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Pharm Respiratory

QuestionAnswer
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
bronchoconstriction allergen binds to IgE on mast cell which causes release of histamine, leukotrienes, interleukins, and prostaglandins
inflammation infiltration of inflammatory cells and mediators
symptoms breathlessness, tightening of chest, wheezing, dyspnea, cough
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
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
Dry Powder Inhaler (DPI) deliver drugs in the form of dry, micronized powder to lungs, no propellant
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
Metered Dose Inhaler Advantages useful for acute attacks, pressurized, so patient doesnt have to breath in (might be hard during attack)
Metered Dose Inhaler Disadvantages need hand lung coordination, not much actually gets into lungs (a lot gets in oropharynx)
Dry Powder Inhaler Advantages no environmental risk, easier to use, no hand lung coordination, stability of delivery (more gets into the lungs vs oropharynx)
Dry Powder Inhaler Disadvantages bad for asthma patients because they cant breathe, mostly used for controller substances
Anti Inflammatory Asthma medication classes Corticosteroids, Leukotriene Modifiers, Mast Cell Stabilizers (Cromones), Anti IgE
Corticosteroids (Glucocorticoids)- MOA decrease synthesis of inflammatory mediators (histamine, leukotrienes, prostaglandins) and inflammatory cells (eosinophils, leukocytes), decrease airway edema, airway mucous production and hypersecretion
Corticosteroids- Uses controller/prophylaxis of chronic asthma (improve lung function, reduce exacerbations), delayed response, need fixed schedule, not PRN
Oral Corticosteroids Methylprednisolone (Medrol) and Prednisone used for severe asthma, potential for toxicity.
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)
Common side effects of corticosteroids oral thrush, cough/wheezing, dysphonia (hoarseness) --> gargle to reduce
Acute adverse effects of glucocorticoids occur within a couple of days: - sodium/water retention -hyperglycemia -behavioral/CNS stimulation or depression -increased appetite/weight gain
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
Leukotriene Modifiers- MOA suppress effects of leukotrienes, the compounds that promote bronchoconstriction and eosinophil infiltration, mucous production, and airway edema
Leukotriene Modifiers- Uses alternative long term control for step 2,3,4
2 types of leukotriene modifiers 5 Lipooxygenase Inhibitors and Leukotriene D4 receptor Antagonists
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)
5 Lipooxygenase inhibitors- prototype Zileuton (Zyflo)
Leukotriene D4 receptor antagonists- MOA prevent leukotrienes from interacting with their receptors. Bronchodilatory action and lessens mucous secretion.
2 Leukotriene D4 receptor antagonists Zarfirlukast (Accolate) and Montelukast (Singulair)
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
Leukotriene Modifiers- adverse effects most common side effects: headaches, GI Zileuton: hepatotoxicity
Mast Cell stabilizers (Cromones) - MOA inhibits mast cell degranulation, prevents releas eof histamine and inflammatory mediators
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
Mast Cell Stabilizers (Cromones)- prototype Cromolyn (Intal)- prophylaxis of asthma, not useful for acute attacks, administered through inhalation
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
Anti IgE- prototype Omalizumab - given subQ, very expensive
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
Adverse Effects of Anti IgE increased risk of malignancies, injection site reactions, risk of anaphylaxis
3 classes of bronchodilators Beta 2 Agonists, Anticholinergics, Methylxanthines
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
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
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
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
Oral beta 2 Agonists used only for long term, onset is too slow to abort ongoing attack. (Terbutaline/Brethine)
Terbutaline (Brethine) approved to treat bronchospasm associated with asthma, bronchitis, and emphysema. Used off label for treating preterm labor and uterine hyperstimulation
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
Adverse Effects of Beta 2 Agonists (Inhaled Short Acting) well tolerated, systemic effects= tahcycardia, angina, tremor
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)
Adverse Effects of Beta 2 agonists (Oral long acting) systemic sympathetic effects
Anticholinergics- MOA block cholinergic receptors in the bronchi = decreased cGMP, increased cAMP, bronchial smooth muscle relaxation
Anticholinergics- Uses FDA approved for COPD, but off label for asthma
Ipratropium Bromide (atrovent) short acting inhaled anticholinergic agent (duraiton<4 hrs)
Tiotropium Bromide (Spiriva) long acting inhaled anticholinergic agent (duration 24 hours dosing interval)
Adverse effects of anticholinergic agents dry mouth, constipation, blurred vision, urinary retention, tahcycardia, additive anticholinergic effects when given with other anticholinergics
methyxanthines- MOA inhibition of phosphodiesterase = less degradation of cAMP = increased cAMP levels = smooth muscle relaxation of bronchi. Decreases airway inflammation and improves mucous clearance
phosphodiesterase enzymes that degrade the phosphodiester bond in cAMP and cGMP (inhibitors increase cAMP and cGMP)
Methylxanthines- indication for asthma alternative long term control for step 2,3,4
Methylxanthines- prototype Theophylline (Theocap)
Methylxanthines- adverse effects narrow therapeutic index (requires PK monitoring) - insomnia -GI irritation (N/V) -toxicity (plasma levels >30 mcg/mL)= arrythmias, convulsions, sezures
Drugs for ACUTE asthma attacks SABA, anticholingergic (short acting)
Drugs for CHRONIC asthma control inhaled corticosteroids!! (first line) Leukotriene Modifiers (alternative) Mast cell stabilizers (alternative) Anti IgE (alternative) LABA + ICS methylxanthines
which medications are useful in treatment of exercise induced asthma? SABA most effective Can also take: Montelukast (over 15 yrs) or Cromones
Drug classes for COPD short acting bronchodilators (Beta Agonists, anticholinergics) long acting bronchodilators (beta agonists, anticholinergics, theophylline) Glucocorticoids
Allergic Rhinitis (definition) hypersensitivity to nasal allergens
4 Drug classes for Allergic Rhinitis Antihistamines, Glucocorticoids, Intranasal Cromolyn Sodium, Decongestants
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
First Generation Antihistamines Benadryl
Second Generation Antihistamines Claritin, Zyrtec
Third Generation Antihistamines Clarinex(rx)
Antihistamines- use generally begin working within 15-20 min, oral antihistamines are more effective when taken prophylactically
Adverse effects of First Generation Antihistamines (Benadryl) sedation most common, anticholinergic effects
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
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
Adverse effects of glucocorticoids when used for allergic rhinitis mild drying of nasal mucosa/nasal ulcerations, bleeding, burning/itching sensation- systemic effects rare
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
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
Decongestant Drugs (3) Phenylephrine HCl (Neosynephrine) Pseudoephedrine (Sudafed) Naphazoline (Privine)
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
Aantitussives- MOA either central (suppressing cough center in medulla oblongata) or peripheral (lessen irritation of the respiratory tract)
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
Non opioid antitussives dextromethorpan, diphenhydramine, benzonatate
Dextromethorpan suppresses CNS through cough center (overdose= respiratory depression)
Diphenhydramine (Benadryl) as antitussive antihistamine, ability to suppress cough, sedative and anticholinergic properties. Cough suppression achieved only at dose that causes sedation
Mucolytics ACETYLCYSTEINE (MUCOMYST) breaks up respiratory mucoprotein into smaller strands, makes mucus thinner
Expectorants ROBITUSSIN/MUCINEX facilitate removal of mucus from respiratory tract, lowers viscosity of secretions in trachea and bronchi
Created by: alexadianna