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Clinical Pharmacology Exam 3 > Respiratory SA > Flashcards

Respiratory SA Flashcards

1
Q

Purpose of cough reflex

A
  • Protect airways and lungs

- Clear airways of accumulated secretions

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2
Q

Which nerves initiate the cough reflex?

A
  • Vagal afferent nerves
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3
Q

Cough reflex

A
  1. Stimuli (chemical, physical, temperature/pH) stimulates larynx, trachea, or bronchi
  2. Afferent limb of vagal nerves carries to cough center in the medulla oblongata
  3. Efferent limb (motor nerves) signals to to laryngeal and respiratory muscles to cough
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4
Q

4 phases of the cough reflex?

A
  1. Action potentials by afferent nerves to stimulus
  2. Enhanced inspiratory effort
  3. Expiration against occluded upper airway
  4. Expulsive: upper airways dilate, forceful expiration
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5
Q

Common SA respiratory diseases

A
  1. Bronchitis
  2. Asthma
  3. Tracheal/bronchial collapse
  4. Pneumonia (think viral, bacterial, protozoal, parasitic)
  5. Neoplasia
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6
Q

What are the classes of anti-tussives?

A
  • Opiates

- Non-opiates

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7
Q

Indication of anti-tussives?

A
  • Coughing that interferes with quality of life
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8
Q

Contraindications for anti-tussives?

A
  • DO NOT USE WITH INFECTIVE COUGHS
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9
Q

MOA of anti-tussives

A
  • Depress coughing center in the medulla oblongata

- Mu or kappa receptors

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10
Q

What can reverse effects of opioid anti-tussives?

A
  • Naloxone
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11
Q

Toxicity and drug interactions of opiates

A
  • Potential for abuse
  • Sedation
  • Constipation
  • Respiratory depression (less of a problem with butorphanol)
  • Excitation/dysphoria (cats)
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12
Q

Actions of mu receptors

A
  • Analgesia
  • Respiratory depression
  • Sedation
  • Euphoria
  • Physical dependence
  • Decreased GI motility
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13
Q

Actions of kappa receptors

A
  • Analgesia
  • Sedation
  • Decreased GI motility
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14
Q

Hydrocodone receptors activated

A
  • Mu and kappa agonist
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15
Q

Schedule of Hydrocodone

A
  • Schedule II (high potential for abuse)
  • Still less abuse potential than morphine
  • Difficult long-term
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16
Q

Combination drugs with hydrocodone

A
  • Hycodan (combined with homatropine, an anticholinergic)

- Chlorpheniramine (antihistamine)

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17
Q

Formulation of hydrocodone

A
  • SYrup

- Can be good for small dogs

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18
Q

Codeine receptors

A
  • Mu and kappa agonist
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19
Q

Schedule of codeine

A
  • Schedule II
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20
Q

Oral bioavailability of codeine

A
  • Poor
  • She prefers hydrocodone
  • Less PK info in cats
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21
Q

Doses of codeine that suppress cough?

A
  • Suppress cough at low doses
  • Below analgesic/sedation dose
  • Above GI effects
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22
Q

Butorphanol receptors

A
  • Partial mu agonist

- Full kappa agonist

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23
Q

Use of butorphanol

A
  • FDA approved as an antitussive for dogs

- Very frequent in cats and little dogs

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24
Q

BUtorphanol schedule

A
  • Low potential for abuse, limited physical dependence

- Schedule IV controlled substance

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25
Q

Oral bioavailability of butorphanol

A
  • Better than codeine
  • Oral dose 10x > parenteral dose
  • can achieve therapeutic levels
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26
Q

Morphine receptors

A
  • Mu and kappa agonist
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27
Q

Morphine schedule

A
  • Schedule II
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28
Q

Oral bioavailability of morphine

A
  • Poor oral bioavailability in dogs
  • Not used orally clinically
  • More used IV
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29
Q

Morphine pharmacokinetics in cats

A
  • Less info

- Not used as much

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30
Q

Relative dosing of morphine used to suppress cough

A
  • Below sedation/analgesia dose

- Above GI effects

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31
Q

Tramadol anti-tussive

A
  • Preliminary data in humans suggests may decrease a neurogenic cough
  • Unknown in dogs and cats
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32
Q

Drug interactions of tramadol

A
  • Active metabolite requires CYP450

- CYP450 inhibitors decrease efficacy

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33
Q

Serotinergic drugs and tramadol

A
  • Can lead to serotonin syndrome if used in combination
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34
Q

Dextromethorphan use

A
  • Non-opioid anti-tussive
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35
Q

Dextromethorphan pharmacokinetic

A
  • Poor bioavailability orally in dogs
  • Short half-life in dogs
  • PK unknown in cats
  • NOT a useful drug in SA
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36
Q

Combination products with dextromethorphan

A
  • Combination products may contain acetaminophen, decongestants, antihistamines - not recommended for dogs
  • Avoid in cats
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37
Q

MOA of dextromethorphan

A
  • NMDA antagonist - role in cough reflex?

- Agonist to some opioid receptors

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38
Q

High dose dextromethorphan side effects

A
  • Vomiting and CNS toxicity in dogs and cats
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39
Q

OTC dextromethorphan

A
  • Robitussin
  • Vicks formula 44
  • NOT RECOMMENDED FOR ANIMALS
40
Q

Use of maropitant as an anti-tussive MOA

A
  • NK-1 receptor antagonist

- MIGHT reduce inflammation and suppress coughs

41
Q

Maropitant treatment in dogs with chronic bronchitis

A
  • One study had it for a 2 week long treatment
  • Bronchitis >2 months
  • No change in BAL (neutrophils, eosinophils)
  • Some limitations of study
42
Q

What are bronchodilators used to treat?

A
  • Bronchoconstriction ;)
43
Q

What reactive airway disease in the cat do bronchodilators treat (potentially)?

A
  • Feline asthma?

- May be targeting the wrong things

44
Q

What reactive airway disease in the dog do bronchodilators treat (potentially)?

A
  • Allergic bronchitis
45
Q

Methylxanthines (theophylline) MOA

A
  • Adenosine receptor antagonist on bronchial smooth muscle (bronchodilation) and inflammatory cells
  • Phosphodiesterase inhibitor (non-selective) that increases intracellular cAMP and reduces inflammation
46
Q

Indications for methylxanthines (theophylline)

A
  • Canine allergic bronchitis?

- Not typically used in feline asthma (dilated airways already and air just can’t move out)

47
Q

Why might methylxanthines (theophylline) not be the best choice for canine allergic bronchitis?

A
  • Disease primarily affects large airways, which are not the site of action of bronchodilators
  • Still can reduce signs by potentially reducing dose of glucorticoid, improving pulmonary perfusion, reducing respiratory effort, stimulating mucociliary clearance, and improving expiratory airflow
48
Q

Adverse effects of methylxanthines (theophylline)

A
  • CNS stimulation (irritability, tremors, seizures, hyperexcitability)
  • Cardiac (Tachyarrhythmias)
  • GI (anorexia, vomiting/nausea, and GI ulceration)
  • Mild diuresis
49
Q

Methylxanthines (theophylline) clearance

A
  • Depends on cytochrome P450 enzyme system

- Drug interactions!

50
Q

Drug interactions with methylxanthines (theophylline)

A
  • CYP inhibitors will increase plasma concentrations (toxicity): cimetidine and fluoroquinolones
  • CYP inducers will decrease plasma concentrations (sub-therapeutic): rifampin and phenobarbital
  • KNOW THAT THERE ARE MANY MANY DRUG INTERACTIONS
51
Q

Vet approved formulations of methylxanthines (theophylline)

A
  • No veterinary approved formulations
  • Adverse effects in people mean limited use and availability continues to decline
  • Do NOT SPLIT sustained release formulations (dogs - BID)
52
Q

Beta 2 adrenergic agonists MOA

A
  • B2 receptors in bronchial smooth muscle increase release of cAMP intracellular –> relaxation (bronchodilation)
  • B2 receptors on mast cells decrease release of inflammatory mediators
  • B2 receptor stimulation may increase mucociliary clearance
53
Q

What are the things that Beta-2 receptor agonists are specifically combatting in asthma?

A
  • Narrowed airway
  • Smooth muscle contraction
  • Edema
  • Increased mucus production
54
Q

Indications for Beta-2 receptor agonists

A
  • Feline asthma*****
  • Canine allergic bronchitis (possibly)
  • Acute asthma attacks (emergency) as epinephrine or isoproteranol IV
55
Q

Toxicity of non-selective Beta-2 receptor agonists, i.e. epinephrine and isoproteranol

A
  • Epinephrine (hypertension and tachycardia)

- Isoproteranol (tachycardia0

56
Q

Toxicity of selective Beta-2 receptor agonists, i.e. Terbutaline (IV) and albuterol (inhalant)

A
  • High doses stimulate B1 receptors (tachycardia)
57
Q

Tolerance and Beta-2 receptor agonists

A
  • Receptor down regulation
  • Should only be used for short periods in emergency situations
  • Due to uncoupling of receptors from adenylate cyclcase
58
Q

Duration of epinephrine and isoproteranol

A
  • <1 hr
59
Q

Nebulization an beta-2 adrenergic agents

A
  • process of creating small droplets of appropriate size for distribution into bronchi
  • Put the inhalant on their mouth and allow them to breathe in
60
Q

Terbutaline and albuterol approval

A
  • Approved for use in humans, and used in vet med
61
Q

Terbutaline formulation***

A
  • Injection, inhalation, tablets
62
Q

Albuterol formulation***

A
  • tablets, syrup, inhalation
63
Q

Anti-cholinergics mechanism of action for anti-tussive

A
  • Inhibit ACh receptor activation

- Remember that ACh causes bronchoconstriction and enhanced bronchial secretions

64
Q

Anti-cholinergics indication

A
  • Short term bronchodilation (emergency)
65
Q

Adverse effects/toxicity of Anti-cholinergics

A
  • Anti-DUMBSLED
  • Tachycardia
  • GI ileus
  • CNS excitation followed by depression/coma
  • Decreased mucociliary clearance
66
Q

Examples of anti-cholinergic agents that could be used

A
  • Atropine and glycopyrrolate
67
Q

Atropine use in SA

A
  • Not typically used in SA
  • Improved bronchoconstriction
  • CNS effects too
68
Q

Glycopyrrolate adverse effects compared to atropine

A
  • Fewer
  • Doesn’t cross BBB
  • Injectable formulation
69
Q

Cromolyn MOA

A
  • Inhibits mast-cell degranulation, interferes with calcium transport across membrane
  • No bronchodilatory effects
70
Q

Cromolyn indication***

A
  • Effective only if administered prior to exposure to the allergen
71
Q

Pharmacokinetics of cromolyn

A
  • Administered via nebulization
72
Q

What dose of steroids do you use to treat respiratory disease?

A
  • Anti-inflammatory dose
73
Q

Mechanism of action of corticosteroids in respiratory disease

A
  • Decreases inflammation of airways by a variety of mechanisms
  • Increases beta-2 adrenergic mediated bronchial smooth muscle relaxation
  • May prevent down regulation of beta-2 adrenergic receptors (tolerance)
  • Synergistic with theophylline???
74
Q

Indications for corticosteroids

A
  • Useful drug for asthma in people/cats
75
Q

How can you minimize systemic side effects of corticosteroids when giving to treat respiratory disease?

A
  • Topical drug delivery (inhalers) may minimize (WILL NOT ELIMINATE) systemic side effects
  • Feline asthma and allergic bronchitis as well as non-septic pulmonary diseases
76
Q

Doses for corticosteroids

A
  • DO KNOW THIS again

- review

77
Q

Toxicity of corticosteroids in dogs

A
  • Weight gain, GI ulceration; secondary infection
78
Q

Drug contraindications with corticosteroids in dogs

A
  • Do NOT use with NSAIDs
79
Q

Toxicity of corticosteroids in cats

A
  • Weight gain
  • Hyperglycemia (risk of diabetes mellitus)
  • 2° infection
80
Q

Oral/injectable of corticosteroids

A
  • prednisone/prednisolone
  • There is a Depo version that can last 3-4 weeks as well
  • Dexamethasone suspension or tablets (potent; avoid in cats and dogs)
81
Q

Anti-inflammatory drugs that are inhaled

A
  • Fluticasone proprionate** (Flovent)

- There are a lot of others too

82
Q

Which steroid (prednisone/prednisolone) do you want to use in cats?

A
  • Prednisolone

- Prednisone is not orally bioavailable in cats

83
Q

Expectorants/mucolytics in dogs and cats

A
  • beneficial?

- Used frequently in people and less so in vet med

84
Q

Rationale for mucolytics/expectorants

A
  • Decrease viscosity of secretions
  • Enhance clearance of bronchial exudate
  • Promote more productive cough
85
Q

Saline expectorant MOA

A
  • Stimulate gastric mucosa –> vagus stimulation –> increased GI AND bronchial secretions
  • Nebulizing
86
Q

Guaifenesin glyceryl usage

A
  • 1° use is muscle relaxant for anesthetic purpose
  • May also have expectorant effects via vagal stimulation
  • OTC formulations (human): robutussin, mucinex
87
Q

N-acetylcysteine overview

A
  • Mucolytic

- True mucolytic - sulfhydryl group breaks disfulide bonds of mucus

88
Q

N-acetylcysteine MOA

A
  • Disulfide bonds hold mucus tight and Mucomyst breaks them up just right, Kind of like a lung shampoo, for breaking up tenacious goo
89
Q

Use of decongestants

A
  • Decrease mucus production
90
Q

Mechanism of decongestants

A
  • Stimulate alpha adrenergic receptors mucosa in nasal mucosa –> vasoconstriction
91
Q

Available agents for decongestants

A
  • Phenylephrine

- Phenylpropanolamine (long acting oxymetazole or Afrin; for urinary continence; appropriate?)

92
Q

Decongestant problems with chronic use

A
  • Rebound vasodilation –> greater mucus production
93
Q

Systemic decongestants available

A
  • Pseudoephedrine

- Phenylpropanolamine

94
Q

Pseudoephedrine, ephedrine, and PPA misuse

A
  • Can be used to manufacture methamphetamine so hard to get
95
Q

Dopram or Doxapram use

A
  • Stimulates respiratory center in emergency situations
  • Anesthetic emergencies
  • Overdoses (opiates, benzodiazepines, macrocyclic lactones)
  • Neonates
  • laryngeal exam
96
Q

Mechanism of Doxapram/dopram

A
  • General CNS stimulant

- Stimulates carotid and aortic chemoreceptors

97
Q

Respiratory pharmacology considerations

A
  • Start with least toxic drugs at lowest effective dose
  • Add drugs/increase doses as needed
  • Step down drugs/doses if well controlled for 2-3 months
  • Address environment, allergens, 2° disease

Clinical Pharmacology Exam 3 (5 decks)

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