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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
Q

Ipratropium Bromide

A 
Muscarinic M3 receptor antagonist
Bronchodilator/anticholinergic
Quaternary ammonium salt
Atropine derivative
Less absorption compared to Atropine
26
Q

Ipratropium Bromide Dose

A

40-80mcg

2-4 puffs via nebulizer

27
Q

Ipratropium Bromide Onset

A

Slow

30 minutes

28
Q

Ipratropium Bromide DOA

A

4-6 hours

29
Q

Ipratropium Bromide Side Effects

A

Inadvertent oral absorption

- Dry mouth & GI upset

30
Q

Tiotropium

A 
Muscarinic receptor antagonist
Bronchodilator/anticholinergic
Quaternary ammonium salt
Long-acting anticholinergic
Not significantly absorbed across the respiratory epithelium
Few side effects
31
Q

Methylxanthines: Phosphodiesterase Inhibitors

A

Bronchodilators

  • Theophylline
  • Aminophylline
32
Q

Methylxanthines: Phosphodiesterase Inhibitors MOA

A

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
Q

Methylxanthines: Phosphodiesterase Inhibitors Side Effects

A 
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
Q

Theophylline

A

PDEi

Caution w/ Halothane

35
Q

Theophylline

Therapeutic Range

A

10-20mcg/mL

TOXIC > 20mcg/mL

36
Q

Anti-Inflammatory Agents

A

Inhaled corticosteroids
Cromolyns
Leukotriene inhibitors
Anti-IgE antibodies

37
Q

Inhaled Corticosteroids MOA

A

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
Q

What’s considered the most important drug to manage asthma?

A

Inhaled corticosteroids

SUPPRESSIVE THERAPY

39
Q

Inhaled Corticosteroids

A

Beclomethasone
Triamcinolone
Fluticasone
Budesonide

40
Q

Inhaled Corticosteroids

Preoperative

A

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
Q

Inhaled Corticosteroids Administration

A

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
Q

Inhaled Corticosteroids Side Effects

A 
Oropharyngeal candidiasis
Osteopenia/osteoporosis
Delayed growth in children
Hoarseness
Hyperglycemia
43
Q

Cromolyn

A 
Stabilizes mast cells 
PREVENTATIVE
Administer via inhalation 8-10% enters systemic circulation
7 days to see full effect
4x daily
44
Q

Cromolyn MOA

A

Inhibits antigen-induced histamine release

45
Q

Cromolyn Use

A 
Prophylactic bronchial asthma therapy
Only preventative treatment
Does NOT relieve an allergic response after initiation
NOT used as rescue inhaler
Side effects rare
46
Q

Cromolyn Side Effects

A

Laryngeal edema
Angioedema
Urticaria
Anaphylaxis

47
Q

Leukotriene Inhibitors

A

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
Q

Leukotrienes

A

Synthesized from arachidonic acid when inflammatory cells are activated

49
Q

Zileuton

A

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
Q

Montelukast (Singulair)

A

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
Q

Anti-IgE Antibodies

A

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
Q

Omalizumab

A

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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