Respiratory Acidosis Medication

No drugs are used to specifically treat respiratory acidosis. Medical therapies are directed at the underlying disease or disorder causing hypoventilation and, therefore, respiratory acidosis, and the drugs for these various conditions are included in this review.

Class Summary

Beta2 agonists decrease muscle tone in both small and large airways in the lungs, increasing ventilation. Beta-2 adrenergic agonists activate the beta2- adrenergic receptors on the surface of smooth muscle cells of the bronchial airways, which increases intracellular cyclic adenosine monophosphate (cAMP). This interaction results in smooth muscle relaxation.

Short acting

The short-acting beta2-agonists (albuterol, levalbuterol, metaproterenol, pirbuterol) are used for the treatment or prevention of bronchospasm. These medications are typically delivered to the bronchial smooth muscles by inhalation of aerosolized or nebulized preparations of these medications. Oral preparation of albuterol and metaproterenol are available but are less effective and more prone to complications.

Long acting

The long-acting beta2-adrenergic agonists (arformoterol, formoterol, indacaterol, salmeterol) are typically used in patients with more persistent symptoms. The bronchodilating effects of these drugs last more than 12 hours. Each requires twice daily dosing, except for indacaterol, which is administered once daily.

Albuterol (ProventilHFA, Ventolin HFA)

Albuterol is a beta-agonist for bronchospasm that is refractory to epinephrine. This agent relaxes bronchial smooth muscle by its action on beta2-receptors, with little effect on cardiac muscle contractility.

Salmeterol (Serevent Diskus)

By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, salmeterol can relieve bronchospasms. It also may facilitate expectoration.

The bronchodilating effect of salmeterol lasts >12 hours. This agent is used on a fixed schedule in addition to regular use of anticholinergic agents. When salmeterol is administered at high or more frequent doses than recommended, the incidence of adverse effects is higher.

Metaproterenol

Metaproterenol is a beta2-adrenergic agonist that relaxes bronchial smooth muscle with little effect on heart rate.

Levalbuterol (Xopenex)

Levalbuterol acts on beta2-receptors, causing relaxation of bronchial smooth muscle.

Pirbuterol (Maxair)

Pirbuterol is a beta2-adrenergic agonist with a similar structure to albuterol. Binding to beta2 adrenergic receptors causes relaxation of bronchial smooth muscle.

Formoterol (Foradil, Perforomist)

Formoterol acts on beta2 receptors with little effect on cardiovascular system. It relaxes the smooth muscles of the bronchioles.

Indacaterol (Arcapta Neohaler)

Indacaterol acts on beta2 receptors with little effect on cardiovascular system. It relaxes the smooth muscles of the bronchioles.

Arformoterol (Brovana)

Arformoterol acts on beta2 receptors with little effect on cardiovascular system. It relaxes the smooth muscles of the bronchioles.

Class Summary

The anticholinergic medications compete with acetylcholine for postganglionic muscarinic receptors, thereby inhibiting cholinergically mediated bronchomotor tone, resulting in bronchodilatation. These agents effectively block vagally mediated reflex arcs that cause bronchoconstriction. When inhaled, these medications are poorly absorbed systemically and are therefore relatively safe.

The inhaled short-acting anticholinergic medication, ipratropium, has equivalent-to-superior bronchodilator activity in stable COPD patients when compared with beta2-adrenergic agents. When used in combination with beta-2 adrenergic agonists, a synergistic effect on bronchodilatation occurs. This medication has a slower onset of action than the beta2-adrenergic agents and is, therefore, less suitable for use on an as-needed basis.

Ipratropium (Atrovent HFA)

Ipratropium is an anticholinergic bronchodilator that is chemically related to atropine.

Tiotropium (Spiriva)

Tiotropium is a quaternary ammonium compound that elicits anticholinergic/antimuscarinic effects with inhibitory effects on M3 receptors on airway smooth muscles, leading to bronchodilation. This agent is available in capsule form containing a dry powder for oral inhalation via the HandiHaler inhalation device. Tiotropium helps patients by dilating narrowed airways and keeping them open for 24 hours. It is dosed once daily.

Class Summary

Xanthine derivatives such as theophylline inhibit phosphodiesterase, resulting in an increase in cyclic adenosine monophosphate (cAMP). The increase in cAMP causes relaxation of bronchial smooth muscle. Theophylline is dosed orally. Its analogue, aminophylline, can be given intravenously. In addition, theophylline may improve diaphragmatic muscle contractility and stimulate the central nervous system respiratory center.

Theophylline (Theo-24, Elixophyllin, Theochron)

Theophylline potentiates exogenous catecholamines by stimulating endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation. The popularity of this agent has decreased because of its narrow therapeutic range and frequent toxicity.

Theophylline's therapeutic range is 10-20 mg/dL, but bronchodilation may require near-toxic (> 20 mg/dL) levels. The clinical efficacy of this agent is controversial, especially in the acute setting.

Class Summary

Inflammation plays a significant role in the pathogenesis of asthma. While the inflammatory pathway mediators differ, inflammation is also important in the pathogenesis of COPD. Thus, glucocorticosteroids are used to temper the inflammation in these diseases.

Inhaled

The inhaled glucocorticosteroids (budesonide, fluticasone, mometasone) provide a direct route of administration of these medications to the airways. They are only minimally absorbed systemically and thus have fewer adverse side effects than do systemic glucocorticosteroids. These agents improve airflow in asthmatic patients by reducing inflammation and, in the long-term, preventing airway remodeling. These medications are less effective in COPD patients. These medications also may slow the rate of progression in patients with COPD.

Systemic

The use of systemic glucocorticoid steroids (methylprednisolone, prednisone, prednisolone) in the treatment of acute exacerbations of asthma is highly efficacious. They are also widely accepted and recommended in the treatment COPD exacerbations. The adverse effect profile must be weighed against the potential benefits for long-term use of these medications.

Budesonide inhaled (Pulmicort Flexhaler, Pulmicort Respules)

Budesonide reduces inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing the production of cytokines and other mediators involved in bronchospasm. This agent is available as Pulmicort Flexhaler, powder for inhalation (90 mcg/actuation and 180 mcg/actuation; each actuation delivers 80 mcg and 160 mcg, respectively) or Pulmicort Respules.

Fluticasone inhaled (Flovent Diskus)

Fluticasone may decrease the number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. It also has vasoconstrictive activity.

Mometasone (Nasonex)

Mometasone reduces inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing the production of cytokines and other mediators involved in bronchospasm.

Methylprednisolone (A-Methapred, Medrol, Solu-Medrol)

Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Prednisone

The immunosuppressant prednisone is a first-line therapy administered for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity and CD4 counts.

Prednisolone (Pediapred, Prelone, Orapred)

Prednisolone may reduce inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity and CD4 counts.

Class Summary

Benzodiazepine antagonists are used in reversing the central nervous system depressant effects of benzodiazepine overdoses. However, these agents' ability to reverse the benzodiazepine-induced respiratory depression is less predictable. Care must be used when reversing the effects of benzodiazepines, as patients may have seizures if benzodiazepine reversal is accomplished too vigorously.

Flumazenil (Romazicon)

Flumazenil reverses the effects of benzodiazepines in an overdose by selectively antagonizing the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. If an overdosed patient has not responded after 5 minutes of administering a cumulative dose of 5 mg, the cause of the sedation is not likely to be benzodiazepines.

Flumazenil is short acting, with a half-life of 0.7-1.3 hours; however, because most benzodiazepines have longer half-lives, multiple doses should be administered so that patients do not relapse into a sedative state.

Class Summary

Opioid abuse, toxicity, and overdose are potential etiologies of hypoventilation and respiratory acidosis. Opioid antagonists can be used to reverse the effects of opiates and to improve ventilation.

Naloxone

Naloxone is a pure opioid antagonist that prevents or reverses opioid effects (eg, hypotension, respiratory depression, sedation), possibly by displacing opiates from their receptors. This agent is used to reverse opioid intoxication.