respiratory drugs Flashcards
Respiratory stimulant
Doxapram (Respiram)
-supposedly direct stimulation of respiratory center
-used in neonatal animals and anesthesia
Depression of respiration
Many drugs that negatively impact respiration
= OPIATES **reversed by Naloxone
=Any highly active sedatives= Barbiturates
Coughing
Protective reflex, not necessary a pathological sign.
Productive (mucus and debris in airway) vs. non-productive cough (irritation, but not there)
Contributors to coughing
-Glottis/trachea/bronchi pathology
-Mechanical stimuli
-inflammation
-pulmonary edema and left sided Heart Failure
-drug adverse events (ACE inhiibition)
Mechanism of coughing
- stimuli
- stimulates larynx, trachea, bronchi
- Afferent limb and vagal nerves to the Cough center in Medulla Oblongata
- Efferent limb motor nerves to the laryngeal and respiratory systems
- COUGH
Antitussive drugs
Opioids- suppress cough center in medulla. Mediated through mu and K receptors
- mu agonists
-Morphine
-Codeine (increased oral bioavailabiliy, decreased analgesia compared to morphine)
-Hydrocodone - K agonists
-Butorphanol (formerly approved in Canada)
1, 5mg oral tablets
-poor oral availability, so higher dose than used for equine IV injection
Dextromethorphan
Robitussin
-not true opioid (no mu or K binding)
-NMDA antagonists
-believed to potentially be a placebo effect
Topical analgesics
Work on preventing stimulation affecting the larynx, trachea, bronchi
“sooth the throat”
Expectorant
increase mucus hydration to volumes more easily expectorated by coughing
eg. Guaifenesin- muscle relaxant
Mucokinetics
-increase mucus transportability by coughing
eg. ambroxol
-no evidence that it works
Mucolytics
-reduce mucus viscosity by cleaving mucin disulfide bonds
-no evidence that they work
eg. N-actylcysteine
Mucoregulators
-reduce mucus hypersecretion
-no evidence they work
-Anticholinergics
Airway inflammation
- infectious
- non-infectious
Infections inflammatory airway disease
-bacterial or viral
-consider antibiotics (anti-virals)
non-infectious inflammatory airway disease
-can occur without infection
-typically some form of allergic disease
-typically use bronchodilators and anti-inflammatories
Goals of therapy for inflammatory airway disease
- maintain near normal pulmonary function
- prevent recurrent episodes of dyspnea and reduce emergency visits
- provide optimal pharmacotherapy with min adverse effects
- improve QOL for animal
feline asthma
-linked with mast cells and feline airway is therefore responsive to serotonin
Canine bronchitis and Equine RAO
-responsive to cyclo-oxygenase pathway products (PGE inhibition)
Species specific effective therapy for inflammatory airway disease
May be species specific due to inflammatory mediators causing bronchoconstriction
**differences in airway reactivity
Treatment of inflammatory airway disease
Combination of anti inflammatories and bronchodilators together!
Inflammatory disease
- Easy to breath in, difficult to breath out (EXPIRATION is issue!)
>more they try and breath out, more that airways collapse
Airway resistance
Resistance and airflow are inversely proportional
*resistance is determined by radius of tube (decrease radius=increased resistance)
Physiology of airway constriction during airway disease
Inflammatory mediators increase= increase in Ach= constriction and mucus= BAD
Physiology of normal relaxation of airways
Beta 2 agonists= muscle relaxation= GOOD
Beta 2= Bronchodilation!
Beta 2 adrenergic receptor agonists and effects on smooth muscle
Bronchial smooth muscle is innervated by beta 2 adrenergic receptors
Results in increased activity of adenylate cyclase= increase in cyclic AMP which leads to relaxation of bronchial smooth muscle
Beta 2 agonists impact on mast cells and mucus
Mast cells
-beta agonists stimulate beta receptors on mast cells leading to decreased release of inflammatory mediators (but not other inflammatory cells)
Increased Mucociliary clearance
Epi
Stimulates both alpha and beta receptors, producing vasopressive and cardiac effects
-reserved for emergency treatment of life threatening bronchoconstriction (eg. anaphylaxis)
Why not use Epi for chronic therapy of respiratory inflammatory conditions?
-side effects (nonspecific stimulation of alpha 1 and beta 1 receptors)
-short duration of action
Clenbuterol (Ventipulmin)
-Oral syrup
-beta 2 agonist approved for RAO in horses
-mostly effects airways in horses, not much on cardio system
-opens airways, but does not deal with the allergy. Open airways mean more of what horse is allergic to can enter
Therefore conflicting evidence of efficacy when used as sole therapy for treating RAO.
Adverse effects of clenbuterol
1.tachycardia and muscle tremors
-beta 2 seletive initially, then becomes beta 1 (increase HR, lipolysis)
- Tocolytic= uterine relaxation
- Banned in food animals.
-Residues in food can cause cardiotoxicity in humans
-residues detected in tissues up to yrs later
-Fat breakdown, muscle build lead to a lot of misuse of the drug =non steroidal anabolic drug
Why would someone misuse Clenbuterol in food animals?
-increased skeletal muscle blood flow
-lipolysis
**non steroidal Anabolic drug but not an anabolic steroid
Compounded clenbuterol
-Very risky
-variation with the potency of the drug can lead to many sick animals and deaths
Salbutamol aka albuterol
-blue inhaler
-Aerosol route= very rapid onset, little systemic effect
-often used in cats and horses
-intended for acute bronchoconstriction events
Why is salbutamol/albuterol not intended for repeated chronic use?
-Can lead to beta receptor down regulation resulting in less bronchodilation effects
-The S-enantiomer may also exacerbate airway inflammation in cats
Salmeterol
-disk inhalers for humans
-longer acting beta 2 agonist
Ideal drug use for respiratory
beta 2 Drugs work in the lungs with minimal systemic effects
-problem is that animals cannot time the puff
Nebulization
Creating tiny drug droplets that can be inhaled in lungs
Puffers
metered dose inhalers
Masks/spacing chambers
-nebulized particles inhaled over multiple breaths
-less drug deposited on oropharynx
-animal use!
Theophylline
-widely used in humans
-injectables, aqueous solutions, elixirs, tablets, capsules
-smilar to beta 2 agonists
-use disappeared
Anticholinegics goal
-inhibit vagally mediated bronchial smooth muscle tone= bronchodilation
anticholinergics Use
- Asthmatic humans may have excessive cholinergic stimulation
- Experimental feline asthma- long term antigen exposure can increase muscarinic receptor response to Ach
Anticholinergic options
- Atropine
- Glycopyrrolate
- Ipratropium bromide
Atropine
-use for RAO in horses
-side effects: colic and ileus
increased HR and mydriasis
Glycopyrrolate
-mostly used during anesthesia
-bronchodilation=decrease in BP
Glucocorticoids
Historic therapy for horses, dogs and cats
-high dose chronic oral glucocorticoids with the beta 2 agonists
Why use steroids?
BLUNT INFLAMMATORY RESPONSE:
-suppress generation of cytokines
-decrease recruitment of airway eosinophils (decreased leukotrienes)
Benefits of glucocorticoids on airway
- decreased severity of airway inflammatory symptoms
- decreased airway response to ongoing allergens
- possibly prevent airway wall remodelling
**increase effective airway radius=increased airflow
Concerns of using glucocorticoids
-side effects
*use lowest effective dose!
Inhalent Glucocorticoids
-less systemic absorption, decreased HPA suppression
-Options: Fluticasone (most potent), Ciclesonide
Fluticasone
-Flovent
-most potent, longest acting glucocorticoids
-available as puffer
Ciclesonide
-for horses
-enzymatically converted to the pharmacologically active metabolite
-expensive
How is ciclesonide administered?
-In horses left nostril
-use intranasal inhaler
-8-12 actuations per dose
-343 mcg ciclesonide/puff
Side effects of Ciclesonide
-coughing
-nasal discharge
**note: a lot of the medication gets stuck in nose rather than reaching airway… likely absorbed by mucosa
Efficacy of Ciclesonide
-52% vs 33% (placebo) improvement in respiratory scores
-73% vs 43% (placebo) after 10 days
Purpose of using bronchodilator for inflammatory airway disease
Treatment of inflammatory airway disease signs
-BUT causes downregulation of beta2 receptors with chronic use
**only use as needed for rescue therapy when clinical signs flare up
Purpose of steroid use for inflammatory airway disease
Prevention of airway inflammation
-used chronically even when clinical signs not apparent
Steps for using both glucocorticoids and bronchodilators together
Use together for best results
-use bronchodilator first to maximize absorption by dilating airways
-use aerosolized steroid second which will be more readily absorbed
Environmental modifications for airway disease
For RAO: hay nets, moisten feed, outdoor vs indoor housing
eg. moldy hay
For small animals: indoor air quality, allergens
Anti-leukotriene drugs
-used in human asthma
-used as chronic therapy of inflammation, not acute bronchoconstriction
**Note: leukotrienes do not cause bronchoconstriction in cats, so drug often no effect
Cyproheptadine
-blocks H1 receptor and serotonin receptor
-may be used in cats who are sensitive to serotonin induced respiratory inflammation
