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PHARMACOLOGY - 2 > 18 – Respiratory Pharmacology > Flashcards

18 – Respiratory Pharmacology Flashcards

1
Q

What are the drugs that impact the respiratory drive?

A
  • (Doxapram: respiratory stimulant)
  • Opiates: depression of respiration
  • Any sedative drug: depression of respiration (ex. Barbiturates)
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2
Q

Doxapram

A
  • Supposedly direct stimulation of respirate center
  • Uses it for neonatal animals and anesthesia
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3
Q

Opiates

A
  • Negatively affect respiratory drive
  • *dose dependent
  • Be careful: too much=stop breathing
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4
Q

What is an opiate antagonist?

A
  • Naloxone
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5
Q

Coughing is a good thing

A
  • It’s a protective reflex!
    o Not necessarily a pathological sign
  • Productive vs. non-productive cough
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6
Q

Productive cough

A
  • Mucous and debris that is being brought up
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7
Q

Non-productive cough

A
  • Irritation of airway
  • Nothing coming up
  • Ex. annoying for small animal owners
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8
Q

What are the contributors to coughing?

A
  • Glottis/trachea/bronchi pathology (IRRITATION)
  • Mechanical stimuli
  • Inflammation: makes things more sensitive
  • Pulmonary edema (ex. L-sided heart failure)
    o Not necessarily pulmonary edema on its own
  • Drug adverse events: ACE inhibitors: ‘pril’ cough
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9
Q

Steps of coughing

A
  1. Stimuli in larynx, trachea, bronchi
  2. Signal via vagal nerves to cough center in medulla oblongata
  3. Efferent limb: motor nerves to laryngeal and respiratory muslces
  4. COUGH
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10
Q

What are some antitussive drugs?

A
  • Opioids
    o Mu-agonists
    o Kappa-agonists
  • (Dextromethorphan: human cough medicine, ‘placebo’)
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11
Q

What are some mu-agonists that can be used for cough suppression?

A
  • Morphine
  • Codeine
    o Increased oral bioavailability
    o Decrease analgesia compared to morphine
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12
Q

Kappa-agonists that can be used for cough suppression?

A
  • Butorphanol
    o Poor oral bioavailability, so higher dose than used for equine IV injection
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13
Q

Where do opioids work on the ‘cough’ pathway?

A
  • Cough center in the medulla oblongata
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14
Q

Where do topical analgesics work on the ‘cough’ pathway?

A
  • Prevent stimuli in the larynx, trachea and bronchi
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15
Q

‘phlegm’ drugs

A
  • Expectorant: help you get more mucous and phlegm=hydrate mucous more
    o Guaifenesin=weak evidence
  • Mucokinetics
  • Mucolytics
  • Mucoregulators
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16
Q

What are 2 ways you can get inflammation in the airway?

A
  • Infectious
  • Non-infectious
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17
Q

Infectious inflammation of the airway

A
  • Bacterial or viral
  • Consider antibiotics (anti-virals)
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18
Q

Non-infectious inflammation of the airway

A
  • Can occur without infection
  • Typically some form of ALLERGIC disease
  • Typically use bronchodilators AND anti-inflammatories
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19
Q

What are the goals of therapy for inflammatory airway disease?

A
  • Maintain near ‘normal’ pulmonary function
  • Prevent recurrent episodes of dyspnea and reduced emergency visits
  • Provide optimal pharmacotherapy with MINIMAL adverse effects
  • *improve QUALITY of life for the animal
  • *species specific
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20
Q

Treatments are species specific to some degree

A
  • Different inflammatory mediators causing bronchoconstriction
    o Cats: serotonin (5-HT) and mast cells
    o Dogs and horses: COX pathway products (PGE inhibition)
    o Humans: different!
  • *using anti-inflammatories and bronchodilators TOGETHER
21
Q

What is the problem of inflammatory respiratory disease?

A
  • EXPIRATION!
    o Decreased radius=increased resistance=decrease airflow
22
Q

Physiology of asthma

A
  • Narrowing of airway due to smooth muscle contraction
  • Inflammation: thicken lining of airway=narrower
    o more inflamed=more mucous=go up airway further
23
Q

what are the 2 pathways to ‘causes’ asthma

A
  1. BAD: Inflammatory mediators: bind to Ach=constriction and increase mucous production
  2. GOOD: beta2-agonists=muscle relaxation
24
Q

Beta2 agonists

A
  • Bronchial smooth muscle is innervated by beta2-receptors
  • Stimulation causes
    o Increased activity of adenylate cyclase=increase cAMP
    o *LEADS TO RELAXATION OF BRONCHIAL SMOOTH MUSCLE
25
Q

Beta2 receptors on mast cells (in humans)

A
  • Decreases release of inflammatory mediators
26
Q

Beta 2 receptors on mucociliary clearance

A
  • Increased
27
Q

Epinephrine

A
  • Stimulates alpha and beta receptors=produces vasopressive and cardiac effects
  • Reserved for emergency treatment of life-threatening bronchoconstriction
    o Ex. anaphylaxis (ex. EpiPen)
28
Q

Why not use Epinephrine for CHRONIC therapy of respiratory inflammatory conditions?

A
  • Side effects (on specific stimulation of alpha1 and beta1 receptors)
  • Short duration of action
29
Q

Clenbuterol (Ventipulmin) in horses!

A
  • Ventipulmin oral syrup
  • Beta2-agonist approved for RAO in horses
  • Conflicting evidence of efficacy when use as sole therapy for treating RAO
    o Increased efficacy when airway INFLAMMATION is controlled too
30
Q

Spores in hay

A
  • Clenbuterol only allows more spores to get in=increases the inflammation
31
Q

What are the adverse effects of Clenbuterol?

A
  • Can cause tachycardia and muscle tremors
    o Not totally beta2 selective as dose increases
  • If in labor=stop uterus from contracting (tocolytic)
    o BANNED IN FOOD ANIMALS!
32
Q

Why is Clenbuterol banned in food animals?

A
  • Residues in food can cause cardiotoxicity in humans
    o Detected in tissues up to years later
  • ‘growth’ promoter in feedlot animals (breakdown fat and increased muscle)

Don’t compound clenbuterol!

33
Q

Salbutamol aka albuterol (Ventolin-human form)

A

blue’ inhaler for acute attacks
o Aerosol route: very rapid onset, little systemic effect
- Often used in cats and horses
- *repeated, chronic uses NOT recommended
- *intended for ACUTE bronchoconstriction events

34
Q

Why is repeated, chronic use of Salbutamol (albuterol) not recommend?

A
  • Can lead to beta-receptor down-regulation
    o Results in less bronchodilation effect
  • S-enantiomer may exacerbate airway inflammation in cats
35
Q

What is Salmeterol?

A
  • Like Salbutamol, but longer acting beta2 agonist
  • Long lipophilic chain on molecules=stuck in mucous and sits there for 12-24hours
36
Q

How can you use inhalant (aerosol) formulations in vet med?

A
  • Nebulization
  • Metered dose inhalers=’puffers’
  • Masks/spacing chambers facilitate animal use
37
Q

What is the goal of anticholinergics ?

A
  • inhibit vagally mediated bronchial smooth muscle tone
  • NET EFFECT=bronchodilation
  • Ex. asthmatic humans may have excessive cholinergic stimulation
38
Q

Atropine test dose for horses

A
  • BUT may cause colic or ileus
  • If HR increases=horse has heaves
  • Can also cause mydriasis
  • *emergency!
39
Q

Why use steroids as an anti-inflammatory drugs?

A
  • Suppress generation of cytokines
  • Decrease recruitment of airway eosinophils (decrease leukotrienes)
40
Q

Why use steroids?

A
  • Blunt inflammatory response
    o Suppres generation of cytokines
    o Decrease recruitment of airway eosinophils (decrease leukotrienes)
41
Q

What are the beneficial effects of glucocorticoids on airway?

A
  • Decrease severity of airway inflammatory symptoms
  • Decrease airway response to ongoing allergens
  • Possible prevent airway wall remodelling?
42
Q

What is the net effect of glucocorticoids (respiratory anti-inflammatory)?

A
  • Increase effective airway radius = INCREASE airflow
43
Q

Systemic glucocorticoids examples

A
  • Use LOWEST effective dose
  • Dogs: Prednisone
  • Cats and horses: PREDNISOLONE (low bioavailability of prednisone)
  • Cats: Methylprednisolone acetate (watch for diabetes)
  • Horse: Dexamethasone powder or injections
44
Q

What are some inhalant (aerosolized) glucocoritocdes?

A
  • *less systemic absorption=decrease HPA suppression
  • Fluticasone: most potent and longest acting
  • Ciclesonide
  • *measure in micrograms (NOT mg like systemic)
    o Small doses=minimize side effects
45
Q

Ciclesonide (Aservo Equilhaler) for horses

A
  • Enzymatically converted to pharmacologically active metabolite
  • Intranasal inhaler (8 or 12 ‘puffs’ per dose)
  • Adverse events: coughing and nasal discharge
  • *expensive
46
Q

Therapy of inflammatory airway disease: Combo of glucocorticoids with bronchodilators

A
  • Bronchodilators: TREATMENT of signs
    o Down regulation of beta2 receptors with chronic use
    o *rescue therapy
  • Steroid: PREVENT of inflammation
    o Used chronically
  • *maybe take bronchodilator first to open airway and then steroid to get into lungs better
47
Q

If you really want to manage the inflammatory airway disease, you need to MANGE the environment!

A
  • Horses: get rid of moldy hay
  • Small animals: not sure what the driving allergen is
48
Q

What is cyproheptadine?

A
  • BLOCKS H1 receptor and serotonin receptor
  • Cats may be sensitive to serotonin-induced respiratory inflammation
  • May or may not be a good therapy?

PHARMACOLOGY - 2 (16 decks)

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