NRSG351 Respiratory Agents in Asthma, COPD, Cough, Cold and Allergy
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Transcript of NRSG351 Respiratory Agents in Asthma, COPD, Cough, Cold and Allergy
Civility Clause….
Students are expected to behave toward lecturers and fellow students with courtesy and consideration. This means that talking and disruptive behavior will be kept to a minimum. Cell phones, pagers, and other electronic devices should be silenced in the classroom. I reserve the right to end a class at any time, for any reason, including the disruptive or rude behavior of anyone in the classroom.
Trigger Mechanism
Respiratory infection Inflammatory response produces bronchial hyperresponsiveness; IgE induction by some viruses; eosinophil activation by some viruses
Allergens Classic allergic pathway
Environment / occupational stimuli
Epithelial damage; inflammation
Emotions Excess parasympathetic activation of bronchial tissue
Exercise Heat loss and water loss from airways;
Drugs , foods Sulfite preservatives stimulate inflammation; aspirin and NSAIDS inhibit cyclooxygenase
http://www.nhlbi.nih.gov/health/health-topics/topics/asthma/
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Asthma COPD
Early onset; family history Mid-life onset
Variable or seasonal symptoms; symptoms worse at night or early morning
Slowly progressing symptoms
Associated with allergies / rhinitis; eczema; dermatitis
History of smoking
REVERSIBLE airway obstruction IRREVERSIBLE (or variably reversible) airway obstruction
Goals of therapy in acute asthma
• Rapid reversal of airway obstruction
• Correction of significant hypoxemia
• Restoration of normal lung function
• Reduction of asthma symptoms
• Development of a plan for future attacks
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Drugs used to treat asthma
• Bronchodilators– Beta 2 agonists– Anticholinergics
• Antiinflammatory agents– Corticosteroids– Leukotriene modifiers– Mast cell stabilizers– Monoclonal antibodies
Agents can be used systemically or via inhalation
Beta-2 agonistsAlbuterol (Ventolin® Proventil® Accuneb® )Levalbuterol (Xopenex®)
Fluticasone / salmeterol (Advair®)Mometasone furoate / formoterol fumarate (Dulera®)
Formoterol fumarate (Foradil®)
Pharmacology (Mechanism of action)
Stimulates b-2 receptors
Activates adenylate cyclase and increases cAMP
cAMP produces relaxation of smooth muscle and bronchodilation
Adverse Effects Pharmacokinetics
Short-acting
Long-acting
Beta-2 agonists
• Contraindications
– Allergy
– Uncontrolled cardiac dysrhythmias (especially tachyarrhythmias)
Beta-2 agonists
• Adverse effects – serious– Urticaria
– Arrhythmia, QT prolongation, angina, hypokalemia
– Paradoxical bronchospasm
• Adverse effects – common– Nervousness, tremor, palpitations, tachycardia
– Bad taste
– Throat irritation
MethylxanthinesTheophylline (Theo-Dur®)Aminophylline (various)
Pharmacology (Mechanism of action)
Block phosphodiesterase enzymes, which leads to increased cAMP in bronchial tissue
Increased cAMP leads to smooth muscle relaxation
Adverse Effects Pharmacokinetics
Anticholinergics Ipratropium bromide (Atrovent®)Tiotropium bromide (Spiriva Handihaler®)
Pharmacology (Mechanism of action)
Blocks post ganglionic vagal pathways
Decreased vagal tone produces bronchodilation
Adverse Effects Pharmacokinetics
N3HCCH
CH3
CH3
O C
O
CH
OH
Br-
Ipratropium bromide
Anticholinergics
• Contraindicated in– Allergy to atropine or components of the
preparation
– Myasthenia gravis, narrow angle glaucoma
– Tiotropium should not be used with ipratropium
• Adverse effects – common– Nausea, vomiting, diarrhea
– Nasal congestion, dyspnea
Corticosteroids Beclomethasone (Beclovent® Vanceril® QVAR80® )Budesonide (Pulmicort®)
Fluticasone / salmeterol (Advair®)
Triamcinolone acetonide (Azmacort®)
Pharmacology (Mechanism of action)
Inhibits neutrophil and eosinophil invasion
Inhibits synthesis of prostaglandins, histamines and leukotrienes
Adverse Effects Pharmacokinetics
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213836.htm
Corticosteroids
• Adverse effects – serious (most are rare when inhaled)– Adrenal suppression– Osteoporosis / growth suppression in children– Bronchospasm– Peptic ulcers
• Adverse effects – common – Sinusitis, rhinitis, hoarseness– Headache, nausea, diarrhea– Oral candidiasis
Leukotriene receptor antagonistsMontelukast (Singulair®)Zileuton (Zyflo®)Zafirlukast (Accolate®)Pharmacology (Mechanism of action)
blocks leukotriene receptors
Prevents leukotrienes from participating in inflammatory responses
Adverse Effects Pharmacokinetics
Arachidonic acid
Lipoxygenase products
lipoxygenase
LTC4 and LTD4
TXA2COX
Bronchoconstrictionand inflammation
Montelukast, zafirlukast(receptor antagonists) act here
Zileuton act here
Leukotriene modifiers
• Adverse effects – serious– Angioedema– Anaphylaxis – Churg-Strauss syndrome (coincidental?)
• Adverse effects – common– Flu like symptoms (cough, fatigue, headache,
abdominal pain)
– Adverse effects have not been well documented and these agents are believed to be very safe
Mast Cell StabilizersCromolyn sodium (Nasalcrom® , Intal®)
Pharmacology (Mechanism of action)
Prevent the release of histamine and inflammatory mediators by mast cells by stabilizing their membranes;
Reduced release of inflammatory and bronchoconstrictive substances reduces bronchoconstriction
Adverse Effects Pharmacokinetics
Monoclonal antibody preparationsOmalizumab (Xolair®)
Pharmacology (Mechanism of action)
inhibits IgE binding to receptors on mast cells and basophils, preventing degranulation
Reduces release of allergic response mediators
Adverse Effects Pharmacokinetics
Upper Respiratory Medications
• Antihistamines, decongestants and other nasal agents
• Common, available OTC and Rx
• Alone and in combination
• Use in children is discouraged
Antihistamines1st generation OTC 2nd generation OTCDimenhydrinate (Dramamine ®) Cetirizine (Zyrtec ®)Diphenhydramine HCl (Benadryl®) loratidine (Claritin®, Chlorpheniramine (Chlor-Trimeton®) des-loratidine (Clarinex®) fexofenadine (Allegra®, Allegra-D®) Pharmacology (Mechanism of action)
Blocks H1 receptors
Histamine cannot bind, produce responses associated with allergic responses
(No effect to decrease histamine release)
Adverse Effects Pharmacokinetics
DecongestantsTopical (intranasal) OTC Systemic OTCOxymetazoline (Afrin®, Allerest®) Pseudoephedrine (Sudafed®)Phenylephrine (Neo-synephrine®)Xylometazoline (Otrivin ®)
Pharmacology (Mechanism of action)
a1 stimulation produces vasoconstriction
Vasoconstriction leads to decreased swelling, edema and stuffy nasal passages
Adverse Effects Pharmacokinetics
Decongestants
• Contraindicated in patients with – Hypertension or CAD– Do not use concurrently with TCAs, beta
blockers, MAOIs
• Adverse effects include– Tachycardia, increased BP, arrhythmias– Restlessness, insomnia, anxiety, tremor– Rebound phenomenon
Intranasal antiinflammatory agentsCorticosteroids - RxTriamcinolone acetonide (Nasacort ®) Budesonide (Rhinocort®) Fluticasone (Flonase®) Pharmacology (Mechanism of action)
Decreases the release of inflammatory mediators
Adverse Effects Pharmacokinetics
Agents used to treat cough
• Antitussives – prevent coughing
• Expectorants – thin mucus secretions, making it easier to cough
ExpectorantsGuaifenesin (Robitussin, Mucinex) Pharmacology (Mechanism of action)
Decreases the viscosity of mucus to aid in its elimination
Adverse Effects Pharmacokinetics
AntitussivesDextromethorphan (Robitussin-DM, Mucinex-DM, Delsym) Pharmacology (Mechanism of action)
Depresses medullary cough center
Adverse Effects Pharmacokinetics
dextromethorphan
Levophoranol (Levo-Dromoran)
Antitussives – Rx codeine containing and derivatives(Tussionex, Tussi-organidin) Pharmacology (Mechanism of action)
Depresses medullary cough center
Adverse Effects Pharmacokinetics
Antitussives – RxNon-codeine derivatives
Benzonatate (Tessalon Perles) Pharmacology (Mechanism of action)
Local anesthetic action on the respiratory passageways and stretch receptors of the lung; decreases cough reflex
Adverse Effects Pharmacokinetics