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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
Q

Route of clenbuterol

A
  • Oral
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26
Q

Which selective B2 agonist is used most in the horse?

A
  • Clenbuterol
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27
Q

How long can you give clenbuterol?

A
  • up to 30 days (but tolerance develops
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28
Q

Bioavailability of clenbuterol

A
  • Excellent

- 87%

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29
Q

Other side effects of clenbuterol

A
  • Anabolic and lipolytic to decrease body fat

- Illegal for a lot of events

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30
Q

Clenbuterol use in dystocia

A
  • Tocolytic effect to slow progress of labor in dystocias
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31
Q

Other fun fact about clenbuterol (lol I don’t know how to address this)

A
  • Anti-inflammatory properties
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32
Q

What size do particles need to be to get into the smallest alveoli for inhaled drugs?

A
  • 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
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33
Q

Size of particles that can reach thoracic inlet?

A
  • 10 to 6 µm
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34
Q

Cost of inhaled drugs

A
  • VERY expensive

- She goes with nebulized now, which won’t get down as far

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35
Q

How can you get maximal deposition of inhaled drugs?

A
  • 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
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36
Q

Albuterol route

A
  • CANNOT be given orally in the horse due to poor bioavailability
  • Can administer with devices such as Aerohippus (very $$$$), which is a nebulizer
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37
Q

How quickly does albuterol work?

A
  • 5 minutes
38
Q

Salmeterol route

A
  • Inhaled
39
Q

Length ofaction of salmeterol

A
  • 8-12 hours in severe asthma horses
40
Q

Salmeterol additional actions

A
  • Anti-inflammatory properties
  • Inhibits leukotriene and histamine release from mast cells
  • Reduction of eosinophils
41
Q

Salmeterol recommended use

A
  • Maintenance in therapy and pre-exercise administration
  • recommended for horses with inflammatory airway disease
  • mild to moderate airway obstruction
42
Q

MOA of anti-cholinergics

A
  • 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
Q

What is the primary mechanism of bronchospasm in severe equine asthma?

A
  • Vagally mediated cholinergic stimulation of M3 receptors
44
Q

Atropine site of action

A
  • Non-selective M1, M2, M3 antagonist
45
Q

Atropine MOA

A
  • Non-selective M1, M2, M3 antagonist

- Decreases release of intracellular calcium from sarcoplasmic reticulum leading to smooth muscle relaxation

46
Q

Atropine route

A
  • IV
47
Q

Atropine speed of action and duration

A
  • Rapid bronchodilation in horses

- Short duration (1/2 hr to 2 hrs)

48
Q

Atropine and equine multinodular pulmonary fibrosis

A
  • Atropine won’t help in these case because they cannot physically bronchodilate
49
Q

Use of atropine in horses

A
  • Limited except as rescue
50
Q

Side effects of atropine in horses**

A
  • SEVERE
  • Ileus
  • CNS toxicity
  • Tachycardia
  • Increased mucus viscosity
  • Impaired mucociliary clearance
51
Q

Ipatromium bromide MOA

A
  • Synthetic anticholinergic compound

- Non-selective muscarinic antagonist

52
Q

Action of ipatromium bromide

A
  • Causes bronchodilation

- Inhibits cough

53
Q

Route of ipatromium bromide

A
  • Nebulized or inhaler
54
Q

How long does ipatromium bromide take to work?

A
  • 15-30 minutes
55
Q

How long does ipatromium bromide last?

A

4-6 hours

56
Q

Buscopan (N-butylscopalammonium bromide) MOA

A
  • Anti-cholinergic, quaternary ammonium compound used for gas/spasmodic colic in horses
57
Q

Buscopan (N-butylscopalammonium bromide) side effects

A
  • minimal
  • Transient tarchycardia** (Don’t forget)
  • Decreased borborygmi
  • Pupillary dilation
58
Q

Buscopan (N-butylscopalammonium bromide) use

A
  • Potent bronchodilator
  • Excellent rescue drug
  • Can use as a rescue and also for testing bronchoconstrictive disease vs fibrosing disease
59
Q

How long does it take for maximum effect of Buscopan (N-butylscopalammonium bromide)?

A
  • 10 minutes after IV administration
60
Q

How long does Buscopan (N-butylscopalammonium bromide) last?

A
  • 1 hr after administration
61
Q

Cromolyn sodium route

A
  • Nebulized or used with inhaler
62
Q

MOA of cromolyn sodium

A
  • Inhibits mast cell degranulation

- Interferes with calcium transport across cell membrane

63
Q

Clinical use of cromolyn sodium

A
  • 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
Q

What drug can you use primarily to combat the inflammatory component of RAO and other horse asthma diseases?

A
  • Glucocorticoids
65
Q

MOA of Glucocorticoids

A
  • 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
Q

Indications for corticosteroids

A
  • Severe asthma (RAO) and some cases of IAD or mild/moderate asthma
  • Improve pulmonary function
  • Reduce inflammation
67
Q

What horses should get systemic corticosteroids vs inhaled corticosteroids?

A
  • Horses with severe diffuse airway disease need systemic corticosteroids
  • Inhaled corticosteroids would not get distributed with severely affected horses
68
Q

How quickly does the benefit of corticosteroids occur?

A
  • 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
Q

What are options for systemic corticosteroids in horses?

A
  • Dexamethasone

- Prednisolone (NOT prednisone)

70
Q

Dexamethasone potential adverse effect

A
  • Laminitis

- NEVER PROVEN, but you must always throw the caveat out there

71
Q

Prednisolone vs dexamethasone for reducing airway inflammation

A
  • Prednisolone does not decrease airway inflammation obstruction as well as dexamethasone
72
Q

Prednisone in horses

A
  • DON’T
  • Poor absorption
  • Rapid excretion
  • Failure of hepatic conversion to prednisolone
73
Q

Indications for inhaled corticosteroids

A
  • Effective in horses with mild to moderate airway obstruction
74
Q

Benefits of inhaled corticosteroids if indicated

A
  • Reduce total therapeutic dose
  • Decrease systemic side effects
  • Allow direct delivery to the lower respiratory tract
75
Q

Three formulas of corticosteroids

A
  • Fluticasone
  • Beclomethasone
  • Flunisolide
76
Q

List from most to least potent the three formulas of corticosteroids

A
  • Fluticasone > Beclomethasone > Flunisolide
77
Q

Relative costs of Fluticasone, beclomethasone, and flunisolide?

A
  • Fluticasone is most expensive
  • Beclomethasone is similar cost
  • Flunisolide is less expensive
78
Q

Inhaled steroids adverse effects

A
  • 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
Q

IFNa clinical use

A
  • Endogenous immunostimulant
  • Antiviral
  • Immunomodulatory
  • Anti-proliferative activity
  • Oral administration for horses with mild asthma/inflammatory airway disease
80
Q

IFN-gamma with mild asthma-inflammatory airway disease

A
  • 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
Q

Inhaled antibiotics for equine pneumonia

A
  1. Gentamicin
  2. Ceftiofur
  3. Cefquinome
82
Q

Side effect of gentamicin that you always have to worry about?

A
  • Kidneys
83
Q

Mucolytics use in equine med

A
  • beneficial?
  • Typically don’t use in equine asthma
  • Use more for bronchopneumonia/pleural pneumonia cases
84
Q

Mucolytic MOA

A
  • Decreases viscosity of secretions
  • Enhances clearance of bronchial exudates
  • Promotes a productive cough
  • Used to treat COPD and cystic fibrosis in people
85
Q

N-acetylcysteine or mucomyst MOA

A
  • Mucolytic effect through free sulfhydryl group
  • Opens up disulfide bonds
  • Lowers viscosity
86
Q

Use of n-acetylcysteine

A
  • Use with nebulizer

- 20-50 mL of 10% solution every 6 hours

87
Q

Dopram use

A
  • Stimulates respiratory center in ER situation
  • Neonates
  • Anesthetic emergencies
  • Overdose of benzodiazepines, opiates
88
Q

MOA of dopram or doxapram

A
  • General CNS stimulant

- Stimulates carotid and aortic chemoreceptors

89
Q

Contraindications of Doxapram

A
  • With cerebral hemorrhage or increased cerebral pressure

- Can increase hemorrhage

90
Q

Caffeine MOA

A
  • enhance ventilatory response
  • Adenosine receptor A1, A2 antagonist
  • Increases respiratory drive

Clinical Pharmacology Exam 3 (5 decks)

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