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Clinical Pharmacology Exam 3 > Respiratory SA > Flashcards

Respiratory SA Flashcards

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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
Oral bioavailability of butorphanol
- Better than codeine - Oral dose 10x > parenteral dose - can achieve therapeutic levels
26
Morphine receptors
- Mu and kappa agonist
27
Morphine schedule
- Schedule II
28
Oral bioavailability of morphine
- Poor oral bioavailability in dogs - Not used orally clinically - More used IV
29
Morphine pharmacokinetics in cats
- Less info | - Not used as much
30
Relative dosing of morphine used to suppress cough
- Below sedation/analgesia dose | - Above GI effects
31
Tramadol anti-tussive
- Preliminary data in humans suggests may decrease a neurogenic cough - Unknown in dogs and cats
32
Drug interactions of tramadol
- Active metabolite requires CYP450 | - CYP450 inhibitors decrease efficacy
33
Serotinergic drugs and tramadol
- Can lead to serotonin syndrome if used in combination
34
Dextromethorphan use
- Non-opioid anti-tussive
35
Dextromethorphan pharmacokinetic
- Poor bioavailability orally in dogs - Short half-life in dogs - PK unknown in cats - NOT a useful drug in SA
36
Combination products with dextromethorphan
- Combination products may contain acetaminophen, decongestants, antihistamines - not recommended for dogs - Avoid in cats
37
MOA of dextromethorphan
- NMDA antagonist - role in cough reflex? | - Agonist to some opioid receptors
38
High dose dextromethorphan side effects
- Vomiting and CNS toxicity in dogs and cats
39
OTC dextromethorphan
- Robitussin - Vicks formula 44 - NOT RECOMMENDED FOR ANIMALS
40
Use of maropitant as an anti-tussive MOA
- NK-1 receptor antagonist | - MIGHT reduce inflammation and suppress coughs
41
Maropitant treatment in dogs with chronic bronchitis
- One study had it for a 2 week long treatment - Bronchitis >2 months - No change in BAL (neutrophils, eosinophils) - Some limitations of study
42
What are bronchodilators used to treat?
- Bronchoconstriction ;)
43
What reactive airway disease in the cat do bronchodilators treat (potentially)?
- Feline asthma? | - May be targeting the wrong things
44
What reactive airway disease in the dog do bronchodilators treat (potentially)?
- Allergic bronchitis
45
Methylxanthines (theophylline) MOA
- Adenosine receptor antagonist on bronchial smooth muscle (bronchodilation) and inflammatory cells - Phosphodiesterase inhibitor (non-selective) that increases intracellular cAMP and reduces inflammation
46
Indications for methylxanthines (theophylline)
- Canine allergic bronchitis? | - Not typically used in feline asthma (dilated airways already and air just can't move out)
47
Why might methylxanthines (theophylline) not be the best choice for canine allergic bronchitis?
- 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
Adverse effects of methylxanthines (theophylline)
- CNS stimulation (irritability, tremors, seizures, hyperexcitability) - Cardiac (Tachyarrhythmias) - GI (anorexia, vomiting/nausea, and GI ulceration) - Mild diuresis
49
Methylxanthines (theophylline) clearance
- Depends on cytochrome P450 enzyme system | - Drug interactions!
50
Drug interactions with methylxanthines (theophylline)
- 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
Vet approved formulations of methylxanthines (theophylline)
- 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
Beta 2 adrenergic agonists MOA
- 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
What are the things that Beta-2 receptor agonists are specifically combatting in asthma?
- Narrowed airway - Smooth muscle contraction - Edema - Increased mucus production
54
Indications for Beta-2 receptor agonists
- Feline asthma***** - Canine allergic bronchitis (possibly) - Acute asthma attacks (emergency) as epinephrine or isoproteranol IV
55
Toxicity of non-selective Beta-2 receptor agonists, i.e. epinephrine and isoproteranol
- Epinephrine (hypertension and tachycardia) | - Isoproteranol (tachycardia0
56
Toxicity of selective Beta-2 receptor agonists, i.e. Terbutaline (IV) and albuterol (inhalant)
- High doses stimulate B1 receptors (tachycardia)
57
Tolerance and Beta-2 receptor agonists
- Receptor down regulation - Should only be used for short periods in emergency situations - Due to uncoupling of receptors from adenylate cyclcase
58
Duration of epinephrine and isoproteranol
- <1 hr
59
Nebulization an beta-2 adrenergic agents
- 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
Terbutaline and albuterol approval
- Approved for use in humans, and used in vet med
61
Terbutaline formulation***
- Injection, inhalation, tablets
62
Albuterol formulation***
- tablets, syrup, inhalation
63
Anti-cholinergics mechanism of action for anti-tussive
- Inhibit ACh receptor activation | - Remember that ACh causes bronchoconstriction and enhanced bronchial secretions
64
Anti-cholinergics indication
- Short term bronchodilation (emergency)
65
Adverse effects/toxicity of Anti-cholinergics
- Anti-DUMBSLED - Tachycardia - GI ileus - CNS excitation followed by depression/coma - Decreased mucociliary clearance
66
Examples of anti-cholinergic agents that could be used
- Atropine and glycopyrrolate
67
Atropine use in SA
- Not typically used in SA - Improved bronchoconstriction - CNS effects too
68
Glycopyrrolate adverse effects compared to atropine
- Fewer - Doesn't cross BBB - Injectable formulation
69
Cromolyn MOA
- Inhibits mast-cell degranulation, interferes with calcium transport across membrane - No bronchodilatory effects
70
Cromolyn indication***
- Effective only if administered prior to exposure to the allergen
71
Pharmacokinetics of cromolyn
- Administered via nebulization
72
What dose of steroids do you use to treat respiratory disease?
- Anti-inflammatory dose
73
Mechanism of action of corticosteroids in respiratory disease
- 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
Indications for corticosteroids
- Useful drug for asthma in people/cats
75
How can you minimize systemic side effects of corticosteroids when giving to treat respiratory disease?
- 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
Doses for corticosteroids
- DO KNOW THIS again | - review
77
Toxicity of corticosteroids in dogs
- Weight gain, GI ulceration; secondary infection
78
Drug contraindications with corticosteroids in dogs
- Do NOT use with NSAIDs
79
Toxicity of corticosteroids in cats
- Weight gain - Hyperglycemia (risk of diabetes mellitus) - 2° infection
80
Oral/injectable of corticosteroids
- 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
Anti-inflammatory drugs that are inhaled
- Fluticasone proprionate**** (Flovent) | - There are a lot of others too
82
Which steroid (prednisone/prednisolone) do you want to use in cats?
- Prednisolone | - Prednisone is not orally bioavailable in cats
83
Expectorants/mucolytics in dogs and cats
- beneficial? | - Used frequently in people and less so in vet med
84
Rationale for mucolytics/expectorants
- Decrease viscosity of secretions - Enhance clearance of bronchial exudate - Promote more productive cough
85
Saline expectorant MOA
- Stimulate gastric mucosa --> vagus stimulation --> increased GI AND bronchial secretions - Nebulizing
86
Guaifenesin glyceryl usage
- 1° use is muscle relaxant for anesthetic purpose - May also have expectorant effects via vagal stimulation - OTC formulations (human): robutussin, mucinex
87
N-acetylcysteine overview
- Mucolytic | - True mucolytic - sulfhydryl group breaks disfulide bonds of mucus
88
N-acetylcysteine MOA
- Disulfide bonds hold mucus tight and Mucomyst breaks them up just right, Kind of like a lung shampoo, for breaking up tenacious goo
89
Use of decongestants
- Decrease mucus production
90
Mechanism of decongestants
- Stimulate alpha adrenergic receptors mucosa in nasal mucosa --> vasoconstriction
91
Available agents for decongestants
- Phenylephrine | - Phenylpropanolamine (long acting oxymetazole or Afrin; for urinary continence; appropriate?)
92
Decongestant problems with chronic use
- Rebound vasodilation --> greater mucus production
93
Systemic decongestants available
- Pseudoephedrine | - Phenylpropanolamine
94
Pseudoephedrine, ephedrine, and PPA misuse
- Can be used to manufacture methamphetamine so hard to get
95
Dopram or Doxapram use
- Stimulates respiratory center in emergency situations - Anesthetic emergencies - Overdoses (opiates, benzodiazepines, macrocyclic lactones) - Neonates - laryngeal exam
96
Mechanism of Doxapram/dopram
- General CNS stimulant | - Stimulates carotid and aortic chemoreceptors
97
Respiratory pharmacology considerations
- 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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