Equine Resp Pharmacology Flashcards
non infectious cough– TTW or BAL
BAL- cells in lower airways
(TTW- more diffuse, infectious)
case example- saw neutrophils and Curshman’s Spirals
RAO vs IAD
RAO over 25% neutrophils
Cough reflex- anatomy
Involuntary reflex
Sensory receptors in airway epithelia –> larynx to resp bronchioles.
Nerve fibers conduct afferent impulses within vagal, glossopharyngeal, trigeminal, phrenic nerves
do horses have more receptors in upper or lower airways
upper airways
Horses are ____ sensitive to upper airway cough receptors than other species
Less
Ex. pass stomach tube…into trachea-..more or may not cough
Anti-tussives in horses- indicated when
Persistent coughing, fatiguing, non productive cough
Not used often in horse
which anti-tussives are used infrequently in horses
Opiate agonists: Hydrocodone, Butorphanol
Non opioids: dextromethorphan
Anti tussives MOA
Direct suppression of cough center
Bronchodilators: methylxanthines (theophylline) MOA
Competitive non selective phosphodiesterase inhibitor (increases cAMP, protein kinase A, inhibits TNF-alpha and leukotriene synthesis)
Non selective adenosine receptor antagonist: Antagonization of A1, A2, A3 receptors + cardiac effects
Methylxantines- side effects
CNS excitation
arrhythmias
narrow safety margin
theophylline- effects on dexamethasone
Theophylline didn’t potentiate the effects of low dose Dexamethasone in horses with RAO
Didn’t improve lung fxn
MOA of Beta 2 adrenergic agonists (see map)
Bronchodilation, Decreased: plasma exudation, cholinergic neurotransmission, Bacterial adherence (good), Neutrophil fxn (not so good)
Increases: MC clearance
What are some selective Beta 2 agonists
Albuterol
Clenbuterol
Salmeterol
What are some non selective Beta 2 agonists
Very short acting (emergencies!)
Epinephrine
Isoproteranol
Can you use albuterol as a rescue drug
No– you get TOLERANCE (down regulation) and Tachypylaxis possibly
Uncoupling of adenylate cyclase
Toxicity/side effects of Beta 2 agonists: non selective Rescue drugs
Epi –> tachycardia, muscle fasiculations, sweating, hypertension
Isoproteranol –> tachycardia
Toxicity/side effects: Selective drugs (which ones are shorter/longer acting)
Albuterol- shorter acting
clenbuterol- longer acting
salmeterol- longer acting
Toxicity/side effects: Selective drugs
All have tachycardia, sweating, muscle fasiculations, excitation
3 indications for beta-2 agonist use
1) emergency therapy in horses w/marked airway obstruction or anaphylaxis (duration under 1 hr)
e. g. Epi and Iso
2) before exercise- relieves mild to moderate airway obstruction
3) before administration of aerosol corticosteroid preparations
why give beta 2 agonist before aerosol corticosteroid preparations
To improve pulmonary distribution of these surface active agents
Most common beta 2 agonist used in the horse
Clenbuterol- oral
Partial beta 2 agonist approved for use in horses
Clenbuterol tolerance? bioavailability? fat? inflammation?
tolerance can develop! start at low dose
excellent F of 87%
anti inflammatory properties
Tocolytic effect of clenbuterol
Slows progress of labor in dystocias
Inhaled drugs vs systemic drugs
Particles >10 micrometer– won’t go far
10 to 6 –> into cardiac inlet
5 to 1 –> into lungs
Particles as large as ____ suspended in gas and administered as aerosol
but only SMALL particles reach distal airways effectively
50 micrometers
Particle size of ___ are thetherapueitc aerosol that are maximally deposited in ___ airways
1-5 micrometers
lower airways
When does maximal deposition of inhaled drug occurs
when patients take slow, deep breaths with large tidal volumes
but difficult to control breathing patterns of aimals
Albuterol- bioavailability in horses
Poor F in horses, give with devices such as Aerohippus or Nebulization instead
Albuterol- how long does it take to work
5 min
Salmeterol- how long does it last?
8-12 hours in severe asthma horses (long acting)
salmeterol- anti inflammatory properties
inhibits leukotriene and histamamine release from mast cells reduces eosinohils (esp with RAO)
when is salmeterol recommended
maintenance in therapy and pre-exercise administration
mild to mod airway obstruction
Anti cholinergics- MOA
Parasymp system= dominant in the pulmonary ANS in mammals
PS innervation throughout tracheobronchial tree of horse
Use Muscarinic antagonist to block M3 receptor –> blocks PS
where is the greatest effect of anti cholinergics
Large central airways
where are muscarinic receptors
abundant in airway smooth muscle –> smooth muscle contraction and bronchoconstriction
M3 receptors is ___ mediated
vagally mediated, cholinergic stimulation
What is the primary mechanism of bronchospasm in severe equine asthma?
vagally mediated cholinergic stimulation of M3 receptors
Atropine
Non selective M1M2M3 antagonist
What does atropine decrease
release of intracellular Ca2+ from SR –> smooth muscle relaxation
Rapid bronchodilation in horses
Atropine duration
short (.5 to 2 hours)
Atropine use in horses
limited- except as rescue
Atropine side effects!!
Ileus
Impaired MC clearance
Increased mucus viscosity
CNS toxicity
Tachycardia
Ipatromium bromide
Synthetic anticholinergic compound
Non selective muscarinic antagonist
Ipatromium bromide usage
Leads to bronchodilation, inhibits cough
Nebulized or inhaler
Ipatromium bromide effect and lasts how long
usually in 15-30 min
Lasts 4-6 hours
N butylscopalammonium bromide AKA buscopan
Anticholinergic
Quatenary ammonium compound used for gas/spasmodic colic in horses
Potent bronchodilator
Buscopan adverse effects
minimal–
TRANSIENT tachycardia, decreased borborygmi, pupillary dilation
Buscopan maximum effect
10 min after IV
usually effect within a few min! good response
Buscopan dissipation
1 hour after admin
Buscopan as a rescue drug?
Excellent rescue drug! AND excellent for determining if bronchostriction is involved!!!
Cromolyn Sodium Intal uses
Nebulized or used with inhaler
Cromolyn MOA
Inhibits mast cell degranulation
Interferes with Ca tarnsport across cell membrane
Cromolyn – bronchodilation?
NO BRONCHODILATORY EFFECTS (must combine with another drug)
Cromolyn uses
limited uses, except in horse with known “triggers”
Cromolyn administration
Given prior to allergen exposure
Bronchconstriction is a PORTION of the problem, while ____ is a huge component
INFLAMATION
Glucocorticoids for anti inflammation, what is MOA
Increases beta 2 adrenergic mediated bronchial smooth muscle
May prevent down regulation of beta receptors
DECREASES inflammatory mediators
Corticosteroids indications
severe asthma and some cases of IAD or mild/mod asthma
horses with severe diffuse airway dz need SYSTEMIC CS
Corticosteroids pros
improves pulmonary fxn, reduces inflammation
systemic vs inhaled CS
Inhaled– won’t get distributed when severely affected horse (need systemic CS)
CS onset and dosing
within hours
increasing dose does NOT help in human or equine med
conservative dosing – why is it recommended with CS
increasing dose doesnt help
NOT DOSE DEPENDENT
CS: systemic
Dexamethasone – watch out for what
LAMINITIS
athough never proven, always worry about CS use and laminitis
CS: prednisolone vs prednisone
Prenisolone- doesn’t decrease airway inflammation obstruction, as well as Dexamethasone does
Predinisone- DOES NOT WORK!
why doesnt prednisone work
poor absorption
rapid excretion
hepatic failure of converting it to Prednisolone
CS: inhaled
effective when
horses with mild to moderate airway obstruction
CS: pros of aerosolized drug
reduces total therapeutic dose
allows direct delivery to lower resp tract
CS: 3 formulas
Fluticasone
Beclomethasone
Flunisolide
Which of the 3 inhaled CS is most potent?
Fluticasone
Fluticasone vs beclomethasone vs Flunisolide in terms of potency and $
FBF
Fluticasone = most potent and $$
Beclomethasone= moderate, similar $
Flunisolide= less potent but less $
corticosteroids and HPA
inhaled steroids can suppress HPA
up to 65% with fluticasone
CS and HPA– effects gone within ___ days
1-2 days
Immunomodulatory drug
IFN alpha
IFN alpha
endogenous immunostimulant
Antiviral
Immunomodulatory
Anti proliferative activity
IFN alpha ADMINISTRATION
ORAL!! for horses with mild asthma/IAD
this activates natural defense system in oropharynx associated with lymphoid tissue
Mucolytics uses (human med vs equine)
human med (COPD and cystic fibrosis)N
typically we don;t use with equine asthma! use more with broncho or pleural pneumonia cases
Mucolytic benefits
decreases viscosity, enhances clearance of bronchial exudates, productive cough
N acetylcysteine- mucomyst MOA
breaks disulfide bonds –> lowers viscosity
mucomyst uses
nebulizer, 20-50 mL of 10% solution q6
respiratory stimulants: Doxapram
Uses
stimulates resp center in emergency situations
neonates , anesthetic emergencies, overdose of benzodiazepines, opiates
Doxapram MOA
General CNS stimulant
Stimulates carotid and aortic chemoreceptors
Doxapram contraindications
Cerebral hemorrhage
Increased cerebral pressure
Resp stimulant: Caffeine
MOA
enhances ventilatory response (adenosine receptor A1 A2 antagonist)
Increases respiratory drive
