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N929 - Anesthesia Pharmacology > Respiratory Drugs > Flashcards

Respiratory Drugs Flashcards

1
Q

beta2 adrenergic agonists drugs

A
  • Terbutaline
  • Albuterol
  • Levalbuterol
  • Salbutamol
  • Salmeterol (long-acting)
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2
Q

beta2 adrenergic agonists MOA

A

-beta receptors coupled to stimulatory G proteins
-activate adenyl cyclase which increases the production of cAMP (adenosine monophosphate)  bronchodilation
-reduced intracellular calcium release and alters membrane conductance
Primary Effect – dilate bronchi by a direct action of b2 adrenergic receptors
-smooth muscle relaxation and bronchodilation
-inhibits mediator release from mast cells
-increase mucous clearance by action of cilia

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3
Q

beta2 adrenergic agonists PK/PD

A
  • rapid onset –> within minutes
  • short DOA –> 4-6 hours
  • short or long acting
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4
Q

beta2 adrenergic agonists dose/route

A

Routes:

  • inhalation or aerosol
  • powder or nebulized
  • orally or injected (SQ)
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5
Q

beta2 adrenergic agonists clinical uses

A

-good for asthma use as rescue inhaler

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6
Q

beta2 adrenergic agonists effects/considerations

A
  • side effect profile minimized by inhalational delivery (bc directly at site of action)
  • tremors
  • tachycardia
  • vasodilation
  • metabolic changes - hyperglycemia, hypokalemia, hypomagnesemia
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7
Q

albuterol PK/PD

A
  • DOA –> 4 hours with some relief evident up to 8 hours

- 2 isomers –> R-albuterol levalbuterol has more affinity for beta2 & S-albuterol has more affinity for beta1

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8
Q

albuterol dose/route

A
  • administered via metered dose  100mcg/puff
  • 2 puffs Q4-6H
  • nebulizer 2.5-5 mg in 5 mL saline
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9
Q

albuterol clinical use

A

asthma rescue inhaler

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10
Q

albuterol effects/considerations

A

-additive effect with volatile anesthetics on bronchomotor tone –> get increased bronchodilation
-preferred selective beta2 agonist and used most commonly in the OR
-if patient takes albuterol for asthma, good practice to have them take a few puffs before going to OR
Common SE:
-tachycardia
-hypokalemia
-anesthetic use – 4 puffs blunt AW responses to tracheal intubation in asthmatic patients

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11
Q

Metaproterenol (Alupent)

A
  • treatment of asthma
  • administered via metered dose
  • do not exceed 16 puffs/day
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12
Q

Pirbuterol (Maxair)

A
  • treatment of asthma
  • 2 puffs (400 mcg) via metered dose
  • do not exceed 12 puffs/day
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13
Q

terbutaline dose

A
  • administered oral, SQ, inhaled
  • SQ dose 0.01 mg/kg (peds); 0.25 mg Q15min (adults)
  • metered dose inhaler 16-20 puffs/day (each dose is 200mcg)
  • SQ admin = similar effects to EPI
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14
Q

terbutaline clinical uses

A
  • treat asthma

- tocolytic to slow down labor (smooth muscle/uterine relaxation)

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15
Q

Long-acting beta2 adrenergic agonists

A

Salmeterol (combo steroid and b2 agonist)

Formoterol

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16
Q

Long-acting beta2 adrenergic agonist MOA

A
  • have lipophilic side chains that resist degradation

- salmeterol = fluticasone (steroid) + salmeterol (b2 agonist)

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17
Q

Long-acting beta2 adrenergic agonist PK/PD

A

-DOA 12-24 hours

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18
Q

Long-acting beta2 adrenergic agonist clinical use

A

-good for prevention of asthma exacerbation but not acute flare-up/rescue

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19
Q

Anticholinergic (Muscarinic Receptor Antagonist) drugs

A
  • Atropine
  • Ipratropium bromide
  • Tiotropium
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20
Q

Anticholinergic (Muscarinic Receptor Antagonist) MOA

A
  • competitive antagonists at muscarinic ACh receptors
  • M1 and M3 expressed in lung and most important in mediating smooth muscle relaxation + decreased mucus gland secretions
  • by antagonizing endogenous ACh  broncho-relaxation + decreased mucus secretions
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21
Q

Anticholinergic (Muscarinic Receptor Antagonist) clinical uses

A
  • treatment of COPD

- secondary line of treatment for asthma in patients resistant to beta agonist or significant cardiac disease

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22
Q

Anticholinergic (Muscarinic Receptor Antagonist) effects/considerations

A

Anticholinergic effects:

  • tachycardia
  • nausea
  • dry mouth
  • GI upset
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23
Q

atropine PK/PD

A

highly absorbed across respiratory epithelium

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24
Q

atropine dose

A

-1-2 mg diluted in 3-5 mL saline via nebulizer

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25
Q

atropine effects

A 
-formerly 1st line treatment for asthma 
Anticholinergic effects:
-tachycardia
-nausea
-dry mouth
-GI upset
26
Q

Ipratropium bromide MOA

A
  • quaternary ammonium salt derivative of atropine

- antagonizes effect of endogenous ACh at M3 receptor subtypes

27
Q

Ipratropium bromide PK/PD

A
  • slow onset 30 min
  • DOA 4-6 hours
  • not significantly absorbed compared to atropine
28
Q

Ipratropium bromide dose

A

-admin via metered dose inhaler 40-80 mcg in 2-4 puffs via nebulizer

29
Q

Ipratropium bromide effects

A

-inadvertent oral absorption (when pt swallows excess med) causes dry mouth and GI upset

30
Q

Tiotropium PK/PD

A
  • long acting

- not significantly absorbed across respiratory epithelium which results in few S/E

31
Q

Tiotropium clinical use

A

approved by FDA for COPD

32
Q

Phosphodiesterase Inhibitors (Methylxanthines) drugs

A

Theophylline

Aminophylline

33
Q

Phosphodiesterase Inhibitors (Methylxanthines) MOA

A

-nonspecific inhibition of phosphodiesterase isoenzymes (types III and IV) which prevents cAMP degradation in airway smooth muscle cell as well as inflammatory cells  airway relaxation + bronchodilation + no histamine release from mast cells

34
Q

Phosphodiesterase Inhibitors (Methylxanthines) PK/PD

A
  • metabolized in liver
  • excreted in kidney
  • susceptible to drug-drug interactions due to metabolism by CYP450 (like cimetidine and antifungals or other CYP 450 inhibitors)
35
Q

Phosphodiesterase Inhibitors (Methylxanthines) clinical use

A
  • COPD

- Asthma

36
Q

Phosphodiesterase Inhibitors (Methylxanthines) effects/considerations

A

-huge side effect profile and narrow therapeutic index ; also need to monitor for toxic blood level
-theophylline plasma level 10-20 mcg/mL (toxic at >20 mcg/mL)
-caution with halothane (combo sensitizes heart to epi and more prone to arrhythmias)
Side Effects:
-HA
-N/V
-irritability/restlessness
-insomnia
-cardiac arrythmias
-seizures
-Stevens Johnson Syndrome

37
Q

Inhaled Corticosteroids drugs

A

Beclomethasone
Triamcinolone
Fluticasone
Budesonide

38
Q

Inhaled Corticosteroids MOA

A
  • alter genetic transcription
  • increases transcription of genes for b2 receptor and anti-inflammatory proteins
  • decreases transcription of genes for pro-inflammatory proteins
  • induce apoptosis in inflammatory cells (eosinophils, TH2 lymphocytes)
  • indirect inhibition of mast cells over time
  • reverses many features of asthma
  • reduce number of inflammatory cells in airways and damage to epithelium
  • vascular permeability reduced which decreases airway edema
  • overall reduction in airway hyper-responsiveness
39
Q

Inhaled Corticosteroids PK/PD

A
  • 25% of inhaled reaches airway
  • 80-90% of inhaled dose reaches oropharynx and is swallowed (unless mouth is rinsed after using inhaler)
  • higher airway concentration than same dose given PO
40
Q

Inhaled Corticosteroids clinical use

A
  • major preventative treatment for patients with asthma (considered most important drug in management of asthma)
  • used as suppressive therapy, not a cure
41
Q

Inhaled Corticosteroids effects/considerations

A

-may consider use of corticosteroid admin 1-2 hours pre-op
-prolong response of beta agonists
-may consider 5-day preop course of combined corticosteroid and albuterol to minimize risk of intubation evoked bronchospasm
-systemic effects decreased through inhalation
Side Effects:
-oropharyngeal candidiasis
-osteopenia/osteoporosis
-delayed growth in children
-hoarseness
-hyperglycemia

42
Q

Mast Cell Stabilizer drug

A

cromolyn

43
Q

Mast Cell Stabilizer MOA

A
  • inhibits antigen-induced release of histamine
  • including release of inflammatory mediators from eosinophils, neutrophils, monocytes, macrophages, lymphocytes, and leukotrienes from pulmonary mast cells
  • inhibits immediate allergic response to an antigen but not the allergic response once it has been activated
44
Q

Mast Cell Stabilizer PK/PD

A
  • 8-10% enters systemic circulation

- takes 7 days to see effect

45
Q

Mast Cell Stabilizer dose

A
  • inhalation

- take 4x daily

46
Q

Mast Cell Stabilizer clinical use

A
  • prophylactic treatment of bronchial asthma
  • does not relieve allergic response after initiation
  • not used as rescue inhaler
47
Q

Mast Cell Stabilizer effects/considerations

A 
-side effects rare
Infrequent but serious side effects include: 
-laryngeal edema
-angioedema 
-urticaria 
-anaphylaxis
48
Q

Leukotriene Inhibitors

A 
Zileuton
Montelukast 
-leukotrienes – synthesized from arachidonic acid when inflammatory cells activated 
-bronchial asthma
-not effective for acute asthma attacks 
-few extrapulmonary effects
49
Q

Zileuton MOA

A

-blocks biosynthesis of leukotrienes from arachidonic acid

50
Q

Zileuton PK/PD

A
  • low bioavailability

- low potency

51
Q

Zileuton clinical use

A

-produces bronchodilation, improves asthma symptoms, shown long term improvement in PFT

52
Q

Zileuton effects/considerations

A
  • significant adverse effects
  • hepatotoxic
  • not widely used
53
Q

Montelukast MOA

A
  • blocks mechanism of bronchoconstriction and smooth muscle effects
  • blocks ability of leukotrienes to bind to Cysteinyl-leukotriene 1 receptor
54
Q

Montelukast clinical use

A

-improve bronchial tone, pulmonary function, and asthma symptoms

55
Q

Montelukast effects/considerations

A
  • caution with co-admin with warfarin which could result in prolonged PT
  • well tolerated/few side effects
56
Q

Anti-IgE Antibodies drug

A

Omalizumab

57
Q

Anti-IgE Antibodies MOA

A
  • humanized mouse monoclonal antibody
  • binds to IgE; decreases quantity of circulating IgE and prevents binding of IgE to mast cells
  • removal of IgE antibodies from circulation to mitigate acute response of inhaled allergen
58
Q

Anti-IgE Antibodies dose

A

-given SQ for 2-4 weeks/parenterally infused

59
Q

Anti-IgE Antibodies clinical use

A
  • for IgE mediated allergenic responses

- given in early and late phase of asthmatic response

60
Q

Anti-IgE Antibodies effects/considerations

A
  • expensive and inconvenient
  • down-regulation of receptors occurs in response to lower levels of circulating IgE; receptors on mast cells, basophils, and dendritic cells are down-regulated
  • rare effect – triggering of immune response

N929 - Anesthesia Pharmacology (12 decks)

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