Antitussive Drugs and Cough Reflex

• The cough reflex, a normal pulmonary defense mechanism, prevents aspiration and removes harmful substances, but excessive coughing can indicate airway disease and impair quality of life.
• Cough suppression should be reserved for excessive, dry, or debilitating coughs.

Antitussive Drugs

• Antitussives are medications used to suppress coughing.

Opioids

• Opioids depress the cough center in the medulla through mu (µ) and kappa (κ) receptor agonism.
• They provide sedation, analgesia, and facilitate intubation pre-surgery, reducing laryngeal spasms and coughing.
• Butorphanol is a kappa-receptor agonist
• Butorphanol is FDA-approved for antitussive use in dogs, has low oral bioavailability, and its effects last up to 10 hours.
• Butorphanol is available in tablet and injectable forms, and it is a US DEA Schedule IV controlled substance.
• Codeine, a mu-receptor agonist, is occasionally used in dogs, but has low and inconsistent oral absorption.
• Hydrocodone, a more potent mu-receptor agonist than codeine, is often combined with anticholinergics to discourage abuse and is a US DEA Schedule II controlled substance.
• Dextromethorphan is a human OTC cough suppressant
• Dextromethorphan is not considered effective in veterinary medicine.

Expectorants and Mucolytic Drugs

• These drugs increase bronchial secretions, although their efficacy in veterinary medicine is not always established.
• Saline expectorants stimulate bronchial mucus through a vagal-mediated reflex action on the gastric mucosa.
• Guaifenesin, typically a muscle relaxant in anesthesia, may stimulate bronchial secretions via vagal pathways and accelerate particle clearance from airways.
• Acetylcysteine has a mucolytic effect and is used in human patients with obstructive airway disease, and in humans and animals to treat some intoxications.

Bronchodilator Drugs

• Bronchodilators are beneficial in treating airway diseases, including asthma and recurrent airway obstruction
• Stimulation of β2 receptors leads to increased intracellular cAMP, causing bronchodilation, decreased release of inflammatory mediators, and increased mucociliary clearance.
• Tolerance can develop with repeated use of bronchodilators, necessitating short-term use and drug-free breaks.

Clinical Use

• Epinephrine is the drug of choice for emergency treatment of life-threatening bronchoconstriction.
• Terbutaline is a longer-acting β2-specific drug used for acute bronchoconstriction relief and in horses for RAO.
• Albuterol is used in small animals at lower doses than in humans, available in various forms.
• Clenbuterol, approved for use in horses with RAO, is a partial agonist with lower clinical efficacy, prohibited in food animals and can cause down regulation of B2 receptors.
• Common adverse effects include cardiovascular and skeletal muscle issues, especially with β1-agonists or high doses of β2-agonists.
• Cromolyn stabilizes mast cells in animals with hypersensitive airways, administered via inhalation before allergen exposure; it does not have bronchodilator action.
• Atropine and glycopyrrolate are effective bronchodilators.
• Ipratropium bromide is an inhaled antimuscarinic agent used for RAO in horses, while N-butylscopolamine bromide is administered intravenously for RAO in horses with rapid onset and short duration.
• Theophylline, used as a bronchodilator in human asthma therapy and tolerated well orally in small animals, relaxes bronchial smooth muscle and stimulates the CNS, but is restricted in horses due to adverse effects.
• Theophylline inhibits phosphodiesterase and adenosine receptors.

Glucocorticoids (GCs)

• Decrease inflammation in pulmonary diseases by inhibiting the transcription of genes that produce inflammatory mediators.
• GCs enhance the action of β2 agonists receptors by preventing down-regulation.
• Prednisolone, methylprednisolone acetate, and inhaled fluticasone are used in cats with feline asthma.
• Oral prednisolone/prednisone and inhaled fluticasone are used in dogs.
• Prednisolone and dexamethasone are used in horses with RAO and IAD, with inhaled corticosteroids beneficial but expensive.
• GCs are best combined with environmental control.

Leukotriene Inhibitors

• Zileuton inhibits 5-lipoxygenase, reducing inflammatory leukotriene synthesis.
• Zafirlukast and montelukast block cysteinyl leukotriene receptors, used for treating asthma in people.
• Leukotrienes contribute to airway inflammation by increasing eosinophil migration, causing bronchoconstriction, and increasing airway wall edema.

Decongestants

• Decongestants are sympathomimetic drugs that stimulate α-receptors in mucus membranes.
• Decongestants produce local vasoconstriction to "dry up" mucus membranes, though topical use is rare in animals.
• Systemic use can cause vasoconstriction and increased blood pressure.

Respiratory Stimulants

• Doxapram stimulates respiration by directly stimulating the medullary respiratory center.
• Doxapram is used in emergencies, to increase suckling in neonatal foals, and to treat respiratory acidosis in foals with hypoxic-ischemic encephalopathy.