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Anti-tussives

1. Opioids for cough
   
   Cough is a common, and at times distressing, symptom. Up to 40% of advanced cancer patients report cough, and while a smaller percentage find their cough distressing, severe cough can lead to dyspnea, nausea/vomiting, sleep impairment, chest and throat pain, and impaired communication.
   
   Common etiologies of cough include infections of the upper and lower airway, asthma and COPD, lung cancer or lung metastases, interstitial pulmonary processes (such as lymphangitic tumor spread or pulmonary edema), gastroesophageal reflux, aspiration, and drugs. Common drug causes include ACE inhibitors, NSAIDs, and inhalant medications.
   Evaluating for reversible causes is appropriate if consistent with the goals of care and prognosis. If feasible, treatment should be directed at the underlying cause. Many patients however will benefit from symptomatic therapy for a distressing cough while waiting for acute therapy to work or have a chronic cough not amenable to treatment (e.g. cough due to advanced lung cancer).
   
   Opioids are the only clearly effective centrally-acting anti-tussive drugs and are thought to work by suppressing the brainstem cough center through mu and kappa opioid receptor agonism.
   They are the first-line symptomatic treatment for severe, distressing cough.
   All opioids used to treat cough have typical opioid side effects such as sedation, constipation, and nausea.
   
   Codeine: duration of action is 4 hours; usual adult dose is 10-20 mg every 4-6 hours. It has shown to be effective for acute and chronic cough in several placebo-controlled trials. It is available alone or as an elixir with guaifenasin.
   Dextromethorphan: duration of action 3-6 hours; usual adult dose is 10-20 mg every 4-6 hours. It is the most commonly used anti-tussive. Confirmed to be as effective as codeine for cough in multiple studies. It is available alone or as an elixir with guaifenasin. Note: dextromethorphan inhibits the cytochrome P450 system and thereby affects the metabolism of many drugs. Dextromethorphan can also cause a serotonin syndrome if used with serotonergic drugs such as antidepressants.
   Hydrocodone: duration of action 4-6 hours; usual dose 5-10 mg every 4 hours. Hydrocodone is only available as a combination product in the US: as a short-acting elixir with the anticholinergic drug homatropine or as an extended release elixir with the antihistamine chlorpheniramine (dosed at 10 mg every 12 hours). These other agents magnify hydrocodone

   Reference: End of Life/Palliative Education Resource Center. Opioids for Cough. September 27, 2009. Available at http://www.eperc.mcw.edu/fastFact/ff_199.htm

2. Cough is a common, and at times distressing, symptom.
   
   Peripherally-acting anti-tussives
   
   Sweet syrups are commonly used as cough suppressants, whether as bases for prescription elixirs (such as codeine with guaifenesin) or home remedies (honey, simple syrup). The mechanism of action is unknown; some authors hypothesize it acts as a protective barrier to sensory receptors in the throat that heighten the cough reflex. A few controlled trials have shown sweet syrups reduce coughing in upper respiratory infections.
   
   Benzonatate inhibits cough by anesthetizing stretch receptors in the respiratory tract. Its duration of action is 3-8 hours; dosed at 100-200 mg three times a day. No published controlled studies confirm its effectiveness but multiple uncontrolled studies support its use. Side effects are uncommon but include sedation, headache, bronchospasm, and nausea. Expert opinion recommends adding it to an opioid.
   
   Antihistamines and anticholinergics are often part of combination anti-tussive elixirs with or without an opioid. Anticholinergics such as hyoscyamine and scopolamine are most helpful in the setting of copious upper respiratory secretions leading to cough.
   
   Expectorants thin bronchial secretions and ease expectoration. Examples include guaifenesin (200-400 mg every 4 hours) and nebulized acetylcysteine or hypertonic saline. Empirically they have been recommended for severe, chronic, wet coughs. Because they may increase fluid in the respiratory tract, they are not recommended if the cough reflex is diminished.
   
   Nebulized local anesthetics are thought to work by anesthetizing afferent receptors in the respiratory tract. There have been no trials evaluating their effectiveness; anecdotally they have been reported to be effective for refractory cough. Published regimens include lidocaine 2% solution, 5 mL nebulized every 6 hours; and bupivacaine 0.25%, 5 mL nebulized every 8 hours. Bronchospasm is a potential side effect.
   
   Other agents such as bronchodilators and corticosteroids have not been shown to be effective apart from specific indications (e.g. for COPD or asthma exacerbations). Paroxetine, amitriptyline, gabapentin, and benzodiazepines have all been anecdotally reported to have efficacy in chronic, refractory cough.
   
   Treatment for cough should be directed at the underlying cause if feasible and consistent with a patient

   Reference: End of Life/Palliative Education Resource Center. Non-Opioid Anti-Tussives. September 27, 2009. Available at http://www.eperc.mcw.edu/fastFact/ff_200.htm