Respiratory Pharmacology Flashcards
How does the cough reflex work? What stimulates it?
afferent arc receives input from sensory nerves in the bronchial and tracheal airways to activate the cough center in the medulla oblongata
foreign bodies or excessive mucus on the surface of the airways
How do opioids work as antitussives? What are the main 2 used? What is the point of administering them before surgery?
directly depress the cough center in the medulla by acting on mu or kappa opiate receptors
- Butorphanol (Torbutrol) - kappa receptor agonist
- Codeine - mu receptor agonist
provides a sedative effect, analgesia, and facilitates intubation by decreasing associated laryngeal spasms and coughing
Why is Codeine only occasionally used in dogs? How does Hydrocodone compare to Codeine?
oral absorption is low and inconsistent
same mechanism of action, more potent
What 3 drugs is Hydrocodone combined with?
- Hycodan - anticholinergic
- Homatropine - discourages abuse
- Acetaminophen
Why is the oral availability of Butorphanol low? How does it compare to Codeine?
first pass metabolism —> oral doses are higher than parenteral doses
maximum effects are reached within 4 hours and persists for 10 hours —> Codeine’s effect is much shorter
What are 5 uses of β-adrenergic agonists in animals?
- airway disease
- allergic bronchitis
- feline asthma
- recurrent airway obstruction (RAO - heaves)
- inflammatory airway disease (IAD) in horses
What is the mechanism of action of β-adrenergic agonists in the respiratory system?
stimulates bronchial smooth muscle, leading to increased activity of adenylate cyclase and cAMP —> smooth muscle relaxation and bronchodilation
What 2 additional effects do β-adrenergic agonists have other than bronchodilation?
- release of inflammatory mediators on mast cells (little effect on other inflammatory cells)
- increase mucociliary clearance in the respiratory tract
What is the main clinical use of β-adrenergic agonists as bronchodilators?
short-term relief of bronchospasm
- repeated administration (several weeks) may diminish response by causing desensitization —> change the receptor!
What short-acting nonspecific bronchodilator is commonly used? What is it considered the drug of choice for?
Epinephrine
emergency treatment of life-threatening bronchoconstriction (anaphylactic reactions)
What are 3 long-acting β2-specific bronchodilators commonly used?
- Terbutaline
- Albuterol
- Clenbuterol
How does Terbutaline compare to Isoproterenol? How is it used in horses?
longer acting (6-8 hours)
treats recurrent airway obstruction (RAO) —> injectiable
What are the 2 isoforms of Albuterol? How is it administered to horses?
- R-isofomrm
- L-isoform: bronchoconstriction and proinflammatory
insertion of a nasal bulb into the horse’s nostril, which is activated when the horse inhales
What is Clenbuterol approved for use in? How does it compare to other β-agonists?
bronchodilator for horses with RAO
lower clinical efficacy —> partial agonist
What are the 2 most adverse effects of β-agonists? In what agonists is this especially common?
tachycardia and muscle tremors
- β1-agonists
- high doses of β2-agonists
What is Cromolyn? What activity does it lack? When must it be administered?
sodium cromoglycate - stabilizes mast cells in hypersensitive airways by inhibiting their release of histamines and leukotrienes
bronchodilation
before the horse is exposed to the allergen (prophylactic)
What are 3 effective parasympatholytic/antimuscarinic drugs used as bronchodilators? What is their mechanism of action?
- Atropine
- Glycopyrrolate
- N-butylscopolamine bromide (horses)
inhibit vagal-mediated cholinergic smooth muscle tone in asthmatic patients with excessive stimulation
What are the best 3 parasympatholytic/antimuscarinic drugs for treating horses with RAO?
Atropine > Isoproterenol > theophylline
What is commonly added to anticholinergic treatment of respiratory disease?
quaternary amines, like glycopyrrolate or propantheline
What is the “topical form” of Atropine?
Ipratropium bromide —> quaternary amine administered as an aerosol to horses to treat RAO
What methylxanthine is used as a bronchodilator? In what animals is its use avoided?
Theophylline
horses —> adverse effects, prohibited substance in equine sports
How does Theophylline affect the respiratory system? What are 5 other non-respiratory effects?
relax bronchial smooth muscle
- CNS stimulation (caffeine)
- mild diuresis
- mild cardiac stimulation
- gastric hypersecretion
- gastroesophageal reflux
What are the 2 mechanisms of action of Theophylline?
- inhibits phosphodiesterase, resulting in increased cAMP
- adenosine (A1 and A2) receptor inhibitor, which is responsible for constricting airways in asthmatic patients via the release of histamine and leukotrienes from mast cells
How are glucocorticoid levels affected by inflammatory pulmonary disease? What are 4 indications?
decreased
- feline tracheobronchitis (feline asthma)
- allergic bronchitis
- RAO and IAD in horses
- asthma in people
What is the mechanism of action of glucocorticoids in the respiratory system? What additional effect do they have?
bind to receptors on neutrophils and eosinophils (not as much mast cells) and inhibit the transcription of genes that produce cytokines and chemokines involved in airway inflammation (PGs, leukotrienes, platelet-activating factor)
enhance the action of β2 agonist receptors by preventing down regulation
What glucocorticoids are used in canine and feline respiratory disease?
DOGS: prednisolone, prednisone, fluticasone in metered-dose inhaler
CATS: prednisolone, methylprednisolone acetate, fluticasone in metered-dose inhaler (feline asthma)
How are glucocorticoids used to treat respiratory disease in horses? What 2 are most commonly used? When are the best results obtained?
management of RAO and IAD
- Prednisolone
- Dexamethasone
GC administration with environmental control
What is the main limitation to inhaled corticosteroids in horses? What drug is given this way?
expense of metered-dose inhaler products
Fluticasone
What are the 5 major corticosteroids available in metered-dose inhalers?
- Beclomethasone dipropionate
- Budesonide
- Flunisolide
- Fluticasone proprionate
- Triamcinolone acetonide
In what 3 ways do leukotrienes contribute to airway inflammation? What are some of these leukotrienes? Which one specifically contributes to RAO in horses?
- increase migration of eosinophils
- bronchoconstriction
- increase airway wall edema
LTB4, LTD4, LTC4, LTE4
What lipoxygenase inhibitor may have clinical significance to treat asthma? How does it work?
Zileuton —> inhibits 5-lipoxygenase, inhibiting synthesis of inflammatory leukotrienes
What 2 leukotriene receptor blockers are used to treat asthma? What receptors do they work on? What significance does this have?
- Zafirlukast
- Montelukast
cysteinyl leukotriene receptors - LTD4, LTC4, LTE4
inability to block LTB4 makes these drugs ineffective for RAO treatment in horses
What is the main function of expectorants and mucolytic drugs?
increase the output of bronchial secretions
What are some saline expectorants? What is their mechanism of action?
- ammonium chloride/carbonate
- potassium/calcium iodide
- ethylenediamine dihydroiodide
- guaifenesin (glyceryl guaiacolate, Mucinex)
- acetylcysteine (NAC, Mucomyst)
vagal-mediated reflex action on the gastric mucosa stimulates the stomach, which triggers a reflex that stimulates bronchial secretions
What is the function of decongestiants? How do they typically work?
dry up mucous membranes when rhinorrhea occurs
sympathomimetic drugs that stimulate α-receptors in mucous membranes, causing local vasoconstriction
What short-acting and long-acting decongestants are commonly used? Which ones are used during surgery?
SHORT-ACTING: Phenylephrine, Phenylpropanolamine (nasal sprays)
LONG-ACTING: Oxymetazoline, xylometazoline
short-acting decongestants are used to decrease bleeding associated with some surgical procedures in horses and dogs
What is the most common systemic decongestant? What other 2 may be used? What side effects are associated?
Pseudoephedrine (Sudafed)
Ephedrine, Pheynpropanolamine proin
oral administration —> vasoconstriction, increased blood pressure
What drug is commonly used as a respiratory stimulant? How does it work?
Doxapram - direct stimulation of medullary respiratory center and activation of the aortic and carotid chemoreceptors sensitive to CO2
What is the most common use of Doxapram?
emergencies, during anesthesia
How is Doxapram used in foals? What adverse effect is associated?
treats respiratory acidosis and increases suckling activity
hypoxic-ischemic encephalopathy (perinatal asphyxia)
