Objective: Increase Respiratory Secretions

Rationale Stimulating the tubulo-acinar cells to increase their production may decrease the viscosity of respiratory secretions so that they can be expelled more easily.

Indications to aid in expectoration of secretions associated with infectious disease, allergy, or chronic irritation.

Saline Expectorants (ammonium chloride, potassium iodide, sodium citrate)

Mechanism stimulate receptors in the gastric mucosa, which reflexly increase glandular secretion by the respiratory epithelium

Efficacy at some dose, these agents do increase respiratory tract fluid secretion. Most doses administered Clear evidence for clinical efficacy is lacking. Effective doses may produce excessive GI irritation.

Toxicity emesis, gastric ulceration.

Guaifenesin

Mechanism stimulate receptors in the gastric mucosa, which reflexly increase glandular secretion by the respiratory epithelium

Efficacy at some dose, these agents do increase respiratory tract fluid secretion. Clinical efficacy is not well documented. Appear to be efficacious in people at OTC doses.

Toxicity emesis, gastric ulceration. At high doses, skeletal muscle relaxation.

Volatile Oils(terpine hydrate, eucalyptus, menthol, pine oil)

Mechanism directly stimulate the tubuloacinar glands following absorption when administered orally or when employed in vaporizers for inhalation.

Efficacy at some dose, these agents do increase respiratory tract fluid secretion. Clear evidence for clinical Efficacy is lacking.

Toxicity relatively non-toxic at concentrations employed.

Suppress the Cough Reflex

Rationale A severe, non-productive cough can have harmful effects, including exhaustion, dissemination of the disease process to other parts of the respiratory tract or other animals, and severe respiratory tract injury such as bulla formation and rupture. Such coughs should be controlled with central acting cough suppressants.

General Indication - control of non- productive cough

• mechanical irritation of the bronchi
• infectious diseases
• limit the exhaustion and fatigue associated with coughing at night
• structural defects (e.g., collapsing trachea)

Contraindications When coughing is truly protective(tracheo-esophageal fistula) or when the cough is truly "productive".

Opiates, Opiods codeine, hydrocodone, butorphanol, dextromethorphan.

Mechanism inhibiting the medullary cough center. The opiates and some opioids are potent inhibitors of this reflex center. Codeine and hydrocodone are very similar and suppress cough reflex with limited vomiting and and central nervous system depression (compared to morphine for example). Butorphanol is a narcotic antagonist with agonist activity for analgesia and cough suppression. Dextromethorphan is a low potency, over-the-counter cough suppressant with very weak ability to suppress the rest of the central nervous system.

Efficacy only limited by other CNS depression. Dextromethorphan distinctly LESS efficacious than the other three. Butorphanol can be given by injection.

Toxicity dominated by opiate effects on CNS

Schedules

Codeine	II - V	depends on the specific drug product and combination
Hydrocodone	III - V	"
Butorphanol	IV	Limited abuse potential
Dextromethophan	None	No abuse potential

 

Modify Airway Resistance

Rationale Obstructive airway disease may be caused by excessive secretions, edema of the mucosa, spasm of the bronchial musculature, foreign bodies or tumors, and fibrosis and infiltration producing anatomic narrowing. Drugs can modify the effects of the first three and, as a consequence, improve the delivery of air to the terminal portions of the respiratory tree.

Indications management of chronic obstructive pulmonary disease, bronchial asthma, decompensated congestive heart failure, intrathoracic tracheal collapse, and bronchospasm associated with inhalation of noxious fumes and foreign material.

Contraindications

• Pre-existing cardiovascular disease (relative)
  
• Pre-existing gastrointestinal disease
  
• Exudative processes as drying mucous membranes making pulmonary clearance of secretions more difficult.

Bronchodilators (β-adrenergic agonists, anticholinergic) Decrease resistance to the flow of air in the small airwayby actions on smooth muscle. Greatest efficacy is associated with disease processes causing spasm of these airways

Decongestants (α-adrenergic agonists)Decrease capillary blood flow in the mucosa of bronchioles, reduce edema and reduce secretions. Greatest efficacy is for non-specific airway obstruction.

Epinephrine is the prototype for this class of drugs. All three receptor types activated.

Indications anaphylaxis, bronchodilation, enhancement of cardiac contractility and automaticity, elevation of vascular resistance, and topically for mucous membrane decongestion

Toxicity sympathetic nervous system Toxicity
tachyarrhythmias
extreme hypertension

Isoproterenol is equivalent to epinephrine in β receptor activity but lacks α effect

Indications bronchodilator (emergency) cardiotonic.

Toxicity as for epinephrine but less chance of hypertension

Norepinephrine is equivalent to epinephrine without β-2 receptor activity.

Indications useful only as a pressor agent or cardiotonic. Never in respiratory therapy.

Toxicity as for epinephrine but greater chance of hypertension

Ephedrine, Pseudoephedrine are similar in clinical effect but less potent than epinephrine

Indications

as for epinphrine but absorbed orally
decongestant in proprietary (over-the-counter) cold remedies
α effect (constriction of mucosal vessels)
occasionally used

Toxicity as for epinephrine but much less potent.

Phenylephrine most familiar of a group of α-adrenergic decongestants.

Indications topical vasoconstriction and support of blood pressure.

Toxicity as for epinephrine but much less potent.

Clenbuterol (oral - inhalation, aeromask), Albuterol (oral - inhaler); Terbutaline (oral; small animal)

Indications bronchodilation

Toxicity tachycardia, elevated blood pressure

Xanthine Bronchodilators

Theophylline is the most clinically useful of the xanthine bronchodilators

Indications bronchodilation

Toxicity signs associated with sympathetic (β-1, β-2) overdose (arrhythmias, insomnia, agitation, nervousness, etc.)

Anticholinergics

The parasympathetic nervous system is reponsible for maintaining tone of bronchiolar smooth muscle and that anticholinergic drugs will augment the bronchodilator effects of the β-adrenergics. Caution: weigh the advantage of this effect against the possibility of drying secretions.

Atropine

Indications as a test drug for evaluating responsiveness of COPD in horses.

Toxicity effects of atropine on the gastrointestinal tract precludes its chronic use in this situation.

Ipratropium

Indications because it is a quarternary ammonium its effects are ALMOST completely restricted to the respiratory tract. If you can figure out how to apply it to your patient, it can be used chronically as anadjunct to other bronchodilator therapy.

Toxicity anticholinergic effects on respiratory secretions

Decrease Inflammatory and Immune Responses

Glucocorticoids

Actions Reduce inflammation by inhibiting release of inflammatory mediators

• Stabilizing membranes
  
• Reduce edema
  
• Suppress immune reactions in allergies.
  
• Sensitize the smooth muscle to the action of adrenergic drugs
  
• Stimulate the rate of synthesis of epinephrine by the adrenal medulla
  
• Inhibit the rate of epinerphrinedestruction

The corticosteroids can be administered parenterally, orally, or by inhalation. For chronic administration, the clinician should strive for the lowest effective dose administered by every other day therapy. The decision to institute corticosteroid therapy must be based on a balance between anticipated therapeutic benefits and the known side effects of the dose and duration of treatment.

Indications allergic reactions

Corticosteroid therapy must not be instituted in the absence of a diagnosis, as it could activate a viral or deep fungal infection if that were the underlying problem.

Cromalyn sodium

A newer drug that is particularly useful in the management of allergic phenomena in the respiratory tract is cromolyn sodium. Used prophylactically by asthmatics, cromolyn inhibits the degranulation and release of histamine and SRS-A by mast cells. These hormones are potent bronchoconstrictors which mediate asthmatic attacks caused by allergens. At the present time cromolyn sodium is available only as a fine powder for inhalation. Its utility in veterinary medicine remains speculative.

Stimulate Respiration

Acute respiratory failure (pathologic apnea) is best managed by intubation and mechanical support of repiration. In certain instances it may be desirable to stimulate respiration with drugs. Such may be the case in drug induced central nervous system depression. Older agents such as nikethamide and pentylenetetrazol produced convulsions at doses very near to those necessary for therapeutic effect.

Doxapram

Mechanism Stimulates peripheral chemoreceptors rather than the brain

Indications

Drug induced depression
CO₂ retention associated with obstructive airuway disease
Neonatal asphyxia

Toxicity Hyperexitability and convulsions.

Adverse Effects of Drugs on the Lungs

Adverse drug effects are of course diseases, albeit iatrogenic. They manifest in the respiratory tract as mimics for increases in disease severity or alteration in disease course. Potential reactions include allergic, idiosyncratic, and direct toxic effect. As a result there is a tendency to add drugs to a regimen rather than remove offending agents. Each new appearance of a clinical sign in a respiratory patient should prompt careful decision making. Can the drug being used cause the effect? Can my original objective be met at a lower dose of the current drug? Is there another drug which meets therapeutic objective one and does not cause the adverse effect? The addition of a new drug may be appropriate but it must always be suspect.

Allergic Reactions

• Bronchospasm

  acetylcysteine, local anesthetics, aspirin, antibiotics, cholinergic and anticholinesterase drugs, iron dextran, propranolol, vaccines, and vitamin K.

• Polyarteritis

  arsenicals, phenytoin, mercurials, phenothiazines, sulfonamides, iodides, and DDT.

• Pulmonary Eosinophilia

  mephenesin, sulfonamides, penicillin, and imipramine but is most commonly associated with nitrofurantoin.

Idiosyncratic

Lidocaine therapy may precipitate respiratory arrest. This effect is probably mediated through the respiratory center. The aminoglycoside antimicrobials block nicotinic receptors in skeletal muscle and may precipitate respiratory arrest, particularly in the presence of other skeletal muscle blockers and gaseous anesthetics.

The rapid adminsitration of certain drugs in propylene glycol may precipitate sudden, usually brief respiratory arrest in ruminants.

Topic Summary (Respiratory Tract Therapy)

1. Establish clear therapeutic objectives before selecting drugs. Many respiratory "recipes" are irrational and combine such things as expectorants (which increase secretions) and alpha adrenergic drugs (which decrease secretions).
2. Expectorants are a logical part of therapy for a variety of respiratory tract conditions. However, efficacy in a clinical setting has never been proven.
3. Cough suppressants are largely derived from opiate and opiate-like drugs. They range from dextromethophan (low potency, no addiction potential) to codeine (a high potency schedule III narcotic).
4. Airway resistance can be modified in two major ways:
   
   
   1. Decongestants - drugs which reduce mucosal blood flow and dry secretions.
      
   2. Bronchodilators - drugs which relax smooth muscle of the lower airways.
      
5. Bonchodilators are further divided into three groups: xanthine bronchodilators, β-2 agonists, anticholinergics.
6. Major advances in pulmonary therapy in human beings included the development of "topical" bronchodilators. There is no reason to think that these would not work in veterinary patients but they are difficult to use. (Some require "training" of human patients in order to provide maximum efficacy).