Since the site or sites of action of some drugs are not known for certain and since it may be determined in the future that some agents may exert their effects on additional sites, this categorization of nonspecific antitussive agents, although not necessarily precise, is meant to serve as a helpful framework for this discussion.

Drugs that May Alter Mucociliary Factors Irritating Cough Receptors
Drugs that are considered in this category are those that might theoretically alter lower respiratory tract secretions by (1) increasing the volume of the secretions (ie, expectorants), (2) decreasing the production of mucus, (3) changing the consistency or regulation of mucus (ie, mucolytics), or (4) increasing mucociliary clearance. proventil inhaler
Although a number of drugs have been shown to increase significantly the volume of the lower respiratory tract secretions in animals when given in excessively large doses and although a number of agents have been shown to change the consistency of mucus in vitro,15 there are few data that have been published to date that have convincingly demonstrated that drugs formulated to alter mucociliary factors function as antitussives. Drugs that have been adequately evaluated in well-designed clinical studies are listed in Table 2.

Table 2—Effects of Antitussive Drugs that May Alter Mucociliary Factors

Drug Reference Study Design Resultt Dosing Schedule^ Patients§
Guaiacol glycerol ether (guaiphenesin)||1l Townley and Bronstein Subjective I 100 mg; PO; tid; 28 days 27 (B; A)
Thomson et al Cough counts I 100 mg; PO; 1 dose 7 B
Kuhn et al Cough counts I 400 mg; PO; qid; 2 days 9 B
Subjective I
Bromhexinel Thomson et al Cough counts I 24 mg; PO; tid; 14 days 9 B
Mossberg et al Cough counts I 8 mg; IV; 1 dose 12 B
Thomson and Reeve Subjective I 16 mg; PO; tid; 21 days 19 B
Valenti and Marenco Subjective E 30 mg; PO; bid; 14 days 235 B
Hypertonic saline||1l Clarke et al Cough counts I Subjective Aerosol; bid; 3 days 11 B
Pavia et al Cough counts I Aerosol; 1 dose 7 B
Mercaptoethane sulfonateH Clarke et al Cough counts I 10%; aerosol; tid; 3 days 11 B
Subjective
Hirsch et al” Subjective I 10%; aerosol; tid; 5 wk 12 B
N-Acetylcysteine||U Hirsch et al Subjective I 10%; aerosol; tid; 5 wk 12 B
Jackson et al Subjective I 200 mg; PO; tid; 3 mo 121 B
Carbocysteine
(S-carboxymethylcysteine)H Edwards et al Subjective E 2.25-3 g; PO; tid; 3 mo 82 B
Thomson et al Cough counts I 4 g; PO; qd; 7 days 16 B
Ipratropium bromide||1I Chafouri et al Subjective E 40|JLg; aerosol; qid; 7 wk 23 B
AmbroxolU Guyatt et al Subjective I 60 mg; PO; bid; 4 wk 78 B
Iodinated glycerol
(iodopropylidene glycerol)||1l Repsher et al Subjective E 60 mg; PO; qid; 28 days 80 A
Petty Subjective E 60 mg; PO; qid; 8 wk 282 B
Pavia et al Cough counts I 60 mg; PO; qid; 7 days 15 B
Dexbrompheniramine maleate||1I plus pseudoephedrine sulfate Curley et al Subjective E 6 mg + 120 mg; PO; bid; 7 days 73 CC
GuaimesalU Jager Subjective E 500 mg; PO; tid; 7 days 140 B