PHRM 203 Allison Beale - Laulima · A Beale PHRM 203 - Respiratory Pharmacology 10 Focus on Cystic...

Respiratory Pharmacology

PHRM 203 Allison Beale

A Beale PHRM 203 - Respiratory Pharmacology

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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 epithelium - 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

PHRM 203 Allison Beale - Laulima · A Beale PHRM 203 - Respiratory Pharmacology 10 Focus on Cystic...

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