Respiratory Pharmacotherapy-I Flashcards
Inflammatory Respiratory Disease drugs are aimed at what
Effective therapy aimed at inflammatory mediators and hyper-reactive bronchiole smooth muscle
common conditions of inflammatory resp disease
qFeline inflammatory bronchiole disease
> aka feline asthma
qCanine chronic bronchitis
q Equine Lower Airway Disease
mainstay drug types of inflammatory resp disease
Bronchodilators and antiinflammatories
goals of therapy for inflammaotry resp disease
qmaintain near “normal” pulmonary function
q prevent recurrent exacerbations of dyspnea reducing emergency visits
q provide optimal pharmacotherapy with minimal to no adverse effects
bronchodilators
- what do they do
- effects
- when they are used
- rapid acting agents include what?
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
bronchodilators mechanism of action?
what is the mechanism of bronchoconstriction
ANS regulates airway smooth muscle tone
- beta2 receptor stimulation > smooth muscle relaxation > bronchodilation
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vs.
Muscarinic stimulation or inflammatory mediator release > bronchoconstriction
types of bronchodilators
- Adrenergic agonists
- Epinephrine (a, ß) and isoproterenol
- Selective ß2-adrenergic agonists
> Terbutaline
> Salbutamol
> Clenbuterol - Anticholinergics
- Ipratropium bromide
- Hyoscine butylbromide (horse) - Methylxanthine Derivatives
- Theophylline, Aminophylline
most effective type of drugs for bronchodilation, why?
Adrenergic agonists
> result in bronchodilation regardless of cause of bronchoconstriction
types of adrenergic agonists used for bronchodilation? what are their effects and when are they used?
- 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
Selective Beta-2 adrenergic agonists used for bronchodilation
- Terbutaline
- Salbutamol
- Clenbuterol
what type of drug is terbutaline?
- admin route, dose considerations
- time of action
- adverse effects
Bronchodilator, Selective Beta-2 adrenergic agonists
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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
what type of drug is salbutamol?
- duration of action
- admin route
- when used, what species
- contraindications
Bronchodilator, Selective Beta-2 adrenergic agonists
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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
what type of drug is clenbuterol?
- animals used in
- duration of action
- efficacy
- what animals?
- contraindications
- adverse effects
Bronchodilator, Selective Beta-2 adrenergic agonists
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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
anticholinerics use in inflammaotry resp disease, mechanism of action
Bronchodilators
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Compete with ACh at muscarinic sites (M3) in the respiratory smooth muscle inhibiting vagal mediated bronchoconstriction
> Reduce bronchoconstriction and sensitivity of irritant receptors
what limits long term use of atropine? what type of drug is it?
anticholinergic
q Systemic adverse effects limit long term use of atropine; can enter CNS
Hyoscine butylbromide
- what type of drug, use
anticholinergic bronchodilator
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(Buscopan®); anticholinergic approved for use in
horses with colic; has been used successfully short term in the horse with inflammatory respiratory disease
Ipratropium bromide
- what type of drug, use
- admin route
anticholinergic bronchodilator
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q May be of benefit; central airway effects > peripheral airway effects
q Administered by nebulizer or aerosal (MDI) spray; largely in horses
types of methylxanthine derivatives used for bronchodilation
- Theophylline, Aminophylline
purpose of methylxanthine derivatives, what they do
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
Theophylline, Aminophylline
- what type of drugs are these?
- mechanism of action
- admin route
- difference between these two
Methylxanthine Derivatives, bronchodilators
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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
theophylline monitoring
- should we do it?
- where should we keep levels
- effects based on blood levels
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
adverse effects of methylxanthine derivatives, eg. Theophylline, Aminophylline
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
what anti-inflammatory drug classes are used in inflammatory respiratory disease?
- corticosteroids
- Cyclooxygenase and Leukotriene receptor antagonists/synthesis inhibitors
- mast-cell stabilizers
what animals are corticosteroids used with for inflammaotry resp disease?
what types of disease?
what are corticosteroids often administered with?
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
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q Given in acute exacerbations with bronchodilators
corticosteroids for IRD mechanism
o not directly relax airway smooth muscle…….
q Potentiate bronchodilatory effects of catecholamines
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Control airway inflammation……..
q Inhibit PLA2 conversion of AA to inflammatory molecules
q Modulating inflammatory cell (PMNs) distribution and function
q Decrease vascular permeability
what corticosteroid drugs are used for inflammatory resp disease? how do we choose?
Drug selection (potency, duration of action) based on severity of clinical signs
- Prednisolone (generic),
- Isoflupredone (Predef®),
- Fluticasone (Flovent®),
- Dexamethasone (generic),
- Ciclesonide (Aservo®, EquinHaler®)
corticosteroids for IRD admin routes, schedule for long term
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
which corticosteroid is one of the most effective options in cases of feline airway disease?
Oral prednisolone
prednisone vs prednisolone for cats, horses
Prednisone bioavailability in horse and cat is low; use prednisolone
Cyclooxygenase and Leukotriene receptor antagonists/synthesis inhibitors
- why they are used
- when they can be used?
- 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
COX and Leukotriene receptor antagonists/synthesis inhibitors
- what process do they stop in the body
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
COX and Leukotriene receptor antagonists/synthesis inhibitors
- which human drugs are questionably / not useful in animals?
- 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
