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2. HDS Pulmonary > Respiratory Pharmacology > Flashcards

Respiratory Pharmacology Flashcards

1
Q

Cough

Treatment

A
  • Mainly treat underlying cause
  • Productive cough should not be suppressed except in special circumstances and not until cause ID’d
    • Exhausts the patient
    • Prevents rest/sleep
    • Sputum needs to be cleared
  • Cough medications are antitussives and expectorants
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2
Q

Centrally-Acting

Antitussives

A

Act by suppressing medullary cough centers or associated higher centers.

  • Non-narcotic
    • Dextromethorphan
    • Chlophedianol
    • Levopropoxyphene
    • Noscapine
  • Narcotics
    • Codeine
    • Hydrocodone
    • Hydromorphone
    • Methadone
    • Morphine
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3
Q

Dextromethorphan

A
  • Centrally-acting antitussive
  • Derivative of the narcotic levorphanol
  • No significant analgesic or sedative properties
  • Does not depress respiration in usual doses
    • Extremely high doses may depress respiration
  • Non-addictive
  • No tolerance
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4
Q

Codeine

A
  • Partial agonist of μ and δ-opiod receptors ⇒ narcotic
  • Effects:
    • Centrally-acting antitussive
    • Analgesic
    • Slight sedative effects
  • Especially useful in relieving painful cough
  • Exerts a drying action on respiratory mucosa
    • Useful ⇒ bronchorrhea
    • Deleterious ⇒ when bronchial secretions already viscous
  • Minimal respiratory depression @ dose for cough
  • Risk for physical dependence and tolerance
  • Potential for abuse low
  • Side effects
    • Nausea/vomiting
    • Constipation
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5
Q

Peripherally-acting

Antitussives

A

Act by reducing irritation.

Can act on afferent or efferent side of cough reflex:

  • Afferent side
    • Mild local analgesic or anesthetic on respiratory mucosa ⇒ ↓ input of stimuli
    • Modify output and viscosity of respiratory tract fluid
    • Relax smooth muscle of bronchi in presence of bronchospasm
  • Efferent side
    • ↑ Efficiency of cough mechanism ⇒ make secretions easier to cough up

Grouped as:

  • Demulcents
  • Local anesthetics
  • Humidifying aerosols and steam inhalations
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6
Q

Demulcents

A
  • Forms protective coating over irritated pharyngeal mucosa
  • Useful for coughs originating above the larynx
  • Usually given as syrups or lozenges
  • Includes:
    • Acacia
    • Licorice
    • Glycerine
    • Honey
    • Wild cherry syrups
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7
Q

Local Anesthetics

A
  • Used to inhibit cough reflex under special circumstances
  • Includes:
    • Lidocaine
    • Benzocaine
    • Hexylcaine hydrochloride
    • Tetracaine
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8
Q

Benzonatate

(Tessalon Perles)

A
  • Local anesthetic
  • Similar to tetracaine
  • Antitussive effect may be due to a combo of:
    • Local anesthesia
    • Depression of pulmonary stretch receptors
    • Nonspecific central depression
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9
Q

Humidifying Aerosols & Steam Inhalations

A

Acts as a demulcent and ↓ viscosity of bronchial secretions

  • Inhaling water as aerosol or steam ± medication ⇒ most common method of humidification
  • Efficacy of added medications not clearly proven
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10
Q

Expectorants

A
  • Help expel bronchial secretions from respiratory tract
    • ↓ Viscosity of mucus
    • ↑ Secretion of respiratory tract fluids ⇒ demulcent effect
  • Most ↑ secretions via reflex irritation of bronchial mucosa
  • Iodides also act directly on bronchial secretory cells
    • Excreted into respiratory tract
  • Use is controversial ⇒ no data to prove it works
  • Use/choice of expectorants based on tradition and widespread clinical impression of effectiveness
  • Adequate hydration ⇒ most important measure to encourage expectoration
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11
Q

Iodides

A
  • Used to liquefy bronchial secretions
    • Late-stages of bronchitis, bronchiectasis, asthma
  • ↑ Expectoration
    • Reflex irritation of bronchial mucosa
    • Act directly on bronchial secretory cells
  • Potassium iodide ⇒ least expensive, most common
  • Iodinated glycerol ⇒ better tolerated, less effective
  • Usefulness limited d/t low pt tolerance
    • Unpleasant taste
    • Side effects
      • Acneiform skin eruptions
      • Coryza ⇒ catarrhal inflammation of the mucous membrane in the nose
      • Erythema of face and chest
      • Painful swelling of salivary glands
      • Hypothyroidism w/ prolonged use
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12
Q

Guaifenesin

A
  • Mostly commonly used expectorant in OTC cough meds
  • No serious adverse effects
  • No clear e/o efficacy
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13
Q

Mucolytics

A
  • Free -SH group that opens mucoprotein disulfide bonds
    • ↓ viscosity of mucus
  • Limited use for conditions where mucous is extremely thick
    • CF and chronic bronchitis
  • Acetylcysteine ⇒ 10-20% solution usually by neb or instillation
    • Also used in acetaminophen poisoning
  • May aggrevate airway obstruction by causing bronchospasm
    • Treat with sympathomimetic bronchodilator or acetylcysteine/isoproterenol before
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14
Q

Mucolytic Enzymes

A
  • DNAses ⇒ breaks up DNA resulting from infections
  • Useful only when grossly purulent sputum is a major problem
  • No advantage over mucolytics
  • Side effects
    • Local irritation of buccal and pharyngeal mucosa
    • Allergic reactions
  • Includes
    • Pancreatic dornase
    • Dornase alfa
      • New highly purified recomb. human deoxyribonuclease I
        • Important in treating CF
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15
Q

Decongestants

Overview

A
  • All α-adrenergic agonists
  • Vasoconstrict nasal blood vessels
    • ↓ Volume of nasal mucosa
    • Opens airways
  • Can be used:
    • Topically ⇒ short-term relief
    • Systemically ⇒ long-term relief
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16
Q

Short-Acting

Topical

Decongestants

A
  • Delivered as nasal sprays
  • Avoids systemic side effects e.g. HTN
  • Most commonly used:
    • Phenylephrine (Neosynephrine)
    • Oxymetazoline (Afrin)
  • Repeated use ⇒ down-regulation of receptors ⇒ rebound hyperemia in nasal blood vessels
    • Shouldn’t use for more than 2-3 days
17
Q

Long-Acting

Systemic

Decongestants

A
  • Prolonged duration of action
  • Increased potential for systemic side-effects
    • Caution in pts with HTN
    • Caution in pts taking MAO inhibitors
  • Pseudoephedrine (Sudafed) ⇒ most commonly used
    • Precursor to meth ⇒ now BTC drug
  • Phenylephrine (Sudafed PE) ⇒ OTC version
  • Ephedrine & Phenylpropanolamine pulled from market
18
Q

Asthma

Pathophysiology

A
  • Disorder of airway hyper-responsiveness
    • Bronchconstriction
    • Mucosal thickening from edema and cell infiltration
    • ↓ FEV1
  • Early stage
    • Mediated by IgE bound to airway mast cells
    • Release of mediators from mast cells
      • Histamine, LTC4, LTD4, prostaglandins
    • Results in bronchoconstriction and vascular leakage
  • Late mediators ⇒ GM-CSF, Interleukins (IL-4, IL-5)
    • Attract/activate eosinophils
    • Stimulate IgE production
  • Mediators also activate neural pathways ⇒ ACh by vagal efferents ⇒ bronchoconstriction
19
Q

Asthma

Therapeutic Approaches

A
  • Prevent mast cell degranulation
  • Reduce bronchial responsiveness
  • Relax airway smooth muscle
20
Q

Cromolyn (Intal)

&

Nedocromil (Alocril)

A
  • ⊗ Cl- channels ⇒ ⊗ mast cell degranulation
  • Only useful prophylactically
  • Cannot reverse bronchospasm or ∆ bronchial tone
  • Inhaled as microfine powder
    • No systemic effects
  • More effective in children than adults
    • Does not work in ⅓ of children
    • Usually do 4 week trial
  • Other uses:
    • Allergic rhinitis
    • Allergic conjunctivitis
21
Q

Sympathomimetic Agents

A
  • β-adrenergic agonists
    • ↑ cAMP ⇒ bronchodilation
  • β2-selective preferred
    • No chronotropic or inotropic effects of β1 activation
    • Non-selective agents like Epi, ephedrine, and isoproterenol are no longer used d/t side effects
  • β2-agonists delivered via MDI or nebulizer
    • Few systemic side effects
22
Q

Short-acting

β2-Agonists

A

Effects last for 3-4 hours.

  • Albuterol (Ventolin)
  • Metaproterenol (Alupent)
  • Terbutaline (Breathaire)
  • Pirbuterol (Maxair)
23
Q

Long-acting

β2-Agonists

A

Effects last 12 hours ⇒ prophylactic use

Formoterol (Foradil)

Salmeterol (serevent)

  • Often used in combo w/ inhaled corticosteroids
  • Due to rare exacerbation of asthma attacks, LABAs are not recommended as first line treatment.
24
Q

Theophylline

A
  • Methylxantine PDE inhibitor
    • ↓ cAMP breakdown ⇒ ↑ MLCK inactivation ⇒ bronchodilation
  • Taken PO ⇒ systemic side effects
    • CNS ⇒ nervousness and tremor
    • CV ⇒ ⊕ chronotropic and inotropic effects
    • GI ⇒ ↑ secretion of gastric acid and digestive enzymes
    • Renal ⇒ diuretic activity
  • Low therapeutic index
  • No longer a first-line therapy
25
Q

Muscarinic Antagonists

A
  • ⊗ Effects of vagal-released Ach @ mAChR
  • Atropine cannot be used d/t systemic effects
  • Quaternary compounds ⇒ poorly absorbed when delivered via inhaler, avoid systemic effects
    • Ipratropium bromide (Atrovent)
      • Short-acting ⇒ lasts for several hours
      • Takes 45 mins to work ⇒ bridge with β2 agonist
    • Tiotropium (Spiriva) & Aclidinum (Tudorza)
      • Longer-acting ⇒ lasts for 24 hours
      • Can be used prophylactically
  • Rarely used in asthma, commmonly used for COPD
26
Q

Corticosteroids

Mechanism

A

⊗ Cytokine production ⇒ anti-inflammatory action ⇒ ↓ airway responsiveness

Does not reverse bronchospasm

27
Q

Oral Corticosteroids

A

Used for severe flare-ups

  • Systemic effects e.g. adrenal suppression
    • Several days of treatment w/ taper to avoid rebound
  • Agents:
    • Prednisone
    • Methylprednisolone
28
Q

Inhaled Corticosteroids

A

Prophylaxis in children and adults

  • Agents:
    • Beclomethasone (Beclovent, Vanceril)
    • Triamcinolone (Azmacort)
    • Fluticasone (Flovent)
  • Avoids systemic effects
  • Children who use daily show 0.5” reduction in height as an adult
  • Most common side effect ⇒ oropharyngeal candidiasis
  • Often used in combo w/ LABA
    • Fluticasone + salmeterol (Advair)
29
Q

Leukotriene Pathway

A
  • Synthesized from arachidonic acid by 5’ lipoxygenase
  • Act via CysLT1 receptor
  • LTC4 and LTD4 invovled in asthma response
    • Causes bronchoconstriction
    • Increases sensitivity to histamine
30
Q

Leukotriene Pathway

Inhibitors

A

Used prophylactically.

Effective in blocking response to Ag challenge.

Only works in ⅓ of patients.

No apparent side effects.

  • 5’ lipooxygenase inhibitors
    • Zileuton (Zyflow) ⇒ PO
  • CysLT1R antagonists
    • Montelukast (Singulair) ⇒ PO
    • Zafirlukast (Accolate) ⇒ PO
31
Q

Asthma

Antibody Treatments

A

Used when other agents don’t work.

  • Anti-IgE antibodies
    • Omalizumab (Xolair)
      • Binds to IgE receptor domain on IgE ⇒ prevents interaction with its receptor
      • Delivered SubQ every 2-4 weeks
  • Anti-IL-5 antibiodies
    • Mepolizumab (Mucala)
      • Blocks IL-5 action
      • Used for eosinophilic asthma
      • Delivered SubQ every 4 weeks
32
Q

Asthma Management

Summary

A
  • Mild asthma w/ occasional sx ⇒ inhaled β2 agonist PRN
  • Persistent asthma ⇒ ICS ± cromolyn prophylaxis
  • Severe asthma ⇒ ICS & salmeterol prophylactically
  • Severe, prolonged attacks ⇒ oral corticosteroids
33
Q

COPD Treatment

Goals

A

No drug can affect the natural progression of COPD.

Treatment geared towards:

Correction of symptoms

Maintenance of lung function

Improvement of quality of life

34
Q

COPD

Management

A
  • Bronchodilators ⇒ first-line therapy
  • Mild cases
    • SABA (albuterol) + SAMA (ipratropium)
    • Used PRN or before exercise
  • Severe cases
    • LABA ⇒ Salmeterol
      or
    • LAMA ⇒ tiotropium (Spiriva), umeclidinium (Incruse), aclidinium (Tudorza)
  • Theophylline ⇒ use when LABA or LAMA ineffective, use decreasing
  • Inhaled corticosteroids ± LABA/LAMA
    • Can result in significant ↑ FEV1
  • Avoid chronic use of oral or systemic corticosteroids
  • Leukotriene pathway inhibitors not adequately tested in COPD ⇒ not currently recommended

2. HDS Pulmonary (28 decks)

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