Respiratory Agents Flashcards
Pulmonary SNS Stimulation
Bronchial smooth muscle relaxation
Bronchodilation via β2 receptors
Pulmonary PSNS Stimulation
Vagus nerve
Bronchial smooth muscle constriction
Bronchoconstriction via muscarinic M3 receptors
↑secretions
Asthma
Chronic airway inflammatory disorder
↑responsiveness to tracheobronchial tree stimuli
Bronchial hypersensitivity/reactivity to irritant stimuli
T2 lymphocytes activation & cytokine release
REVERSIBLE airway obstruction
COPD
Emphysema/bronchitis
IRREVERSIBLE obstruction
Cell death & alveolar destruction d/t impaired lung parenchyma, degraded membranes, & inflammatory cell toxic actions
Enlarged air spaces, fibrosis, & ↑mucus production
Medications to Treat Obstructive Disorders
- Short-acting bronchodilators
- Regular inhaled corticosteroids
- Long-acting bronchodilators
- PDEi, methylxanthines, leukotriene inhibitors
- Oral corticosteroid
- Cromolyns
Medications to Treat Obstructive Disorders
- Short-acting bronchodilators
- Regular inhaled corticosteroids
- Long-acting bronchodilators
- PDEi, methylxanthines, leukotriene inhibitors
- Oral corticosteroid
- Cromolyns
Bronchodilators
β adrenergic agonists
Anticholinergics
Methylxanthines
β Adrenergic Agonists
Epinephrine β1&2 α
Isoproterenolα β1&2
Metaproterenolα β1&2
β2 > β1
200-400x
Short-Acting β Adrenergic Agonists
Terbutaline
Albuterol
Levalbuterol
Salbutamol
Long-Acting β Adrenergic Agonists
Salmeterol
β Adrenergic Agonists MOA
β adrenergic receptors are coupled to stimulatory G proteins
Activate adenyl cyclase ↑cAMP production → bronchodilation
↓intracellular Ca2+ release & alters the membrane conductance
- Smooth muscle relaxation & bronchodilation
- Inhibits mediators released from mast cells
- ↑mucus clearance by ciliary action
β Adrenergic Agonists Onset
RAPID w/in minutes
Ideal rescue inhaler
β Adrenergic Agonists DOA
Short
4-6 hours
β Adrenergic Agonists
Side Effects
Tremors
↑HR
Vasodilation
Metabolic changes - hyperglycemia, hypokalemia, & hypomagnesemia
*Minimized via inhalation delivery
Albuterol
Short-acting β adrenergic agonist 2 isomers - R-albuterol levalbuterol ↑β2 affinity - S-albuterol ↑β1 affinity 100mcg/puff via MDI 2 puffs Q4-6H Nebulizer 2.5-5mg in 5mL NS
Albuterol DOA
4 up to 8 hours
Albuterol
Anesthetic Implications
Additive effects w/ volatile anesthetics
↑bronchodilation
Albuterol Side Effects
Tachycardia
Hypokalemia
4 puffs to blunt airway responses to tracheal intubation in asthmatic patients
Terbutaline
β adrenergic agonist Pediatric SQ 0.01mg/kg Adult SQ 0.25mg Q15min MDI 16-20puffs/day 200mcg per dose
Salmeterol
Long-acting β agonist
Combination w/ Fluticasone (Flonase) steroid
Lipophilic side chains resist degradation
DOA 12-24 hours
Prevention NOT acute flare-u
Muscarinic Receptor Antagonists
MOA
Bronchodilators/anticholinergics
Competitively antagonists at muscarinic acetylcholine receptors → block constriction
3 muscarinic receptor subtypes expressed by the lungs
M1 & M3 primary to mediate smooth muscle relaxation (bronchodilation) & ↓mucus gland secretion
What’s the 2nd line asthma treatment in patients resistant to β agonist or significant cardiac disease?
Muscarinic receptor antagonists
Bronchodilators/anticholinergics
Interrupts cascade ↓Ca2+
& COPD
Atropine
Muscarinic receptor antagonist Bronchodilator/anticholinergic Naturally occurring alkaloid 1-2mg diluted in 3-5mL NS via nebulizer Highly absorbed across respiratory epithelium → systemic effects
Atropine Side Effects
Systemic anticholinergic effects
- Tachycardia, nausea, dry mouth, GI upset
Ipratropium Bromide
Muscarinic M3 receptor antagonist Bronchodilator/anticholinergic Quaternary ammonium salt Atropine derivative Less absorption compared to Atropine
Ipratropium Bromide Dose
40-80mcg
2-4 puffs via nebulizer
Ipratropium Bromide Onset
Slow
30 minutes
Ipratropium Bromide DOA
4-6 hours
Ipratropium Bromide Side Effects
Inadvertent oral absorption
- Dry mouth & GI upset
Tiotropium
Muscarinic receptor antagonist Bronchodilator/anticholinergic Quaternary ammonium salt Long-acting anticholinergic Not significantly absorbed across the respiratory epithelium Few side effects
Methylxanthines: Phosphodiesterase Inhibitors
Bronchodilators
- Theophylline
- Aminophylline
Methylxanthines: Phosphodiesterase Inhibitors MOA
Non-specific phosphodiesterase isoenzymes inhibition (type III & IV) prevents cAMP degradation in airway smooth muscle as well as in inflammatory cells → airway relaxation & bronchodilation
Hepatic metabolism & renal excretion
Methylxanthines: Phosphodiesterase Inhibitors Side Effects
Multiple MOA & non-selective w/ narrow therapeutic index → Susceptible to drug-drug interactions d/t metabolism by cytochrome P450 (CYP450 inhibitors Cimetidine & antifungals) Headache N/V Irritability & restlessness Insomnia Cardiac arrhythmias Seizures Stevens-Johnson syndrome
Theophylline
PDEi
Caution w/ Halothane
Theophylline
Therapeutic Range
10-20mcg/mL
TOXIC > 20mcg/mL
Anti-Inflammatory Agents
Inhaled corticosteroids
Cromolyns
Leukotriene inhibitors
Anti-IgE antibodies
Inhaled Corticosteroids MOA
Asthma preventative treatment
Alters genetic transcription
↑gene transcription for β2 receptor & anti-inflammatory proteins
↓gene transcription for pro-inflammatory proteins ↓inflammatory cells in airway & damage to airway epithelium
Induce apoptosis in inflammatory cells
Indirect mast cell inhibition over time
↓vascular permeability → less airway mucosal edema & inflammation
SUPPRESSIVE therapy NOT curative
What’s considered the most important drug to manage asthma?
Inhaled corticosteroids
SUPPRESSIVE THERAPY
Inhaled Corticosteroids
Beclomethasone
Triamcinolone
Fluticasone
Budesonide
Inhaled Corticosteroids
Preoperative
Admin 1-2 hours preop to optimize patient
Prolongs the response to β agonists
Consider 5-day course combined corticosteroid & Albuterol to minimize intubation induced bronchospasm
Inhaled Corticosteroids Administration
Only 25% reaches the airways
80-90% inhaled dose reached oropharynx & swallowed unless mouth rinsed after using the inhaler
↓systemic effects w/ inhalation administration
Inhaled Corticosteroids Side Effects
Oropharyngeal candidiasis Osteopenia/osteoporosis Delayed growth in children Hoarseness Hyperglycemia
Cromolyn
Stabilizes mast cells PREVENTATIVE Administer via inhalation 8-10% enters systemic circulation 7 days to see full effect 4x daily
Cromolyn MOA
Inhibits antigen-induced histamine release
Cromolyn Use
Prophylactic bronchial asthma therapy Only preventative treatment Does NOT relieve an allergic response after initiation NOT used as rescue inhaler Side effects rare
Cromolyn Side Effects
Laryngeal edema
Angioedema
Urticaria
Anaphylaxis
Leukotriene Inhibitors
Inhibit leukotriene pathway & useful drugs to treat bronchial asthma (block arachidonic acid synthesis or action)
Not effective to treat acute asthma attacks
Few extrapulmonary effects
- Zileuton
- Montelukast (Singulair)
Leukotrienes
Synthesized from arachidonic acid when inflammatory cells are activated
Zileuton
Lipoxygenase inhibitor
Blocks leukotriene biosynthesis from arachidonic acid
Produces bronchodilation, improves asthma symptoms, & shown long-term improvement in pulmonary function tests
Low bioavailability & potency
Significant adverse effects
Hepatotoxic → 2% hepatitis
Not widely used
Montelukast (Singulair)
Leukotriene receptor antagonist
Block the bronchoconstriction mechanism & smooth muscle effects
Receptor antagonist - blocks leukotriene ability to bind to Cysteinyl-Leukotriene 1 receptor
Improve bronchial tone, pulmonary function, & asthma symptoms
Caution w/ co-administration w/ Warfarin → prolonged PT
Anti-IgE Antibodies
Asthma - prominence IgE mediated allergenic responses
Remove IgE antibodies from circulation would mitigate the acute response to the inhaled allergen
Last ditch effort to treat asthma
Omalizumab
Monoclonal antibody derived from DNA
Binds to IgE ↓circulating IgE & prevents IgE from binding to mast cells → receptor down-regulation (basophils & dendritic cells)
Administer in early & late phase asthmatic response
SQ 2-4 weeks or parentally infused
Cost & inconvenience
Rare adverse effect = triggers an immune response
