Respiratory Pharmacology Flashcards
__________ and _________ are part of the normal pulmonary defenses
- should not be suppressed unless they are _________, _____ or _________ debilitating to the animal
Coughing and sneezing are part of the normal pulmonary defenses
- should not be suppressed unless they are excessive, dry or physically debilitating to the animal
Cough reflex
____________ arc of the cough reflex receives input from sensory nerves in the __________ and ________ airways
→ activate the cough center in the __________ _________.
* ________ material or ________ amounts of mucus on surface of the airways can stimulate the cough reflex.
Cough reflex
Afferent arc of the cough reflex receives input from sensory nerves in the bronchial and
tracheal airways
→ activate the cough center in the medulla oblongata
* Foreign material or excessive amounts of mucus on surface of the airways can stimulate the cough reflex
Antitussives: opioids
They directly depress the cough center in the _________
→ The site of action may be either ___ or _____ opiate receptors:
* Butorphanol (Torbutrol®) → _____-receptor _____
* Codeine → ____-receptor ______
* Opioids are administered _____ to surgery to provide a ______ effect, _______ and may facilitate ________
→ Inhibition of the cough reflex may decrease ________ spasms and ______ associated with intubation
Antitussives: opioids
They directly depress the cough center in the medulla
→ The site of action may be either mu or kappa opiate receptors
* Butorphanol (Torbutrol®) → kappa-receptor agonist
* Codeine → mu-receptor agonist
* Opioids are administered prior to surgery to provide a sedative effect, analgesia and may facilitate intubation
→ Inhibition of the cough reflex may decrease laryngeal spasms and coughing associated with intubation
Antitussives: opioids
Codeine
* Occasional use in _______
* It is available as 15, 30, 60 mg tablets and oral syrups (2mg/ml)
* Codeine oral absorption in dogs is _____ and __________
Antitussives: opioids
Codeine
* Occasional use in dogs
* It is available as 15, 30, 60 mg tablets and oral syrups (2mg/ml)
* Codeine oral absorption in dogs is low and inconsistent
Antitussives: opiods
____________: Tussigon®, Hycodan®
* It is similar to codeine (______) → ____ potent
*This drug is combined with an ____________ drug → Hycodan®
→ ____________ is added to discourage abuse rather than for a respiratory indication
* It is also combined with ___________
* Oral doses administered to dogs: 0.22 – 0.25 mg/Kg q 6 – 8 h
Antitussives: opiods
Hydrocodone: Tussigon®, Hycodan®
* It is similar to codeine (MOA) → more potent
* This drug is combined with an anticholinergic drug → Hycodan®
→ homatropine is added to discourage abuse rather than for a respiratory indication
* It is also combined with acetaminophen
* Oral doses administered to dogs: 0.22 – 0.25 mg/Kg q 6 – 8 h
Antitussives: opioids
_____________: Torbutrol®, Torbugesic®
* The oral bioavailability is ____ because of the _____ pass metabolism
→ in dogs the ______ doses are higher than _________ doses
* After oral administration, the maximum effects were observed ~ __ h but persisted up to ___ h
→ Codeine’s effect in dogs is much ________
* Butorphanol is available as 1, 5, and 10 mg tablets and as an injectable solution
Antitussives: opioids
Butorphanol: Torbutrol®, Torbugesic®
* The oral bioavailability is low because of the first pass metabolism
→ in dogs the oral doses are higher than parenteral doses
* After oral administration, the maximum effects were observed ~ 4 h but
persisted up to 10 h
→ Codeine’s effect in dogs is much shorter
* Butorphanol is available as 1, 5, and 10 mg tablets and as an injectable solution
β-adrenergic receptor agonists
* They have a beneficial effect in the treatment of some airway diseases
* β –agonist are commonly used for the treatment of _____ in people
* In animals they are used for:
➢ _________ disease
➢ Allergic ________
➢ Feline ________
➢ ________ (“heaves”)
➢ ____________ airway disease (IAD) in horses
β-adrenergic receptor agonists
* They have a beneficial effect in the treatment of some airway diseases
* β –agonist are commonly used for the treatment of asthma in people
* In animals they are used for:
➢ Airway disease
➢ Allergic bronchitis
➢ Feline asthma
➢ Recurrent airway obstruction (RAO) (“heaves”)
➢ Inflammatory airway disease (IAD) in horses
β-adrenergic receptor agonists –> MOA
* Bronchial smooth muscle is innervated by ____-_____________ receptors
* The stimulation of these receptors leads to ↑ activity of ________ _______ and thus ↑ intracellular cAMP
β-adrenergic receptor agonists –> MOA
* Bronchial smooth muscle is innervated by β2-adrenergic receptors
* The stimulation of these receptors leads to ↑ activity of adenylate cyclase and thus ↑ intracellular cAMP
β-adrenergic receptor agonists MOA cont.
* Stimulation of β-receptor activity on mast cells decreases release of __________
mediators
* There is _____ effect on other inflammatory cells
* β-adrenergic agonists increase mucociliary ________ in the respiratory tract
β-adrenergic receptor agonists MOA cont.
* Stimulation of β-receptor activity on mast cells decreases release of inflammatory
mediators
* There is little effect on other inflammatory cells
* β-adrenergic agonists increase mucociliary clearance in the respiratory tract
β-adrenergic receptor agonists
Clinical use
* β-receptor agonists should be used for short-term relief of ____________.
* Repeated administrations may ________ the response (when drugs are administered
regularly for several ______).
→ Change in ______: avoid ____-term use -
1. ______________ (drug tolerance)
2. Allow drug-_____ breaks in treatment
β-adrenergic receptor agonists
Clinical use
* β-receptor agonists should be used for short-term relief of bronchospasm
* Repeated administrations may diminish the response (when drugs are administered
regularly for several weeks
→ Change in receptor: avoid long-term use :
1. Desensitization (drug tolerance)
2. Allow drug-free breaks in treatment
B-adrenergic receptor agonists
–> ______-acting _________ bronchodilators
- Epinephrine (________) is considered the drug of choice for the emergency treatment of life- threatening ___________.
→ anaphylactic reaction
Dosage: 10 μg/Kg IV or IM (it can be repeated in 15 min)
B-adrenergic receptor agonists
–> Short acting nonspecific bronchodilators
- Epinephrine (adrenaline) is considered the drug of choice for the emergency treatment of life- threatening bronchoconstriction
→ anaphylactic reaction
Dosage: 10 μg/Kg IV or IM (it can be repeated in 15 min)
β-adrenergic receptor agonists
–> _______-acting β__-specific drugs
___________: Brethine® Bricanyl®
* It is similar to _____________, but it is ______ acting (6 to 8 h)
* This drug may be injected ____ to relieve an acute episode of _____________
Dosage: → 2.5 mg q 8 h for dogs
→ 0.625 mg q 12 h for cats
→ 0.01 mg/Kg IV or IM in cats (acute case)
* It has been used in horses to treat ______. _______ preparations must be used.
β-adrenergic receptor agonists
–> longer-acting β2-specific drugs
Terbutaline: Brethine® Bricanyl®
* It is similar to isoproterenol, but it is longer acting (6 to 8 h)
* Terbutaline may be injected SC to relieve an acute episode of bronchoconstriction
Dosage: → 2.5 mg q 8 h for dogs
→ 0.625 mg q 12 h for cats
→ 0.01 mg/Kg IV or IM in cats (acute case)
* It has been used in horses to treat recurrent airway obstruction (RAO). Injectable preparations must be used
β-adrenergic receptor agonists
–> ______-acting β2-specific drugs
A. ________ (______): Proventil® Ventolin®
* It is similar to _________
- This drug has has 2 isoforms: → ___-isoform
→ ___-isoform: Broncho-________ and
_____-inflammatory properties
β-adrenergic receptor agonists
–> Longer-acting β2-specific drugs
A. Albuterol (salbutamol): Proventil® Ventolin®
* It is similar to terbutaline
Albuterol has 2 isoforms: → R-isoform
→ S-isoform Broncho-constrictive and
pro-inflammatory properties
Albuterol (Torpex®)
→ the nasal bulb is inserted into the horse’s
nostril and is activated when the horse inhales
β-adrenergic receptor agonists
________-acting β2-specific drugs
A. ____________: Ventipulmin®
* It is approved for use in horses as a _____________ (______)
* This drug has ________ clinical efficacy compared to other β-agonists (__________)
→ Partial agonist
* It is available as a syrup (100 ml and 33 ml bottles, 72.5 μg/ml) → Ventipulmin®syrup
for horses
A study in rats showed that _______-regulation of β2 receptors occurs after ten days
of treatment → 45% _______
β-adrenergic receptor agonists
longer-acting β2-specific drugs
A. Clenbuterol: Ventipulmin®
* It is approved for use in horses as a bronchodilator (RAO)
* Clenbuterol has lower clinical efficacy compared to other β-agonists (terbutaline)
→ Partial agonist
* It is available as a syrup (100 ml and 33 ml bottles, 72.5 μg/ml) → Ventipulmin®syrup
for horses
A study in rats showed that down-regulation of β2 receptors occurs after ten days
of treatment → 45% decrease
β-adrenergic receptor agonists
Adverse effects from β-agonists
* The most common adverse effects involve the __________ system and _______ muscle
→ _________
→ muscle __________
* This kind of effects can be prominent with β___-________ and can be produced by
β___-________ at high doses
* These drugs have been abused in humans and animals for the muscle-_________
properties
β-adrenergic receptor agonists
Adverse effects from β-agonists
* The most common adverse effects involve the cardiovascular system and skeletal muscle
→ tachycardia
→ muscle tremors
* This kind of effects can be prominent with β1-agonists and can be produced by
β2-agonists at high doses
* These drugs have been abused in humans and animals for the muscle-building
properties
_______ (________): Intal®
* It is used occasionally to stabilize _____ cells → ___________ airways
* This drug has no intrinsic _________ action
* This drug inhibits _____ cells release of histamine, __________ from sensitized cells
* It has been administered via inhalation ____ daily for 1 – 4 days (80 mg) to treat ____ in horses
* To be effective, it must be administered _______ the horse is exposed to the allergen → ___________ therapy
Cromolyn
Cromolyn (sodium cromoglycate): Intal®
* It is used occasionally to stabilize mast cells → hypersensitive airways
* Cromolyn has no intrinsic bronchodilator action
* Cromolyn inhibits mast cells release of histamine, leukotrienes from sensitized cells
* It has been administered via inhalation once daily for 1 – 4 days (80 mg) to treat RAO in horses
* To be effective, it must be administered before the horse is exposed to the allergen → prophylactic therapy
Cromolyn
Cromolyn (sodium cromoglycate): Intal®
* It is used occasionally to stabilize mast cells → hypersensitive
airways
* Cromolyn has no intrinsic bronchodilator action
* Cromolyn inhibits mast cells release of histamine, leukotrienes
from sensitized cells
* It has been administered via inhalation once daily for 1 – 4 days
(80 mg) to treat RAO in horses
* To be effective, it must be administered before the horse is
exposed to the allergen → prophylactic therapy
Anticholinergic Drugs - Parasympatholytic/ antimuscarinic drugs
* Atropine and glycopyrrolate are effective ___________
*_______ (______ injectable) is an effective agent for horses
MOA: Cholinergic stimulation causes _______
➢ Anticholinergic drugs ____ vagal-mediated cholinergic smooth muscle tone
➢ Asthmatic patients have _____ stimulation of cholinergic receptors
Anticholinergic Drugs - Parasympatholytic/ antimuscarinic drugs
* Atropine and glycopyrrolate are effective bronchodilators
* N-butylscopolamine bromide (NBB) (Buscopan injectable) is an effective agent for
horses
MOA: Cholinergic stimulation causes bronchoconstriction
➢ Anticholinergic drugs inhibit vagal-mediated cholinergic smooth muscle tone
➢ Asthmatic patients have excessive stimulation of cholinergic receptors
A study compared the effects of atropine, isoproterenol, and theophylline in horses with RAO. _______ at dose of 0.02 mg/Kg IV was better at relieving some signs.
________ > ________ > ______
A study compared the effects of atropine, isoproterenol, and theophylline in horses with RAO. Atropine at dose of 0.02 mg/Kg IV was better at relieving some signs.
Atropine > isoproterenol > theophylline
Parasympatholytic/antimuscarinic drugs
* Atropine is acceptable for _____-term use. 5 mg IV dose has been used as a ______ test in horses
* If anticholinergic drugs are administered, __________ ______ such as glycopyrrolate (Robinul-V®), propantheline (ProBanthine®) should be used
Parasympatholytic/antimuscarinic drugs
* Atropine is acceptable for short-term use. 5 mg IV dose has been used as a response test in horses
* If anticholinergic drugs are administered, quaternary amines such as glycopyrrolate (Robinul-V®), propantheline (ProBanthine®) should be used
“topical form of atropine”:
___________ _________ (Atrovet®) a _______ amines is administered as an ________ to horses for treatment of RAO → 180 mcg aerosol/horse.
–> _________ effects
“topical form of atropine”:
Ipratropium bromide (Atrovet®) a quaternary amines is administered as an aerosol to horses for treatment of RAO → 180 mcg aerosol/horse.
–> Adverse effects
Methylxanthines (Xanthines)
Methylxanthines: Theophylline
* Methylxanthines (theophylline) have been used as ___________ (therapy of human asthma)
* In small animals, theophylline is _____ tolerated, and _____ dosing is convenient
* In horses it is restricted by _______- effects. Theophylline is a _________ substance in
equine sports.
—> Pharmacological effects
Methylxanthines ______ bronchial smooth muscle
Nonrespiratory effects
* CNS _________ (caffeine)
* ________ (mild)
* Cardiac _________ (mild)
* Gastric ____________
* __________ reflux
Methylxanthines (Xanthines)
Methylxanthines: Theophylline
* Methylxanthines (theophylline) have been used as bronchodilators (therapy of human asthma)
* In small animals, theophylline is well tolerated, and oral dosing is convenient
* In horses it is restricted by adverse effects. Theophylline is a prohibited substance in
equine sports
—> Pharmacological effects
Methylxanthines relax bronchial smooth muscle
Nonrespiratory effects
* CNS stimulation (caffeine)
* Diuresis (mild)
* Cardiac stimulation (mild)
* Gastric hypersecretion
* Gastroesophageal reflux
