Respiratory Drugs PDF

1/28/25 Drugs for the respiratory system Benjamin Brainard VMD VMED 5291 Pulmonary response to irritation Stretch receptors J receptors...

1/28/25 Drugs for the respiratory system Benjamin Brainard VMD VMED 5291 Pulmonary response to irritation Stretch receptors J receptors Irritant receptors Inflammatory cell infiltrates Release of histamine stimulates afferent nerves à bronchoconstriction Stimulate mucus Increase permeability Li D. Molecules. 2023; 28(3):1139. 1  1/28/25 Bronchodilatory drugs Smooth muscle Sympathomimetics Beta agonists Albuterol Non specific bronchus Ephedrine Methylxanthines Aminophylline vein Theophylline Caffeine alveolus Anticholinergics https://blogs.lsc.edu/brianbich/portfolio-item/k-bronchiole-100x-2/ Beta agonist drugs ß1-primarily cardiac ß2- primarily respiratory, uterine and vascular smooth muscle Inhibit smooth muscle contraction by decreasing intracellular calcium Activates adenyl cyclase ATP à cAMP Decreased calcium release àbronchodilation https://pharmacologymentor.com/beta-agonists-an-in- depth-overview/ 2  1/28/25 Beta agonist drugs Rapid onset of action; can be emergent therapy for acute bronchoconstriction (esp. inhalational therapy) Onset 5-15 min, duration 2-4 h. Some formulations have slower onset but longer duration Increase ciliary activity Decrease mucus viscosity Decrease release of inflammatory mediators from mast cells, eosinophils Synergistic with corticosteroids Johnson M.J Allergy Clin Immunol. 2002;110(6 Suppl):S282 Beta agonist drugs Specific (𝛽2 only) Albuterol (salbutamol; inhalation) Only 𝛽2 receptors in airways Terbutaline (PO, IV) Clenbuterol (equine, prohibited in food animals, PO) Has anabolic abuse potential 20-30 d. withdrawl prior to competition Less specific (𝛽1 and 𝛽2) Ephedrine; indirect (PO, IV) Also has alpha activity 3  1/28/25 Beta agonist side effects At higher doses lose ß2 specificity Tachycardia* Hypertension* Pharmacokinetics Tachyphylaxis can occur Oral drugs have reduced bioavailability First pass effect Oral dose > parenteral dose Methylxanthines Inhibit phosphodiesterase (PDE) à bronchodilation (smooth muscle) PDE breaks down cAMP Increased cAMP à decreased intracellular calcium. Adenosine receptor binding Increase heart rate Increase mental awareness Occasionally used in patients with diaphragmatic fatigue and hypoventilation Yang. Front Pediatr. 2021 Oct 1:9:724161. 4  1/28/25 Methylxanthines Available drugs Theophylline (PO) IR or slow release (bid vs tid dosing) Variable absorption, anhydrous preparation preferred Longer t1/2 cat vs dog Aminophylline (IV, PO) 80% theophylline Caffeine (IM) Oral administration variable in horses; may require dose adjustment Side effects Tachycardia Decreased appetite/nausea/vomiting Agitation/restlessness/tremors Diuresis Anticholinergic drugs Parasympatholytic Block M3 muscarinic receptors Inhibits calcium release from myocytes Impairs bronchoconstriction response Decreased sensitivity to irritants Less effective in humans vs. ß2 agonist drugs Longer onset of action vs sympathomimetics Side effects Decreased salivation Tachycardia Decreased GI motility Decreased mucociliary clearance Mydriasis Li D. Molecules. 2023; 28(3):1139. 5  1/28/25 Anticholinergic drugs Atropine (injection, inhaled): work, but associated w/side effects Glycopyrrolate lasts longer Ipatropium (inhaled): not well-absorbed, limits side effects Does not alter ciliary clearance (dogs) Greater clinical effect (more bronchodilation) vs atropine N- Butylscopolammonium Bromide (Buscopan) (injectable, equine) Short acting Use in spasmodic colic as well Combination with ß2 agonists Foreman JH. VCNA Equine. 1999;15(3):665-86 6  1/28/25 Corticosteroids: antiinflammatory Glucocorticoid receptors à inhibit nuclear factor–kβ Inhibits PLA2 à cannot process AA à PG and LT’s Downregulates expression of inflammatory cytokines Inhibit release of TNF and IL-2 from macrophages Inhibit platelet activating factor (PAF) release Decreased bronchoconstriction, vascular permeability Immunosuppression Corticosteroids Inhalational, oral, injectable Inhalational has fewer side effects, but longer onset MDI vs nebulizer IV/PO has rapid onset but increased side effects Side effects Hyperglycemia Hunger (dogs) Suppression of HPA axis Iatrogenic hyperadrenocorticism Laminitis (horses) GI ulceration Immunosuppression 7  1/28/25 Corticosteroids Injectable: Dexamethasone Oral: prednisone, prednisolone Inhaled: Higher lipophilicity à prolonged receptor contact à longer duration of action Fluticasone (Flovent) In humans, detectable in lungs up to 20 hours after inhalation. Does not seem to cause immunosuppression even with chronic use Does not seem to cause significant alteration of HPA axis 300 x more lipophilic than others Beclomethasone dipropionate (equine use) Next most commonly used Budesonide and dexamethasone have been used in nebulizers (equine) Nebulization Increased mucus secretion 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 escalator Can add drugs N-acetyl cysteine: sulfur integrates into mucus and breaks it up Causes bronchoconstriction in cats, contraindicated with asthma Gentamycin: equine 8  1/28/25 Inhalational therapies Administration of aerosols into the airway Particle size: determines site of deposition in airways Large aerosols (>10 μm) à upper respiratory tract (URT) Very small particles ( codeine (PO) Mu, delta opioid agonist Alters central cough sensitivity, acute > chronic cough Less respiratory depression, constipation vs other opioids Dextromethorphan (potency similar to codeine) NMDA-antagonist Unclear MOA to prevent cough. Maropitant (NK-1 antagonist) Substance P associated with pulmonary irritation Decreases frequency in chronic bronchitis (vs acute) Aoki T Vet Med Sci. 2024;10(5):e1549. 11  1/28/25 Peripheral cough suppressants Guaifenesin (glyceryl guaiacolate, GG) Expectorant, decrease tenacity of mucus Muscle relaxant, central or spinal (?) Local anesthetics Lidocaine, applied topically to larynx Guajacum officinale 12