Pharm Respiratory
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| asthma | chronic inflammatory disorder of the airways (results from immune response to known allergen.environment/emotions/exercise/drugs or unknown cause). Causes bronchoconstriction and inflammation
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| bronchoconstriction | allergen binds to IgE on mast cell which causes release of histamine, leukotrienes, interleukins, and prostaglandins
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| inflammation | infiltration of inflammatory cells and mediators
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| symptoms | breathlessness, tightening of chest, wheezing, dyspnea, cough
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| Metered Dose Inhaler (MDI) (definition) | small,hand held pressurized device that delivers measured dose of drug with each inhalation/puff. Use HFA as propellant, . Dose is normally 1-2 puffs
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| Metered Dose Inhaler (instructions for use) | canister inverted, need to keep clean, measured doses, need slow and deep inspiratory flow, need hand-lung coordination, need to prime and shake device, can use a spacer to eliminate need for hand-lung coordination
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| Dry Powder Inhaler (DPI) | deliver drugs in the form of dry, micronized powder to lungs, no propellant
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| Dry powder Inhaler (instructions for use) | breath activated (no hand lung coordination needed), counter tells you how any doses left, inspiratory flow deep and forceful, mostly used as controller of symptoms
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| Metered Dose Inhaler Advantages | useful for acute attacks, pressurized, so patient doesnt have to breath in (might be hard during attack)
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| Metered Dose Inhaler Disadvantages | need hand lung coordination, not much actually gets into lungs (a lot gets in oropharynx)
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| Dry Powder Inhaler Advantages | no environmental risk, easier to use, no hand lung coordination, stability of delivery (more gets into the lungs vs oropharynx)
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| Dry Powder Inhaler Disadvantages | bad for asthma patients because they cant breathe, mostly used for controller substances
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| Anti Inflammatory Asthma medication classes | Corticosteroids, Leukotriene Modifiers, Mast Cell Stabilizers (Cromones), Anti IgE
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| Corticosteroids (Glucocorticoids)- MOA | decrease synthesis of inflammatory mediators (histamine, leukotrienes, prostaglandins) and inflammatory cells (eosinophils, leukocytes), decrease airway edema, airway mucous production and hypersecretion
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| Corticosteroids- Uses | controller/prophylaxis of chronic asthma (improve lung function, reduce exacerbations), delayed response, need fixed schedule, not PRN
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| Oral Corticosteroids | Methylprednisolone (Medrol) and Prednisone
used for severe asthma, potential for toxicity.
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| Inhaled Corticosteroids | • Beclomethasone Dipropionate (QVAR)
• Budenoside (Pulmicort)*
• Fluticasone (Flovent)*
first line therapy, used daily in all patients with moderate to severe asthma (less systemic effects than oral)
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| Common side effects of corticosteroids | oral thrush, cough/wheezing, dysphonia (hoarseness) --> gargle to reduce
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| Acute adverse effects of glucocorticoids | occur within a couple of days:
- sodium/water retention
-hyperglycemia
-behavioral/CNS stimulation or depression
-increased appetite/weight gain
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| chronic adverse effects of corticosteroids | within weeks; growth suppression in children, Cushing syndrome, acne, hirsutism, decreased bone mineral density, myopathy, muscle wasting, peptic ulcer, adrenal suppression
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| Leukotriene Modifiers- MOA | suppress effects of leukotrienes, the compounds that promote bronchoconstriction and eosinophil infiltration, mucous production, and airway edema
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| Leukotriene Modifiers- Uses | alternative long term control for step 2,3,4
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| 2 types of leukotriene modifiers | 5 Lipooxygenase Inhibitors and Leukotriene D4 receptor Antagonists
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| 5 lipooxygenase inhibitors- MOA | prevent the formation of leukotrienes (inhibits 5-lipooxygenase, which is the enzyme that converts arachidonic acid to leukotrienes). Antiinflammatory and bronchodilatory action. Effects within 1-2 hours (not effective for acute attacks)
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| 5 Lipooxygenase inhibitors- prototype | Zileuton (Zyflo)
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| Leukotriene D4 receptor antagonists- MOA | prevent leukotrienes from interacting with their receptors. Bronchodilatory action and lessens mucous secretion.
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| 2 Leukotriene D4 receptor antagonists | Zarfirlukast (Accolate) and Montelukast (Singulair)
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| Montelukast (Singulair) | prophylaxis and maintenance of asthma in patients > 1 year old. Prevention of exercise induced bronchospasm in patients over 15 year old, relief of allergic rhinitis, maximum effects within 24 hours, maintained with once daily dosing
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| Leukotriene Modifiers- adverse effects | most common side effects: headaches, GI
Zileuton: hepatotoxicity
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| Mast Cell stabilizers (Cromones) - MOA | inhibits mast cell degranulation, prevents releas eof histamine and inflammatory mediators
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| Mast Cell Stabilizers (Cromones)- uses | alternative long term control for step 2, prophylaxis of exercise induced bronchospasm (15 min before exercising), may take 4-6 weeks of regular use to see max benefits
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| Mast Cell Stabilizers (Cromones)- prototype | Cromolyn (Intal)- prophylaxis of asthma, not useful for acute attacks, administered through inhalation
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| Anti IgE- MOA | Recombinant humanized IgG monoclonal antibody that binds to IgE. forms complexes with free IgE in blood and reduces amount of IgE available to bind with allergens/receptors on mast cells. Prevents Mast cell degranulation/release of inflammatory mediators
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| Anti IgE- prototype | Omalizumab
- given subQ, very expensive
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| Anti IgE- uses | maintenance therapy (long term control) for step 5-6 and patients who have positive skin test or in vitro reactivity to allergen and cannot be controlled with ICS
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| Adverse Effects of Anti IgE | increased risk of malignancies, injection site reactions, risk of anaphylaxis
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| 3 classes of bronchodilators | Beta 2 Agonists, Anticholinergics, Methylxanthines
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| Beta 2 Agonists- MOA | Produce selective activation of beta 2 receptors. Stimulate intracellular adenyl cyclase, increase cAMP, cAMP activates beta2 receptors in smooth muscle of lung. Causes bronchodilation and inhibits mediatory release, increase ciliary motility
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| Beta 2 Agonists- uses | given by inhalation, relieve ACUTE bronchospasm and prevent exercise induced bronchospasm. Long actin form can protect against bronchospasm over an extended period of timr
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| Short Acting Bronchodilators (SABA) | ALBUTEROL;
onset of action in 5 minutes or less, duration of 4-6 hours. All patients will get SABA prn. Most effective drugs for prevention of exercise induced bronchospasm
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| Long Acting Bronchodilators (LABA) | SALMOTEROL (SEREVENT)
long term contorl for step 3,4,5,6. when combined with ICS, reduces daytime and especially night time symptoms, improves lung function, reduces risk of exacerbations, minimizes dose of ICS
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| Oral beta 2 Agonists | used only for long term, onset is too slow to abort ongoing attack. (Terbutaline/Brethine)
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| Terbutaline (Brethine) | approved to treat bronchospasm associated with asthma, bronchitis, and emphysema. Used off label for treating preterm labor and uterine hyperstimulation
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| Terbutaline (Brethine) Warnings/Contraindications | injectable shouldnt be used in pregnant women for prevention or prolonged tx of preterm labor because of potential for serious maternal heart probelms and death. oral should not be used for prevention or any tx of preterm labor
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| Adverse Effects of Beta 2 Agonists (Inhaled Short Acting) | well tolerated, systemic effects= tahcycardia, angina, tremor
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| adverse effects of Beta 2 agonists (Inhaled Long acting) | BLACK BOX WARNING (Salmoterol)= may increase risk of asthma related death WHEN USED ALONE. Should only be used as additional therapy for patients not adequately controlled on other meds of disease severity warrants tx with 2 maintenance therapies(USE ICS)
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| Adverse Effects of Beta 2 agonists (Oral long acting) | systemic sympathetic effects
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| Anticholinergics- MOA | block cholinergic receptors in the bronchi = decreased cGMP, increased cAMP, bronchial smooth muscle relaxation
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| Anticholinergics- Uses | FDA approved for COPD, but off label for asthma
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| Ipratropium Bromide (atrovent) | short acting inhaled anticholinergic agent (duraiton<4 hrs)
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| Tiotropium Bromide (Spiriva) | long acting inhaled anticholinergic agent (duration 24 hours dosing interval)
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| Adverse effects of anticholinergic agents | dry mouth, constipation, blurred vision, urinary retention, tahcycardia, additive anticholinergic effects when given with other anticholinergics
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| methyxanthines- MOA | inhibition of phosphodiesterase = less degradation of cAMP = increased cAMP levels = smooth muscle relaxation of bronchi. Decreases airway inflammation and improves mucous clearance
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| phosphodiesterase | enzymes that degrade the phosphodiester bond in cAMP and cGMP (inhibitors increase cAMP and cGMP)
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| Methylxanthines- indication for asthma | alternative long term control for step 2,3,4
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| Methylxanthines- prototype | Theophylline (Theocap)
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| Methylxanthines- adverse effects | narrow therapeutic index (requires PK monitoring)
- insomnia
-GI irritation (N/V)
-toxicity (plasma levels >30 mcg/mL)= arrythmias, convulsions, sezures
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| Drugs for ACUTE asthma attacks | SABA, anticholingergic (short acting)
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| Drugs for CHRONIC asthma control | inhaled corticosteroids!! (first line)
Leukotriene Modifiers (alternative)
Mast cell stabilizers (alternative)
Anti IgE (alternative)
LABA + ICS
methylxanthines
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| which medications are useful in treatment of exercise induced asthma? | SABA most effective
Can also take: Montelukast (over 15 yrs) or Cromones
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| Drug classes for COPD | short acting bronchodilators (Beta Agonists, anticholinergics)
long acting bronchodilators (beta agonists, anticholinergics, theophylline)
Glucocorticoids
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| Allergic Rhinitis (definition) | hypersensitivity to nasal allergens
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| 4 Drug classes for Allergic Rhinitis | Antihistamines, Glucocorticoids, Intranasal Cromolyn Sodium, Decongestants
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| Antihistamines- MOA | reduce the effects of histamine release- reduce degranulation of mast cells and inhibit histamine release; antagonize effects of histamine at the receptor site (H1)= histamine H1 antagonists
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| First Generation Antihistamines | Benadryl
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| Second Generation Antihistamines | Claritin, Zyrtec
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| Third Generation Antihistamines | Clarinex(rx)
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| Antihistamines- use | generally begin working within 15-20 min, oral antihistamines are more effective when taken prophylactically
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| Adverse effects of First Generation Antihistamines (Benadryl) | sedation most common, anticholinergic effects
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| Adverse Effects of Second and third generation antihistamines | most dont cross BBB (minimal CNS AEs), better tolerated (fewer AEs than 1st generation), more selective and more potent, Zyrtec has some sedative effects
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| glucocorticoids for allergic rhinitis | drug of choice, first line therapy for moderate to severe seasonal and perennial allergic rhinitis, can be topical (intranasal)
Antiinflammatory: prevent/suppress congestion, rhinorrhea, sneezing, nasal itching, erythema
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| Adverse effects of glucocorticoids when used for allergic rhinitis | mild drying of nasal mucosa/nasal ulcerations, bleeding, burning/itching sensation- systemic effects rare
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| Intranasal Cromolyn Sodium | - inhibits mast cell degranulation
- anti-inflammatory effects
- safe, but moderately effective for treatment of allergies
-best suited for prophylaxis- a week or 2 before symptoms start
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| Decongestants- MOA | stimulate alpha1 receptors on the smooth muscle of the nasal blood vessels – vasoconstriction, reduced blood flow, decreased fluid exudation and decreased mucosal edema result in decreased swelling of nasal membranes
- topical agents- immediate response
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| Decongestant Drugs (3) | Phenylephrine HCl (Neosynephrine)
Pseudoephedrine (Sudafed)
Naphazoline (Privine)
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| Adverse Effects of Decongestants | - rebound congestion when used more than 3-5 days
-CNS (irritability, anxiety, insomnia)
CV (systemic vasoconstriction) in patients with HTN and CAD
abuse: methamphetamines
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| Aantitussives- MOA | either central (suppressing cough center in medulla oblongata) or peripheral (lessen irritation of the respiratory tract)
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| Opioid Antitussives | CODEINE; suppressed the CNS cough center and inhibits the effect of excitatory neuropeptides through an action at mu opioid receptors located on sensory nerves in bronchi
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| Non opioid antitussives | dextromethorpan, diphenhydramine, benzonatate
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| Dextromethorpan | suppresses CNS through cough center (overdose= respiratory depression)
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| Diphenhydramine (Benadryl) as antitussive | antihistamine, ability to suppress cough, sedative and anticholinergic properties. Cough suppression achieved only at dose that causes sedation
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| Mucolytics | ACETYLCYSTEINE (MUCOMYST)
breaks up respiratory mucoprotein into smaller strands, makes mucus thinner
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| Expectorants | ROBITUSSIN/MUCINEX
facilitate removal of mucus from respiratory tract, lowers viscosity of secretions in trachea and bronchi
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