Exam 4: Pulmonary Pharmacology Flashcards
Pulmonary SNS innervation:
SNS fibers from thoracic ganglia innervating smooth muscles of bronchi, pulmonary blood vessels
Sympathetic tone: bronchodilation via β2 receptors
Pulmonary PSNS innervation:
Vagus nerve
Parasympathetic tone: bronchoconstriction via M3 receptors
β2 receptors in the lungs cause these effects (3):
Bronchodilation
Increased cAMP
Greater sensitivity to epi vs. norepi
NANC nerves & role:
Non-adrenergic, non-cholinergic; relax airway smooth muscle by releasing NO and VIP
M3 receptors in the lungs cause these effects (2):
Bronchoconstriction via IP3 –> ↑Ca2+
Increased mucus secretions
Effects of M3 stimulation on pulmonary blood vessels:
None
Asthma is:
Chronic inflammatory disorder of airways with increased responsiveness of tracheobronchial tree to stimuli
Characteristics of asthma obstruction:
Variable and reversible
Characteristics of airways during asthma:
Inflamed
Edematous
Hypersensitive to irritant stimuli
Cells activated in the bronchial mucosa by allergens:
Th2 lymphocytes (which release cytokines)
Mediator cells in asthma:
Eosinophils
Mast cells
Neutrophils
Macrophages
Basophils
T lymphocytes
Chemical mediators in asthma:
Cytokines
Histamines
Interleukins 3-4-5
Leukotrienes
Prostaglandins
Adenosine
Platelet activating factor
Atopic asthma:
Mediated by IgE
Goal of medications in asthma:
Flattening the response to mediators
Characteristics of COPD obstruction:
Non- or incompletely reversible
Causes (3) of cell damage in COPD:
Impaired lung parenchyma
Degraded matrix
Toxic action of macrophages and neutrophils
Changes to lung tissue in COPD:
Enlarged air spaces
Fibrosis
↑ mucus production
Steroid and bronchdilator efficacy in COPD:
Steroids: limited effect
Bronchodilators: modest role in breathlessness
Step 1 of airway outflow d/o treatment:
Short-acting bronchodilators
Step 2 of airway outflow d/o treatment:
Regular inhaled corticosteroid
Step 3 of airway outflow d/o treatment:
Long-acting bronchodilators
Step 4 of airway outflow d/o treatment:
Phosphodiesterase inhibitors
Methylxanthines
Leukotriene inhibitors
Step 5 of airway outflow d/o treatment:
Oral corticosteroid
Three classes of bronchodilators:
β-agonists
Anticholinergics
Methylxanthines
Short-acting β2-agonists:
Terbutaline
Albuterol
Levalbuterol
Salbutamol
Long-acting β2-agonist:
Salmeterol
Indication for long-acting β2-agonists:
Nocturnal asthma
Refresh: Stimulatory G-protein cascade?
Gαs → ↑cAMP → ↓Ca++
Onset of action of β-agonists:
Rapid; 15-30 min
Duration of action of β-agonists:
30-60 minutes
Salmeterol up to 4 hours
Indication for β-agonists:
Rescue inhaler
Delivery of β-agonists:
Inhalation/aerosol, powder or nebulized
Exception: terbutaline is SC
Side effects of β-agonists:
Tremor
↑ HR
Vasodilation
Hyperglycemia, hypokalemia (d/t insulin release), hypomag
Preferred β2-selective agonist:
Albuterol
Dosing of albuterol:
100 mcg/puff
2 puffs q4-6hr
2.5 - 5.0mg nebulized in 5ml saline
Duration of action of albuterol:
4 hours; some relief up to 8 hours
Anesthetic considerations for albuterol:
Additive effect with volatile anesthetics on bronchomotor tone
2 isomers of albuterol:
R-albuterol more β2 affinity
S-albuterol more β1 affinity
Side effects of albuterol:
Tachycardia
Hypokalemia
Anesthesia uses of albuterol:
4 puffs to blunt AW response to tracheal intubation in asthmatics
Dosage of metaproterenol:
No more than 16 puffs/day
Advantage of bitolterol:
Longer lasting
CV side effects rare
Dosage of bitolterol:
16-20 puffs/day
270 mcg/puff
Indications for terbutaline:
Asthma, esp. status asthmaticus
Preterm labor
Delivery of terbutaline:
Oral, SC, inhalation
Dosage of terbutaline:
SC: 0.25mg q15min (adult)
SC: 0.01 mg/kg (child)
MDI: 16-20 puffs/day
(200 mcg/puff)
Examples of long-acting β-agonists:
Salmeterol
Advair: fluticasone and salmeterol
Formoterol
Long-acting β-agonists are long acting because:
Lipophilic side chains resisting degradation
Duration of action of long-acting β-agonists:
12-24 hours
Indications for long-acting β-agonists:
Prevention, not flare-up
Indications for anticholinergics:
Treatment of COPD
Secondary tx for asthma (resistant to β-agonist or w/ cardiac disease)
Model of asthma exacerbation d/t viral infection:
Activated T-cell → eosinophilic activation → mediator release via degranulation → deposition on airway smooth muscle and stimulate PSNS bronchoconstriction
Classification of atropine:
Naturally occuring tertiary amide alklaoid
Dosing of atropine for asthma:
1-2mg neb in 3-5ml NS
Side effects of atropine:
Tachycardia
Nausea
Dry mouth
GI upset
Classification of ipratropium bromide:
Quaternary ammonium salt derived from atropine
Dosing of ipratropium bromide:
40-80mcg in 2 puffs MDI or via neb
Onset of ipratropium bromide:
Slow; 30-90 min
Duration of action of ipratropium bromide:
4-6 hours
Absorption of ipratropium bromide relative to atropine:
Not significantly absorbed, so less cardiac/systemic side effects
Side effects of ipratropium bromide:
If inadvertently orally ingested, dry mouth/GI upset
Structure of tiotropium:
Quaternary ammonium salt
Duration of action of tiotropium:
Long acting
Advantage of tiotropium:
Not significantly absorbed so few systemic side effects
Indication for tiotropium:
COPD
MoA for methylxanthines:
Nonspecific inhibition of phosphodiesterase isoenzymes
Function of phosphodiesterase isoenzymes:
Prevent cAMP degradation → ↑cAMP → ↓Ca++ → bronchodilation
Indications for methylxanthines:
COPD/asthma
Examples of methylxanthines:
Theophylline
Aminophylline
Therapeutic plasma level of theophylline:
10-20 mg/ml
Toxic level of theophylline:
> 20 mg/ml
Toxic level of theophylline:
> 20 mg/ml
Drug interactions with theophylline:
Halothane (not in US)
Activates CYP450
Side effects of methylxanthines:
Arrythemias N/V Irritability Insomnia Seizures Brain damage Hyperglycemia Hypokalemia Hypotension
Indication for inhaled corticosteroids:
Major preventative treatment for asthma
MoA (3) of inhaled corticosteroids:
Alters genetic transcription to ↓ pro-inflammatory protein synthesis, ↑ anti-inflammatory proteins and β2 receptors
Induces apoptosis of inflammatory cells
Indirectly inhibits mast cells over time
Relative importance of inhaled corticosteroids for asthma mgmt:
Most important drug in the arsenal!!
Examples of inhaled corticosteroids:
Beclomethasone
Triamcinolone
Fluticasone
Budesonide
Anesthesia uses of inhaled corticosteroids:
Consider using 1-2 hours pre-op
Consider 5 day course of combined inhaled corticosteroids/albuterol to minimize risk of intubation bronchospasm
Drug interactions with inhaled corticosteroids:
Prolong the response of β-agonists (hence combination drugs like Advair)
% of inhaled corticosteroids that reach the airway vs. the oropharynx:
25% into airway
80-90% into oropharynx
Side effects of inhaled corticosteroids:
Osteopenia/porosis Delayed growth in children Oropharyngeal thrush Hoarseness Hyperglycemia
MoA of cromolyn:
Stabilizes mast cells and inhibits antigen-induced release of histamine
Inhibits the immediate allergic response to an antigen, BUT NOT the response once activated
Indications for cromolyn:
Prevention, not rescue!
Delivery of cromolyn:
Inhalation; 8-10% enters systemic circulation
Dosing of cromolyn:
4 times daily
7 days to effect!
Side effects of cromolyn:
Infrequent but serious: Laryngeal edema Angioedema Urticaria Anaphylaxis
Leukotrienes synthesized from:
Arachidonic acid in the presence of activated inflammatory cells
MoA of zileuton:
Blocks the biosynthesis of leukotrienes
Disadvantages of zileuton:
Low bioavailability
Low potency
Significant adverse effects
Hepatotoxic
MoA of monteleukast:
Blocks the Cysteinyl-Leukotriene 1 receptors on the smooth muscle
Drug interaction with monteleukast:
Coadministration with warfarin can prolong PT
MoA of omalizumab:
Short-term: Binds to IgE antibodies and prevents their binding to mast cells to mitigate the acute response to inhaled allergen
Long-term: IgE receptors on mast cells/basophils/dendritic cells are down-regulated
Delivery of omalizumab:
Given SQ for 2-4 weeks or parenterally infused; during early and late phase of asthmatic response
