Respiratory Pharmacology Flashcards
describe the pulmonary response to irritation
many receptors:
-stretch receptors: respond to velocity increases
-J receptors: juxtabronchial, sensitive to stuff further down in the lungs, send vagal signal to the heart to slow heart down
-irritant receptors: trigger cough or other responses when you inhale a bunch of particulate
-most signals from the brain are parasympathetic, muscarinic; mucus production, airway constriction
inflammatory cell infiltrates trigger:
1. release of histamine which stimulates afferent nerves that results in bronchoconstriction
- stimulate mucus production and increase permeability
describe bronchodilatory drugs
- sympathomimetics:
-beta agonists: albuterol
-nonspecific: ephedrine - methylxanthines:
-aminophylline
-theophylline
-caffeine - anticholinergics
describe beta agonist drugs (B1 and B2) (sympathetic drugs)
- at B1 receptors: primarily cardiac: increase heart rate and contractility
- at B2 receptors: primarily respiratory, uterine and vascular smooth muscle
-G protein coupled receptors inhibit smooth muscle contraction by decreasing intracellular calcium
-activates adenyl cyclase, converts ATP to cAMP
-decreased calcium release results in bronchodilation
describe use of beta agonist drugs at beta 2 receptors (sympathetic drugs)
- rapid onset of action; can be emergent therapy for acute bronchoconstriction, esp inhalational therapy
-onset 5-15 min, duration 2-4 hours
-some formulations have slower onset but longer duration - increase ciliary activity
- decrease mucus viscosity
- decrease release of inflammatory mediators from mast cells and eosinophils
-synergistic with corticosteroids
describe the types of beta agonist drugs (sympathetic drugs)
- specific (B2 only)
-albuterol (salbutamol; inhalation route): only acts on B2 receptors in airways
-terbutaline (PO, IV)
-clenbuterol (equine, prohibited in food animals, PO): has anabolic abuse potential; 20-30d withdrawal; prior to competition - less specific (B1 and B2)
-ephedrine, indirect (PO, IV)
-also has alpha activity (general increase in sympathetic tone, release extra norepi from brain, will eventually be translated into sympathetic tone in context of bronchodilation)
describe side effects and pharmacokinetics of beta agonist drugs (sympathetic drugs)
- at higher doses lose B2 specificity, resulting in:
-tachycardia, anxiety
-hypertension - pharmacokinetics:
-tachyphylaxis can occur
-oral drugs have reduced bioavailability thanks to first pass effect (oral route in theory only acts on receptors in lungs thanks to this first pass effect)
describe methylxanthines (sympathetic drugs)
- inhibit phosphodiesterase (PDE), resulting in bronchodilation (SMOOTH MUSCLE)
-PDE breaks down cAMP
-increased cAMP decreases intracellular calcium - adenosine receptor binding causes:
-increased heart rate
-increased mental awareness - occasionally used in patients with diaphragmatic fatigue and hypoventilation
describe use of methylxanthines (sympathetic drugs)
- available drugs:
-theophylline (PO): immediate or slow release (bid vs. tid dosing); variable absorption, anhydrous prep preferred; longer t1/2 in cats than dogs
-only oral drug so only one for longterm management
-aminophylline (IV, PO): 80% theophylline, 20 min infusion if give IV so tricky
-caffeine: IM
- oral admin variable in horses, may require dose adjustment
- side effects:
-tachycardia
-decreased appetite/nausea/vomiting
-agitation/restlessness/tremors
-diuresis
describe anticholinergic drugs (parasympatholytic)
- parasympatholytic
-block M3 muscarinic receptors to
–inhibit calcium release from myocytes
–impairs bronchoconstriction response
-decreased sensitivity to irritants
-less effective in humans vs. B2 agonists
–longer onset of action vs. sympathomimetics
- side effects (a ton)
-decreased salivation
-tachycardia
-decreased GI motility (HESITATE IN HORSES)
-decreased mucociliary clearance
-mydriasis
describe the specific anticholinergic drugs
- atropine (injection, inhaled): work, but associated with side effects
-gylcopyrrolate lasts longer - ipatropium (inhaled): not well absorbed, limits side effects
-does not alter ciliary clearance in dogs
-greater clinical effect (more bronchodilation) vs. atropine - N-Butylscopolammonium Bromide (Buscopan) (injectable, equine)
-short acting
-use in spasmodic colic as well
-most used in equine ER (to allow good rectal in face of colic, or in context of COPD or asthma in horses)
can use in combo with B2 agonists
describe antiinflammatory corticosteroids
- act on glucocorticoid receptors and inhibit nuclear factor-kB
-inhibit phospholipase A2, so body cannot break down/process arachidonic acid, so no production of prostaglandins and leukotrienes (decreasing inflammation)
-downregulates expression of inflammatory cytokines
-inhibits release of TNF and IL-2 from macrophages
-inhibit platelet activating factor (PAF) release, resulting in decreased bronchoconstriction and vascular permeability
-immuno suppression
describe use of corticosteroids
- inhalational, oral, injectable
-inhalational has fewer side effects, but longer onset
-IV/PO has rapid onsent but increased side effects - side effects:
-hyperglycemia
-hunger (dogs)
-suppression of HPA axis
-iatrogenic hypoadrenocorticism
-laminitis (horses)
-GI ulceration
-immunosuppression - injectable: dexamethasone
-oral: prednisone, prednisolone
-inhaled: higher lipophilicity means longer receptor contact and longer duration of action
–fluticasone/flovent: does not seem to cause immunosuppression even with chronic use, does not seem to alter HPA axis
–beclemathasone diproprionate (equine)
-budesonie and dexamethasone have been used in nebulizers (equine)
describe nebulization
- increased mucus production occurs with airway inflammation
-pneumonia
-asthma/lower airway disease (asthma) - physiologic saline is mucolytic
-disturbs bonds that hold mucus together, reduces viscosity
-allows for clearance via mucociliary clearance - can add drugs:
-N-acetyl cysteine: sulfure integrates into mucus and breaks it up; causes borncho constriction in cats so contraindicated with plasma
-gentamycin: equine
describe inhalational therapies
- admin of aerosols into the airway
- particle size: determines site of deposition in airways
-large aerosols (>10um): upper resp tract
-very small particles (<1um): 50:50% alveoli, exhaled - hydophobicity: hydrophilic particles attract water so penetrate deeper into tracheobronchial tree
- patient factors:
-depth of breathing
-airway patency
-bronchospasm
-coughing - pros:
-targeted drug therapy
-bypass gastric/hepatic degradation
-preserve GI flora
-minimize systemic side effects: tachycardia, anxiety, arrhythmias, tremors - cons:
-shorter half life
-variable drug disposition: required coordinated inhalation
-diseased lung may impact distribution: mucus/fluid, abnormal respiration, coughing
describe delivery of inhalational drugs
- variable devices
- spacer devices help to time inhalation
-disperse drug into chamber and allow animal to breathe at own pace
-horses = obligate nasal breathers so must deliver through nostrils
