18 – Respiratory Pharmacology Flashcards
(48 cards)
1
Q
What are the drugs that impact the respiratory drive?
A
- (Doxapram: respiratory stimulant)
- Opiates: depression of respiration
- Any sedative drug: depression of respiration (ex. Barbiturates)
2
Q
Doxapram
A
- Supposedly direct stimulation of respirate center
- Uses it for neonatal animals and anesthesia
3
Q
Opiates
A
- Negatively affect respiratory drive
- *dose dependent
- Be careful: too much=stop breathing
4
Q
What is an opiate antagonist?
A
- Naloxone
5
Q
Coughing is a good thing
A
- It’s a protective reflex!
o Not necessarily a pathological sign - Productive vs. non-productive cough
6
Q
Productive cough
A
- Mucous and debris that is being brought up
7
Q
Non-productive cough
A
- Irritation of airway
- Nothing coming up
- Ex. annoying for small animal owners
8
Q
What are the contributors to coughing?
A
- Glottis/trachea/bronchi pathology (IRRITATION)
- Mechanical stimuli
- Inflammation: makes things more sensitive
- Pulmonary edema (ex. L-sided heart failure)
o Not necessarily pulmonary edema on its own - Drug adverse events: ACE inhibitors: ‘pril’ cough
9
Q
Steps of coughing
A
- Stimuli in larynx, trachea, bronchi
- Signal via vagal nerves to cough center in medulla oblongata
- Efferent limb: motor nerves to laryngeal and respiratory muslces
- COUGH
10
Q
What are some antitussive drugs?
A
- Opioids
o Mu-agonists
o Kappa-agonists - (Dextromethorphan: human cough medicine, ‘placebo’)
11
Q
What are some mu-agonists that can be used for cough suppression?
A
- Morphine
- Codeine
o Increased oral bioavailability
o Decrease analgesia compared to morphine
12
Q
Kappa-agonists that can be used for cough suppression?
A
- Butorphanol
o Poor oral bioavailability, so higher dose than used for equine IV injection
13
Q
Where do opioids work on the ‘cough’ pathway?
A
- Cough center in the medulla oblongata
14
Q
Where do topical analgesics work on the ‘cough’ pathway?
A
- Prevent stimuli in the larynx, trachea and bronchi
15
Q
‘phlegm’ drugs
A
- Expectorant: help you get more mucous and phlegm=hydrate mucous more
o Guaifenesin=weak evidence - Mucokinetics
- Mucolytics
- Mucoregulators
16
Q
What are 2 ways you can get inflammation in the airway?
A
- Infectious
- Non-infectious
17
Q
Infectious inflammation of the airway
A
- Bacterial or viral
- Consider antibiotics (anti-virals)
18
Q
Non-infectious inflammation of the airway
A
- Can occur without infection
- Typically some form of ALLERGIC disease
- Typically use bronchodilators AND anti-inflammatories
19
Q
What are the goals of therapy for inflammatory airway disease?
A
- Maintain near ‘normal’ pulmonary function
- Prevent recurrent episodes of dyspnea and reduced emergency visits
- Provide optimal pharmacotherapy with MINIMAL adverse effects
- *improve QUALITY of life for the animal
- *species specific
20
Q
Treatments are species specific to some degree
A
- Different inflammatory mediators causing bronchoconstriction
o Cats: serotonin (5-HT) and mast cells
o Dogs and horses: COX pathway products (PGE inhibition)
o Humans: different! - *using anti-inflammatories and bronchodilators TOGETHER
21
Q
What is the problem of inflammatory respiratory disease?
A
- EXPIRATION!
o Decreased radius=increased resistance=decrease airflow
22
Q
Physiology of asthma
A
- Narrowing of airway due to smooth muscle contraction
- Inflammation: thicken lining of airway=narrower
o more inflamed=more mucous=go up airway further
23
Q
what are the 2 pathways to ‘causes’ asthma
A
- BAD: Inflammatory mediators: bind to Ach=constriction and increase mucous production
- GOOD: beta2-agonists=muscle relaxation
24
Q
Beta2 agonists
A
- Bronchial smooth muscle is innervated by beta2-receptors
- Stimulation causes
o Increased activity of adenylate cyclase=increase cAMP
o *LEADS TO RELAXATION OF BRONCHIAL SMOOTH MUSCLE
25
Beta2 receptors on mast cells (in humans)
- Decreases release of inflammatory mediators
26
Beta 2 receptors on mucociliary clearance
- Increased
27
Epinephrine
- Stimulates alpha and beta receptors=produces vasopressive and cardiac effects
- Reserved for emergency treatment of life-threatening bronchoconstriction
o Ex. anaphylaxis (ex. EpiPen)
28
Why not use Epinephrine for CHRONIC therapy of respiratory inflammatory conditions?
- Side effects (on specific stimulation of alpha1 and beta1 receptors)
- Short duration of action
29
Clenbuterol (Ventipulmin) in horses!
- Ventipulmin oral syrup
- Beta2-agonist approved for RAO in horses
- Conflicting evidence of efficacy when use as sole therapy for treating RAO
o Increased efficacy when airway INFLAMMATION is controlled too
30
Spores in hay
- Clenbuterol only allows more spores to get in=increases the inflammation
31
What are the adverse effects of Clenbuterol?
- Can cause tachycardia and muscle tremors
o Not totally beta2 selective as dose increases
- If in labor=stop uterus from contracting (tocolytic)
o BANNED IN FOOD ANIMALS!
32
Why is Clenbuterol banned in food animals?
- Residues in food can cause cardiotoxicity in humans
o Detected in tissues up to years later
- ‘growth’ promoter in feedlot animals (breakdown fat and increased muscle)
Don’t compound clenbuterol!
33
Salbutamol aka albuterol (Ventolin-human form)
blue’ inhaler for acute attacks
o Aerosol route: very rapid onset, little systemic effect
- Often used in cats and horses
- *repeated, chronic uses NOT recommended
- *intended for ACUTE bronchoconstriction events
34
Why is repeated, chronic use of Salbutamol (albuterol) not recommend?
- Can lead to beta-receptor down-regulation
o Results in less bronchodilation effect
- S-enantiomer may exacerbate airway inflammation in cats
35
What is Salmeterol?
- Like Salbutamol, but longer acting beta2 agonist
- Long lipophilic chain on molecules=stuck in mucous and sits there for 12-24hours
36
How can you use inhalant (aerosol) formulations in vet med?
- Nebulization
- Metered dose inhalers=’puffers’
- Masks/spacing chambers facilitate animal use
37
What is the goal of anticholinergics ?
- inhibit vagally mediated bronchial smooth muscle tone
- NET EFFECT=bronchodilation
- Ex. asthmatic humans may have excessive cholinergic stimulation
38
Atropine test dose for horses
- BUT may cause colic or ileus
- If HR increases=horse has heaves
- Can also cause mydriasis
- *emergency!
39
Why use steroids as an anti-inflammatory drugs?
- Suppress generation of cytokines
- Decrease recruitment of airway eosinophils (decrease leukotrienes)
40
Why use steroids?
- Blunt inflammatory response
o Suppres generation of cytokines
o Decrease recruitment of airway eosinophils (decrease leukotrienes)
41
What are the beneficial effects of glucocorticoids on airway?
- Decrease severity of airway inflammatory symptoms
- Decrease airway response to ongoing allergens
- Possible prevent airway wall remodelling?
42
What is the net effect of glucocorticoids (respiratory anti-inflammatory)?
- Increase effective airway radius = INCREASE airflow
43
Systemic glucocorticoids examples
- Use LOWEST effective dose
- Dogs: Prednisone
- Cats and horses: PREDNISOLONE (low bioavailability of prednisone)
- Cats: Methylprednisolone acetate (watch for diabetes)
- Horse: Dexamethasone powder or injections
44
What are some inhalant (aerosolized) glucocoritocdes?
- *less systemic absorption=decrease HPA suppression
- Fluticasone: most potent and longest acting
- Ciclesonide
- *measure in micrograms (NOT mg like systemic)
o Small doses=minimize side effects
45
Ciclesonide (Aservo Equilhaler) for horses
- Enzymatically converted to pharmacologically active metabolite
- Intranasal inhaler (8 or 12 ‘puffs’ per dose)
- Adverse events: coughing and nasal discharge
- *expensive
46
Therapy of inflammatory airway disease: Combo of glucocorticoids with bronchodilators
- Bronchodilators: TREATMENT of signs
o Down regulation of beta2 receptors with chronic use
o *rescue therapy
- Steroid: PREVENT of inflammation
o Used chronically
- *maybe take bronchodilator first to open airway and then steroid to get into lungs better
47
If you really want to manage the inflammatory airway disease, you need to MANGE the environment!
- Horses: get rid of moldy hay
- Small animals: not sure what the driving allergen is
48
What is cyproheptadine?
- BLOCKS H1 receptor and serotonin receptor
- Cats may be sensitive to serotonin-induced respiratory inflammation
- May or may not be a good therapy?
