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Clinical Pharmacology Exam 3 > Respiratory LA > Flashcards

Respiratory LA Flashcards

1
Q

Which CN conduct afferent nerve fibers for the cough reflex?

A
  • Vagal, glossopharyngeal, trigeminal, and phrenic nerve
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2
Q

Relative sensitivity of horse upper airway cough receptors

A
  • In general horses are less sensitive to upper airway cough receptors
  • Example: passing stomach tube accidentally into the trachea, they may or may not cough
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3
Q

Causes of coughing in horses

A
  • Extensive
  • Infectious: Influenza, EHV 1, EHV4, pneumonia, pleural pneumonia, pleuritis, pharyngitis, post-viral hyperactive airways
  • Non-infectious: Equine asthma, mechanical causes
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4
Q

When are anti-tussives indicated?

A
  • Persistent
  • Fatiguing
  • Non-productive cough
  • If productive, cough is an important pulmonary defense mechanism
  • Helps assistance with clearance of secretions and debris from lower respiratory tract
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5
Q

In general, how often are anti-tussives used in horses?

A
  • Infrequently
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6
Q

Opiate agonist anti-tussives

A
  • Hydrocodone

- Butorphanol

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7
Q

Non-opioid anti-tussives

A
  • Dextromethorphan

- NOT USEFUL IN HORSES

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8
Q

MOA of anti-tussives in general

A
  • Direct supprssion of cough center
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9
Q

Bronchodilators (methylxanthine) MOA

A
  1. ) Competitive non-selective phosphodiesterase inhibitor

2. ) Nonselective adenosine receptor antagonist (A1, A2, A3)

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10
Q

Bronchodilator methylxanthine - what are consequences of action as competitive non-selective phosphodiesterase inhibitor?

A
  • Increases cAMP, protein kinase A, inhibits TNF-alpha and leukotriene synthesis
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11
Q

Bronchodilator methylxanthine - what are consequences of action as nonselective adenosine receptor antagonist?

A
  • Cardiac effects (tachycardia)

- In humans, reverse steroid insensitivity

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12
Q

Therapeutic index of bronchodilators (methylxanthine) in horses

A
  • NARROW
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13
Q

Side effects of methylxanthine in horses

A
  • CNS excitation
  • Arrhythmia
  • Narrow safety margin
  • Theophylline did not potentiate the effects of low dose dexamethasone in horses with recurrent airway obstruction
  • Also found did not improve lung function
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14
Q

Actions of Beta-2 adrenergic agonists

A
  • Decrease plasma exudation
  • Decrease cholinergic neurotransmission
  • Increase bronchodilation***
  • Increase mucociliary clearance
  • Decrease neutrophil function
  • Decrease bacterial adherence
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15
Q

Selective Beta-2 Agonists

A
  • Albuterol
  • Clenbuterol
  • Salmeterol
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16
Q

Non-selective Beta-2 agonists

A
  • Epinephrine

- Isoproteranol

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17
Q

Tolerance and beta-2 agonists

A
  • Tolerance or tachyphylaxis will occur
  • Receptor down regulation and uncoupling of adenylate cyclase
  • This is why you don’t use albuterol as a rescue drug repeatedly
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18
Q

How long do epinephrine and isoproteranol work?

A
  • ULTRA SHORT ACTING
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19
Q

Side effects of epinephrine

A
  • Tachycardia
  • Muscle fasciculations
  • Sweating
  • Hypertension
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20
Q

Isoproteranol side effects

A
  • Tachycardia
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21
Q

Relative length of action of albuterol, clenbuterol, and salmeterol

A
  • Albuterol is shorter acting

- Clenbuterol and salmeterol are longer acting

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22
Q

Side effects of albuterol, clenbuterol, and salmetrol?

A
  • Tachycardia
  • Sweating
  • Muscle fasciculations
  • Excitation
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23
Q

Three indications for beta-2 agonist use in horses?

A
  1. Emergency therapy in horses with marked airway obstruction or anaphylaxis (duration less than 1 hr)
  2. Before exercise to relieve mild to moderate airway obstruction
  3. Before administration of aerosol corticosteroid preparations (and improve pulmonary distribution of these surface active agents)
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24
Q

Of the three indications for Beta-2 agonist use, which does Dr. Gold tend to use the most?

A
  • Before administering aerosol corticosteroid preparations

- Improves pulmonary distribution of these surface active agents

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25
Route of clenbuterol
- Oral
26
Which selective B2 agonist is used most in the horse?
- Clenbuterol
27
How long can you give clenbuterol?
- up to 30 days (but tolerance develops
28
Bioavailability of clenbuterol
- Excellent | - 87%
29
Other side effects of clenbuterol
- Anabolic and lipolytic to decrease body fat | - Illegal for a lot of events
30
Clenbuterol use in dystocia
- Tocolytic effect to slow progress of labor in dystocias
31
Other fun fact about clenbuterol (lol I don't know how to address this)
- Anti-inflammatory properties
32
What size do particles need to be to get into the smallest alveoli for inhaled drugs?
- 5µm to 1 µm are therapeutic aerosol that get maximally deposited in lower airways - Some inhaled drugs are 50µm but won't reach distal airways
33
Size of particles that can reach thoracic inlet?
- 10 to 6 µm
34
Cost of inhaled drugs
- VERY expensive | - She goes with nebulized now, which won't get down as far
35
How can you get maximal deposition of inhaled drugs?
- Pattern of breathing impacts distribution - Maximal deposition occurs when patients take slow deep breaths with large tidal volumes - Difficult to control breathing pattern of animals
36
Albuterol route
- CANNOT be given orally in the horse due to poor bioavailability - Can administer with devices such as Aerohippus (very $$$$), which is a nebulizer
37
How quickly does albuterol work?
- 5 minutes
38
Salmeterol route
- Inhaled
39
Length ofaction of salmeterol
- 8-12 hours in severe asthma horses
40
Salmeterol additional actions
- Anti-inflammatory properties - Inhibits leukotriene and histamine release from mast cells - Reduction of eosinophils
41
Salmeterol recommended use
- Maintenance in therapy and pre-exercise administration - recommended for horses with inflammatory airway disease - mild to moderate airway obstruction
42
MOA of anti-cholinergics
- Parasympathetic system is dominant in the pulmonary autonomic nervous system in mammals - PNS innervation throughout tracheobronchial tree of the horse - Smooth muscle contraction more pronounced in trachea and large central airways - Parasympathetic blockade of M3 receptor with a muscarinic antagonist - Greatest effect in large central airways - Bronchodilation - Muscarinic receptors abundant in airways smooth muscle (normally laeds to smooth muscle contraction and bronchoconstriction)
43
What is the primary mechanism of bronchospasm in severe equine asthma?
- Vagally mediated cholinergic stimulation of M3 receptors
44
Atropine site of action
- Non-selective M1, M2, M3 antagonist
45
Atropine MOA
- Non-selective M1, M2, M3 antagonist | - Decreases release of intracellular calcium from sarcoplasmic reticulum leading to smooth muscle relaxation
46
Atropine route
- IV
47
Atropine speed of action and duration
- Rapid bronchodilation in horses | - Short duration (1/2 hr to 2 hrs)
48
Atropine and equine multinodular pulmonary fibrosis
- Atropine won't help in these case because they cannot physically bronchodilate
49
Use of atropine in horses
- Limited except as rescue
50
Side effects of atropine in horses****
- SEVERE - Ileus - CNS toxicity - Tachycardia - Increased mucus viscosity - Impaired mucociliary clearance
51
Ipatromium bromide MOA
- Synthetic anticholinergic compound | - Non-selective muscarinic antagonist
52
Action of ipatromium bromide
- Causes bronchodilation | - Inhibits cough
53
Route of ipatromium bromide
- Nebulized or inhaler
54
How long does ipatromium bromide take to work?
- 15-30 minutes
55
How long does ipatromium bromide last?
4-6 hours
56
Buscopan (N-butylscopalammonium bromide) MOA
- Anti-cholinergic, quaternary ammonium compound used for gas/spasmodic colic in horses
57
Buscopan (N-butylscopalammonium bromide) side effects
- minimal - Transient tarchycardia**** (Don't forget) - Decreased borborygmi - Pupillary dilation
58
Buscopan (N-butylscopalammonium bromide) use
- Potent bronchodilator - Excellent rescue drug - Can use as a rescue and also for testing bronchoconstrictive disease vs fibrosing disease
59
How long does it take for maximum effect of Buscopan (N-butylscopalammonium bromide)?
- 10 minutes after IV administration
60
How long does Buscopan (N-butylscopalammonium bromide) last?
- 1 hr after administration
61
Cromolyn sodium route
- Nebulized or used with inhaler
62
MOA of cromolyn sodium
- Inhibits mast cell degranulation | - Interferes with calcium transport across cell membrane
63
Clinical use of cromolyn sodium
- NO BRONCHODILATORY effects - Limited use in horses except with known "triggers" as it's more of a preventative - Administered prior to exposure to allergen
64
What drug can you use primarily to combat the inflammatory component of RAO and other horse asthma diseases?
- Glucocorticoids
65
MOA of Glucocorticoids
- Decrease inflammation by a huge variety of actions - Increase beta-2 adrenergic mediated bronchial smooth muscle - May prevent down-regulation of beta receptors - Decrease inflammatory mediators
66
Indications for corticosteroids
- Severe asthma (RAO) and some cases of IAD or mild/moderate asthma - Improve pulmonary function - Reduce inflammation
67
What horses should get systemic corticosteroids vs inhaled corticosteroids?
- Horses with severe diffuse airway disease need systemic corticosteroids - Inhaled corticosteroids would not get distributed with severely affected horses
68
How quickly does the benefit of corticosteroids occur?
- Within hours of administration - May not be detected clinically for 24-72 hours - Increasing dose does not help in human or equine asthma - Conservative dosing regiments recommended
69
What are options for systemic corticosteroids in horses?
- Dexamethasone | - Prednisolone (NOT prednisone)
70
Dexamethasone potential adverse effect
- Laminitis | - NEVER PROVEN, but you must always throw the caveat out there
71
Prednisolone vs dexamethasone for reducing airway inflammation
- Prednisolone does not decrease airway inflammation obstruction as well as dexamethasone
72
Prednisone in horses
- DON'T - Poor absorption - Rapid excretion - Failure of hepatic conversion to prednisolone
73
Indications for inhaled corticosteroids
- Effective in horses with mild to moderate airway obstruction
74
Benefits of inhaled corticosteroids if indicated
- Reduce total therapeutic dose - Decrease systemic side effects - Allow direct delivery to the lower respiratory tract
75
Three formulas of corticosteroids
- Fluticasone - Beclomethasone - Flunisolide
76
List from most to least potent the three formulas of corticosteroids
- Fluticasone > Beclomethasone > Flunisolide
77
Relative costs of Fluticasone, beclomethasone, and flunisolide?
- Fluticasone is most expensive - Beclomethasone is similar cost - Flunisolide is less expensive
78
Inhaled steroids adverse effects
- Suppression of HPA still occurs, so you still need to wean them off of steroids if discontinuing them - Up to 65% with fluticasone - Effects will be gone in 1-2 days - Thought to be safer overall than systemic use for long term
79
IFNa clinical use
- Endogenous immunostimulant - Antiviral - Immunomodulatory - Anti-proliferative activity - Oral administration for horses with mild asthma/inflammatory airway disease
80
IFN-gamma with mild asthma-inflammatory airway disease
- Activates natural defense system in oropharynx associated lymphoid tissue - Cellular communication occurs - amplification of biologic response - Likely amplification and dissemination of endogenous IFN-gamma activity
81
Inhaled antibiotics for equine pneumonia
1. Gentamicin 2. Ceftiofur 3. Cefquinome
82
Side effect of gentamicin that you always have to worry about?
- Kidneys
83
Mucolytics use in equine med
- beneficial? - Typically don't use in equine asthma - Use more for bronchopneumonia/pleural pneumonia cases
84
Mucolytic MOA
- Decreases viscosity of secretions - Enhances clearance of bronchial exudates - Promotes a productive cough - Used to treat COPD and cystic fibrosis in people
85
N-acetylcysteine or mucomyst MOA
- Mucolytic effect through free sulfhydryl group - Opens up disulfide bonds - Lowers viscosity
86
Use of n-acetylcysteine
- Use with nebulizer | - 20-50 mL of 10% solution every 6 hours
87
Dopram use
- Stimulates respiratory center in ER situation - Neonates - Anesthetic emergencies - Overdose of benzodiazepines, opiates
88
MOA of dopram or doxapram
- General CNS stimulant | - Stimulates carotid and aortic chemoreceptors
89
Contraindications of Doxapram
- With cerebral hemorrhage or increased cerebral pressure | - Can increase hemorrhage
90
Caffeine MOA
- enhance ventilatory response - Adenosine receptor A1, A2 antagonist - Increases respiratory drive

Clinical Pharmacology Exam 3 (5 decks)

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