Respiratory Pharmacology Flashcards
Cough reflex- what is cough initiated by?
By vagal afferent nerves
Cough stimulus –> larynx, trachea, bronchi –> afferent limb vagal nerves –> central control cough –> efferent limb motor nerves –> laryngeal respiratory muscles –> cough
What triggers the cough reflex receptors?
Chemicals (i.e. disinfectants), physical things, temperature/pH
What are the 4 phases of cough reflex?
Stimulus –> afterent nerves –> action potentials
Enhanced INSPIRATORY effort
Expiration against occluded upper airway
Expulsive: upper airways dilate, forceful expiration
dogs vs cats: respiratory or cardiac disease
cat- mostly respiratory (think viral!)
dog coughs- think respiratory or cardiac!!!
what are some common SA diseases?
Bronchitis (dogs)
Asthma (cats)
Tracheal/bronchial collapse (more dogs than cats i.e. maltese, shihtzu)
Pneumonia: 4 types (Viral, fungal, protozoa, bacterial)
Neoplasia
What are some generalized classes of cough therapy
anti tussives anti microbials anti inflammatories bronchodilators mucolytics other (obesity, temp, env)
Anti-tussives- categories, indication, when NOT to use?
Opiates vs non opiates
Coughing that interferes with QOL
**do NOT use cough suppressants with INFECTIVE causes
Anti tussives: Opioids MOA
Depress cough center in medulla oblongata (Mu or kappa receptors)
Naloxone = reversal
Anti tussives: Opioids– Toxicity/Drug interactions
Abuse Sedation Constipation Respiratory depression (less so with butorphanol) Excitation/Dysphoria (cats)
“S.C.A.R.E”
Mu vs Kappa- actions of opioid receptors
See chart
FYI…???
Anti tussives: Opioids
Hydrocodone (what is it, schedule, abuse potential, combination uses)
Mu and kappa agonist
Schedule II (usually)
Less abuse potential than morphine
Avail in combination with homatropine (hycodan) or chlorpheniramine (tuxxionex)
Anti tussives: Opioids
Codeine (what is it, schedule, abuse potential, bioavailability, doses)
Mu and kappa agonist
Schedule II (usually)
Less abuse potential than morphine
POOR ORAL BIOAVAILABILITY in dogs/ less PK info in cats
Can suppress cough at low doses- below analgesic/sedation dose. Not good if animal has GI problems
Anti tussives: Opioids
Butorphanol aka Torbutrol (what is it, schedule, abuse potential, bioavail)
Partial mu agonist, full kappa agonist
FDA approved as antitussive for dogs
Schedule IV controlled substance
Oral bio availability is LOW: Oral dose 10x > parenteral dose. Can achieve therapuetic levels
Why use butorphanol in small vs large patients
Small tablet sizes (vs giving 10 tablets to a large dog)
Anti tussives: Opioids
Morphine (what is it, schedule, abuse potential, bioavail, use in cats)
Mu and j=kappa agonist
Schedule II
Poor oral bioavailability in dogs- Not used clinically (Butorphanol and Hydro are more avail)
Morphine- can suppress cough at low doses below _____ and above _____
Analgesic/sedation dose
GI effects
Anti tussives: opioid
Tramadol (data in humans, drug interactions)
Humans- may decrease neurogenic cough, studies in cats/dogs lacking
Drug interactions- Active metabolite requires CYP2D (so if using CYP2D inhibitors –> decreased efficacy).
Used with other serotonergic drugs –> Serotonin syndrome
MULTIMODAL = IMPORTANT
Antitussives- non opioid
Dextromethorphan
(Bioavial, short HL, PK in cats, combination products)
Poor oral bioavailablity in dogs + short HL
PK = unknown in cats
Combination products (may contain Acetominophen, decongestants, antihistamines– not rec for dogs. AVOID IN CATS)
Dextromethorphan mechanism
Opiate derivative- does not stimulate opiate receptors
NMDA antagonist- role in cough reflex??
Dextromorphan high dose effects
Vomiting and CNS toxicity (dogs and cats)
Dextromorphan OTC
not rec in animals (robitussin, Vicks formula 44)
anti-tussives Non opioid
NK1 Receptor antagonist = Maropitant
2 weeks TX
Bronchitis >2 months
No change in BAL (neutrophils, eosinphils)
Bronchdodilators used to treat what in cats vs dogs
Used to treat “reactive airway disease”
cats- Feline asthma?
Dogs- allergic bronchitis
Bronchodilator- Methylxanthine (theophylline) (what kind of receptor, administration, selectivity)
Beta 2 adrenergic agonist – systemic and/or inhaled
Selective or non-selective
Anticholinergics
Theophylline MOA (name 2 things)
Adenosine receptor antagonist, esp on Bronchial smooth muscle and Inflammatory cells
PDE inhibitor (non selective): Increases intracellular cAMP + reduces inflammation
Theophylline indications
Canine allergic bronchitis?
(Dz primarily affects large airways, which are NOT the site of BRONCHODILATORS)
Can reduce signs by allowing reduction of GC dose, improve pulmonary perfusion, reduce resp effort, stimulate mucociliary clerance, improve expiratory airflow
Theophylline- cats?
not typically used in feline asthma (airways are already dilated– just cannot move air out)
Theophylline adverse effects
CCDG
CNS stimulatory effects: irritability, tremors, seizures
Cardiac: tachycarrthmias
Diuresis (mild)
GI : Anorexia, vomiting, GI ulcers
Theophylline drug interactions
Need CYP 450 system for CLEARANCE
If using CYP INHIBITORS –> decreased clearance, increases plasma concentrations (toxicity)
ex. Fluoroquinolones, Cimetidine
What are CYP inducers
Phenobarbital, Rifampin
–> increases clearance, decreased plasma concentrations (SUB-therapeutic)
Theophylline drug interactions
Know there are MANY!!! (giant chart) DO NOT PRESCRIBE if dog is on a lot of other drugs
Theophylline - approved formulations? adverse effects?
No veterinary approved formulations
Adverse effects in people. Dogs– do not split sustained release formulations
Beta 2 adrenergic agonists MOA (effect on smooth muscle and cAMP, mast cells, and MC clearance)
Beta 2 receptors in bronchial smooth muscle increase intracellular cAMP –> Relaxation (bronchodilation)
Beta 2 receptors on mast cells –> decreases release of inflammatory mediators + inceases mucociliary clearance
Effects of Beta 2 adrenergic agonists on Narrowed airways
Smooth muscle contraction
Edema
Mucus production
Beta 2 adrenergic agonist Indications
Feline asthma!!!
Canine allergic bronchitis (possibly)
Acute asthma attacks (emergency– epinpephrine IV or isoproteranol IV)
Beta 2 adrenergic agonist toxicity: non selective vs selective
Non selective (beta 1 and beta 2) i.e. Epinephrine (hypertension and tachycardia) and isoproteranol (tachycardia)
B2 selective agents = Terbutaline, Albuterol (high doses would stimulate B1 receptors –> tachycardia)
Beta 2 adrenergic agonists: tolerance
Receptor down regulation
Uncoupling of receptors from adenylate cyclase
DO NOT USE FOR MONTHS ETC, mostly for emergencies!! Best during ACUTE attacks
Beta 2 adrenergic agonists: PK considerations
Epinephrine and isoproteranol: duration <1 hour (CPR or ACUTE reactions!)
Nebulization: process of creating small droplets of appropriate size –> distribute into bronchi
Beta 2 adrenergic agonists: 2 drugs taht are approved for humans and used in vet med
Terbutaline - inhalation, tablets
Albuterol - tabltes, syrup, inhaler
Anticholinergics MOA
Inhibit Ach receptor activation
Ach –> bronchoconstriction, enhanced bronchial secretions
Anticholinergics Indications
Short term bronchodilation (crisis situations)
Anticholinergics Adverse effects/toxicity
Limit long term use!
Cardiac (tachycardia)
GI (ileus, constipation, dry mouth)
CNS- excitation + depression/coma
Depressed MC clearance
“CCGD”
Anticholinergics- atropine (use in SA, effects)
not typ use in SA
Improved bronchoconstriction, CNS effects
Anticholinergics- glycopyrrolate
Injectable formulation
Fewer adverse effects (does not cross BBB)
Anticholinergics: cromolyn MOA
Inhibits mast cell degranulation, interferes with Ca2+ transport across cell membrane
No bronchodilatory effects
Cromolyn Toxicity/drug interactions
None reported for vet patients
Cromolyn indications
Effective only if administered prior to allergen exposure
Cromolyn PK considerations
Administered via nebulization
Bronchodilator use
Bronchoconstriction is only PART of the problem
Airway inflammation = key component
Anti inflammatory agents - Corticosteroids MOA
Decreases inflammation by a variety of mechs
Increases beta 2 adrenegic mediated bronchial smooth muscle relaxation
May prevent down regulation of beta 2 adrenergic receptors/Tolerance
Synergistic with theophylline?
Corticosteroids- indications
Useful for asthma in people and cats
Topical drug delivery (inhalers) minimize (not eliminate) systemic side effects
- Feline asthma
- allergic bronchitis and non septic pulmonary disease
Corticosteroid toxicity/drug interactions in Dogs
weight gain
GI ulcers
Secondary infxns
DO NOT USE IN COMBO WITH NSAIDS
Corticosteroid toxicity/drug interactions in cats
weight gain
Hyperglycemia (risk of DM), secondary infxn
Corticosteroid oral/injectables (which is IM? which is suspension tablets?)
Prenisone/Prenisolone = oral Methylprednisolone acetate (Depo-Medro) - IM injection, used occasionally in fractious cats (lasts 3-4 weeks)
Dexamethasone tablets or suspension (potent- avoid in cats and dogs)
Flunisolide Dose per puff
250 micrograms
Budesonide dose per pfuf
200 micrograms
Triamcinolone dose per pfuf
100 micrograms
Beclomethasone dipropionate dose per pfuf
40 or 80 micrograms
Fluticasone proprionate dose per puff
44, 110, or 220 micrograms
Corticosteroid PK considerations: prednisone
Not orally bioavail in cats, use Prenisolone instead
Inhaler/adapters avail for cats, dogs
Expectorants/Mucolytics (what does itdo in people)
decreases viscosity of secretions
enhances bronchial exudate clearance
more productive cough
Saline expectorants MOA
Stimulate gastric mucosa –> vagus stimulation –> Increased GI AND bronchial secretions
Mucolytic- Guaifenesin (glyceryl guaiacolate) and guaiacol
primary use =muscle relaxant for anesthetic purpose
May have vagal stimulation –> expectorant effects
Guaifenesin OTC formulations (people)
Robutussin
Mucinex
Mucolytic - N-Acetylcysteine (Mucomyst)
What is a true mucolytic?
True mucolytic– sulfhydrl group breaks disulfide bonds of mucus
N acetylcystine MOA
Breaks up Disulfide bonds
Decongestants- use
Decrease mucus production
Decongestants Mechanisms
Stimulate alpha adrenergic receptor in Nasal mucosa –> vasoconstriction
Decongestants- Available agents (name 2 nasal sprays)
Phenylephrine Phenylpropanolamine (long acting= oxymetazoline)
Phenylpropanolamine also used for what
urinary incontinence
Decongestants- effect of chronic use
“rebound vasodilation” –> greater mucus production
Decongestants: systemic agents
Psudoephedrine (Sudafed)
Phenylpropanolamine (PPA) – limited avail
Why is there semi RX status with Sudafed
Illegal manufacturing of methamphetamine from psudoephedrine, ephedrine, and PPA
Respiratory stimulants: Doxapram (dopram) use
Stimulates resp center in emergency situations (anesthetic emergencies, overdoses of opiates/benzodiazepines/macrocyclic lactones, neonates, laryngeal exam)
Doxapram mechanism
General CNS stimulant
Stimulates carotid and aortic chemoreceptors
Resp pharmacology dosing
start with least toxic drug at lowest effective dose, add drugs or increase doses as needed
step down drugs if well controlled for 2-3 months
address environment, allergens, secondary diseaes
