Hypoventilation Syndromes Medication

Updated: Dec 05, 2017
  • Author: Jazeela Fayyaz, DO; Chief Editor: Guy W Soo Hoo, MD, MPH  more...
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Medication

Medication Summary

Several drugs may be used to treat hypoventilation syndromes. Most produce the desired effect by stimulating the central respiratory drive, by reversing the effects of other medications that can depress the central respiratory drive, or by inducing bronchial dilatation.

For example, bronchodilators such as beta-agonists (eg, albuterol), anticholinergic agents (eg, atropine), and methylxanthines (eg, theophylline) are helpful in treating patients with obstructive lung disease and severe bronchospasm. Additionally, theophylline may improve diaphragm muscle contractility and stimulate the respiratory center.

Over the past several years, multiple long-acting beta-2 agonists and long-acting acting anticholinergics have become available for use in COPD. Patients may benefit from long-acting bronchodilators, such as salmeterol, formoterol, vilanterol, or olodaterol or a long-acting anticholinergic such as tiotropium, umeclidinium, or aclidinium. Patients often are started on a combination product with both these medications. Inhaled steroids might help in select COPD patients or for short-term treatment.

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Beta2 Agonists

Class Summary

Bronchodilators act to decrease the muscle tone in small and large airways in the lungs, thereby increasing ventilation. These drugs include beta adrenergic agonists, methylxanthines, and anticholinergic agonists.

Albuterol (Proventil HFA, Ventolin HFA, ProAir HFA)

Albuterol is a beta agonist for the reversal of bronchospasm. It relaxes bronchial smooth muscle by its action on beta2 receptors, with little effect on cardiac muscle contractility.

Ipratropium (Atrovent)

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

Theophylline (Elixophyllin Elixir, Theo-24)

Theophylline potentiates exogenous catecholamines, stimulates endogenous catecholamine release, and stimulates diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation.

The drug's popularity has decreased because of theophylline's narrow therapeutic range and frequent toxicity. The therapeutic range is 10-20 mg/dL, but bronchodilation may require near-toxic (>20 mg/dL) levels. The clinical efficacy is controversial, especially in an acute setting

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Opioid Reversal Agents

Class Summary

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

Naloxone

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

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Benzodiazepine Toxicity Antidotes

Class Summary

These drugs are used to reverse the CNS-depressant effects of benzodiazepine overdose. Their ability to reverse benzodiazepine-induced respiratory depression is less predictable.

Flumazenil (Romazicon)

Flumazenil reverses the effects of benzodiazepines in an overdose by selectively antagonizing the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. If the patient who is overdosed has not responded after 5 minutes of administering a cumulative dose of 5 mg, the cause of sedation is not likely due to 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 to avoid relapse into a sedative state. Flumazenil also has a risk for provoking seizures. 

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Pulmonary, Other

Class Summary

These agents inhibit the enzyme carbonic anhydrase, which, in turn, increases HCO3 excretion and causes metabolic acidosis. The metabolic acidosis subsequently stimulates ventilation.

Acetazolamide (Diamox Sequels)

Acetazolamide improves symptomatic periodic breathing and hypoxia.

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Progestins

Class Summary

These agents stimulate the central respiratory drive and may be beneficial in patients with hypoventilation.

Medroxyprogesterone acetate (Provera, Depo-Provera)

Medroxyprogesterone acetate increases the central respiratory drive and stimulates ventilation. It may increase upper airway muscular tone. For the treatment of hypoventilation, higher doses than usual of medroxyprogesterone acetate are required to induce significant reductions in hypercapnia.

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Long acting beta agonists

Class Summary

Most of these are available in a combination product, and have been shown to be beneficial in stable COPD. Examples of these include salmeterol, formoterol, vilanterol, and olodaterol. These are contraindicated in asthmatics without the concomitant use of a long acting asthma control medication. 

 

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Long-Acting Muscarinic Agents

Class Summary

These medications interrupt vagal-induced bronchoconstriction, and are also known as long-acting anticholinergics. These are mainly used in COPD.

Tiotropium (Spiriva HandiHaler, Spiriva Respimat)

Tiotropium, a bronchodilator similar to ipratropium, is a once-daily, long-acting anticholinergic medication that has been shown to have significant clinical benefit. A quaternary ammonium compound, it elicits anticholinergic/antimuscarinic effects, with inhibitory effects on M3 receptors on airway smooth muscles, leading to bronchodilation. Tiotropium is the only long-acting muscarinic agent available at this time and has become a first-line therapy in patients with persistent symptoms. Tiotropium is more effective than salmeterol in preventing exacerbations.

Umeclidinium bromide (Incruse Ellipta)

Umeclidinium bromide is a long-acting muscarinic antagonist (LAMA) inhalation powder, often referred to as an anticholinergic. It blocks action of acetylcholine at muscarinic receptors (M1 to M5) in the bronchial airways (M3) by preventing an increase in intracellular calcium concentration, leading to relaxation of airway smooth muscle, improved lung function, and decreased mucus secretion. Umeclidinium dissociates slowly from M3 muscarinic receptors extending its duration of action. It is indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with COPD), including chronic bronchitis and/or emphysema.

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Long-Acting Beta Agonists

Class Summary

Most of these are available in a combination product, and have been shown to be beneficial in stable COPD. Examples of these include salmeterol, formoterol, vilanterol, and olodaterol. These are contraindicated in asthmatic patients without the concomitant use of a long-acting asthma control medication.

Formoterol (Perforomist)

Formoterol relaxes the smooth muscles of the bronchioles and relieves bronchospasms. This effect also may facilitate expectoration. It is shown to improve symptoms and morning peak flows. When administered at high or more frequent doses than recommended, incidence of adverse effects is higher. Bronchodilating effect lasts more than 12 hours. It is used in addition to anticholinergic agents.

Salmeterol (Serevent Diskus)

By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, salmeterol can relieve bronchospasms. The effect also may facilitate expectoration. It is shown to improve symptoms and morning peak flows. When administered at high or more frequent doses than recommended, incidence of adverse effects is higher. Bronchodilating effect lasts more than 12 hours. It is used on a fixed schedule in addition to regular use of anticholinergic agents.

Vilanterol/fluticasone furoate inhaled (Breo Ellipta)

LABA and corticosteroid combination inhaler indicated for long-term, once-daily, maintenance treatment of airflow obstruction with COPD, including chronic bronchitis and/or emphysema. It is also approved to reduce COPD exacerbations. The product contains fluticasone fumarate, which has shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor that is approximately 29.9 times that of dexamethasone and 1.7 times that of fluticasone propionate.

Olodaterol inhaled (Striverdi Respimat)

Olodaterol is a once-daily LABA inhaler indicated for maintenance bronchodilator treatment in patients with COPD, including chronic bronchitis and/or emphysema in patients who are experiencing airflow obstruction. LABAs activate specific β2-adrenergic receptors on the surface of smooth muscle cells, which increases intracellular cAMP and smooth muscle relaxation.

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