Pharmacology of Respiratory Drugs

Drugs for the Respiratory System

• Drugs for the respiratory system are discussed, including bronchodilatory drugs, anticholinergics, beta agonists, methylxanthines, and corticosteroids.

Pulmonary Response to Irritation

• Stretch receptors, irritant receptors, and J receptors are involved in the pulmonary response to irritation.
• Stimulation of these receptors leads to inflammatory cell infiltrates, histamine release, and afferent nerve stimulation.
• These stimuli ultimately cause bronchoconstriction, mucus hypersecretion, and increased airway permeability.

Bronchodilatory Drugs

• Sympathomimetics (Beta Agonists):
  • Albuterol, a non-specific beta agonist, is primarily used.
  • Epinephrine is another example..
  • Beta agonists act by increasing intracellular cAMP, decreasing intracellular calcium, and inhibiting smooth muscle contraction leading to bronchodilation.
• Methylxanthines:
  • Aminophylline and theophylline are examples.
  • These drugs inhibit phosphodiesterase, increasing cAMP and thus decreasing calcium levels, resulting in bronchodilation.
• Anticholinergics:
  • These drugs block muscarinic receptors, reducing the parasympathetic nervous system's influence on the airways, leading to bronchodilation.

Beta Agonist Drugs

• B1 receptors primarily affect the heart, while B2 receptors primarily affect the respiratory, uterine, and vascular smooth muscles.
• Beta agonists increase intracellular cAMP, decrease calcium release, and thus result in bronchodilation.
• Beta agonists have rapid onset but shorter duration of action.
• Some beta agonists are specific for B2 receptors, while others affect both B1 and B2 receptors.

Beta Agonist Side Effects

• At higher doses, beta agonists may lose their beta-2 specificity, leading to adverse effects such as tachycardia and hypertension.
• Pharmacokinetics can affect bioavailability, including first-pass effects.
• Oral administration is often less effective than intravenous administration.

Methylxanthines (Side Effects)

• Increased mental awareness and heart rate.
• Can be used for patients with diaphragmatic fatigue and hypoventilation.

Methylxanthines (Available Drugs)

• Theophylline (in various forms including immediate-release and sustained release), Aminophylline, and Caffeine.
• Dosage adjustments may be necessary for different species, especially horses, due to variable absorption and metabolism.
• Side effects may include decreased appetite, nausea, vomiting, agitation, tremors, and diuresis.

Anticholinergic Drugs

• Anticholinergics block M3 muscarinic receptors, reducing parasympathetic nervous system activation, thus leading to bronchodilation.
• Side effects may include decreased salivation, tachycardia, decreased gastrointestinal motility, decreased mucociliary clearance, and mydriasis.
• Anticholinergics are less effective in humans compared to B2 agonists.

Corticosteroids (Anti-inflammatory)

• Corticosteroids function by inhibiting nuclear factor-κβ.
• They decrease inflammatory mediator production.
• Corticosteroids are effective anti-inflammatory agents, suppressing the immune response.
• Inhalational administration is preferred to systemic administration (oral/IV) due to fewer side effects but slower onset of action.

Corticosteroids (Administration)

• Inhalational corticosteroids provide localized treatment, minimizing systemic side effects.
• Injectable and oral corticosteroids provide systemic action with rapid onset but may be associated with pronounced side effects like hyperglycemia, suppression of the HPA axis, etc..

Nebulization

• Nebulization is a method of administering drugs in the respiratory tract.
• Increased mucus secretions can be reduced by mucolytic drugs (saline, etc), allowing for mucociliary clearance.

Inhalational Therapies

• Inhalational therapies provide targeted drug delivery.
• Particle size affects site of deposition, with smaller particles reaching deep lung tissues.
• Patient factors like depth of breathing and airway patency influence drug delivery. Inhalant drug administration is designed such that the drug is deposited in the specific area of the respiratory system.

Delivery of Inhalational Drugs

• Spacers are used to aid in administering inhalants by allowing for controlled inhalation and timing.
• Certain species, like horses, must inhale through the nostrils.

Cough

• Coughing is triggered by various factors, including mechanical stimuli (mucus or foreign bodies).
• Cough is a physiological reflex to remove irritants from the respiratory tract.
• Chemical stimuli (substance P released by nerve endings on the resp tract) can trigger a cough response.

Antitussives

• Antitussives are drugs that reduce or stop coughing.
• Centrally acting antitussives may have some side effects; but have an effect on the cough center in the medulla
• Peripherally acting antitussives may act through the peripheral (nerves) aspects of the respiratory system.
• It is important to treat underlying causes (infection) instead of just suppressing coughing in general.

Peripheral Cough Suppressants

• Guaifenesin (glyceryl guaiacolate) acts as an expectorant, decreasing mucus viscosity.
• Lidocaine is a local anesthetic that can be used topically to suppress cough at the larynx.