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Appropriate Use of Antitussives and Protussives

A Practical Review

  • Practical Therapeutics
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Summary

As a symptom of an underlying condition, cough is one of the most common reasons patients see physicians. To the majority, a cough means that ‘something is wrong’ and it causes exhaustion and/or self-consciousness. Patients find these reasons as well as effects on lifestyle, fear of cancer and/or AIDS or tuberculosis to be the most troublesome concerns for which they seek medical attention.

The treatment of cough can be divided into two main categories: (a) therapy that controls, prevents or eliminates cough (i.e. antitussive); and (b) therapy that makes cough more effective (i.e. protussive).

Antitussive therapy can be either specific or nonspecific. Definitive or specific antitussive therapy depends on determining the aetiology or operant pathophysiological mechanism, and then initiating specific treatment. Since the cause of chronic cough can almost always be determined, it is possible to prescribe specific therapy that can be almost uniformly successful. Nonspecific antitussive therapy is directed at the symptom; it is indicated when definitive therapy cannot be given. Practically speaking, the efficacy of nonspecific therapy must be evaluated in double-blind, placebo-controlled, randomised studies of pathological cough in humans.

Such studies have demonstrated the efficacy of dextromethorphan, codeine and ipratropium bromide aerosol in patients with chronic bronchitis. While the preferred treatment for patients with cough due to angiotensin converting enzyme (ACE) inhibitor therapy is withdrawal of the offending drugs, it may be possible to ameliorate the cough by adding nifedipine, sulindac or indomethacin to the treatment regimen.

The efficacy of protussive therapy has not been well documented. Although hypertonic saline aerosol and erdosteine in patients with bronchitis, and amiloride aerosol in patients with cystic fibrosis have been shown to improve mucus clearance, their clinical utility has not been adequately studied.

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References

  • Adcock JJ. Peripheral opioid receptors and the cough reflex. Respiratory Medicine 85 (Suppl. A): 43–46, 1991

    Article  PubMed  Google Scholar 

  • Allegra L, Bossi R. Clinical trials with the new antitussive levodropropizine in adult bronchitic patients. Arzneimittel-Forschung 38: 1163–1166, 1988

    PubMed  CAS  Google Scholar 

  • App EM, King M, Helfesrieder R, Kohler D, Matthys H. Acute and long-term amiloride inhalation in cystic fibrosis lung disease: a rational approach to cystic fibrosis therapy. American Review of Respiratory Disease 141: 605–612, 1990

    Article  PubMed  CAS  Google Scholar 

  • Aylward M, Maddock J. Davies DE, Portheroe DA, Leideman T. Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects. European Journal of Respiratory Disease 65: 283–291, 1984

    CAS  Google Scholar 

  • Baraniuk JN, Kaliner MA. Neuropeptides and nasal secretion. Journal of Allergy Clinical Immunology 86: 620–627, 1990

    Article  CAS  Google Scholar 

  • Bariffi F, Tranfa C, Vatrella A, Ponticiello A. Protective effect of levodropropizine against cough induced by inhalation of nebulized distilled water in patients with obstructive lung disease. Drugs Under Experimental Clinical Research 18: 113–118, 1992

    CAS  Google Scholar 

  • Berkowitz RB, Connell JT, Dietz AJ, Greenstein SM, Tinkelman DG. The effectiveness of nonsedating antihistamine loratadine plus pseudoephedrine in the symptomatic management of the common cold. Annals of Allergy 63: 336–339, 1989

    PubMed  CAS  Google Scholar 

  • Berkowitz RB, Tinkelman DG. Evaluation of oral terfenadine for the treatment of the common cold. Annals of Allergy 67: 593–597, 1991

    PubMed  CAS  Google Scholar 

  • Beumer HM, Hardonk HJ, Boter J, Van Eijnsbergen B. Objective evaluation of antitussive agents under clinical conditions. Respiration 33: 9–13, 1976

    Article  PubMed  CAS  Google Scholar 

  • Bouhuys A, Van de Woestijne KP. Mechanical consequences of airway smooth muscle relaxation. Journal of Applied Physiology 30: 670–676, 1971

    PubMed  CAS  Google Scholar 

  • Boyd EM. Expectorants and respiratory tract fluid. Pharmacological Reviews 6: 521–542, 1954

    PubMed  CAS  Google Scholar 

  • Braun SR, Giovannoni R, O’Connor M. Improving the cough in patients with spinal cord injury. American Journal of Physical Medicine 63: 1–10, 1984

    PubMed  CAS  Google Scholar 

  • Cass LJ, Frederik WS. Quantitative comparison of cough-suppressing effects of Romilar and other antitussives. Journal of Laboratory and Clinical Medicine 48: 879–885, 1956

    PubMed  CAS  Google Scholar 

  • Chafouri MA, Patil KD, Kass I. Sputum changes associated with the use of ipratropium bromide. Chest 86: 387–393, 1984

    Article  Google Scholar 

  • Chernish SM, Lewis G, Kraft B, Howell J. Clinical evaluation of a new antitussive preparation. Annals of Allergy 21: 677–682, 1963

    PubMed  CAS  Google Scholar 

  • Christensen V, Ladegaard-Pedersen HJ, Skovsted P. Intravenous lidocaine as a suppressant of persistent cough caused by bronchoscopy. Acta Anaesthesiologica Scandinavica 67 (Suppl): 84–86, 1978

    PubMed  CAS  Google Scholar 

  • Christensen EF, Nedergaard T, Dahl R. Long-term treatment of chronic bronchitis with positive expiratory pressure mask and chest physiotherapy. Chest 97: 645–650, 1990

    Article  PubMed  CAS  Google Scholar 

  • Clarke SW, Lopez-Vidriero MT, Pavia D, Thomson ML. The effect of sodium 2-mercaptoethane sulphonate and hypertonic saline aerosols on bronchial clearance in chronic bronchitis. British Journal of Clinical Pharmacology 7: 39–44, 1979

    Article  PubMed  CAS  Google Scholar 

  • Cox ID, Wallis PJW, Hughes DTD, Empey DW, Osman RCA, et al. An electromyographic method of objectively assessing cough intensity and use of the method to assess effects of codeine on the dose-response curve to citric acid. British Journal of Clinical Pharmacology 18: 377–382, 1984

    Article  PubMed  CAS  Google Scholar 

  • Curley FJ, Irwin RS, Pratter MR, Stivers DH, Doern GV, et al. Cough and the common cold. American Review of Respiratory Disease 138: 305–311, 1988

    PubMed  CAS  Google Scholar 

  • de Boeck C, Zinman R. Cough versus chest physiotherapy. American Review of Respiratory Disease 129: 182–184, 1984

    PubMed  Google Scholar 

  • Dierckx P, Leblanc G, Decoster A, Criscuolo D. Double-blind study of glaucine in chronic cough. International Journal of Clinical Pharmacology Therapy and Toxicology 19: 396–399, 1981

    CAS  Google Scholar 

  • Eccles R, Morris S, Jawad M. Lack of effect of codeine in the treatment of cough associated with acute upper respiratory infection. Journal of Clinical Pharmacy and Therapeutics 17: 175–180, 1992

    Article  PubMed  CAS  Google Scholar 

  • Eddy NB, Friebel H, Hahn K-J, Halbach H. Codeine and its alternates for pain and cough relief: 4. Potential alternatives for cough relief. Bulletin of the World Health Organization 40: 639–719, 1969

    PubMed  CAS  Google Scholar 

  • Edwards GF, Steel AE, Scott JK, Jordan JW. S-carboxymethylcysteine in the fluidification of sputum and treatment of chronic airway obstruction. Chest 70: 506–513, 1976

    Article  PubMed  CAS  Google Scholar 

  • Edwards GF, Lewis HE, Stafford D. The effect of pholcodine with and without an antihistamine on cough and expectoration. British Journal Diseases of the Chest 71: 245–252, 1977

    Article  CAS  Google Scholar 

  • Estenne M, De Troyer A. Cough in tetraplegic subjects: an active process. Annals of Internal Medicine 112: 22–28, 1990

    PubMed  CAS  Google Scholar 

  • Evald T, Munch EP, Kok-Jensen A. Chronic non-asthmatic cough is not affected by inhaled beclomethasone dipropionate: a controlled double-blind clinical trial. Allergy 44: 510–514, 1989

    Article  PubMed  CAS  Google Scholar 

  • Fogari R, Zoppi A, Tettamanti, Malamani GD, Tinelli C, et al. Effects of nifedipine and indomethacin on cough induced by angiotensin-converting enzyme inhibitors: a double-blind, randomized, cross-over study. Journal of Cardiovascular Pharmacology 19: 670–673, 1992

    PubMed  CAS  Google Scholar 

  • Frigerio G, Lodola E, Sperotti L. The antitussive activity of diviminol (Z.424). Current Therapeutic Research 12: 516–519, 1970

    PubMed  CAS  Google Scholar 

  • Fuller, RW, Jackson, DM. Physiology and treatment of cough. Thorax 45: 425–430, 1991

    Article  Google Scholar 

  • Gaffey MJ, Kaiser DL, Hayden, FG. Ineffectiveness of oral terfenadine in natural colds: evidence against histamine as a mediator of common cold symptoms. Pediatric Infectious Disease Journal 7: 215–242, 1988

    Article  Google Scholar 

  • Gastpar H, Criscuolo D, Dieterich HA. Efficacy and tolerability of glaucine as an antitussive agent. Current Medical Research Opinion 9: 21–27, 1984

    Article  CAS  Google Scholar 

  • Guffanti EE. Drugs with direct peripheral action. In Braga & Allegra (Eds) Cough, pp. 197–225, Raven Press, New York, 1989

    Google Scholar 

  • Guyatt GH, Townsend M, Kazim F, Newhouse MT. A controlled trial of ambroxol in chronic bronchitis. Chest 92: 618–620, 1987

    Article  PubMed  CAS  Google Scholar 

  • Hirsch SR, Viernes PF, Kory RC. Clinical and physiological evaluation of mucolytic agents nebulized with isoproterenol: 10% N-acetylcysteine versus 10% 2-mercaptoethane sulphonate. Thorax 25: 737–743, 1970

    Article  PubMed  CAS  Google Scholar 

  • Holinger LD. Chronic cough in infants and children. Laryngoscope 96: 316–322, 1986

    Article  PubMed  CAS  Google Scholar 

  • Holinger LD, Sanders, AD. Chronic cough in infants and children: an update. Laryngoscope 101: 596–605, 1991

    Article  PubMed  CAS  Google Scholar 

  • Holmes PW, Barter CE, Pierce RJ. Chronic persistent cough: use of ipratropium bromide in undiagnosed cases following upper respiratory tract infection. Respiratory Medicine 86: 425–429, 1992

    Article  PubMed  CAS  Google Scholar 

  • Hutton N, Wilson MH, Mellits ED, Baumgardner R, Wissow LS, et al. Effectiveness of an anti-histamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial. Journal of Pediatrics 118: 125–130, 1991

    Article  PubMed  CAS  Google Scholar 

  • Irwin RS, Rosen MJ, Braman SS. Cough: a comprehensive review. Archives of Internal Medicine 137: 1186–1191, 1977

    Article  PubMed  CAS  Google Scholar 

  • Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy. American Review of Respiratory Disease 123: 413–417, 1981

    PubMed  CAS  Google Scholar 

  • Irwin RS, Pratter MR, Holland PS, Corwin RW, Hughes JP. Postnasal drip causes cough and is associated with reversible upper airway obstruction. Chest 85: 346–352, 1984

    Article  PubMed  CAS  Google Scholar 

  • Irwin RS, Curley FJ, Pratter MR. The effects of drugs on cough. European Journal of Respiratory Diseases 71 (Suppl. 153): 173–181, 1987

    Google Scholar 

  • Irwin RS, Curley FJ. Is the anatomic, diagnostic work-up of chronic cough not all that it is hacked up to be? Chest 95: 711–713, 1989

    Article  PubMed  CAS  Google Scholar 

  • Irwin RS, Curley FJ, French CL. Chronic cough: the spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. American Review of Respiratory Disease 141: 640–647, 1990

    Article  PubMed  CAS  Google Scholar 

  • Irwin RS, Curley FJ. The treatment of cough: a comprehensive review. Chest 99: 1477–1484, 1991

    Article  PubMed  CAS  Google Scholar 

  • Jackson IM, Barnes J, Cooksey P. Efficacy and tolerability of oral acetylcysteine (‘Fabrol’) in chronic bronchitis: a double-blind placebo controlled study. Journal of International Medical Research 12: 198–206, 1984

    PubMed  CAS  Google Scholar 

  • Jager EGH. Double-blind, placebo-controlled clinical evaluation of Guaimesal in outpatients. Clinical Therapeutics 11: 341–362, 1989

    PubMed  CAS  Google Scholar 

  • Kirby NA, Barnerias MJ, Siebens AA. An evaluation of assisted cough in quadriparetic patients. Archives of Physical Medicine and Rehabilitation. 47: 705–710, 1966

    PubMed  CAS  Google Scholar 

  • Kuhn JJ, Hendley JO, Adams KF, Clark JW, Gwaltney Jr JM. Antitussive effect of guaifenesin in young adults with natural colds: objective and subjective assessment. Chest 82: 713–718, 1982

    Article  PubMed  CAS  Google Scholar 

  • Leitcn AG, Lumb EM, Kay AB. Disodium cromoglycate relieves symptoms in symptomatic young smokers: a double-blind, placebo-controlled trial. Allergy 39: 211–215, 1984

    Article  Google Scholar 

  • Lilienfield LS, Rose JC, Princiotto JV. Antitussive activity of diphenhydramine in chronic cough. Clinical Pharmacology and Therapeutics 19: 421–425, 1976

    PubMed  CAS  Google Scholar 

  • Livingston CR, Andrews MA, Jenkins SM, Marriott C. Model systems for the evaluation of mucolytic drugs: acetylcysteine and S-carboxymethylcysteine. Journal of Pharmacy and Pharmacology 42: 73–78, 1990

    Article  Google Scholar 

  • Mathys H, Bleicher B, Bleicher U. Dextromethorphan and codeine: objective assessment of antitussive activity in patients with chronic cough. Journal of International Medical Research 11: 92–100, 1983

    Google Scholar 

  • McEwan JR, Choudry NB, Fuller RW. The effect of Sulindac on the abnormal cough reflex associated with dry cough. Journal of Pharmacology and Experimental Therapeutics 255: 161–164, 1990

    PubMed  CAS  Google Scholar 

  • Mossberg B, Philipson K, Strandberg K, Camner P. Clearance by voluntary coughing and its relationship to subjective assessment and effect of intravenous bromhexine. European Journal of Respiratory Disease 62: 173–179, 1981

    CAS  Google Scholar 

  • Naclerio RM, Proud D, Lichtenstein LM, Kagey-Sobotka A, Hendley JO, et al. Kinins are generated during experimental rhinovirus colds. Journal of Infectious Diseases 157: 133–142, 1988

    Article  PubMed  CAS  Google Scholar 

  • National Health Survey. Vital and Health Statistics. Office visits to internists: the national ambulatory medical care survey, United Sates 1975, Series 13, No. 36, Department of Health, Education and Welfare Publication No. (Public Health Service) 79-1787, pp. 4–29, 1978

  • Olivieri D, Del Donno M, Casalini A, D’Ippolito R, Fregnan GB. Activity of Erdosteine on mucociliary transport in patients affected by chronic bronchitis. Respiration 58: 91–94, 1991

    Article  PubMed  CAS  Google Scholar 

  • Packman EW, London SJ. The utility of artificially induced cough as a clinical model for evaluating the antitussive effects of aromatics delivered by inunction. European Journal of Respiratory Disease 61 (Suppl.): 101–109, 1980

    Google Scholar 

  • Pavia D, Thomson ML, Clarke SW. Enhanced clearance of secretions from the human lung after the administration of hypertonic saline aerosol. American Review of Respiratory Disease 117: 199–203, 1978

    PubMed  CAS  Google Scholar 

  • Pavia D, Agnew JE, Glassman JM, Sutton PP, Lopez-Vidriero MT, et al. Effects of iodopropylidene glycerol on tracheobronchial clearance in stable, chronic bronchitic patients. European Journal of Respiratory Disease 67: 177–184, 1985

    CAS  Google Scholar 

  • Petty TL. The National Mucolytic Study: results of a randomized, double-blind, placebo-controlled study of iodinated glycerol in chronic obstructive bronchitis. Chest 97: 75–83, 1990

    Article  PubMed  CAS  Google Scholar 

  • Poe RH, Harder RV, Israel RH, Kallay MC. Chronic persistent cough: experience in diagnosis and outcome using an anatomic diagnostic protocol. Chest 95: 723–728, 1989

    Article  PubMed  CAS  Google Scholar 

  • Proud D, Reynolds CJ, Lacapra S, Kagey-Sobotka A, Lichtenstein LM, et al. Nasal provocation with bradykinin induces symptoms of rhinitis and a sore throat. American Review of Respiratory Disease 137: 613–616, 1988

    PubMed  CAS  Google Scholar 

  • Proud D, Naclerio RM, Gwaltney JM, Hendley JO. Kinins are generated in nasal secretions during natural rhinovirus colds. Journal of Infectious Diseases 161: 120–123, 1990

    Article  PubMed  CAS  Google Scholar 

  • Repsher LH, Glassman JM, Soyka JP. Evaluation of iodopropylidene glycerol as adjunctive therapy in stable, chronic asthmatic patients on theophylline maintenance. Today’s Therapeutic Trends 1: 77–89, 1983

    Google Scholar 

  • Richardson PS, Phipps RJ. The anatomy, physiology, pharmacology and pathology of tracheobronchial mucus secretion and the use of expectorant drugs in human disease. Pharmacology and Therapeutics 3: 441–479, 1978

    CAS  Google Scholar 

  • Rossman CM, Waldes R, Sampson D, Newhouse MT. Effect of chest physiotherapy on the removal of mucus in patients with cystic fibrosis. American Review of Respiratory Disease 126: 131–135, 1982

    PubMed  CAS  Google Scholar 

  • Ruhle KH, Criscuolo D, Dieterich HA, Kohler D, Riedel G. Objective evaluation of dextromethorphan and glaucine as antitussive agents. British Journal of Clinical Pharmacology 17: 521–524, 1984

    Article  PubMed  CAS  Google Scholar 

  • Sabot G, Bagnato A, Frigerio G. Controlled evaluation of the antitussive activity of viminol p-hydroxybenzoate. International Journal of Clinical Pharmacology 15: 181–183, 1977

    CAS  Google Scholar 

  • Sackner MA. Effect of respiratory drugs on mucociliary clearance. Chest 73 (Suppl.): 958–966, 1978

    PubMed  CAS  Google Scholar 

  • Sevelius H, Colmore JP. Antitussive effect of ethyl dibunate in patients with chronic cough. Clinical Pharmacology and Therapeutics 8: 381–384, 1967

    PubMed  CAS  Google Scholar 

  • Simon SR, Black HR, Moser M, Berland WE. Cough and ACE inhibitors. Archives of Internal Medicine 152: 1698–1700, 1992

    Article  PubMed  CAS  Google Scholar 

  • Sperber SJ, Hendley JO, Gayden FG, Riker DK, Sorrentino JV, et al. Effects of naproxen on experimental rhinovirus colds. Annals of Internal Medicine 117: 37–41, 1992

    PubMed  CAS  Google Scholar 

  • Sutton PP, Pavia D, Bateman JRM, Clarke SW. The effect of oral aminophylline on lung mucociliary clearance in man. Chest 80 (Suppl.): 889–892, 1981

    PubMed  CAS  Google Scholar 

  • Thomas JT, Heurich AE, Shepherd DA, Sanzari NP. A system for the clinical assessment of the antitussive activity of caramiphen. Current Therapy Research 16: 1082–1090, 1974

    CAS  Google Scholar 

  • Thompson KJ, Reeve J. A clinical trial of bromhexine. New Zealand Medical Journal 76: 73–76, 1972

    PubMed  CAS  Google Scholar 

  • Thomson ML, Pavia D, Gregg I, Stark JE. The effect of bromhexine on mucociliary clearance from the human lung in chronic bronchitis. Scandinavian Journal of Respiratory Disease 90 (Suppl.): 75–79, 1974

    CAS  Google Scholar 

  • Thomson ML, Pavia D, McNicol MW. A preliminary study of the effect of guaiphenesin on mucociliary clearance from the human lung. Thorax 28: 742–747, 1973

    Article  PubMed  CAS  Google Scholar 

  • Thomson ML, Pavia D, Jones CJ, McQuiston TAC. No demonstrable effect of S-carboxymethylcysteihe on clearance of secretions from the human lung. Thorax 30: 669–673, 1975

    Article  PubMed  CAS  Google Scholar 

  • Townley RG, Bronstein SB. A double blind clinical evaluation of glycerol guaiacolate. Annals of Allergy 21: 683–691, 1963

    PubMed  CAS  Google Scholar 

  • Ucelay M, Labeaga L, Orjales A, Zubiaur L, Quintana A. Evaluation of bronchospasmolytic, antiallergic, anti-inflammatory, mucolytic and antitussive activities of decasilate in experimental models. Arzneimittel-Forschung 41: 528–532, 1991

    PubMed  CAS  Google Scholar 

  • Valenti S, Marenco G. Italian multicenter study on the treatment of chronic obstructive lung disease with bromhexine: a doubleblind, placebo-controlled trial. Respiration 56: 11–15, 1989

    Article  PubMed  CAS  Google Scholar 

  • Vesco D, Kleisbauer J-P, Orehek J. Attenuation of bronchofi-berscopy-induced cough by an inhaled β2-adrenergic agonist, Fenoterol. American Review of Respiratory Disease 138: 805–806, 1988

    Article  PubMed  CAS  Google Scholar 

  • Widdicombe JG. Physiology of cough. In Braga & Allegra (Eds) Cough, pp. 3–25, Raven Press, New York, 1989

    Google Scholar 

  • Woolf CR, Rosenberg A. Objective assessment of cough suppressants under clinical conditions using a tape recorder system. Thorax 19: 125–130, 1964

    Article  PubMed  CAS  Google Scholar 

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  1. Division of Pulmonary and Critical Care Medicine, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts, 01655, USA

    Richard S. Irwin & Frederick J. Curley

  2. Department of Anesthesia and Critical Care, Beth Israel Hospital, Boston, Massachusetts, USA

    Frederick M. Bennett

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Irwin, R.S., Curley, F.J. & Bennett, F.M. Appropriate Use of Antitussives and Protussives. Drugs 46, 80–91 (1993). https://doi.org/10.2165/00003495-199346010-00006

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