Respiratory Pharmacology Flashcards
Objectives of drugs affecting resp. system
Suppress protective reflexes
Control inflamm.
↓ pulmonary pressure
Dilate bronchioles
Alteration of resp. tract fluids
Control resp. rate
Control infection (antimicrobial therapy)
Resp. defence mechanism
Upper resp. tract = mucociliary apparatusl, cough and sneezing
Lower resp. tract = mononuclear phagocyte system
Coughing
Central and peripherally acting (chemoreceptor and stretch receptor→ constriction)
Goal for cough suppression
↓ frequency and severity without impairing mucocilary defenses
Cough suppression drug uses
Dissemination of infection to healthy tissue or other animals
Rupture fo lung abscesses
Interference with sleep
Cough suppression contraindication
Productive cough (mucous out lungs)
Symptomatic therapy without diagnosis (tracheo-esophageal fistula → aspiration)
Peripheral acting antitussives
Mucosal anesthetics (lidocaine, benzocaine)
Demulcents (soothing effects, syrups)
Bronchodilators (inhalers)
Centrally acting antitussives MOA
Suppression of medullary cough center at opiate receptors (mu and K receptors)
Non-narcotic centrally acting antitussives
Dextromethorphan: semisynthetic agents
Narcotic (opioid) centrally acting antitussives
Morphine, codeine, hydrocodone
Narcotic agonist/ antagonists centrally acting antitussives
Butorphanol
Drugs used as antitussives with less established efficacy
Maropitant (cerenia)
Diphenoxylate + atropine (Lomotil)
Maropitant
Neurokinin receptor (NK1-R) antagonist
Antiemetic in dogs and cats (+ motion sickness)
Diphenoxylate + atropine
Antitussive in chronic bronchitis and tracheal collapse
Enough concentration crosses BBB
Adverse: constipation
Respiratory mononuclear phagocyte system
In cats, cattle, pigs, sheep, goats
Pulmonary alveolar macros and pulmonary intravascular macros
Phagocytic properties
Release inflamm. mediators: histamine, serotonin, PG, leukotrines, PAF
↓ airway caliber size, edema, chemotaxis, ↑ mucous production, bronchospasm
Drugs that target inflammatory response
Glucocorticoids
Locally acting steroids
Drugs targeting leukotrienes
NSAIDs
Antihistamines
Glucocorticoids
Allergic resp. conditions
Good short- term effects
Locally acting steroids
Resp. inhaler using spacer
Beclomehtasone, fluticasone
Drugs that target leukotrienes
Zafirlukast, montelukast
NSAIDs
Aspirin: inhibits TXA2
Tepoxalin: Both PG2 and LTs
Antihistamines
H1R antagonists
Benadryl
Cromolyn
Target inflamm. mediators
Mast cell stabilizer
Inhibits calcium influx into mast cells (prevent degranulation)
Cyproheptadine
Targets inflamm. mediators
Antihistmine and antiserotonin
Binds to 5HT2 receptors
Appetite stimulant
Pulmonary capillary pressure
Pulmonary edema due to fluid overload, left heart failure, mitral valve obstruction
Drugs that ↓ pulmonary capillary pressure
Morphine: ↓ preload via vasodilation
Furosemide: ↓ preload, produce vasodilatory PG in lung
Methyxanthines: bronchodilator
Pulmonary hypertension
Pulmonary vessel vasoconstriction: compensatory mechanism
Complication from chronic lung disease (bronchitis, fibrosis)
Vasodilators
O2: emergency
Sildenafil (viagra)
Peripherally acting antitussives
Mucolytics (breaks down mucous)
Expectorants (pushes mucous out by liquifying lower resp. tract)
Bronchodilators
Dilate bronchioles
Airway caliber changes:
1. Parasympath. sys (baseline tone, mild bronchoconstriction)
2. Sympathetic sys (B2 adrenergic receptor, bronchodilation)
3. Purinergic sys (adenosine, vagal stimulation, irritant receptor and astham)
Bronchodilators
B2 adrenergic receptor agonists
Methylxanthines
Cholinergic antagonists
Bronchodilator additional effects
↓ mucosal edema
Anti-inflammatory effect
Bronchodilator MOA
Reverse contraction by ↑ cAMP, ↓ Ca2+
B- adrenergic agonists
Non-selective: adverse cardiac effects
Selective: Inhaled (albuterol), oral (clenbuterol), parenteral (terbutaline)
B-adrenergic receptor agonists
Most effective bronchodilators
↓ fluid viscosity, ↑ mucocilary clearance
B-adrenergic receptor agonists adverse effects
Sympathetic response: tachycardia, hypertension, m. tremors
Hyokalemia, hyperglycemia
Terbutaline
Tablet, elixir, injectable forms
Not well absorption in horses»_space; parenteral route
Clenbuterol
Lower clinical efficacy
FDA approved for use in horse
Methylxanthine
Relaxes bronchial smooth m.
Stimulate CNS and heart
Mild diuretic and anti-inflamm. effects
↑ strength of resp. m. (diaphragm)
Theophylline use
Longterm for bronchodilatory therapy
Theophylline MOA
Inhibits phoshodiesterases (PDE)- ↑ cAMP → smooth m. relaxation, anti-inflamm. effect
Binding purinergic receptors
Theophylline adverse effects
CNS excitation, GI upset, diuresis, cardiac stimulation
Anticholinergic drugs
Atropine or butylscopolamine challenge test in equine COPD
Chronic fibrosis in COPD
Alteration of resp. tract fluids
↓ viscosity
↑ surfactant production
↓ foam resp. tract
Mucocilliary apparatus function
Warming, humidifying air and trapping particles
Fluid blanket covering the mucoid apparatus
Mocoid/ gel layer: goblets, traps materials and transports, glycoprotein
Water/ sol layer: tubular-acinar gland, parasympathetic control
↓ viscosity
Adding moisture/ hydration
Stimulation of tubule-acinar gland
Chemical cleavage
Humidification of O2
Aerosolization
Aerosolization
Nebulization: local admin
Enhances efficacy, minimize toxicity, rapid response
Factors influencing airway deposition
Diameter, shape, electrical charge, density, mass, prep type
Method, devices, diseases, drugs
Expectorants
Stilumation of tubule-acinar glands
MOA: irritation → reflex bronchial secretion
Guaifenesin, iodide preps, volatile oils
Iodide preparations (potassium iodide)
Gastric mucosa irritation by iodide salts
Contrain: hyperthyroid, pregnant, milk-producing animals
Decreasing viscosity of secretion
Hydration
↑ ionic strength: Na2CO3 and saline
Rupturing sulfur linkages in mucus: N-acetylcysteine or iodine
N- acetylcysteine
Breakdown disulfide bonds
Anti-inflamm. effects
Increasing surfactant production
Neonatal respiratory distress syndrome
Suction airway if intubated
Avoid humidification of air
Nebulized 20-40% ethanol
Neonatal respiratory distress syndrome
Inadequate surfactant
Premature born
Resp. complication
Dexamethasone or betamethasone
Resp. stimulants
Doxapram: CNS stimulant for anesthesia and neonatal animals
Naloxone: Stimulates resp. in narcotic OD
Yohimbine stimualtes resp. in xylazine OD
Resp. suppressants
Opioids
Relieve fear and anxiety
Adverse effects of drugs on the lungs
Bronchospasm
Drying resp. tract (anticholinergics and antihistamines)
Pulmonary edema (cisplatin in cats, vol overload)
Pneumonitis (bromide in cats)
Bronchospasm
Topical or aerosol (acetylcysteine)
Cholinergic drugs
Propranolol and aspirin
Type 1 hypersensitivity
