phrm 203 allison beale - laulima · a beale phrm 203 - respiratory pharmacology 10 focus on cystic...
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Respiratory Pharmacology
PHRM 203 Allison Beale
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Respiratory Tract • Upper Respiratory
Tract – Conducting airways
• Nose, mouth, pharynx, larynx, trachea, bronchi
• Lower Respiratory Tract – Respiratory airways
• Bronchioles, alveoli
Mucous in lungs
• Consists of mucins (large glycoproteins), water, lipids, salts and antibodies (mostly IgA).
• Produced by goblet cells and submucosal seromucous glands (glands containing cells that secrete serous fluid + cells that secrete mucous).
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Upper Tract Defense mechanisms
• Defense mechanisms – Hair (inside nostrils) – Goblet cells produce
mucous • Cystic fibrosis
– Ciliated epithelial cells – Cough and sneeze reflexes – Large numbers of WBCs
• Macrophages • Mast cells
Actually, intestinal mucosa, but great goblet cells.
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Conducting Airways Nose
Nasal epithelium
Bronchi (have cartilage and glands)
Pulmonary vein
Hyaline cartilage
30 microns
100 microns
250 microns
250 microns
Smooth muscle
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Conducting airways
• Green arrow – Bronchiole
• Note absence of cartilage and glands
• Note smooth muscle
• Red arrow – Pulmonary vein
• Blue arrow – Pulmonary artery
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Transition to LRT
Terminal bronchiole has ciliated columnar or cuboidal epi- thelium - no gas exchange
Respiratory bronchiole has some ciliated cuboidal epithelium, no smooth muscle and is interrupted by alveolar openings
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Alveoli
• Blue arrows – Type I Pneumocyte
• Provide blood:air contact • Squamous (flat)
• Green arrows – Type II Pneumocyte
• Secrete surfactant • Cuboidal
• Red arrow – Macrophage
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Lower Tract Defense mechanisms
• Clara cells – Produce component(s) of surfactant – Metabolize toxicants via SER bound P450s
• Type II alveolar cells – Differentiate into Type I alveolar cells that
allow gas diffusion – Produce majority of surfactant
• WBCs - macrophages
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Focus on Cystic Fibrosis • 1:3900 have CF in US
– Autosomal recessive w/>1K possible mutations • Disease of secretory glands (lungs, guts, repro)
– Sweat >100nM versus ~25nM NaCl (skin tastes salty) – 95% males sterile (vas deferens degenerates) – 90% fibrotic cysts in pancreas (hence name)
• Cystic Fibrosis-related diabetes - mixed Type I and II – 99% opacified sinuses (most missing frontal sinuses) – 10% of CF infants fail to pass feces (meconium ileus) – 100% chronic lung infections
• Ultimately cause of death – Pseudomonas aeruginosa, Burkholderia cepacia or Aspergillus
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Antitussives
Drug Indications
Benzonatate Treatment of nonproductive cough Codeine C-V Dextromethorphan (DXM or DM) !
Contraindications - do not use in patients needing to cough to maintain airways (those with asthma or
Hydrocodone C-II (with Homatropine, Hycodan) !
emphysema); or in patients allergic to the medication
PO
PO
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Topical nasal decongestants
Drug Indications (Sympathomimetics)
Ephedrine Nasal congestion caused by common cold, sinusitis, allergic rhinitis, relief of pressure caused by otitis media
Oxymetazoline (Afrin) !
Nasal congestion caused by common cold, sinusitis, allergic rhinitis
Tetrahydrozoline Nasal congestion caused by common cold, sinusitis, allergic rhinitis, relief of pressure caused by otitis media
Topical nasal spray
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ADRs for Select Drugs
Drug ADRs Dextromethorphan Mild: drowsiness, dizziness, nausea, vomiting.
Don’t take with MAOI, TCAs, SSRIs, β⊗s…
Hydrocodone (C-II with homatropine, Hycodan)
Psychic/physical dependence &/or tolerance possible. Respiratory depression (dose dependant), ↑Intracranial pressure, anxiety, nausea, vomiting, urinary retention, rash
Oxymetazoline
Cardiac arrhythmias, headache; insomnia; sweating; delirium; anxiety; tremor; weakness; dizziness; rebound congestion (nasal use). Nausea; vomiting; anorexia; dry mouth; urinary retention. Don’t take with COMT-I, MAOI, TCAs, β⊗s, digoxin, bromocriptine….
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Oral decongestant
Drug Indications Pseudoephedrine ! (Sudafed, Triaminic, etc.)
Nasal congestion caused by common cold, sinusitis, allergic rhinitis. Combat Meth. Epidemic Act (2006) – required recordkeeping and behind the counter storage.
Phenylephrine ! (Neo-Synephrine, etc.)
Shock, hypotension, antiarrhythmic, nasal decongestant, hemorrhoids, to prolong local anesthesia, etc.
ADRs - Arrhythmias; CV collapse with hypotension; tachycardia; bradycardia; transient hypertension. Nervousness; excitability; dizziness; tremor; insomnia; depression. Pallor. Anorexia; nausea; vomiting; dry mouth. Difficulty urinating.
PO α & β
α1&2 PO, IV, IM, SC, PR, topical
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Orally Inhaled & Topical steroid nasal decongestants
Drug Indications Budesonide ! (Rhinocort Aqua, Pulmicort)
All topical steroid decongestants are indicated for the treatment of seasonal allergic rhinitis in patients who are not obtaining relief with other decongestants and for the relief of inflammation following the removal of nasal polyps. They are also used to treat inflammation associated with asthma and COPD. Budesonide used in Crohn’s therapy.
Not for emergency use or use during an asthma attack (or status asthmaticus).
Mometasone (Nasonex) !
Flunisolide (AeroBid) !
Fluticasone (Flonase, Veramyst) !
Metered (powder & spray) inhalers, solutions (nebulizer), aerosols & PO
Steroid nasal decongestant and anti inflammatory ADRs
• Nasal burning/stinging , epistaxis, nasal dryness, pharyngitis, cough increased. Nausea. Aftertaste. Hoarseness. Abnormal sense of smell. Viral skin infections, oral candidiasis
• Do not use (1) pregnant or lactating; (2) respiratory infection.
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Replacing a systemic with a topical steroid may result in symptoms of adrenal insufficiency &/or withdrawal symptoms of joint and/or muscle pain, lassitude and depression. May be life-threatening.
Rinse mouth after oral inhalation to reduce risk of candidiasis.
Withdrawal of systemic corticosteroid may unmask a condition previously controlled: rhinitis, conjunctivitis, eczema, arthritis, or an eosinophilia.
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1st generation Antihistamines
Drug Indications
Cetirizine (Zyrtec) Seasonal and perennial allergic rhinitis, chronic urticaria
Clemastine Seasonal and perennial allergic rhinitis, allergic conjunctivitis, urticaria and angioedema, discomfort of dermographism, adjunct to anaphylaxis therapy
Diphenhydramine (Benadryl) !
Seasonal and perennial allergic rhinitis, allergic conjunctivitis, urticaria and angioedema, discomfort of dermographism, adjunct to anaphylaxis therapy, sleeping aid, parkinsonism, antiemetic, motion sickness
PO, IV, IM, Topical
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2nd Generation Antihistamines
Drug Indications Azelastine (Astelin) !
Seasonal and perennial allergic rhinitis
Desloratadine (Clarinex) Seasonal allergic rhinitis, chronic idiopathic urticaria
Fexofenadine (Allegra) !
Seasonal allergic rhinitis and urcaria. Note: don’t take with Al++ or Mg++ antacids
Loratadine (Claritin) !
Seasonal and perennial allergic rhinitis, allergic conjunctivitis, urticaria and angioedema, discomfort of dermographism, adjunct to anaphylaxis therapy.
Loratadine often causes a headache. It may cause photosensitivity and sleeplessness.
PO
PO
Topical (metered nasal spray, ophthalmic drops)
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Expectorant
Drug Indications
Guaifenesin (Mucinex, etc.) !
Relief of dry, nonproductive cough
ADRs: Very mild - possible nausea, vomiting, rash, headache.
PO
GRAS (Generally Recognized as Safe) since 1952
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Mucolytics
Drug Indications Acetylcysteine (Mucomyst, Acetadote) !
Acute pneumonia, bronchitis, chronic emphysema, TB, amyloidosis of lung, cystic fibrosis. Liquefication of secretions, clearing of secretions for Dx tests, post-op. to facilitate clearing of secretions, PO to attempt to protect the liver from acetaminophen toxicity.
Must monitor to ensure cough is sufficient to remove loosened mucous.
Dormase alfa Decrease cystic fibrosis secretions
Acetylcysteine ADRs - tachycardia, BP changes, angioedema, flushing, nausea, vomiting, bronchospasm, anaphylactoid reactions, fever, clamminess. Some people are “REACTORS” and will have anaphylactoid reaction - no way to tell.
PO/IV – APAP antidote
Topical (inhalation solution) - mucolytic
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Xanthine Bronchodilators
Drug Indications
Aminophylline All xanthine bronchodilators are indicated for relief or prevention of asthma and reversal of bronchospasm associated with COPD
Caffeine Dyphylline
Theophylline (Theo-24) ! ADRs: cardiac arrhythmias, headache, seizures,
nausea, vomiting, transient diuresis, fine skeletal muscle tremors, sudden death (smokers and the elderly at greater risk for ADRs). PO, IV
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Sympathomimetic Bronchodilators
Drug Indications
Albuterol (Proventil) !
Treatment and prophylaxis of bronchospasm, prevention of exercise-induced bronchospasm
Ephedrine Treatment of acute bronchospasm
Epinephrine ! Treatment of choice for acute bronchospasm
PO, Inhaled
IV, SC, IM, Intracardiac
β2
α & β
Mostly β
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Sympathomimetics, continued
Drug Indications
Isoproterenol (Isuprel) !
Bronchospasm during anesthesia and prophylaxis of bronchospasm (also shock and heart block)
Salmeterol Prophylaxis of bronchospasm and prevention of exercise-induced asthma (LABA)
Terbutaline Treatment and prophylaxis of acute bronchospasm
Metered aerosol, IV, IM, SC, Intracardiac β
β2
β2
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Anticholinergic bronchodilators
Drug Indications
Ipratropium (Atrovent) !
COPD maintenance
Tiotropium Treatment of bronchospasm associated with COPD
ADRs - Arrhythmias; hypertension; aggravated hypertension; hypotension. Cough, bronchospasm (including paradoxical bronchospasm). Nervousness; dizziness; headache. Blurred vision; mydriasis; epistaxis, nasal dryness, nasal congestion, increased intraocular pressure, pharyngitis, rhinitis, sinusitis (0.06% nasal spray formulation only). Nausea; dry mouth; GI distress; constipation; taste perversion; dyspepsia. Allergic-type reactions (rash; pruritus; angioedema of the tongue, lips, and face; urticaria; laryngospasm; anaphylacitc reactions), arthritis, back pain, influenza-like symptoms, rash, urine retention, UTI.
Inhalation (metered spray/aerosol, solutions)
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Leukotriene Receptor Antagonists
Drug Indications
Montelukast (Singulair) ! Asthma, exercise-induced
bronchoconstriction, allergic rhinitis Zafirlukast ! (Accolate)
Zileuton (Zyflo) Prophylaxis and chronic treatment of bronchial asthma in patients ≥12 yrs
(actually blocks LOX activity)
PO
PO
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Lung Surfactants
Drug Indications
Beractant (Survanta) !
Natural bovine lung extract used for the rescue of infants with respiratory distress syndrome (RDS) or those likely to develop RDS
Calfactant Rescue of infants with respiratory distress syndrome (RDS) or those likely to develop RDS
Poractant Rescue of infants with RDS
Intratracheal suspension
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Mast Cell Stabilizers
Drug Indications
Cromolyn (Nasalcrom)!
Chronic, severe, bronchial asthma, exercise-induced asthma, and allergic rhinitis, and to alleviate symptoms of mastocytosis (available as metered oral inhaler, nasal solution, ophthalmic solution, and oral solution)
Topical (ophthalmic drops), Inhalation (nebulizer solution, metered spray)
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Antiviral drugs for respiratory infections
Drug Indications
Amantadine (Symmetrel) !
Parkinson’s, drug-induced extrapyramidal symptoms, treatment and prophylaxis for influenza A infections (Mechanism: Ion channel M2 protein inhibitor)
Oseltamivir (Tamiflu) !
Uncomplicated influenza and possibly avian flu (Mechanism: Neuraminidase inhibitor)
Ribavirin Chronic hepatitis C, influenza A, respiratory syncytial virus, herpes (Mechanism: unclear)
Zanamivir (Relenza) !
Uncomplicated influenza (A & B) infections (Mechanism: Neuraminidase inhibitor)
All PO