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AS - N929 Pharmacology II > Respiratory Agents > Flashcards

Respiratory Agents Flashcards

1
Q

Pulmonary SNS Stimulation

A

Bronchial smooth muscle relaxation

Bronchodilation via β2 receptors

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2
Q

Pulmonary PSNS Stimulation

A

Vagus nerve
Bronchial smooth muscle constriction
Bronchoconstriction via muscarinic M3 receptors
↑secretions

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3
Q

Asthma

A

Chronic airway inflammatory disorder
↑responsiveness to tracheobronchial tree stimuli
Bronchial hypersensitivity/reactivity to irritant stimuli
T2 lymphocytes activation & cytokine release
REVERSIBLE airway obstruction

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4
Q

COPD

A

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

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5
Q

Medications to Treat Obstructive Disorders

A
  1. Short-acting bronchodilators
  2. Regular inhaled corticosteroids
  3. Long-acting bronchodilators
  4. PDEi, methylxanthines, leukotriene inhibitors
  5. Oral corticosteroid
  6. Cromolyns
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6
Q

Medications to Treat Obstructive Disorders

A
  1. Short-acting bronchodilators
  2. Regular inhaled corticosteroids
  3. Long-acting bronchodilators
  4. PDEi, methylxanthines, leukotriene inhibitors
  5. Oral corticosteroid
  6. Cromolyns
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7
Q

Bronchodilators

A

β adrenergic agonists
Anticholinergics
Methylxanthines

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8
Q

β Adrenergic Agonists

A

Epinephrine β1&2 α
Isoproterenolα β1&2
Metaproterenolα β1&2

β2 > β1
200-400x

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9
Q

Short-Acting β Adrenergic Agonists

A

Terbutaline
Albuterol
Levalbuterol
Salbutamol

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10
Q

Long-Acting β Adrenergic Agonists

A

Salmeterol

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11
Q

β Adrenergic Agonists MOA

A

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
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12
Q

β Adrenergic Agonists Onset

A

RAPID w/in minutes

Ideal rescue inhaler

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13
Q

β Adrenergic Agonists DOA

A

Short

4-6 hours

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14
Q

β Adrenergic Agonists

Side Effects

A

Tremors
↑HR
Vasodilation
Metabolic changes - hyperglycemia, hypokalemia, & hypomagnesemia

*Minimized via inhalation delivery

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15
Q

Albuterol

A 
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
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16
Q

Albuterol DOA

A

4 up to 8 hours

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17
Q

Albuterol

Anesthetic Implications

A

Additive effects w/ volatile anesthetics

↑bronchodilation

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18
Q

Albuterol Side Effects

A

Tachycardia
Hypokalemia
4 puffs to blunt airway responses to tracheal intubation in asthmatic patients

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19
Q

Terbutaline

A 
β adrenergic agonist
Pediatric SQ 0.01mg/kg
Adult SQ 0.25mg Q15min
MDI 16-20puffs/day
200mcg per dose
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20
Q

Salmeterol

A

Long-acting β agonist
Combination w/ Fluticasone (Flonase) steroid
Lipophilic side chains resist degradation
DOA 12-24 hours
Prevention NOT acute flare-u

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21
Q

Muscarinic Receptor Antagonists

MOA

A

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

22
Q

What’s the 2nd line asthma treatment in patients resistant to β agonist or significant cardiac disease?

A

Muscarinic receptor antagonists
Bronchodilators/anticholinergics
Interrupts cascade ↓Ca2+

& COPD

23
Q

Atropine

A 
Muscarinic receptor antagonist
Bronchodilator/anticholinergic
Naturally occurring alkaloid
1-2mg diluted in 3-5mL NS via nebulizer
Highly absorbed across respiratory epithelium → systemic effects
24
Q

Atropine Side Effects

A

Systemic anticholinergic effects

- Tachycardia, nausea, dry mouth, GI upset

25
Ipratropium Bromide
``` Muscarinic M3 receptor antagonist Bronchodilator/anticholinergic Quaternary ammonium salt Atropine derivative Less absorption compared to Atropine ```
26
Ipratropium Bromide Dose
40-80mcg | 2-4 puffs via nebulizer
27
Ipratropium Bromide Onset
Slow | 30 minutes
28
Ipratropium Bromide DOA
4-6 hours
29
Ipratropium Bromide Side Effects
Inadvertent oral absorption | - Dry mouth & GI upset
30
Tiotropium
``` Muscarinic receptor antagonist Bronchodilator/anticholinergic Quaternary ammonium salt Long-acting anticholinergic Not significantly absorbed across the respiratory epithelium Few side effects ```
31
Methylxanthines: Phosphodiesterase Inhibitors
Bronchodilators - Theophylline - Aminophylline
32
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
33
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 ```
34
Theophylline
PDEi | Caution w/ Halothane
35
Theophylline | Therapeutic Range
10-20mcg/mL | TOXIC > 20mcg/mL
36
Anti-Inflammatory Agents
Inhaled corticosteroids Cromolyns Leukotriene inhibitors Anti-IgE antibodies
37
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
38
What's considered the most important drug to manage asthma?
Inhaled corticosteroids | SUPPRESSIVE THERAPY
39
Inhaled Corticosteroids
Beclomethasone Triamcinolone Fluticasone Budesonide
40
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
41
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
42
Inhaled Corticosteroids Side Effects
``` Oropharyngeal candidiasis Osteopenia/osteoporosis Delayed growth in children Hoarseness Hyperglycemia ```
43
Cromolyn
``` Stabilizes mast cells PREVENTATIVE Administer via inhalation 8-10% enters systemic circulation 7 days to see full effect 4x daily ```
44
Cromolyn MOA
Inhibits antigen-induced histamine release
45
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 ```
46
Cromolyn Side Effects
Laryngeal edema Angioedema Urticaria Anaphylaxis
47
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)
48
Leukotrienes
Synthesized from arachidonic acid when inflammatory cells are activated
49
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
50
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
51
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
52
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

AS - N929 Pharmacology II (10 decks)

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