Autonomic ganglia
3. Postganglionic fibers release ACh which binds to Muscarinic receptors on bronchial smooth muscle -> Bronchoconstriction
What are the 2 separate ways in which inhaled irritants can cause Bronchoconstriction?
1. releasing chemical mediators from Mast cells

2. stimulating Afferent Vagal receptors to initiate reflex bronchoconstriction
What 2 things does Bronchospasm in Asthma result from?
1. Mediator release

2. Bronchial hyperreactivity
Class of antiasthmatic drugs that relax smooth muscles, but will not relieve mucosal edema, cellular infiltration, or mucus formation
Bronchodilators
List the 5 B2-adrenergic agonist Bronchodilators
Albu-terol
Bitol-terol
Pirbu-terol
Meta-proter-enol
Terbut-aline
List the 2 Long-acting B2-adrenergic agonist Bronchodilators
Salme-terol

Formo-terol
List the 3 Sympathomimetic Bronchodilators
Epinephrine

Ephedrine

Iso-proter-enol
List the 4 Methylxanthine Bronchodilators
Amino-phylline

Theo-phylline

Dy-phylline

Pentoxi-fylline
List the 3 Muscarinic Antagonist Bronchodilators
Ipra-tropium

Tio-tropium

Atropine
Class of Antiasthmatic drugs that reduce bronchial responsiveness
Anti-inflammatory
List the 6 Glucocorticoids used as anti-inflammatories to treat Asthma
Beclo-methasone
Bud-eso-nide
Dexa-meth-asone
Flu-nisolide
Flu-tic-asone
Momet-asone
List the 2 Leukotriene antagonists used as Anti-inflammatories to treat Asthma
Monte-lukast

Zafir-lukast
Anti-IgE Antibody used as anti-inflammatory to treat Asthma
Omalizumab
What is the mechanism of action of prophylactics used to prevent asthma?
prevent Mast cell degranulation
Name the 2 prophylactic anti-asthmatic drugs
Cromolyn sodium

Nedo-cromil sodium
What is the theoretical goal of the Aerosol delivery of antiasthmatic drugs?
-producing high local drug concentration in the lungs

-LOW systemic absorption
Aerosol delivery to the lungs with low systemic absorption is especially important for these 2 groups of antiasthmatic drugs
B2-adrenergic agonists

Glucocorticoids

**have potentially serious side-effects when absorbed systematically
Even under ideal conditions, only __1__% of the aerosolized drug is deposited in the lungs and most of the remainder is __2__
1. 2-10%

2. Swallowed
In order to have minimal systemic effects, Aerosolized drugs should have one of these 2 properties
1. poor absorption from GI tract

2. rapidly inactivated by first-pass hepatic metabolism
The ratio of inhaled to swallowed drug can be improved by these 2 things
1. Large-volume 'spacer'

2. proper technique
What is Bronchodilation promoted by?

What 2 things can cause this and how?
cAMP

1. B2-adrenergic agonists = increase cAMP synthesis by activating Adenylyl Cyclase

2. Phosphodiesterase inhibitors (Theophylline) to slow cAMP degradation
What 2 things can inhibit Bronchoconstriction?
1. Muscarinic antagonists (Ipratropium)

2. Adenosine antagonists (Theophylline)
What are each of the following Methylxanthines found in?
1. Theophylline
2. Theobromine
3. Caffeine
1. Tea
2. Cocoa
3. Coffee
How are aminophylline, dyphylline, pentoxifylline, and theophylline administered?
Oral sustained-release or Parenteral preps
The Methylxanthines are declining in use b/c of greater effectiveness of other drugs except one...which one and why?
Theophylline b/c it is cheap
What is Theophylline's mechanism of action? (2)
1. inhibits Phosphodiesterase that usually degrades cAMP = causes increase intracellular cAMP = Cardiac stimulation and Smooth Muscle relaxation

2. acts partly as Adenosine Antagonist
What is the main therapeutic action of Theophylline (Methylxanthine)?
Bronchodilation
List the Pharmacodynamics of the Methylxanthines
1. CNS stimulation results in alertness and deferred fatigue
-side effects = nervousness, insomnia, tremors, convulsions

2. Positive Inotropic and Chronotropic effects with increased Cardiac Output may produce Arrhythmias and increase BP

3. Stimulate secretion of Gastric Acid and Digestive enzymes

4. are weak Diuretics due to increased GFR and diminished tubular Na+ reabsorption

5. Improve contractility of Skeletal muscle and the diaphragm; improved diaphragmatic fxn will diminish dyspnea

**think of Caffeine's effects
What is the most effective Methylxanthine bronchodilator?
Theophylline
Theophylline relieves airflow obstruction in __1__ and reduces symptom severity in __2__
1. acute asthma

2. chronic asthma
Sustained-release oral tablets of Theophylline produce therapeutic blood levels for how long?
12 hours or more
When should Theophylline only be used? Why?
When blood levels can be measured

b/c Therapeutic and Toxic effects are related to plasma levels
What may toxic doses of Theophylline cause?
Insomnia
Anorexia
NVD
Heachache
Anxiety
Arrhythmias
Seizures

***Neurotoxicity and Cardiotoxicity
Would Theophylline toxicity be increased in Liver or Renal disease? Why?

What 3 drugs increase the toxicity of Theophylline?
Liver b/c that is what metabolizes it = toxicity may increase in liver disease...beware!!!

Cimetidine, Fluoroquinilone (-floxacin's), & Macrolides (Erythromycin)
What is the mechanism of action of the Beta-2-Adrenergic agonists?
stimulate Adenylyl Cyclase -> increase cAMP -> Smooth muscle relaxation and bronchodilation
What is the drug of choice for Acute Asthmatic attacks?
β2-adrenergic agonists
-Albuterol
-Terbutaline
-Metaproterenol
-Pirbuterol
-Bitolterol
Which β2-adrenergic agonists are used for Prophylaxis?
Longer acting
= Sal-met-erol & Formo-terol
β2-adrenergic agonists have a longer duration of action than _______ when given orally or by inhalation
Epinephrine
The bronchodilation with β2-adrenergic agonists is maximal by __1__ and lasts for __2__
1. 30 min

2. 3-4 hrs
What are the common adverse effects of β2-adrenergic agonists?
Skeletal muscle tremor

Nervousness

Occasional weakness

**generally safe and effective when given in doses that avoid adverse systemic effects
What are the 2 Sympathomimetics used as Bronchodilators?
Ephedrine

Epinephrine
What is the downside of the Sympathomimetics?
by stimulating β1-adrenergic receptors they cause more cardiac side-effects = tachycardia, arrhythmia, worsening of angina

**also stimulate β2-adrenergic receptors to cause Bronchodilation
Sympathomimetic that is administered by inhalation or SubQ injection, is effective and rapid acting for Acute Asthmatic attacks
Epinephrine
Mechanism of action of Muscarinic Antagonists?
block Acetycholine at muscarinic receptors = prevent Bronchoconstriction
What 2 effects do Muscarinic Antagonists ultimately cause?
1. inhibit vagal stimulation to relax bronchial smooth muscle = prevent bronchoconstriction

2. decrease mucus secretion

**but do so without affecting those to NONMUSCARINIC stimuli
Why do Muscarinic Antagonists not always work?
Parasympathetic involvement in bronchospastic responses varies widely
Muscarinic Antagonist that is given by IV or by Inhalation and produces Bronchodilation lasting for 5 hours, but may cause dry mouth, urinary retention, tachycardia, loss of visual accomidation, and agitation
Atropine
Muscarinic antagonist that is given by Aerosol or Nasal spray and allows delivery of large doses because it is poorly absorbed and therefore has minimal CNS effects
Ipra-tropium bromide
Muscarinic antagonist that has a longer duration of 24 hours
Tio-tropium
List the 6 Corticosteroids used to treat Asthma
1. Beclo-methasone
2. Budes-onide
3. Flu-niso-lide
4. Flu-tica-sone
5. Mo-metasone
6. Triam-cino-lone
What is the mechanism of Corticosteroids in treating Asthma?
Inhibit the production of Inflammatory cytokines
1. reduce bronchial reactivity
2. increase airway caliber
3. reduce frequency of asthmatic attacks
By what modes of administration are the Glucocorticoids given?
Orally

Injection

Aerosol
Which routes of administration of Glucocorticoids may produce severe adverse effects?
Oral or Parenteral
When is systemic administration of Glucocorticoids only given?
patients requiring urgent treatment
Inhaled preparation of Corticosteroids may cause what 2 adverse effects?
1. Oropharyngeal candidiasis

2. Hoarseness from vocal cord irritation
What 2 Leukotrienes are potent Bronchoconstrictors secreted in Asthma and Anaphylaxis?
LTC4 & LTD4
What 2 drugs are LTD4-receptor antagonists?
Monte-lukast

Zafir-lukast
How are Monte-lukast and Zafir-lukast administered? Who are they especially useful for? What type of asthma are they especially good for?
Orally

children unable to comply with inhalation therapy

Aspirin-induced asthma
Antileukotriene that inhibits 5-lipoxygenase to reduce leukotriene formation but has been withdrawn due to Liver toxicity
Zi-leu-ton
What is the mechanism of action of Omalizumab?
Monoclonal Ab that inhibits binding of IgE to mast cells

***does NOT inactivate already bound IgE
Antiasthmatic that lessens the severity of asthma and reduces corticosteroid requirement
Omalizumab
Lowers plasma IgE levels and reduces bronchospastic antigen responses
Omalizumab
2 antiasthmatic drugs that are only effective when given prophylactically
Cromolyn

Nedocromil
Cromolyn and Nedocromil have an acute protective effect when given before these 2 things
1. Exercise

2. Allergen exposure
Cromolyn and Nedocromil inhibit bronchial hyper-reactivity in these 2 things
Antigen- & allergen-induced asthma
Cromolyn and Nedocromil do not affect these 2 things
Bronchial smooth muscles

Asthmatic bronchospasm
What is the mechanism of action of Cromolyn and Nedocromil?
Alter delayed chloride channels in cell membranes to:
1. inhibit mast cell activation
2. reduce release of histamine and other mediators
How are Cromolyn and Nedocromil administered? Why?
Aerosols b/c of poor GI absorption
Cromolyn and Nedocromil are less potent or effective when compared to _________
inhaled Corticosteroids
What are the characteristics of Mild Asthma?
Occasional symptoms occuring on exposure to allergens or pollutants, after exercise or Upper Respiratory viral infection
What are the characteristics of Severe Asthma?
Frequent attacks of wheezing dyspnea especially at NIGHT, resulting in limitation of activity