Respiratory SA Flashcards
Purpose of cough reflex
- Protect airways and lungs
- Clear airways of accumulated secretions
Which nerves initiate the cough reflex?
- Vagal afferent nerves
Cough reflex
- Stimuli (chemical, physical, temperature/pH) stimulates larynx, trachea, or bronchi
- Afferent limb of vagal nerves carries to cough center in the medulla oblongata
- Efferent limb (motor nerves) signals to to laryngeal and respiratory muscles to cough
4 phases of the cough reflex?
- Action potentials by afferent nerves to stimulus
- Enhanced inspiratory effort
- Expiration against occluded upper airway
- Expulsive: upper airways dilate, forceful expiration
Common SA respiratory diseases
- Bronchitis
- Asthma
- Tracheal/bronchial collapse
- Pneumonia (think viral, bacterial, protozoal, parasitic)
- Neoplasia
What are the classes of anti-tussives?
- Opiates
- Non-opiates
Indication of anti-tussives?
- Coughing that interferes with quality of life
Contraindications for anti-tussives?
- DO NOT USE WITH INFECTIVE COUGHS
MOA of anti-tussives
- Depress coughing center in the medulla oblongata
- Mu or kappa receptors
What can reverse effects of opioid anti-tussives?
- Naloxone
Toxicity and drug interactions of opiates
- Potential for abuse
- Sedation
- Constipation
- Respiratory depression (less of a problem with butorphanol)
- Excitation/dysphoria (cats)
Actions of mu receptors
- Analgesia
- Respiratory depression
- Sedation
- Euphoria
- Physical dependence
- Decreased GI motility
Actions of kappa receptors
- Analgesia
- Sedation
- Decreased GI motility
Hydrocodone receptors activated
- Mu and kappa agonist
Schedule of Hydrocodone
- Schedule II (high potential for abuse)
- Still less abuse potential than morphine
- Difficult long-term
Combination drugs with hydrocodone
- Hycodan (combined with homatropine, an anticholinergic)
- Chlorpheniramine (antihistamine)
Formulation of hydrocodone
- SYrup
- Can be good for small dogs
Codeine receptors
- Mu and kappa agonist
Schedule of codeine
- Schedule II
Oral bioavailability of codeine
- Poor
- She prefers hydrocodone
- Less PK info in cats
Doses of codeine that suppress cough?
- Suppress cough at low doses
- Below analgesic/sedation dose
- Above GI effects
Butorphanol receptors
- Partial mu agonist
- Full kappa agonist
Use of butorphanol
- FDA approved as an antitussive for dogs
- Very frequent in cats and little dogs
BUtorphanol schedule
- Low potential for abuse, limited physical dependence
- Schedule IV controlled substance
Oral bioavailability of butorphanol
- Better than codeine
- Oral dose 10x > parenteral dose
- can achieve therapeutic levels
Morphine receptors
- Mu and kappa agonist
Morphine schedule
- Schedule II
Oral bioavailability of morphine
- Poor oral bioavailability in dogs
- Not used orally clinically
- More used IV
Morphine pharmacokinetics in cats
- Less info
- Not used as much
Relative dosing of morphine used to suppress cough
- Below sedation/analgesia dose
- Above GI effects
Tramadol anti-tussive
- Preliminary data in humans suggests may decrease a neurogenic cough
- Unknown in dogs and cats
Drug interactions of tramadol
- Active metabolite requires CYP450
- CYP450 inhibitors decrease efficacy
Serotinergic drugs and tramadol
- Can lead to serotonin syndrome if used in combination
Dextromethorphan use
- Non-opioid anti-tussive
Dextromethorphan pharmacokinetic
- Poor bioavailability orally in dogs
- Short half-life in dogs
- PK unknown in cats
- NOT a useful drug in SA
Combination products with dextromethorphan
- Combination products may contain acetaminophen, decongestants, antihistamines - not recommended for dogs
- Avoid in cats
MOA of dextromethorphan
- NMDA antagonist - role in cough reflex?
- Agonist to some opioid receptors
High dose dextromethorphan side effects
- Vomiting and CNS toxicity in dogs and cats
OTC dextromethorphan
- Robitussin
- Vicks formula 44
- NOT RECOMMENDED FOR ANIMALS
Use of maropitant as an anti-tussive MOA
- NK-1 receptor antagonist
- MIGHT reduce inflammation and suppress coughs
Maropitant treatment in dogs with chronic bronchitis
- One study had it for a 2 week long treatment
- Bronchitis >2 months
- No change in BAL (neutrophils, eosinophils)
- Some limitations of study
What are bronchodilators used to treat?
- Bronchoconstriction ;)
What reactive airway disease in the cat do bronchodilators treat (potentially)?
- Feline asthma?
- May be targeting the wrong things
What reactive airway disease in the dog do bronchodilators treat (potentially)?
- Allergic bronchitis
Methylxanthines (theophylline) MOA
- Adenosine receptor antagonist on bronchial smooth muscle (bronchodilation) and inflammatory cells
- Phosphodiesterase inhibitor (non-selective) that increases intracellular cAMP and reduces inflammation
Indications for methylxanthines (theophylline)
- Canine allergic bronchitis?
- Not typically used in feline asthma (dilated airways already and air just can’t move out)
Why might methylxanthines (theophylline) not be the best choice for canine allergic bronchitis?
- Disease primarily affects large airways, which are not the site of action of bronchodilators
- Still can reduce signs by potentially reducing dose of glucorticoid, improving pulmonary perfusion, reducing respiratory effort, stimulating mucociliary clearance, and improving expiratory airflow
Adverse effects of methylxanthines (theophylline)
- CNS stimulation (irritability, tremors, seizures, hyperexcitability)
- Cardiac (Tachyarrhythmias)
- GI (anorexia, vomiting/nausea, and GI ulceration)
- Mild diuresis
Methylxanthines (theophylline) clearance
- Depends on cytochrome P450 enzyme system
- Drug interactions!
Drug interactions with methylxanthines (theophylline)
- CYP inhibitors will increase plasma concentrations (toxicity): cimetidine and fluoroquinolones
- CYP inducers will decrease plasma concentrations (sub-therapeutic): rifampin and phenobarbital
- KNOW THAT THERE ARE MANY MANY DRUG INTERACTIONS
Vet approved formulations of methylxanthines (theophylline)
- No veterinary approved formulations
- Adverse effects in people mean limited use and availability continues to decline
- Do NOT SPLIT sustained release formulations (dogs - BID)
Beta 2 adrenergic agonists MOA
- B2 receptors in bronchial smooth muscle increase release of cAMP intracellular –> relaxation (bronchodilation)
- B2 receptors on mast cells decrease release of inflammatory mediators
- B2 receptor stimulation may increase mucociliary clearance
What are the things that Beta-2 receptor agonists are specifically combatting in asthma?
- Narrowed airway
- Smooth muscle contraction
- Edema
- Increased mucus production
Indications for Beta-2 receptor agonists
- Feline asthma*****
- Canine allergic bronchitis (possibly)
- Acute asthma attacks (emergency) as epinephrine or isoproteranol IV
Toxicity of non-selective Beta-2 receptor agonists, i.e. epinephrine and isoproteranol
- Epinephrine (hypertension and tachycardia)
- Isoproteranol (tachycardia0
Toxicity of selective Beta-2 receptor agonists, i.e. Terbutaline (IV) and albuterol (inhalant)
- High doses stimulate B1 receptors (tachycardia)
Tolerance and Beta-2 receptor agonists
- Receptor down regulation
- Should only be used for short periods in emergency situations
- Due to uncoupling of receptors from adenylate cyclcase
Duration of epinephrine and isoproteranol
- <1 hr
Nebulization an beta-2 adrenergic agents
- process of creating small droplets of appropriate size for distribution into bronchi
- Put the inhalant on their mouth and allow them to breathe in
Terbutaline and albuterol approval
- Approved for use in humans, and used in vet med
Terbutaline formulation***
- Injection, inhalation, tablets
Albuterol formulation***
- tablets, syrup, inhalation
Anti-cholinergics mechanism of action for anti-tussive
- Inhibit ACh receptor activation
- Remember that ACh causes bronchoconstriction and enhanced bronchial secretions
Anti-cholinergics indication
- Short term bronchodilation (emergency)
Adverse effects/toxicity of Anti-cholinergics
- Anti-DUMBSLED
- Tachycardia
- GI ileus
- CNS excitation followed by depression/coma
- Decreased mucociliary clearance
Examples of anti-cholinergic agents that could be used
- Atropine and glycopyrrolate
Atropine use in SA
- Not typically used in SA
- Improved bronchoconstriction
- CNS effects too
Glycopyrrolate adverse effects compared to atropine
- Fewer
- Doesn’t cross BBB
- Injectable formulation
Cromolyn MOA
- Inhibits mast-cell degranulation, interferes with calcium transport across membrane
- No bronchodilatory effects
Cromolyn indication***
- Effective only if administered prior to exposure to the allergen
Pharmacokinetics of cromolyn
- Administered via nebulization
What dose of steroids do you use to treat respiratory disease?
- Anti-inflammatory dose
Mechanism of action of corticosteroids in respiratory disease
- Decreases inflammation of airways by a variety of mechanisms
- Increases beta-2 adrenergic mediated bronchial smooth muscle relaxation
- May prevent down regulation of beta-2 adrenergic receptors (tolerance)
- Synergistic with theophylline???
Indications for corticosteroids
- Useful drug for asthma in people/cats
How can you minimize systemic side effects of corticosteroids when giving to treat respiratory disease?
- Topical drug delivery (inhalers) may minimize (WILL NOT ELIMINATE) systemic side effects
- Feline asthma and allergic bronchitis as well as non-septic pulmonary diseases
Doses for corticosteroids
- DO KNOW THIS again
- review
Toxicity of corticosteroids in dogs
- Weight gain, GI ulceration; secondary infection
Drug contraindications with corticosteroids in dogs
- Do NOT use with NSAIDs
Toxicity of corticosteroids in cats
- Weight gain
- Hyperglycemia (risk of diabetes mellitus)
- 2° infection
Oral/injectable of corticosteroids
- prednisone/prednisolone
- There is a Depo version that can last 3-4 weeks as well
- Dexamethasone suspension or tablets (potent; avoid in cats and dogs)
Anti-inflammatory drugs that are inhaled
- Fluticasone proprionate** (Flovent)
- There are a lot of others too
Which steroid (prednisone/prednisolone) do you want to use in cats?
- Prednisolone
- Prednisone is not orally bioavailable in cats
Expectorants/mucolytics in dogs and cats
- beneficial?
- Used frequently in people and less so in vet med
Rationale for mucolytics/expectorants
- Decrease viscosity of secretions
- Enhance clearance of bronchial exudate
- Promote more productive cough
Saline expectorant MOA
- Stimulate gastric mucosa –> vagus stimulation –> increased GI AND bronchial secretions
- Nebulizing
Guaifenesin glyceryl usage
- 1° use is muscle relaxant for anesthetic purpose
- May also have expectorant effects via vagal stimulation
- OTC formulations (human): robutussin, mucinex
N-acetylcysteine overview
- Mucolytic
- True mucolytic - sulfhydryl group breaks disfulide bonds of mucus
N-acetylcysteine MOA
- Disulfide bonds hold mucus tight and Mucomyst breaks them up just right, Kind of like a lung shampoo, for breaking up tenacious goo
Use of decongestants
- Decrease mucus production
Mechanism of decongestants
- Stimulate alpha adrenergic receptors mucosa in nasal mucosa –> vasoconstriction
Available agents for decongestants
- Phenylephrine
- Phenylpropanolamine (long acting oxymetazole or Afrin; for urinary continence; appropriate?)
Decongestant problems with chronic use
- Rebound vasodilation –> greater mucus production
Systemic decongestants available
- Pseudoephedrine
- Phenylpropanolamine
Pseudoephedrine, ephedrine, and PPA misuse
- Can be used to manufacture methamphetamine so hard to get
Dopram or Doxapram use
- Stimulates respiratory center in emergency situations
- Anesthetic emergencies
- Overdoses (opiates, benzodiazepines, macrocyclic lactones)
- Neonates
- laryngeal exam
Mechanism of Doxapram/dopram
- General CNS stimulant
- Stimulates carotid and aortic chemoreceptors
Respiratory pharmacology considerations
- Start with least toxic drugs at lowest effective dose
- Add drugs/increase doses as needed
- Step down drugs/doses if well controlled for 2-3 months
- Address environment, allergens, 2° disease
