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3. Clin Pharm 2 > Respiratory Pharmacotherapy-I > Flashcards

Respiratory Pharmacotherapy-I Flashcards

1
Q

Inflammatory Respiratory Disease drugs are aimed at what

A

Effective therapy aimed at inflammatory mediators and hyper-reactive bronchiole smooth muscle

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2
Q

common conditions of inflammatory resp disease

A

qFeline inflammatory bronchiole disease
> aka feline asthma
qCanine chronic bronchitis
q Equine Lower Airway Disease

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3
Q

mainstay drug types of inflammatory resp disease

A

Bronchodilators and antiinflammatories

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4
Q

goals of therapy for inflammaotry resp disease

A

qmaintain near “normal” pulmonary function
q prevent recurrent exacerbations of dyspnea reducing emergency visits
q provide optimal pharmacotherapy with minimal to no adverse effects

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5
Q

bronchodilators
- what do they do
- effects
- when they are used
- rapid acting agents include what?

A

Result in bronchodilation when bronchonstriction exists !!
q Usually also anti-inflammatory effects
q Can decrease mucosal edema
q Are symptomatic therapy and not curative
q Used in acute and chronic management of airway disease
q Rapid acting agents include adrenergic agonists, anticholinergics and methylxanthines

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6
Q

bronchodilators mechanism of action?
what is the mechanism of bronchoconstriction

A

ANS regulates airway smooth muscle tone
- beta2 receptor stimulation > smooth muscle relaxation > bronchodilation
<><>
vs.
Muscarinic stimulation or inflammatory mediator release > bronchoconstriction

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7
Q

types of bronchodilators

A
  1. Adrenergic agonists
    - Epinephrine (a, ß) and isoproterenol
    - Selective ß2-adrenergic agonists
    > Terbutaline
    > Salbutamol
    > Clenbuterol
  2. Anticholinergics
    - Ipratropium bromide
    - Hyoscine butylbromide (horse)
  3. Methylxanthine Derivatives
    - Theophylline, Aminophylline
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8
Q

most effective type of drugs for bronchodilation, why?

A

Adrenergic agonists
> result in bronchodilation regardless of cause of bronchoconstriction

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9
Q

types of adrenergic agonists used for bronchodilation? what are their effects and when are they used?

A
  • Epinephrine (a, ß) and isoproterenol (Isuprel®) (ß1,ß2) limited to acute emergencies; short acting but effective
    > Epinephrine is choice for life threatening emergency (anaphylaxis); IV route
    > Isoproterenol can be given IV or inhalation
    <><><><>
  • Selective ß2-adrenergic agonists preferred over mixed adrenergic agonists
    > do not get undesirable ß1 effects in heart
    > bronchiole smooth muscle relaxation -> bronchodilation
    > stabilize mast cells -> antiinflammatory effects
    > possible increased mucociliary clearance
    > chronic use can result in receptor desensitization
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10
Q

Selective Beta-2 adrenergic agonists used for bronchodilation

A
  • Terbutaline
  • Salbutamol
  • Clenbuterol
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11
Q

what type of drug is terbutaline?
- admin route, dose considerations
- time of action
- adverse effects

A

Bronchodilator, Selective Beta-2 adrenergic agonists
<><>
q Terbutaline by inhalation in Canada; compounded (tablets, injectable)
> High first-pass effect requires higher oral doses vs parenteral
-> Horses given injectable as oral absorption very poor
> Considered a short-acting Beta-2 agonist
q Can produce CNS and cardiac stimulation in horses; caution

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12
Q

what type of drug is salbutamol?
- duration of action
- admin route
- when used, what species
- contraindications

A

Bronchodilator, Selective Beta-2 adrenergic agonists
<><>
q Similar to terbutaline in duration of action (short)
q Usually given by inhalation; also orally (tablet, syrup) and IV available
q Used in horse and companion animals
q Use in cats with hyperresponsive airways may be
discouraged as may exacerbate airway inflammation

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13
Q

what type of drug is clenbuterol?
- animals used in
- duration of action
- efficacy
- what animals?
- contraindications
- adverse effects

A

Bronchodilator, Selective Beta-2 adrenergic agonists
<><>
q Approved for use in horses; available as syrup in Canada/Us
q Effects last for about 8 hrs following single dose
> Bronchodilating efficacy has been questioned
q Banned in food animals including horses intended for human food; avoid in pregnant mares near term
q Can get some cardiac stimulation, tachycardia, restlessness and muscle tremors as adverse effects

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14
Q

anticholinerics use in inflammaotry resp disease, mechanism of action

A

Bronchodilators
<><>
Compete with ACh at muscarinic sites (M3) in the respiratory smooth muscle inhibiting vagal mediated bronchoconstriction
> Reduce bronchoconstriction and sensitivity of irritant receptors

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15
Q

what limits long term use of atropine? what type of drug is it?

A

anticholinergic
q Systemic adverse effects limit long term use of atropine; can enter CNS

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16
Q

Hyoscine butylbromide
- what type of drug, use

A

anticholinergic bronchodilator
<><>
(Buscopan®); anticholinergic approved for use in
horses with colic; has been used successfully short term in the horse with inflammatory respiratory disease

17
Q

Ipratropium bromide
- what type of drug, use
- admin route

A

anticholinergic bronchodilator
<><>
q May be of benefit; central airway effects > peripheral airway effects
q Administered by nebulizer or aerosal (MDI) spray; largely in horses

18
Q

types of methylxanthine derivatives used for bronchodilation

A
  • Theophylline, Aminophylline
19
Q

purpose of methylxanthine derivatives, what they do

A

Long-term bronchodilatory therapy in companion animals; canine bronchitis, collapsing trachea
q Produce bronchodilation
q Antiinflammatory effects
q Inhibit mast cell degranulation
q May increase mucociliary clearance
q May increase strength of respiratory muscle contraction, reducing work
load

20
Q

Theophylline, Aminophylline
- what type of drugs are these?
- mechanism of action
- admin route
- difference between these two

A

Methylxanthine Derivatives, bronchodilators
<><>
q Phosphodiesterase inhibition and adenosine receptor antagonism may explain mechanism of action and effects
q Oral or injectable formulations available
> Slow release preparations are also used in dogs, cats, horses
q Aminophylline is a salt of theophylline; more water-soluble

21
Q

theophylline monitoring
- should we do it?
- where should we keep levels
- effects based on blood levels

A

Therapeutic drug monitoring for theophylline recommended
q Plasma concentrations of 10-20 ug/mL considered therapeutic
q Antiinflammatory effects at lower levels than bronchodilation effects

22
Q

adverse effects of methylxanthine derivatives, eg. Theophylline, Aminophylline

A

q Most concerning are cardiac stimulation effects including heart rate and possible arrhythmia
q Seen more with rapid IV administration
q CNS stimulation and excitement more noted with horses
> can also see tremors, sweating in the horse
q Careful with drug interactions
> Fluoroquinolones, cimetidine may inhibit theophylline metabolism

23
Q

what anti-inflammatory drug classes are used in inflammatory respiratory disease?

A
  • corticosteroids
  • Cyclooxygenase and Leukotriene receptor antagonists/synthesis inhibitors
  • mast-cell stabilizers
24
Q

what animals are corticosteroids used with for inflammaotry resp disease?
what types of disease?
what are corticosteroids often administered with?

A

Traditional component of airway therapy in dogs, cats, horses with inflammatory pulmonary disease…….most useful with chronic disease
q Lower airway disease in horses
q Chronic bronchitis and collapsing trachea in dogs
q Feline inflammatory bronchiole disease (feline asthma) in cats
<><>
q Given in acute exacerbations with bronchodilators

25
Q

corticosteroids for IRD mechanism

A

o not directly relax airway smooth muscle…….
q Potentiate bronchodilatory effects of catecholamines
<><>
Control airway inflammation……..
q Inhibit PLA2 conversion of AA to inflammatory molecules
q Modulating inflammatory cell (PMNs) distribution and function
q Decrease vascular permeability

26
Q

what corticosteroid drugs are used for inflammatory resp disease? how do we choose?

A

Drug selection (potency, duration of action) based on severity of clinical signs
- Prednisolone (generic),
- Isoflupredone (Predef®),
- Fluticasone (Flovent®),
- Dexamethasone (generic),
- Ciclesonide (Aservo®, EquinHaler®)

27
Q

corticosteroids for IRD admin routes, schedule for long term

A

q Administered PO or by injection, primarily in small animals, but also administered by inhalation (Fluticasone, Ciclesonide),especially in the horse)
q Taper patient off with prolonged use—withdrawal symptoms
> Not as much a concern with inhalant delivery usually

28
Q

which corticosteroid is one of the most effective options in cases of feline airway disease?

A

Oral prednisolone

29
Q

prednisone vs prednisolone for cats, horses

A

Prednisone bioavailability in horse and cat is low; use prednisolone

30
Q

Cyclooxygenase and Leukotriene receptor antagonists/synthesis inhibitors
- why they are used
- when they can be used?

A
  • Glucocorticoids remain the “gold-standard” for antiinflammatory therapy in respiratory disease, however they can result in adverse systemic effects
    <><>
  • Role of COX inhibitors in the treatment of respiratory inflammatory disease needs to be better defined…..some uses include:
    q Anti-endotoxin effects in pulmonary disease; flunixin meglumine
    q Pulmonary thromboembolic disease; antiplatelet effects of aspirin
    q Bovine respiratory disease; flunixin meglumine
31
Q

COX and Leukotriene receptor antagonists/synthesis inhibitors
- what process do they stop in the body

A

Leukotrienes are produced by 5-lipoxygenase conversion of arachiodonic acid
- LTB4, LTC4, LTD4, LTE4 can contribute to respiratory inflammation
> Chemotactic, vascular permeability, mucus secretion, bronchoconstriction
> Little evidence of a role for LTs in feline asthma
> LTB4 role in equine inflammatory respiratory disease possibly

32
Q

COX and Leukotriene receptor antagonists/synthesis inhibitors
- which human drugs are questionably / not useful in animals?

A
  • Zafirlukast, Zileuton
    > Zafirlukast is an LTC4, LTD4, LTE4 receptor antagonist but no activity at LTB4 receptors; not effective in animals
    > Zileuton is a 5-lipoxygenase inhibitor; usefulness in airway
    inflammation in animals unclear

3. Clin Pharm 2 (12 decks)

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