respiratory

what are the respiratory protective mechanisms?

• upper respiratory tract expels foreign objects by sneezing and excessive nasal mucus production

• stimulation if larynx, trachea, bronchi, and larger bronchioles elicits response

• vocal folds in the larynx can slam shut if anything stimulates the larynx

• trachea and larger bronchioles have a sheet of sticky mucus that traps particles

• constriction of bronchioles

• macrophages engulf particles in the alveoli

what controls bronchoconstriction?

• parasympathetic system (muscarinic receptors, increase in cGMP

• histamine (mild impact)

• can be induced by stimulation of irritant receptors

• blocking B2 receptors allows parasympathetic to dominate → constriction

what controls bronchodilation?

• sympathetic system (beta2-receptor stimulation, increase in cAMP)

• blocking cholinergic receptors allow sympathetic domination → dilation

what inflammatory mediators cause bronchoconstriction?

• prostaglandins

• leukotrienes

• serotonin (in cats mainly)

• histamine (barely)

what is the mucociliary apparatus?

the cells lining the trachea, bronchi, and the larger bronchioles have ciliated epithelium

how does the mucociliary apparatus work?

• mucus glands excrete sticky mucus onto the surface of the epithelial cells to form a sheet covering the cilia

• particles inhaled land on the sticky mucus (like fly paper)

• cilia sweep the mucus up to the larynx where the mucus is expelled or swallowed

• mucus sheet + ciliated epithelium = mucociliary apparatus

what does the mucociliary system do?

secretory action and mechanical action

how does the mucociliary system produce its secretory and ciliary action?

• secretory: induced by muscarinic stimulation

• ciliary: increased by beta-receptor agonists

what is the respiratory mononuclear phagocyte system?

• protects against infection

• comprised of monocytes, macrophages, and dendritic cells

• releases mediators of inflammation → decrease in airway diameter

what are the 4 types of synergistic approach?

1. modify airway resistance

2. increase respiratory secretions

3. suppress the cough reflex

4. stimulate respiration

why do we modify airway resistance?

• to improve delivery of air to the terminal portions of the respiratory tree

• to eliminate obstruction due to excessive secretions, edema of the mucosa, and spasms

what are bronchodilators?

beta-adrenergic agonists and anticholinergic agents (most effective, regardless of stimulus)

how do beta-adrenergic agonists and anticholinergic agents work?

• act on smooth muscle (reverse contraction) and decreases mucosal edema

• anti-inflammatory action (decrease release of inflammatory mediators)

where do bromchodilators act on?

• Beta2 receptors: bronchodilation, increase watery secretion and rate of ciliary movement (only in airways)

• Beta1 receptors: inotropic and chronotropic effect, relaxation of GI tract (results in the side effects of this drug class)

what are decongestants?

alpha-adrenergic agonists

what do alpha-adrenergic agonists do?

• induce vascular smooth muscle constriction

• decrease capillary blood flow in the bronchial mucosa = decreased edema

what are the clinical application of bronchodilators and decongestants?

• chronic obstructive pulmonary disease (COPD)

• asthma

• decompensated congestive heart failure

• intrathoracic tracheal collapse

• bronchospasm (foreign origin)

• sinusitis, rhinitis, rhinorrhea

what are the different types of sympathomimetic amines we use?

• mixed agonists (bronchodilators and/or decongestant)

• beta agonists

which mixed agonist(s) do we use as a respiratory drug?

epinephrine

which beta agonist(s) do we use as a respiratory drug?

1. isoproterenol

2. terbutaline

3. albuterol

4. clenbuterol

5. salmeterol

what is epinephrine and what do we use it for?

• prototype of adrenaline (alpha 1, beta 1, and beta 2 receptors agonist)

  • bronchodilation

  • inotropic and chronotropic effect

  • vasoconstriction (increase BP)

• used for: anaphylaxis, acute episodes of bronchospasm, mucous membrane decongestion (topical nasal spray)

what are the risks of using epinephrine?

tremors, tachyarrhythmia, hypertension (DON’T USE IN ANIMALS WITH A KNOWN HEART CONDITION)

what is isoproterenol and what do we use it for?

• beta agonist (beta1 + beta2-adrenergic )

• bronchodilator of short duration (<1 hour) so it should only be use in emergencies, esp for horses to treat bronchospasms

• given via inhalation or SLOW IV infusion after being diluted with saline

when should you discontinue isoprotenerol?

when heart rate doubles

what is terbutaline and what do we use it for?

• beta agonist (beta 2 selective)

• longer acting (6-8 hours) and more selective than isoproterenol

• for cats having severe bronchoconstriction episodes despite being on corticosteroids

• oral formulation given 2x daily

when should you not use terbutaline?

in cats with cardiomyopathy or glaucoma

what is albuterol and what do we use it for?

• short acting beta agonist

• MDI or nebulization for acute bronchoconstriction in cats, horses, and cattle

what happens if you do long-term use of albuterol?

results in beta2-receptors sown-regulation

what is clenbuterol and what do we use it for?

• used for equine asthma only

• short term unless concurrent with anti-inflammatories

• inhibits uterine contractions in horses and cattle

what is salmeterol (inhalation) and what do we use it for?

• beta agonist and long acting albuterol analog (lipophilic)

• used in horses and cats to improve airway conduction in bronchial asthma and bronchospasm due to bronchitis or emphysema, and for COPD and pneumonia in horses

what toxicity signs are seen with salmeterol use?

• tremors (beta2 receptor stimulation in skeletal muscles), tachycardia if high doses (e.g., terbutaline) because of beta1-adrenergic effect

• be aware of albuterol toxicosis in dogs, as a result of chewing on albuterol-containing inhalers and liquid vials used in nebulizers for humans

what is a metered dose inhaler (MDI)?

each depression of plunger on canister in the inhaler “doses” out a
measured amount of drug

what is the job os a “spacer” in a MDI?

the “spacer” allows the drug mist to mix with room air and dilute out
some of the taste of the concentrated drug

what is a nebulizer?

create a mist that is inhaled

why are nebulizers not as preferred as a MDI?

the droplets strike the airway walls and adhere to it so it’s difficult to get drug deep into respiratory tree

for what are nebulizers used?

• in horses with recurrent airway obstruction (RAO) – formerly chronic obstructive pulmonary disease (COPD)

• easier to administer to fractious cats

which decongestant(s) do we use as a respiratory drug?

phenylephrine

what is phenylephrine and how can we administer it?

• alpha 1 agonist decongestant

• oral formulation: low bioavailability in our species

  • often combined with other ingredients toxic to our
    patients

• IV formulation: used to increase blood pressure via peripheral vasoconstriction

  • avoid in pregnant animals due to cause of uterine vasoconstriction

• topical administration (ophthalmic, nasal spray)

  • topical vasoconstriction

what are xanthine bronchodilators and what do they do?

• increases the strength of respiratory muscles

• used in chronic asthma (prophylactic and treatment), myocardial failure and pulmonary edema

• in cats with asthma it’s used as sustained release oral theophylline because of short half life

what toxicity can we see when using xanthine bronchodilators?

sympathic activity, agitation, tremors, seizures, etc.

what xanthine bronchodilator(s) do we use as respiratory drugs?

oral theophylline

how is theophylline used?

dose depends on the percent of theophylline (IR vs ER)

• bronchodilator (may increase cAMP via inhibition of
  phosphodiesterase)

• anti-inflammatory (inhibits mast cells degranulation)

• increases mucociliary clearance

how do anticholinergics work?

• compete with acetylcholine at muscarinic receptors

• antagonize vagally-mediated bronchoconstriction

• reduce sensitivity to irritant receptors

• augment the bronchodilator effect of beta-adrenergics

• but....remember side effects

  • can’t SEE

  • can’t PEE

  • can’t SPIT

  • can’t SHIT

which anticholinergic(s) do we use as respiratory drugs?

• atropine

• ipratropium bromide

• glycopyrrolate

how does atropine work as a respiratory drug?

• aerosol (central airways) or IV (central and peripheral airways)

• increases heart rate (commonly used in anesthesia)

• facilitates bronchodilation in dyspneic animals

• drug of choice for respiratory distress caused by anti-cholinesterases

what side effects do we see with chronic atropine use?

• educes mucociliary clearance

• induces tachycardia

• urine retention

• decreases gastric motility

how does ipratropium bromide work as a respiratory drug?

• less systemic effects than atropine (not absorbed as well as atropine following aerolization)

• no reduction of mucociliary clearance or drying of mucus secretions

• may be given chronically (adjunct to other bronchodilator therapy)

how does glycopyrrolate work as a respiratory drug?

• bronchodilator in small animal

• longer duration of action compared to atropine and fewer side effects

• twice as potent as atropine when used as an aerosol

how is a cough produced?

1. stimulus for cough comes from irritation in the larynx, trachea, bronchi, and bronchioles → sends signal to the cough center in the brain stem

2. motor impulses travel down to diaphragm and respiratory muscles to produce a forceful expiration

where is the cough produced?

• larynx and upper trachea produces a sudden, retching, gagging cough (maybe laryngospasm)

• lower trachea, bronchi, larger bronchioles produce a more
  controlled, coordinated deep cough

T/F - stimulus from terminal bronchioles or alveoli does NOT produce a cough (e.g., pulmonary edema)

true

what are the 2 types of cough? explain each type.

1. productive cough: characterized by mucus being coughed up and expelled
   • excessive fluid/mucus secretions stimulated by inflammation (secondary to infection or irritant substances)

2. non-productive cough: characterized by sharp cough but no
   mucus brought up
   • early stages of respiratory disease
   • Inspissated mucus (dried out mucus)
   • dehydrated animals

when should you suppress the cough reflex?

• mechanical irritation of bronchi

• infectious diseases if non productive

• exhaustion associated with coughing

• collapsing trachea

which drugs do we use to suppress the cough reflex?

• central acting cough suppressants (for non productive cough)

• bronchodilators

• mucokinetic drugs and expectorants (removal of the irritant)