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Clinical Pharmacology > Respiratory Pharmacology > Flashcards

Respiratory Pharmacology Flashcards

1
Q

Cough reflex- what is cough initiated by?

A

By vagal afferent nerves
Cough stimulus –> larynx, trachea, bronchi –> afferent limb vagal nerves –> central control cough –> efferent limb motor nerves –> laryngeal respiratory muscles –> cough

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2
Q

What triggers the cough reflex receptors?

A

Chemicals (i.e. disinfectants), physical things, temperature/pH

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3
Q

What are the 4 phases of cough reflex?

A

Stimulus –> afterent nerves –> action potentials
Enhanced INSPIRATORY effort
Expiration against occluded upper airway
Expulsive: upper airways dilate, forceful expiration

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4
Q

dogs vs cats: respiratory or cardiac disease

A

cat- mostly respiratory (think viral!)

dog coughs- think respiratory or cardiac!!!

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5
Q

what are some common SA diseases?

A

Bronchitis (dogs)
Asthma (cats)
Tracheal/bronchial collapse (more dogs than cats i.e. maltese, shihtzu)
Pneumonia: 4 types (Viral, fungal, protozoa, bacterial)
Neoplasia

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6
Q

What are some generalized classes of cough therapy

A 
anti tussives
anti microbials
anti inflammatories
bronchodilators
mucolytics
other (obesity, temp, env)
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7
Q

Anti-tussives- categories, indication, when NOT to use?

A

Opiates vs non opiates
Coughing that interferes with QOL
**do NOT use cough suppressants with INFECTIVE causes

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8
Q

Anti tussives: Opioids MOA

A

Depress cough center in medulla oblongata (Mu or kappa receptors)
Naloxone = reversal

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9
Q

Anti tussives: Opioids– Toxicity/Drug interactions

A 
Abuse
Sedation 
Constipation 
Respiratory depression (less so with butorphanol)
Excitation/Dysphoria (cats)

“S.C.A.R.E”

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10
Q

Mu vs Kappa- actions of opioid receptors

A

See chart

FYI…???

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11
Q

Anti tussives: Opioids

Hydrocodone (what is it, schedule, abuse potential, combination uses)

A

Mu and kappa agonist
Schedule II (usually)
Less abuse potential than morphine
Avail in combination with homatropine (hycodan) or chlorpheniramine (tuxxionex)

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12
Q

Anti tussives: Opioids

Codeine (what is it, schedule, abuse potential, bioavailability, doses)

A

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

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13
Q

Anti tussives: Opioids

Butorphanol aka Torbutrol (what is it, schedule, abuse potential, bioavail)

A

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

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14
Q

Why use butorphanol in small vs large patients

A

Small tablet sizes (vs giving 10 tablets to a large dog)

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15
Q

Anti tussives: Opioids

Morphine (what is it, schedule, abuse potential, bioavail, use in cats)

A

Mu and j=kappa agonist
Schedule II
Poor oral bioavailability in dogs- Not used clinically (Butorphanol and Hydro are more avail)

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16
Q

Morphine- can suppress cough at low doses below _____ and above _____

A

Analgesic/sedation dose

GI effects

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17
Q

Anti tussives: opioid

Tramadol (data in humans, drug interactions)

A

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

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18
Q

Antitussives- non opioid
Dextromethorphan
(Bioavial, short HL, PK in cats, combination products)

A

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)

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19
Q

Dextromethorphan mechanism

A

Opiate derivative- does not stimulate opiate receptors

NMDA antagonist- role in cough reflex??

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20
Q

Dextromorphan high dose effects

A

Vomiting and CNS toxicity (dogs and cats)

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21
Q

Dextromorphan OTC

A

not rec in animals (robitussin, Vicks formula 44)

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22
Q

anti-tussives Non opioid

NK1 Receptor antagonist = Maropitant

A

2 weeks TX
Bronchitis >2 months
No change in BAL (neutrophils, eosinphils)

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23
Q

Bronchdodilators used to treat what in cats vs dogs

A

Used to treat “reactive airway disease”
cats- Feline asthma?
Dogs- allergic bronchitis

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24
Q

Bronchodilator- Methylxanthine (theophylline) (what kind of receptor, administration, selectivity)

A

Beta 2 adrenergic agonist – systemic and/or inhaled
Selective or non-selective
Anticholinergics

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25
Q

Theophylline MOA (name 2 things)

A

Adenosine receptor antagonist, esp on Bronchial smooth muscle and Inflammatory cells

PDE inhibitor (non selective): Increases intracellular cAMP + reduces inflammation

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26
Q

Theophylline indications

A

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

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27
Q

Theophylline- cats?

A

not typically used in feline asthma (airways are already dilated– just cannot move air out)

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28
Q

Theophylline adverse effects

A

CCDG

CNS stimulatory effects: irritability, tremors, seizures
Cardiac: tachycarrthmias
Diuresis (mild)
GI : Anorexia, vomiting, GI ulcers

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29
Q

Theophylline drug interactions

A

Need CYP 450 system for CLEARANCE
If using CYP INHIBITORS –> decreased clearance, increases plasma concentrations (toxicity)
ex. Fluoroquinolones, Cimetidine

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30
Q

What are CYP inducers

A

Phenobarbital, Rifampin

–> increases clearance, decreased plasma concentrations (SUB-therapeutic)

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31
Q

Theophylline drug interactions

A

Know there are MANY!!! (giant chart) DO NOT PRESCRIBE if dog is on a lot of other drugs

32
Q

Theophylline - approved formulations? adverse effects?

A

No veterinary approved formulations

Adverse effects in people. Dogs– do not split sustained release formulations

33
Q

Beta 2 adrenergic agonists MOA (effect on smooth muscle and cAMP, mast cells, and MC clearance)

A

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

34
Q

Effects of Beta 2 adrenergic agonists on Narrowed airways

A

Smooth muscle contraction
Edema
Mucus production

35
Q

Beta 2 adrenergic agonist Indications

A

Feline asthma!!!
Canine allergic bronchitis (possibly)
Acute asthma attacks (emergency– epinpephrine IV or isoproteranol IV)

36
Q

Beta 2 adrenergic agonist toxicity: non selective vs selective

A

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)

37
Q

Beta 2 adrenergic agonists: tolerance

A

Receptor down regulation
Uncoupling of receptors from adenylate cyclase

DO NOT USE FOR MONTHS ETC, mostly for emergencies!! Best during ACUTE attacks

38
Q

Beta 2 adrenergic agonists: PK considerations

A

Epinephrine and isoproteranol: duration <1 hour (CPR or ACUTE reactions!)

Nebulization: process of creating small droplets of appropriate size –> distribute into bronchi

39
Q

Beta 2 adrenergic agonists: 2 drugs taht are approved for humans and used in vet med

A

Terbutaline - inhalation, tablets

Albuterol - tabltes, syrup, inhaler

40
Q

Anticholinergics MOA

A

Inhibit Ach receptor activation

Ach –> bronchoconstriction, enhanced bronchial secretions

41
Q

Anticholinergics Indications

A

Short term bronchodilation (crisis situations)

42
Q

Anticholinergics Adverse effects/toxicity

A

Limit long term use!

Cardiac (tachycardia)
GI (ileus, constipation, dry mouth)
CNS- excitation + depression/coma
Depressed MC clearance

“CCGD”

43
Q

Anticholinergics- atropine (use in SA, effects)

A

not typ use in SA

Improved bronchoconstriction, CNS effects

44
Q

Anticholinergics- glycopyrrolate

A

Injectable formulation

Fewer adverse effects (does not cross BBB)

45
Q

Anticholinergics: cromolyn MOA

A

Inhibits mast cell degranulation, interferes with Ca2+ transport across cell membrane

No bronchodilatory effects

46
Q

Cromolyn Toxicity/drug interactions

A

None reported for vet patients

47
Q

Cromolyn indications

A

Effective only if administered prior to allergen exposure

48
Q

Cromolyn PK considerations

A

Administered via nebulization

49
Q

Bronchodilator use

A

Bronchoconstriction is only PART of the problem

Airway inflammation = key component

50
Q

Anti inflammatory agents - Corticosteroids MOA

A

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?

51
Q

Corticosteroids- indications

A

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
52
Q

Corticosteroid toxicity/drug interactions in Dogs

A

weight gain
GI ulcers
Secondary infxns

DO NOT USE IN COMBO WITH NSAIDS

53
Q

Corticosteroid toxicity/drug interactions in cats

A

weight gain

Hyperglycemia (risk of DM), secondary infxn

54
Q

Corticosteroid oral/injectables (which is IM? which is suspension tablets?)

A 
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)

55
Q

Flunisolide Dose per puff

A

250 micrograms

56
Q

Budesonide dose per pfuf

A

200 micrograms

57
Q

Triamcinolone dose per pfuf

A

100 micrograms

58
Q

Beclomethasone dipropionate dose per pfuf

A

40 or 80 micrograms

59
Q

Fluticasone proprionate dose per puff

A

44, 110, or 220 micrograms

60
Q

Corticosteroid PK considerations: prednisone

A

Not orally bioavail in cats, use Prenisolone instead

Inhaler/adapters avail for cats, dogs

61
Q

Expectorants/Mucolytics (what does itdo in people)

A

decreases viscosity of secretions
enhances bronchial exudate clearance
more productive cough

62
Q

Saline expectorants MOA

A

Stimulate gastric mucosa –> vagus stimulation –> Increased GI AND bronchial secretions

63
Q

Mucolytic- Guaifenesin (glyceryl guaiacolate) and guaiacol

A

primary use =muscle relaxant for anesthetic purpose

May have vagal stimulation –> expectorant effects

64
Q

Guaifenesin OTC formulations (people)

A

Robutussin

Mucinex

65
Q

Mucolytic - N-Acetylcysteine (Mucomyst)

What is a true mucolytic?

A

True mucolytic– sulfhydrl group breaks disulfide bonds of mucus

66
Q

N acetylcystine MOA

A

Breaks up Disulfide bonds

67
Q

Decongestants- use

A

Decrease mucus production

68
Q

Decongestants Mechanisms

A

Stimulate alpha adrenergic receptor in Nasal mucosa –> vasoconstriction

69
Q

Decongestants- Available agents (name 2 nasal sprays)

A 
Phenylephrine
Phenylpropanolamine (long acting= oxymetazoline)
70
Q

Phenylpropanolamine also used for what

A

urinary incontinence

71
Q

Decongestants- effect of chronic use

A

“rebound vasodilation” –> greater mucus production

72
Q

Decongestants: systemic agents

A

Psudoephedrine (Sudafed)

Phenylpropanolamine (PPA) – limited avail

73
Q

Why is there semi RX status with Sudafed

A

Illegal manufacturing of methamphetamine from psudoephedrine, ephedrine, and PPA

74
Q

Respiratory stimulants: Doxapram (dopram) use

A

Stimulates resp center in emergency situations (anesthetic emergencies, overdoses of opiates/benzodiazepines/macrocyclic lactones, neonates, laryngeal exam)

75
Q

Doxapram mechanism

A

General CNS stimulant

Stimulates carotid and aortic chemoreceptors

76
Q

Resp pharmacology dosing

A

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

Clinical Pharmacology (7 decks)

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