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Pharmacology > Respiratory Pharmacology > Flashcards

Respiratory Pharmacology Flashcards

1
Q

Respiratory protective mechanisms

A
  • Upper respiratory tract expels foreign objects (dust, foreign bodies) by sneezing and excessive nasal mucus production (runny nose)
  • Stimulation of larynx, trachea, bronchi, and larger bronchioles elicits a coughing response
  • Vocal folds in the larynx slam shut if anything stimulates the larynx (laryngospasm) (can use lidocaine when intubating a cat to prevent this)
  • Trachea and larger bronchioles have a sheet of sticky mucus that traps particles
  • Constriction of bronchioles (bronchospasm)
  • Macrophages engulf particles in the alveoli (can use them to deliver medications)
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2
Q

Airway diameter changes

A
  • Bronchoconstriction: parasympathetic system (rest and digest)
  • -Muscarinic receptors, increase in cGMP
  • -Histamine (has a mild impact)
  • -Can be induced by stimulation of irritant receptors
  • Bronchodilation: sympathetic system (fight or flight)
  • -Beta2-receptor stimulation, increase in cAMP
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3
Q

Pathophysiology of bronchoconstriction

A
  • Blocking B2 receptors allows parasympathetic to dominate –> constriction
  • Blocking cholinergic receptors allow sympathetic domination –> dilation
  • Other inflammatory mediators constrict: prostaglandins, leukotrienes
  • Serotonin plays a role in cat asthma but little in dog bronchoconstriction
  • Histamine plays a minor role (less effect than what we used to think)
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4
Q

Protective mechanisms - mucociliary apparatus

A
  • The cells lining the trachea, bronchi, and larger bronchioles have ciliated epithelium
  • 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)
  • The cilia sweep the mucus up to the larynx where the mucus is expelled or swallowed
  • The mucus sheet + the ciliated epithelium = mucociliary apparatus or mucociliary elevator (helps clean out the gunk)
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5
Q

Defense mechanism - Mucociliary system

A
  • Includes secretory action and mechanical action
  • -Ciliary action (secretory and mechanical) is increased by beta-receptor agonists
  • -Secretory action is also induced by muscarinic stimulation
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6
Q

Defense mechanism - Respiratory mononuclear phagocyte system

A
  • Protects against infection

- Releases mediators of inflammation –> decrease in airway diameter

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7
Q

Treatment

A
  1. Modify airway resistance
  2. Increase respiratory secretions
  3. Suppress the cough reflex
  4. Stimulate respiration
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8
Q

Modification of airway resistance

A
  • To improve delivery of air to the terminal portions of the respiratory tree
  • Drugs act on obstruction due to excessive secretions, edema of the mucosa
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9
Q

Bronchodilators

A

Beta-adrenergic agonists and anticholinergic agents: most effective, regardless of stimulus
-Decongestants

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10
Q

Beta-adrenergic agonists

A
  • Act on smooth muscle (reverse contraction) and decrease mucosal edema
  • Anti-inflammatory action (decrease release of inflammatory mediators)
  • May act on beta2 receptors (bronchodilation, increase watery secretion (less viscous) and rate of ciliary movement)
  • -Only beta2-receptors present in airways
  • May act on beta1 receptors (inotropic and chronotropic effect, relaxation of GI tract)
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11
Q

Decongestants

A
  • Alpha-adrenergic agonists

- Induce vascular smooth muscle constriction, decrease capillary blood flow in the bronchial mucosa (reduce edema)

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12
Q

Clinical Uses

A
  • Chronic obstructive pulmonary disease (COPD)
  • Asthma
  • Decompensated congestive heart failure
  • Intrathoracic tracheal collapse
  • Bronchospasm (foreign origin)
  • Sinusitis, rhinitis, rhinorrhea
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13
Q

Sympathomimetic Amines

A
  • Mixed agonists (bronchodilators and/or decongestants)
  • Decongestants
  • Beta agonists
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14
Q

Mixed agonists

A
  • Epinephrine
  • Ephedrine, pseudoephedrine
  • Norepinephrine
  • Isoproterenol
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15
Q

Epinephrine

A

=Prototype of adrenaline (emergency drug)

  • Hits multiple receptors: alpha1, beta1, and beta2 receptor agonist (“dirty drug”; more side-effects as a result)
  • Effects:
  • -Bronchodilation
  • -Ionotropic and chronotropic effect
  • -Vasoconstriction (increased blood pressure)
  • Uses: anaphylaxis, acute episodes of bronchospasm, mucous membrane decongestion (topical)
  • Toxicity: tremors, tachyarrhythmia, hypertension (can be catastrophic on the heart); do not use in animals with heart condition
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16
Q

Ephedrine, pseudophedrine

A
  • Less potent than epinephrine
  • Can be given orally
  • OTC decongestant
  • Occasionally used
  • Not an emergency drug
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17
Q

Norepinephrine

A
  • Alpha and beta1-adrenergic
  • Not used in respiratory therapy
  • Cardiotonic
  • Helps with tenacity of the heart
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18
Q

Isoproterenol

A
  • Beta1 and beta2-adrenergic
  • Bronchodilator and cardiotonic
  • Mainly used via inhalation to treat bronchospasm
  • Good for emergency situation
  • Low risk of cardiovascular adverse effect because no alpha adrenergic action
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19
Q

Decongestants

A

-Phenylephrine

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20
Q

Phenylephrine

A
  • Alpha-agonist
  • Used to support blood pressure
  • Topical vasoconstriction
  • Need to be careful not to increase blood pressure too much
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21
Q

Beta Agonist

A
  • Uses: to improve airway conduction in bronchial asthma and bronchospasm due to bronchitis or emphysema, and for COPD and pneumonia in horses
  • Toxicity: tremors (beta2 receptor stimulation in skeletal muscles), tachycardia (if high doses because of beta1-adrenergic effect, ex: terbutaline)
  • -Be aware of common albuterol toxicosis in dogs, as a result of chewing on albuterol-containing inhalers and liquid vials used in nebulizers for humans
  • Long-term use results in beta2-receptor down-regulation (less effective)
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22
Q

Beta Agonist examples

A
  • Clenbuterol (orally, inhalation)
  • Albuterol (orally, inhalation; emergency inhaler)
  • Terbutaline (orally, small animal)
  • Salmeterol (maintenance inhaler; horse, cat)
  • Fenoterol (longer acting; horse)
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23
Q

Albuterol

A
  • Short-acting beta2-adrenergic
  • Oral or inhaler
  • ER inhaler
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24
Q

Salmeterol

A
  • Long-acting chemical analog of albuterol (modified)
  • Maintenance inhaler
  • Used in horses and cats
  • Has better selectivity, affinity, and potency
  • Is more lipophilic compared to albuterol
  • Anti-inflammatory action: inhibits leukotriene and histamine release from mast cells
  • Recommended for maintenance therapy and pre-exercise administration for horses with mild-to-moderate airway obstruction; treats asthma in cats
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25
Q

Metered dose inhaler (MDI)

A
  • Each depression of the plunger on the canister in the inhaler “doses” out a measured amount of drug
  • The “spacer” allows the drug mist to mix with room air and dilute out some of the taste of the concentrated drug
  • Other nebulizer machines create a mist that is inhaled
  • -Problem is the droplets strike the airway walls and adhere to it - difficult to get drug deep into the respiratory tree
  • -Used in horses with recurrent airway obstruction (RAO) - formerly known as chronic obstructive pulmonary disease (COPD)
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26
Q

Albuterol sulfate HFA inhaler

A
  • FDA approved
  • Efficient way to manage feline asthma
  • Chronic regular treatment for cats with mild signs
  • For severe cases: several times a day
  • Effect of inhaled corticosteroids is less immediate - beta2-agonist inhalation helps deposit corticosteroids in small airways
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27
Q

Xanthine bronchodilators

A
  • Theophylline

- Aminophylline

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28
Q

Theophylline

A
  • Per os or injection
  • Dose depends on the percent of theophylline (multiple percentages available)
  • Effects:
  • -Bronchodilator - may increase cAMP via inhibition of phosphodiesterase
  • -Anti-inflammatory - inhibits mast cell degranulation and induces histone-D acetylase (HDAC) mucociliary clearance (to suppress the production of pro-inflammatory cytokines and alveolar macrophages)
  • -Increases mucociliary clearance
  • -Increases the strength of respiratory muscles
  • Uses:
  • -Chronic asthma (prophylactic and treatment), myocardial failure, and pulmonary edema
  • -Used as sustained release oral theophylline in cats with asthma because of the narrow therapeutic window
  • Toxicity: sympathetic activity, agitation, tremors, seizures, etc.
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29
Q

Aminophylline

A

Used IV with O2 therapy in foals with respiratory distress syndrome

30
Q

Anticholinergics

A

“Can’t pee, can’t see, can’t spit, can’t shit”
=Block the action of acetylcholine
-Primarily sympathetic (fight or flight)
-Compete with acetylcholine at muscarinic receptors
-Antagonize vagally-mediated bronchoconstriction
-Reduce sensitivity to irritant receptors
-Augment the bronchodilator effect of beta-adrenergics
-May dry secretions
-Can treat urinary incontinence

31
Q

Anticholinergic examples

A
  • Atropine
  • Ipratropium bromide
  • Glycopyrrolate
32
Q

Atropine

A
  • Aerosol (central airways) or IV (central and peripheral airways)
  • Facilitates bronchodilation in dyspneic animals
  • Drug of choice for respiratory distress caused by anti-cholinesterases
  • Many systemic side effects
  • -Reduces mucociliary clearance, induces tachycardia, urine retention, decreases gastric motility
  • -Do not use chronically in horses as it can lead to colic
33
Q

Anticholinesterase

A

Prevent destruction of acetylcholine

34
Q

Ipratropium bromide

A
  • Less systemic effects than atropine (not absorbed as well as atropine following aerolization)
  • No reduction of mucociliary clearance or drying of mucus secretions
  • Might be given chronically (adjunct to other bronchodilator therapy)
35
Q

Glycopyrrolate

A
  • 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
36
Q

Protective mechanisms - cough

A
  • Stimulus for cough comes from irritation in the larynx, trachea, bronchi, and bronchioles –> sends signals to the cough center in the brainstem
  • Motor impulses travel down to the diaphragm and respiratory muscles to produce a forceful expiration
  • Nature of cough varies due to location of stimulation
  • -Larynx and upper trachea produce a sudden retching, gagging cough (maybe laryngo-spasm)
  • -Lower trachea, bronchi, and larger bronchioles produce a more controlled, fuller, coordinated deep cough
  • Stimulus from terminal bronchioles or alveoli does NOT produce a cough (ex: pulmonary edema)
37
Q

Cough classifications

A

Productive:

  • Characterized by mucus being coughed up and expelled
  • -Excessive fluid/mucus secretions stimulated by inflammation (secondary to infection or irritant substances)

Non-productive:

  • Characterized by a sharp cough without mucus
  • -Early stages of respiratory disease
  • -Inspissated mucus (=dried out)
  • -Dehydrated animal
  • –Rehydrate patient before giving a cough suppressant
38
Q

Suppression of the cough reflex

A

Uses:

  • Mechanical irritation of bronchi
  • Infectious diseases
  • Exhaustion associated with coughing
  • Collapsing trachea
39
Q

Cough suppressant drug classifications

A
  • Central acting cough suppressants (for non-productive coughs)
  • Bronchodilators
  • Mucokinetic drugs and expectorants (removal of the irritant)
40
Q

Central acting cough suppressants

A
  • Inhibit medullary cough center by reducing its sensitivity to stimuli
  • Do not use if productive cough
  • Drugs: opioids
  • Toxicity: opioid effects on CNS (ex: sedation, respiratory depression)
41
Q

Centrally acting antitussives

A
  • Codeine
  • Hydrocodone
  • Butorphanol
  • Dextromethorphan
42
Q

Codeine

A
  • Narcotic
  • Good antitussive
  • Limited side effects (sedation, GI effects)
  • Risk of respiratory depression in a patient at risk or with high doses
43
Q

Hydrocodone

A
  • Narcotic (most commonly abused RX opioid)
  • Commonly used in dogs
  • More potent than codeine and less respiratory depressive effects
44
Q

Butorphanol

A
  • Narcotic
  • Agonist activity for analgesia and cough suppression
  • Injection possible
45
Q

Dextromethorphan

A
  • Non-narcotic
  • Low potency
  • OTC
46
Q

Mucokinetic drugs

A
  • To remove secretions
  • Increase ciliary action (beta-receptor agonists, methylxanthines)
  • Decrease viscosity of secretions (acetylcysteine that disrupts linkages in mucus)
  • -Used in bronchitis, COPD, asthma, etc.
47
Q

Expectorants

A
  • Stimulate tubulo-acinar cells indirectly (via gastric mucosa receptors) or directly, thus decrease viscosity of secretions
  • Used with infectious disease, allergy, or chronic irritation
  • Drugs: saline expectorants, guaifenesin, volatile oils (no evidence of clinical efficacy)
  • Not really a suppressant (just helps get rid of the cause of the cough faster)
48
Q

Anti-inflammatory and immunosuppressant drugs

A
  • Corticosteroids

- Mast cell stabilizers

49
Q

Corticosteroids

A
  • Inhibit phospholipase A2
  • Stabilize cell membranes, reduce edema, help suppress immune reactions
  • Sensitize smooth muscle to the action of adrenergic drugs
  • Stimulate epinephrine synthesis and inhibits its destruction
  • Usual caution for use
50
Q

Corticosteroid examples

A
  • Prednisone (oral): for chronic or allergic bronchitis and asthma in patients unresponsive to bronchodilators
  • Triamcinolone (inhaled): for patients that require beta2-agonist treatment more than twice a day
  • Fluticasone, beclomethasone, dipropionate: for foals that require several inhalations per day
51
Q

Mast cell stabilizers

A

Chromolyn sodium (but ineffective for acute asthma)

52
Q

Resistance to therapy in cases of asthma and COPD

A
  • It is recommended to use long-acting beta2-agonist in combination with corticosteroids
  • It is possible to encounter resistance to corticosteroids
53
Q

Diuretics

A

Furosemide (lasix):

  • Indications: primarily pulmonary edema or secondary to heart disease; edema associated with choking
  • Side effects: PU/PD, hyperglycemia (do not use in diabetic patients), ototoxicity (toxic to the ear)
  • Serious contraindications due to interactions with other drugs:
  • -With vasodilator - wait for stabilization of kidney function and electrolyte balance
  • -With digitalis derivatives - risk of arrhythmia
  • -With theophylline - should decrease dosage of theophylline
  • -With prednisone - potassium loss
  • -With aminoglycoside antibiotics - ototoxicity enhanced
  • Used in horses displaying frequent exercise-induced pulmonary hemorrhage (considered performance enhancing)
54
Q

Respiratory stimulants

A

Doxapram:

  • Used in drug-induced CNS depression, obstructive airway disease, neonatal asphyxia, and functional laryngeal examination
  • Side effects: hyperexcitability and convulsions
55
Q

Respiratory distress

A

=Clinically evident inability to adequately ventilate and/or oxygenate

56
Q

Possible symptoms

A
  • Abnormal sounds, posture, and/or mucus color
  • Weakness
  • Altered respiratory effort
  • Resistance to restraint
  • Dyspnea
  • Tachypnea
  • Orthopnea
  • Hyperventilation
  • Hypoventilation
57
Q

Dyspnea

A

Conscious perception of shortness of breath

58
Q

Tachypnea

A

Greater than normal respiratory rate

59
Q

Orthopnea

A

Increased respiratory distress when the patient is lying down or the chest is compressed

60
Q

Hyperventilation

A

Ventilation that exceeds metabolic demand

PaCO2 <35 mmHg at sea level

61
Q

Hypoventilation

A

Ventilation that does not meet metabolic demand

PaCO2 > 45 mmHg at sea level

62
Q

Respiratory distress - treatment

A
  • Initial and immediate treatment: re-establish adequate arterial oxygen tension and, if necessary, remove excess CO2
  • Establish airway, ventilation, and supplemental oxygen
  • Treat cause rapidly: pleural space disease, asthma (cats), pulmonary edema and contusion, pneumonia, pulmonary thromboembolism, laryngeal edema or paralysis, foreign body aspiration
63
Q

Fulminant pulmonary edema

A
  • Acute cardiogenic edema

- Non-cardiogenic edema

64
Q

Acute cardiogenic edema

A

Minimize cardiac work, improve oxygenation, resolve pulmonary edema (diuretics, vasodilators)

65
Q

Non-cardiogenic edema

A
  • Increased capillary permeability
  • Oxygen is a key element, mechanical ventilation, cautious fluid therapy, only use diuretics and vasodilators if the patient is normo-volemic, inotropic support
66
Q

Acute small airway disease

A

=Cat asthma

  • Emergency
  • -Oxygen
  • -Corticosteroids as injection (methylprednisolone sodium succinate, or dexamethasone)
  • -Bronchodilators (ex: aminophylline IM or slow IV, albuterol or salmeterol as inhalant)
  • If first line of treatment fails or if severe respiratory distress:
  • -Epinephrine (only temporary, to avoid cardiac side effects)
  • -Beta-adrenergic agonists (ex: terbutaline)
  • -Parasympathetic (ex: atropine; only temporary to avoid inspissation of secretions)
67
Q

Oxygen

A
  • Indicated for animals that are hypoxic from inadequate oxygenation (either animal is not ventilating properly or respiratory control is depressed)
  • Oxygen is very dry:
  • -Will reduce effectiveness of mucociliary apparatus by making the mucus less runny
  • -Gas should be humidified
  • Using an oxygen cage is preferable to mask in animals that are not recumbent or markedly depressed because they may fight the mask (increasing heart rate, increasing demand by the heart for oxygen which is not available –> heart problem)
68
Q

Acute respiratory distress syndrome (ARDS)

A

=Life threatening form of respiratory failure (ex: acute lung injury, non-cardiogenic pulmonary edema)

  • Severe respiratory distress refractory to supplemental oxygen
  • Clinical signs of severe pulmonary edema and inflammatory response
  • Treatment:
  • -Correct hypoxemia (mechanical ventilation, transfusion), fluids, and nutritional therapy
  • -Furosemide IV (use caution) and vasodilators if capillary pressure increases
  • -Broad spectrum antimicrobial therapy if necessary
69
Q

Collapsing trachea

A
  • ER care: oxygenotherapy, rapidly acting corticosteroids, cough suppressants, and light tranquilization
  • Long term treatment: airway dilator (aminophylline, theophylline), cough suppressant, corticosteroids, antibiotics
70
Q

Foal pneumonia

A

Treatment:

  • Antibiotherapy
  • Bronchodilators (ex: methylxanthine derivatives, theophylline or aminophylline, beta2-adrenergic agonists sometimes administered via inhalation)
  • NSAIDs to control hyperthermia (in case of severe pneumonia)
  • Oxygen delivery (when severe hypoxia)

Pharmacology (6 decks)

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